国外数据库各学科高被引论文TOP5

2015-01-30 12:37

中国学术期刊文摘 2015年7期

关键词：出版物邮箱来源

国外数据库各学科高被引论文TOP5

数据来源：Web of Science文献出版时间：2013.1—2015.2检索时间：2015.3.6

Acoustics 声学

被引频次：88

来源出版物：Ultraschall in Der Medizin， 2013， 34（2）：169-184联系邮箱：Bamber， J； jeff@icr.ac.uk

被引频次：72

EFSUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography. Part 2：Clinical Applications

Cosgrove， D； Piscaglia， F； Bamber， J； et al.

Abstract：The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography， stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section， reflecting the wide experience with transient and shear wave elastography. Then follow the breast， thyroid， gastro-intestinal tract， endoscopic elastography， the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.

Keywords：radiation force impulse； real-time elastography； chronic hepatitis-c； liver stiffness measurement； shear-wave elastography；malignant thyroid-nodules； associazione medici endocrinologi； inflammatory-bowel-disease； prostate-cancer detection； focal pancreatic lesions

来源出版物：Ultraschall in Der Medizin， 2013， 34（3）：238-253联系邮箱：Cosgrove， D； d.cosgrove@imperial.ac.uk

被引频次：58

Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound（CEUS） in the Liver - Update 2012 A WFUMB-EFSUMB Initiative in Cooperation with Representatives of AFSUMB， AIUM， ASUM， FLAUS and ICUS

Claudon， M； Dietrich， CF； Choi， BI； et al.

Abstract：Initially， a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver， as well as implementing some non-liver applications. Time has moved on， and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound（CEUS） using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations（i.e.， Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB）. These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents（UCA）. They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Keywords：small hepatocellular-carcinoma； gastrointestinal stromal tumors； guided radiofrequency ablation； hepatic-artery thrombosis；degum multicenter trial； intraoperative ultrasonography； colorectal-cancer； b-mode； peripheral cholangiocarcinoma； quantitative assessment

来源出版物：Ultraschall in Der Medizin， 2013， 34（1）：11-29联系邮箱：Dietrich， CF； christoph.dietrich@ckbm.de

被引频次：45

Non-invasive prenatal testing for aneuploidy：current status and future prospects

Benn， P； Cuckle， H； Pergament， E

Abstract：Non-invasive prenatal testing（NIPT） for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis. We review NIPT in the context of established screening and invasive technologies， the range of cytogenetic abnormalities detectable， cost， counseling and ethical issues. Current NIPT approaches involve whole-genome sequencing， targeted sequencing and assessment of single nucleotide polymorphism（SNP） differences between mother and fetus. Clinical trials have demonstrated the efficacy of NIPT for Down and Edwards syndromes， and possibly Patau syndrome， in high-risk women. Universal NIPT is not cost-effective， but using NIPT contingently in women found at moderate or high risk by conventional screening is cost-effective. Positive NIPT results must be confirmed using invasive techniques. Established screening， fetal ultrasound and invasive procedures with microarray testing allow the detection of a broad range of additional abnormalities not yet detectable by NIPT. NIPT approaches that take advantage of SNP information potentially allow the identification of parent of origin for imbalances， triploidy， uniparental disomy and consanguinity， and separate evaluation of dizygotic twins. Fetal fraction enrichment， improved sequencing and selected analysis of the most informative sequences should result in tests for additional chromosomal abnormalities. Providing adequate prenatal counseling poses a substantial challenge given the broad range of prenatal testing options now available.

Keywords：free fetal dna； confined placental mosaicism； cell-free dna； balanced chromosome rearrangements； maternal plasma； parental origin； down-syndrome； x-chromosome； messenger-rna； trisomies 13

来源出版物：Ultrasound in Obstetrics & Gynecology， 2013， 42（1）：15-33联系邮箱：Benn， P； benn@nso1.uchc.edu

被引频次：42

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound（CEUS） in the liver - update 2012 a WFUMB-EFSUMB initiative in cooperation with representatives of afsumb， aium， asum， flaus and icus

Claudon， M； Dietrich， CF； Choi， BI； et al.

来源出版物：Ultrasound in Medicine and Biology， 2013， 39（2）：187-210联系邮箱：Dietrich， CF； Christoph.dietrich@ckbm.de

Agricultural Engineering 农业工程

被引频次：38

Role and significance of beta-glucosidases in the hydrolysis of cellulose for bioethanol production

Singhania， RR； Patel， AK； Sukumaran， RK； et al.

Abstract：One of the major challenges in the bioconversion of lignocellulosic biomass into liquid biofuels includes the search for a glucose tolerant beta-gulucosidase. Beta-glucosidase is the key enzyme component present in cellulase and completes the final step during cellulose hydrolysis by converting the cellobiose to glucose. This reaction is always under control as it gets inhibited by its product glucose. It is a major bottleneck in the efficient biomass conversion by cellulase. To circumvent this problem several strategies have been adopted which we have discussed in the article along with its production strategies and general properties. It plays a very significant role in bioethanol production from biomass through enzymatic route. Hence several amendments took place in the commercial preparation of cellulase for biomass hydrolysis， which contains higher and improved beta-glucosidase for efficient biomass conversion. This article presents beta-glucosidase as the key component for bioethanol from biomass through enzymatic route.

Keywords：trichoderma-reesei cellulase； myceliophthora sp imi-387099； pichia-pastoris； family 3； paecilomyces-thermophila； differentialexpression； functional expression； aspergillus-fumigatus； glycosyl hydrolases； enhanced production

来源出版物：Bioresource Technology， 2013， 127：500-507联系邮箱：Singhania， RR； reetasinghania@gmail.com

被引频次：36

Hydrothermal liquefaction（HTL） of microalgae for biofuel production：State of the art review and future prospects

Barreiro， DL； Prins， W； Ronsse， F； et al.

Abstract：Among the various types of biomass， microalgae have the potential of becoming a significant energy source for biofuel production in the coming years. Currently， research is mainly focusing on optimization of the cultivation methods and the conversion of just a single microalgae fraction（lipids for biodiesel production）. Hydrothermal liquefaction is a method for thermochemical conversion of wet microalgae， producing a liquid energy carrier called 'bio-oil' or 'biocrude'， next to gaseous， aqueous and solid by-products. A review of the available literature is presented here， analyzing the influence of parameters such as temperature， holding time and catalyst dosage on the yield and properties of the different product fractions. Also， the strain selection and the status of the technology for hydrothermal processes are analyzed. Finally， based on the findings obtained from the literature review， directions for future research are suggested.

Keywords：supercritical water； oil production； chlorella-protothecoides； dunaliella-tertiolecta； nannochloropsis sp； bio-oil； thermochemical liquefaction； catalytic gasification； marine microalgae； renewable fuels

来源出版物：Biomass & Bioenergy， 2013， 53：113-127联系邮箱：Barreiro， DL； Diego.LopezBarreiro@UGent.be

被引频次：36

Inhibitory effect of lignin during cellulose bioconversion：The effect of lignin chemistry on non-productive enzyme adsorption

Rahikainen， JL； Martin-Sampedro， R； Heikkinen， H； et al.

Abstract：The effect of lignin as an inhibitory biopolymer for the enzymatic hydrolysis of lignocellulosic biomass was studied； specially addressing the role of lignin in non-productive enzyme adsorption. Botanical origin and biomass pre-treatment give rise to differences in lignin structure and the effect of these differences on enzyme binding and inhibition were elucidated. Lignin was isolated from steam explosion（SE） pre-treated and non-treated spruce and wheat straw and used for the preparation of ultrathin films for enzyme binding studies. Binding of Trichoderma reesei Cel7A（CBHI） and the corresponding Cel7A-core， lacking the linker and the cellulose-binding domain， to the lignin films was monitored using a quartz crystal microbalance（QCM）. SE pre-treatment altered the lignin structure， leading to increased enzyme adsorption. Thus， the positive effect of SE pre-treatment， opening the cell wall matrix to make polysaccharides more accessible， may be compromised by the structural changes of lignin that increase non-productive enzyme adsorption.

Keywords：steam-explosion pretreatment； trichoderma-reesei； cellobiohydrolase-i； wheat-straw； thin-films； hydrolysis； wood； softwood；surface； delignification

来源出版物：Bioresource Technology， 2013， 133：270-278联系邮箱：Rahikainen， JL； jenni.rahikainen@vtt.fi

被引频次：31

Biosynthesis， characterisation and anti-bacterial effect of plant-mediated silver nanoparticles using Artemisia nilagirica

Vijayakumar， M； Priya， K； Nancy， FT； et al.

Abstract：Currently， there is an increasing commercial demand for nanoparticles due to their wide applicability in various markets， such as medicine， catalysis， electronics， chemistry and energy. In this report， a simple and eco-friendly chemical reaction for the synthesis of silver nanoparticles（AgNPs） from Artemisia nilagirica（Asteraceae） has been developed. Silver nitrate was used as the metal precursor and hydrazine hydrate as a reducing agent. Scanning electron microscopy（SEM） and energy-dispersive spectroscopy（EDX） were used to characterise the nanoparticles obtained from A. nilagirica. The morphology of the AgNPs was determined by SEM and the average diameter of the particles was determined as 70-90 nm. The EDX analysis of the nanoparticles dispersion， using a range of 2-4 keV. confirmed the presence of elemental silver， with no other impurity peaks detected. In addition， the characterised AgNPs has the potential for various medical and industrial applications. The results showed that microbial susceptibility to AgNPs is different for each microorganism.

Keywords：antimicrobial activity； escherichia-coli； microscopy； reduction； bacteria； extract

来源出版物：Industrial Crops and Products， 2013， 41：235-240联系邮箱：Vijayakumar， M； drvijay@um.edu.my

被引频次：30

Development of model for mechanical properties of tapioca starch based edible films

Maran， JP； Sivakumar， V； Sridhar， R； et al.

Abstract：Eco-efficient products are the new generation of bio-based products prepared with sustainable materials， which agree with eco-logical and economic requirements including environmentally acceptable disposal of post-user waste. Increasing environmental concerns associated with handling of plastic waste has emphasized the importance of developing biodegradable edible films from starch. The objective of this study is to develop models and study the individual and interactive effects of the process variables on the mechanical properties of tapioca starch-based edible films using Box-Behnken design. Box-Behnken design with four factors at three levels was employed to evaluate the individual and interactive effects of process parameters（tapioca starch 1-3 g； glycerol 0.5-1.0 ml； agar 0.5-1.0 g； and span 80：0.1-0.5 ml） on the tensile strength， elongation. Young's modulus， puncture force， and puncture deformation respectively. The results were analyzed using Pareto analysis of variance（ANOVA）. For each response， second order polynomial regression models were developed and it showed good fit of the experimental data with high coefficient of determination（R-2） and a close agreement between experimental and predicted values was found. The response surface and contour plots were constructed for representing the relationship between the process parameters and the responses.

Keywords：response-surface methodology； water-vapor permeability； box-behnken design； physical-properties； cassava starch； microstructural characterization； functional-properties； plasticized starch； tensile properties； thermal-properties

来源出版物：Industrial Crops and Products， 2013， 42：159-168联系邮箱：Sivakumar， V； prakashmaran@gmail.com

Agriculture Dairy Animal Science 农业，乳品和动物科学

被引频次：31

Recent developments in altering the fatty acid composition of ruminant-derived foods

Shingfield， KJ； Bonnet， M； Scollan， ND

Abstract：There is increasing evidence to indicate that nutrition is an important factor involved in the onset and development of several chronic human diseases including cancer， cardiovascular disease（CVD）， type II diabetes and obesity. Clinical studies implicate excessive consumption of medium-chain saturated fatty acids（SFA） and trans-fatty acids（TFA） as risk factors for CVD， and in the aetiology of other chronic conditions. Ruminant-derived foods are significant sources of medium-chain SFA and TFA in the human diet， but also provide high-quality protein， essential micronutrients and several bioactive lipids. Altering the fatty acid composition of ruminant-derived foods offers the opportunity to align the consumption of fatty acids in human populations with public health policies without the need for substantial changes in eating habits. Replacing conserved forages with fresh grass or dietary plant oil and oilseed supplements can be used to lower medium-chain and total SFA content and increase cis-9 18：1， total conjugated linoleic acid（CLA）， n-3 and n-6 polyunsaturated fatty acids（PUFA） to a variable extent in ruminant milk. However， inclusion of fish oil or marine algae in the ruminant diet results in marginal enrichment of 20- or 22-carbon PUFA in milk. Studies in growing ruminants have confirmed that the same nutritional strategies improve the balance of n-6/n-3 PUFA， and increase CLA and long-chain n-3 PUFA in ruminant meat， but the potential to lower medium-chain and total SFA is limited. Attempts to alter meat and milk fatty acid composition through changes in the diet fed to ruminants are often accompanied by several-fold increases in TFA concentrations. In extreme cases， the distribution of trans 18：1 and 18：2 isomers in ruminant foods may resemble that of partially hydrogenated plant oils. Changes in milk fat or muscle lipid composition in response to diet are now known to be accompanied by tissue-specific alterations in the expression of one or more lipogenic genes. Breed influences both milk and muscle fat content， although recent studies have confirmed the occurrence of genetic variability in transcript abundance and activity of enzymes involved in lipid synthesis and identified polymorphisms for several key lipogenic genes in lactating and growing cattle. Although nutrition is the major factor influencing the fatty acid composition of ruminant-derived foods， further progress can be expected through the use of genomic or marker-assisted selection to increase the frequency of favourable genotypes and the formulation of diets to exploit this genetic potential.

Keywords：conjugated linoleic-acid； stearoyl-coa desaturase； japanese black cattle； lactating dairy-cows； subcutaneous adipose-tissue；element-binding protein-1； fed maize silage； mammary lipogenic enzymes； sunflower-seed oil； red-clover silage

来源出版物：Animal， 2013， 7：132-162联系邮箱：Shingfield， KJ； kevin.shingfield@mtt.fi

被引频次：30

Genomic imputation and evaluation using high-density Holstein genotypes

VanRaden， PM； Null， DJ； Sargolzaei， M； et al.

Abstract：Genomic evaluations for 161341 Holsteins were computed by using 311725 of 777962 markers on the IIlumina BovineHD Genotyping BeadChip（HD）. Initial edits with 1741 HD genotypes from 5 breeds revealed that 636967 markers were usable but that half were redundant. Holstein genotypes were from 1510 animals with HD markers， 82358 animals with 45187（50K） markers， 1797 animals with 8031（8K） markers， 20177 animals with 6836（6K） markers， 52270 animals with 2683（3K） markers； and 3229 nongenotyped dams（OK）with ＞90% of haplotypes imputable because they had 4 or more genotyped progeny. The Holstein HD genotypes were from 1142 US， Canadian， British； and Italian sires， 196 other sires， 138 cows in a US Department of Agriculture research herd（Beltsville； MD）， and 34 other females. Percentages of correctly imputed genotypes were tested by applying the programs findhap and FImpute to a simulated chromosome for an earlier population that had only 1112 animals with HD genotypes and none with 8K genotypes. For each chip， 1% of the genotypes were missing and 0.02% were incorrect initially. After imputation of missing markers with findhap； percentages of genotypes cor-rect were 99.9% from HD； 99.0% from 50K， 94.6% from 6K， 90.5% from 3K， and 93.5% from OK. With FImpute， 99.96% were correct from HD， 99.3% from 50K， 94.7% from 6K， 91.1% from 3K， and 95.1% from OK genotypes. Accuracy for the 3K and 6K genotypes further improved by approximately 2 percentage points if imputed first to 50K and then to HD instead of imputing all genotypes directly to HD. Evaluations were tested by using imputed actual genotypes and August 2008 phenotypes to predict deregressed evaluations of US bulls proven after August 2008. For 28 traits tested； the estimated genomic reliability averaged 61.1% when using 311725 markers vs. 60.7% when using 45187 markers vs. 29.6% from the traditional parent average. Squared correlations with future data were slightly greater for 16 traits and slightly less for 12 with HD than with 50K evaluations. The observed 0.4 percentage point average increase in reliability was less favorable than the 0.9 expected from simulation but was similar to actual gains from other HD studies. The largest HD and 50K marker effects were often located at very similar positions. The single-breed evaluation tested here and previous single-breed or multibreed evaluations have not produced large gains. Increasing the number of HD genotypes used for imputation above 1；074 did not improve the reliability of Holstein genomic evaluations.

Keywords：predictions； traits； panels

来源出版物：Journal of Dairy Science， 2013， 96（1）：668-678联系邮箱：VanRaden， PM； paul.vanraden@ars.usda.gov

被引频次：29

Prospects from agroecology and industrial ecology for animal production in the 21st century

Dumont， B； Fortun-Lamothe， L； Jouven， M； et al.

Abstract：Agroecology and industrial ecology can be viewed as complementary means for reducing the environmental footprint of animal farming systems：agroecology mainly by stimulating natural processes to reduce inputs， and industrial ecology by closing system loops，thereby reducing demand for raw materials， lowering pollution and saving on waste treatment. Surprisingly， animal farming systems have so far been ignored in most agroecological thinking. On the basis of a study by Altieri， who identified the key ecological processes to be optimized， we propose five principles for the design of sustainable animal production systems：（i） adopting management practices aiming to improve animal health，（ii） decreasing the inputs needed for production，（iii） decreasing pollution by optimizing the metabolic functioning of farming systems，（iv） enhancing diversity within animal production systems to strengthen their resilience and（v） preserving biological diversity in agroecosystems by adapting management practices. We then discuss how these different principles combine to generate environmental， social and economic performance in six animal production systems（ruminants， pigs， rabbits and aquaculture） covering a long gradient of intensification. The two principles concerning economy of inputs and reduction of pollution emerged in nearly all the case studies， a finding that can be explained by the economic and regulatory constraints affecting animal production. Integrated management of animal health was seldom mobilized， as alternatives to chemical drugs have only recently been investigated， and the results are not yet transferable to farming practices. A number of ecological functions and ecosystem services（recycling of nutrients， forage yield， pollination，resistance to weed invasion， etc.） are closely linked to biodiversity， and their persistence depends largely on maintaining biological diversity in agroecosystems. We conclude that the development of such ecology-based alternatives for animal production implies changes in the positions adopted by technicians and extension services， researchers and policymakers. Animal production systems should not only be considered holistically， but also in the diversity of their local and regional conditions. The ability of farmers to make their own decisions on the basis of the close monitoring of system performance is most important to ensure system sustainability.

Keywords：recirculating aquaculture systems； crop-livestock systems； life-cycle assessment； carp cyprinus-carpio； farming systems； grazing intensity； sustainable aquaculture； pollinating insects； species richness； food-production

来源出版物：Animal， 2013， 7（6）：1028-1043联系邮箱：Dumont， B； bertrand.dumont@clermont.inra.fr

被引频次：24

Gastrointestinal health and function in weaned pigs：a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds

Heo， JM； Opapeju， FO； Pluske， JR； et al.

Abstract：For the last several decades， antimicrobial compounds have been used to promote piglet growth at weaning through the prevention of subclinical and clinical disease. There are， however， increasing concerns in relation to the development of antibiotic-resistant bacterial strains and the potential of these and associated resistance genes to impact on human health. As a consequence， European Union（EU）banned the use of antibiotics as growth promoters in swine and livestock production on 1 January 2006. Furthermore， minerals such as zinc（Zn） and copper（Cu） are not feasible alternatives/replacements to antibiotics because their excretion is a possible threat to the environment. Consequently， there is a need to develop feeding programs to serve as a means for controlling problems associated with the weaning transition without using antimicrobial compounds. This review， therefore， is focused on some of nutritional strategies that are known to improve structure and function of gastrointestinal tract and（or） promote post-weaning growth with special emphasis on probiotics， prebiotics， organic acids， trace minerals and dietary protein source and level.

Keywords：enterotoxigenic escherichia-coli； conjugated linoleic-acid； antibiotic growth promoters； small-intestinal morphology； me-dium-chain triglycerides； digestive enzyme-activity； spray-dried porcine； cereal nonstarch polysaccharides； receptor gene-expression； human colonic microbiota

来源出版物：Journal of Animal Physiology and Animal Nutrition， 2013， 97（2）：207-237

联系邮箱：Nyachoti， CM； nyachoti@cc.umanitoba.ca

被引频次：22

Accuracy of prediction of genomic breeding values for residual feed intake and carcass and meat quality traits in Bos taurus， Bos indicus， and composite beef cattle

Bolormaa， S； Pryce， JE； Kemper， K； et al.

Abstract：The aim of this study was to assess the accuracy of genomic predictions for 19 traits including feed efficiency， growth， and carcass and meat quality traits in beef cattle. The 10181 cattle in our study had real or imputed genotypes for 729068 SNP although not all cattle were measured for all traits. Animals included Bos taurus， Brahman， composite， and crossbred animals. Genomic EBV（GEBV） were calculated using 2 methods of genomic prediction ［BayesR and genomic BLUP（GBLUP）［ either using a common training dataset for all breeds or using a training dataset comprising only animals of the same breed. Accuracies of GEBV were assessed using 5-fold cross-validation. The accuracy of genomic prediction varied by trait and by method. Traits with a large number of recorded and genotyped animals and with high heritability gave the greatest accuracy of GEBV. Using GBLUP， the average accuracy was 0.27 across traits and breeds， but the accuracies between breeds and between traits varied widely. When the training population was restricted to animals from the same breed as the validation population， GBLUP accuracies declined by an average of 0.04. The greatest decline in accuracy was found for the 4 composite breeds. The BayesR accuracies were greater by an average of 0.03 than GBLUP accuracies， particularly for traits with known genes of moderate to large effect mutations segregating. The accuracies of 0.43 to 0.48 for IGF-I traits were among the greatest in the study. Although accuracies are low compared with those observed in dairy cattle， genomic selection would still be beneficial for traits that are hard to improve by conventional selection， such as tenderness and residual feed intake. BayesR identified many of the same quantitative trait loci as a genomewide association study but appeared to map them more precisely. All traits appear to be highly polygenic with thousands of SNP independently associated with each trait.

Keywords：single nucleotide polymorphism； phenotypic characterization； genotypes； tenderness； multibreed； efficiency； temperate； genetics； descent； impact

来源出版物：Journal of Animal Science， 2013， 91（7）：3088-3104联系邮箱：Bolormaa， S； bolormaa.sunduimijid@dpi.vic.gov.au

Agriculture Multidisciplinary 综合农业

被引频次：55

The knowns， known unknowns and unknowns of sequestration of soil organic carbon

Stockmann， U； Adams， MA； Crawford， JW； et al.

Abstract：Soil contains approximately 2344 Gt（1 gigaton = 1 billion tonnes） of organic carbon globally and is the largest terrestrial pool of organic carbon. Small changes in the soil organic carbon stock could result in significant impacts on the atmospheric carbon concentration. The fluxes of soil organic carbon vary in response to a host of potential environmental and anthropogenic driving factors. Scientists worldwide are contemplating questions such as：What is the average net change in soil organic carbon due to environmental conditions or management practices？ How can soil organic carbon sequestration be enhanced to achieve some mitigation of atmospheric carbon dioxide？ and Will this secure soil quality？ These questions are far reaching， because maintaining and improving the world's soil resource is imperative to providing sufficient food and fibre to a growing population. Additional challenges are expected through climate change and its potential to increase food shortages. This review highlights knowledge of the amount of carbon stored in soils globally， and the potential for carbon sequestration in soil. It also discusses successful methods and models used to determine and estimate carbon pools and fluxes. This knowledge and technology underpins decisions to protect the soil resource.

Keywords：land-use change； microbial community structure； natural c-13 abundance； matter dynamics； litter decomposition； climate-change； nitrogen mineralization； temperature sensitivity； environmental-change； agricultural soils

来源出版物：Agriculture Ecosystems & Environment， 2013， 164：80-99联系邮箱：Stockmann， U； uta.stockmann@sydney.edu.au

被引频次：24

Using sediment tracing to assess processes and spatial patterns of erosion in grazed rangelands，Burdekin River basin， Australia

Wilkinson， SN； Hancock， GJ； Bartley， R； et al.

Abstract：Identifying how agricultural practices can be changed to reduce sediment loss requires knowledge of the erosion processes and spatial areas contributing to end of catchment sediment loads. The Burdekin River basin in northeast Australia is a priority for such knowledge because of its large size（130000 km2）， ongoing public investment in changing agricultural practices， and because sediment exportsare known to affect the health of a significant aquatic ecosystem， the Great Barrier Reef（GBR）. This study applied sediment tracing techniques within the Burdekin River basin to identify the contributions of surface versus subsurface soil， and spatial areas to fine sediment export. Tracer properties included fallout radionuclides and geochemistry. The contributions of each sediment source to river sediment were identified with 95% confidence intervals using a Monte-Carlo numerical mixing model. Between 77% and 89% of fine sediment loss in the study area was derived from subsurface soil sources. High-resolution monitoring of river suspended sediment concentrations indicated that sediment sources were in close proximity to the drainage network， since concentrations were higher on the rising limb than the falling limb of large hydrographs. Gully erosion is likely to be the dominant subsurface soil erosion process， although channel bank erosion and hillslope filling cannot be discounted. The results contrast with previous sediment budget spatial modelling， which predicted that hillslope erosion was the dominant sediment source in the area， thus demonstrating the need to independently verify modelling predictions where input datasets are poor. The contribution of surface soil to river sediment was generally similar between catchments which were currently grazed and two catchments where livestock grazing ceased 7 years ago. Concurrent increases in vegetation cover in the non-grazed catchments indicate that surface erosion rates had declined， suggesting that subsurface soil erosion rates had also declined by a similar amount. The estimated contributions of spatial source areas within the large study catchments had narrower confidence intervals when source areas were defined using sediment from geologically distinct river tributaries， rather than using soil sampled from geological units in the catchment， since tributary sediment had less-variable geochemistry than catchment soil. Programs to reduce fine sediment losses from the Burdekin River basin should primarily focus on reducing sub-surface soil erosion proximal to the basin's drainage network. Understanding the biophysical processes of pollutant generation is important to help guide on-ground activities to improve water quality.

Keywords：great-barrier-reef； grazing land management； suspended sediment； fallout radionuclides； gully erosion； water-quality； catchment； coral； queensland； impacts

来源出版物：Agriculture Ecosystems & Environment， 2013， 180：90-102联系邮箱：Wilkinson， SN； scott.wilkinson@csiro.au

被引频次：24

Does landscape composition affect pest abundance and their control by natural enemies？ A review

Veres， A； Petit， S； Conord， C； et al.

Abstract：Landscape management could contribute to sustainable pest control. Landscape composition， in particular， could either directly impact a pest abundance by affecting its dispersal， mortality or reproduction， or indirectly by affecting its natural enemies. We performed an analysis of the scientific literature to assess how the proportion of different land covers at the landscape level is related to the abundance of pests or to their control by natural enemies. Of 72 independent case studies， 45 reported an effect of landscape composition. Results confirmed the suspected suppressive effect of landscape scale amounts of semi-natural areas on in-field pests：landscapes with higher proportions of semi-natural areas exhibited lower pest abundance or higher pest control in fields. Contrarily， there was no clear direction in relationships between pests and pest control and landscape when the latter was described as the overall proportion of cultivated area or as that of crops host to particular pests. The analysis of original articles indicates that this lack of direction may be due to the diversity of land use intensity in the studied landscapes and to a too rough categorizing of land covers. This pleads for a better consideration of the functionality of crops and of their management in landscapes.

Keywords：winter oilseed rape； biological-control； land-use； agricultural landscapes； parasitoid interactions； ecosystem service； farming practices； biodiversity； diversity； agroecosystems

来源出版物：Agriculture Ecosystems & Environment， 2013， 166：110-117联系邮箱：Lavigne， C； Claire.lavigne@avignon.inra.fr

被引频次：23

Nitrogen losses from the soil/plant system：a review

Cameron， KC； Di， HJ； Moir， JL

Abstract：Losses of nitrogen from the soil/plant system not only reduce soil fertility and plant yield but can also create adverse impacts on the environment. Ammonia emissions into the atmosphere contribute to acid rain and represent an indirect source of nitrous oxide greenhouse gas emissions. Nitrate leaching losses into rivers and lakes can cause eutrophication resulting in excessive growth of aquatic weeds and algae， which can reduce fish populations and the recreational value of the water. Nitrate contamination of drinking water supplies can cause health risks. Legislation that is designed to limit nitrate leaching losses from land has become a constraint on agricultural land use in many countries. Nitrous oxide emissions into the atmosphere contribute to the depletion of the ozone layer and also make a significant contribution to climate change. This review describes the nitrogen cycle in temperate soil/plant systems， the processes involved in each of the individual nitrogen loss pathways， the factors affecting the amounts of losses and the methods that are available to reduce these losses. The review has shown that careful management of temperate soil/plant systems using best management practices and newly developed technologies can increase the sustainability of agriculture and reduce its impact on the environment.

Keywords：nitrification inhibitor dicyandiamide； surface-applied urea； ammonia-oxidizing bacteria； nitrate leaching losses； dairy shed effluent； 3，4-dimethylpyrazole phosphate dmpp； grazed pasture soil； new-zealand pasture； filled pore-space； oxide emissions

来源出版物：Annals of Applied Biology， 2013， 162（2）：145-173联系邮箱：Cameron， KC； keith.cameron@lincoln.ac.nz

被引频次：21

Concentrations and Profiles of Bisphenol A and Other Bisphenol Analogues in Foodstuffs from the United States and Their Implications for Human Exposure

Liao， CY； Kannan， K

Abstract：As the concern over the safety of bisphenol A（BPA） continues to grow， this compound is gradually being replaced， in industrial applications， with compounds such as bisphenol F（BPF） and bisphenol S（BPS）. Occurrence of bisphenols， including BPA and BPS， has been reported in paper products and in environmental matrices. Information on the occurrence of bisphenols， other than BPA， in foodstuffs，however， is scarce. In this study， several bisphenol analogues， including BPA， BPF， and BPS， were analyzed in foodstuffs（N = 267） collected from Albany， NY， USA， using high-performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS）. Foodstuffs were divided into nine categories of beverages， dairy products， fats and oils， fish and seafood， cereals， meat and meat products， fruits， vegetables， and "others". Bisphenols were found in the majority（75%） of the food samples， and the total concentrations of bisphenols（Sigma BPs：sum of eight bisphenols） were in the range of below the limit of quantification（LOQ） to 1130 ng/g fresh weight， with an overall mean value of 4.38 ng/g. The highest overall mean concentration of Sigma BPs was found in the "others" category， which included condiments（preserved， ready-to-serve foods）. A sample of mustard（dressing） and ginger， placed in the category of vegetables， contained the highest concentrations of 1130 ng/g for bisphenol F（BPF） and 237 ng/g for bisphenol P（BPP）. Concentrations of BPs in beverages（mean = 0.341 ng/g） and fruits（0.698 ng/g） were low. The predominant bisphenol analogues found in foodstuffs were BPA and BPF， which accounted for 42 and 17% of the total BP concentrations， respectively. Canned foods contained higher concentrations of individual and total bisphenols in comparison to foods sold in glass， paper， or plastic containers. On the basis of measured concentrations and daily ingestion rates of foods，the daily dietary intakes of bisphenols（calculated from the mean concentration） were estimated to be 243， 142， 117， 63.6， and 58.6 ng/kg body weight（bw）/day for toddlers， infants， children， teenagers， and adults， respectively.

Keywords：chromatography-mass spectrometry； diglycidyl ether bfdge； liquid infant formula； canned foods； polycarbonate baby； water bottles； migration； derivatives； products； dietary

来源出版物：Journal of Agricultural and Food Chemistry， 2013， 61（19）：4655-4662联系邮箱：Kannan， K； kkannan@wadsworth.org

Agronomy 农学

被引频次：76

Climate change， phenology， and phenological control of vegetation feedbacks to the climate system

Richardson， AD； Keenan， TF； Migliavacca， M； et al.

Abstract：Vegetation phenology is highly sensitive to climate change. Phenology also controls many feedbacks of vegetation to the climate system by influencing the seasonality of albedo， surface roughness length， canopy conductance， and fluxes of water， energy， CO2 and biogenic volatile organic compounds. In this review， we first discuss the environmental drivers of phenology， and the impacts of climate change on phenology， in different biomes. We then examine the vegetation-climate feedbacks that are mediated by phenology， and assess the potential impact on these feedbacks of shifts in phenology driven by climate change. We finish with an overview of phenological modeling and we suggest ways in which models might be improved using existing data sets. Several key weaknesses in our current understanding emerge from this analysis. First， we need a better understanding of the drivers of phenology， particularly in under-studied biomes（e.g. tropical forests）. We do not have a mechanistic understanding of the role of photoperiod， even in well-studied biomes. In all biomes， the factors controlling senescence and dormancy are not well-documented. Second， for the most part（i.e. with the exception of phenology impacts on CO2 exchange） we have only a qualitative understanding of the feedbacks between vegetation and climate that are mediated by phenology. We need to quantify the magnitude of these feedbacks， and ensure that they are accurately reproduced by models. Third， we need to work towards a new understanding of phenological processes that enables progress beyond the modeling paradigms currently in use. Accurate representation of phenological processes in models that couple the land surface to the climate system is particularly important，especially when such models are being used to predict future climate.

Keywords：terrestrial biosphere model； net ecosystem productivity； volatile organic-compounds； northern hardwood forest； carbon-dioxide exchange； spring starting earlier； boreal aspen forest； leaf bud burst； deciduous forest； interannual variability

来源出版物：Agricultural and Forest Meteorology， 2013， 169：156-173联系邮箱：Richardson， AD； arichardson@oeb.harvard.edu

被引频次：60

Hyperaccumulators of metal and metalloid trace elements：Facts and fiction

van der Ent， A； Baker， AJM； Reeves， RD； et al.

Abstract：Plants that accumulate metal and metalloid trace elements to extraordinarily high concentrations in their living biomass have inspired much research worldwide during the last decades. Hyperaccumulators have been recorded and experimentally confirmed for ele-ments such as nickel， zinc， cadmium， manganese， arsenic and selenium. However， to date， hyperaccumulation of lead， copper， cobalt，chromium and thallium remain largely unconfirmed. Recent uses of the term in relation to rare-earth elements require critical evaluation.

Since the mid-1970s the term 'hyperaccumulator' has been used millions of times by thousands of people， with varying degrees of precision，aptness and understanding that have not always corresponded with the views of the originators of the terminology and of the present authors. There is therefore a need to clarify the circumstances in which the term 'hyperaccumulator' is appropriate and to set out the conditions that should be met when the terms are used. We outline here the main considerations for establishing metal or metalloid hyperaccumulation status of plants，（re）define some of the terminology and note potential pitfalls.

Unambiguous communication will require the international scientific community to adopt standard terminology and methods for confirming the reliability of analytical data in relation to metal and metalloid hyperaccumulators.

Keywords：rare-earth-elements； thlaspi-caerulescens； arabidopsis-halleri； new-caledonia； cadmium hyperaccumulator； manganese accumulation； nickel accumulation； contaminated soils； hyper-accumulator； ultramafic soils

来源出版物：Plant and Soil， 2013， 362（1-2）：319-334联系邮箱：van der Ent， A； a.vanderent@uq.edu.au

被引频次：54

Improvement of the Oryza sativa Nipponbare reference genome using next generation sequence and optical map data

Kawahara， Y； de la Bastide， M； Hamilton， JP； et al.

Abstract：Rice research has been enabled by access to the high quality reference genome sequence generated in 2005 by the International Rice Genome Sequencing Project（IRGSP）. To further facilitate genomic-enabled research， we have updated and validated the genome assembly and sequence for the Nipponbare cultivar of Oryza sativa（japonica group）.

The Nipponbare genome assembly was updated by revising and validating the minimal tiling path of clones with the optical map for rice. Sequencing errors in the revised genome assembly were identified by re-sequencing the genome of two different Nipponbare individuals using the Illumina Genome Analyzer II/IIx platform. A total of 4886 sequencing errors were identified in 321 Mb of the assembled genome indicating an error rate in the original IRGSP assembly of only 0.15 per 10000 nucleotides. A small number（five） of insertions/deletions were identified using longer reads generated using the Roche 454 pyrosequencing platform. As the re-sequencing data were generated from two different individuals， we were able to identify a number of allelic differences between the original individual used in the IRGSP effort and the two individuals used in the re-sequencing effort. The revised assembly， termed Os-Nipponbare-Reference-IRGSP-1.0， is now being used in updated releases of the Rice Annotation Project and the Michigan State University Rice Genome Annotation Project， thereby providing a unified set of pseudomolecules for the rice community.

A revised， error-corrected， and validated assembly of the Nipponbare cultivar of rice was generated using optical map data， re-sequencing data， and manual curation that will facilitate on-going and future research in rice. Detection of polymorphisms between three different Nipponbare individuals highlights that allelic differences between individuals should be considered in diversity studies.

Keywords：single-nucleotide polymorphisms； rice genome； annotation； dna； association； resolution； alignment； resource； japonica； indica

来源出版物：Rice， 2013， 6：4联系邮箱：Itoh， T； taitoh@affrc.go.jp

被引频次：49

Biochar and its effects on plant productivity and nutrient cycling：a meta-analysis

Biederman， LA； Harpole， WS

Abstract：Biochar is a carbon-rich coproduct resulting from pyrolyzing biomass. When applied to the soil it resists decomposition， effectively sequestering the applied carbon and mitigating anthropogenic CO2emissions. Other promoted benefits of biochar application to soil include increased plant productivity and reduced nutrient leaching. However， the effects of biochar are variable and it remains unclear if recent enthusiasm can be justified. We evaluate ecosystem responses to biochar application with a meta-analysis of 371 independent studies culled from 114 published manuscripts. We find that despite variability introduced by soil and climate， the addition of biochar to soils resulted， on average， in increased aboveground productivity， crop yield， soil microbial biomass， rhizobia nodulation， plant K tissue concentration， soil phosphorus（P）， soil potassium（K）， total soil nitrogen（N）， and total soil carbon（C） compared with control conditions. Soil pH also tended to increase，becoming less acidic， following the addition of biochar. Variables that showed no significant mean response to biochar included belowground productivity， the ratio of aboveground：belowground biomass， mycorrhizal colonization of roots， plant tissue N， and soil P concentration， and soil inorganic N. Additional analyses found no detectable relationship between the amount of biochar added and aboveground productivity. Our results provide the first quantitative review of the effects of biochar on multiple ecosystem functions and the central tendencies suggest that biochar holds promise in being a win-win-win solution to energy， carbon storage， and ecosystem function. However，biochar's impacts on a fourth component， the downstream nontarget environments， remain unknown and present a critical research gap.

Keywords：arbuscular mycorrhizal fungi； soil microbial biomass； coastal-plain soil； climate-change； black carbon； nitrogen-fixation； activated carbon； chemical-properties； charcoal hearths； field experiment

来源出版物：Global Change Biology Bioenergy， 2013， 5（2）：202-214联系邮箱：Biederman， LA； lbied@iastate.edu

被引频次：48

Yield gap analysis with local to global relevance-A review

van Ittersum， MK； Cassman， KG； Grassini， P； et al.

Abstract：Yields of crops must increase substantially over the coming decades to keep pace with global food demand driven by population and income growth. Ultimately global food production capacity will be limited by the amount of land and water resources available and suitable for crop production， and by biophysical limits on crop growth. Quantifying food production capacity on every hectare of current farmland in a consistent and transparent manner is needed to inform decisions on policy， research， development and investment that aim to affect future crop yield and land use， and to inform on-ground action by local farmers through their knowledge networks. Crop production capacity can be evaluated by estimating potential yield and water-limited yield levels as benchmarks for crop production under， respectively，irrigated and rainfed conditions. The differences between these theoretical yield levels and actual farmers' yields define the yield gaps， and precise spatially explicit knowledge about these yield gaps is essential to guide sustainable intensification of agriculture. This paper reviews methods to estimate yield gaps， with a focus on the local-to-global relevance of outcomes. Empirical methods estimate yield potential from 90 to 95th percentiles of farmers' yields， maximum yields from experiment stations， growers' yield contests or boundary functions； these are compared with crop simulation of potential or water-limited yields. Comparisons utilize detailed data sets from western Kenya， Nebraska（USA） and Victoria（Australia）. We then review global studies， often performed by non-agricultural scientists， aimed at yield and sometimes yield gap assessment and compare several studies in terms of outcomes for regions in Nebraska， Kenya and The Netherlands. Based on oar review we recommend key components for a yield gap assessment that can be applied at local to global scales. Given lack of data for some regions， the protocol recommends use of a tiered approach with preferred use of crop growth simulation models applied to relatively homogenous climate zones for which measured weather data are available. Within such zones simulations are performed for the dominant soils and cropping systems considering current spatial distribution of crops. Need for accurate agronomic and current yield data together with calibrated and validated crop models and upscaling methods is emphasized. The bottom-up application of this global protocol allows verification of estimated yield gaps with on-farm data and experiments.

Keywords：crop water productivity； high-resolution； use efficiency； food security； vegetation model； irrigated maize； surface climate；western kenya； weather data； wheat yield

来源出版物：Field Crops Research， 2013， 143：4-17联系邮箱：van Ittersum， MK； martin.vanittersum@wur.nl

Allergy 过敏

被引频次：58

Update on allergy immunotherapy：American Academy of Allergy， Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report

Burks， AW； Calderon， MA； Casale， T； et al.

Abstract：Allergy immunotherapy（AIT） is an effective treatment for allergic asthma and rhinitis， as well as venom-induced anaphylaxis. In addition to reducing symptoms， AIT can change the course of allergic disease and induce allergen-specific immune tolerance. In current clinical practice immunotherapy is delivered either subcutaneously or sublingually； some allergens， such as grass pollen， can be delivered through either route， whereas others， such as venoms， are only delivered subcutaneously. Both subcutaneous and sublingual immunotherapy appear to have a duration of efficacy of up to 12 years， and both can prevent the development of asthma and new allergen sensitivities. In spite of the advances with AIT， safer and more effective AIT strategies are needed， especially for patients with asthma， atopic dermatitis， or food allergy. Novel approaches to improve AIT include use of adjuvants or recombinant allergens and alternate routes of administration. As part of the PRACTALL initiatives， the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy，Asthma & Immunology nominated an expert team to develop a comprehensive consensus report on the mechanisms of AIT and its use in clinical practice， as well as unmet needs and ongoing developments in AIT. This resulting report is endorsed by both academies.

Keywords：grass-pollen immunotherapy； oral tolerance induction； t-regulatory-cells； cows milk allergy； sublingual immunotherapy；double-blind； subcutaneous immunotherapy； rush immunotherapy； systemic reactions； food allergy

来源出版物：Journal of Allergy and Clinical Immunology， 2013， 131（5）：1288-U65联系邮箱：Burks， AW； wburks@email.unc.edu

被引频次：52

Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease

Barnes， PJ

Abstract：Reduced responsiveness to the anti-inflammatory effects of corticosteroids is a major barrier to effective management of asthma in smokers and patients with severe asthma and in the majority of patients with chronic obstructive pulmonary disease（COPD）. The molecular mechanisms leading to steroid resistance are now better understood， and this has identified new targets for therapy. In patients withsevere asthma， several molecular mechanisms have been identified that might account for reduced steroid responsiveness， including reduced nuclear translocation of glucocorticoid receptor（GR） alpha after binding corticosteroids. This might be due to modification of the GR by means of phosphorylation as a result of activation of several kinases（p38 mitogen-activated protein kinase alpha， p38 mitogen-activated protein kinase gamma， and c-Jun N-terminal kinase 1）， which in turn might be due to reduced activity and expression of phosphatases， such as mitogen-activated protein kinase phosphatase 1 and protein phosphatase A2. Other mechanisms proposed include increased expression of GR beta， which competes with and thus inhibits activated GR alpha； increased secretion of macrophage migration inhibitory factor； competition with the transcription factor activator protein 1； and reduced expression of histone deacetylase（HDAC） 2. HDAC2 appears to mediate the action of steroids to switch off activated inflammatory genes， but in patients with COPD， patients with severe asthma， and smokers with asthma， HDAC2 activity and expression are reduced by oxidative stress through activation of phosphoinositide 3-kinase delta. Strategies for managing steroid resistance include alternative anti-inflammatory drugs， but a novel approach is to reverse steroid resistance by increasing HDAC2 expression， which can be achieved with theophylline and phosphoinositide 3-kinase delta inhibitors. Long-acting beta（2）-agonists can also increase steroid responsiveness by reversing GR alpha phosphorylation. Identifying the molecular mechanisms of steroid resistance in asthmatic patients and patients with COPD can thus lead to more effective anti-inflammatory treatments.

Keywords：glucocorticoid-receptor-beta； migration inhibitory factor； blood mononuclear-cells； histone deacetylase 2； inhaled combination therapy； regulatory t-cells； gene-expression； airway inflammation； insensitive asthma； bronchial-asthma

来源出版物：Journal of Allergy and Clinical Immunology， 2013， 131（3）：636-645联系邮箱：Barnes， PJ； p.j.barnes@imperial.ac.uk

被引频次：46

Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis：A prospective study on the food cause of the disease

Lucendo， AJ； Arias， A； Gonzalez-Cervera， J； et al.

Abstract：Background：Although empiric exclusion from the diet of the 6 food groups most likely to trigger allergies achieves eosinophilic esophagitis（EoE） remission in children， data on its prolonged efficacy and effects on adults are lacking.

Objective：We sought to evaluate the efficacy of a 6-food elimination diet in inducing and maintaining prolonged remission in patients with adult EoE.

Methods：Sixty-seven consecutive patients with adult EoE were prospectively recruited and treated exclusively with a diet avoiding cereals，milk， eggs， fish/seafood， legumes/peanuts， and soy for 6 weeks. Subsequent challenge was undertaken by sequentially reintroducing all excluded single foods， followed by endoscopy and biopsies， which were developed every 6 weeks in case of response（eosinophil peak count reduction to ＜15/high-power field ［hpf［）. A food was considered a trigger for EoE and removed from the diet if pathologic eosinophilic infiltration（≥15 eosinophils/hpf） reappeared. Food-specific serum IgE measurements and skin prick tests were performed before initiating the diet.

Results：Forty-nine（73.1%） patients exhibited significantly reduced eosinophil peak counts（＜15 eosinophils/hpf） before sequential single-food reintroduction. A single offending food antigen was identified in 35.71% of patients， 2 food triggers were identified in 30.95%，and 3 or more food triggers were identified in 33.3%. Cow's milk was the most common food antigen（61.9%）， followed by wheat（28.6%），eggs（26.2%）， and legumes（23.8%）. Prior allergy tests showed no concordance with food-reintroduction challenge results. All patients who continued to avoid the offending foods maintained histopathologic and clinical EoE remission for up to 3 years.

Conclusions：An empiric 6-food elimination diet effectively induced remission of active adult EoE， which was maintained for up to 3 years with individually tailored， limited exclusion diets.

Keywords：causative foods； patch tests； skin prick； children； allergy； prevalence； identification； population； therapy

来源出版物：Journal of Allergy and Clinical Immunology， 2013， 131（3）：797-804联系邮箱：Lucendo， AJ； alucendo@vodafone.es

被引频次：44

Sublingual immunotherapy for peanut allergy：A randomized， double-blind，placebo-controlled multicenter trial

Fleischer， DM； Burks， AW； Vickery， BP； et al.

Abstract：Background：There are presently no available therapeutic options for patients with peanut allergy.

Objective：We sought to investigate the safety， efficacy， and immunologic effects of peanut sublingual immunotherapy（SLIT）.

Methods：After a baseline oral food challenge（OFC） of up to 2 g of peanut powder（approximately 50% protein； median successfully consumed dose ［SCD［， 46 mg）， 40 subjects， aged 12 to 37 years（median， 15 years）， were randomized 1：1 across 5 sites to daily peanut or placebo SLIT. A 5-g OFC was performed after 44 weeks， followed by unblinding； placebo-treated subjects then crossed over to higher dose peanut SLIT， followed by a subsequent crossover Week 44 5-g OFC. Week 44 OFCs from both groups were compared with baseline OFCs；subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. Results：After 44 weeks of SLIT， 14（70%） of 20 subjects receiving peanut SLIT were responders compared with 3（15%） of 20 subjects receiving placebo（P ＜0.001）. In peanut SLIT responders， median SCD increased from 3.5 to 496 mg. After 68 weeks of SLIT， median SCDsignificantly increased to 996 mg（compared with Week 44， P =0.05）. The median SCD at the Week 44 Crossover OFC was significantly higher than baseline（603 vs 71 mg， P =0.02）. Seven（44%） of 16 crossover subjects were responders； median SCD increased from 21 to 496 mg among responders. Of 10855 peanut doses through the Week 44 OFCs， 63.1% were symptom free； excluding oral-pharyngeal symptoms， 95.2% were symptom free.

Conclusions：Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo. Longer duration of therapy showed statistically significant increases in the SCD.

Keywords：quality-of-life； oral tolerance induction； hazelnut food allergy； cows milk allergy； natural-history； anaphylactic reactions； resource implications； budget impact； kiwi fruit； children

来源出版物：Journal of Allergy and Clinical Immunology， 2013， 131（1）：119-184

联系邮箱：Fleischer， DM； Fleischerd@njhealth.org

被引频次：43

The multifunctional role of filaggrin in allergic skin disease

McAleer， MA； Irvine， AD

Abstract：Filaggrin is a major structural protein in the stratum corneum of the epidermis. Mutations in the filaggrin gene are the most significant known genetic risk factor for the development of atopic dermatitis. Mutations in the human filaggrin gene（FLG） also confer risk for the associated allergic diseases of food allergy， asthma， and allergic rhinitis. These discoveries have highlighted the importance of skin barrier function in the pathogenesis of atopic diseases and have motivated a surge in research characterizing the filaggrin-deficient skin barrier and its consequences. In this review we discuss the mechanisms through which mutations in this protein contribute to the pathogenesis of atopic dermatitis and associated atopic conditions. We focus on recent human and murine discoveries characterizing the filaggrin-deficient epidermis with respect to biophysical， immunologic， and microbiome abnormalities.

Keywords：thymic stromal lymphopoietin； transepidermal water-loss； down-regulates filaggrin； of-function mutations； in-vivo expression；atopic-dermatitis； staphylococcus-aureus； null mutations； t-cells； epithelial-cells

来源出版物：Journal of Allergy and Clinical Immunology， 2013， 131（2）：280-291联系邮箱：Irvine， AD； irvinea@tcd.ie

Anatomy Morphology 解剖学和形态学

被引频次：31

Hippocampal microRNA-132 mediates stress-inducible cognitive deficits through its acetylcholinesterase target

Shaltiel， G； Hanan， M； Wolf， Y； et al.

Abstract：Diverse stress stimuli induce long-lasting cognitive deficits， but the underlying molecular mechanisms are still incompletely understood. Here， we report three different stress models demonstrating that stress-inducible increases in microRNA-132（miR-132） and consequent decreases in its acetylcholinesterase（AChE） target are causally involved. In a mild model of predator scent-induced anxiety， we demonstrate long-lasting hippocampal elevation of miR-132， accompanied by and associated with reduced AChE activity. Using lentiviral-mediated suppression of "synaptic" AChE-S mRNA， we quantified footshock stress-inducible changes in miR-132 and AChE and its corresponding cognitive damages. Stressed mice showed long-lasting impairments in the Morris water maze. In contrast， pre-stress injected AChE-suppressing lentivirus， but not a control virus， reduced hippocampal levels of both miR-132 and AChE and maintained similar cognitive performance to that of na ＜ ve， non-stressed mice. To dissociate between miR-132 and synaptic AChE-S as potential causes for stress-inducible cognitive deficits， we further used engineered TgR mice with enforced over-expression of the soluble "readthrough" AChE-R variant without the 3'-untranslated region binding site for miR-132. TgR mice displayed excess AChE-R in hippocampal neurons，enhanced c-fos labeling and correspondingly intensified reaction to the cholinergic agonist pilocarpine. They further showed excessive hippocampal expression of miR-132， accompanied by reduced host AChE-S mRNA and the GTPase activator p250GAP target of miR-132. At the behavioral level， TgR mice showed abnormal nocturnal locomotion patterns and serial maze mal-performance in spite of their reduced AChE-S levels. Our findings attribute stress-inducible cognitive impairments to cholinergic-mediated induction of miR-132 and consequently suppressed ACHE-S， opening venues for intercepting these miR-132-mediated damages.

Keywords：long-term potentiation； anterior cingulate cortex； messenger-RNA； readthrough acetylcholinesterase； circadian-clock； fear memory； in-vivo； c-fos； expression； brain

来源出版物：Brain Structure & Function， 2013， 218（1）：59-72联系邮箱：Soreq， H； soreq@cc.huji.ac.il

被引频次：28

Novel sex-determining genes in fish and sex chromosome evolution

Kikuchi， K； Hamaguchi， S

Abstract：Although the molecular mechanisms underlying many developmental events are conserved across vertebrate taxa， the lability atthe top of the sex-determining（SD） cascade has been evident from the fact that four master SD genes have been identified：mammalian Sry；chicken DMRT1； medaka Dmy； and Xenopus laevis DM-W. This diversity is thought to be associated with the turnover of sex chromosomes， which is likely to be more frequent in fishes and other poikilotherms than in therian mammals and birds. Recently， four novel candidates for vertebrate SD genes were reported， all of them in fishes. These include amhy in the Patagonian pejerrey， Gsdf in Oryzias luzonensis， Amhr2 in fugu and sdY in rainbow trout. These studies provide a good opportunity to infer patterns from the seemingly chaotic picture of sex determination systems. Here， we review recent advances in our understanding of the master SD genes in fishes.

Keywords：anti-mullerian hormone； turtle trachemys-scripta； germ-cell proliferation； medaka oryzias-latipes； cytochrome-b gene；dm-domain gene； inhibiting substance； y-chromosome； odontesthes-bonariensis； patagonina-hatcheri

来源出版物：Developmental Dynamics， 2013， 242（4）：339-353联系邮箱：Kikuchi， K； akikuchi@mail.ecc.u-tokyo.ac.jp

被引频次：26

Analysis of the subcomponents and cortical terminations of the perisylvian superior longitudinal fasciculus：a fiber dissection and DTI tractography study

Martino， J； Hamer， PCD； Berger， MS； et al.

Abstract：The anatomy of the perisylvian component of the superior longitudinal fasciculus（SLF） has recently been reviewed by numerous diffusion tensor imaging tractography（DTI） studies. However， little is known about the exact cortical terminations of this tract. The aim of the present work is to isolate the different subcomponents of this tract with fiber dissection and DTI tractography， and to identify the exact cortical connections. Twelve postmortem human hemispheres（6 right and 6 left） were dissected using the cortex-sparing fiber dissection. In addition， three healthy brains were analyzed using DTI-based tractography software. The different components of the perisylvian SLF were isolated and the fibers were followed until the cortical terminations. Three segments of the perisylvian SLF were identified：（1）anterior segment， connecting the supramarginal gyrus and superior temporal gyrus with the precentral gyrus，（2） posterior segment， connecting the posterior portion of the middle temporal gyrus with the angular gyrus， and（3） long segment of the arcuate fasciculus that connects the middle and inferior temporal gyri with the precentral gyrus and posterior portion of the inferior and middle frontal gyri. In the present study， three different components of the perisylvian SLF were identified. For the first time， our dissections revealed that each component was connected to a specific cortical area within the frontal， parietal and temporal lobes. By accurately depicting not only the trajectory but also cortical connections of this bundle， it is possible to develop new insights into the putative functional role of this tract.

Keywords：human brain； white-matter； language pathways； arcuate fasciculus； anatomic dissection； temporal-lobe； in-vivo； occipitofrontal fasciculus； neurocognitive networks； functional-anatomy

来源出版物：Brain Structure & Function， 2013， 218（1）：105-121联系邮箱：Martino， J； juan.martino@hotmail.com

被引频次：24

Predictions not commands：active inference in the motor system

Adams， RA； Shipp， S； Friston， KJ

Abstract：The descending projections from motor cortex share many features with top-down or backward connections in visual cortex； for example， corticospinal projections originate in infragranular layers， are highly divergent and（along with descending cortico-cortical projections） target cells expressing NMDA receptors. This is somewhat paradoxical because backward modulatory characteristics would not be expected of driving motor command signals. We resolve this apparent paradox using a functional characterisation of the motor system based on Helmholtz's ideas about perception； namely， that perception is inference on the causes of visual sensations. We explain behaviour in terms of inference on the causes of proprioceptive sensations. This explanation appeals to active inference， in which higher cortical levels send descending proprioceptive predictions， rather than motor commands. This process mirrors perceptual inference in sensory cortex，where descending connections convey predictions， while ascending connections convey prediction errors. The anatomical substrate of this recurrent message passing is a hierarchical system consisting of functionally asymmetric driving（ascending） and modulatory（descending）connections：an arrangement that we show is almost exactly recapitulated in the motor system， in terms of its laminar， topographic and physiological characteristics. This perspective casts classical motor reflexes as minimising prediction errors and may provide a principled explanation for why motor cortex is agranular.

Keywords：ventral premotor cortex； classical receptive-field； posterior parietal cortex； optimal feedback-control； upper-limb motoneurons；visual cortical areas； free-energy principle； dorsal column nuclei； frontal-lobe inputs； mouse barrel cortex

来源出版物：Brain Structure & Function， 2013， 218（3）：611-643联系邮箱：Adams， RA； rick.adams@ucl.ac.uk

被引频次：24

Frontal terminations for the inferior fronto-occipital fascicle：anatomical dissection，DTI study and functional considerations on a multi-component bundle

Sarubbo， S； De Benedictis， A； Maldonado， IL； et al.

Abstract：The anatomy and functional role of the inferior fronto-occipital fascicle（IFOF） remain poorly known. We accurately analyze itscourse and the anatomical distribution of its frontal terminations. We propose a classification of the IFOF in different subcomponents. Ten hemispheres（5 left， 5 right） were dissected with Klingler's technique. In addition to the IFOF dissection， we performed a 4-T diffusion tensor imaging study on a single healthy subject. We identified two layers of IFOF. The first one is superficial and antero-superiorly directed， terminating in the inferior frontal gyrus. The second is deeper and consists of three portions：posterior， middle and anterior. The posterior component terminates in the middle frontal gyrus（MFG） and dorso-lateral prefrontal cortex. The middle component terminates in the MFG and lateral orbito-frontal cortex. The anterior one is directed to the orbito-frontal cortex and frontal pole. In vivo tractography study confirmed these anatomical findings. We suggest that the distribution of IFOF fibers within the frontal lobe corresponds to a fine functional segmentation. IFOF can be considered as a "multi-function" bundle， with each anatomical subcomponent subserving different brain processing. The superficial layer and the posterior component of the deep layer， which connects the occipital extrastriate， temporobasal and inferior frontal cortices， might subserve semantic processing. The middle component of the deep layer could play a role in a multimodal sensory-motor integration. Finally， the anterior component of the deep layer might be involved in emotional and behavioral aspects.

Keywords：diffusion tensor tractography； white-matter tracts； human brain； prefrontal cortex； fiber tracts； language； association； disconnection； pathways； connectivity

来源出版物：Brain Structure & Function， 2013， 218（1）：21-37联系邮箱：Duffau， H； h-duffau@chu-montpellier.fr

Andrology 男科

被引频次：16

High-energy diets may induce a pre-diabetic state altering testicular glycolytic metabolic profile and male reproductive parameters

Rato， L； Alves， MG； Dias， TR； et al.

Abstract：Diabetes mellitus is a metabolic disorder that may arise from diet habits and is growing to epidemic proportions. Young male diabetic patients present high infertility/subfertility prevalence resulting from impaired reproductive function and poor semen quality. We aimed to evaluate the effects of a high-energy diet（HED） on glucose tolerance/insulin levels and correlate the observed effects on male reproductive function with overall testicular metabolism. After 1month， HED fed rats showed increased glycaemic levels， impaired glucose tolerance and hypoinsulinaemia. Moreover， an imbalance of intratesticular and serum testosterone levels was observed， whereas those of 17-estradiol were not altered. High-energy diet also affected the reproductive parameters， with HED rats exhibiting a significant increase in abnormal sperm morphology. Glycolytic metabolism was favoured in testicles of HED rats with an increased expression of both glucose transporters 1（GLUT1） and 3（GLUT3） and the enzyme phosphofrutokinase 1. Moreover， lactate production and the expression of metabolism-associated genes and proteins involved in lactate production and transport were also enhanced by HED. Alanine testicular content was decreased and thus intratesticular lactate/alanine ratio in HED rats was increased， suggesting increased oxidative stress. Other energetic substrates such as acetate and creatine were not altered in testis from HED rats， but intratesticular glycine content was increased in those animals. Taken together， these results suggest that HED induces a pre-diabetic state that may impair reproductive function by modulating overall testicular metabolism. This is the first report on testicular metabolic features and mechanisms related with the onset of a pre-diabetic state.

Keywords：rat sertoli-cells； diabetes-mellitus； insulin-secretion； glucose-tolerance； oxidative stress； body-weight； in-vitro； transport；hyperglycemia； testis

来源出版物：Andrology， 2013， 1（3）：495-504联系邮箱：Oliveira， PF； pfobox@gmail.com

被引频次：15

Digit ratio（2D：4D） in Klinefelter's syndrome

Manning， JT； Kilduff， LP； Trivers， R

Abstract：The ratio of second to fourth digit length（2D：4D） is a correlate of prenatal testosterone. High 2D：4D is associated with low prenatal testosterone， and reduced sensitivity to testosterone. Klinefelter's syndrome（KS； 47 XXY） affects the endocrine system， such that low testosterone levels are found in KS foetuses， new-borns and adults. To date， there are no published data regarding the pattern of 2D：4D in KS males. Here we consider 2D：4D in KS individuals（n = 51）， their relatives（16 fathers and 15 mothers） and an unaffected control sample of 153 men and 153 women. Adult KS individuals were taller than their fathers and had shorter fingers than fathers and male controls. Compared with fathers， male controls and mothers， KS males had shorter fingers relative to height. With regard to 2D：4D， KS individuals had higher 2D：4D than fathers（right and left hands）， male controls（right and left hands） and mothers（left hands）. Among KS males older than 13 years there were 34 individuals currently prescribed testosterone and nine not prescribed. In comparison to the former， the latter individuals had higher right 2D：4D and higher right-left 2D：4D. We conclude that KS males have mean 2D：4D values similar to those found in female population norms. In addition， testosterone supplementation in KS males may be most common for individuals with low right 2D：4D.

Keywords：androgen receptor polymorphism； finger length； testosterone； 2nd； patterns； males； 2d/4d； inactivation； phenotype； children

来源出版物：Andrology， 2013， 1（1）：94-99联系邮箱：Manning， JT； j.manning@swansea.ac.uk

被引频次：13

Microdissection testicular sperm extraction：an update

Dabaja， AA； Schlegel， PN

Abstract：Patients with non-obstructive azoospermia（NOA） were once considered to be infertile with few treatment options due to the absence of sperm in the ejaculate. In the last two decades， the advent of intracytoplasmic sperm injection（ICSI）， and the application of various testicular sperm retrieval techniques， including fine needle aspiration（FNA）， conventional testicular sperm extraction（TESE） and microdissection testicular sperm extraction（micro-TESE） have revolutionized treatment in this group of men. Because most men with NOA will have isolated regions of spermatogenesis within the testis， studies have illustrated that sperm can be retrieved in most men with NOA， including Klinefelter's syndrome（KS）， prior history of chemotherapy and cryptorchidism. Micro-TESE， when compared with conventional TESE has a higher sperm retrieval rate（SRR） with fewer postoperative complications and negative effects on testicular function. In this article， we will compare the efficacy of the different procedures of sperm extraction， discuss the medical treatment and the role of testosterone optimization in men with NOA and describe the micro-TESE surgical technique. Furthermore， we will update our overall experience to allow counseling on the prognosis of sperm retrieval for the specific subsets of NOA.

Keywords：nonobstructive azoospermia； klinefelter-syndrome； enzymatic digestion； men； injection； tissue； retrieval； spermatogenesis；multiple； spermatozoa

来源出版物：Asian Journal of Andrology， 2013， 15（1）：35-39联系邮箱：Schlegel， PN； pnschleg@med.cornell.edu

被引频次：11

Obesity leads to higher risk of sperm DNA damage in infertile patients

Dupont， C； Faure， C； Sermondade， N； et al.

Abstract：There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity， and conventional semen parameter values seem to be altered in case of high body mass index（BMI）. A few studies assessing the impact of BMI on sperm DNA integrity have been published， but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI， through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling（TUNEL） assay， we observed an increased rate of sperm DNA damage in obese men（odds ratio（95% confidence interval）：2.5（1.2-5.1））.

Keywords：body-mass index； assisted reproductive technology； in-vitro fertilization； blastocyst development； oxidative stress； embryo quality； impact； parameters； integrity； men

来源出版物：Asian Journal of Andrology， 2013， 15（5）：622-625联系邮箱：Dupont， C； charlotte.dupont@jvr.aphp.fr

被引频次：11

Oxidative status in granulosa cells of infertile women undergoing IVF

Karuputhula， NB； Chattopadhyay， R； Chakravarty， B； et al.

Abstract：Studies on elevated reactive oxygen species（ROS） levels in granulosa cells（GC） and its subsequent effect on fertilization are limited. Oxidative stress（OS） mediated alterations in GC of infertile women undergoing in vitro fertilization（IVF） and embryo transfer（ET）was investigated. GC were obtained from 28 women with endometriosis（Group A）， 26 women with polycystic ovary syndrome（PCOS）（Group B）， and 32 women with tubal factor infertility（Group C）. GC characteristics including cell count， viability， morphology and number of oocytes retrieved， and oocyte quality were assessed. OS parameters such as ROS， mitochondrial membrane potential（MMP）， and DNA fragmentation were also studied and IVF outcome parameters assessed. An similar to 20 fold increase in GC ROS generation was observed in Group B as compared to Group C. Though not as high as Group B， Group A also showed significantly high ROS levels compared with Group C. More than 100-fold decrease in MMP in Group B compared with Group C was observed. A similar trend was observed in Group A， where MMP decreased 7 fold. Significant apoptosis was evident in Groups A and B supported by depolarization of MMP and significant increase in DNA damage. IVF outcome parameters including fertilization rate， good quality embryo formation rate， and pregnancy outcome were adversely affected in Group B. It is hypothesized that similar to 20 fold increase in ROS generation in GC of PCOS women plays an adverse role in affecting the IVF success rate. It was of note that the IVF outcome parameters of women with endometriosis were not affected.

Keywords：in-vitro fertilization； polycystic-ovary-syndrome； follicular-fluid； apoptosis； program； proliferation； receptor； quality； oocytes； embryos

来源出版物：Systems Biology in Reproductive Medicine， 2013， 59（2）：91-98联系邮箱：Chaudhury， K； koel@smst.iitkgp.ernet.in

Anesthesiology 麻醉学

被引频次：79

Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

Kozek-Langenecker， SA； Afshari， A； Albaladejo， P； et al.

Abstract：The aims of severe perioperative bleeding management are three-fold. First， preoperative identification by anamesis and labora-tory testing of those patients for whom the perioperative bleeding risk may be increased. Second， implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient's tolerance to bleeding. Third，targeted procoagulant interventions to reduce the amount of bleeding， morbidity， mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology（ESA） formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20664 abstracts. Relevant systematic reviews with meta-analyses， randomised controlled trials， cohort studies， case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee， the Scottish Intercollegiate Guidelines Network（SIGN） grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development， the official position of the ESA changed to favour the Grading of Recommendations Assessment， Development and Evaluation（GRADE） system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete， the Guidelines Committee and ESA Board ratified the guidelines.

Keywords：activated factor-vii； recombinant-factor-viia； prothrombin complex concentrate； fresh-frozen plasma； von-willebrand-disease；red-blood-cell； randomized controlled-trial； orthotopic liver-transplantation； bypass graft-surgery； total hip-replacement

来源出版物：European Journal of Anaesthesiology， 2013， 30（6）：270-382联系邮箱：Kozek-Langenecker， SA； sibylle.kozek@aon.at

被引频次：53

Effects of Fibrinogen Concentrate as First-line Therapy during Major Aortic Replacement Surgery A Randomized， Placebo-controlled Trial

Rahe-Meyer， N； Solomon， C； Hanke， A； et al.

Abstract：Background：Fibrinogen is suggested to play an important role in managing major bleeding. However， clinical evidence regarding the effect of fibrinogen concentrate（derived from human plasma） on transfusion is limited. The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative， targeted， first-line hemostatic therapy in bleeding patients undergoing aortic replacement surgery.

Methods：In this single-center， prospective， placebo-controlled， double-blind study， patients aged 18 yr or older undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to fibrinogen concentrate or placebo， administered intraoperatively. Study medication was given if patients had clinically relevant coagulopathic bleeding immediately after removal from cardiopulmonary bypass and completion of surgical hemostasis. Dosing was individualized using the fibrin-based thromboelastometry test. If bleeding continued， a standardized transfusion protocol was followed.

Results：Twenty-nine patients in the fibrinogen concentrate group and 32 patients in the placebo group were eligible for the efficacy analysis. During the first 24 h after the administration of study medication， patients in the fibrinogen concentrate group received fewer allogeneic blood components than did patients in the placebo group（median， 2 vs. 13 U； P ＜ 0.001； primary endpoint）. Total avoidance of transfusion was achieved in 13（45%） of 29 patients in the fibrinogen concentrate group， whereas 32（100%） of 32 patients in the placebo group received transfusion（P ＜ 0.001）. There was no observed safety concern with using fibrinogen concentrate during aortic surgery.

Conclusions：Hemostatic therapy with fibrinogen concentrate in patients undergoing aortic surgery significantly reduced the transfusion of allogeneic blood products. Larger multicenter studies are necessary to confirm the role of fibrinogen concentrate in the management of perioperative bleeding in patients with life-threatening coagulopathy.

Keywords：cardiopulmonary bypass-surgery； cardiac-surgery； transfusion； plasma； trauma； thromboelastometry； management； thrombocytopenia； cryoprecipitate； hemostasis

来源出版物：Anesthesiology， 2013， 118（1）：40-50联系邮箱：Rahe-Meyer， N； niels.rahe-meyer@franziskus.de

被引频次：47

Protective Mechanical Ventilation during General Anesthesia for Open Abdominal Surgery Improves Postoperative Pulmonary Function

Severgnini， P； Selmo， G； Lanza， C； et al.

Abstract：Background：The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function.

Methods：Prospective randomized， open-label， clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure（standard ventilation strategy） or tidal volumes of 7 ml/kg ideal body weight， 10 cm H2O positiveend-expiratory pressure， and recruitment maneuvers（protective ventilation strategy）. Modified Clinical Pulmonary Infection Score， gas exchange， and pulmonary functional tests were measured preoperatively， as well as at days 1， 3， and 5 after surgery.

Results：Patients ventilated protectively showed better pulmonary functional tests up to day 5， fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1， 3， and 5（mmHg； mean±SD）：77.1±13.0 versus 64.9±11.3（P = 0.0006）， 80.5±10.1 versus 69.7±9.3（P = 0.0002）， and 82.1±10.7 versus 78.5±21.7（P = 0.44） respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups（7 vs. 15% respectively， P=0.42）.

Conclusion：A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.

Keywords：lower tidal volumes； acute lung injury； end-expiratory pressure； respiratory-distress-syndrome； randomized clinical-trial； college-of-physicians； cardiac-surgery； inflammatory response； noncardiothoracic surgery； cardiopulmonary bypass

来源出版物：Anesthesiology， 2013， 118（6）：1307-1321联系邮箱：Severgnini， P； paolo.severgnini@uninsubria.it

被引频次：46

Safety of Modern Starches Used During Surgery

Van Der Linden， P； James， M； Mythen， M； et al.

Abstract：Various hydroxyethyl starch（HES） preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting， especially in patients with septic shock. However， the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus， different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently， we assessed the safety of tetrastarches when used during surgery， using a formal search， that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy（39 trials， 3389 patients）， increased blood loss（38 trials，3280 patients）， allogeneic erythrocyte transfusion（20 trials， 2151 patients； odds ratio for HES transfusion 0.73 ［95% confidence interval = 0.61-0.87［， P = 0.0005）， or increased mortality（odds ratio for HES mortality = 0.51 ［0.24-1.05［， P =0.079）.

Keywords：randomized clinical-trial； major orthopedic-surgery； acute normovolemic hemodilution； impair blood-coagulation； primary hip-arthroplasty； 6-percent hes 130/0.42； hydroxyethyl starch； cardiac-surgery； volume replacement； renal-function

来源出版物：Anesthesia and Analgesia， 2013， 116（1）：35-48联系邮箱：Weiskopf， RB； richardweiskopf@hot-mail.com

被引频次：36

Managing New Oral Anticoagulants in the Perioperative and Intensive Care Unit Setting

Levy， JH； Faraoni， D； Spring， JL； et al.

Abstract：Managing patients in the perioperative setting receiving novel oral anticoagulation agents for thromboprophylaxis or stroke prevention with atrial fibrillation is an important consideration for clinicians. The novel oral anticoagulation agents include direct Factor Xa inhibitors rivaroxaban and apixaban， and the direct thrombin inhibitor dabigatran. In elective surgery， discontinuing their use is important，but renal function must also be considered because elimination is highly dependent on renal elimination. If bleeding occurs in patients who have received these agents， common principles of bleeding management as with any anticoagulant（including the known principles for warfarin） should be considered. This review summarizes the available data regarding the management of bleeding with novel oral anticoagulation agents. Hemodialysis is a therapeutic option for dabigatran-related bleeding， while in vitro studies showed that prothrombin complex concentrates are reported to be useful for rivaroxaban-related bleeding. Additional clinical studies are needed to determine the best method for reversal of the novel oral anticoagulation agents when bleeding occurs.

Keywords：direct thrombin inhibitor； prothrombin complex concentrate； factor xa inhibitors； nonvalvular atrial-fibrillation； total knee arthroplasty； vitamin-k antagonists； activated factor-vii； dabigatran etexilate； renal impairment； venous thromboembolism

来源出版物：Anesthesiology， 2013， 118（6）：1466-1474联系邮箱：Levy， JH； docmd2@yahoo.com

Astronomy Astrophysics 天文学与天体物理学

被引频次：600

Nine-year wilkinson microwave anisotropy probe（wmap） observations：cosmological parameter results

Hinshaw， G； Larson， D； Komatsu， E； et al.

Abstract：We present cosmological parameter constraints based on the final nine-year Wilkinson Microwave Anisotropy Probe（WMAP）data， in conjunction with a number of additional cosmological data sets. The WMAP data alone， and in combination， continue to be re-markably well fit by a six-parameter Delta CDM model. When WMAP data are combined with measurements of the high-l cosmic microwave background anisotropy， the baryon acoustic oscillation scale， and the Hubble constant， the matter and energy densities， Omega（b）h（2），Omega（c）h（2）， and Omega（Lambda）， are each determined to a precision of similar to 1.5%. The amplitude of the primordial spectrum is measured to within 3%， and there is now evidence for a tilt in the primordial spectrum at the 5 sigma level， confirming the first detection of tilt based on the five-year WMAP data. At the end of the WMAP mission， the nine-year data decrease the allowable volume of the six-dimensional Delta CDM parameter space by a factor of 68，000 relative to pre-WMAP measurements. We investigate a number of data combinations and show that their Delta CDM parameter fits are consistent. New limits on deviations from the six-parameter model are presented， for example：the fractional contribution of tensor modes is limited to r ＜ 0.13（95% CL）； the spatial curvature parameter is limited to Omega（k） = -0.0027（-0.0038）（+0.0039）； the summed mass of neutrinos is limited to Sigma m（nu）＜ 0.44 eV（95% CL）； and the number of relativistic species is found to lie within N-eff = 3.84 +/- 0.40， when the full data are analyzed. The joint constraint on N-eff and the primordial helium abundance， Y-He， agrees with the prediction of standard big bang nucleosynthesis. We compare recent Planck measurements of the Sunyaev-Zel' dovich effect with our seven-year measurements， and show their mutual agreement. Our analysis of the polarization pattern around temperature extrema is updated. This confirms a fundamental prediction of the standard cosmological model and provides a striking illustration of acoustic oscillations and adiabatic initial conditions in the early universe.

Keywords：baryon acoustic-oscillations； south-pole telescope； digital sky survey； supernova legacy survey； hubble-space-telescope； background power spectrum； brightest cluster sample； massive galaxy clusters； ia supernovae； dark energy

来源出版物：Astrophysical Journal Supplement Series， 2013， 208（2）联系邮箱：Hinshaw， G； hinshaw@physics.ubc.ca

被引频次：282

Nine-year wilkinson microwave anisotropy probe（wmap） observations：final maps and results

Bennett， CL； Larson， D； Weiland， JL； et al.

Abstract：We present the final nine-year maps and basic results from the Wilkinson Microwave Anisotropy Probe（WMAP） mission. The full nine-year analysis of the time-ordered data provides updated characterizations and calibrations of the experiment. We also provide new nine-year full sky temperature maps that were processed to reduce the asymmetry of the effective beams. Temperature and polarization sky maps are examined to separate cosmic microwave background（CMB） anisotropy from foreground emission， and both types of signals are analyzed in detail. We provide new point source catalogs as well as new diffuse and point source foreground masks. An updated template-removal process is used for cosmological analysis； new foreground fits are performed， and new foreground reduced CMB maps are presented. We now implement an optimal C-1 weighting to compute the temperature angular power spectrum. The WMAP mission has resulted in a highly constrained Delta CDM cosmological model with precise and accurate parameters in agreement with a host of other cosmological measurements. When WMAP data are combined with finer scale CMB， baryon acoustic oscillation， and Hubble constant measurements， we find that big bang nucleosynthesis is well supported and there is no compelling evidence for a non-standard number of neutrino species（N-eff = 3.84±0.40）. The model fit also implies that the age of the universe is t（0） = 13.772±0.059 Gyr， and the fit Hubble constant is H-0 = 69.32±0.80 km s-1Mpc-1. Inflation is also supported：the fluctuations are adiabatic， with Gaussian random phases； the detection of a deviation of the scalar spectral index from unity， reported earlier by the WMAP team， now has high statistical significance（n（s） = 0.9608±0.0080）； and the universe is close to flat/Euclidean（Omega（k） = -0.0027（-0.0038）（+0.0039））. Overall， the WMAP mission has resulted in a reduction of the cosmological parameter volume by a factor of 68000 for the standard six-parameter Delta CDM model，based on CMB data alone. For a model including tensors， the allowed seven-parameter volume has been reduced by a factor 117000. Other cosmological observations are in accord with the CMB predictions， and the combined data reduces the cosmological parameter volume even further. With no significant anomalies and an adequate goodness of fit， the inflationary flat Delta CDM model and its precise and accurate parameters rooted in WMAP data stands as the standard model of cosmology.

Keywords：nrao pmn surveys； observations cosmological interpretation； galactic foreground emission； systematic-error limits； angular power spectrum； point-source search； h-alpha emission； source catalog； radiometer characterization； background anisotropies

来源出版物：Astrophysical Journal Supplement Series， 2013， 208（2）联系邮箱：Bennett， CL； cbennett@jhu.edu

被引频次：245

Planetary candidates observed by kepler. iii. analysis of the first 16 months of data

Batalha， NM； Rowe， JF； Bryson， ST； et al.

Abstract：New transiting planet candidates are identified in 16 months（2009 May-2010 September） of data from the Kepler spacecraft. Nearly 5000 periodic transit-like signals are vetted against astrophysical and instrumental false positives yielding 1108 viable new planet candidates， bringing the total count up to over 2300. Improved vetting metrics are employed， contributing to higher catalog reliability. Most notable is the noise-weighted robust averaging of multiquarter photo-center offsets derived from difference image analysis that identifies likely background eclipsing binaries. Twenty-two months of photometry are used for the purpose of characterizing each of the candidates. Ephemerides（transit epoch， T-0， and orbital period， P） are tabulated as well as the products of light curve modeling：reduced radius（R-P /R-star）， reduced semimajor axis（d / R-star）， and impact parameter（b）. The largest fractional increases are seen for the smallest planet candidates（201% for candidates smaller than 2R（circle plus）. compared to 53% for candidates larger than 2R.） and those at longer orbital periods（124% for candidates outside of 50 day orbits versus 86% for candidates inside of 50 day orbits）. The gains are larger than expected from increasing the observing window from 13 months（Quarters 1-5） to 16 months（Quarters 1-6） even in regions of parameter space where one would have expected the previous catalogs to be complete. Analyses of planet frequencies based on previous catalogs will be affected by such incompleteness. The fraction of all planet candidate host stars with multiple candidates has grown from 17% to 20%， and the paucity of short-period giant planets in multiple systems is still evident. The progression toward smaller planets at longer orbital periods with each new catalog release suggests that Earth-size planets in the habitable zone are forthcoming if， indeed， such planets are abundant.

Keywords：solar-type stars； sun-like star； target stars； eclipsing binaries； habitable planets； input catalog； data release； low-mass； systems；metallicities

来源出版物：Astrophysical Journal Supplement Series， 2013， 204（2）：24联系邮箱：Batalha， NM； Natalie.Batalha@nasa.gov

被引频次：164

The baryon oscillation spectroscopic survey of SDSS-III

Dawson， KS； Schlegel， DJ； Ahn， CP； et al.

Abstract：The Baryon Oscillation Spectroscopic Survey（BOSS） is designed to measure the scale of baryon acoustic oscillations（BAO） in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large-scale structure. BOSS uses 1.5 million luminous galaxies as faint as i = 19.9 over 10000 deg（2） to measure BAO to redshifts z ＜ 0.7. Observations of neutral hydrogen in the Ly alpha forest in more than 150，000 quasar spectra（g ＜ 22） will constrain BAO over the redshift range 2.15 ＜ z ＜ 3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Ly alpha forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance d（A） to an accuracy of 1.0% at redshifts z =0.3 and z =0.57 and measurements of H（z） to 1.8% and 1.7% at the same redshifts. Forecasts for Ly alpha forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate D-A（z） and H-1（z） parameters to an accuracy of 1.9% at z similar to 2.5 when the survey is complete. Here， we provide an overview of the selection of spectroscopic targets， planning of observations， and analysis of data and data quality of BOSS.

Keywords：digital-sky-survey； ly-alpha forest； broad-absorption-line； luminous red galaxies； active galactic nuclei； large-area telescope；principal component analysis； quasar target selection； high-redshift quasars； probing dark energy

来源出版物：Astronomical Journal， 2013， 145（1）：10联系邮箱：Dawson， KS； kdawson@astro.utah.edu

被引频次：149

The average star formation histories of galaxies in dark matter halos from z=0-8

Behroozi， PS； Wechsler， RH； Conroy， C

Abstract：We present a robust method to constrain average galaxy star formation rates（SFRs）， star formation histories（SFHs）， and the intracluster light（ICL） as a function of halo mass. Our results are consistent with observed galaxy stellar mass functions， specific star formation rates（SSFRs）， and cosmic star formation rates（CSFRs） from z = 0 to z = 8. We consider the effects of a wide range of uncertainties on our results， including those affecting stellar masses， SFRs， and the halo mass function at the heart of our analysis. As they are relevant to our method， we also present new calibrations of the dark matter halo mass function， halo mass accretion histories， and halo-subhalo merger rates out to z = 8. We also provide new compilations of CSFRs and SSFRs； more recent measurements are now consistent with the buildup of the cosmic stellar mass density at all redshifts. Implications of our work include：halos near 10（12） M-circle dot are the most efficient at forming stars at all redshifts， the baryon conversion efficiency of massive halos drops markedly after z similar to 2.5（consistent with theories of cold-mode accretion）， the ICL for massive galaxies is expected to be significant out to at least z similar to 1-1.5， and dwarf galaxies at low redshifts have higher stellar mass to halo mass ratios than previous expectations and form later than in most theoretical models. Finally， we provide new fitting formulae for SFHs that are more accurate than the standard declining tau model. Our approach places a wide variety of observations relating to the SFH of galaxies into a self-consistent framework based on the modern understanding of structure formation in Lambda CDM. Constraints on the stellar mass-halo mass relationship and SFRs are available for download online.

Keywords：stellar mass function； brightest cluster galaxies； lyman-break galaxies； observations cosmological interpretation； extragalactic legacy survey； uv luminosity function； formation rate density； early release science； k-selected galaxies； medium-band survey

来源出版物：Astrophysical Journal， 2013， 770（1）：57

Automation Control Systems 自动化与控制系统

被引频次：134

Data-driven monitoring for stochastic systems and its application on batch process

Yin， S； Ding， SX； Sari， AHA； et al.

Abstract：Batch processes are characterised by a prescribed processing of raw materials into final products for a finite duration and play animportant role in many industrial sectors due to the low-volume and high-value products. Process dynamics and stochastic disturbances are inherent characteristics of batch processes， which cause monitoring of batch processes a challenging problem in practice. To solve this problem， a subspace-aided data-driven approach is presented in this article for batch process monitoring. The advantages of the proposed approach lie in its simple form and its abilities to deal with stochastic disturbances and process dynamics existing in the process. The kernel density estimation， which serves as a non-parametric way of estimating the probability density function， is utilised for threshold calculation. An industrial benchmark of fed-batch penicillin production is finally utilised to verify the effectiveness of the proposed approach.

Keywords：principal component analysis； subspace identification； fault-detection； missing measurements； model； diagnosis； pca

来源出版物：International Journal of Systems Science， 2013， 44（7）：1366-1376联系邮箱：Yin， S； shen.yin@uni-due.de

被引频次：119

Real-Time Implementation of Fault-Tolerant Control Systems With Performance Optimization

Yin， S； Luo， H； Ding， SX

Abstract：In this paper， two online schemes for an integrated design of fault-tolerant control（FTC） systems with application to Tennessee Eastman（TE） benchmark are proposed. Based on the data-driven design of the proposed fault-tolerant architecture whose core is an observer/residual generator based realization of the Youla parameterization of all stabilization controllers， FTC is achieved by an adaptive residual generator for the online identification of the fault diagnosis relevant vectors， and an iterative optimization method for system performance enhancement. The performance and effectiveness of the proposed schemes are demonstrated through the TE benchmark model.

Keywords：diagnosis； drives； identification； strategies； design

来源出版物：IEEE Transactions on Industrial Electronics， 2014， 61（5）：2402-2411联系邮箱：Yin， S； shen.yin2011@googlemail.com

被引频次：93

Adaptive Sliding-Mode Control for Nonlinear Active Suspension Vehicle Systems Using T-S Fuzzy Approach

Li， HY； Yu， JY； Hilton， C； et al.

Abstract：This paper deals with the adaptive sliding-mode control problem for nonlinear active suspension systems via the Takagi-Sugeno（T-S） fuzzy approach. The varying sprung and unsprung masses， the unknown actuator nonlinearity， and the suspension performances are taken into account simultaneously， and the corresponding mathematical model is established. The T-S fuzzy system is used to describe the original nonlinear system for the control-design aim via the sector nonlinearity approach. A sufficient condition is proposed for the asymptotical stability of the designing sliding motion. An adaptive sliding-mode controller is designed to guarantee the reachability of the specified switching surface. The condition can be converted to the convex optimization problems. Simulation results for a half-vehicle active suspension model are provided to demonstrate the effectiveness of the proposed control schemes.

Keywords：h-infinity control； time-delay； car model； feedback； design

来源出版物：IEEE Transactions on Industrial Electronics， 2013， 60（8）：3328-3338联系邮箱：Li， HY； lihongyi2009@gmail.com

被引频次：86

Network-Induced Constraints in Networked Control Systems-A Survey

Zhang， LX； Gao， HJ； Kaynak， O

Abstract：Networked control systems（NCSs） have， in recent years， brought many innovative impacts to control systems. However， great challenges are also met due to the network-induced imperfections. Such network-induced imperfections are handled as various constraints，which should appropriately be considered in the analysis and design of NCSs. In this paper， the main methodologies suggested in the literature to cope with typical network-induced constraints， namely time delays， packet losses and disorder， time-varying transmission intervals，competition of multiple nodes accessing networks， and data quantization are surveyed； the constraints suggested in the literature on the first two types of constraints are updated in different categorizing ways； and those on the latter three types of constraints are extended.

Keywords：limited information feedback； input-output stability； to-state stability； h-infinity control； linear-systems； predictive control；special-issue； communication delays； nonlinear-systems； packet drop

来源出版物：IEEE Transactions on Industrial Informatics， 2013， 9（1）：403-416联系邮箱：Zhang， LX； lixianzhango@hit.edu.cn

被引频次：69

Distributed H-infinity Filtering for a Class of Markovian Jump Nonlinear Time-Delay Systems Over Lossy Sensor Networks

Dong， HL； Wang， ZD； Gao， HJ

Abstract：This paper is concerned with the distributed H-infinity filtering problem for a class of discrete-time Markovian jump nonlinear time-delay systems with deficient statistics of mode transitions. The system measurements are collected through a lossy sensor networksubject to randomly occurring quantization errors and randomly occurring packet dropouts. The description of deficient statistics of mode transitions that account for known， unknown， and uncertain transition probabilities is comprehensive. A distributed filter design scheme is outlined by explicitly characterizing the filter gains in terms of some matrix inequalities. Simulation results demonstrate the effectiveness of the proposed filtering scheme.

Keywords：missing measurements； wireless sensor； stochastic-systems； actuator networks； probabilities

来源出版物：IEEE Transactions on Industrial Electronics， 2013， 60（10）：4665-4672联系邮箱：Dong， HL； shiningdhl@gmail.com

Biochemical Research Methods 生化研究方法

被引频次：376

GROMACS 4.5：a high-throughput and highly parallel open source molecular simulation toolkit

Pronk， S； Pall， S； Schulz， R； et al.

Abstract：Motivation：Molecular simulation has historically been a low-throughput technique， but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of， for instance， many conformers or mutants of biomolecules with or without a range of ligands. At the same time， advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters， web servers， distributed computing or cloud resources.

Results：Here， we present a range of new simulation algorithms and features developed during the past 4 years， leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules， such as proteins， nucleic acids and lipids， and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models， as well as new free-energy algorithms， and the software now uses multithreading for efficient parallelization even on low-end systems， including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization， this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations.

Keywords：force-field； free-energy； biomolecular simulation； dynamics； model； refinement； transition； efficient； constant； proteins

来源出版物：Bioinformatics， 2013， 29（7）：845-854联系邮箱：Lindahl， E； erik.lindahl@scilifelab.se

被引频次：308

Integrative Genomics Viewer（IGV）：high-performance genomics data visualization and exploration

Thorvaldsdottir， H； Robinson， JT； Mesirov， JP

Abstract：Data visualization is an essential component of genomic data analysis. However， the size and diversity of the data sets produced by today's sequencing and array-based profiling methods present major challenges to visualization tools. The Integrative Genomics Viewer（IGV） is a high-performance viewer that efficiently handles large heterogeneous data sets， while providing a smooth and intuitive user experience at all levels of genome resolution. A key characteristic of IGV is its focus on the integrative nature of genomic studies， with support for both array-based and next-generation sequencing data， and the integration of clinical and phenotypic data. Although IGV is often used to view genomic data from public sources， its primary emphasis is to support researchers who wish to visualize and explore their own data sets or those from colleagues. To that end， IGV supports flexible loading of local and remote data sets， and is optimized to provide high-performance data visualization and exploration on standard desktop systems.

Keywords：sequence； format

来源出版物：Briefings in Bioinformatics， 2013， 14（2）：178-192联系邮箱：Robinson， JT； jrobinso@broadinstitute.org

被引频次：127

STAR：ultrafast universal RNA-seq aligner

Dobin， A； Davis， CA； Schlesinger， F； et al.

Abstract：Motivation：Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure， relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates， low mapping speed， read length limitation and mapping biases.

Results：To align our large（＞ 80 billon reads） ENCODE Transcriptome RNA-seq dataset， we developed the Spliced Transcripts Alignment to a Reference（STAR） software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of ＞ 50 in mapping speed， aligning to the human genome 550 million 2 x 76 bp paired-end reads per hour on a modest 12-core server，while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions，STAR can discover non-canonical splices and chimeric（fusion） transcripts， and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons， we experimentally validated 1960 novel inter-genic splice junctions with an 80%-90% success rate， corroborating the high precision of the STAR mapping strategy.

Keywords：splice junctions； alignment； reads； algorithms； sequence； genomes； encode

来源出版物：Bioinformatics， 2013， 29（1）：15-21联系邮箱：Dobin， A； dobin@cshl.edu

被引频次：124

Cas9 as a versatile tool for engineering biology

Mali， P； Esvelt， KM； Church， GM

Abstract：RNA-guided Cas9 nucleases derived from clustered regularly interspaced short palindromic repeats（CRISPR）-Cas systems have dramatically transformed our ability to edit the genomes of diverse organisms. We believe tools and techniques based on Cas9， a single unifying factor capable of colocalizing RNA， DNA and protein， will grant unprecedented control over cellular organization， regulation and behavior. Here we describe the Cas9 targeting methodology， detail current and prospective engineering advances and suggest potential applications ranging from basic science to the clinic.

Keywords：rna-guided endonuclease； zinc-finger nucleases； crispr rna； gene-expression； transcription factors； lentiviral vector； mammalian-cells； seed sequence； immune-system； genome

来源出版物：Nature Methods， 2013， 10（10）：957-963联系邮箱：Mali， P； pmali@genetics.med.harvard.edu

被引频次：117

Paper-based microfluidic point-of-care diagnostic devices

Yetisen， AK； Akram， MS； Lowe， CR

Abstract：Dipstick and lateral-flow formats have dominated rapid diagnostics over the last three decades. These formats gained popularity in the consumer markets due to their compactness， portability and facile interpretation without external instrumentation. However， lack of quantitation in measurements has challenged the demand of existing assay formats in consumer markets. Recently， paper-based microfluidics has emerged as a multiplexable point-of-care platform which might transcend the capabilities of existing assays in resource-limited settings. However， paper-based microfluidics can enable fluid handling and quantitative analysis for potential applications in healthcare，veterinary medicine， environmental monitoring and food safety. Currently， in its early development stages， paper-based microfluidics is considered a low-cost， lightweight， and disposable technology. The aim of this review is to discuss：（1） fabrication of paper-based microfluidic devices，（2） functionalisation of microfluidic components to increase the capabilities and the performance，（3） introduction of existing detection techniques to the paper platform and（4） exploration of extracting quantitative readouts via handheld devices and camera phones. Additionally， this review includes challenges to scaling up， commercialisation and regulatory issues. The factors which limit paper-based microfluidic devices to become real world products and future directions are also identified.

Keywords：resource-poor settings； lab-on-paper； low-cost； electrochemical detection； 2-dimensional paper； colorimetric detection； developing-world； global health； whole-blood； electrochemiluminescence immunodevice

来源出版物：Lab on A Chip， 2013， 13（12）：2210-2251联系邮箱：Yetisen， AK； ay283@cam.ac.uk

Biochemistry Molecular Biology 生物化学与分子生物学

被引频次：696

MEGA6：Molecular Evolutionary Genetics Analysis Version 6.0

Tamura， K； Stecher， G； Peterson， D； et al.

Abstract：We announce the release of an advanced version of the Molecular Evolutionary Genetics Analysis（MEGA） software， which currently contains facilities for building sequence alignments， inferring phylogenetic histories， and conducting molecular evolutionary analysis. In version 6.0， MEGA now enables the inference of timetrees， as it implements the RelTime method for estimating divergence times for all branching points in a phylogeny. A new Timetree Wizard in MEGA6 facilitates this timetree inference by providing a graphical user interface（GUI） to specify the phylogeny and calibration constraints step-by-step. This version also contains enhanced algorithms to search for the optimal trees under evolutionary criteria and implements a more advanced memory management that can double the size of sequence data sets to which MEGA can be applied. Both GUI and command-line versions of MEGA6 can be downloaded from www.megasoftware.net free of charge.

Keywords：divergence times

来源出版物：Molecular Biology and Evolution， 2013， 30（12）：2725-2729联系邮箱：Kumar， S； s.kumar@asu.edu

被引频次：477

MAFFT Multiple Sequence Alignment Software Version 7：Improvements in Performance and Usability

Katoh， K； Standley， DM

Abstract：We report a major update of the MAFFT multiple sequence alignment program. This version has several new features， includingoptions for adding unaligned sequences into an existing alignment， adjustment of direction in nucleotide alignment， constrained alignment and parallel processing， which were implemented after the previous major update. This report shows actual examples to explain how these features work， alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments， and our ongoing efforts to overcome such limitations.

Keywords：protein sequences； unaligned sequences； rna sequences； database； tree； algorithm； accuracy； clustal； information； sensitivity

来源出版物：Molecular Biology and Evolution， 2013， 30（4）：772-780联系邮箱：Katoh， K； kazutaka.katoh@aist.go.jp

被引频次：393

The Proteomics Identifications（PRIDE） database and associated tools：status in 2013

Vizcaino， JA； Cote， RG； Csordas， A； et al.

Abstract：The PRoteomics IDEntifications（PRIDE， http：//www.ebi.ac.uk/pride） database at the European Bioinformatics Institute is one of the most prominent data repositories of mass spectrometry（MS）-based proteomics data. Here， we summarize recent developments in the PRIDE database and related tools. First， we provide up-to-date statistics in data content， splitting the figures by groups of organisms and species， including peptide and protein identifications， and post-translational modifications. We then describe the tools that are part of the PRIDE submission pipeline， especially the recently developed PRIDE Converter 2（new submission tool） and PRIDE Inspector（visualization and analysis tool）. We also give an update about the integration of PRIDE with other MS proteomics resources in the context of the ProteomeXchange consortium. Finally， we briefly review the quality control efforts that are ongoing at present and outline our future plans.

Keywords：peptide identifications； public repository； protein； standard； workflows； visualize； platform； datasets； library； service

来源出版物：Nucleic Acids Research， 2013， 41（D1）：D1063-D1069联系邮箱：Vizcaino， JA； pst@ebi.ac.uk

被引频次：363

One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering

Wang， HY； Yang， H； Shivalila， CS； et al.

Abstract：Mice carrying mutations in multiple genes are traditionally generated by sequential recombination in embryonic stem cells and/or time-consuming inter-crossing of mice with a single mutation. The CRISPR/Cas system has been adapted as an efficient gene-targeting technology with the potential for multiplexed genome editing. We demonstrate that CRISPR/Cas-mediated gene editing allows the simultaneous disruption of five genes（Tet1， 2， 3， Sry， Uty - 8 alleles） in mouse embryonic stem（ES） cells with high efficiency. Coinjection of Cas9 mRNA and single-guide RNAs（sgRNAs） targeting Tet1 and Tet2 into zygotes generated mice with biallelic mutations in both genes with an efficiency of 80%. Finally， we show that coinjection of Cas9 mRNA/sgRNAs with mutant oligos generated precise point mutations simultaneously in two target genes. Thus， the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes， an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions.

Keywords：zinc-finger nucleases； embryo microinjection； postnatal-development； knockout rats； bacteria； systems； cells； cas9； tet2； endonuclease

来源出版物：Cell， 2013， 153（4）：910-918联系邮箱：Jaenisch， R； jaenisch@wi.mit.edu

被引频次：363

STRING v9.1：protein-protein interaction networks， with increased coverage and integration

Franceschini， A； Szklarczyk， D； Frankild， S； et al.

Abstract：Complete knowledge of all direct and indirect interactions between proteins in a given cell would represent an important milestone towards a comprehensive description of cellular mechanisms and functions. Although this goal is still elusive， considerable progress has been made-particularly for certain model organisms and functional systems. Currently， protein interactions and associations are annotated at various levels of detail in online resources， ranging from raw data repositories to highly formalized pathway databases. For many applications， a global view of all the available interaction data is desirable， including lower-quality data and/or computational predictions. The STRING database（http：//string-db.org/） aims to provide such a global perspective for as many organisms as feasible. Known and predicted associations are scored and integrated， resulting in comprehensive protein networks covering ＞ 1100 organisms. Here， we describe the update to version 9.1 of STRING， introducing several improvements：（i） we extend the automated mining of scientific texts for interaction information， to now also include full-text articles；（ii） we entirely re-designed the algorithm for transferring interactions from one model organism to the other； and（iii） we provide users with statistical information on any functional enrichment observed in their networks.

Keywords：molecular interaction database； large gene lists； metabolic pathways； evolution； prediction； organisms； screens； visualization；enrichment； proteomics

来源出版物：Nucleic Acids Research， 2013， 41（D1）：D808-D815联系邮箱：von Mering， C； bork@embl.de

Biodiversity Conservation 生物多样性保护

被引频次：127

Collinearity：a review of methods to deal with it and a simulation study evaluating their performance

Dormann， CF； Elith， J； Bacher， S； et al.

Abstract：Collinearity refers to the non independence of predictor variables， usually in a regression-type analysis. It is a common feature of any descriptive ecological data set and can be a problem for parameter estimation because it inflates the variance of regression parameters and hence potentially leads to the wrong identification of relevant predictors in a statistical model. Collinearity is a severe problem when a model is trained on data from one region or time， and predicted to another with a different or unknown structure of collinearity. To demonstrate the reach of the problem of collinearity in ecology， we show how relationships among predictors differ between biomes， change over spatial scales and through time. Across disciplines， different approaches to addressing collinearity problems have been developed， ranging from clustering of predictors， threshold-based pre-selection， through latent variable methods， to shrinkage and regularisation. Using simulated data with five predictor-response relationships of increasing complexity and eight levels of collinearity we compared ways to address collinearity with standard multiple regression and machine-learning approaches. We assessed the performance of each approach by testing its impact on prediction to new data. In the extreme， we tested whether the methods were able to identify the true underlying relationship in a training dataset with strong collinearity by evaluating its performance on a test dataset without any collinearity. We found that methods specifically designed for collinearity， such as latent variable methods and tree based models， did not outperform the traditional GLM and threshold-based pre-selection. Our results highlight the value of GLM in combination with penalised methods（particularly ridge） and threshold-based pre-selection when omitted variables are considered in the final interpretation. However， all approaches tested yielded degraded predictions under change in collinearity structure and the folk lore'-thresholds of correlation coefficients between predictor variables of |r| ＞0.7 was an appropriate indicator for when collinearity begins to severely distort model estimation and subsequent prediction. The use of ecological understanding of the system in pre-analysis variable selection and the choice of the least sensitive statistical approaches reduce the problems of collinearity， but cannot ultimately solve them.

Keywords：latent root regression； principal component regression； sliced inverse regression； partial least-squares； dimension reduction；multiple-regression； climate-change； logistic-regression； ridge-regression； ecological data

来源出版物：Ecography， 2013， 36（1）：27-46联系邮箱：Dormann， CF； carsten.dormann@biom.uni-freiburg.de

被引频次：101

Impacts of ocean acidification on marine organisms：quantifying sensitivities and interaction with warming

Kroeker， KJ； Kordas， RL； Crim， R； et al.

Abstract：Ocean acidification represents a threat to marine species worldwide， and forecasting the ecological impacts of acidification is a high priority for science， management， and policy. As research on the topic expands at an exponential rate， a comprehensive understanding of the variability in organisms' responses and corresponding levels of certainty is necessary to forecast the ecological effects. Here， we perform the most comprehensive meta-analysis to date by synthesizing the results of 228 studies examining biological responses to ocean acidification. The results reveal decreased survival， calcification， growth， development and abundance in response to acidification when the broad range of marine organisms is pooled together. However， the magnitude of these responses varies among taxonomic groups， suggesting there is some predictable trait-based variation in sensitivity， despite the investigation of approximately 100 new species in recent research. The results also reveal an enhanced sensitivity of mollusk larvae， but suggest that an enhanced sensitivity of early life history stages is not universal across all taxonomic groups. In addition， the variability in species' responses is enhanced when they are exposed to acidification in multi-species assemblages， suggesting that it is important to consider indirect effects and exercise caution when forecasting abundance patterns from single-species laboratory experiments. Furthermore， the results suggest that other factors， such as nutritional status or source population， could cause substantial variation in organisms' responses. Last， the results highlight a trend towards enhanced sensitivity to acidification when taxa are concurrently exposed to elevated seawater temperature.

Keywords：climate-change； coral； metaanalysis； carbon； temperature； responses； exposure； fish； ph； calcification

来源出版物：Global Change Biology， 2013， 19（6）：1884-1896联系邮箱：Kroeker， KJ； kjkroeker@ucdavis.edu

被引频次：60

The conservation status of the world's reptiles

Bohm， M； Collen， B； Baillie， JEM； et al.

Abstract：Effective and targeted conservation action requires detailed information about species， their distribution， systematics and ecologyas well as the distribution of threat processes which affect them. Knowledge of reptilian diversity remains surprisingly disparate， and innovative means of gaining rapid insight into the status of reptiles are needed in order to highlight urgent conservation cases and inform environmental policy with appropriate biodiversity information in a timely manner. We present the first ever global analysis of extinction risk in reptiles， based on a random representative sample of 1500 species（16% of all currently known species）. To our knowledge， our results provide the first analysis of the global conservation status and distribution patterns of reptiles and the threats affecting them， highlighting conservation priorities and knowledge gaps which need to be addressed urgently to ensure the continued survival of the world's reptiles. Nearly one in five reptilian species are threatened with extinction， with another one in five species classed as Data Deficient. The proportion of threatened reptile species is highest in freshwater environments， tropical regions and on oceanic islands， while data deficiency was highest in tropical areas， such as Central Africa and Southeast Asia， and among fossorial reptiles. Our results emphasise the need for research attention to be focussed on tropical areas which are experiencing the most dramatic rates of habitat loss， on fossorial reptiles for which there is a chronic lack of data， and on certain taxa such as snakes for which extinction risk may currently be underestimated due to lack of population information. Conservation actions specifically need to mitigate the effects of human-induced habitat loss and harvesting，which are the predominant threats to reptiles.

Keywords：molecular phylogeny； biodiversity conservation； global biodiversity； species-diversity； classification； vertebrates； amphibians；climate； distributions； radiation

来源出版物：Biological Conservation， 2013， 157：372-385联系邮箱：Bohm， M； monika.bohm@ioz.ac.uk

被引频次：50

Climate change and ocean acidification effects on seagrasses and marine macroalgae

Koch， M； Bowes， G； Ross， C； et al.

Abstract：Although seagrasses and marine macroalgae（macro-autotrophs） play critical ecological roles in reef， lagoon， coastal and open-water ecosystems， their response to ocean acidification（OA） and climate change is not well understood. In this review， we examine marine macro-autotroph biochemistry and physiology relevant to their response to elevated dissolved inorganic carbon ［DIC［， carbon dioxide ［CO2［， and lower carbonate ［CO32-［ and pH. We also explore the effects of increasing temperature under climate change and the interactions of elevated temperature and ［CO2［. Finally， recommendations are made for future research based on this synthesis. A literature review of ＞100 species revealed that marine macro-autotroph photosynthesis is overwhelmingly C3（= 85%） with most species capable of utilizing HCO3-； however， most are not saturated at current ocean ［DIC［. These results， and the presence of CO2-only users， lead us to conclude that photosynthetic and growth rates of marine macro-autotrophs are likely to increase under elevated ［CO2［ similar to terrestrial C3species. In the tropics， many species live close to their thermal limits and will have to up-regulate stress-response systems to tolerate sublethal temperature exposures with climate change， whereas elevated ［CO2［ effects on thermal acclimation are unknown. Fundamental linkages between elevated ［CO2［ and temperature on photorespiration， enzyme systems， carbohydrate production， and calcification dictate the need to consider these two parameters simultaneously. Relevant to calcifiers， elevated ［CO2［ lowers net calcification and this effect is amplified by high temperature. Although the mechanisms are not clear， OA likely disrupts diffusion and transport systems of H+ and DIC. These fluxes control micro-environments that promote calcification over dissolution and may be more important than CaCO3mineralogy in predicting macroalgal responses to OA. Calcareous macroalgae are highly vulnerable to OA， and it is likely that fleshy macroalgae will dominate in a higher CO2ocean； therefore， it is critical to elucidate the research gaps identified in this review.

Keywords：carbon-concentrating mechanisms； reactive oxygen-metabolism； crustose coralline algae； zostera-noltii hornemann； inorganic carbon； atmospheric CO2； elevated CO2； photosynthetic utilization； tropical seagrass； halophila-ovalis

来源出版物：Global Change Biology， 2013， 19（1）：103-132联系邮箱：Koch， M； mkoch@fau.edu

被引频次：49

The Microbial Efficiency-Matrix Stabilization（MEMS） framework integrates plant litter decomposition with soil organic matter stabilization：do labile plant inputs form stable soil organic matter？

Cotrufo， MF； Wallenstein， MD； Boot， CM； et al.

Abstract：The decomposition and transformation of above- and below-ground plant detritus（litter） is the main process by which soil organic matter（SOM） is formed. Yet， research on litter decay and SOM formation has been largely uncoupled， failing to provide an effective nexus between these two fundamental processes for carbon（C） and nitrogen（N） cycling and storage. We present the current understanding of the importance of microbial substrate use efficiency and C and N allocation in controlling the proportion of plant-derived C and N that is incorporated into SOM， and of soil matrix interactions in controlling SOM stabilization. We synthesize this understanding into the Microbial Efficiency-Matrix Stabilization（MEMS） framework. This framework leads to the hypothesis that labile plant constituents are the dominant source of microbial products， relative to input rates， because they are utilized more efficiently by microbes. These microbial products of decomposition would thus become the main precursors of stable SOM by promoting aggregation and through strong chemical bondingto the mineral soil matrix.

Keywords：stoichiometric controls； mineral associations； temperate soils； carbon； nitrogen； dynamics； mechanisms； bacterial； lignin； degradation

来源出版物：Global Change Biology， 2013， 19（4）：988-995联系邮箱：Cotrufo， MF； Francesca.cotrufo@colostate.edu

Biology 生物学

被引频次：166

RNA-programmed genome editing in human cells

Jinek， M； East， A； Cheng， A； et al.

Abstract：Type II CRISPR immune systems in bacteria use a dual RNA-guided DNA endonuclease， Cas9， to cleave foreign DNA at specific sites. We show here that Cas9 assembles with hybrid guide RNAs in human cells and can induce the formation of double-strand DNA breaks（ DSBs） at a site complementary to the guide RNA sequence in genomic DNA. This cleavage activity requires both Cas9 and the complementary binding of the guide RNA. Experiments using extracts from transfected cells show that RNA expression and/or assembly into Cas9 is the limiting factor for Cas9-mediated DNA cleavage. In addition， we find that extension of the RNA sequence at the 3' end enhances DNA targeting activity in vivo. These results show that RNA-programmed genome editing is a facile strategy for introducing site-specific genetic changes in human cells.

Keywords：bacteria； immunity； systems； nuclease； archaea

来源出版物：Elife， 2013， 2联系邮箱：Doudna， J； doudna@berkeley.edu

被引频次：77

The role of biotic interactions in shaping distributions and realised assemblages of species：implications for species distribution modelling

Wisz， MS； Pottier， J； Kissling， WD； et al.

Abstract：Predicting which species will occur together in the future， and where， remains one of the greatest challenges in ecology， and requires a sound understanding of how the abiotic and biotic environments interact with dispersal processes and history across scales. Biotic interactions and their dynamics influence species' relationships to climate， and this also has important implications for predicting future distributions of species. It is already well accepted that biotic interactions shape species' spatial distributions at local spatial extents， but the role of these interactions beyond local extents（e.g. 10 km2to global extents） are usually dismissed as unimportant. In this review we consolidate evidence for how biotic interactions shape species distributions beyond local extents and review methods for integrating biotic interactions into species distribution modelling tools. Drawing upon evidence from contemporary and palaeoecological studies of individual species ranges， functional groups， and species richness patterns， we show that biotic interactions have clearly left their mark on species distributions and realised assemblages of species across all spatial extents. We demonstrate this with examples from within and across trophic groups. A range of species distribution modelling tools is available to quantify species environmental relationships and predict species occurrence， such as：（i） integrating pairwise dependencies，（ii） using integrative predictors， and（iii） hybridising species distribution models（SDMs） with dynamic models. These methods have typically only been applied to interacting pairs of species at a single time， require a priori ecological knowledge about which species interact， and due to data paucity must assume that biotic interactions are constant in space and time. To better inform the future development of these models across spatial scales， we call for accelerated collection of spatially and temporally explicit species data. Ideally， these data should be sampled to reflect variation in the underlying environment across large spatial extents， and at fine spatial resolution. Simplified ecosystems where there are relatively few interacting species and sometimes a wealth of existing ecosystem monitoring data（e.g. arctic， alpine or island habitats） offer settings where the development of modelling tools that account for biotic interactions may be less difficult than elsewhere.

Keywords：habitat distribution models； higher-order interactions； climate-change； plant-communities； north-america； soil biota； competitive interactions； ecological communities； spatial-distribution； environmental-change

来源出版物：Biological Reviews， 2013， 88（1）：15-30联系邮箱：Wisz， MS； msw@dmu.dk

被引频次：55

Ribosome structures to near-atomic resolution from thirty thousand cryo-EM particles

Bai， XC； Fernandez， IS； McMullan， G； et al.

Abstract：Although electron cryo-microscopy（cryo-EM） single-particle analysis has become an important tool for structural biology of large and flexible macro-molecular assemblies， the technique has not yet reached its full potential. Besides fundamental limits imposed by radiation damage， poor detectors and beam-induced sample movement have been shown to degrade attainable resolutions. A new generation of direct electron detectors may ameliorate both effects. Apart from exhibiting improved signal-to-noise performance， these cameras are also fast enough to follow particle movements during electron irradiation. Here， we assess the potentials of this technology for cryo-EMstructure determination. Using a newly developed statistical movie processing approach to compensate for beam-induced movement， we show that ribosome reconstructions with unprecedented resolutions may be calculated from almost two orders of magnitude fewer particles than used previously. Therefore， this methodology may expand the scope of high-resolution cryo-EM to a broad range of biological specimens.

Keywords：electron cryomicroscopy； radiation-damage； transfer-rna； microscopy； ice； macromolecules； limitations； specimens； contrast；tilt

来源出版物：Elife， 2013， 2：e00461联系邮箱：Scheres， SHW； scheres@mrc-lmb.cam.ac.uk

被引频次：49

How does climate change cause extinction？

Cahill， AE； Aiello-Lammens， ME； Fisher-Reid， MC； et al.

Abstract：Anthropogenic climate change is predicted to be a major cause of species extinctions in the next 100 years. But what will actually cause these extinctions？ For example， will it be limited physiological tolerance to high temperatures， changing biotic interactions or other factors？ Here， we systematically review the proximate causes of climate-change related extinctions and their empirical support. We find 136 case studies of climatic impacts that are potentially relevant to this topic. However， only seven identified proximate causes of demonstrated local extinctions due to anthropogenic climate change. Among these seven studies， the proximate causes vary widely. Surprisingly， none show a straightforward relationship between local extinction and limited tolerances to high temperature. Instead， many studies implicate species interactions as an important proximate cause， especially decreases in food availability. We find very similar patterns in studies showing decreases in abundance associated with climate change， and in those studies showing impacts of climatic oscillations. Collectively， these results highlight our disturbingly limited knowledge of this crucial issue but also support the idea that changing species interactions are an important cause of documented population declines and extinctions related to climate change. Finally， we briefly outline general research strategies for identifying these proximate causes in future studies.

Keywords：mytilus-edulis l.； land-use change； global-change； el-nino； biological invasions； species interactions； population declines； range margins； marine fishes； national-park

来源出版物：Proceedings of The Royal Society B-biological Sciences， 2013， 280（1750）：20121890

联系邮箱：Wiens， JJ； wiensj@life.bio.sunysb.edu

被引频次：47

Reprogramming DNA methylation in the mammalian life cycle：building and breaking epigenetic barriers

Seisenberger， S； Peat， JR； Hore， TA； et al.

Abstract：In mammalian development， epigenetic modifications， including DNA methylation patterns， play a crucial role in defining cell fate but also represent epigenetic barriers that restrict developmental potential. At two points in the life cycle， DNA methylation marks are reprogrammed on a global scale， concomitant with restoration of developmental potency. DNA methylation patterns are subsequently re-established with the commitment towards a distinct cell fate. This reprogramming of DNA methylation takes place firstly on fertilization in the zygote， and secondly in primordial germ cells（PGCs）， which are the direct progenitors of sperm or oocyte. In each reprogramming window， a unique set of mechanisms regulates DNA methylation erasure and re-establishment. Recent advances have uncovered roles for the TET3 hydroxylase and passive demethylation， together with base excision repair（BER） and the elongator complex， in methylation erasure from the zygote. Deamination by AID， BER and passive demethylation have been implicated in reprogramming in PGCs， but the process in its entirety is still poorly understood. In this review， we discuss the dynamics of DNA methylation reprogramming in PGCs and the zygote， the mechanisms involved and the biological significance of these events. Advances in our understanding of such natural epigenetic reprogramming are beginning to aid enhancement of experimental reprogramming in which the role of potential mechanisms can be investigated in vitro. Conversely， insights into in vitro reprogramming techniques may aid our understanding of epigenetic reprogramming in the germline and supply important clues in reprogramming for therapies in regenerative medicine.

Keywords：primordial germ-cells； embryonic stem-cells； mouse preimplantation embryos； maternal genomic imprints； zygotic paternal genome； base excision-repair； de-novo methylation； active-demethylation； transposable elements； repetitive sequences

来源出版物：Philosophical Transactions of The Royal Society B-biological Sciences， 2013， 368（1609）：20110330

联系邮箱：Reik， W； stefanie.seisenberger@babraham.ac.uk

Biophysics生物物理学

被引频次：122

Regulation of nucleosome dynamics by histone modifications

Zentner， GE； Henikoff， S

Abstract：Chromatin is a dynamic structure that must respond to myriad stimuli to regulate access to DNA， and chemical modification of histones is a major means by which the cell modulates nucleosome mobility and turnover. Histone modifications are linked to essentially every cellular process requiring DNA access， including transcription， replication and repair. Here we consider properties of the major types of histone modification in the context of their associated biological processes to view them in light of the cellular mechanisms that regulate nucleosome dynamics.

Keywords：double-strand breaks； dna-replication； saccharomyces-cerevisiae； h2b ubiquitylation； active chromatin； set2 methylation；adp-ribosylation； gene-expression； h3 methylation； variant h3.3

来源出版物：Nature Structural & Molecular Biology， 2013， 20（3）：259-266联系邮箱：Henikoff， S； steveh@fhcrc.org

被引频次：118

Investigation of the freely available easy-to-use software 'EZR' for medical statistics

Kanda， Y

Abstract：Although there are many commercially available statistical software packages， only a few implement a competing risk analysis or a proportional hazards regression model with time-dependent covariates， which are necessary in studies on hematopoietic SCT. In addition， most packages are not clinician friendly， as they require that commands be written based on statistical languages. This report describes the statistical software 'EZR'（Easy R）， which is based on R and R commander. EZR enables the application of statistical functions that are frequently used in clinical studies， such as survival analyses， including competing risk analyses and the use of time-dependent covariates，receiver operating characteristics analyses， meta-analyses， sample size calculation and so on， by point-and-click access.

Keywords：bone-marrow transplants； competing risk； cumulative incidence； clinician； tests； guide

来源出版物：Bone Marrow Transplantation， 2013， 48（3）：452-458联系邮箱：Kanda， Y； ycanda-tky@umin.ac.jp

被引频次：117

Structure and function of long noncoding RNAs in epigenetic regulation

Mercer， TR； Mattick， JS

Abstract：Genomes of complex organisms encode an abundance and diversity of long noncoding RNAs（IncRNAs） that are expressed throughout the cell and fulfill a wide variety of regulatory roles at almost every stage of gene expression. These roles， which encompass sensory， guiding， scaffolding and allosteric capacities， derive from folded modular domains in IncRNAs. In this diverse functional repertoire， we focus on the well-characterized ability for IncRNAs to function as epigenetic modulators. Many IncRNAs bind to chromatin-modifying proteins and recruit their catalytic activity to specific sites in the genome， thereby modulating chromatin states and impacting gene expression. Considering this regulatory potential in combination with the abundance of IncRNAs suggests that IncRNAs may be part of a broad epigenetic regulatory network.

Keywords：x-chromosome inactivation； xist rna； antisense transcription； chromatin modification； binding proteins； gene-expression； encode regions； hox loci； sequences； evolution

来源出版物：Nature Structural & Molecular Biology， 2013， 20（3）：300-307联系邮箱：Mattick， JS； j.mattick@garvan.org.au

被引频次：98

Natural products：A continuing source of novel drug leads

Cragg， GM； Newman， DJ

Abstract：Background：Nature has been a source of medicinal products for millennia， with many useful drugs developed from plant sources. Following discovery of the penicillins， drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry（late 1980s）， shifted the focus of drug discovery efforts from Nature to the laboratory bench.

Scope of Review：This review traces natural products drug discovery， outlining important drugs from natural sources that revolutionized treatment of serious diseases. It is clear Nature will continue to be a major source of new structural leads， and effective drug development depends on multidisciplinary collaborations.

Major Conclusions：The explosion of genetic information led not only to novel screens， but the genetic techniques permitted the implementation of combinatorial biosynthetic technology and genome mining. The knowledge gained has allowed unknown molecules to be identified. These novel bioactive structures can be optimized by using combinatorial chemistry generating new drug candidates for many diseases.

General Significance：The advent of genetic techniques that permitted the isolation / expression of biosynthetic cassettes from microbesmay well be the new frontier for natural products lead discovery. It is now apparent that biodiversity may be much greater in those organisms. The numbers of potential species involved in the microbial world are many orders of magnitude greater than those of plants and multi-celled animals. Coupling these numbers to the number of currently unexpressed biosynthetic clusters now identified（＞10 per species）the potential of microbial diversity remains essentially untapped.

Keywords：solid-phase synthesis； uncultivated bacterial symbionts； microtubule-stabilizing agents； sponge kirkpatrickia-varialosa； compound library development； diversity-oriented synthesis； biosynthetic gene-cluster； metastatic breast-cancer； fungal cell-wall； marine actinomycete

来源出版物：Biochimica Et Biophysica Acta-general Subjects， 2013， 1830（6）：3670-3695

联系邮箱：Newman， DJ； newmand@mail.nih.gov

被引频次：81

Optimization of parameters for semiempirical methods VI：more modifications to the NDDO approximations and re-optimization of parameters

Stewart， JJP

Abstract：Modern semiempirical methods are of sufficient accuracy when used in the modeling of molecules of the same type as used as reference data in the parameterization. Outside that subset， however， there is an abundance of evidence that these methods are of very limited utility. In an attempt to expand the range of applicability， a new method called PM7 has been developed. PM7 was parameterized using experimental and high-level ab initio reference data， augmented by a new type of reference data intended to better define the structure of parameter space. The resulting method was tested by modeling crystal structures and heats of formation of solids. Two changes were made to the set of approximations：a modification was made to improve the description of noncovalent interactions， and two minor errors in the NDDO formalism were rectified. Average unsigned errors（AUEs） in geometry and Delta H（f） for PM7 were reduced relative to PM6；for simple gas-phase organic systems， the AUE in bond lengths decreased by about 5 % and the AUE in Delta H（f） decreased by about 10 %； for organic solids， the AUE in Delta H（f） dropped by 60 % and the reduction was 33.3 % for geometries. A two-step process（PM7-TS）for calculating the heights of activation barriers has been developed. Using PM7-TS， the AUE in the barrier heights for simple organic reactions was decreased from values of 12.6 kcal/mol-1in PM6 and 10.8 kcal/mol-1in PM7 to 3.8 kcal/mol-1. The origins of the errors in NDDO methods have been examined， and were found to be attributable to inadequate and inaccurate reference data. This conclusion provides insight into how these methods can be improved.

Keywords：structure model chemistries； density-functional theory； molecular-orbital theory； h-bonding correction； interaction energies；ground-states； pm6 method； noncovalent complexes； barrier heights； solid-state

来源出版物：Journal of Molecular Modeling， 2013， 19（1）：1-32联系邮箱：Stewart， JJP； MrMopac@openmopac.net

Biotechnology Applied Microbiology 生物技术和应用微生物学

被引频次：376

GROMACS 4.5：a high-throughput and highly parallel open source molecular simulation toolkit

Pronk， S； Pall， S； Schulz， R； et al.

Keywords：force-field； free-energy； biomolecular simulation； dynamics； model； refinement； transition； efficient； constant； proteins

来源出版物：Bioinformatics， 2013， 29（7）：845-854联系邮箱：Lindahl， E； erik.lindahl@scilifelab.se

被引频次：358

Efficient genome editing in zebrafish using a CRISPR-Cas system

Hwang， WY； Fu， YF； Reyon， D； et al.

Abstract：In bacteria， foreign nucleic acids are silenced by clustered， regularly interspaced， short palindromic repeats（CRISPR）CRISPR-associated（Gas） systems. Bacterial type II CRISPR systems have been adapted to create guide RNAs that direct site-specificDNA cleavage by the Cas9 endonuclease in cultured cells. Here we show that the CRISPR-Cas system functions in vivo to induce targeted genetic modifications in zebrafish embryos with efficiencies similar to those obtained using zinc finger nucleases and transcription activator like effector nucleases.

Keywords：zinc-finger nucleases； talens； prokaryotes； bacteria； immunity

来源出版物：Nature Biotechnology， 2013， 31（3）：227-229联系邮箱：Joung， JK； jyeh1@partners.org

被引频次：328

ZFN， TALEN， and CRISPR/Cas-based methods for genome engineering

Gaj， T； Gersbach， CA； Barbas， CF

Abstract：Zinc-finger nucleases（ZFNs） and transcription activator-like effector nucleases（TALENs） comprise a powerful class of tools that are redefining the boundaries of biological research. These chimeric nucleases are composed of programmable， sequence-specific DNA-binding modules linked to a nonspecific DNA cleavage domain. ZFNs and TALENs enable a broad range of genetic modifications by inducing DNA double-strand breaks that stimulate error-prone nonhomologous end joining or homology-directed repair at specific genomic locations. Here， we review achievements made possible by site-specific nuclease technologies and discuss applications of these reagents for genetic analysis and manipulation. In addition， we highlight the therapeutic potential of ZFNs and TALENs and discuss future prospects for the field， including the emergence of clustered regulatory interspaced short palindromic repeat（CRISPR）/Cas-based RNA-guided DNA endonucleases.

Keywords：zinc-finger nucleases； targeted gene disruption； pluripotent stem-cells； dna-sequence specificity； double-strand breaks； transcription factors； in-vivo； embryo microinjection； effector nucleases； nicking enzyme

来源出版物：Trends in Biotechnology， 2013， 31（7）：397-405联系邮箱：Barbas， CF； carlos@scripps.edu

被引频次：286

TopHat2：accurate alignment of transcriptomes in the presence of insertions，

deletions and gene fusions

Kim， D； Pertea， G； Trapnell， C； et al.

Abstract：TopHat is a popular spliced aligner for RNA-sequence（RNA-seq） experiments. In this paper， we describe TopHat2， which incorporates many significant enhancements to TopHat. TopHat2 can align reads of various lengths produced by the latest sequencing technologies， while allowing for variable-length indels with respect to the reference genome. In addition to de novo spliced alignment， TopHat2 can align reads across fusion breaks， which can occur after genomic translocations. TopHat2 combines the ability to identify novel splice sites with direct mapping to known transcripts， producing sensitive and accurate alignments， even for highly repetitive genomes or in the presence of pseudogenes. TopHat2 is available at http：//ccb.jhu.edu/software/tophat.

Keywords：RNA-seq； human genome； pseudogenes； discovery； ultrafast； reads

来源出版物：Genome Biology， 2013， 14（4）：R36联系邮箱：Kim， D； infphilo@umiacs.umd.edu

被引频次：266

High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells

Fu， YF； Foden， JA； Khayter， C； et al.

Abstract：Clustered， regularly interspaced， short palindromic repeat（CRISPR） RNA-guided nucleases（RGNs） have rapidly emerged as a facile and efficient platform for genome editing. Here， we use a human cell-based reporter assay to characterize off-target cleavage of CRISPR-associated（Cas） 9-based RGNs. We find that single and double mismatches are tolerated to varying degrees depending on their position along the guide RNA（gRNA）-DNA interface. We also readily detected off-target alterations induced by four out of six RGNs targeted to endogenous loci in human cells by examination of partially mismatched sites. The off-target sites we identified harbored up to five mismatches and many were mutagenized with frequencies comparable to（or higher than） those observed at the intended on-target site. Our work demonstrates that RGNs can be highly active even with imperfectly matched RNA-DNA interfaces in human cells， a finding that might confound their use in research and therapeutic applications.

Keywords：zinc-finger nucleases； systems； endonuclease； generation； bacteria； archaea； mice

来源出版物：Nature Biotechnology， 2013， 31（9）：822联系邮箱：Joung， JK； jjoung@partners.org

Cardiac Cardiovascular Systems 心脏及心血管系统

被引频次：165

Fifth INTERMACS annual report：Risk factor analysis from more than 6，000 mechanical circulatory support patients

Kirklin， JK； Naftel， DC； Kormos， RL et al.

Abstract：The 5th annual report of the Interagency Registry for Mechanically Assisted Circulatory Support（INTERMACS） summarizesand analyzes the first 6 years of patient and data collection. The current analysis includes more than 6000 patients and updated risk factors for continuous flow pumps. Among continuous flow pumps， actuarial survival is 80% at 1 year and 70% at 2 years. Quality of life indicators are generally favorable and adverse event burden will likely influence patient selections of advanced heart failure therapies.

来源出版物：Journal of Heart and Lung Transplantation， 2013， 32（2）：141-156联系邮箱：Kirklin， JK； jkirklin@uab.edu

被引频次：140

2013ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Stone， NJ； Robinson， JG； Lichtenstein， AH； et al.

Abstract：Atherosclerotic cardiovascular disease is the most important public health problem of our time in both Europe and the rest of the world， accounting for the greatest expenditure in most healthcare budgets. Achieving consistency of clinical care， incorporating new evidence and their synthesis into practical recommendations for clinicians is the task of various guideline committees throughout the world. Any change in a set of guidelines therefore can have far reaching consequences， particularly if they appear to be at variance with the existing guidelines. The present article discusses the recent American College of Cardiology（ACC）/American Heart Association（AHA） guidelines 2013 on the control of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults. When compared with the ESC/EAS guidelines on lipid modification in 2011， the ACC/AHA guidelines of 2013 differ markedly. Specifically，（i） the scope is limited to randomized trials only， which excludes a significant body of data and promotes essentially a statin centric approach only；（ii） the abolition of low-density lipoprotein cholesterol（LDL-C） targets in favour of specific statin regimens that produce a 30-50% reduction in LDL-C we believe will confuse many physicians and miss the opportunity for medication adherence and patient engagement in self-management；（iii） the absence of target LDL-C levels in very high-risk patients with high absolute risk or residual risk factors will discourage clinicians to consider the addition of lipid modification treatments and individualize patient care；（iv） a reduction in the threshold for treatment in primary prevention will result in a greater number of patients being prescribed statin therapy， which is potentially good in young patients with high life time risk， but will result in a very large number of older patients offered therapy； and（v） the mixed pool risk calculator used to asses CVD risk in the guidelines for primary prevention has not been fully evaluated. This article discusses the potential implications of adopting the ACC/AHA guidelines on patient care in Europe and beyond and concludes with the opinion that the ESC/EAS guidelines from 2011 seem to be the most wide ranging， pragmatic and appropriate choice for European countries.

Keywords：randomized controlled-trial； type-2 diabetes-mellitus； primary-prevention trial； placebo-controlled trial； acute coronary syndromes； density-lipoprotein cholesterol； clinical-practice guidelines； chronic kidney-disease； multiple chronic conditions； transient ischemic attack

来源出版物：Journal of The American College of Cardiology， 2014， 63（25）：2889-2934

Cell Tissue Engineering 细胞与组织工程学

被引频次：122

A TALEN Genome-Editing System for Generating Human Stem Cell-Based Disease Models

Ding， QR； Lee， YK； Schaefer， EAK； et al.

Abstract：Transcription activator-like effector nucleases（TALENs） are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells， the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease-dyslipidemia， insulin resistance， hypoglycemia， lipodystrophy， motor-neuron death， and hepatitis C infection. We found little evidence of TALEN off-target effects， but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines， we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease.

Keywords：insulin-resistance； adipose-tissue； mice lacking； dna； effectors； perilipin； nucleases； sortilin； mutation； akt2

来源出版物：Cell Stem Cell， 2013， 12（2）：238-251联系邮箱：Musunuru， K； kiranmusunuru@gmail.com

被引频次：79

The Sox Family of Transcription Factors：Versatile Regulators of Stem and Progenitor Cell Fate

Sarkar， A； Hochedlinger， K

Abstract：Sox family transcription factors are well-established regulators of cell fate decisions during development. Accumulating evidence documents that they play additional roles in adult tissue homeostasis and regeneration. Remarkably， forced expression of Sox factors，in combination with other synergistic factors， reprograms differentiated cells into somatic or pluripotent stem cells. Dysregulation of Soxfactors has been further implicated in diseases including cancer. Here， we review molecular and functional evidence linking Sox proteins with stem cell biology， cellular reprogramming， and disease with an emphasis on Sox2.

Keywords：sex-determining region； self-renewal； gene-expression； neural crest； dna-binding； tgf-beta； neuronal differentiation； reprogramming factors； human fibroblasts； identifies Sox2

来源出版物：Cell Stem Cell， 2013， 12（1）：15-30联系邮箱：Hochedlinger， K； khochedlinger@helix.mgh.harvard.edu

被引频次：73

Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells

Guha， P； Morgan， JW； Mostoslavsky， G； et al.

Abstract：The prospects for using autologous induced pluripotent stem cells（iPSCs） in cell replacement therapy have been tempered by evidence that undifferentiated， syngeneic mouse iPSCs are immunogenic upon transplantation. However， the immunogenicity of more therapeutically relevant differentiated cells remains unexplored. Here， we differentiated mouse iPSCs into embryoid bodies（EBs） or representative cell types spanning the three embryonic germ layers and assessed their immunogenicity in vitro and after their transplantation into syngeneic recipients. We found no evidence of increased T cell proliferation in vitro， rejection of syngeneic iPSC-derived EBs/tissue-specific cells（TSCs） after transplantation， or an antigen-specific secondary immune response. Thus， differentiated cells derived from syngeneic iPSCs do not appear to be rejected after transplantation. We also found little evidence of an immune response to undifferentiated， syngeneic iPSCs. Our data support the idea that differentiated cells generated from autologous iPSCs could be applied for cell replacement therapy without eliciting immune rejection.

Keywords：mouse

来源出版物：Cell Stem Cell， 2013， 12（4）：407-412联系邮箱：Boyd， AS； asboyd@bu.edu

被引频次：67

Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells：a joint statement of the International Federation for Adipose Therapeutics and Science（IFATS） and the International Society for Cellular Therapy（ISCT）

Bourin， P； Bunnell， BA； Casteilla， L； et al.

Abstract：Background aims. Adipose tissue is a rich and very convenient source of cells for regenerative medicine therapeutic approaches. However， a characterization of the population of adipose-derived stromal and stem cells（ASCs） with the greatest therapeutic potential remains unclear. Under the authority of International Federation of Adipose Therapeutics and International Society for Cellular Therapy， this paper sets out to establish minimal definitions of stromal cells both as uncultured stromal vascular fraction（SVF） and as an adherent stromal/stem cells population. Methods. Phenotypic and functional criteria for the identification of adipose-derived cells were drawn from the literature. Results. In the SVF， cells are identified phenotypically by the following markers：CD45-CD235a-CD31-CD34+. Added value may be provided by both a viability marker and the following surface antigens：CD13， CD73， CD90 and CD105. The fibroblastoid colony-forming unit assay permits the evaluation of progenitor frequency in the SVF population. In culture， ASCs retain markers in common with other mesenchymal stromal/stem cells（MSCs）， including CD90， CD73， CD 105， and CD44 and remain negative for CD45 and CD31. They can be distinguished from bone-marrow-derived MSCs by their positivity for CD36 and negativity for CD106. The CFU-F assay is recommended to calculate population doublings capacity of ASCs. The adipocytic， chondroblastic and osteoblastic differentiation assays serve to complete the cell identification and potency assessment in conjunction with a quantitative evaluation of the differentiation either biochemically or by reverse transcription polymerase chain reaction. Conclusions. The goal of this paper is to provide initial guidance for the scientific community working with adipose-derived cells and to facilitate development of international standards based on reproducible parameters.

Keywords：mesenchymal stem-cells； human-bone-marrow； hematopoietic stem； progenitor cells； in-vitro； subpopulations； translation；features； surface

来源出版物：Cytotherapy， 2013， 15（6）：641-648联系邮箱：Bourin， P； p.bourin@csa21.com

被引频次：61

Modeling Alzheimer's Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular A beta and Differential Drug Responsiveness

Kondo， T； Asai， M； Tsukita， K； et al.

Abstract：Oligomeric forms of amyloid-beta peptide（A beta） are thought to play a pivotal role in the pathogenesis of Alzheimer's disease（AD）， but the mechanism involved is still unclear. Here， we generated induced pluripotent stem cells（iPSCs） from familial and sporadic AD patients and differentiated them into neural cells. A beta oligomers accumulated in iPSC-derived neurons and astrocytes in cells frompatients with a familial amyloid precursor protein（APP）-E693 Delta mutation and sporadic AD， leading to endoplasmic reticulum（ER） and oxidative stress. The accumulated A beta oligomers were not proteolytically resistant， and docosahexaenoic acid（DHA） treatment alleviated the stress responses in the AD neural cells. Differential manifestation of ER stress and DHA responsiveness may help explain variable clinical results obtained with the use of DHA treatment and suggests that DHA may in fact be effective for a subset of patients. It also illustrates how patient-specific iPSCs can be useful for analyzing AD pathogenesis and evaluating drugs.

Keywords：pluripotent stem-cells； endoplasmic-reticulum stress； oxidative stress； mouse model； in-vivo； protein； oligomers； memory；neurodegeneration； generation

来源出版物：Cell Stem Cell， 2013， 12（4）：487-496联系邮箱：Iwata， N； iwata-n@nagasaki-u.ac.jp

Cell Biology 细胞生物学

被引频次：363

One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering

Wang， HY； Yang， H； Shivalila， CS； et al.

Keywords：zinc-finger nucleases； embryo microinjection； postnatal-development； knockout rats； bacteria； systems； cells； cas9； tet2； endonuclease

来源出版物：Cell， 2013， 153（4）：910-918联系邮箱：Jaenisch， R； jaenisch@wi.mit.edu

被引频次：212

INNOVATION TALENs：a widely applicable technology for targeted genome editing

Joung， JK； Sander， JD

Abstract：Engineered nucleases enable the targeted alteration of nearly any gene in a wide range of cell types and organisms. The newly-developed transcription activator-like effector nucleases（TALENs） comprise a nonspecific DNA-cleaving nuclease fused to a DNA-binding domain that can be easily engineered so that TALENs can target essentially any sequence. The capability to quickly and efficiently alter genes using TALENs promises to have profound impacts on biological research and to yield potential therapeutic strategies for genetic diseases.

Keywords：zinc-finger nucleases； pluripotent stem-cells； double-strand breaks； effector nucleases； gene disruption； dna recognition； embryo microinjection； transcription factors； efficient generation； cleavage domain

来源出版物：Nature Reviews Molecular Cell Biology， 2013， 14（1）：49-55联系邮箱：Joung， JK； jjoung@partners.org

被引频次：197

Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression

Qi， LS； Larson， MH； Gilbert， LA； et al.

Abstract：Targeted gene regulation on a genome-wide scale is a powerful strategy for interrogating， perturbing， and engineering cellular systems. Here， we develop a method for controlling gene expression based on Cas9， an RNA-guided DNA endonuclease from a type II CRISPR system. We show that a catalytically dead Cas9 lacking endonuclease activity， when coexpressed with a guide RNA， generates a DNA recognition complex that can specifically interfere with transcriptional elongation， RNA polymerase binding， or transcription factor binding. This system， which we call CRISPR interference（CRISPRi）， can efficiently repress expression of targeted genes in Escherichia coli， with no detectable off-target effects. CRISPRi can be used to repress multiple target genes simultaneously， and its effects are reversible. We also show evidence that the system can be adapted for gene repression in mammalian cells. This RNA-guided DNA recognition platform provides a simple approach for selectively perturbing gene expression on a genome-wide scale.

Keywords：fluorescent protein； adaptive immunity； transcription； bacteria； systems； interference； evolution； cleavage； archaea； complex

来源出版物：Cell， 2013， 152（5）：1173-1183联系邮箱：Qi， LS； stanley.qi@ucsf.edu

被引频次：180

Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia

Landau， DA； Carter， SL； Stojanov， P； et al.

Abstract：Clonal evolution is a key feature of cancer progression and relapse. We studied intratumoral heterogeneity in 149 chronic lymphocytic leukemia（CLL） cases by integrating whole-exome sequence and copy number to measure the fraction of cancer cells harboring each somatic mutation. We identified driver mutations as predominantly clonal（e.g.， MYD88， trisomy 12， and del（13q）） or subclonal（e.g.，SF3B1 and TP53）， corresponding to earlier and later events in CLL evolution. We sampled leukemia cells from 18 patients at two time points. Ten of twelve CLL cases treated with chemotherapy（but only one of six without treatment） underwent clonal evolution， predominantly involving subclones with driver mutations（e.g.， SF3B1 and TP53） that expanded over time. Furthermore， presence of a subclonal driver mutation was an independent risk factor for rapid disease progression. Our study thus uncovers patterns of clonal evolution in CLL，providing insights into its stepwise transformation， and links the presence of subclones with adverse clinical outcomes.

Keywords：acute myeloid-leukemia； copy-number alteration； b-cell lymphoma； clonal evolution； human cancer； somatic mutations； multiple-myeloma； genomic aberrations； breast cancers； short survival

来源出版物：Cell， 2013， 152（4）：714-726联系邮箱：Getz， G； gadgetz@broadinstitute.org

被引频次：179

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes

Whyte， WA； Orlando， DA； Hnisz， D； et al.

Abstract：Master transcription factors Oct4， Sox2， and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells（ESCs）. We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains， which we call super-enhancers， consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size， transcription factor density and content， ability to activate transcription， and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes， suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells， super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of mammalian cell identity.

Keywords：embryonic stem-cells； wnt signaling pathway； human genome； self-renewal； rnai screen； coactivator complex； expression；pluripotency； differentiation； circuitry

来源出版物：Cell， 2013， 153（2）：307-319联系邮箱：Young， RA； young@wi.mit.edu

Chemistry Analytical 化学分析

被引频次：79

Biomimetic sensor for certain catecholamines employing copper（II） complex and silver nanoparticle modified glassy carbon paste electrode

Sanghavi， BJ； Mobin， SM； Mathur， P； et al.

Abstract：A dimeric Cu（II） complex ［Cu（mu（2）-heP）（heP-H）［2 center dot 2ClO4（1） containing bidentate（hep-H=2-（2-hydroxyethyl）pyridine）ligand was synthesized and characterized by single crystal X-ray diffraction studies. Each Cu-ion in 1 is in a distorted square pyramidal geometry. Further 1 along with silver nanoparticles（SNPs） have been used as modifier in the construction of a biomimetic sensor（1-SNP-GCPE） for determining certain catecholamines viz.， dopamine（DA）， levodopa（L-Dopa）， epinephrine（EP） and norepinephrine（NE）using cyclic voltammetry， chronocoulometry， electrochemical impedance spectroscopy and adsorptive stripping square wave voltammetry（AdSSWV）. Finally， the catalytic properties of the sensor were characterized by chronoamperometry. Employing AdSSWV， the calibration curves showed linear response ranging between 10-6and 10-9M for all the four analytes with detection limits（S/N=3） of 8.52×10-10M，2.41×10-9M， 3.96×10-1M and 3.54×10-1M for DA， L-Dopa， EP and NE respectively. The lifetime of the biomimetic sensor was 3 months at room temperature. The prepared modified electrode shows several advantages such as simple preparation method， high sensitivity， high stability， ease of preparation and regeneration of the electrode surface by simple polishing along with excellent reproducibility. The method has been applied for the selective and precise analysis of DA， L-Dopa， EP and NE in pharmaceutical formulations， urine and blood serum samples.

Keywords：potentiometric stripping analysis； hydrophilic interaction chromatography； chemically-modified electrodes； ascorbic-acid；uric-acid； voltammetric determination； electrochemical sensor； folic-acid； capillary-electrophoresis； chloride complex

来源出版物：Biosensors & Bioelectronics， 2013， 39（1）：124-132联系邮箱：Srivastava， AK； aksrivastava@chem.mu.ac.in

被引频次：61

A simple electrochemical approach to fabricate a glucose biosensor based on graphene-glucose oxidase biocomposite

Unnikrishnan， B； Palanisamy， S； Chen， SM

Abstract：We report a simple electrochemical approach for the immobilization of glucose oxidase（GOx） on reduced graphene oxide（RGO）. The immobilization of GOx was achieved in a single step without any cross linking agents or modifiers. A simple solution phase approach was used to prepare exfoliated graphene oxide（GO）， followed by electrochemical reduction to get RGO-GOx biocomposite. The direct electrochemistry of GOx was revealed at the RGO-GOx modified glassy carbon electrode（GCE）. The electrocatalytic and electroanalytical applications of the proposed film were studied by cyclic voltammetry（CV） and amperometry. It is notable that the glucose determination has been achieved in mediator-free conditions. RGO-GOx film showed very good stability， reproducibility and high selectivity. The developed biosensor exhibits excellent catalytic activity towards glucose over a wide linear range of 0.1-27 mM with a sensitivity of 1.85 mu A mM-1cm-2. The facile and easy electrochemical approach used for the preparation of RGO-GOx may open up new horizons in the production of cost-effective biosensors and biofuel cells.

Keywords：one-step immobilization； graphite oxide； ionic liquid； nanosheets； enzyme； electrode； layer； reduction； polymers； matrix

来源出版物：Biosensors & Bioelectronics， 2013， 39（1）：70-75联系邮箱：Chen， SM； smchen78@ms15.hinet.net

被引频次：55

Direct electrochemistry of glucose oxidase at electrochemically reduced graphene oxidemultiwalled carbon nanotubes hybrid material modified electrode for glucose biosensor

Mani， V； Devadas， B； Chen， SM

Abstract：Direct electrochemistry of glucose oxidase（GOx） at an electrochemically reduced graphene oxide-multiwalled carbon nanotubes hybrid（ERGO-MWCNT） modified glassy carbon electrode（GCE） has been reported. The pi-pi stacking interaction operating between the MWCNT and graphene oxide（GO） has been revealed by UV-Vis absorption spectroscopy. GOx was well immobilized onto the ERGO-MWCNT hybrid film， as a result direct electrochemistry of GOx has been achieved. Compared with pristine MWCNT， 2.1 fold higher peak current and very low peak to peak separation（Delta E-p） of 26 mV were observed at the hybrid film， demonstrating faster electron transfer between GOx and the modified electrode surface. Moreover， the modified film exhibited high electrocatalytic activity towards glucose via reductive detection of oxygen consumption and in the presence of mediator. The proposed biosensor exhibits low detection limit of 4.7 mu M with wide linear range of 0.01-6.5 mM and acquires excellent storage and operational stabilities. The accurate glucose determination in human blood serum and good recoveries achieved in spiked urine samples revealed their great potential in the practical applications.

Keywords：composites； dispersion

来源出版物：Biosensors & Bioelectronics， 2013， 41：309-315联系邮箱：Chen， SM； smchen78@ms15.hinet.net

被引频次：54

Glutathione-Protected Silver Nanoclusters as Cysteine-Selective Fluorometric and Colorimetric Probe

Yuan， X； Tay， YQ； Dou， XY； et al.

Abstract：The integration of the unique thiol-Ag chemistry and the specific steric hindrance from the organic layer of fluorescent Ag nanoclusters（AgNCs） was first developed in this work to achieve a simple detection of cysteine（Cys） with high selectivity and sensitivity. The key design is a strongly red-emitting AgNC protected by the interference biothiol， glutathione， or GSH（hereafter referred to as GSH-AgNCs）， where both the physicochemical properties（Ag surface chemistry and fluorescence） of the NC core and the physical properties（e.g.， steric hindrance） of the organic shell were fully utilized for Cys detection with three major features. First， owing to the specific thiol-Ag interaction， the fluorescent GSH-AgNCs showed superior selectivity for Cys over the other 19 natural amino acids（nonthiol-containing）. Second， the GSH protecting layer on the NC surface made possible the differentiation of Cys from GSH（or other large-sized thiol molecules） simply by their size. Third， the ultrasmall size of GSH-AgNCs and the high affinity of the thiol-Ag interaction provided high sensitivity for Cys detection with a detection limit of ＜3 nM. The assay developed in this study is of interest not only because it provides a simple Cys sensor with high selectivity and sensitivity but also because it exemplifies the utilization of the physical properties of organic ligands on the nanomaterial surface to further improve the sensor performance， which could open a new design strategy for other sensor development.

Keywords：gold nanoparticles； liquid-chromatography； fluorescent； clusters； thiols； nanocrystals； aggregation； monolayers； complexes；nanorods

来源出版物：Analytical Chemistry， 2013， 85（3）：1913-1919联系邮箱：Xie， JP； chexiej@nus.edu.sg

被引频次：53

Graphene wrapped Cu2O nanocubes：Non-enzymatic electrochemical sensors for the detection of glucose and hydrogen peroxide with enhanced stability

Liu， MM； Liu， R； Chen， W

Abstract：In this study， a sensor for the detection of glucose and hydrogen peroxide was developed on the basis of Cu2O nanocubes wrapped by graphene nanosheets（Cu2O/GNs） as electrocatalysts. Cubic Cu2O nanocrystals/graphene hybrid has been successfully fabricated by a chemical reduction method at low temperature. The morphologies of the synthesized materials were characterized by scanning electron microscopy（SEM） and powder X-ray diffraction measurements（XRD）. As a non-enzymatic amperometric sensor， the resulting Cu2O/graphene composite exhibited high sensitivity for the detection of glucose and H2O2. Moreover， the graphene coating was found to be able to effectively improve the electrochemical cycling stability of the fabricated sensor. With the Cu2O/GNs modified electrode， amperometric sensing of glucose was realized with a linear response over the concentration range from 0.3 to 3.3 mM， a detection limit of 3.3 mu M（SIN=3）， high selectivity and short response time（＜ 9 s）. Compared to unsupported Cu2O nanocubes， the graphene-wrapped Cu2O nanocubes exhibited higher catalytic activity for glucose oxidation with higher sensitivity and lower detection limit. The enzymeless sensor also exhibited good response toward H2O2， with the linear response ranging from 0.3 to 7.8 mM at 0.4 V and the detection limit of 20.8 mu M. Moreover， because the surface is covered by graphene nanosheets， the as-synthesized Cu2O/GN5 exhibited improved electrochemical stability. Such novel graphene nanosheets wrapped Cu2O nanocubes represent promising enzyme-free glucose and hydrogen peroxide sensors with high sensitivity and selectivity， improved stability and fast amperometric response.

Keywords：glassy-carbon electrode； facile synthesis； composite film； cuo nanowires； nanoparticles； oxide； functionalization； nanostructures； nanocrystals； biosensor

来源出版物：Biosensors & Bioelectronics， 2013， 45：206-212联系邮箱：Chen， W； weichen@ciac.jl.cn

Chemistry Applied 应用化学

被引频次：113

Recent Advances in Asymmetric Organocatalytic Construction of 3，3'-Spirocyclic Oxindoles

Hong， L； Wang， R

Abstract：The asymmetric organocatalysis is definitely one of the most powerful and versatile tools for the rapid construction of various spirocyclic oxindoles. In the past few years， a number of successful strategies based on organocatalysis have been developed for the construction of 3，3-spirocyclic oxindoles in high yields and excellent enantioselectivities under mild conditions. In this review， recent advances in this area are summarized and classified according to the spiro ring fused at the 3-position of the oxindole core.

Keywords：catalyzed 3+2 annulation； structure-based design； highly enantioselective synthesis； quaternary carbon stereocenters； intramolecular heck reactions； baylis-hillman carbonates； pictet-spengler reactions； diels-alder reactions； stereoselective-synthesis； spirocyclic oxindoles

来源出版物：Advanced Synthesis & Catalysis， 2013， 355（6）：1023-1052联系邮箱：Wang， R； wangrui@lzu.edu.cn

被引频次：74

Direct Trifluoromethylation of the CH Bond

Liu， H； Gu， ZH； Jiang， XF

Abstract：Trifluoromethylation meets CH activation：after transition metal-catalyzed trifluoromethylation became more and more popular，trifluoromethylation via CH activation is now emerging as the latest attraction. Several pioneering examples and their mechanisms are discussed in this review.

Keywords：catalyzed oxidative trifluoromethylation； enantioselective alpha-trifluoromethylation； pd（ii）-catalyzed ortho-trifluoromethylation；carbon-hydrogen bonds； room-temperature； boronic acids； mediated trifluoromethylation； heteroaromatic-compounds； h trifluoromethylation； photoredox catalysis

来源出版物：Advanced Synthesis & Catalysis， 2013， 355（4）：617-626联系邮箱：Jiang， XF； xfjiang@chem.ecnu.edu.cn

被引频次：64

Recent advances in the synthesis of hierarchically nanoporous zeolites

Na， K； Choi， M； Ryoo， R

Abstract：Hierarchically nanoporous zeolites possessing mesopores as well as the inherent micropores of zeolite structures are garnering attention as a solution to the diffusion limitation problem of solely microporous classical zeolites. The hierarchical structure enables zeolites to have maximum structural functions in a limited space and volume owing to the high diffusion efficiency. Hierarchical zeolites are in high demand for the development of advanced materials for applications in adsorption， separation and catalysis. Herein， recent advances insynthesis routes to hierarchically nanoporous zeolites are reviewed with their catalytic contributions. Particular emphasis is given to the recently developed synthesis method which uses surfactants that are functionalized with a zeolite-structure-directing group. This type of surfactants can direct porous structures in micro- and meso-length scales simultaneously.

Keywords：ordered mesoporous materials； unit-cell thickness； molecular-sieve； single-crystals； mfi zeolite； catalytic-properties； porous materials； carbon aerogels； zsm-5 zeolite； organosilane surfactant

来源出版物：Microporous and Mesoporous Materials， 2013， 166：3-19联系邮箱：Ryoo， R； rryoo@kaist.ac.kr

被引频次：61

Metal organic framework based mixed matrix membranes：An increasingly important field of research with a large application potential

Zornoza， B； Tellez， C； Coronas， J； et al.

Abstract：The combination of metal organic frameworks（MOFs） and polymers in the form of mixed matrix membranes（MMMs） has become an increasingly important field of research over the last few years. The first examples of membranes outperforming state of the art polymers have already been presented， emphasizing the high application potential of these composites. In this paper， the recent progress on the topic is thoroughly reviewed and the main advantages and limitations of the use of MOFs as MMMs fillers are evaluated.

Keywords：zeolitic imidazolate frameworks； porous coordination polymers； in-situ diffraction； x-ray-scattering； gas-separation； selective flakes； silicalite-1 membranes； modeling permeation； thermal-stability； inorganic fillers

来源出版物：Microporous and Mesoporous Materials， 2013， 166：67-78联系邮箱：Gascon， J； j.gascon@tudelft.ni

被引频次：59

Metal Organic Frameworks as Solid Catalysts in Condensation Reactions of Carbonyl Groups

Dhakshinamoorthy， A； Opanasenko， M； Cejka， J； et al.

Abstract：This review summarizes the use of metal organic frameworks（MOFs） as solid catalysts for condensation reactions. After an introductory section， in which condensation reactions are generally presented， a list of the MOFs employed as condensation catalyst is given. The main part of the present review is organized according to the use of MOFs as solid acids， solid bases or as bi-functional solids containing both acid and basic sites. Throughout the review， the emphasis has been made on discussing the stability of the MOFs， their reusability and in providing a comparison of the performance of MOFs with respect to other homogeneous and heterogeneous catalysts. Finally，we summarize the current state-of-the-art and provide our view on future trends and developments in this field.

Keywords：coordinatively unsaturated sites； ray crystal-structure； one-pot synthesis； knoevenagel condensation； heterogeneous catalysts；functionalized mil-101； friedlander reaction； henry reaction； acid； lewis

来源出版物：Advanced Synthesis & Catalysis， 2013， 355（2-3）：247-268联系邮箱：Dhakshinamoorthy， A； admguru@gmail.com

Chemistry Inorganic Nuclear 无机化学与核化学

被引频次：144

Semiconducting Tin and Lead Iodide Perovskites with Organic Cations：Phase Transitions，High Mobilities， and Near-Infrared Photoluminescent Properties

Stoumpos， CC； Malliakas， CD； Kanatzidis， MG

Abstract：A broad organic-inorganic series of hybrid metal iodide perovskites with the general formulation AMI（3）， where A is the methylammonium（CH3NH3+） or formamidinium（HC（NH2）2+） cation and M is Sn（1 and 2） or Pb（3 and 4） are reported. The compounds have been prepared through a variety of synthetic approaches， and the nature of the resulting materials is discussed in terms of their thermal stability and optical and electronic properties. We find that the chemical and physical properties of these materials strongly depend on the preparation method. Single crystal X-ray diffraction analysis of 1-4 classifies the compounds in the perovskite structural family. Structural phase transitions were observed and investigated by temperature-dependent single crystal X-ray diffraction in the 100-400 K range. The charge transport properties of the materials are discussed in conjunction with diffuse reflectance studies in the mid-IR region that display characteristic absorption features. Temperature-dependent studies show a strong dependence of the resistivity as a function of the crystal structure. Optical absorption measurements indicate that 1-4 behave as direct-gap semiconductors with energy band gaps distributed in the range of 1.25-1.75 eV. The compounds exhibit an intense near-IR photoluminescence（PL） emission in the 700-1000 nm range（1.1-1.7 eV）at room temperature. We show that solid solutions between the Sn and Pb compounds are readily accessible throughout the composition range. The optical properties such as energy band gap， emission intensity， and wavelength can be readily controlled as we show for the isostructural series of solid solutions CH3NH3Sn1-xPbxI3（5）. The charge transport type in these materials was characterized by Seebeck coefficient and Hall-effect measurements. The compounds behave as p- or n-type semiconductors depending on the preparation method. The samples with the lowest carrier concentration are prepared from solution and are n-type； p-type samples can be obtained through solid state reactions exposed in air in a controllable manner. In the case of Sri compounds， there is a facile tendency toward oxidation whichcauses the materials to be doped with Sn4+ and thus behave as p-type semiconductors displaying metal-like conductivity. The compounds appear to possess very high estimated electron and hole mobilities that exceed 2000 cm2/（V s） and 300 cm2/（V s）， respectively， as shown in the case of CH3NH3SnI3（1）. We also compare the properties of the title hybrid materials with those of the all inorganic CsSnI3and CsPbI3prepared using identical synthetic methods.

Keywords：organometal halide perovskites； group-theoretical analysis； ion-exchange properties； sensitized solar-cell； x-ray-diffraction；crystal-structure； inorganic semiconductors； layered perovskites； thermal-properties； twin boundaries

来源出版物：Inorganic Chemistry， 2013， 52（15）：9019-9038联系邮箱：Kanatzidis， MG； m-kanatzidis@northwestern.edu

被引频次：139

Design and construction of coordination polymers with mixed-ligand synthetic strategy

Du， M； Li， CP； Liu， CS； et al.

Abstract：The rational construction of coordination polymers（CPs）， normally existing as infinite crystalline lattices extended from inorganic vertices and organic struts， essentially benefits from the development of crystal engineering strategies. In this review， we summarily comment on the key advances in the design of CPs using mixed-ligand synthetic strategy and discuss the relationship between the specifically selected mixed organic ligands and the resulting CPs. Significantly， fine tuning on the structural features of organic ligands， such as spacers， positional isomers， and substituents， can lead to a delicate regulation of the diverse network structures of CPs. Additionally， such mixed-ligand coordination assemblies may also be heavily affected by metal ion， synthetic route， and some other external stimuli such as solvent and pH condition， etc. The advantages of mixed-ligand systems as promising approaches to construct CPs-based crystalline materials with interesting structures and useful properties will also be demonstrated.

Keywords：metal-organic frameworks； gas-adsorption properties； r-isophthalate r； crystal-structures； sorption properties； building-blocks；structural diversification； co-ligands； supramolecular isomerism； carboxylate frameworks

来源出版物：Coordination Chemistry Reviews， 2013， 257（7-8）：1282-1305联系邮箱：Du， M； dumiao@public.tpt.tj.cn

被引频次：88

Recent advances in dysprosium-based single molecule magnets：Structural overview and synthetic strategies

Zhang， P； Guo， YN； Tang， JK

Abstract：The last few years have seen a huge renaissance in the study of the magnetism of lanthanide coordination complexes， especially in the field of single molecule magnets（SMMs） due to the large inherent anisotropy of lanthanide metal ions. It has led to intense activity on the part of synthetic chemists to produce systems suitable for detailed study by physicists and materials scientists， thus synthetic development has been playing a major role in the advancement of this field. In this review， we demonstrate the research developed in the few years in the fascinating and challenging field of Dy-based SMMs with particular focus on how recent studies tend to address the issue of relaxation dynamics in these systems from synthetic point of view. In addition， the assembly of multinuclear Dy SMMs using various ligands is summarized， showing that several typical motifs are favorable structural units which could be exploited in the formation of new Dy-based SMMs and supramolecular architectures.

Keywords：sharing dy-3 triangles； lanthanide complexes； transition-metal； slow relaxation； chain magnets； ground-state； ion magnets；zero-field； anisotropic barrier； terbium complex

来源出版物：Coordination Chemistry Reviews， 2013， 257（11-12）：1728-1763联系邮箱：Tang， JK； tang@ciac.jl.cn

被引频次：87

Abnormal， mesoionic and remote N-heterocyclic carbene complexes

Crabtree， RH

Abstract：Three different structural classes of NHC ligands can be distinguished：normal（nNHC）， abnormal（aNHC）， alternatively called mesoionic（MIC）， and remote（rNHC）. General principles， synthetic strategies as well as recent results in the area of transition metal complexes of aNHC/MICs and rNHCs are discussed. The special properties of aNHC/MICs are discussed including their somewhat debateable status as true carbenes in the full sense of the term， as contrasted with their close analogy with nNHCs in the bound state. Some applications to catalysis are included and future prospects outlined.

Keywords：norbornene polymerization behavior； c-h activation； palladium complexes； imidazolium salts； catalytic-activity； nhc ligands；organometallic catalysis； coordination chemistry； electronic parameters； olefin metathesis

来源出版物：Coordination Chemistry Reviews， 2013， 257（3-4）：755-766联系邮箱：Crabtree， RH； robert.crabtree@yale.edu

被引频次：76

State of the art in gold nanoparticle synthesis

Zhao， PX； Li， N； Astruc， D

Abstract：General principles and recent developments in the synthesis of gold nanoparticles（AuNPs） are reviewed. The "in situ" Turkevich-Frens and Brust-Schiffrin methods are still major synthetic routes， with citrate and thiolate ligands， respectively， that have been improved and extended to macromolecules including biomacromolecules with a large biomedical potential of optical and theranostic applications. Along this line， however， recently developed seed-growth methods have allowed a precise control of AuNP sizes in a broad range and multiple shapes. AuNPs and core@shell bimetallic MAuNPs loosely stabilized by nitrogen and oxygen atoms of embedding polymers and dendrimers and composite solid-state materials containing AuNPs with supports including oxides， carbons， mesoporous materials and molecular organic frameworks（MOFs） have attracted much interest because of their catalytic applications.

Keywords：seed-mediated synthesis； dendrimer-encapsulated nanoparticles； surface-plasmon resonance； block-copolymer micelles；one-pot synthesis； porous coordination polymers； radiation-induced synthesis； colloidal au nanoparticles； room-temperature synthesis；shape-controlled synthesis

来源出版物：Coordination Chemistry Reviews， 2013， 257（3-4）：638-665联系邮箱：Astruc， D； d.astruc@ism.u-bordeaux1.fr

Chemistry Medicinal 医药化学

被引频次：190

Marine natural products

Blunt， JW； Copp， BR； Keyzers， RA； et al.

Abstract：This review covers the literature published in 2011 for marine natural products， with 870 citations（558 for the period January to December 2011） referring to compounds isolated from marine microorganisms and phytoplankton， green， brown and red algae， sponges，cnidarians， bryozoans， molluscs， tunicates， echinoderms， mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds（1152 for 2011）， together with the relevant biological activities， source organisms and country of origin. Biosynthetic studies， first syntheses， and syntheses that lead to the revision of structures or stereochemistries， have been included.

Keywords：formosan soft coral； south china sea； cyanobacterium lyngbya-majuscula； eunicellin-based diterpenoids； sponge xestospongia-testudinaria； penicillium-chrysogenum qen-24s； prenylated indole alkaloids； alga laurencia-nidifica； octocoral cladiella sp； fungus aspergillus-sp

来源出版物：Natural Product Reports， 2013， 30（2）：237-323联系邮箱：Blunt， JW； john.blunt@canterbury.ac.nz

被引频次：137

Ribosomally synthesized and post-translationally modified peptide natural products：overview and recommendations for a universal nomenclature

Arnison， PG； Bibb， MJ； Bierbaum， G； et al.

Abstract：This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides（RiPPs）， a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the ＞20 distinct compound classes is also reviewed， and commonalities are discussed.

Keywords：biosynthetic gene-cluster； elongation-factor-tu； carbon cross-links； bacillus-amyloliquefaciens fzb42； promotes secondary metabolism； cyclotide cycloviolacin O2； pyrrolo-quinoline-quinone； bacterial rna-polymerase； in-vitro reconstitution； antibiotic microcin j25

来源出版物：Natural Product Reports， 2013， 30（1）：108-160

被引频次：109

The Future of Peptide-based Drugs

Craik， DJ； Fairlie， DP； Liras， S； et al.

Abstract：The suite of currently used drugs can be divided into two categories traditional small molecule drugs with typical molecular weights of ＜500 Da but with oral bioavailability， and much larger biologics typically ＞5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size， conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side-effects， whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them， but this comes at a cost of low bioavailability， poor membrane permeability， and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes， with the goal of combining advantages of small molecules（cost， conformational restriction， membrane permeability， metabolic stability， oral bioavailability） with those of proteins（natural components， target specificity， high potency）. This article uses selected examples of peptides to highlight the importance of peptide drugs， some potential new opportunities for their exploitation， and some difficult challenges ahead in this field.

Keywords：protein-coupled receptors； calcium-channel blocker； cyclic-peptides； n-methylation； oral bioavailability； molecular scaffolds；medicinal chemistry； integrin expression； living subjects； alpha-helices

来源出版物：Chemical Biology & Drug Design， 2013， 81（1）：136-147联系邮箱：Craik， DJ； d.craik@imb.uq.edu.au

被引频次：89

Principles and Applications of Halogen Bonding in Medicinal Chemistry and Chemical Biology

Wilcken， R； Zimmermann， MO； Lange， A； et al.

Abstract：Halogen bonding. has been known in material science for decades， but until recently， halogen bonds in protein-ligand interactions were largely the result of serendipitous discovery rather than rational design. In this Perspective， we provide insights into the phenomenon of halogen bonding， with special focus on its role in drug discovery. We summarize the theoretical background defining its strength and directionality， provide a systematic analysis of its occurrence and interaction geometries in protein-ligand complexes， and give recent examples where halogen bonding has been successfully harnessed for lead identification and optimization. In light of these data， we discuss the potential and limitations of exploiting halogen bonds for molecular recognition and rational drug design.

Keywords：protein-ligand interactions； resolution crystal-structures； HIV-1 reverse-transcriptase； empirical scoring functions； mechanical method pm6-dh2x； density-functional theory； cross-coupling reactions； human-serum-albumin； structural basis； force-field

来源出版物：Journal of Medicinal Chemistry， 2013， 56（4）：1363-1388联系邮箱：Boeckler， FM； frank.boeckler@uni-tuebingen.de

被引频次：55

Prediction of Allergenic Proteins by Means of the Concept of Chou's Pseudo Amino Acid Composition and a Machine Learning Approach

Mohabatkar， H； Beigi， MM； Abdolahi， K； et al.

Abstract：Because of the importance of proteins in inducing allergenic reactions， the ability of predicting their potential allergenicity has become an important issue. Bioinformatics presents valuable tools for analyzing allergens and these complementary approaches can help traditional techniques to study allergens. This work proposes a computational method for predicting the allergenic proteins. The prediction was performed using pseudo-amino acid composition（PseAAC） and Support Vector Machines（SVMs）. The predictor efficiency was evaluated by fivefold cross-validation. The overall prediction accuracies and Matthew's correlation coefficient（MCC） obtained by this method were 91.19% and 0.82， respectively. Furthermore， the minimum Redundancy and Maximum Relevance（mRMR） feature selection method was utilized for measuring the effect and power of each feature. Interestingly， in our study all six characters（hydrophobicity， hydrophilicity，side chain mass， pK1， pK2 and pI） are present among the 10 higher ranked features obtained from the mRMR feature selection method.

Keywords：web-server； cross-reactivity； evolution information； computational tools； wavelet transform； identification； peptides； sequence；features； database

来源出版物：Medicinal Chemistry， 2013， 9（1）：133-137联系邮箱：Mohabatkar， H； h.mohabatkar@ast.ui.ac.ir

Chemistry Multidisciplinary 综合化学

被引频次：450

The chemistry of two-dimensional layered transition metal dichalcogenide nanosheets

Chhowalla， M； Shin， HS； Eda， G； et al.

Abstract：Ultrathin two-dimensional nanosheets of layered transition metal dichalcogenides（TMDs） are fundamentally and technologically intriguing. In contrast to the graphene sheet， they are chemically versatile. Mono-or few-layered TMDs - obtained either through exfoliation of bulk materials or bottom-up syntheses - are direct-gap semiconductors whose bandgap energy， as well as carrier type（n- or p-type），varies between compounds depending on their composition， structure and dimensionality. In this Review， we describe how the tunable electronic structure of TMDs makes them attractive for a variety of applications. They have been investigated as chemically active electrocatalysts for hydrogen evolution and hydrosulfurization， as well as electrically active materials in opto-electronics. Their morphologies and properties are also useful for energy storage applications such as electrodes for Li-ion batteries and supercapacitors.

Keywords：chemical-vapor-deposition； lithium storage properties； mos2 atomic layers； ws2 thin-films； molybdenum-disulfide； hydrogen evolution； large-area； valley polarization； integrated-circuits； liquid exfoliation

来源出版物：Nature Chemistry， 2013， 5（4）：263-275联系邮箱：Chhowalla， M； manish1@rci.rutgers.edu

被引频次：282

The Li-Ion Rechargeable Battery：A Perspective

Goodenough， JB； Park， KS

Abstract：Each cell of a battery stores electrical energy as chemical energy in two electrodes， a reductant（anode） and an oxidant（cathode），separated by an electrolyte that transfers the ionic component of the chemical reaction inside the cell and forces the electronic component outside the battery. The output on discharge is an external electronic current I at a voltage V for a time Delta t. The chemical reaction of arechargeable battery must be reversible on the application of a charging I and V. Critical parameters of a rechargeable battery are safety，density of energy that can be stored at a specific power input and retrieved at a specific power output， cycle and shelf life， storage efficiency，and cost of fabrication. Conventional ambient-temperature rechargeable batteries have solid electrodes and a liquid electrolyte. The positive electrode（cathode） consists of a host framework into which the mobile（working） cation is inserted reversibly over a finite solid solution range. The solid solution range， which is reduced at higher current by the rate of transfer of the working ion across electrode/electrolyte interfaces and within a host， limits the amount of charge per electrode formula unit that can be transferred over the time Delta t = Delta t（I）. Moreover， the difference between energies of the LUMO and the HOMO of the electrolyte， i.e.， electrolyte window， determines the maximum voltage for a long shelf and cycle life. The maximum stable voltage with an aqueous electrolyte is 1.5 V； the Li-ion rechargeable battery uses an organic electrolyte with a larger window， which increase the density of stored energy for a given Delta t. Anode or cathode electrochemical potentials outside the electrolyte window can increase V， but they require formation of a passivating surface layer that must be permeable to Li+and capable of adapting rapidly to the changing electrode surface area as the electrode changes volume during cycling. A passivating surface layer adds to the impedance of the Li+transfer across the electrode/electrolyte interface and lowers the cycle life of a battery cell. Moreover， formation of a passivation layer on the anode robs Li from the cathode irreversibly on an initial charge， further lowering the reversible Delta t. These problems plus the cost of quality control of manufacturing plague development of Li-ion rechargeable batteries that can compete with the internal combustion engine for powering electric cars and that can provide the needed low-cost storage of electrical energy generated by renewable wind and/or solar energy. Chemists are contributing to incremental improvements of the conventional strategy by investigating and controlling electrode passivation layers， improving the rate of Li+transfer across electrode/electrolyte interfaces， identifying electrolytes with larger windows while retaining a Li+conductivity sigma（Li）＞ 10-3S cm-1， synthesizing electrode morphologies that reduce the size of the active particles while pinning them on current collectors of large surface area accessible by the electrolyte， lowering the cost of cell fabrication， designing displacement-reaction anodes of higher capacity that allow a safe，fast charge， and designing alternative cathode hosts. However， new strategies are needed for batteries that go beyond powering hand-held devices， such as using electrode hosts with two-electron redox centers； replacing the cathode hosts by materials that undergo displacement reactions（e.g. sulfur） by liquid cathodes that may contain flow-through redox molecules， or by catalysts for air cathodes； and developing a solid electrolyte separator membrane that allows an organic and aqueous liquid electrolyte on the anode and cathode sides， respectively. Opportunities exist for the chemist to bring together oxide and polymer or graphene chemistry in imaginative morphologies.

Keywords：lithium batteries； cathode materials； redox-couple； 5 v； lifepo4； intercalation； electrolyte； stability； phosphates； extraction

来源出版物：Journal of The American Chemical Society， 2013， 135（4）：1167-1176

联系邮箱：Goodenough， JB； jgoodenough@mail.utexas.edu

被引频次：270

Progress， Challenges， and Opportunities in Two-Dimensional Materials Beyond Graphene

Butler， SZ； Hollen， SM； Cao， LY； et al.

Abstract：Graphene's success has shown that it is possible to create stable， single and few-atom-thick layers of van der Waals materials，and also that these materials can exhibit fascinating and technologically useful properties. Here we review the state-of-the-art of 2D materials beyond graphene. Initially， we will outline the different chemical classes of 2D materials and discuss the various strategies to prepare single-layer， few-layer， and multilayer assembly materials in solution， on substrates， and on the wafer scale. Additionally， we present an experimental guide for identifying and characterizing single-layer-thick materials， as well as outlining emerging techniques that yield both local and global information. We describe the differences that occur in the electronic structure between the bulk and the single layer and discuss various methods of tuning their electronic properties by manipulating the surface. Finally， we highlight the properties and advantages of single-， few-， and many-layer 2D materials in field-effect transistors， spin- and valley-tronics， thermoelectrics， and topological insulators， among many other applications.

Keywords：chemical-vapor-deposition； der-waals epitaxy； hexagonal boron-nitride； single-layer mos2； field-effect transistors； transition-metal dichalcogenides； scanning-tunneling-microscopy； topological insulator nanoribbons； lithium intercalation properties； langmuir-blodgett deposition

来源出版物：ACS Nano， 2013， 7（4）：2898-2926联系邮箱：Goldberger， JE； goldberger@chemistry.ohio-state.edu

被引频次：249

Chemical Management for Colorful， Efficient， and Stable Inorganic-Organic Hybrid Nanostructured Solar Cells

Noh， JH； Im， SH； Heo， JH； et al.

Abstract：Chemically tuned inorganic-organic hybrid materials， based on CH3NH3=MAPbI1-xBrx3perovskites， have been studied using UV-vis absorption and X-ray diffraction patterns and applied to nanostructured solar cells. The band gap engineering brought about by the chemical management of MAPbI1-xBrx3perovskites can be controllably tuned to cover almost the entire visible spectrum， enabling therealization of colorful solar cells. We demonstrate highly efficient solar cells exhibiting 12.3% in a power conversion efficiency of under standard AM 1.5， for the most efficient device， as a result of tunable composition for the light harvester in conjunction with a mesoporous TiO2film and a hole conducting polymer. We believe that the works highlighted in this paper represent one step toward the realization of low-cost， high-efficiency， and long-term stability with colorful solar cells.

Keywords：organometal halide perovskites； nanowires； crystals

来源出版物：Nano Letters， 2013， 13（4）：1764-1769联系邮箱：Seok， SI； seoksi@krict.re.kr

被引频次：233

Sodium-Ion Batteries

Slater， MD； Kim， D； Lee， E； et al.

Abstract：The status of ambient temperature sodium ion batteries is reviewed in light of recent developments in anode， electrolyte and cathode materials. These devices， although early in their stage of development， are promising for large-scale grid storage applications due to the abundance and very low cost of sodium-containing precursors used to make the components. The engineering knowledge developed recently for highly successful Li ion batteries can be leveraged to ensure rapid progress in this area， although different electrode materials and electrolytes will be required for dual intercalation systems based on sodium. In particular， new anode materials need to be identified，since the graphite anode， commonly used in lithium systems， does not intercalate sodium to any appreciable extent. A wider array of choices is available for cathodes， including high performance layered transition metal oxides and polyanionic compounds. Recent developments in electrodes are encouraging， but a great deal of research is necessary， particularly in new electrolytes， and the understanding of the SEI films. The engineering modeling calculations of Na-ion battery energy density indicate that 210 Wh kg-1in gravimetric energy is possible for Na-ion batteries compared to existing Li-ion technology if a cathode capacity of 200 mAh g-1and a 500 mAh g-1anode can be discovered with an average cell potential of 3.3 V.

Keywords：rechargeable lithium batteries； electrochemical insertion； cathode material； nanocrystalline Fe3O4； negative electrodes； petroleum cokes； phase-diagram； Na； intercalation； carbon

来源出版物：Advanced Functional Materials， 2013， 23（8）：947-958联系邮箱：Slater， MD； cjohnson@anl.gov

Chemistry Organic 有机化学

被引频次：190

Marine natural products

Blunt， JW； Copp， BR； Keyzers， RA； et al.

来源出版物：Natural Product Reports， 2013， 30（2）：237-323联系邮箱：Blunt， JW； john.blunt@canterbury.ac.nz

被引频次：137

Ribosomally synthesized and post-translationally modified peptide natural products：overview and recommendations for a universal nomenclature

Arnison， PG； Bibb， MJ； Bierbaum， G et al.

来源出版物：Natural Product Reports， 2013， 30（1）：108-160

被引频次：113

Recent Advances in Asymmetric Organocatalytic Construction of 3，3 '-Spirocyclic Oxindoles

Hong， L； Wang， R

Abstract：The asymmetric organocatalysis is definitely one of the most powerful and versatile tools for the rapid construction of variousspirocyclic oxindoles. In the past few years， a number of successful strategies based on organocatalysis have been developed for the construction of 3，3-spirocyclic oxindoles in high yields and excellent enantioselectivities under mild conditions. In this review， recent advances in this area are summarized and classified according to the spiro ring fused at the 3-position of the oxindole core.

来源出版物：Advanced Synthesis & Catalysis， 2013， 355（6）：1023-1052联系邮箱：Wang， R； wangrui@lzu.edu.cn

被引频次：90

Synthetic applications of photoredox catalysis with visible light

Xi， YM； Yi， H； Lei， AW

Abstract：In the past five years， visible-light mediated photoredox catalysis has been emerging as one of the fastest growing fields in organic chemistry because of its low cost， easy availability and environmental benignness. This review intends to summarize recent research progress in novel methodology development and application in organic synthesis， and is organized in terms of key reactive intermediates.

Keywords：C-H functionalization； transfer radical cyclization； atom-transfer addition； electron-transfer； metal-complexes； solar-energy；intramolecular cyclobutanation； photochemical conversion； organic-synthesis； amino radicals

来源出版物：Organic & Biomolecular Chemistry， 2013， 11（15）：2387-2403联系邮箱：Lei， AW； aiwenlei@whu.edu.cn

被引频次：74

Direct Trifluoromethylation of the CH Bond

Liu， H； Gu， ZH； Jiang， XF

Keywords：catalyzed oxidative trifluoromethylation； enantioselective alpha-trifluoromethylation； Pd（ii）-catalyzed ortho-trifluoromethylation； carbon-hydrogen bonds； room-temperature； boronic acids； mediated trifluoromethylation； heteroaromatic-compounds； H trifluoromethylation； photoredox catalysis

来源出版物：Advanced Synthesis & Catalysis， 2013， 355（4）：617-626联系邮箱：Jiang， XF； xfjiang@chem.ecnu.edu.cn

Chemistry Physical 物理化学

被引频次：270

Progress， Challenges， and Opportunities in Two-Dimensional Materials Beyond Graphene

Butler， SZ； Hollen， SM； Cao， LY； et al.

Keywords：chemical-vapor-deposition； der-waals epitaxy； hexagonal boron-nitride； single-layer mos2； field-effect transistors； transitionmetal dichalcogenides； scanning-tunneling-microscopy； topological insulator nanoribbons； lithium intercalation properties； langmuirblodgett deposition

来源出版物：ACS Nano， 2013， 7（4）：2898-2926联系邮箱：Goldberger， JE； goldberger@chemistry.ohio-state.edu

被引频次：249

Chemical Management for Colorful， Efficient， and Stable Inorganic-Organic Hybrid Nanostructured Solar Cells

Noh， JH； Im， SH； Heo， JH； et al.

Abstract：Chemically tuned inorganic-organic hybrid materials， based on CH3NH3=MA）PbI1-xBrx3perovskites， have been studied using UV-vis absorption and X-ray diffraction patterns and applied to nanostructured solar cells. The band gap engineering brought about by thechemical management of MA）PbI1-xBrx3perovskites can be controllably tuned to cover almost the entire visible spectrum， enabling the realization of colorful solar cells. We demonstrate highly efficient solar cells exhibiting 12.3% in a power conversion efficiency of under standard AM 1.5， for the most efficient device， as a result of tunable composition for the light harvester in conjunction with a mesoporous TiO2film and a hole conducting polymer. We believe that the works highlighted in this paper represent one step toward the realization of low-cost， high-efficiency， and long-term stability with colorful solar cells.

Keywords：organometal halide perovskites； nanowires； crystals

来源出版物：Nano Letters， 2013， 13（4）：1764-1769联系邮箱：Seok， SI； seoksi@krict.re.kr

被引频次：233

Sodium-Ion Batteries

Slater， MD； Kim， D； Lee， E； et al.

来源出版物：Advanced Functional Materials， 2013， 23（8）：947-958联系邮箱：Slater， MD； cjohnson@anl.gov

被引频次：190

Perovskites：The Emergence of a New Era for Low-Cost， High-Efficiency Solar Cells

Snaith， HJ

Abstract：Over the last 12 months， we have witnessed an unexpected breakthrough and rapid evolution in the field of emerging photovoltaics， with the realization of highly efficient solid-state hybrid solar cells based on organometal trihalide perovskite absorbers. In this Perspective， the steps that have led to this discovery are discussed， and the future of this rapidly advancing concept have been considered. It is likely that the next few years of solar research will advance this technology to the very highest efficiencies while retaining the very lowest cost and embodied energy. Provided that the stability of the perovskite-based technology can be proven， we will witness the emergence of a contender for ultimately low-cost solar power.

Keywords：organometal halide perovskites； photovoltaic cells； heterojunctions； semiconductors； electrodes； deposition； 20-percent； conversion； absorbers； layer

来源出版物：Journal of Physical Chemistry Letters， 2013， 4（21）：3623-3630联系邮箱：Snaith， HJ； h.snaith1@physics.ox.ac.uk

被引频次：174

Organometal Perovskite Light Absorbers Toward a 20% Efficiency Low-Cost Solid-State Mesoscopic Solar Cell

Park， NG

Abstract：Recently， perovskite CH3NH3PbI3sensitizer has attracted great attention due to its superb light-harvesting characteristics. Organometallic or organic materials were mostly used as sensitizers for solid-state dye-sensitized solar cells at early stages. Inorganic nanocrystals have lately received attention as light harvesters due to their high light-absorbing properties. Metal chalcogenides have been investigated with solid-state dye-sensitized solar cells； however， the best power conversion efficiency was reported to be around 6%. CH3NH3PbX3（X = Cl， Br， or I） perovskite sensitizer made a breakthrough in solid-state mescoscopic solar cells， where the first record efficiency of around 10% was reported in 2012 using submicrometer-thick TiO2film sensitized with CH3NH3PbI3. A rapid increase in efficiency approaching 14% followed shortly. In this Perspective， recent progress in perovskite-sensitized solid-state mesoscopic solar cells is reviewed. On the basis of the recent achievements， a power conversion efficiency as high as 20% is expected based on optimized perovskite-based solid-state solar cells.

Keywords：photovoltaic performance； mesoporous titania； halide perovskites； organic-dye； TiO2films； electrolyte； improvement； sensitizer；device； superconductivity

来源出版物：Journal of Physical Chemistry Letters， 2013， 4（15）：2423-2429联系邮箱：Park， NG； npark@skku.edu

Clinical Neurology 临床神经病学

被引频次：383

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Jauch， EC； Saver， JL； Adams， HP； et al.

Abstract：Background and Purpose：The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audiences are prehospital care providers， physicians， allied health professionals， and hospital administrators responsible for the care of acute ischemic stroke patients within the first 48 hours from stroke onset. These guidelines supersede the prior 2007 guidelines and 2009 updates.

Methods：Members of the writing committee were appointed by the American Stroke Association Stroke Council's Scientific Statement Oversight Committee， representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Panel members were assigned topics relevant to their areas of expertise， reviewed the stroke literature with emphasis on publications since the prior guidelines， and drafted recommendations in accordance with the American Heart Association Stroke Council's Level of Evidence grading algorithm.

Results：The goal of these guidelines is to limit the morbidity and mortality associated with stroke. The guidelines support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition； emergency medical services activation， transport， and triage； through the initial hours in the emergency department and stroke unit. The guideline discusses early stroke evaluation and general medical care， as well as ischemic stroke， specific interventions such as reperfusion strategies， and general physiological optimization for cerebral resuscitation.

Conclusions：Because many of the recommendations are based on limited data， additional research on treatment of acute ischemic stroke remains urgently needed.

Keywords：middle-cerebral-artery； tissue-plasminogen-activator； randomized controlled-trial； magnetic-resonance angiography； internal carotid-artery； placebo-controlled trial； diffusion-weighted mri； digital-subtraction-angiography； computed-tomography angiography；emergency medical-services

来源出版物：Stroke， 2013， 44（3）：870-947

被引频次：238

Tracking pathophysiological processes in Alzheimer's disease：an updated hypothetical model of dynamic biomarkers

Jack， CR； Knopman， DS； Jagust， WJ； et al.

Abstract：In 2010， we put forward a hypothetical model of the major biomarkers of Alzheimer's disease（AD）. The model was received with interest because we described the temporal evolution of AD biomarkers in relation to each other and to the onset and progression of clinical symptoms. Since then， evidence has accumulated that supports the major assumptions of this model. Evidence has also appeared that challenges some of our assumptions， which has allowed us to modify our original model. Refinements to our model indude indexing of individuals by time rather than clinical symptom severity； incorporation of interindividual variability in cognitive impairment associated with progression of AD pathophysiology； modifications of the specific temporal ordering of some biomarkers； and recognition that the two major proteinopathies underlying AD biomarker changes， amyloid beta（A beta） and tau， might be initiated independently in sporadic AD，in which we hypothesise that an incident A beta pathophysiology can accelerate antecedent limbic and brainstem tauopathy.

Keywords：mild cognitive impairment； positron-emission-tomography； cerebrospinal-fluid a-beta（42）； pittsburgh compound-b； amyloid deposition； in-vivo； a-beta； apolipoprotein-e； csf biomarkers； brain atrophy

来源出版物：Lancet Neurology， 2013， 12（2）：207-216联系邮箱：Jack， CR； jack.clifford@mayo.edu

被引频次：158

Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis：an observational cohort study

Titulaer， MJ； McCracken， L； Gabilondo， I； et al.

Abstract：Background：Anti-NMDA receptor（NMDAR） encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined. We aimed to assess the presentation of the disease， the spectrum of symptoms， immunotherapies used， timing of improvement， and long-term outcome.

Methods：In this multi-institutional observational study， we tested for the presence of NMDAR antibodies in serum or C SF samples ofpatients with encephalitis between Jan 1，2007， and Jan 1， 2012. All patients who tested positive for NMDAR antibodies were included in the study； patients were assessed at symptom onset and at months 4，8，12，18， and 24， by use of the modified Rankin scale（mRS）. Treatment included first-line immunotherapy（steroids， intravenous immunoglobulin， plasmapheresis）， second-line immunotherapy（ritincimab， cydophosphamide）， and tumour removal. Predictors of outcome were determined at the Universities of Pennsylvania（PA， USA） and Barcelona（Spain） by use of a generalised linear mixed model with binary distribution.

Results：We enrolled 577 patients（median age 21 years， range 8 months to 85 years）， 211 of whom were children（＜18 years）. Treatment effects and outcome were assessable in 501（median follow-up 24 months， range 4-186）：472（94%） underwent first-line immunotherapy or tumour removal， resulting in improvement within 4 weeks in 251（53%）. Of 221 patients who did not improve with first-line treatment， 125（57%） received second-line immunotherapy that resulted in a better outcome（mRS 0-2） than those who did not（odds ratio ［OR［ 2.69， CI 1-24-5.80； p=0.012）. During the first 24 months， 394 of 501 patients achieved a good outcome（mRS 0-2； median 6 months， IQR 2-12） and 30 died. At 24 months' follow-up， 203（81%） of 252 patients had good outcome. Outcomes continued to improve for up to 18 months after symptom onset. Predictors of good outcome were early treatment（0.62，0.50-0.76； p ＜0.0001） and no admission to an intensive care unit（0.12，0.06-0-22； p＜0.0001）. 45 patients had one or multiple relapses（representing a 12% risk within 2 years）； 46（67%） of 69 relapses were less severe than initial episodes（p＜0.0001）. In 177 children， predictors of good outcome and the magnitude of effect of second-line immunotherapy were similar to those of the entire cohort.

Interpretation：Most patients with anti-NMDAR encephalitis respond to immunotherapy. Second-line immunotherapy is usually effective when first-line treatments fail. In this cohort， the recovery of some patients took up to 18 months.

Keywords：ovarian teratoma； pathogenesis； disorders

来源出版物：Lancet Neurology， 2013， 12（2）：157-165联系邮箱：Dalmau， J； josep.dalmau@uphs.upenn.edu

被引频次：156

The global prevalence of dementia：A systematic review and metaanalysis

Prince， M； Bryce， R； Albanese， E； et al.

Abstract：Background：The evidence base on the prevalence of dementia is expanding rapidly， particularly in countries with low and middle incomes. A reappraisal of global prevalence and numbers is due， given the significant implications for social and public policy and planning.

Methods：In this study we provide a systematic review of the global literature on the prevalence of dementia（1980-2009） and metaanalysis to estimate the prevalence and numbers of those affected， aged ＞= 60 years in 21 Global Burden of Disease regions.

Results：Age-standardized prevalence for those aged≥60 years varied in a narrow band， 5%-7% in most world regions， with a higher prevalence in Latin America（8.5%）， and a distinctively lower prevalence in the four sub-Saharan African regions（2%-4%）. It was estimated that 35.6 million people lived with dementia worldwide in 2010， with numbers expected to almost double every 20 years， to 65.7 million in 2030 and 115.4 million in 2050. In 2010， 58% of all people with dementia lived in countries with low or middle incomes， with this proportion anticipated to rise to 63% in 2030 and 71% in 2050.

Conclusion：The detailed estimates in this study constitute the best current basis for policy-making， planning， and allocation of health and welfare resources in dementia care. The age-specific prevalence of dementia varies little between world regions， and may converge further. Future projections of numbers of people with dementia may be modified substantially by preventive interventions（lowering incidence），improvements in treatment and care（prolonging survival）， and disease-modifying interventions（preventing or slowing progression）. All countries need to commission nationally representative surveys that are repeated regularly to monitor trends.

Keywords：dwelling brazilian population； alzheimers-disease； elderly-people； african-americans； cognitive impairment； developing-countries； major subtypes； 2 communities； west-africa； sao-paulo

来源出版物：Alzheimers & Dementia， 2013， 9（1）：63-75联系邮箱：Prince， M； Martin.Prince@kcl.ac.uk

被引频次：148

2013Alzheimer's disease facts and figures Alzheimer's Association

Thies， W； Bleiler， L

Abstract：This report provides information to increase understanding of the public health impact of Alzheimer's disease（AD）， including incidence and prevalence， mortality rates， health expenditures and costs of care， and effect on caregivers and society in general. It also explores the roles and unique challenges of long-distance caregivers， as well as interventions that target those challenges. An estimated 5.2 million Americans have AD. Approximately 200000 people younger than 65 years with AD comprise the younger onset AD population； 5 million comprise the older onset AD population. Throughout the coming decades， the baby boom generation is projected to add about 10 million to the total number of people in the United States with AD. Today， someone in America develops AD every 68 seconds. By 2050，one new case of AD is expected to develop every 33 seconds， or nearly a million new cases per year， and the total estimated prevalence is expected to be 13.8 million. AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americansage 65 years or older. Between 2000 and 2010， the proportion of deaths resulting from heart disease， stroke， and prostate cancer decreased 16%， 23%， and 8%， respectively， whereas the proportion resulting from AD increased 68%. The number of deaths from AD as determined by official death certificates（83494 in 2010） likely underrepresents the number of AD-related deaths in the United States. A projected 450000 older Americans with AD will die in 2013， and a large proportion will die as a result of complications of AD. In 2012， more than 15 million family members and other unpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other dementias， a contribution valued at more than $216 billion. Medicare payments for services to beneficiaries age 65 years and older with AD and other dementias are three times as great as payments for beneficiaries without these conditions， and Medicaid payments are 19 times as great. Total payments in 2013 for health care， long-term care， and hospice services for people age 65 years and older with dementia are expected to be $203 billion（not including the contributions of unpaid caregivers）. An estimated 2.3 million caregivers of people with AD and other dementias live at least 1 hour away from the care recipient. These "long-distance caregivers" face unique challenges， including difficulty in assessing the care recipient's true health condition and needs， high rates of family disagreement regarding caregiving decisions，and high out-of-pocket expenses for costs related to caregiving. Out-of-pocket costs for long-distance caregivers are almost twice as high as for local caregivers.

Keywords：mild cognitive impairment； nursing-home placement； traumatic brain-injury； vascular risk-factors； population-based cohort；c-reactive protein； 3 decades later； late-life； national institute； leisure activities

来源出版物：Alzheimers & Dementia， 2013， 9（2）：208-245

Computer Science Artificial Intelligence 计算机科学，人工智能

被引频次：86

A Novel Control Design on Discrete-Time Takagi-Sugeno Fuzzy Systems With Time-Varying Delays

Su， XJ； Shi， P； Wu， LG； et al.

Abstract：This paper focuses on analyzing a new model transformation of discrete-time Takagi-Sugeno（T-S） fuzzy systems with time-varying delays and applying it to dynamic output feedback（DOF） controller design. A new comparison model is proposed by employing a new approximation for time-varying delay state， and then， a delay partitioning method is used to analyze the scaled small gain of this comparison model. A sufficient condition on discrete-time T-S fuzzy systems with time-varying delays， which guarantees the corresponding closed-loop system to be asymptotically stable and has an induced l2 disturbance attenuation performance， is derived by employing the scaled small-gain theorem. Then， the solvability condition for the induced l2 DOF control is also established， by which the DOF controller can be solved as linear matrix inequality optimization problems. Finally， examples are provided to illustrate the effectiveness of the proposed approaches.

Keywords：output-feedback control； h-infinity control； stability analysis； nonlinear-systems； lmi approach； fault-detection； model； stabilization

来源出版物：IEEE Transactions on Fuzzy Systems， 2013， 21（4）：655-671联系邮箱：Su， XJ； suxiaojie1985@gmail.com

被引频次：85

State-of-the-Art in Visual Attention Modeling

Borji， A； Itti， L

Abstract：Modeling visual attention-particularly stimulus-driven， saliency-based attention-has been a very active research area over the past 25 years. Many different models of attention are now available which， aside from lending theoretical contributions to other fields， have demonstrated successful applications in computer vision， mobile robotics， and cognitive systems. Here we review， from a computational perspective， the basic concepts of attention implemented in these models. We present a taxonomy of nearly 65 models， which provides a critical comparison of approaches， their capabilities， and shortcomings. In particular， 13 criteria derived from behavioral and computational studies are formulated for qualitative comparison of attention models. Furthermore， we address several challenging issues with models，including biological plausibility of the computations， correlation with eye movement datasets， bottom-up and top-down dissociation， and constructing meaningful performance measures. Finally， we highlight current research trends in attention modeling and provide insights for future.

Keywords：human eye-movements； selective attention； spatiotemporal saliency； discriminant saliency； neurobiological model； patternrecognition； bayesian-inference； neural mechanisms； video compression； spatial attention

来源出版物：IEEE Transactions on Pattern Analysis and Machine Intelligence， 2013， 35（1）：185-207

联系邮箱：Borji， A； borji@usc.edu

被引频次：72

Stochastic Synchronization of Markovian Jump Neural Networks With Time-Varying Delay Using Sampled Data

Wu， ZG； Shi， P； Su， HY； et al.

Abstract：In this paper， the problem of sampled-data synchronization for Markovian jump neural networks with time-varying delay and variable samplings is considered. In the framework of the input delay approach and the linear matrix inequality technique， two delay-dependent criteria are derived to ensure the stochastic stability of the error systems， and thus， the master systems stochastically synchronize with the slave systems. The desired mode-independent controller is designed， which depends upon the maximum sampling interval. The effectiveness and potential of the obtained results is verified by two simulation examples.

Keywords：exponential stability analysis； distributed delays； discrete； parameters； systems； stabilization

来源出版物：IEEE Transactions on Cybernetics， 2013， 43（6）：1796-1806联系邮箱：Wu， ZG； nashwzhg@gmail.com

被引频次：66

Robust Recovery of Subspace Structures by Low-Rank Representation

Liu， GC； Lin， ZC； Yan， SC； et al.

Abstract：In this paper， we address the subspace clustering problem. Given a set of data samples（vectors） approximately drawn from a union of multiple subspaces， our goal is to cluster the samples into their respective subspaces and remove possible outliers as well. To this end， we propose a novel objective function named Low-Rank Representation（LRR）， which seeks the lowest rank representation among all the candidates that can represent the data samples as linear combinations of the bases in a given dictionary. It is shown that the convex program associated with LRR solves the subspace clustering problem in the following sense：When the data is clean， we prove that LRR exactly recovers the true subspace structures； when the data are contaminated by outliers， we prove that under certain conditions LRR can exactly recover the row space of the original data and detect the outlier as well； for data corrupted by arbitrary sparse errors， LRR can also approximately recover the row space with theoretical guarantees. Since the subspace membership is provably determined by the row space，these further imply that LRR can perform robust subspace clustering and error correction in an efficient and effective way.

Keywords：motion segmentation； multibody factorization； matrix completion； gpca algorithm； mixed data； objects

来源出版物：IEEE Transactions on Pattern Analysis and Machine Intelligence， 2013， 35（1）：171-184

联系邮箱：Liu， GC； gutty.liu@gmail.com

被引频次：59

Distributed Synchronization in Networks of Agent Systems With Nonlinearities and Random Switchings

Tang， Y； Gao， HJ； Zou， W； et al.

Abstract：In this paper， the distributed synchronization problem of networks of agent systems with controllers and nonlinearities subject to Bernoulli switchings is investigated. Controllers and adaptive updating laws injected in each vertex of networks depend on the state information of its neighborhood. Three sets of Bernoulli stochastic variables are introduced to describe the occurrence probabilities of distributed adaptive controllers， updating laws and nonlinearities， respectively. By the Lyapunov functions method， we show that the distributed synchronization of networks composed of agent systems with multiple randomly occurring nonlinearities， multiple randomly occurring controllers， and multiple randomly occurring updating laws can be achieved in mean square under certain criteria. The conditions derived in this paper can be solved by semi-definite programming. Moreover， by mathematical analysis， we find that the coupling strength， the probabilities of the Bernoulli stochastic variables， and the form of nonlinearities have great impacts on the convergence speed and the terminal control strength. The synchronization criteria and the observed phenomena are demonstrated by several numerical simulation examples. In addition， the advantage of distributed adaptive controllers over conventional adaptive controllers is illustrated.

Keywords：complex dynamical networks； multiagent systems； neural-networks； exponential synchronization； adaptive synchronization；missing measurements； consensus seeking； stability； discrete； delay

来源出版物：IEEE Transactions on Cybernetics， 2013， 43（1）：358-370联系邮箱：Tang， Y； tangtany@gmail.com

（责任编辑姚玉琴）

EFSUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography. Part 1：Basic Principles and Technology

Bamber， J； Cosgrove， D； Dietrich， CF； et al.

The technical part of these Guidelines and Recommendations， produced under the auspices of EFSUMB， provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described， and guidance is provided on optimisation of scanning technique， image display， image interpretation and some of the known image artefacts.

acoustic radiation force； in-vivo demonstration； transient elastography； elastic properties； soft-tissue； liver fibrosis； hepatitis-c；breast； strain； contrast