简介：AbstractBackground:Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.Methods:CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.Results:Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.Conclusion:Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

简介：AbstractImportance:First branchial cleft anomalies (FBCAs) are rare congenital malformations, accounting for < 8% of all branchial cleft anomalies. However, little is currently known about the cause of FBCAs at the molecular level.Objective:To identify genomic alterations related to the genetic etiology of FBCAs in Chinese children.Methods:We performed whole-exome sequencing of samples from 10 pediatric patients with FBCAs. Data analysis was carried out using the Burrow-Wheeler Alignment software package, and the dbSNP database for comparisons. Rare variants were further validated by Sanger sequencing. Insertion/deletions (indels) were examined using the Genome Analysis Toolkit.Results:We identified 14 non-synonymous mutations in seven potential FBCA-susceptibility genes (TRAPPC12, NRP2, NPNT, SH3RF2, RHPN1, TENM4, and ARMCX4). We also detected 133 shared small indels in 125 genes. Gene Ontology analysis indicated that most of the identified genes played critical roles in development and differentiation pathways involved in regulating organ development.Interpretation:We characterized the mutational landscape in pathways involved in development and differentiation in Chinese children with FBCA. The results identified potential pathogenic genes and mutations related to FBCA, and provide molecular-level support for the branchial theory of FBCA pathogenesis.

简介：AbstractObjective:He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia, and the causative gene locus was mapped to chromosome 10q11.2. The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency.Methods:Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated. The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants. The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows-Wheeler Aligner software, Sequence Alignment/Map tools and ANNOVAR tool. In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression. R environment was used to conduct t-tests. The study protocol was approved by the Research Ethics Committee of Bio-X Institutes, Shanghai Jiao Tong University (M2011004).Results:The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1α as the molecular etiology of the disease. The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12, at which time the primary teeth should have been replaced with permanent teeth. Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity.Conclusion:c.-144 C>A variant of PRKG1α involving odontoclast-associated root resorption is responsible for He-Zhao deficiency, unlike other forms of hypodontia, which typically involve odontoblast dysfunction.

简介：AbstractImportance:Pathogenic variants in the RBM20 gene are associated with aggressive dilated cardiomyopathy (DCM). Recently, RBM20 was found to be associated with left ventricular non-compaction cardiomyopathy (LVNC). Thus far, only five families with LVNC have been reported to carry variants in RBM20. It remains unknown whether the variants in RBM20 associated with DCM can also cause LVNC.Objective:To elucidate the causative RBM20 variant in two unrelated patients with both LVNC and DCM, and to identify the clinical characteristics associated with variants in RBM20.Methods:Trio whole-exome sequencing (WES) was performed. Variants were filtered and classified in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG).Results:We identified two distinct de novo variants in RBM20 (one per patient) in these two patients with LVNC. Both variants have been reported in patients with DCM, without the LVNC phenotype. Patient 1 was an 11-year-old girl who had DCM, LVNC, and heart failure; the ratio of noncompacted-to-compacted myocardium was 2.7:1. A de novo heterozygous variant c.1907G>A (p.Arg636His) in exon 9 was identified in this patient. Patient 2 was a 13-year-old boy who had clinical phenotypes identical to those of Patient 1; the ratio of noncompacted-to-compacted myocardium was 3.2:1 in this patient. WES revealed a de novo heterozygous variant c.1909A>G (p.Ser637Gly) in exon 9. Both variants were previously characterized as pathogenic, and our study classified them as pathogenic variants based on the ACMG guidelines.Interpretation:We found that two patients with LVNC had variants in RBM20. Our results extended the clinical spectrum of the two RBM20 variants and illustrated that the same variant in RBM20 can cause DCM, with or without the LVNC phenotype.

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简介：Inrecentyears,heavyionbeamshavebeenrecognizedasaneffectiveandefficientphysicalmutagenduetotheircapacitytoinducemutationswithhighfrequencyandbroadspectrum.Nowadays,itisnotsodifficulttoproducevariousmutantsinplants.However,tominetheresponsiblemutatedgeneshasbeenanimportantchallenge.Formutationisolation,map-basedcloningisoneofthemajortraditionalwaystoisolatethemutantgenesthatcontroltraitsofinterestinforwardgeneticsstudies.However,theprocessofmap-basedcloningisusuallycomplicatedandtime-consuming.

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简介：1.有时这两个词大致同义,只是位置不同:all要放在冠词、指示代词、物主代词等之前,而whole应放在这些词之后。allthefamily/thewholefamily全家2.在复数名词前一般用all,在单数可数名词前一般用whole.

简介：Wholelanguage,arelativelynewapproachemergedintheNorthAmericaaboutmorethanthirtyyearsago,hasbecomeoneofthetwomajorphilosophies(PhonicsandWholeLanguage)inteachingandlearninglanguage."Thefutureofwholelanguageisthefutureofeducation."(Goodman,1992).Wholelanguageisgainingitspopularityallovertheworldandhasfounditswayintovariouslanguagesettings.Ithasalsobeenusheredintothefieldofsecondlanguageeducation.Wholelan-guageentailswholelearners,wholeteachers,wholetexts,wholemethods,wholeskillsandwholeenvironments.Thispaperat-temptstointroduceitsdefinitionsandexploreitsimplicationsinteachingandlearningEnglishasaforeignlanguage(EFL).Italsoanalyzesitslimitationssothatinstructors,whenimple-mentingthisapproachinEFLclassrooms,couldmakenecessaryadaptationsbytakingintoconsiderationthecharacteristicsofEFLlearners,includingtheirlinguisticproficiency,sociocultur-alvariables,andcareerorientations,andatthesametimemakesurethatEFLclassroomactivitiesreflectwholenessofthemajorcomponentsunderlyingthisapproach.

简介：Theworkingprofileofwholecycloidalgearismadeupofepicycloidandhypocycloidentirely,accordingtothetheoryofmeshingofgearsandthepropertiesofthecycloid,dealswiththederivationofthepressureangleformulaforthewholecycloidalgearintheory,andrevealschangesofthepressureangleofwholecycloidalgearthroughexamples,findstheapplicationrelationshipsbetweenthepressureangleandotherdesignparametersofthewholecycloidalgear,provesthepossibilitythatthewholecycloidalgearcanbeusedininternalparallelmovegearmechanism,alsoprovidestheoreticfundamentfordesigninginternalparallelmovewholecycloidalgearcorrectly.

简介：虽然all和whole的意思差不多，作“全部的，全体的”解时，是同义词，但它们的用法仍有区别。

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简介：AbstractAlthough whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders, about half of the patients still do not receive a molecular diagnosis. The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing (RNA-seq) in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence. RNA-seq data can be used to identify aberrantly spliced genes, detect allele-specific expression, and identify gene expression outliers. Amongst eight studies utilizing RNA-seq, a mean diagnostic uplift of 15% has been reported. Here, we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.

简介：ThetotalinstalledcapacityofelectricpowerintheTibetAutonomousRegionisnearly0.5millionkilo-watts,theannualelectricenergy,productionachieved12hundredmillionkilowatts-hour.NearlyeveryCountyinTibetrealizedelectrification.Bytheendof2004,thepopulationwhichusedelec-tricityhasreachedmorethan1600000,therateofelec-tricityusedpopulationcovered57%ofthewholere-gion,71%ofthesmalltownsand40%ofthevillagesinTibethavebeenelectrified.In1965,whentheTibetAutonomousRegionwas

简介：AmutuallyorthogonalsystemofrationalSomeapproximationresultsareestablishedfunctionsonthewholelineisintroduced.Asanexampleofapplications,amodifiedLegendrerationalspectralschemeisgivenfortheDiracequation.Itsnumericalsolutionkeepsthesameconservationasthegenuinesolution.Thisfeaturenotonlyleadstoreasonablenumericalsimulationofnonlinearwaves,butalsosimplifiestheanalysis.Theconvergenceoftheproposedschemeisproved.Numericalresultsdemonstratetheefficiencyofthisnewapproachandcoincidewiththeanalysiswell.

简介：Thesimulationofthewholeship-bridgecollisionprocesscanbeeffectivelycarriedoutbynonlineardynamicfiniteelementmethod.Basedonthesimpledescriptionofthetheory,ascenarioofa40000DWToiltankercollidingwithabridgeacrosstheYangtzeRiverisdesignedforsimulation.Thetechnologyofstructuremodelingandthedeterminationofrelatedparametersareintroduced.Thedeformationofthebulbbow,thehistoryofcollisionforcechange,theexchangeofcollisionenergyandthestressdistributionofthebridgepieraredescribedindetail,whichareofgreatvaluetobridgede-signandbridgepierdamageestimation,Somemechanicalcharactersintheprocessofship-bridgecollisionaredescribed.Moreaccurateresultscanbeproducedbyfiniteelementmethodthanthatbyempiricalformulasandsimplifiedanalyticalmethods.

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简介：Next-generationsequencing(NGS)isanewtechnologyusedforDNAandRNAsequencingandvariant/mutationdetection.NGScansequencehundredsandthousandsofgenesorwholegenomeinashortperiodoftime.Thesequencevariants/mutationsdetectedbyNGShavebeenwidelyusedfordiseasediagnosis,prognosis,therapeuticdecision,andfollowupofpatients.Thecapacityofitsmassiveparallelsequencingoffersnewopportunitiesforpersonalizedprecisionmedicine.