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Predicting responses to platin chemotherapy agents with biochemically-inspired machine learning

Signal Transduction and Targeted Therapy 2019年第1期4卷 636-647页

作者： Eliseos J.Mucaki Jonathan Z.L.Zhao Daniel J.Lizotte peter k.rogan Department of Biochemistry Schulich School of Medicine and DentistryWestern UniversityLondonON N6A 2C1Canada Department of Computer Science Faculty of ScienceWestern UniversityLondonON N6A 2C1Canada Department of Epidemiology&Biostatistics Schulich School of Medicine and DentistryWestern UniversityLondonON N6A 2C1Canada Cytognomix Inc.LondonON N5X 3X5Canada Department of Oncology Schulich School of Medicine and DentistryWestern UniversityLondonON N6A 2C1Canada

The selection of effective genes that accurately predict chemotherapy responses might improve cancer *** compare optimized gene signatures for cisplatin,carboplatin,and oxaliplatin responses in the same cell lines and validate each signature using data from patients with *** support vector machine learning is used to derive gene sets whose expression is related to the cell line GI 50 values by backwards feature selection with *** genes and functional pathways distinguishing sensitive from resistant cell lines are identified by contrasting signatures obtained at extreme and median GI 50 *** of gene signatures at different thresholds are combined to reduce the dependence on specific GI 50 values for predicting drug *** most accurate gene signatures for each platin are:cisplatin:BARD1,BCL2,BCL2L1,CDkN2C,FAAP24,FEN1,MAP3k1,MAPk13,MAPk3,NFkB1,NFkB2,SLC22A5,SLC31A2,TLR4,and TWIST1;carboplatin:AkT1,EIF3k,ERCC1,GNGT1,GSR,MTHFR,NEDD4L,NLRP1,NRAS,RAF1,SGk1,TIGD1,TP53,VEGFB,and VEGFC;and oxaliplatin:BRAF,FCGR2A,IGF1,MSH2,NAGk,NFE2L2,NQO1,PANk3,SLC47A1,SLCO1B1,and *** from The Cancer Genome Atlas(TCGA)patients with bladder,ovarian,and colorectal cancer were used to test the cisplatin,carboplatin,and oxaliplatin signatures,resulting in 71.0%,60.2%,and 54.5%accuracies in predicting disease recurrence and 59%,61%,and 72%accuracies in predicting remission,*** cisplatin signature predicted 100%of recurrence in non-smoking patients with bladder cancer(57%disease-free;N=19),and 79%recurrence in smokers(62%disease-free;N=35).This approach should be adaptable to other studies of chemotherapy responses,regardless of the drug or cancer types.

关键词： bladder chemotherapy signature

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Interpretation, Stratification and Evidence for Sequence Variants Affecting mRNA Splicing in Complete Human Genome Sequences

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Genomics, Proteomics & Bioinformatics 2013年第2期11卷 77-85页

作者： Ben C.Shirley Eliseos J.Mucaki Tyson Whitehead Paul I.Costea Pelin Akan peter k.rogan Department of Computer Science Middlesex CollegeThe University of Western Ontario Department of Biochemistry Schulich School of Medicine and DentistryThe University of Western Ontario SHARCNET Royal Institute of Technology Science for Life Laboratory Cytognomix Inc.

Information theory-based methods have been shown to be sensitive and specific for pre- dicting and quantifying the effects of non-coding mutations in Mendelian diseases. We present the Shannon pipeline software for genome-scale mutation analysis and provide evidence that the soft- ware predicts variants affecting mRNA splicing. Individual information contents （in bits） of refer- ence and variant splice sites are compared and significant differences are annotated and prioritized. The software has been implemented for CLC-Bio Genomics platform. Annotation indicates the context of novel mutations as well as common and rare SNPs with splicing effects. Potential natural and cryptic mRNA splicing variants are identified, and null mutations are distinguished from leaky mutations. Mutations and rare SNPs were predicted in genomes of three cancer cell lines （U2OS, U251 and A431）, which were supported by expression analyses. After filtering, tractable numbers of potentially deleterious variants are predicted by the software, suitable for further laboratory investigation. In these cell lines, novel functional variants comprised 6-17 inactivating mutations, 1 5 leaky mutations and 6-13 cryptic splicing mutations. Predicted effects were validated by RNA-seq analysis of the three aforementioned cancer cell lines, and expression microarray analysis of SNPs in HapMap cell lines.

关键词： Mutation mRNA splicing Information theory Next-generation sequencing Genome interpretation

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Web-service Available for the Shannon Human Splicing Pipeline for inRNA Splicing Mutation Analysis

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Genomics,Proteomics & Bioinformatics 2014年第3期 151-151页

作者： peter k.rogan Department of Biochemistry Schulich School of Medicine and Dentistry University of Western Ontario

The Shannon Human Splicing Pipeline for mRNA Splicing Mutation Analysis,the software described previously[1],is now available as a web-service at http://***-ins to the CLC bio Genomics workbench and server are also su... 详细信息

关键词： Web-service Available for the Shannon Human Splicing Pipeline for inRNA Splicing Mutation Analysis

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Disentangling confusions in inflorescence morphology:Patterns and diversity of reproductive shoot ramification in angiosperms

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Journal of Systematics and Evolution 2010年第4期48卷 225-239页

作者： peter k.ENDRESS Institute of Systematic Botany University of Zurich

Terminology of inflorescence diversity has often been used in a confusing way in the literature,partly because it was based on uncritical and outdated *** particular,the terms cyme,thyrse,and panicle have been *** a more critical classification worked out by several authors is available,it is unfortunately not in general use because most of the relevant publications are written in *** addition,some terms have not been used in the same way by morphologists and developmental *** present review attempts to remedy the situation with a simple outline of a classification based on:(i)different branching patterns;(ii)differential elongation of axes of different orders;and(iii)repetition of basic ramification patterns in different *** and cymose branching are two extreme patterns;the former with limitation of axial orders to two,the second with limitation of lateral axes of each order to *** a branching system,a sequence of racemose→cymose and,within the cyme,of dichasial→monochasial is common,but the reverse sequence generally does not *** and evolutionary aspects of inflorescences are briefly *** patterns are often stable in larger *** of mutants studied in developmental genetic studies are mainly altered in flower or branch numbers or relative branch length,but not in branching *** is also a contribution towards the goal of a unified terminology for the different fields of biology dealing with inflorescences.

关键词： branching patterns cymose inflorescence panicle racemose reproductive shoot thyrse

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Hydrogenic Donor in a Spherical Quantum Dot with Different Confinements

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Chinese Physics Letters 2009年第8期26卷 309-312页

作者： A. John peter k. Navaneethakrishnan Govt. Arts College Melur-625 106 Madurad India Madurai kamaraj-University Madurai-625 021 India

Binding energies of a hydrogenic donor in a spherical GaAs quantum dot surrounded by Ga1-xA4xAs matrix are calculated. The results are presented for realistie barrier heights corresponding to different values of x （x 〈 0.4）. The calculations are performed under two different conditions：（i） a spherical dot with square well confinement and （ii） a dot with parabolic potential well confinement. The results show that （i） the donor ionization energies are always higher under parabolic confinement as compared to a dot of the same radius under square well confinement and （ii） the oscillator strengths coupling ground state with excited states are two orders larger under parabolic confinement. Our results are in agreement with the results of other researchers.

关键词： No English keyword

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Influence of degree of interlock on confined strength of jointed hard rock masses

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Journal of Rock Mechanics and Geotechnical Engineering 2020年第6期12卷 1152-1170页

作者： Navid Bahrani peter k.kaiser a Department of Civil and Resource Engineering Dalhousie UniversityHalifaxNova ScotiaCanada b Bharti School of Engineering Laurentian UniversitySudburyOntarioCanada

The strength of jointed rock mass is strongly controlled by the degree of interlock between its constituent rock *** degree of interlock constrains the kinematic freedom of individual rock blocks to rotate and slide along the block forming *** HoekeBrown(HB)failure criterion and the geological strength index(GSI)were developed based on experiences from mine slopes and tunneling projects in moderately to poorly interlocked jointed rock *** has since then been demonstrated that the approach to estimate the HB strength parameters based on the GSI strength scaling equations(called the‘GSI strength equations’)tends to underestimate the confined peak strength of highly interlocked jointed rock masses(***>65),where the rock mass is often non-persistently jointed,and the intact rock blocks are strong and *** estimation of the confined strength of such rock masses is relevant when designing mine pillars and abutments at great depths,where the confining pressure is high enough to prevent block rotation and free sliding on block *** this article,a grain-based distinct element modeling approach is used to simulate jointed rock masses of various degrees of interlock and to investigate the influences of block shape,joint persistence and joint surface condition on the confined peak *** focus is on non-persistently jointed and blocky(persistently jointed)rock masses,consisting of hard and homogeneous rock blocks devoid of any strength degrading defects such as *** results from this investigation confirm that the GSI strength equations underestimate the confined strength of highly interlocked and non-persistently jointed rock ***,the GSI strength equations are found to be valid to estimate the confined strength of persistently jointed rock masses with smooth and non-dilatant joint surfaces.

关键词： Rock mass strength Degree of interlock Non-persistently jointed rock mass Blocky rock mass Geological strength index(GSI) GSI strength equations

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Integrating Early Cretaceous fossils into the phylogeny of living angiosperms:Magnoliidae and eudicots

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Journal of Systematics and Evolution 2010年第1期48卷 1-35页

作者： James A.DOYLE peter k.ENDRESS Department of Evolution and Ecology University of California DavisCA 95616 USA Institute of Systematic Botany University of Zurich 8008 ZurichSwitzerland

Over the past 25 years, discoveries of Early Cretaceous fossil flowers, often associated with pollen and sometimes with vegetative parts, have revolutionized our understanding of the morphology and diversity of early ***, few of these fossils have been integrated into the increasingly robust phylogeny of living angiosperms based primarily on molecular *** remedy this situation, we have used a morphological dataset for living basal angiosperms(including basal eudicots and monocots) to assess the most parsimonious positions of early angiosperm fossils on cladograms of Recent plants, using constraint trees that represent the current range of hypotheses on higher-level relationships, and concentrating on Magnoliidae(the clade including Magnoliales, Laurales, Canellales, and Piperales) and *** magnoliids, our results confirm proposed relationships of Archaeanthus(latest Albian?) to Magnoliaceae, Endressinia(late Aptian) to Magnoliales(the clade comprising Degeneria, Galbulimima, Eupomatia, and Annonaceae), and Walkeripollis pollen tetrads(late Barremian?) to Winteraceae, but they indicate that Mauldinia(early Cenomanian) was sister to both Lauraceae and Hernandiaceae rather than to Lauraceae *** middle Albian to early Cenomanian eudicots, we confirm relationships of Nelumbites to Nelumbo, platanoid inflorescences and Sapindopsis to Platanaceae, and Spanomera to *** the possible exception of Archaeanthus, these fossils are apparently not crown group members of living families but rather stem relatives of one or more families.

关键词： angiosperms Cretaceous eudicots flowers Magnoliidae paleobotany phylogeny pollen.

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Contribution of precursor compounds to the release of per-and polyfluoroalkyl substances(PFASs) from waste water treatment plants(WWTPs)

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Journal of Environmental Sciences 2017年第11期29卷 80-90页

作者： Ulrika Eriksson peter Haglund Anna k?rrman Man-Technology-Environment (MTM) Research Centre School of Science and Technology ?rebro University Department of Chemistry Umea University

Per-and polyfluoroalkyl substances（PFASs） are ubiquitous in sludge and water from waste water treatment plants, as a result of their incorporation in everyday products and industrial processes. In this study, we measured several classes of persistent PFASs,precursors, transformation intermediates, and newly identified PFASs in influent and effluent sewage water and sludge from three municipal waste water treatment plants in Sweden, sampled in 2015. For sludge, samples from 2012 and 2014 were analyzed as *** of precursors in sludge exceeded those of perfluoroalkyl acids and sulfonic acids（PFCAs and PFSAs）, in 2015 the sum of polyfluoroalkyl phosphoric acid esters（PAPs） were 15–20 ng/g dry weight, the sum of fluorotelomer sulfonic acids（FTSAs） was 0.8–1.3 ng/g,and the sum of perfluorooctane sulfonamides and ethanols ranged from non-detected to 3.2 ng/g. Persistent PFSAs and PFCAs were detected at 1.9–3.9 ng/g and 2.4–7.3 ng/g dry weight, respectively. The influence of precursor compounds was further demonstrated by an observed substantial increase for a majority of the persistent PFCAs and PFSAs in water after waste water treatment. Perfluorohexanoic acid（PFHxA）, perfluorooctanoic acid（PFOA）, perfluorohexane sulfonic acid（PFHxS）, and perfluorooctane sulfonic acid（PFOS）had a net mass increase in all WWTPs, with mean values of 83%, 28%, 37% and 58%,respectively. The load of precursors and intermediates in influent water and sludge combined with net mass increase support the hypothesis that degradation of precursor compounds is a significant contributor to PFAS contamination in the environment.

关键词： diPAPs FTSAs Waste water Daily discharge PFCA precursor

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Blind spots in climate finance for innovation peter WARREN

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Advances in Climate Change Research 2020年第1期11卷 60-64页

作者： peter WARREN School of Public Policy University College London(UCL)LondonWCIH 9QUUK

International climate finance is a sub-set of green finance and refers to investments specifically in climate change mitigation and adaptation activities,which primarily involve public finance and the leveraging of private finance in developing *** addition to continued international support for scaling low carbon solutions and facilitating replicability in developing countries,there remains an important need to increase the amount of climate finance provided to innovation,particularly demonstration(for technology innovation)and pilot implementation(for policy innovation),and to channel a greater proportion of Official Development Assistance(ODA)to‘hard-to-abate'areas,such as industrial decarbonisation,international transport and cross-sectoral issues like cooling and behavioural insights,to accelerate the commercialisation and implementation of technological,linancial and policy solutions to contribute to meeting the Paris Agreement's goal of limiting global warming to‘well-below'2℃ in these *** research,development and demonstration(RD&D)support with technical assistance is important in providing the route to obtain wider donor finance(concessional finance)and private finance to enable deployment through scalability and replicability.

关键词： Climate finance Climate policy Paris Agreement Official development assistance Industrial decarbonisation Sustainable cooling Behavioural insights International transport

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Ultrastrong and ductile BCC high-entropy alloys with low-density via dislocation regulation and nanoprecipitates

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Journal of Materials Science & Technology 2022年第15期110卷 109-116页

作者： Xuehui Yan peter k.Liaw Yong Zhang Beijing Advanced Innovation Center of Materials Genome Engineering State Key Laboratory for Advanced Metals and MaterialsUniversity of Science and Technology BeijingBeijing 100083China Department of Materials Science and Engineering The University of TennesseeKnoxvilleTN 37996United States of America

The high strength is a typical advantage of body-centered-cubic high-entropy alloys(BCC–HEAs).However,brittleness and weak strain-hardening ability are still their Achilles'***,extraordinary strength together with good tensile ductility are achieved in(Zr_(0.5)Ti_(0.35)Nb_(0.15))_(100-x)Al_(x) alloys(at.%,x=10 and 20)at room *** low densities of less than 6 g/cm^(3)are exhibited in these *** nanoprecipitates and diversifying dislocation motions are the keys to achieving such salient *** is worth noting that the tensile strength of 1.8 GPa in(Zr_(0.5)Ti_(0.35)Nb_(0.15))_(80)Al_(20)alloy is a record-high value known in reported BCC–HEAs,as well as a tensile strain over 8%.Furthermore,the maximum strain of~25%in(Zr_(0.5)Ti_(0.35)Nb_(0.15))_(90)Al_(10)alloy can challenge existing limit value,and is accompanied with a tensile strength of 1.2 *** current work does not only provide novel ultra-strong and tough structural materials with low density,but also sheds new light on designing BCC–HEAs with attractive performances and strain-hardening ability.

关键词： High-entropy alloys Mechanical properties Dislocation Nanoprecipitates Strain hardening

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