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Comparison of methods for deriving phenotypes from incomplete observation data with an application to age at puberty in dairy cattle

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Journal of Animal Science and Biotechnology 2024年第2期15卷 535-545页

作者： melissa a.stephen Chris R.Burke Jennie E.Pryce Nicole M.Steele Peter R.Amer Susanne Meier Claire V.C.Phyn Dorian J.Garrick DairyNZ Ltd 605 Ruakura RoadHamilton 3240New Zealand AL Rae Centre for Genetics and Breeding-Massey University RuakuraHamilton 3214New Zealand Agriculture Victoria Research AgriBioCentre for AgriBioscienceBundooraVictoria 3083Australia School of Applied Systems Biology La Trobe UniversityBundooraVictoria 3083Australia AbacusBio DunedinNew Zealand

Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure *** include time-dependent traits such as reproductive status,or *** measures for these traits result in phenotypes that are subject to left-,interval-and rightcensoring,where phenotypes are only known to fall below an upper bound,between a lower and upper bound,or above a lower bound *** we compare three methods for deriving phenotypes from incomplete data using age at first elevation(>1 ng/mL)in blood plasma progesterone(AGEP4),which generally coincides with onset of puberty,as an example *** We produced AGEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian×Jersey cross-bred dairy heifers managed in 54 seasonal-calving,pasture-based herds in New *** used these actual data to simulate 7 different visit scenarios,increasing the extent of censoring by disregarding data from one or two of the three *** methods for deriving phenotypes from these data were explored:1)ordinal categorical variables which were analysed using categorical threshold analysis;2)continuous variables,with a penalty of 31 d assigned to right-censored phenotypes;and 3)continuous variables,sampled from within a lower and upper bound using a data augmentation *** Credibility intervals for heritability estimations overlapped across all methods and visit scenarios,but estimated heritabilities tended to be higher when left censoring was *** sires with at least 5 daughters,the correlations between estimated breeding values(EBVs)from our three-visit scenario and each reduced data scenario varied by method,ranging from 0.65 to *** estimated breed effects also varied by method,but breed differences were smaller as phenotype censoring *** Our results indicate that using

关键词： Cattle Gibbs sampler Markov-chain Monte Carlo(MCMC) Puberty

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A lead role for a“secondary”axonal injury response

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Neural Regeneration Research 2025年第2期20卷 469-470页

作者： melissa A.Rudy Trent A.Watkins Division of Neuroimmunology and Glial Biology Department of NeurologyUniversity of California at San FranciscoSan FranciscoCAUSA Development Disease Modelsand Therapeutics Graduate ProgramBaylor College of MedicineHoustonTXUSA

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system ***,this stress response drives neuronal apoptosis in non-regenerative *** duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative *** dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve *** this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

关键词： injury axonal stress

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The Power Allocation Game on A Network:A Paradox

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IEEE/CAA Journal of Automatica Sinica 2018年第4期5卷 771-776页

作者： Yuke Li a.stephen Morse the department of political science yale university ieee the department of electrical engineering yale university

The well-known Braess paradox in congestion games states that adding an additional road to a transportation network may increase the total travel time, and consequently decrease the overall efficiency. This paper presents a paradox in a similar spirit and involves a distributed resource allocation game on networks, namely the power allocation game between countries developed in Li and Morse(2017). The paradox is that by having additional friends may actually decrease a country's total welfare in equilibrium. Conditions for this paradox to occur as well as the price of anarchy results are also derived.

关键词： Friends paradox price of anarchy resource allocation game success survival utility

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Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

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Neural Regeneration Research 2025年第7期20卷 1991-1992页

作者： Fengwen Huang stephen Temitayo Bello Department of Neuroscience City University of Hong KongKowloon TongHong Kong Special Administrative RegionChina Center for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong Special Administrative RegionChina

Spatial memory is crucial for survival within external surroundings and wild *** hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and *** neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal ***(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target *** instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety ***,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

关键词： abundant functions modulator

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Easy access to pharmaceutically relevant heterocycles by catalytic reactions involving a-imino gold carbene intermediates

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Frontiers of Chemical Science and Engineering 2020年第3期14卷 317-349页

作者： Ximei Zhao Matthias Rudolph Abdullah M.Asiri a.stephen K.Hashmi Organisch-Chemisches Institut Heidelberg University69120 HeidelbergGermany Chemistry Department Faculty of Science21589 JeddahSaudi Arabia

This review summarizes recent advances in the field of gold-catalyzed synthesis of pharmaceutically relevant aza-heterocycles via in situ generated a-imino gold carbene complexes as intermediates.

关键词： gold heterocycles alkynes

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Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study

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World Journal of Gastroenterology 2025年第2期31卷 102-112页

作者： Thanaboon Chaemsupaphan Aviv Pudipeddi Hui-Yu Lin Sudarshan Paramsothy Viraj C Kariyawasam melissa Kermeen Rupert W Leong Department of Gastroenterology and Liver Services Concord Repatriation General HospitalSydney 2139New South WalesAustralia Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Faculty of Medicine and Health University of SydneySydney 2139New South WalesAustralia Department of Gastroenterology Tan Tock Seng HospitalSingapore 308433Singapore Faculty of Medicine and Health Sciences Macquarie UniversitySydney 2139New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversitySydney 2148New South WalesAustralia

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and *** is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is *** To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance *** This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to *** in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving *** evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine *** There were 62 UC participants with mean age of 43.4 years and 42%were *** participants received vedolizumab as maintenance therapy with 67.7%withdrew *** serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies ***-tients with clinical remission had higher trough concentrations at week *** quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving *** A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be *** thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remi

关键词： Pharmacokinetic Vedolizumab Thiopurine Ulcerative colitis Trough concentration Antibody Inflammatory bowel diseases

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Gold-catalysed synthesis of phosphonatesubstituted oxetan-3-ones–an easy access to highly strained HWE reagents

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Organic Chemistry Frontiers 2022年第1期9卷 117-122页

作者： Shaista Tahir Jonas F.Wunsch Matthias Rudolph Frank Rominger a.stephen K.Hashmi Organisch-Chemisches Institut Heidelberg UniversityIm Neuenheimer Feld 27069120 HeidelbergGermany Chemistry Department Faculty of ScienceKing Abdulaziz University21589 JeddahSaudi Arabia

A convenient approach for the attainment of strained phosphonate-substituted oxetan-3-ones,starting from easy to synthesise alkynyl phosphonates,is *** the aid of a pyridine-N-oxide,in a goldcatalysed step anα-oxo carbene species is generated as a key *** formal OH-insertion,synthetically useful HWE reagents can be *** synthetic utility of the obtained building blocks could be demonstrated,which yielded the 2-alkenyl oxetan-3-one scaffold in high yields after the HWE reaction.

关键词： reaction substituted synthesis

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Practical and modular construction of benzo[c]phenanthridine compounds

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Science China Chemistry 2022年第7期65卷 1338-1346页

作者： Cheng Zhang Qian Chen Lei Wang Qiaoying Sun Yangyang Yang Matthias Rudolph Frank Rominger a.stephen K.Hashmi Organisch-Chemisches Institut Heidelberg UniversityHeidelberg 69120Germany Chemistry Department Faculty of ScienceKing Abdulaziz University(KAU)Jeddah 21589Saudi Arabia Cellular Immunotherapy Lab the Medical Faculty of Heidelberg UniversityHeidelberg University HospitalHeidelberg 69120Germany

Here,we describe a general and modular strategy for the rapid assembly of benzo[c]phenanthridine(BCP)derivatives using homogeneous gold ***,in contrast to traditional methods based on the specially preformed substrates that have an inherent preference for the formation of this class of compounds with limited flexibility,this protocol is achieved via a selectively intramolecular cascade of a diazo-tethered alkyne and subsequently an intermolecular cyclization with a nitrile to facilitate the successive C–N and C–C bonds *** methodology uses readily available nitriles as the nitrogen source to deliver the products in good yield with excellent functional group compatibility.A preliminary anti-tumor activity study of these generated products exhibits high anticancer potency against five tumor cell lines,including He La,Mel624,SW-480,8505C,***,we report a catalyst-controlled intermolecular cycloaddition/intramolecular insertion of the substrate with a fulvene to provide fused polycarbocycles containing a seven-membered ring.

关键词： selectivity homogeneous gold catalysis domino cyclization benzo[c]phenanthridine(BCP) anticancer activity

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Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

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Neural Regeneration Research 2025年第11期20卷 3063-3075页

作者： stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles W.Plant Department of Neuroscience Ohio State UniversityColumbusOHUSA

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative *** the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained *** work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as *** embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns *** barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem *** advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal *** precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed *** the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma *** of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of *** the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor ***,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support ***,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for *** to a clinical setting wi

关键词： axon regeneration central nervous system regeneration induced pluripotent stem cells neurotrauma regenerative medicine spinal cord injury stem cell therapy

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Imbalanced Classification in Diabetics Using Ensembled Machine Learning

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Computers, Materials & Continua 2022年第9期72卷 4397-4409页

作者： M.Sandeep Kumar Mohammad Zubair Khan Sukumar Rajendran Ayman Noor a.stephen Dass J.Prabhu School of Information Technology and Engineering Vellore Institute of TechnologyVelloreTamil Nadu632014India Department of Computer Science and Information Taibah UniversityMedinaSaudi Arabia College of Computer Science and Engineering Taibah UniversityMedinaSaudi Arabia

Diabetics is one of the world’s most common diseases which are caused by continued high levels of blood *** risk of diabetics can be lowered if the diabetic is found at the early *** recent days,several machine learning models were developed to predict the diabetic presence at an early *** this paper,we propose an embedded-based machine learning model that combines the split-vote method and instance duplication to leverage an imbalanced dataset called PIMA Indian to increase the prediction of *** proposed method uses both the concept of over-sampling and under-sampling along with model weighting to increase the performance of *** measures such as Accuracy,Precision,Recall,and F1-Score are used to evaluate the *** results we obtained using K-Nearest Neighbor(kNN),Naïve Bayes(NB),Support Vector Machines(SVM),Random Forest(RF),Logistic Regression(LR),and Decision Trees(DT)were 89.32%,91.44%,95.78%,89.3%,81.76%,and 80.38%*** SVM model is more efficient than other models which are 21.38%more than exiting machine learning-based works.

关键词： Diabetics classification imbalanced data split-vote instance duplication

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