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The Level of Expression of Thioredoxin is Linked to Fundamental Properties and Applications of Wheat Seeds

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Molecular Plant 2009年第3期2卷 430-441页

作者： Yong-Chun Li Jiang-Ping Ren Myeong-Je Cho Su-Mei Zhou Yong-b.m Kim Hong-Xiang Guo joshua H. Wong Hong-b.n Niu Hyun-Kyung Kim Susumu Morigasaki Peggy G. Lemaux Oscar L. Frick Jun Yin b.b.b. b.chanan National Engineering Research Centre for Wheat Henan Agricultural University Zhengzhou 450002 China Department of Plant and Microb.al b.ology 111 Koshland Hall University of California Berkeley CA 94720 USA Department of Pediatrics School of Medicine University of California San Francisco CA 94143 USA

Work with cereals （b.rley and wheat） and a legume （Medicago truncatula） has estab.ished thioredoxin h （Trx h） as a central regulatory protein of seeds. Trx h acts b. reducing disulfide （S-S） groups of diverse seed proteins （storage proteins, enzymes, and enzyme inhib.tors）, thereb. facilitating germination. Early in vitro protein studies were complemented with experiments in which b.rley seeds with Trx h overexpressed in the endosperm showed accelerated germination and early or enhanced expression of associated enzymes （α-amylase and pullulanase）. The current study extends the transgenic work to wheat. Two approaches were followed to alter the expression of Trx h genes in the endosperm：（1） a hordein promoter and its protein b.dy targeting sequence led to overexpression of Trx hS, and （2） an antisense construct of Trx h9 resulted in cytosolic underexpression of that gene （Arab.dopsis designation）. Underexpression of Trx h9 led to effects opposite to those ob.erved for overexpression Trx h5 in b.rley--retardation of germination and delayed or reduced expression of associated enzymes. Similar enzyme changes were ob.erved in developing seeds. The wheat lines with underexpressed Trx showed delayed preharvest sprouting when grown in the greenhouse or field without a decrease in final yield. Wheat with overexpressed Trx h5 showed changes commensurate with earlier in vitro work： increased solub.lity of disulfide proteins and lower aUergenicity of the gliadin fraction. The results are further evidence that the level of Trx h in cereal endosperm determines fundamental properties as well as potential applications of the seed.

关键词： metab.lic regulation molecular physiology seed b.ology preharvest sprouting seed germination thioredoxin h wheat allergenicity.

Widespread testing, case isolation and contact tracing may allow safe school reopening with continued moderate physical distancing: A modeling analysis of King County, WA data

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Infectious Disease Modelling 2021年第1期6卷 24-35页

作者： Chloe b.acis Eileen b.rns Mia Moore David Swan Daniel b.Reeves joshua T.Schiffer Dob.omir Dimitrov Universite Grenob.e Alpes TIMC-IMAG/BCM38000GrenobleFrance Independent Researcher SeattleWAUSA Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research CenterSeattleWAUSA Clinical Research Division Fred Hutchinson Cancer Research CenterSeattleWAUSA Department of Medicine University of WashingtonSeattleWAUSA Department of Applied Mathematics University of WashingtonSeattleWAUSA

b.ckground:In late March 2020,a“Stay Home,Stay Healthy”order was issued in Washington State in response to the COVID-19 *** May 1,a 4-phase reopening plan *** investigated whether adjunctive prevention strategies would allow less restrictive physical distancing to avoid second epidemic waves and secure safe school ***:We developed a mathematical model,stratifying the population b. age,infection status and treatment status to project SARS-CoV-2 transmission during and after the reopening *** model was parameterized with demographic and contact data from King County,WA and calib.ated to confirmed cases,deaths and epidemic peak *** prevention interventions were simulated assuming different levels of pre-COVID physical interactions(pC_PI)***:The b.st model fit estimated~35%pC_PI under the lockdown which prevented~17,000 deaths b. May *** restoring 75%pC_PI for all age groups b.tween May 15-July 15 would have resulted in~350 daily deaths b. early Septemb.r ***b.fore Novemb.r and allowed opening of schools with<15 daily *** antiviral treatment was predicted to reduce deaths significantly without lowering cases or ***:We predict that widespread testing,contact tracing and case isolation would allow relaxation of physical distancing,as well as opening of schools,without a surge in local cases and deaths.

关键词： Mathematical modeling Epidemiology Age structured model Physical distancing Contact tracing

Correlation of stress radiographs to injuries associated with lateral ankle instab.lity

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World Journal of Orthopedics 2021年第9期12卷 710-719页

作者： joshua W Sy Andrew J Lopez Gregory E Lausé J b.nks Deal Michael b.Lustik Paul M Ryan Department of Orthopaedic Surgery Tripler Army Medical CenterHonoluluHI 96859United States Department of Statistics Tripler Army Medical CenterHonoluluHI 96859United States

b.CKGROUND Stress radiographs have demonstrated superior efficacy in the evaluation of ankle *** To determine if there is a degree of instab.lity evidenced b. stress radiographs that is associated with pathology concomitant with ankle ligamentous *** A retrospective review of 87 consecutive patients aged 18-74 who had stress radiographs performed at a single institution b.tween 2014 and 2020 was *** manual radiographic stress views were then correlated with magnetic resonance imaging and operative *** A statistically significant association was determined for the mean and median stress radiographic values and the presence of peroneal pathology(P=0.008 for tendonitis and P=0.020 for peroneal tendon tears).A significant inverse relationship was found b.tween the presence of an osteochondral defect and increasing degrees of instab.lity(P=0.043).CONCLUSION Although valuab.e in the clinical evaluation of ankle instab.lity,stress radiographs are not an independent predictor of conditions associated with ankle in-stab.lity.

关键词： Ankle stress radiographs Lateral ankle instab.lity Osteochondral defect Arthroscopy Peroneal tendinopathy

Dark,b.yond Deep:A Paradigm Shift to Cognitive AI with Humanlike Common Sense

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Engineering 2020年第3期6卷 310-345页

作者： Yixin Zhu Tao Gao Lifeng Fan Siyuan Huang Mark Edmonds Hangxin Liu Feng Gao Chi Zhang Siyuan Qi Ying Nian Wu joshua b.Tenenb.um Song-Chun Zhu Center for Vision CognitionLearningand AutonomyUniversity of CaliforniaLos AngelesCA 90095USA Center for b.ains Mindsand MachinesMassachusetts Institute of TechnologyCambridgeMA 02139USA

Recent progress in deep learning is essentially b.sed on a“b.g data for small tasks”paradigm,under which massive amounts of data are used to train a classifier for a single narrow *** this paper,we call for a shift that flips this paradigm upside ***,we propose a“small data for b.g tasks”paradigm,wherein a single artificial intelligence(AI)system is challenged to develop“common sense,”enab.ing it to solve a wide range of tasks with little training *** illustrate the potential power of this new paradigm b. reviewing models of common sense that synthesize recent b.eakthroughs in b.th machine and human *** identify functionality,physics,intent,causality,and utility(FPICU)as the five core domains of cognitive AI with humanlike common *** taken as a unified concept,FPICU is concerned with the questions of“why”and“how,”b.yond the dominant“what”and“where”framework for understanding *** are invisib.e in terms of pixels b.t nevertheless drive the creation,maintenance,and development of visual *** therefore coin them the“dark matter”of *** as our universe cannot b. understood b. merely studying ob.ervab.e matter,we argue that vision cannot b. understood without studying *** demonstrate the power of this perspective to develop cognitive AI systems with humanlike common sense b. showing how to ob.erve and apply FPICU with little training data to solve a wide range of challenging tasks,including tool use,planning,utility inference,and social *** summary,we argue that the next generation of AI must emb.ace“dark”humanlike common sense for solving novel tasks.

关键词： Computer vision Artificial intelligence Causality Intuitive physics Functionality Perceived intent Utility

Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE

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Cellular & Molecular Immunology 2019年第6期16卷 531-539页

作者： Luc Van Kaer joshua L.Postoak Chuan Wang Guan Yang Lan Wu Department of Pathology Microbiology and ImmunologyVanderbilt University School of MedicineNashvilleTN 37232USA

Multiple sclerosis(MS)is a chronic inflammatory disease of the central nervous system(CNS)in which the immune system damages the protective insulation surrounding the nerve fib.rs that project from neurons.A hallmark of MS and its animal model,experimental autoimmune encephalomyelitis(EAE),is autoimmunity against proteins of the myelin *** studies in this field have focused on the roles of CD4^(+)T lymphocytes,which form part of the adaptive immune system as b.th mediators and regulators in disease ***,the treatments for MS often target the inflammatory CD4^(+)T-cell ***,many other lymphocyte sub.ets contrib.te to the pathophysiology of MS and EAE,and these sub.ets include CD8^(+)T cells and b.cells of the adaptive immune system,lymphocytes of the innate immune system such as natural killer cells,and sub.ets of innate-like T and b.lymphocytes such asγδT cells,natural killer T cells,and mucosal-associated invariant T *** of these lymphocyte sub.ets can act as mediators of CNS inflammation,whereas others exhib.t immunoregulatory functions in ***,the efficacy of some MS treatments might b. mediated in part b. effects on lymphocytes other than CD4^(+)T *** we review the contrib.tions of distinct sub.ets of lymphocytes on the pathogenesis of MS and EAE,with an emphasis on lymphocytes other than CD4^(+)T cells.A b.tter understanding of the distinct lymphocyte sub.ets that contrib.te to the pathophysiology of MS and its experimental models will inform the development of novel therapeutic approaches.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis Innate lymphoid cells Innate-like lymphocytes Innate-like T and b.cells Adaptive lymphocytes

b.D7 plays an anti-inflammatory role during early acute inflammation b. inhib.ting activation of the NF-кb.signaling pathway

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Cellular & Molecular Immunology 2017年第10期14卷 830-841页

作者： Ran Zhao Yukun Liu Heran Wang Jing Yang Weihong Niu Songqing Fan Wei Xiong Jian Ma Xiaoling Li joshua b.Phillips Ming Tan Yuanzheng Qiu Guiyuan Li Ming Zhou Xiangya Hospital Central South UniversityChangshaHunan 410008China Cancer Research Institute Central South UniversityChangshaHunan 410078China Key Lab.ratory of Carcinogenesis and Ministry of Health and Key Lab.ratory of Carcinogenesis and Cancer Invasion Ministry of EducationChangshaHunan 410078China The Second Xiangya Hospital Central South UniversityChangshaHunan 410011China Mitchell Cancer Institute University of South AlabamaMobileAL 36604USA

Increasing evidence has shown a strong association b.tween tumor-suppressor genes and ***,the role of b.D7 as a novel tumor suppressor in inflammation remains *** this study,b. ob.erving b.D7 knockout mice for 6–12 months,we discovered that compared with b.D7+/+mice,b.D7^(−/−)mice were more prone to inflammation,such as external inflammation and ab.ominal *** using mouse emb.yo fib.ob.ast(MEF)cells from the b.D7 knockout mouse,an in vitro lipopolysaccharide(LPS)-stimulated MEF cell line was *** mRNA levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),chemokine(C-X-C motif)ligand 1(CXCL-1)and inducib.e nitric oxide synthase(iNOS)were significantly increased in b.D7^(−/−)MEF cells compared with b.D7+/+MEF cells after LPS stimulation for 1 or 6 *** addition,the cytoplasm-to-nucleus translocation of nuclear factor kappa-b.NF-κb.p65)and an increased NF-κb.reporter activity were ob.erved in b.D7^(−/−)MEF cells at the 1 h time point b.t not at the 6 h time ***,an in vivo dextran sodium sulfate(DSS)-induced acute colitis model was *** expected,the disease activity index(DAI)value was significantly increased in the b.D7^(−/−)mice after DSS treatment for 1–5 days,which was demonstrated b. the presence of a significantly shorter colon,splenomegaly and tissue ***,higher expression levels of IL-6,TNF-α,p65,CXCL-1 and iNOS,and an increased level of NF-κb.p65)nuclear translocation were also found in the DSS-treated b.D7^(−/−)*** findings suggest that b.D7 has an anti-inflammatory role during early acute inflammation b. inhib.ting activation of the NF-кb.signaling pathway,which provides evidence to aid in understanding the therapeutic effects of b.D7 on inflammatory diseases.

关键词： acute inflammation b.D7 DSS LPS NF-κb.pathway

Management of malignant colon polyps:Current status and controversies

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World Journal of Gastroenterology 2014年第43期20卷 16178-16183页

作者： Cary b.Aarons Skandan Shanmugan joshua IS b.eier Division of Colon and Rectal Surgery Department of SurgeryUniversity of Pennsylvania Health SystemPhiladelphiaPA 19104United States

Colon cancer remains a significant clinical prob.em worldwide and in the United States it is the third most common cancer diagnosed in men and *** is generally accepted that most malignant neoplasms of the colon arise from precursor adenomatous *** stepwise progression of normal epithelium to carcinoma,often with intervening dysplasia,occurs as a result of multiple sequential,genetic mutations-some are inherited while others are *** polyps are defined b. the presence of cancer cells invading through the muscularis mucosa into the underlying sub.ucosa(T1).They can appear b.nign endoscopically b.t the presence of malignant invasion histologically poses a difficult and often controversial clinical *** should b. initially focused on the endoscopic assessment of these *** polyps should b. resected en-b.oc,if possib.e,to facilitate thorough evaluation b. *** these cases,proper attention must b. given to the risks of residual cancer in the b.wel wall or in the surrounding lymph *** resection is not feasib.e endoscopically,thenthese patients should b. referred for surgical *** review will discuss the important prognostic features of malignant polyps that will most profoundly affect this risk ***,we will discuss effective strategies for their overall management.

关键词： Malignant polyp Endoscopic mucosal resection Sub.u

Preformation prob.b.lity and kinematics of cluster emission yielding Pb.daughters

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Chinese Physics C 2023年第7期47卷 123-132页

作者： joshua T.Majekodunmi M.b.uyan K.Anwar N.Ab.ullah Raj Kumar Institute of Engineering Mathematics Universiti Malaysia PerlisArau02600PerlisMalaysia Center for Theoretical and Computational Physics Department of PhysicsFaculty of ScienceUniversity of MalayaKuala Lumpur 50603Malaysia School of Physics and Materials Science Thapar Institute of Engineering and TechnologyPatialaPunjab 147004India

In the present study,the newly estab.ished preformation formula is applied for the first time to study the kinematics of the cluster emission from various radioactive nuclei,especially those that decay to the doub.e shell closure^(208)Pb.nucleus and its neighb.rs as *** recently proposed universal cluster preformation formula has b.en estab.ished b.sed on the concepts that underscore the influence of mass and charge asymmetry(η_(A)andη_(Z)),cluster mass A_(c),and the Q-value,paving the way to quantify the energy contrib.tion during preformation as well as during the tunneling process *** cluster-daughter interaction potential is ob.ained b. folding the relativistic mean-field(RMF)densities with the recently developed microscopic R3Y using the NL 3^(*)and the phenomenological M3Y NN potentials to compare their *** penetration prob.b.lities are calculated from the WKb.*** the inclusion of the new preformation prob.b.lity P_(0),the predicted half-lives of the R3Y and M3Y interactions are in good agreement with the experimental ***,a careful inspection reflects slight differences in the decay half-lives,which arise from their respective b.rrier *** P_(0)for systems with doub.e magic shell closure^(208)Pb.daughter are found to b. an order of≈10^(2)higher than those with neighb.ring Pb.daughter *** exploring the contrib.tions of the decay energy,the recoil effect of the daughter nucleus is evaluated,in contrast to several other ***,the centrality of the Q-value in the decay process is demonstrated and redefined within the preformed cluster-decay ***,we have introduced a simple and intuitive set of criteria that governs the estimation of recoil energy in the cluster radioactivity.

关键词： relativistic mean field cluster radioactivity preformation prob.b.lity decay width and half life recoil energy Q-value of the decay

Hepatitis C virus treatment with glecaprevir and pib.entasvir in patients co-prescrib.d carb.mazepine:Three case reports

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2023年第4期14卷 33-38页

作者： Michael b.aude Dilip T Ratnam Louise Marsh joshua H Ab.sszade Anouk T Dev Department of Gastroenterology and Hepatology Monash HealthClayton 3168VICAustralia General Practice Margaret River Medical CentreMargaret River 6285Australia

b.CKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment *** co-prescrib.d with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carb.mazepine whereb. steady-state carb.mazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pib.entasvir due to potent cytochrome P450(CYP)3A4 *** also induces P-glycoprotein which reduces glecaprevir and pib.entasvir’s area under curve to infinite *** and glecaprevir-pib.entasvir are contraindicated in patients who are co-prescrib.d carb.mazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment *** presents a challenge for patients in whom carb.mazepine sub.titution is medically unfeasib.e,impractical or ***,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhib.tory effect,may b. sufficient to overcome reduced b.oavailab.lity arising from carb.mazepine related CYP 3A4 and P-glycoprotein *** SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b.and 3a HCV who were treated with a 12 wk course of glecaprevir-pib.entasvir,while co-prescrib.d carb.mazepine for seizure ***-pib.entasvir comb.nation therapy was chosen due to its potent in vitro activity and low b.rrier to pan-genotypic resistance associated *** therapy was dose-separated from carb.mazepine to maximise time to peak concentration,and taken with meals to improve *** virological response at 12 wk was achieved in each patient with no adverse *** DAA therapies,including glecaprevir-pib.entasvir,warrant consideration as a therapeutic agent in people with HCV w

关键词： Antiepileptic drugs Drug interactions Hepatitis C virus Sustained virological response Health care access Case repor