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Profiling of immune features to predict immunotherapy efficacy

The Innovation 2022年第1期3卷 71-82页

作者： Youqiong Ye Yongchang Zhang Nong Yang Qian Gao Xinyu Ding Xinwei Kuang Rujuan Bao Zhao Zhang Chaoyang Sun Bingying Zhou li wang Qingsong Hu Chunru lin Jianjun Gao Yanyan lou steven Hlin lixia Diao Hong liu Xiang Chen Gordon B.Mills leng Han Shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston McGovern Medical SchoolHoustonTX 77030USA Department of Medical Oncology Lung Cancer and Gastrointestinal UnitHunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunan 410008China Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China State Key laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Molecular and Cellular Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Genitourinary Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Division of Hematology and Oncology Mayo ClinicJacksonvilleFL 32224USA Department of Radiation Oncology Division of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Knight Cancer Institute Oregon Health and Science UniversityPortlandOR 97239USA Center for Epigenetics and Disease Prevention Institute of Biosciences and TechnologyTexas A&M UniversityHoustonTX 77030USA Department of Translational Medical Sciences College of MedicineTexas A&M UniversityHoustonTX 77030 USA

Immune checkpoint blockade(ICB)therapies exhibit substantial clinical benefit in different cancers,but relatively low response rates in the majority of patients highlight the need to understand mutual relationships among immune ***,we reveal overall positive correlations among immune checkpoints and immune cell ***,patients benefiting from ICB exhibited increases for both immune stimulatory and inhibitory features after initiation of therapy,suggesting that the activation of the immune microenvironment might serve as the biomarker to predict immune *** proof-of-concept,we demonstrated that the immune activation score(ISD)based on dynamic alteration of interleukins in patient plasma as early as two cycles(4-6 weeks)after starting immunotherapy can accurately predict immunotherapy *** results reveal a systematic landscape of associations among immune features and provide a noninvasive,cost-effective,and time-efficient approach based on dynamic profiling of pre-and on-treatment plasma to predict immunotherapy efficacy.

关键词： immunotherapy features mutual

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Impacts of 1-Aminocyclopropane-1-Carboxylic Acid as a late Post-Bloom Thinner on Fruit Set, Yield, and Fruit Quality in “Gala” and “Fuji” Apples

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American Journal of Plant Sciences 2022年第4期13卷 481-493页

作者： Esmaeil Fallahi steven J. McArtney Pomology and Viticulture Program Department of Plant Sciences University of Idaho Parma Research and Extension Center Parma ID USA Valent BioSciences Corporation Libertyville IL USA

A few post-bloom thinners are available for apple (Malus domestica Borkh.) and the prospects for additional thinners appear to be limited. Application of blossom thinners may present a risk of overthining in the areas where weather is less predictable. Thus, we studied the impacts of various rates of 1-aminocyclopropane-1-carboxylic acid (ACC) in three strains of “Fuji” apple and different rates of ACC and one rate of Ethrel in “Buckeye Gala” apple, when fruitlet diameter was about 20 mm, on fruit set, yield and fruit quality attributes at harvest, and return bloom in southwest Idaho in the Intermountain West region, USA. In 2013, application of Ethrel at 300 mg·l-1 did not affect fruit set, fruit weight, diameter (D), length(l), or l/D ratio 34 days after application, or yield, fruit weight, color, russet, and starch degradation pattern (SDP) at harvest, while application of ACC at 150 mg·l-1 or higher reduced fruit set by 19% to 34% in “Buckeye Gala” apple. In this cultivar, application of ACC at 350 mg·l-1 significantly increased fruit weight, diameter and length 34 days after application, and increased fruit weight, color, and SDP at harvest time. Application of ACC at all rates reduced total yield per tree in “Buckeye Gala”. Application of ACC at 300 mg·l-1 significantly reduced fruit set but applications of 150 mg·l-1 or 300 mg·l-1 ACC did not affect yield or quality attributes of “Sun Fuji” apple in Sunny Slope area in 2013. Application of ACC reduced fruit set and slightly increased fruit size in “Top Export Fuji” in 2013. Application of ACC at 600 mg·l-1 significantly reduced fruit set in “Aztec Fuji” apple in 2014. Application of ACC in a season never reduced bloom density (return bloom) of the next season. Overall, we conclude that ACC is an excellent tool as a late-season post-bloom fruit thinner and can be effective when applied

关键词： Bio-Regulators Crop load Adjustment Ethylene Thinning

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Patient Characteristics, Safety, and Tolerability With Telaprevir Treatment for HCV in the Clinic:a Retrospective, Multicenter Study

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Journal of Clinical and Translational Hepatology 2014年第2期2卷 65-73页

作者： steven l. Flamm Paul J. Pockros leif Bengtsson Mark Friedman Northwestern University Feinberg School of Medicine Chicago Illinois USA Scripps Clinic and Scripps Translational Science Institute La Jolla California USA Vertex Pharmaceuticals Incorporated Boston Massachusetts USA

Background and Aims: There is a paucity of information regarding similarities and differences between patients from the phase 3 studies of telaprevir and those receiving telaprevir in clinical practice. Methods: This retrospective chart review evaluated baseline characteristics and follow-up safety and tolerability data for patients with hepatitis C virus (HCV) infection treated with telaprevir and peginterferon alfa and ribavirin (PR) in clinical practice. Results: In total, 338 charts from patients at four academic and three community US treatment centers who received telaprevir and PR and had at least 12 weeks of follow-up data were included;62%were from academic centers and 38% were from community centers. Of the 338 patients, 269 completed 12 weeks of telaprevir and PR;32 discontinued due to adverse events. Mean age was 55 years;patients were predominantly white (79.3%) males (58.9%) with genotype 1a HCV infection (61.8%);35.5%were reported to have cirrhosis at baseline;and 55.3%previously received PR. Hypertension and depres-sion were the most common comorbidities. Patient charac-teristics outside the per-protocol minimum criteria used in the phase 3 studies of telaprevir were, e.g., hemoglobin, 9.2%;albumin, 5.3%;platelets, 11.5%;and neutrophil count, 5.6%. Adverse events occurred in 329/338 (97.3%) patients, with anemia, fatigue, nausea, and rash being the most common. Of 38 hospitalizations, 26 were deemed related to telaprevir and PR. Three patients died due to pneumonia, septic shock, and hepatorenal syndrome (n=1 each). Conclusions: These findings complement those reported from rigorous, randomized controlled studies with telaprevir-based treatment and provide a general assess-ment of similarities and/or differences between patients from the phase 3 studies of telaprevir and those treated with telaprevir in clinical practice.

关键词： Hepatitis C virus Combination drug therapy Protease inhibitors liver diseases

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ζ-Carotene Isomerase Suppresses Tillering in Rice through the Coordinated Biosynthesis of Strigolactone and Abscisic Acid

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Molecular Plant 2020年第12期13卷 1784-1801页

作者： Xue liu Qingliang Hu Jijun Yan Kai Sun Yan liang Meiru Jia Xiangbing Meng Shuang Fang Yiqin wang Yanhui Jing Guifu liu Dianxing Wu Chengcai Chu steven M.Smith Jinfang Chu Yonghong wang Jiayang li Bing wang State Key laboratory of Plant Genomics and National Center for Plant Gene Research(Beijing)Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key laboratory of Rice Biology Institute of Nuclear Agriculture SciencesZhejiang UniversityHangzhou 310029China School of Natural Sciences University of TasmaniaHobart 7001Australia State Key laboratory of Plant Genomics and National Center for Plant Gene Research(Beijing)Institute of Genetics and Developmental BiologyThe CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesBeijing 100101China College of life Sciences Shandong Agricultural UniversityTaian 271018China

Rice tillering is an important agronomic trait affecting grain ***,we identified a high-tillering mutant tillering20(t20),which could be restored to the wild type by treatment with the strigolactone(Sl)analog rac-GR24.T20 encodes a chloroplast ζ-carotene isomerase(Z-ISO),which is involved in the biosynthesis of ca-rotenoids and their metabolites,Sl and abscisic acid(ABA).The t20 mutant has reduced Sl and ABA,raising the question of how Sl and ABA biosynthesis is coordinated,and whether they have overlapping functions in *** discovered that rac-GR24 stimulated T20 expression and enhanced all-trans-p-carotene ***,rac-GR24 also stimulated expression of Oryza sativa 9-CIS-EPOXY-CAROTENOID DIOXYGENASE 1(OsNCED1)through induction of Oryza sativa HOMEOBOX12(0sHOX12),promoting ABA biosynthesis in shoot *** the other hand,ABA treatment significantly repressed Sl biosynthesis and the ABA biosynthetic mutants displayed elevated Sl *** treatment reduced the number of basal tillers in both t20 and wild-type ***,while ABA-deficient mu-tants aba1 and aba2 had the same number of basal tillers as wild type,they had more unproductive upper tillers at *** work demonstrates complex interactions in the biosynthesis of carotenoid,Sls and ABA,and reveals a role for ABA in the regulation of rice tillering.

关键词： rice(Oryza sativa l.) tillering ζ-carotene isomerase carotenoid strigolactones abscisic acid

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Sex-specific sterility caused by extreme temperatures is likely to create cryptic changes to the operational sex ratio in Drosophila virilis

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Current Zoology 2021年第3期67卷 341-343页

作者： Benjamin S.Walsh Natasha l.M.Manimion Tom A.R.Price steven R.Parratt Institute of Integrative Biology University of LiverpoolCrown StreetLiverpoolL697ZBUK

Climate change is increasing the frequency and severity of short-term heat shocks that threaten the persistence of natural ***,most work addressing the evolutionary consequences of anthropogenic environmental change has focused on natural selection,with less attention paid to the impacts on sexual *** conditions under which sexual selection operates is a topic of debate,but a generally observed pattern is that the oper-ational sex ratio(OSR)of a population is key to determining both the extent of competition for fertilizations and the scope for mate choice(Weir et al.2011)

关键词： climate change reproduction sexual selection fertility

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The potential role of DEK over-expression in the radiation response of head and neck cancer

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Radiation Medicine and Protection 2021年第1期2卷 28-32页

作者： Hui Xiao Bismarck Odei steven K.Clinton Darrion l.Mitchell Department of Radiation Oncology The Ohio State UniversityOH43210USA The Ohio State University Comprehensive Cancer Center The Ohio State UniversityOH43210USA Division of Medical Oncology Department of Internal MedicineThe Ohio State UniversityOH43221USA

Objective:To determine if DEK over-expression is associated with radiation resistance in HPV positive head and neck cancer ***:Control and DEK over-expressing keratinocytes and an HPV positive head and neck cancer cell line respectively were irradiated with 2–10 Gy and the impact on cell survival,γ-H2AX(a marker of DNA damage)and RAD51(homologous recombination)were analyzed via clonogenic assays,and immunofluorescence measurements ***:Upon exposure to increasing doses of radiation,DEK over-expression in keratinocytes at 2,4(Pll line at 2,4,8,and 10 Gy(Pled to improved clonogenic cell *** parallel,irradiation decreased the percent ofγ-H2AX foci at 6,24,and 48 h post-irradiation(Ply)in NIKS,and at 0,6,24,48 h post-irradiation(Plls but enhanced the percent of RAD51 foci in both DEK over-expressing cell lines relative to their respective control cells at all times points(Plusion:These results suggest DEK over-expression contributes to radio-resistance in HPV positive head and neck cancer cells,potentially by improving repair of DNA double strand breaks through homologous *** molecular mechanisms and relevance to in vivo responses needs further investigation.

关键词： HPV Oropharynx Radiation DEK

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Processing, Recovery and Analysis of Precious Metals Using Molecular Recogntion Technology

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贵金属 2012年第A1期33卷 88-95页

作者： IZATT steven R. BRUENING Ronald l. IZATT Nell E. IBC Advanced Technologies Inc.856 East Utah Valley DriveAmerican ForkUT 84003USA

IBC Advanced Technologies' Molecular Recognition Technology(MRT) products,trade named Superlig,selectively and rapidly bind with target metal ions to remove them from *** MRT process can produce a high purity separation product of maximum added value at low *** this paper,applications of MRT in the precious metals industry,including selective commercial separations involving Au,Pd,Pt,Rh,and Ru,are described and *** of MRT to the analytical determination of precious metals is *** use of MRT in recovering precious metals from end-of-life(EOl) products is discussed.

关键词： selective metal separations molecular recognition technology metal recovery from waste electronics palladium platinum rhodium ruthenium gold analytical determinations

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long-term antifibrotic action of interferon-γ treatment in patients with chronic hepatitis B virus infection

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Hepatobiliary & Pancreatic Diseases International 2011年第2期10卷 151-157页

作者： Peter R Mertens steven Dooley Department of Nephrology and Hypertension Otto-von-Guericke-University First Affiliated Hospital Zhejiang University School of Medicine Molecular Hepatology-Alcohol Dependent Diseases II. Medical Clinic Faculty of Medicine at MannheimUniversity of Heidelberg

BACKGROUND:The first priority in treating fibrosis is to eliminate the causes that result in liver injury,e.g.,hepatitis B and C ***,in many liver diseases the cause is either unknown or *** present study was designed to investigate the long-term antifibrotic effect of interferon-gamma(IFN-γ)treatment in patients chronically infected with hepatitis B virus. METHODS:A total of 42 patients,30 treated with IFN-γand 12 controls,were enrolled from an original clinical trial(Clin Gastroenterol Hepatol 2005;3:819.).Three serial liver biopsies that were obtained at the initiation and end of IFN-γtreatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system. RESUlTS:Twenty-five out of 30 IFN-γ-treated patients were followed up until 4 to 6 years after the treatment was stopped. However,all controls were excluded from follow-up due to death,loss and elevated virus level within 2 ***-five IFN-γ-treated patients had stable serum liver function and liver fibrosis indices without any further antiviral or anti-fibrotic *** inflammatory and fibrotic scores were found after nine months of IFN-γtreatment according to the modified Chevallier scoring system(inflammation:11.8±6.5 at the beginning of IFN-γtreatment vs.9.2±4.1 after 9 months, Pline vs.12.6±6.8 after 9 months, Pl liver biopsy 4 to 6 years after treatment discontinuation,and the fibrotic score was increased(14.2±8.3 vs.11.9±7.6 after 9 months, PlUSIONS:Nine-month IFN-γtreatment significantly improves the fibrosis score in patients with chronic HBV *** majority of patients demonstrate stable serum biochemical indices and quality of ***,they do not show a long-term benefit according to histological criteria. Given the limited sample size,long-term IFN-γtreatment regimens should be assessed in further

关键词： hepatic stellate cells hepatitis B virus liver fibrosis inflammation interferon-gamma

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Dual enzyme activated fluorescein based fluorescent probe

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Frontiers of Chemical Science and Engineering 2020年第1期14卷 117-121页

作者： Maria l.Odyniec Jordan E.Gardiner Adam C.Sedgwick Xiao-Peng He steven D.Bull Tony D.James Department of Chemistry University of BathBathBA27AYUK Department of Chemistry University of Texas at AustinAustinTX 78712-1224USA Key laboratory for Advanced Materials&Feringa Nobel Prize Scientist Joint Research Center East China University of Science and TechnologyShanghai 200237China

A simple dual analyte fluorescein-based probe(PF3-Glc)was synthesised containingβ-glucosidase(β-glc)and hydrogen peroxide(H2O2)trigger *** presence ofβ-glc,resulted in fragmentation of the parent molecule releasing glucose and the slightly fluorescent mono-boronate fluorescein(PF3).Subsequently,in the presence of glucose oxidase(GOx),the released glucose was catalytically converted to D-glucono-δ-lactone,which produced H2O2 as a *** GOx-produced H2O2,resulted in classic H2O2-mediated boronate oxidation and the release of the highly emissive fluorophore,*** unique cascade reaction lead to an 80-fold increase in fluorescence intensity.

关键词： chemosensors dual-activation GOx fluorescence β-glucosidase molecular logic

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A New Family of High Order Unstructured MOOD and ADER Finite Volume Schemes for Multidimensional Systems of Hyperbolic Conservation laws

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Communications in Computational Physics 2014年第8期16卷 718-763页

作者： Raphael loubere Michael Dumbser steven Diot CNRS and Institut de Mathematiques de Toulouse(IMT)Universite Paul-Sabatier ToulouseFrance Department of Civil Environmental and Mechanical EngineeringUniversity of TrentoVia Mesiano77-38123 TrentoItaly Fluid Dynamics and Solid Mechanics(T-3) Los Alamos National LaboratoryNM 87545 USA.

In this paper,we investigate the coupling of the Multi-dimensional Optimal Order Detection(MOOD)method and the Arbitrary high order DERivatives(ADER)approach in order to design a new high order accurate,robust and computationally efficient Finite Volume(FV)scheme dedicated to solve nonlinear systems of hyperbolic conservation laws on unstructured triangular and tetrahedral meshes in two and three space dimensions,*** Multi-dimensional Optimal Order Detection(MOOD)method for 2D and 3D geometries has been introduced in a recent series of papers for mixed unstructured *** is an arbitrary high-order accurate Finite Volume scheme in space,using polynomial reconstructions with a posteriori detection and polynomial degree decrementing processes to deal with shock waves and other *** the following work,the time discretization is performed with an elegant and efficient one-step ADER *** so,we retain the good properties of the MOOD scheme,that is to say the optimal high-order of accuracy is reached on smooth solutions,while spurious oscillations near singularities are *** ADER technique permits not only to reduce the cost of the overall scheme as shown on a set of numerical tests in 2D and 3D,but it also increases the stability of the overall scheme.A systematic comparison between classical unstructured ADER-WENO schemes and the new ADER-MOOD approach has been carried out for high-order schemes in space and time in terms of cost,robustness,accuracy and *** main finding of this paper is that the combination of ADER with MOOD generally outperforms the one of ADER and WENO either because at given accuracy MOOD is less expensive(memory and/or CPU time),or because it is more accurate for a given grid resolution.A large suite of classical numerical test problems has been solved on unstructured meshes for three challenging multi-dimensional systems of conservation laws:the Euler equations of compressible gas dynamics

关键词： Finite Volume high-order conservation law polynomial reconstruction ADER MOOD hyperbolic PDE unstructured meshes finite volume one-step time discretization local continuous space-time Galerkin method WENO Euler equations MHD equations relativistic MHD equations.

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