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Integrated Single-cell Multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

Genomics, Proteomics & Bioinformatics 2024年第1期22卷 67-88页

作者： Manickam Ashokkumar Wenwen Mei jackson j.Peterson Yuriko Harigaya david M.Murdoch david M.margolis Caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia d.Rudin Yuchao jiang Edward P.Browne department of Medicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA department of Biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA department of Microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA department of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA department of Medicine Duke UniversityDurhamNC 27708USA department of Computer Science Duke UniversityDurhamNC 27708USA department of Statistics Texas A&M UniversityCollege StationTX 77843USA department of Biology Texas A&M UniversityCollege StationTX 77843USA department of Biomedical Engineering Texas A&M UniversityCollege StationTX 77843USA

despite the success of antiretroviral therapy,human immunodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the mechanisms of HIV latency,we employed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chromatin with sequencing(scATAC-seq)approach to simultaneously profile the transcriptomic and epigenomic characteristics of~125,000 latently infected primary Cd4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXP1 and GATA3,in viral *** data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal Primary Cd4þT cell Single-cell multiomics HIV-regulating factor Machine learning

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Kinetics of glyphosate and aminomethylphosphonic acid sorption onto montmorillonite clays in soil and their translocation to genetically modified corn

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journal of Environmental Sciences 2024年第1期135卷 669-680页

作者： Meichen Wang Kelly j Rivenbark Timothy d Phillips Veterinary Physiology and Pharmacology College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityTX 77845USA

The co-occurrence of glyphosate(GLP)and aminomethylphosphonic acid(AMPA)in contaminated water,soil,sediment and plants is a cause for concern due to potential threats to the ecosystem and human health.A major route of exposure is through contact with contaminated soil and consumption of crops containing GLP and AMPA ***,clay-based sorption strategies for mixtures of GLP and AMPA in soil,plants and garden produce have been very *** this study,in vitro soil and in vivo genetically modified corn models were used to establish the proof of concept that the inclusion of clay sorbents in contaminated soils will reduce the bioavailability of GLP and AMPA in soils and their adverse effects on plant *** of chemical concentration(1–10 mg/kg),sorbent dose(0.5%-3%in soil and 0.5%-1%in plants)and duration(up to 28 days)on sorption kinetics were *** time course results showed a continuous GLP degradation to *** inclusion of calcium montmorillonite(CM)and acid processed montmorillonite(APM)clays at all doses significantly and consistently reduced the bioavailability of both chemicals from soils to plant roots and leaves in a dose-and time-dependent manner without detectable *** treated with 0.5%and 1%APM inclusion showed the highest growth rate(p≤0.05)and lowest chemical bioavailability with up to 76%reduction in roots and57%reduction in *** indicated that montmorillonite clays could be added as soil supplements to reduce hazardous mixtures of GLP and AMPA in soils and plants.

关键词： Glyphosate AMPA Adsorption Soil remediation Plant Hydroponic system

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Generalized polynomial chaos expansion by reanalysis using static condensation based on substructuring

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Applied Mathematics and Mechanics(English Edition) 2024年第5期45卷 819-836页

作者： d.LEE S.CHANG j.LEE department of Automotive Engineering Hanyang UniversitySeoul 04763Republic of Korea School of Mechanical Engineering Chungnam National UniversityDaejeon 34134Republic of Korea department of Mechanical Robotics and Energy EngineeringDongguk UniversitySeoul 04620Republic of Korea

This paper presents a new computational method for forward uncertainty quantification(UQ)analyses on large-scale structural systems in the presence of arbitrary and dependent random *** method consists of a generalized polynomial chaos expansion(GPCE)for statistical moment and reliability analyses associated with the stochastic output and a static reanalysis method to generate the input-output data *** the reanalysis,we employ substructuring for a structure to isolate its local regions that vary due to random *** allows for avoiding repeated computations of invariant substructures while generating the input-output data *** substructuring with static condensation further improves the computational efficiency of the reanalysis without losing ***,the GPCE with the static reanalysis method can achieve significant computational saving,thus mitigating the curse of dimensionality to some degree for UQ under high-dimensional *** numerical results obtained from a simple structure indicate that the proposed method for UQ produces accurate solutions more efficiently than the GPCE using full finite element analyses(FEAs).We also demonstrate the efficiency and scalability of the proposed method by executing UQ for a large-scale wing-box structure under ten-dimensional(all-dependent)random inputs.

关键词： forward uncertainty quantification(UQ) generalized polynomial chaos expansion(GPCE) static reanalysis method static condensation substructuring

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肾透明细胞癌:多期相多层CT成像特征帮助预测遗传核型

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国际医学放射学杂志 2012年第1期 84-84页

作者： S.C.Sauk M.S.Hsu d.j.margolis A.S.Belldegrun 王迪 department of Radiology David Geffen School of Medicine at UCLARonald Reagan UCLA Medical Center757 Westwood BlvdLos AngelesCA 90095-the 2008 RSNA Annual Meeting

目的明确肾透明细胞癌(ccRCC)病人在多期相多层CT上的成像特征是否与普通染色体核型异常相关。材料与方法此项经HIPAA批准的回顾性研究已获得了机构审查委员会的支持,并豁免了知情同意书。从2000年1

关键词：核型成像特征排泄期 CT

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Insm1:orchestrating cellular mimicry in the thymus medulla

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Cellular & Molecular Immunology 2024年第4期21卷 414-416页

作者： K.d.james j.E.Cowan UCL Institute of Immunity and Transplantation The Pears BuildingRowland Hill StreetLondonNW32PPUK

The thymus is the primary production site for a functional and self-tolerant T-cell *** establishment of immune tolerance is mediated by the generation and presentation of tissue-restricted self-antigens(TRAs)by medullary thymic epithelial cells(mTECs),which screen T-cell receptors for self-reactivity to eliminate autoreactive T *** studies have extended our understanding of mTEC heterogeneity by examining the mechanisms by which mTECs mimic the peripheral self[1].

关键词： medullary eliminate restricted

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Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

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Neural Regeneration Research 2024年第2期19卷 355-359页

作者： Courtney j.Rouse Victoria N.jensen Coy d.Heldermon Lacerta Therapeutics AlachuaFLUSA University of Florida College of Medicine GainesvilleFLUSA

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for *** results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological *** treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢ***-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential *** group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy ***,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

关键词： adeno-associated virus central nervous system gene therapy heparan sulfate immune response mucopolysaccharidoses type IIIB N-acetyl-alpha-glucosaminidase newborn screening

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Generalized time-dependent generator coordinate method for induced fission dynamics

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Frontiers of physics 2024年第4期19卷 1-12页

作者： B.Li d.Vretenar T.Nikšić j.Zhao P.W.Zhao j.Meng State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China Physics department Faculty of ScienceUniversity of Zagreb10000 ZagrebCroatia Center for Circuits and Systems Peng Cheng LaboratoryShenzhen 518055China

The generalized time-dependent generator coordinate method(Td-GCM)is extended to include pairing *** correlated GCM nuclear wave function is expressed in terms of time-dependent generator states and weight *** particle–hole channel of the effective interaction is determined by a Hamiltonian derived from an energy density functional,while pairing is treated dynamically in the standard BCS approximation with time-dependent pairing tensor and single-particle occupation *** the inclusion of pairing correlations,various time-dependent phenomena in open-shell nuclei can be described more *** model is applied to the description of saddle-to-scission dynamics of induced *** generalized Td-GCM charge yields and total kinetic energy distribution for the fission of 240Pu,are compared to those obtained using the standard time-dependent density functional theory(Td-dFT)approach,and with available data.

关键词： nuclear density functional theory generator coordinate method fission dynamics

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应用多参数MRI和dNA全外显子基因组测序对前列腺癌病人前列腺微环境的多区域放射基因组学评价

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国际医学放射学杂志 2017年第5期 588-588页

作者： N.jamshidi d.j.margolis S.Raman j.Huang R.E.Reiter M.d.Kuo 杨晓旭 department of Radiological Sciences University of CaliforniaLos Angeles-David Geffen School of Medicine

摘要目的结合多参数MRI与全外显子基因组测序正常和异常区域组织病理学评价,评价前列腺癌病人前列腺微环境的潜在基因变异。材料与方法收集6例接受机器人前

关键词： MRI 多参数前列腺癌 dNA 基因组学外显子微环境

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3 TMR引导下经直肠前列腺穿刺活检:基于前列腺影像报告和数据系统(PI-RAdS)第2版诊断前列腺癌

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国际医学放射学杂志 2017年第3期 346-346页

作者： N.Tan W.C.Lin P.Khoshnoodi N.H.Asvadi j.Yoshida d.j.margolis 张单霞 The UCLA Prostate Imaging Research Group Department of Radiologyand Department of Pathology.David Geffen School of Medicine at UCLARonald Reagan UCLA Medical Center

摘要目的依据PI-RAdS第1版和第2版判断在3 T MR引导下前列腺活检的诊断率。材料与方法本研究符合HIPAA并经机构伦理委员会批准。对106例男性病人行3 T MR引导下前列腺穿刺活检,获得134个活检组织。入组标准:1以往未行前列腺活检者,2以... 详细信息

摘要目的依据PI-RAdS第1版和第2版判断在3 T MR引导下前列腺活检的诊断率。材料与方法本研究符合HIPAA并经机构伦理委员会批准。对106例男性病人行3 T MR引导下前列腺穿刺活检,获得134个活检组织。入组标准:1以往未行前列腺活检者,2以前前列腺活检阴性,但前列腺特异性抗原(PSA)水平升高者,或3具有前列腺癌病史且PSA水平升高者。临床采用3 T MR对前列腺进行引导穿刺活检并搜集病理资料。对每例病人及每个活检组织进行

关键词：穿刺活检前列腺癌 PI-RAdS

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Malargüe Site Remediation: A Successful Solution for Uranium Mill Tailings

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原子能科学技术 2024年

作者： BARARI E díAZ j G GIOMIA KEMPF R A National Atomic Energy Commission Av.Del Libertador 8250 Ciudad Autónoma de Buenos AiresC1429BNP Argentina

Comisión Nacional de Energía Atómica(CNEA) has the responsibility for restoring uranium mining facilities once the operations have finished. CNEA, within its Environmental Program and in compliance with its legal responsibilities, decides to implement a restoration project for all sites related to the mining and processing of uranium ores. The Malargüe Site is located within the Province of Mendoza in the city of Malargüe. It is the first site to successfully complete its remediation. The activities consist of relocation of tailings to an engineering repository. The tailings management(encapsulation) and rehabilitation of the area was finished in june 2017. The remediation alternative for the ore tailings was selected after conducting comparative studies and submitted the project to the society for consideration. The objective of the encapsulation of the mineral tails is to isolate them from the environment, also proceeding with the decontamination and rehabilitation of the area(landscaping,post-closure monitoring and 20 years monitoring period). Encapsulation consisted of the construction of a containment cell for the mine tailings, to isolate them and prevent pollutants from entering the environment through the transfer routes. To clean the impacted areas, the soil was removed, it was incorporated into the encapsulation, and the filling was carried out with natural soils from the *** prevents radon transfer to the environment, as 222Ra is an alpha emitter with a half-life of four days, which produces its own radioactive progeny. Radon progeny are solids, and when a 222Ra nucleus emits an alpha particle into the air, the resulting 218Po nucleus, momentarily electrically charged, adheres to any dust particle. Remediation prevents the discharge into the air containing radon and also containing dust particles charged with intensely radioactive radon progeny. The tasks mentioned make it possible to decrease radon emanation, reduce radiological risks to the

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