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Sino-U.S. partnerships in research, education, and patient care：The experience of the university of pittsburgh and UPMC

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Science China(Life Sciences) 2017年第10期60卷 1150-1156页

作者： S.Levine Margaret C.McDonald Charles E.Bogosta university of pittsburgh Schools of the Health Sciences Pittsburgh PA 15261 USA university of pittsburgh Medical Center (UPMC) Pittsburgh PA 15219 USA

In 2011, the university of pittsburgh School of Medicine(UPSOM) and Tsinghua university formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two *** labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South university Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(university of pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.

关键词： medical education research training partnership

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The oxidative DNA damage response： A review of research undertaken with Tsinghua and Xiangya students at the university of pittsburgh

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Science China(Life Sciences) 2017年第10期60卷 1077-1080页

作者： S.Levine Luxi Sun Rong Tan Ying Gao Lu Yang Hao Chen Yaqun Teng Li Lan UPMC Hillman Cancer Center pittsburgh PA 15213 USA Department of Microbiology and Molecular Genetics University of Pittsburgh School of Medicine Pittsburgh PA 15219 USA School of Medicine Tsinghua University Beijing 100084 China Xiangya Hospital Central South University Changsha 410008 China

Endogenous stress and exogenous toxicants(chemicals and UV light) alter genetic information either directly or indirectly through the production of reactive oxygen species(ROS), thereby driving genomic instability in cells and promoting tumorigenesis. All living cells try to faithfully preserve and transmit their genomic information from one generation to the next using DNA repair mechanisms to repair oxidative DNA damage to prevent cancer or premature aging. Oxidative DNA damage comprises a mixture of DNA lesions including base damage, DNA single strand breaks(SSBs), and DNA double strand breaks(DSBs). This review summarizes some of the studies on DNA damage response at a defined genome locus that are performed by students from the Tsinghua university School of Medicine and the School of Medicine of Central South university(Xiangya Hospital) at the university of pittsburgh School of Medicine. A summary of their work highlights the continuous contribution of the students to a particular research program and exemplifies the achievements of this China-U.S. collaborative training program.

关键词： DNA damage chromatin telomere DNA repair

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Music as medicine for traumatic brain injury:a perspective on future research directions

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Neural Regeneration Research 2024年第10期19卷 2105-2106页

作者： Anthony E.Kline Eleni H.Moschonas Corina O.Bondi Department of Physical Medicine&Rehabilitation University of PittsburghPittsburghPAUSA Safar Center for Resuscitation Research University of PittsburghPittsburghPAUSA Center for Neuroscience University of PittsburghPittsburghPAUSA Department of Critical Care Medicine University of PittsburghPittsburghPAUSA Center for the Neural Basis of Cognition University of PittsburghPittsburghPAUSA Department of Psychology University of PittsburghPittsburghPAUSA Department of Neurobiology University of PittsburghPittsburghPAUSA

Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their *** a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.

关键词： injury traumatic

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Fully flexible implantable neural probes for electrophysiology recording and controlled neurochemical modulation

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Microsystems & Nanoengineering 2024年第3期10卷 317-333页

作者： Mohammad Hassan Malekoshoaraie Bingchen Wu Daniela DKrahe Zabir Ahmed Stephen Pupa Vishal Jain Xinyan Tracy Cui Maysamreza Chamanzar Electrical and Computer Engineering Carnegie Mellon UniversityPittsburghPA 15213USA Bioengineering University of PittsburghPittsburghPA 15260USA Center for Neural Basis of Cognition University of Pittsburgh and Carnegie Mellon UniversityPittburgh 15213USA McGowan Institute for Regenerative Medicine University of PittsburghPittsburgh 15219USA Carnegie Mellon Neuroscience Institute Carnegie Mellon UniversityPittsburgh 15213USA

Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that,in addition to electrical recording and stimulation,enables a more thorough investigation of neural circuit *** have designed a novel,flexible,implantable neural probe capable of controlled,localized chemical stimulation and electrophysiology *** neural probe was implemented using planar micromachining processes on Parylene C,a mechanically flexible,biocompatible *** probe shank features two large microelectrodes(chemical sites)for drug loading and sixteen small microelectrodes for electrophysiology recording to monitor neuronal response to drug *** reduce the impedance while keeping the size of the microelectrodes small,poly(3,4-ethylenedioxythiophene)(PEDOT)was electrochemically coated on recording *** addition,PEDOT doped with mesoporous sulfonated silica nanoparticles(SNPs)was used on chemical sites to achieve controlled,electrically-actuated drug loading and *** neurotransmitters,including glutamate(Glu)and gamma-aminobutyric acid(GABA),were incorporated into the SNPs and electrically triggered to release *** in vitro experiment was conducted to quantify the stimulated release profile by applying a sinusoidal voltage(0.5 V,2 Hz).The flexible neural probe was implanted in the barrel cortex of the wild-type Sprague Dawley *** expected,due to their excitatory and inhibitory effects,Glu and GABA release caused a significant increase and decrease in neural activity,respectively,which was recorded by the recording *** novel flexible neural probe technology,combining on-demand chemical release and high-resolution electrophysiology recording,is an important addition to the neuroscience toolset used to dissect neural circuitry and investigate neural network connectivity.

关键词： Parylene recording release

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Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： Charles H.Nelson Udai B.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding *** the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent *** many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its *** this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder ***,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of *** review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

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A new database of building-space-specific internal loads and load schedules for performance based code compliance modeling of commercial buildings

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Building Simulation 2024年第6期17卷 877-892页

作者： Yunyang Ye Cary A.Faulkner Wooyoung Jung Jian Zhang Eli Brock Pacific Northwest National Laboratory RichlandWA99354USA university of pittsburgh PittsburghPA15260USA

Building-level loads and load schedules prescribed by current modeling rules save modelers time and provide standards during whole building performance ***,recent studies show that they sometimes insufficiently capture the entire building performance due to the varied loads and load schedules for different space *** a solution to this issue,this paper presents a database of default building-space-specific loads and load schedules for use in energy modeling,and in particular code compliance modeling for commercial *** existing sets of default loads and load schedules are reviewed and the challenges behind using them for specific research topics are ***,the proposed method to develop the building-space-specific loads and load schedules is *** that,the database for these building-space-specific loads and load schedules is *** addition,one case is studied to demonstrate the applications of these loads and load *** this case study,three methods are used to develop building energy models:space-specific(using knowledge of the distribution and location of space types and applying the space-specific data in the developed database),building-level(assuming a lack of knowledge of the space types and using the building-level data in the developed database),and calculated-ratio(assuming knowledge of the distribution of space types but not their locations and calculating weighted average values based on the space-specific data in the developed database).The energy results simulated by using these three methods are compared,which shows building-level methods can produce significantly different absolute energy and energy savings results than the results using space-specific ***,this paper discusses the application scope and maintenance of this new database.

关键词： load load schedule space specific building energy modeling code compliance

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Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei Xu Yue Xi Jong-Won Kim Junjie Zhu Min Zhang Meishu Xu Songrong Ren Da Yang Xiaochao Ma Wen Xie Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Department of Hepatobiliary and Pancreatic Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor *** involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been ***,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon *** epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)***^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory *** sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal *** summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin *** sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR

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Coreference resolution helps visual dialogs to focus

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High-Confidence Computing 2024年第2期4卷 129-135页

作者： Tianwei Yue Wenping Wang Chen Liang Dachi Chen Congrui Hetang Xuewei Wang Carnegie Mellon university Pittsburgh 15213USA

Visual Dialog is a multi-modal task involving both computer vision and dialog *** goal is to answer multiple questions in conversation style,given an image as the *** networks with attention modules are widely used for this task,because of their effectiveness in reasoning the relevance between the texts and *** this work,we study how to further improve the quality of such reasoning,which is an open *** baseline is the Recursive Visual Attention(RVA)model,which refines the vision-text attention by iteratively visiting the dialog *** on top of that,we propose to improve the attention mechanism with contrastive *** train a Matching-Aware Attention Kernel(MAAK)by aligning the deep feature embeddings of an image and its caption,to provide better attention *** show consistent improvements from *** addition,we study the effect of using Multimodal Compact Bilinear(MCB)pooling as a three-way feature fusion for the visual,textual and dialog history *** analyze the performance of both methods in the discussion section,and propose further ideas to resolve current limitations.

关键词： Multi-model machine learning Visual dialog Co-reference resolution

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On the inviscid limit of the compressible Navier-Stokes equations near Onsager's regularity in bounded domains

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Science China Mathematics 2024年第1期67卷 1-22页

作者： Robin Ming Chen Zhilei Liang Dehua Wang Runzhang Xu Department of Mathematics University of PittsburghPittsburghPA 15260USA School of Mathematics Southwestern University of Finance and EconomicsChengdu 611130China College of Mathematical Sciences Harbin Engineering UniversityHarbin 150001China

The viscous dissipation limit of weak solutions is considered for the Navier-Stokes equations of compressible isentropic flows confined in a bounded *** establish a Kato-type criterion for the validity of the inviscid limit for the weak solutions of the Navier-Stokes equations in a function space with the regularity index close to Onsager’s critical *** particular,we prove that under such a regularity assumption,if the viscous energy dissipation rate vanishes in a boundary layer of thickness in the order of the viscosity,then the weak solutions of the Navier-Stokes equations converge to a weak admissible solution of the Euler *** approach is based on the commutator estimates and a subtle foliation technique near the boundary of the domain.

关键词： inviscid limit Navier-Stokes equations Euler equations weak solutions bounded domain Katotype criterion Onsager’s regularity

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High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FLOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： Joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang Joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke Li Jiarong Wu Yingshi Ouyang Yoel Sadovsky Luke P.Lee Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA Department of Microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA Department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various ***,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low ***,we report a high-yield(>90%)and rapid(<10 min)EV isolation method called FLocculation via Orbital Acoustic Trapping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid *** adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the *** demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid *** to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating

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