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Update on the Development of Anti-Viral Agents Against Hepatitis C

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Journal of Clinical and Translational Hepatology 2013年第1期1卷 9-21页

作者： kristin l. macarthur Robert Smolic Martina V. Smolic Catherine H. Wu George Y. Wu Department of Medicine Beth Israel Deaconess Medical Center Boston MA02215 Faculty of Medicine Osijek Croatia University of Connecticut Health Center Farmington CT USA Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV. Direct data from agents in phase Ⅲ/Ⅳ clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly important public health concern, and it is important for physicians to stay up to date on the rapidly growing novel therapeutic options.

关键词： HCV Protease Polymerase Triple therapy Drug.

Implementation of Caterpillar Inspired Rolling Gait and Nonlinear Control Strategy in a Spherical Robot

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Journal of Bionic Engineering 2018年第2期15卷 313-328页

作者： Abhra Roy Chowdhury Gim Song Soh Shaohui Foong kristin l. Wood Temasek laboratories Engineering Product Development Pillar Singapore University of Technology and Design Singapore 487372 SUTD-MIT International Design Centre Singapore University of Technology and Design Singapore 487372

This paper presents a novel Central Pattern Generator （CPG） based rolling gait generation in a small-sized spherical robot and its nonlinear control mechanism. A rhythmic rolling pattern mimicking Pleurotya caterpillar is produced for the spherical robot locomotion. A synergetically combined feedforward-feedback control strategy is proposed. The feedforward component is generated from centrally connected network of CPGs in conjunction with nonlinear robot dynamics. Two nonlinear feedback control methods namely integral （first order） Sliding Mode Control （SMC） and High （or second） Order Sliding Mode Control （HOSMC） are proposed to regulate robot stability and gait robustness in the presence of matched parameter uncertainties and bounded external disturbances. Design, implementation and experimental evaluation of both roll gait control strategies for the spherical robot are done on smooth （indoor） and irregular （outdoor） ground surfaces, The performance of robot control is quantified by measuring the roll angle stability, phase plane convergence and wheel velocities. Experimental results show that proposed novel strategy is efficient in producing a stable rolling gait and robust control of a spherical robot on two different types of surfaces. It further shows that proposed high HOSMC strategy is more efficient in robust rolling gait control of a spherical robot compared to an integral first-order SMC on two different ground conditions.

关键词： bioinspired spherical robot rolling gait CPG rolling friction integral first-order SMC control HOSMC

The effects of temperature and resource availability on denitrification and relative N_(2)O production in boreal lake sediments

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Journal of Environmental Sciences 2016年第9期28卷 82-90页

作者： Maria Myrstener Anders Jonsson Ann-kristin Bergstrom Department of Ecology and Environmental Science Umea University90187 UmeaSweden

Anthropogenic environmental stressors（like atmospheric deposition,land use change,and climate warming） are predicted to increase inorganic nitrogen and organic carbon loading to northern boreal lakes,with potential consequences for denitrification in ***,our ability to predict effects of these changes is currently limited as northern boreal lakes have been largely neglected in denitrification *** aim of this study was therefore to assess how maximum potential denitrification and N_2O production rates,and the relationship between the two（relative N_2O production）,is controlled by availability of nitrate（NO_3^-）,carbon（C）,phosphorus（P）,and *** were performed using the acetylene inhibition technique on sediments from a small,nutrient poor boreal lake in northern Sweden in *** potential denitrification and N_2O production rates at 4°C were reached already at NO_3^-additions of 106–120 μg NO_3^-–N/l,and remained unchanged with higher NO_3 *** incubation temperatures increased maximum potential denitrification and N_2O production rates,and Q10 was somewhat higher for N_2O production（1.77） than for denitrification（1.69）.The relative N_2O production ranged between 13% and 64%,and was not related to NO_3^-concentration,but the ratio increased when incubations were amended with C and P（from a median of 16% to 27%）.Combined,our results suggests that unproductive northern boreal lakes currently have low potential for denitrification but are susceptible to small changes in NO_3 loading especially if these are accompanied by enhanced C and P availability,likely promoting higher N_2O production relative to N_2.

关键词： Acetylene NO3 Carbon DOC Nitrous oxide ratio Sediment

Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CDIO7a

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Cellular & Molecular Immunology 2016年第1期13卷 57-64页

作者： Heidi Vego kristin l Sand Rune A Hoglund lars-Egil Fallang Glenn Gundersen Trygve Holmoy Azzam A Maghazachi Departmentof Physiology Institute of Medical Basic Sciences University of Oslo Oslo Norway Medical Department Biogen Idec Norway AS OsloNorway Department of Neurology Akershus University Hospital and institute of Clinical Medicine University of Oslo Oslo Norway

Dimethyl fumarate （DMF） is a new drug used to treat multiple sclerosis （MS） patients. Here, we examined the effects of DMF and the DMF metabolite monomethyl fumarate （MMF） on various activities of natural killer （NK） cells. We demonstrated that MMF augments the primary CD56^＋, but not CD56^-, NK cell lysis of K562 and RAJI tumor cells. MMF induced NKp46 expression on the surface of CD56^＋, but not CD56^-, NK cells after incubation for 24 h. This effect was closely correlated with the upregulation of CD107a expression on the surface of CD56＋ NK cells and the induction of Granzyme B release from these cells through this metabolite. An anti-NKp46 antibody inhibited the MMF-induced upregulation of CD107a and the lysis of tumor cells through CD56^＋ NK cells. Thus, these results are the first to show that MMF augments CD56^＋ NK cell lysis of tumor target cells, an effect mediated through NKp46. This novel effect suggests the use of MMF for therapeutic and/or preventive protocols in cancer.

关键词： cancer prevention cancer treatment CDlO7a cytotoxicity dimethyl fumarate Granzyme B monomethyl fumarate natural killer cells NKp46

Hybrid quantum-classical convolutional neural networks

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Science China(Physics,Mechanics & Astronomy) 2021年第9期64卷 1-8页

作者： Junhua liu Kwan Hui lim kristin lWood Wei Huang Chu Guo He-liang Huang Information Systems Technology and Design Singapore University of Technology and DesignSingapore 487372Singapore Forth AI Singapore 487372Singapore College of Engineering Design and ComputingUniversity of Colorado DenverColorado 80208USA Guangxi Key laboratory of Optoelectronic Information Processing Guilin University of Electronic TechnologyGuilin 541004China Key laboratory of low-Dimensional Quantum Structures and Quantum Control of Ministry of Education Department of Physics and Synergetic Innovation Center for Quantum Effects and ApplicationsHunan Normal UniversityChangsha 410081China Hefei National laboratory for Physical Sciences at Microscale and Department of Modern Physics University of Science and Technology of ChinaHefei 230026China Shanghai Branch CAS Centre for Excellence and Synergetic Innovation Centre in Quantum Information and Quantum PhysicsUniversity of Science and Technology of ChinaHefei 201315China Henan Key laboratory of Quantum Information and Cryptography Zhengzhou 450000China

Deep learning has been shown to be able to recognize data patterns better than humans in specific circumstances or *** parallel,quantum computing has demonstrated to be able to output complex wave functions with a few number of gate operations,which could generate distributions that are hard for a classical computer to *** we propose a hybrid quantum-classical convolutional neural network(QCCNN),inspired by convolutional neural networks(CNNs)but adapted to quantum computing to enhance the feature mapping *** is friendly to currently noisy intermediate-scale quantum computers,in terms of both number of qubits as well as circuit’s depths,while retaining important features of classical CNN,such as nonlinearity and *** also present a framework to automatically compute the gradients of hybrid quantum-classical loss functions which could be directly applied to other hybrid quantum-classical *** demonstrate the potential of this architecture by applying it to a Tetris dataset,and show that QCCNN can accomplish classification tasks with learning accuracy surpassing that of classical CNN with the same structure.

关键词： quantum computing quantum machine learning hybrid quantum-classical algorithm convolutional neural network

Integration of solid phase extraction with HIlIC-MS/MS for analysis of free amino acids in source water

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Journal of Environmental Sciences 2022年第7期34卷 190-196页

作者： Junlang Qiu Caley Craven Nicholas Wawryk kristin Carroll Xing-Fang li Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyUniversity of AlbertaEdmontonT6G 2G3Canada School of Environmental Science and Engineering Sun Yat-sen UniversityGuangzhou 510006China

Amino acids(AAs) are prevalent in source water, particularly during spring run-off. Monitoring of amino acids in source water is desirable for water treatment plants(WTP) to indicate changes in source water quality. The objective of this study was to establish analytical procedures for reliable monitoring of amino acids in source water. Therefore, we examined two different methods, large volume inject(lVI) and solid phase extraction(SPE), for sample preparation prior to HIlIC-MS/MS. The lVI-HIlIC-MS/MS method can provide fast and sensitive detection for clean samples, but suffers from matrix effects, resulting in irreproducible separation and shortening column lifetime. We have demonstrated that SPE was necessary prior to HIlIC-MS/MS to achieve reproducible and reliable quantification of AAs in source water. A natural heterocyclic amine 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid(MTCCA) was also included in the method to indicate changes in other natural nitrogenous compounds in source water. The SPE-HIlIC-MS/MS method was able to achieve limits of detection from 2.6-3400 ng/l for the amino acids and MTCCA with RSDs( n = 3) of 1.1%-4.8%. As well, retention times(RT) of the analytes were reproducible with variation less than 0.01 min( n = 3) through the entire project. We further applied the SPE-HIlICMS/MS method to determine AAs in authentic source water samples collected from two drinking water treatment plants(WTPs) during the 2021 spring run-off season. The results support that the SPE-HIlIC-MS/MS method does not require derivatization and can provide reliable, accurate, and robust analysis of AAs and MTCCA in source water, supporting future monitoring of source water quality.

关键词： Water analysis Disinfection byproducts Amino acids HPlC MS HIlIC

Impact loading in female runners with single and multiple bone stress injuries during fresh and exerted conditions

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Journal of Sport and Health Science 2023年第3期12卷 406-413页

作者： kristin l.Popp Jereme Outerleys Sarah Gehman Margaret Garrahan Sara Rudolph Elizabeth loranger Kathryn E.Ackerman Adam S.Tenforde Mary l.Bouxsein Irene S.Davis Military Performance Division United States Army Research Institute of Environmental MedicineNatickMA 01760USA Endocrine Unit Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA Department of Physical Medicine and Rehabilitation Spaulding Rehabilitation HospitalHarvard Medical SchoolCambridgeMA 02138USA Department of Sports Medicine Boston Children's HospitalHarvard Medical SchoolBostonMA 02115USA Center for Advanced Orthopedic Studies Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA

Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are *** work suggests an association between higher impact loading during running and tibial ***,it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple *** study compared impact variables at the beginning of a treadmill run to exertion andthe changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple ***:We enrolled 45 female runners(aged 18-40 years)for this cross-sectional study:having no history of diagnosed lower extremity BSI(N-BSI,n=14);a history of 1 lower extremity BSI(1-BSI,n=16);and diagnosed by imaging,or a history of multiple(>3)lower extremity BSIs(M-BSI,n=15).Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement *** vertical average loading rate(VAlR),vertical instantaneous loading rate(VIlR),vertical stiffness during impact via instrumented treadmill,and tibial shock determined as the peak po sitive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the ***:There were no differences between groups in VAlR,VIlR,vertical stiffness,or tibial shock in a fresh or exerted ***,compared to N-BSI,women with M-BSI had greater increase with exertion in VAlR(-1.8%vs.6.1%,p=0.01)and VIlR(1.5%vs.4.8%,p=0.03).Similarly,compared to N-BSI,vertical stiffness increased more with exertion among women with M-BSI(-0.9%vs.7.3%,p=0.006)and 1-BSI(-0.9%vs.1.8%,p=0.05).Finally,compared to N-BSI,the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI(0.9%vs.5.5%,p=0.03)and 1-BSI(0.9%vs.11.2%,p=0.02).Conclusion:Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with *** observations impl

关键词： Biomechanics Bone stress injuries Fatigue Runners Stress fracture

Preliminary evaluation of a decision support tool for biochar amendment

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Biochar 2020年第1期2卷 93-105页

作者： Claire l.Phillips Sarah E.light Adam lindsley Thomas A.Wanzek Kylie M.Meyer kristin M.Trippe USDA-ARS Forage Seed and Cereal Research Unit 3450 SW Campus WayCorvallisOR 97331USA University of California Cooperative Extension 142A Garden HighwayYuba CityCA 95991USA Department of Crop and Soil Science Oregon State UniversityCorvallisOR 97331USA

Meta-analyses have shown that only about half of biochar addition studies report improved plant *** improve yield response,here we describe a decision support tool(DST)for selecting a biochar type and amendment rate to meet soil and crop management goals,based on soil and biochar tests values and crop requirements as reported by regional extension *** data from a greenhouse wheat trial,we assessed whether this approach could predict changes in soil chemistry and whether it could identify soils in which amendment would stimulate crop *** data indicated that the DST could provide semi-quantitative predictions of biochar amendment rates needed to meet target soil pH levels,with recommended rates averaging 25%higher than were *** DST was better at predicting biochar application rates to provision P and *** six soil types,post-harvest measurements of extractable-K showed an average 104%recovery of the quantities estimated to be provisioned by conifer wood or wheat straw ***-P recovery averaged 101%in two sandy soils with low P-retention but was considerably lower in four soils with higher P-retention ***-house data also showed that wheat growth improved only when biochar alleviated pH that was substantially below critical thresholds for plant growth,and supported the principle of using crop-specific pH requirements as part of an approach for biochar *** field trials that evaluate yield responses in several nutrient-deficient or acidified soils will be needed to provide a robust evaluation of this DST.

关键词： Wheat liming Phosphorous Potassium Yield response

Creation of an optic nerve sheath diameter ultrasound model for Neuro ICU education

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Military Medical Research 2021年第1期8卷 116-120页

作者： Heidi M.Felix kristin A.Rosenbush Amy M.lannen Robert A.Pooley Jason l.Siegel Benjamin l.Brown Melissa l.Mc Mullan Christina I.Collins William D.Freeman J.Wayne and Delores Barr Weaver Simulation Center Mayo Clinic4500 San Pablo RoadJacksonvilleFL 32224USA Division of Medical Physics Mayo ClinicJacksonvilleFL 32224USA Department of Critical Care Medicine Mayo ClinicJacksonvilleFL 32224USA Department of Neurology Mayo ClinicJacksonvilleFL 32224USA Department of Neurologic Surgery Mayo ClinicJacksonvilleFL 32224USA Department of Radiology Mayo ClinicJacksonvilleFL 32224USA Department of Nursing Mayo ClinicJacksonvilleFL 32224USA

Background: Using ultrasound to measure optic nerve sheath diameter(ONSD) is an emerging bedside technique to noninvasively assess intracranial pressure(ICP) in patients with brain injury. This technique is unique among bedside ultrasonography and is often performed by providers who have no formal ultrasound training. We sought to create a low-cost, 3 D, reusable ONSD model to train neurology, neurosurgery, and critical care providers in measuring ***: We identified 253 articles, of which 15 were associated with models and 2 with simulation. One gelatin model was reported, upon which we based our initial design. We could not validate the visual findings of this model;however, after constructing multiple beta models, the design most representative of human eye anatomy was a globe made of ballistics gel and either a 3 mm, 5 mm, or 7 mm×50 mm 3 D-printed optic nerve inserted into a platform composed of ballistics gel, all of which sat inside a 3 D-printed skull. This model was used to teach ONSD measurements with ultrasound at a continuing medical education event prior to training on a live human ***: A simple 3 D ballistic ONSD model allows learners to practice proper hand placement and pressure, basic landmarks, and ONSD measurement prior to operating on a human eye. This model is replicable and sustainable given that the globe and platform are composed of ballistics gel.

关键词： Intracranial pressure Simulation Task trainer Ultrasound