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International Journal of Digital Earth 2020年第9期13卷 1040-1054页

作者： James M.Fitton Martin Lehmann david c.Major Department of Planning Aalborg UniversityAalborgDenmark The Earth Institute Columbia UniversityNew YorkNYUSA

coastal settlements face many hazards from climate ***,there has been extensive focus on developing and implementing ***,these efforts have prodominantly centred on larger *** towns and small cities(urban areas between 1000 and 100,000 people)have received little attention,despite experiencing a number of barriers to *** absence of information on the global scale of the adaptation challenge within coastal towns and small cities may have contributed to these settlements being *** paper develops a method that can be used to estimate the numbers,sizes,and locations of coastal towns and small cities worldwide from global population data(Global Human Settlement data).Denmark is used as a pilot for this method with settlements over 1000 people classified with relatively high *** method developed here represents a potentially fruitful approach to supporting coastal adaptation,as coastal towns and small cities are identifiable globally,they can be classified into *** will support an assessment of their risk to coastal hazards,and could facilitate knowledge and practice sharing between similar coastal towns and small cities.

关键词： climate change adaptation global data coastal hazards Denmark small urban areas

Autophagic activity in neuronal cell death

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Neuroscience Bulletin 2015年第4期31卷 382-394页

作者： Robert W.Button Shouqing Luo david c.Rubinsztein Peninsula Schools of Medicine and Dentistry Institute of Translational and Stratified MedicineUniversity of Plymouth Department of Medical Genetics Cambridge Institute for Medical ResearchUniversity of Cambridge

As post-mitotic cells with great energy demands, neurons depend upon the homeostatic and waste-recycling functions provided by autophagy. In addition, autophagy also promotes survival during periods of harsh stress and targets aggregate-prone proteins associated with neurodegeneration for degradation. Despite this, autophagy has also been controversially described as a mechanism of programmed cell death. Instances of autophagic cell death are typically associated with elevated numbers of cytoplasmic autophagosomes, which have been assumed to lead to excessive degradation of cellular components. Due to the high activity and reliance on autophagy in neurons, these cells may be particularly susceptible to autophagic death. In this review, we summarize and assess current evidence in support of autophagic cell death in neurons, as well as how the dysregulation of autophagy commonly seen in neurodegeneration can contribute to neuron loss. From here, we discuss potential treatment strategies relevant to such cell-death pathways.

关键词： autophagy autophagic cell death programmed cell death apoptosis necrosis autosis neurodegeneration

Tekcrete Fast~: Fiber-reinforced, rapid-setting sprayed concrete for rib and surface control

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International Journal of Mining Science and Technology 2018年第1期28卷 29-34页

作者： Stephen c.Tadolini Peter S.Mills david R.Burkhard Minova USA IncGeorgetownKYUSA San Juan coal company WaterflowNMUSA

Fiber-reinforced spayed concrete has been used for several years in civil and tunneling *** conducted to reduce cure times and increase compressive and flexural strengths resulted in the development of Tekcrete Fast~, a cementitious product capable of obtaining 41 MPa compressive strength and 8 MPa flexural strength in only 3 h and reaching 7 d strengths of 62 and 11.7 MPa, respectively.A single bag product that uses conventional shotcrete and gunite application systems makes it a natural crossover product for mining *** discovery of incredible adhesion properties and high resistance to chloride permeability helps ensure long-term stability and increases the ease of *** results from Disaster city~ in Texas and the application for rehabilitating a coal mine belt entry are *** case study illustrates the effectiveness of the product in stabilizing a coal mine beltway and adjacent cross-cuts that were subjected to progressive sloughage due to humidity and cyclical loading.

关键词： Sprayed concrete coal mine High strength concrete Polypropylene fiber

Randomness in the Hybrid Modeling and Simulation of Insulin Secretion Pathways in Pancreatic Islets

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Tsinghua Science and Technology 2015年第5期20卷 441-452页

作者： Yang Pu david c.Samuels Layne T.Watson Yang cao the Department of computer Science Virginia Polytechnic Institute and State University the Department of Molecular Physiology and Biophysics Vanderbilt University

Insulin secreted by pancreatic islet ˇ-cells is the principal regulating hormone of glucose *** of insulin secretion may cause glucose to accumulate in the blood, and result in diabetes *** deterministic models of the insulin secretion pathway have been developed, the stochastic aspect of this biological pathway has not been explored. The first step in this direction presented here is a hybrid model of the insulin secretion pathway, in which the delayed rectifying Kcchannels are treated as stochastic events. This hybrid model can not only reproduce the oscillation dynamics as the deterministic model does, but can also capture stochastic dynamics that the deterministic model does not. To measure the insulin oscillation system behavior, a probability-based measure is proposed and applied to test the effectiveness of a new remedy.

关键词： insulin secretion mathematical modeling hybrid model and simulation stochastic dynamics

An extracellular matrix paradox in myocardial scar formation

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1139-1140页

作者： Sangkyun cho david T.Paik Joseph c.Wu Stanford cardiovascular Institute Stanford University School of MedicineStanfordCAUSA Department of Medicine Division of Cardiovascular MedicineStanford University School of MedicineStanfordCAUSA Department of Radiology Stanford University School of MedicineStanfordCAUSA

In a recent article in cell,Yokota et al.1 demonstrate that type V collagen,a minor component of the cardiac extracellular matrix,plays a paradoxical role in limiting scar size after myocardial infarction by altering the mechanical properties of the developing scar tissue and by regulating integrindependent activation of cardiac fibroblasts(Fig.1).

关键词： scar al cardiac

Specific serum antibody binding to phosphorylated and non-phosphorylated tau in non-cognitively impaired,mildly cognitively impaired,and Alzheimer’s disease subjects:an exploratory study

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Translational Neurodegeneration 2017年第1期6卷 324-332页

作者： Andrea c.Klaver Mary P.coffey david A.Bennett david A.Loeffler Department of Neurology Beaumont Research InstituteBeaumont HealthRoyal OakMIUSA Department of Biostatistics Beaumont Research InstituteBeaumont HealthRoyal OakMIUSA Rush Alzheimer’s Disease center ChicagoIL 60612USA

Background:Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy,suggesting that therapies which increase anti-tau antibodies might slow the development and/or progression of Alzheimer’s disease(AD).The extent to which individuals with no cognitive impairment(NcI)possess serum anti-tau antibodies,and whether their concentrations of these antibodies differ from anti-tau antibody levels in persons with mild cognitive impairment(McI)or AD,are *** studies measuring these antibodies did not account for antibody polyvalent binding,which can be extensive,nor that antibody binding to phosphorylated tau peptides could be due to binding to non-phosphorylated epitopes on those ***:An ELISA controlling for these factors was used to measure the specific binding of serum IgG and IgM to phosphorylated(“pTau;”phosphorylated at Serine-199 and Serine-202)and non-phosphorylated(“non-pTau”)tau 196-207 in subjects with NcI,McI,or AD(n=10/group).Between-group differences in these antibody levels were evaluated for statistical significance,and correlations were examined in pooled data from all subjects between these antibody levels and subject age,global cognitive functioning,and NFT ***:Specific IgG binding to pTau and non-pTau was detected in all subjects except for one NcI *** IgM binding was detected to pTau in all subjects except for two AD patients,and to non-pTau in all *** pTau IgG was increased in McI subjects by 53% and 70% *** and NcI subjects respectively(both pcant differences were found between groups for non-pTau IgG(p=0.052),pTau IgM,or non-pTau ***-pTau IgG was negatively associated with global cognition(Spearman rho=−0.50).conclusions:Specific binding of serum IgG and IgM to phosphorylated and non-phosphorylated tau may be present in older persons regardless of their cognitive *** IgG

关键词： Alzheimer’s disease Antibodies Elisa ELISA Mild cognitive impairment Phosphorylated tau

Herbal extracts as hepatoprotectants against acetaminophen hepatotoxicity

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World Journal of Gastroenterology 2010年第19期16卷 2448-2450页

作者： Hartmut Jaeschke c david Williams Mitchell R McGill Anwar Farhood Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS 66160 United States Department of Pathology Brackenridge Hospital Austin TX 78701 United States

Many plant-derived natural products have the potential to be hepatoprotective and therefore can be used to treat acute and chronic liver diseases. The challenge is to identify the most promising compounds and evaluate their protective mechanism. In a recently published article, Wang et al evaluated extracts of the plant Gentiana manshurica Kitagawa (GM) in a model of acetaminophen hepatotoxicity. The authors concluded that GM is hepatoprotective against acetaminopheninduced liver injury due to its antioxidant properties and anti-apoptotic capacity. We would like to discuss the limitations of this experimental approach and question the conclusion based on the data presented in this manuscript and the published literature.

关键词： Acetaminophen Drug hepatotoxicity Herbal extracts N-acetylcysteine

Insights on the use of biosimilars in the treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2017年第11期23卷 1932-1943页

作者： Michael K Zheng david Q Shih Gary c chen F.Widjaja Foundation Inflammatory Bowel and Immunobiology Research InstituteCedars-Sinai Medical Center comprehensive Digestive Institute of Nevada

Biologic therapy, such as those that target tumor necrosis factor(TNF) signaling, has proven to be an efficacious method of treatment for patients with inflammatory bowel disease(IBD) with regards to symptom management and mucosal healing. However, the rising prevalence of IBD worldwide and the everincreasing burden of biologic pharmaceuticals in the health care industry is alarming for insurance companies, clinicians, and patients. The impending patent expiry and the relatively high costs of biologics, particularly anti-TNF agents, have paved the way for biosimilar development for IBD. The United States Food and Drug Administration defines a biosimilar as a biological product that is highly similar to its reference medicinal product, with no clinically meaningful differences in terms of safety, purity, and potency. The hope with biosimilars is that their entry into the market will be able to drive competition between pharmaceutical companies to reduce prices like that of the generic market, and that access to appropriate biologic treatments for IBD patients is increased in the long-term. Yet, there are challenging issues such as indication extrapolation and interchangeability that are still being debated in the field of IBD and must be addressed in future issued guidance. This review will discuss the issues and implications concerning the use of biosimilar therapy for IBD.

关键词： Biosimilar Biologic Inflammatory bowel disease Ulcerative colitis crohn’s disease Indication extrapolation Interchangeability

Investigation of the compressible Flow through the Tip-Section Turbine Blade cascade with Supersonic Inlet

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Journal of Thermal Science 2016年第2期25卷 138-144页

作者： Martin Luxa Jaromír Príhoda david Simurda Petr Straka Jaroslav Synác Institute of Thermomechanics AS cR v.v.i. Dolejskova 1402/5 18200 Prague Czech Republic Aerospace Research and Test Establishment Plc Beranovych 130 19905 Prague Czech Republic Doosan Skoda Power co. Ltd. Tylova 1/57 30128 Pilsen Czech Republic

The contribution deals with the experimental and numerical investigation of compressible flow through the tip-section turbine blade cascade with the blade 54″ long. Experimental investigations by means of optical(interferometry and schlieren method) and pneumatic measurements provide more information about the behaviour and nature of basic phenomena occurring in the profile cascade flow field. The numerical simulation was carried out by means of the EARSM turbulence model according to Hellsten [5] completed by the bypass transition model with the algebraic equation for the intermittency coefficient proposed by Straka and P?íhoda [6] and implemented into the in-house numerical code. The investigation was focused particularly on the effect of shock waves on the shear layer development including the laminar/turbulent transition. Interactions of shock waves with shear layers on both sides of the blade result usually in the transition in attached and/ or separated flow and so to the considerable impact to the flow structure and energy losses in the blade cascade.

关键词： long turbine rotor blade supersonic tip section optical methods transition modelling cFD

Depletion and dysfunction of Vy,2Vo2 T cells in HIV disease： mechanisms, impacts and therapeutic implications

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cellular & Molecular Immunology 2013年第1期10卷 42-49页

作者： Haishan Li Suchita chaudry Bhawna Poonia Yiming Shao c david Pauza Institute of Human Virology and Department of Medicine University of Maryland School of Medicine Baltimore MD USA and State Key Laboratory for Infectious Disease controland Prevention National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China

Infection with human immunodeficiency virus （HIV） disrupts the balance among yT cell subsets, with increasing Vo1＋ cells and substantial depletion of circulating Vo2＋ cells. Depletion is an indirect effect of HIV in cD4-negative Vo2 cells, but is specific for phosphoantigen-responsive subpopulations identified by the Vy2-Jy1.2 （also called Vy9-JyP） T cell receptor rearrangement. The extent of cell loss and recovery is related closely to clinical status, with highest levels of functional V cells present in virus controllers （undetectable viremia in the absence of antiretroviral therapy）. We review the mechanisms and clinical consequences for V cell depletion in HIV disease. We address the question of whether HIV-mediated V cell depletion, despite being an indirect effect of infection, is an important part of the immune evasion strategy for this virus. The important roles for V cells, as effectors and immune regulators, identify key mechanisms affected by HIV and show the strong relationships between V62 cell loss and immunodeficiency disease. This field is moving toward immune therapies based on targeting V cells and we now have clear goals and expectations to Ruide interventional clinical trials.

关键词： HIV disease ST cells mechanisms impacts therapeutic implications