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Neuronal failure in Alzheimer's disease: a view through the oxidative stress looking-glass

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Neuroscience Bulletin 2014年第2期30卷 243-252页

作者： David j. Bonda Xinglong Wang Hyoung-Gon Lee Mark A. smith George Perry Xiongwei Zhu Department of Pathology Case Western Reserve University UTSA Neurosciences Institute and Department of Biology University of Texas at San Antonio

Considerable debate and controversy surround the cause（s） of AIzheimer＇s disease （AD）. To date, several theories have gained notoriety, however none is universally accepted. In this review, we provide evidence for the oxidative stress-induced AD cascade that posits aged mitochondria as the critical origin of neurodegeneration in AD.

关键词： Alzheimer's disease amyloid-beta free radicals mitochondria mitochondrial dynamics oxidativestress

A Model to Describe the Fracture of Porous Polygranular Graphite Subject to Neutron Damage and radiolytic Oxidation

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Computers, Materials & Continua 2016年第3期51卷 163-185页

作者： G.smith E.Schlangen P.E.j.Flewitt A.G.Crocker A.Hodgkins Interface Analysis Centre School of PhysicsUniversity of BristolBristolBS81TLUK Faculty of Civil Engineering and Geosciences Delft University of TechnologyDelftNetherlands HH Wills Physics Laboratory School of PhysicsUniversity of BristolBristolBS81TLUK Physics Department University of SurreyGuildfordGU27XH AMEC Clean Energy now AMEC Foster-WheelerWalton House404 Faraday StreetBirchwood ParkWarringtonCheshireWA36GAUK

Two linked models have been developed to explore the relationship between the amount of porosity arising in service from both radiolytic oxidation and fast neutron damage that influences both the strength and the force-displacement(load-displacement)behaviour and crack propagation in pile grade A graphite used as a nuclear reactor moderator *** models of the microstructure of the porous graphite for both unirradiated and irradiated graphite are *** form the input for the second stage,simulating fracture in lattice-type finite element models,which predicts force(load)-displacement and crack propagation *** comprising aligned filler particles,typical of needle coke,in a porous matrix have been *** purpose was to isolate the contributions of filler particles and porosity to fracture strength and crack paths and consider their implications for the overall failure of reactor core graphite.

关键词： reactor core graphite Modelling microstructure FE lattice model Fracture strength Crack path

The emergence of pandemic influenza viruses

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Protein & Cell 2010年第1期1卷 9-13页

作者： Yi Guan Dhanasekaran Vijaykrishna justin Bahl Huachen Zhu jia Wang Gavin j.D.smith State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Pandemic influenza has posed an increasing threat to public health worldwide in the last *** the 20th century,three human pandemic influenza outbreaks occurred in 1918,1957 and 1968,causing significant mortality.A number of hypotheses have been proposed for the emergence and development of pandemic viruses,including direct introduction into humans from an avian origin and reassortment between avian and previously circulating human viruses,either directly in humans or via an intermediate mammalian ***,the evolutionary history of the pandemic viruses has been controversial,largely due to the lack of background genetic information and rigorous phylogenetic *** pandemic that emerged in early April 2009 in North America provides a unique opportunity to investigate its emergence and development both in human and animal *** genetic analyses of data accumulated through long-term influenza surveillance provided insights into the emergence of this novel pandemic *** this review,we summarise the recent literature that describes the evolutionary pathway of the pandemic *** also discuss the implications of these findings on the early detection and control of future pandemics.

关键词： pandemic influenza influenza virus pandemics control

Anticancer and Antimicrobial Activity of Aspergillus protuberus SP1 Isolated from Marine Sediments of South Indian Coast

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中国天然药物 2011年第4期9卷 286-292页

作者： S.Mathan A.Anton smith j.Kumaran S.Prakash Department of Pharmacy Karpagam UniversityCoimbatoreTamil NaduIndia Department of Pharmacy Annamalai UniversityAnnamalai nager 608002Tamil NaduIndia Sreekrishna College of Pharmacy & research Centre ParassalaThiruvananthapuramKeralaIndia Department of Biotechnology Udaya School of EngineeringAmmandivilai PostKanyakumari District 629204Tamil NaduIndia

AIM:To explore the antimicrobial and anticancer activity of the fungi isolated from marine sediments of south India coastal ***:Marine sediments were collected from different coastal locations of Kanyakumari District,South *** collected marine sediment samples were serially diluted and cultured using SDA media with seawater under appropriate culture *** activity was confirmed by crowded plate *** activity of marine fungi isolate was evaluated against six human pathogenic bacteria viz.,Enterobacter aerogenes.,Escherichia coli,Proteus mirabilis,Bacillus subtilis,Staphylococcus aureus,and Klebsiella pneumoniae.,with different solvents like n-butanol,chloroform,water and *** activity of the selective fungal extracts was tested against Hep 2 cells using MTT ***:Fungus isolated from Muttom coast of south India showed activity against human *** fungi isolate Aspergillus protuberus SP1 was identified by partial sequence of large subunit ribosomal rNA(GenBank accession No.:HQ 386016).Different polar and non-polar solvent extracts of the marine-derived fungus isolate showed antibacterial activity towards various Gram-positive and Gram-negative human *** n-butanol extract of mycelium showed maximum *** on antibacterial activity,the n-butanol extract was selected for anticancer test against Hep 2 cell *** n-butanol extract was subjected to column chromatographic separation using different solvent compositions with ethanol:methanol(9:1) giving better *** fraction was analyzed by GC-MS study showing the presence of nine ***:These results are useful for further investigation of the fungus in the future.

关键词： Aspergillus protuberus SP1 Antibacterial Anticancer Marine sediment

Food Safety and Health—Past Problems and Future Solutions

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Engineering 2020年第4期6卷 384-388页

作者： Christopher j.smith Department of Clinical Sciences and Nutrition University of ChesterChester CH14BJUK

The dictum of Hippocrates“Let thy food be thy medicine and medicine be thy food”is potentially both more accurate and more dangerous than ever *** dictum can only be realistically applied if all foods are known to be *** foods are being produced,which are processed in a variety of ways with ingredients sourced from many different countries and processed in a variety of *** processing may include the addition of supplements which are intended to improve health and of adulterants which are potentially ***,foods may be contaminated with pesticides and other materials encountered during production and *** there is a need to identify“unsafe”*** question may be better put as:Which foods are safe?

关键词： pesticides intended dangerous

Synthetically engineered microbes reveal interesting principles of cooperation

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Frontiers of Chemical Science and Engineering 2017年第1期11卷 3-14页

作者： Michael D. Dressier Corey j. Clark Chelsea A. Thachettu Yasmine Zakaria Omar Tonsi Eldakar robert P. smith Department of Marine Biology and Environmental Science Halmos College of Natural Sciences and Oceanography Nova Southeastern University Fort Lauderdale FL 33314-7796 USA Department of Biological Sciences Halmos College of Natural Sciences and Oceanography Nova Southeastern University Fort Lauderdale FL 33314-7796 USA

Cooperation is ubiquitous in biological sys- tems. However, if natural selection favors traits that confer an advantage to one individual over another, then helping others would be paradoxical. Nevertheless, cooperation persists and is critical in maintaining homeostasis in systems ranging from populations of bacteria to groupings of mammals. Developing an understanding of the dynamics and mechanisms by which cooperation operates is critical in understanding ecological and evolutionary relationships. Over the past decade, synthetic biology has emerged as a powerful tool to study social dynamics. By engineering rationally controlled and modulatable beha- vior into microbes, we have increased our overall under- standing of how cooperation enhances, or conversely constrains, populations. Furthermore, it has increased our understanding of how cooperation is maintained within populations, which may provide a useful framework to influence populations by altering cooperation. As many bacterial pathogens require cooperation to infect the host and survive, the principles developed using synthetic biology offer promise of developing novel tools and strategies to treat infections, which may reduce the use of antimicrobial agents. Overall, the use of engineered cooperative microbes has allowed the field to verify existing, and develop novel, theories that may govern cooperative behaviors at all levels of biology.

关键词： synthetic biology engineered bacteria coop-eration cheater quorum sensing

A review of direct numerical simulations of astrophysical detonations and their implications

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Frontiers of physics 2013年第2期8卷 189-198页

作者： Suzanne T. Parete-Koon Christopher r. smith Thomas L. Papatheodore O. E. Bronson Messer National Center for Computational Sciences Oak Ridge National Laboratory Oak Ridge USA TN 37831-6354 Department of Physics and Astronomy University of Tennessee KnoxvilleUSA TN 37996-1200

Multi-dimensional direct numerical simulations （DNS） of astrophysical detonations in degenerate matter have revealed that the nuclear burning is typically characterized by cellular structure caused by transverse instabilities in the detonation front. Type Ia supernova modelers often use one- dimensional DNS of detonations as inputs or constraints for their whole star simulations. While these one-dimensional studies are useful tools, the true nature of the detonation is multi-dimensional. The multi-dimensional structure of the burning influences the speed, stability, and the composition of the detonation and its burning products, and therefore, could have an impact on the spectra of Type Ia supernovae. Considerable effort has been expended modeling Type Ia supernovae at densities above 1 ~ 107 ***-3 where the complexities of turbulent burning dominate the flame propagation. How- ever, most full star models turn the nuclear burning schemes off when the density falls below 1 ~ 107 ***-3 and distributed burning begins. The deflagration to detonation transition （DDT） is believed to occur at just these densities and consequently they are the densities important for studying the properties of the subsequent detonation. This work will review the status of DNS studies of detona- tions and their possible implications for Type Ia supernova models. It will cover the development of Detonation theory from the first simple Chapman-jouguet （C j） detonation models to the current models based on the time-dependent, compressible, reactive flow Euler equations of fluid dynamics.

关键词： supernova detonations direct numerical simulations

role of Notch signaling in regulating innate immunity and inflammation in health and disease

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Protein & Cell 2016年第3期7卷 159-174页

作者： Yingli Shang Sinead smith Xiaoyu Hu School of Medicine and Institute for Immunology Tsinghua University Beijing 100084 China Department of Clinical Medicine Trinity College Dublin Dublin 2 Ireland

The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.

关键词： inflammation innate immunity macrophages Notch signaling rBP-j

Determinants of the impact of blood pressure variability on neurological outcome after acute ischaemic stroke

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Stroke & Vascular Neurology 2017年第1期2卷 1-6页

作者： Adam de Havenon Alicia Bennett Gregory j Stoddard Gordon smith Lee Chung Steve O’Donnell j Scott McNally David Tirschwell jennifer j Majersik Department of Neurology University of UtahSaltLake CityUtahUSA University of Utah SaltLake CityUtahUSA University of Washington SeattleWashingtonUSA

Introduction: Increased blood pressure variability (BPV) is detrimental after acute ischaemic stroke, but the interaction between BPV and neuroimaging factors that directly influence stroke outcome has not been explored. Methods: We retrospectively reviewed inpatients from 2007 to 2014 with acute anterior circulation ischaemic stroke, CT perfusion and angiography at hospital admission, and a modified rankin Scale (MrS) 30- 365 days after stroke onset. BPV indices included SD, coefficient of variation and successive variation of the systolic blood pressure between 0 and 120 hours after admission. Ordinal logistic regression models were fitted to MrS with predictor variables of BPV indices. Models were further stratified by CT perfusion volumetric measurements, proximal vessel occlusion and collateral score. results: 110 patients met the inclusion criteria. The likelihood of a 1-point rise in the MrS increased with every 10 mm Hg increase in BPV (Or for the 3 BPV indices ranged from 2.27 to 5.54), which was more pronounced in patients with larger ischaemic core volumes (Or 8.37 to 18.0) and larger hypoperfused volumes (Or 6.02 to 15.4). This association also held true for patients with larger mismatch volume, proximal vessel occlusion and good collateral vessels. Conclusions: These results indicate that increased BPV is associated with worse neurological outcome after stroke, particularly in patients with a large lesion core volume, concurrent viable ischaemic penumbra, proximal vessel occlusion and good collaterals. This subset of patients, who are often not candidates for or fail acute stroke therapies such as intravenous tissue plasminogen activator or endovascular thrombectomy, may benefit from interventions aimed at reducing BPV.

关键词： impaired perfusion cerebral