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MicroRNAs as diagnostic markers and therapeutic targets for traumatic brain injury

Neural Regeneration Research 2017年第11期12卷 1749-1761页

作者： bridget Martinez philip V.Peplow Department of Molecular and Cellular biology University of California Department of Anatomy University of Otago

Traumatic brain injury （TbI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TbI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as develop- ment, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TbI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma （miR-425-p, -21, -93, -191 and -499） and cerebro-spinal fluid （CSF）（miR-328, -362-3p, -451, -486a） as possible indicators of the diagnosis, severity, and prognosis of TbI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TbI （e.g., miR-21, miR-23b）. MicroRNA profil- ing was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TbI （e.g., miR-21） have also been reported. Further large-scale studies with TbI patients are needed to provide more information on the changes in microRNA profiles in different age groups （children, adults, and elderly）.

关键词： traumatic brain injury microRNAs diagnostic markers therapeutic targets: humans animal models

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Immunomodulators and microRNAs as neurorestorative therapy for ischemic stroke

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Neural Regeneration Research 2017年第6期12卷 865-874页

作者： bridget Martinez philip V.Peplow Department of Molecular and Cellular biology University of California Department of Anatomy University of Otago

Most of all strokes are ischemic due to occlusion of a vessel, and comprise two main types, thrombotic and embolic. Inflammation and immune response play an important role in the outcome of ischemic stroke. Pharmaceutical and cell-based therapies with immunomodulatory properties could be of benefit in treating ischemic stroke. Possible changes in micro RNAs brought about by immunomodulatory treatments may be important. The pharmaceutical studies described in this review have identified several differentially regulated mi RNAs associated with disregulation of m RNA targets or the upregulation of several neuroprotective genes, thereby highlighting the potential neuroprotective roles of specific mi RNAs such as mi R-762,-1892,-200 a,-145. Mi R-124,-711,-145 are the strongly associated mi RNAs predicted to mediate anti-inflammatory pathways and microglia/macrophage M2-like activation phenotype. The cell-based therapy studies reviewed have mainly utilized mesenchymal stem cells or human umbilical cord blood cells and shown to improve functional and neurological outcomes in stroke animals. Mi R-145 and mi R-133 b were implicated in nerve cell remodeling and functional recovery after stroke. Human umbilical cord blood cells decreased proinflammatory factors and promoted M2 macrophage polarization in stroke diabetic animals.

关键词： neurological umbilical microglia occlusion thrombotic macrophage remodeling utilized neuronal comprise

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MicroRNAs in Parkinson's disease and emerging therapeutic targets

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Neural Regeneration Research 2017年第12期12卷 1945-1959页

作者： bridget Martinez philip V.Peplow Department of Molecular and Cellular biology University of California Department of Anatomy University of Otago

Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons. Oxidative stress is also recognized as one of the main causes of PD, and excessive reactive oxygen species（ROS） and reactive nitrogen species can lead to dopaminergic neuron vulnerability and eventual death. Micro RNAs control a range of physiological and pathological functions, and may serve as potential targets for intervention against PD to mitigate damage to the brain. Several studies have demonstrated that micro RNAs can regulate oxidative stress and prevent ROS-mediated damage to dopaminergic neurons, suggesting that specific micro RNAs may be putative targets for novel therapeutic strategies in PD. Recent human and animal studies have identified a large number of dysregulated micro RNAs in PD brain tissue samples, many of which were downregulated. The dysregulated micro RNAs affect downstream targets such as SNCA, PARK2, LRRK2, TNFSF13 b, LTA, SLC5 A3, PSMb2, GSR, GbA, LAMP-2 A, HSC. Apart from one study, none of the studies reviewed had used agomirs or antagomirs to reverse the levels of downregulated or upregulated micro RNAs, respectively, in mouse models of PD or with isolated human or mouse dopaminergic cells. Further large-scale studies of brain tissue samples collected with short postmortem interval from human PD patients are warranted to provide more information

关键词： Parkinson's disease brain tissue microRNAs therapeutic targets humans animal models

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MicroRNAs as disease progression biomarkers and therapeutic targets in experimental autoimmune encephalomyelitis model of multiple sclerosis

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Neural Regeneration Research 2020年第10期15卷 1831-1837页

作者： bridget Martinez philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to *** demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal *** tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and ***(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord *** expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord *** using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis ***,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and *** studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease ***,studies should be performed with male mice of a similar age,and with aged male and female mice.

关键词： animal model blood plasma blood serum brain tissue disease biomarkers experimental autoimmune encephalomyelitis microRNAs multiple sclerosis spinal cord therapeutic targets urine exosomes

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Does financial development lower energy intensity?

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Frontiers in Energy 2020年第3期14卷 620-634页

作者： philip Kofi ADOM Michael Owusu APPIAH Mawunvo Prosper AGRADI Department of Development Policy School of Public Service and GovernanceGhana Institute of Management and Public Administration(GIMPA)AchimotaGhana Department of Finance Business SchoolUniversity of Cape CoastAccraGhana Department of banking and Finance University of Professional StudiesAccraGhana

The growth-induced effects of financial development have been well-established in the empirical literature,as well as the significance of financial development to energy demand ***,the empirical evidence on the relationship between financial development and energy intensity remains sparse in the *** the multifaceted nature of the effects of financial development,the proposed relationship seems a complex one and warrants an empirical *** the case of Ghana,this study provides an empirical answer to the question:does financial development lower energy intensity?To provide solid grounds for either rejection or acceptance of the null hypothesis,this study performed several robustness ***,the evidence revealed that financial development lowers energy ***,the results revealed that the price of energy,trade liberalization and industry structure play significant *** results have important implications for the design of macro energy efficiency policies and the creation of a‘Green bank’.

关键词： financial development energy intensity energy efficiency Ghana

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φ-meson photoproduction off the protons by using linearly polarized photons in the mid- to higher-t regimes at threshold energies

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Chinese Physics C 2009年第12期33卷 1349-1353页

作者： Julian Salamanca philip L. Cole Idaho State University Department of Physics Pocatello ID 83209-8106 USA Thomas Jefferson National Laboratory. Newport News VA 23606 USA

Observables from vector meson photoproduction by linearly-polarized photons can be expressed in term of bilinear combinations of helicity amplitudes parameterized by the Spin Density Matrix Elements （SDMEs）. These SDMEs give straightforward relations for understanding the nature of the parity exchange at threshold energies, as well as for extracting signatures of the Okubo-Zweig-Iizuka violation. This paper will show preliminary measurements of SDMEs for γp →φp in the photon energy range of 1.7 to 1.9 GeV （momentum transfer squared t range of -1.2 to -0.25 GeV2） and 1.9 to 2.1 CeV （t range of -1.4 to -0.25 GeV2） from the g8b experimental data collected in the summer of 2005 in the Hall b of Jefferson Lab.

关键词： photoproduction of Ф-mesons linearly-polarized photons polarization observables

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Slope failure simulations with MPM

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Journal of Hydrodynamics 2017年第3期29卷 445-451页

作者： philip J.Vardon bin Wang Michael A.Hicks Geo-Engineering Section Faculty of Civil Engineering and GeosciencesDelft University of Technology State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of Sciences

The simulation of slope failures,including both failure initiation and development,has been modelled using the material point method（MPM）.Numerical case studies involving various slope angles,heterogeneity and rainfall infiltration are *** is demonstrated that,by utilising a constitutive model which encompasses,in a simplified manner,both pre-and post-failure behaviour,the material point method is able to simulate commonly observed failure *** is a step towards being able to better quantify slope failure consequence and risk.

关键词： Heterogeneity material point method(MPM) rainfall-induced slope failure strain softening

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A Survey of Human-centered Intelligent Robots:Issues and Challenges

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IEEE/CAA Journal of Automatica Sinica 2017年第4期4卷 602-609页

作者： Wei He Zhijun Li C.L.philip Chen IEEE School of Automation and Electrical Engineering University of Science and Technology Beijing College of Automation Science and Engineering South China University of Technology Department of Computer and Information Science Faculty of Science and Technology University of Macao

Intelligent techniques foster the dissemination of new discoveries and novel technologies that advance the ability of robots to assist and support humans. The human-centered intelligent robot has become an important research field that spans all of the robot capabilities including navigation, intelligent control, pattern recognition and human-robot interaction. This paper focuses on the recent achievements and presents a survey of existing works on human-centered robots. Furthermore, we provide a comprehensive survey of the recent development of the human-centered intelligent robot and discuss the issues and challenges in the field.

关键词： Human-centered robots human-robot interaction intelligent control navigation path planning pattern recognition

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Ad Hoc File Systems for High-Performance Computing

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Journal of Computer Science & Technology 2020年第1期35卷 4-26页

作者： Andrébrinkmann Kathryn Mohror Weikuan Yu philip Carns Toni Cortes Scott A.Klasky Alberto Miranda Franz-Josef Pfreundt Robert b.Ross Marc-AndréVef Zentrum für Datenverarbeitung Johannes Gutenberg University MainzMainz 55128Germany Center for Applied Scientific Computing Lawrence Livermore National LaboratoryLivermoreCA 94550U.S.A Department of Computer Science Florida State UniversityTallahasseeFL 32306U.S.A Mathematics and Computer Science Division Argonne National LaboratoryLemontIL 60439U.S.A Department of Computer Architecture Universitat Politecnica de CatalunyaBarcelona 08034Spain Computer Science and Mathematics Division Oak Ridge National LaboratoryOak RidgeTN 37831U.S.A Computer Science Department Barcelona Supercomputing CenterBarcelona 08034Spain Fraunhofer Institute for Industrial Mathematics ITWM Fraunhofer-Platz 1Kaiserslautern 67663Germany

Storage backends of parallel compute clusters are still based mostly on magnetic disks,while newer and faster storage technologies such as flash-based SSDs or non-volatile random access memory(NVRAM)are deployed within compute *** these new storage technologies into scientific workflows is unfortunately today a mostly manual task,and most scientists therefore do not take advantage of the faster storage *** approach to systematically include nodelocal SSDs or NVRAMs into scientific workflows is to deploy ad hoc file systems over a set of compute nodes,which serve as temporary storage systems for single applications or longer-running *** paper presents results from the Dagstuhl Seminar 17202"Challenges and Opportunities of User-Level File Systems for HPC"and discusses application scenarios as well as design strategies for ad hoc file systems using node-local storage *** discussion includes open research questions,such as how to couple ad hoc file systems with the batch scheduling environment and how to schedule stage-in and stage-out processes of data between the storage backend and the ad hoc file *** presented are strategies to build ad hoc file systems by using reusable components for networking and how to improve storage device *** interfaces and semantics are presented,for example those used by the three ad hoc file systems beeOND,GekkoFS,and *** presentation covers a range from file systems running in production to cutting-edge research focusing on reaching the performance limits of the underlying devices.

关键词： parallel architectures distributed file system high-performance computing burst buffer POSIX(portable operating system interface)

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Lessons learned from the Youngstown, Ohio induced earthquake sequence from January 2011 to January 2012

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Journal of Rock Mechanics and Geotechnical Engineering 2017年第5期9卷 783-796页

作者： A.P.Morris D.A.Ferrill G.R.Walter A.M.price K.J.Smart R.J.Skoumal M.R.brudzinski b.S.Currie Southwest Research Institute Culebra Road 6220 San Antonio TX 78238-5166 USA United States Geological Survey Earthquake Science Center 345 Middlefield Rd Building 3A RM 113 Menlo Park CA 94025 USA Department of Geology and Environmental Earth Science Miami University Oxford OH 45056 USA

The Youngstown earthquake sequence of 2011 is one of the clearest examples of inadvertently induced seismicity for which detailed documentation is *** this paper,we investigate(i) likely stress states in the vicinity of the injection well,(ii) a range of likely permeability scenarios,and(iii) relatively simple methods by which induced seismicity can be evaluated and *** use relocated hypocenters from the seismic sequence to construct a basement fault structure,which is then used to serve as a reference surface within the basement,and on which we calculate the effects of pore pressure changes induced by the injection activities of the Northstar #1 injection *** also deduce an in situ(preinjection) strike-slip stress regime,where ρ2≈ρ3,and it is consistent with both recent earthquake data and published stress estimates for the *** the reactivation characteristics of the basement are known or assumed,a critical or threshold slip tendency can be determined and the basement faults can be analyzed for the likelihood of reactivation in a perturbed pore pressure *** of well injection pressures and simulated pore pressure perturbations within the basement below the injection well indicates that permeability anisotropy is necessary to generate sufficient pore pressure perturbation to induce fault *** of the well’s injection history show that our estimate of in situ stress state,coupled with a highly anisotropic permeability structure,can generate sufficient pore pressure perturbation on the inferred basement structure to cause reactivation,potentially slipping an area of approximately 4×10~5 m~2.

关键词： Induced seismicity Wastewater injection Slip tendency

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