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Search Results: 1 - 10 of 173224 matches for " Thomas B. Kuhn "
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A Nonpolar Blueberry Fraction Blunts NADPH Oxidase Activation in Neuronal Cells Exposed to Tumor Necrosis Factor-α
Sally J. Gustafson,Kriya L. Dunlap,Colin M. McGill,Thomas B. Kuhn
Oxidative Medicine and Cellular Longevity , 2012, DOI: 10.1155/2012/768101
Abstract: Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS.
Quality of human-computer interaction - results of a national usability survey of hospital-IT in Germany
Bettina B Bundschuh, Raphael W Majeed, Thomas Bürkle, Klaus Kuhn, Ulrich Sax, Christof Seggewies, Cornelia Vosseler, Rainer R?hrig
BMC Medical Informatics and Decision Making , 2011, DOI: 10.1186/1472-6947-11-69
Abstract: To evaluate the usability of clinical-IT according to the design principles of EN ISO 9241-10 the IsoMetrics Inventory, an assessment tool, was used. The focus of this paper has been put on suitability for task, training effort and conformity with user expectations, differentiated by information systems. Effectiveness has been evaluated with the focus on interoperability and functionality of different IT systems.4521 persons from 371 hospitals visited the start page of the study, while 1003 persons from 158 hospitals completed the questionnaire. The results show relevant variations between different information systems.Specialised information systems with defined functionality received better assessments than clinical information systems in general. This could be attributed to the improved customisation of these specialised systems for specific working environments. The results can be used as reference data for evaluation and benchmarking of human computer engineering in clinical health IT context for future studies.The aim of clinical-IT systems is to support the staff in high quality and cost-efficient patient care [1]. It is important to provide the appropriate information, at the appropriate location, to the appropriate individuals and in appropriate time [2]. The added benefit of information technology (IT) in hospitals has steadily grown during the last years due to increasing functionalities and penetration of medical processes. At present IT-systems are getting continuously more complex. Different studies have shown that users adjustments are associated with technology use and innovation acceptance [3,4]. A positive user attitude towards IT, IT-friendly environment and good communication can have beneficial influence on the system adoption [5]. Therefore, usability and especially the design of dialogues between humans and information systems is one of the most important issues to enable IT in health care [6]. The usability of a product is considered as a pre
Postnatal PPARδ Activation and Myostatin Inhibition Exert Distinct yet Complimentary Effects on the Metabolic Profile of Obese Insulin-Resistant Mice
Barbara L. Bernardo,Timothy S. Wachtmann,Patricia G. Cosgrove,Max Kuhn,Alan C. Opsahl,Kyle M. Judkins,Thomas B. Freeman,John R. Hadcock,Nathan K. LeBrasseur
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011307
Abstract: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARδ agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice.
A Genetically Encoded Reporter for Real-Time Imaging of Cofilin-Actin Rods in Living Neurons
Jianjie Mi, Alisa E. Shaw, Chi W. Pak, Keifer P. Walsh, Laurie S. Minamide, Barbara W. Bernstein, Thomas B. Kuhn, James R. Bamburg
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0083609
Abstract: Filament bundles (rods) of cofilin and actin (1:1) form in neurites of stressed neurons where they inhibit synaptic function. Live-cell imaging of rod formation is hampered by the fact that overexpression of a chimera of wild type cofilin with a fluorescent protein causes formation of spontaneous and persistent rods, which is exacerbated by the photostress of imaging. The study of rod induction in living cells calls for a rod reporter that does not cause spontaneous rods. From a study in which single cofilin surface residues were mutated, we identified a mutant, cofilinR21Q, which when fused with monomeric Red Fluorescent Protein (mRFP) and expressed several fold above endogenous cofilin, does not induce spontaneous rods even during the photostress of imaging. CofilinR21Q-mRFP only incorporates into rods when they form from endogenous proteins in stressed cells. In neurons, cofilinR21Q-mRFP reports on rods formed from endogenous cofilin and induced by all modes tested thus far. Rods have a half-life of 30–60 min upon removal of the inducer. Vesicle transport in neurites is arrested upon treatments that form rods and recovers as rods disappear. CofilinR21Q-mRFP is a genetically encoded rod reporter that is useful in live cell imaging studies of induced rod formation, including rod dynamics, and kinetics of rod elimination.
Determination of the strong coupling constant from the CLEO measurement of the total hadronic cross section in $e^+e^-$ annihilation below 10.56 GeV
Kuhn, Johann H.;Steinhauser, Matthias;Teubner, Thomas
High Energy Physics - Phenomenology , 2007, DOI: 10.1103/PhysRevD.76.074003
Abstract: Using recent CLEO III results for the cross section for $e^+e^- \to {\rm hadrons}$ at seven centre-of-mass energies between 6.964 and 10.538 GeV, we derive a value for the strong coupling constant $\alpha_s(M_Z^2)=0.110_{-0.012}^{-0.010}{}_{-0.011}^{+0.010}$ where the uncertainties are uncorrelated and correlated, respectively. Our result differs significantly from the one derived by CLEO III, as a consequence of inclusion of quark mass effects and the proper matching between the effective theories with four and five flavours. Combining this new result with an analysis based on earlier cross section measurements in the energy region between 2 and 10.6 GeV, we obtain $\alpha_s(M_Z^2)=0.119^{+0.009}_{-0.011}$, well consistent with the current world average.
Lifetime analysis of individual-atom contacts and crossover to geometric-shell structures in unstrained silver nanowires
Christian Obermair,Holger Kuhn,Thomas Schimmel
Beilstein Journal of Nanotechnology , 2011, DOI: 10.3762/bjnano.2.81
Abstract: We study the crossover of quantum point contacts from (i) individual-atom contacts to (ii) electronic-shell effects and finally to (iii) geometric-shell effects in electrochemically deposited silver contacts. The method allows the fabrication of mechanically unstrained structures, which is a requirement for determining the individual atomic configuration by means of a detailed lifetime analysis of their conductance. Within the geometric-shell model, the sequence of conductance maxima is explained quantitatively based on the crystal structure data of silver, and the growth mechanism of the nanowires is discussed.
The gains from early intervention in Europe: Fiscal surveillance and fiscal planning using cash data
Andrew Hughes Hallett,Moritz Kuhn,Thomas Warmedinger
European Journal of Government and Economics , 2012,
Abstract: The use of real-time cash data allows us to make accurate intra-annual forecasts of an economy’s fiscal position, and to issue early warning signals for the need to correct fiscal imbalances. This paper shows how those signals can be used to design the necessary fiscal corrections, and discusses the gains that can be achieved from such interventions. Examples from Germany and Italy show that large corrections are often necessary early on to make adjustments later on acceptable and to keep debt ratios from escalating. There is a credibility issue here; we find the difference between front-loaded and back-loaded adjustment schemes is likely to be vital for the time consistency of fiscal policymaking. We also show that, without early interventions, the later deficit reductions typically double in size – meaning governments become subject to the excessive deficit procedure and significant improve-ment tests more often. Thus the budget savings from early intervention and the use of cash data are significant; in our examples they are similar in size to the operating budget of the department of housing and urban development in Germany. Similar results apply in other Eurozone countries.
Local Computation: Lower and Upper Bounds
Fabian Kuhn,Thomas Moscibroda,Roger Wattenhofer
Computer Science , 2010,
Abstract: The question of what can be computed, and how efficiently, are at the core of computer science. Not surprisingly, in distributed systems and networking research, an equally fundamental question is what can be computed in a distributed fashion. More precisely, if nodes of a network must base their decision on information in their local neighborhood only, how well can they compute or approximate a global (optimization) problem? In this paper we give the first substantial lower bound on such local computation for (optimization) problems including minimum vertex cover, minimum (connected) dominating set, maximum matching, maximal independent set, and maximal matching. In addition we present a new distributed algorithm for solving general covering and packing linear programs. For some problems this algorithm is tight with the lower bounds, for others it is a distributed approximation scheme. Together, our lower and upper bounds establish the local computability and approximability of a large class of problems, characterizing how much local information is required to solve these tasks.
Amyloid-β and Proinflammatory Cytokines Utilize a Prion Protein-Dependent Pathway to Activate NADPH Oxidase and Induce Cofilin-Actin Rods in Hippocampal Neurons
Keifer P. Walsh, Laurie S. Minamide, Sarah J. Kane, Alisa E. Shaw, David R. Brown, Bruce Pulford, Mark D. Zabel, J. David Lambeth, Thomas B. Kuhn, James R. Bamburg
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095995
Abstract: Neurites of neurons under acute or chronic stress form bundles of filaments (rods) containing 1:1 cofilin:actin, which impair transport and synaptic function. Rods contain disulfide cross-linked cofilin and are induced by treatments resulting in oxidative stress. Rods form rapidly (5–30 min) in >80% of cultured hippocampal or cortical neurons treated with excitotoxic levels of glutamate or energy depleted (hypoxia/ischemia or mitochondrial inhibitors). In contrast, slow rod formation (50% of maximum response in ~6 h) occurs in a subpopulation (~20%) of hippocampal neurons upon exposure to soluble human amyloid-β dimer/trimer (Aβd/t) at subnanomolar concentrations. Here we show that proinflammatory cytokines (TNFα, IL-1β, IL-6) also induce rods at the same rate and within the same neuronal population as Aβd/t. Neurons from prion (PrPC)-null mice form rods in response to glutamate or antimycin A, but not in response to proinflammatory cytokines or Aβd/t. Two pathways inducing rod formation were confirmed by demonstrating that NADPH-oxidase (NOX) activity is required for prion-dependent rod formation, but not for rods induced by glutamate or energy depletion. Surprisingly, overexpression of PrPC is by itself sufficient to induce rods in over 40% of hippocampal neurons through the NOX-dependent pathway. Persistence of PrPC-dependent rods requires the continuous activity of NOX. Removing inducers or inhibiting NOX activity in cells containing PrPC-dependent rods causes rod disappearance with a half-life of about 36 min. Cofilin-actin rods provide a mechanism for synapse loss bridging the amyloid and cytokine hypotheses for Alzheimer disease, and may explain how functionally diverse Aβ-binding membrane proteins induce synaptic dysfunction.
Collaborative Governance for Sustainable Development in China  [PDF]
Berthold Kuhn
Open Journal of Political Science (OJPS) , 2016, DOI: 10.4236/ojps.2016.64037
Abstract: The global sustainable development agenda of the United Nations stresses governance and partnerships involving public and private actors as key elements for achieving the sustainable development goals. This paper relates the analysis of China’s growing engagement for sustainable development to the concept of collaborative governance. Based on the analysis of literature, policy documents, participation in conferences as well as interviews with experts, it proposes five factors to explain the promising developments of collaborative governance for sustainable development in China: political leadership, discourses, in-country expertise, institutional density and international cooperation. Against the backdrop of a strong government and tightened political supervision in many policy areas under the Xi Jinping administration, Chinese academics as well as practitioners largely agree that the “green development agenda” stands out in providing opportunities for the business community, think tanks and universities as well as nonprofit organisations to implement projects and gradually influence policies and practices related to the promotion of sustainable development.
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