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Search Results: 1 - 10 of 208286 matches for " L. Cumiskey "
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Methods and Tools Supporting Urban Resilience Planning: Experiences from Cork, Ireland  [PDF]
K. M. de Bruijn, H. van der Most, L. Cumiskey, M. Hounjet, M. Mens
Journal of Geoscience and Environment Protection (GEP) , 2018, DOI: 10.4236/gep.2018.64018
Abstract: To prevent flood disasters, policymakers call for resilient cities which are better able to cope with flood hazards. However, actual adoption of resilience measures in urban planning is still limited, partly because it is not sufficiently clear how and to what extent resilience should and can be enhanced. To develop resilience strategies, information on the current resilience and on the effects of measures should be available. Since cities are complex systems, an assessment of resilience requires the input of different actors. To obtain and combine this input, a comprehensive approach which brings together many actors is required. Furthermore, resilience must be integrated in planning frameworks in order to enhance adoption by city policy makers. Tools which support and structure the contribution of different disciplines and actors will help to obtain information on the current resilience and to develop a shared vision on measures to enhance urban resilience. We illustrate our view with an example on Cork, Ireland.
Dual targeting of CCR2 and CX3CR1 in an arterial injury model of vascular inflammation
Maya R Jerath, Peng Liu, Mary Struthers, Julie A DeMartino, Roche Peng, Laurence B Peterson, Anne-Marie Cumiskey, Lihu Yang, Mauricio Rojas, Dhavalkumar D Patel, Alan M Fong
Thrombosis Journal , 2010, DOI: 10.1186/1477-9560-8-14
Abstract: The novel CCR2 antagonist MRL-677 was characterized using an in vivo model of monocyte migration. To determine the relative roles of CCR2 and CX3CR1 in vascular remodeling, normal or CX3CR1 deficient mice were treated with MRL-677. After 14 days, the level of intimal hyperplasia in the artery was visualized by paraffin sectioning and histology of the hind limbs.MRL-677 is a CCR2 antagonist that is effective in blocking macrophage trafficking in a peritoneal thioglycollate model. Intimal hyperplasia resulting from vascular injury was also assessed in mice. Based on the whole-blood potency of MRL-677, sufficient drug levels were maintained for the entire 14 day experimental period to afford good coverage of mCCR2 with MRL-677. Blocking CCR2 with MRL-677 resulted in a 56% decrease in the vascular injury response (n = 9, p < 0.05) in normal animals. Mice in which both CCR2 and CX3CR1 pathways were targeted (CX3CR1 KO mice given MRL-677) had an 88% decrease in the injury response (n = 6, p = 0.009).In this study we have shown that blocking CCR2 with a low molecular weight antagonist ameliorates the inflammatory response to vascular injury. The protective effect of CCR2 blockade is increased in the presence of CX3CR1 deficiency suggesting that CX3CR1 and CCR2 have non-redundant functions in the progression of vascular inflammation.Atherosclerosis is an inflammatory process that is initiated by endothelial dysfunction leading to an increase in adhesiveness of platelets and lymphocytes to the injured region of the artery[1]. The inflammatory response continues with the migration of monocyte derived macrophages, dendritic cells, and a subset of T cells to the area. Finally, smooth muscle cell migration and proliferation occurs. Chemokines and their receptors play an important regulatory role for these processes and genetic studies have revealed specific polymorphisms that are associated with coronary artery disease and carotid artery occlusive disease in man[2,3]. Two chemok
An Anti-PCSK9 Antibody Reduces LDL-Cholesterol On Top Of A Statin And Suppresses Hepatocyte SREBP-Regulated Genes
Liwen Zhang, Timothy McCabe, Jon H. Condra, Yan G. Ni, Laurence B. Peterson, Weirong Wang, Alison M. Strack, Fubao Wang, Shilpa Pandit, Holly Hammond, Dana Wood, Dale Lewis, Ray Rosa, Vivienne Mendoza, Anne Marie Cumiskey, Douglas G. Johns, Barbara C. Ha
International Journal of Biological Sciences , 2012,
Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising therapeutic target for treating coronary heart disease. We report a novel antibody 1B20 that binds to PCSK9 with sub-nanomolar affinity and antagonizes PCSK9 function in-vitro. In CETP/LDLR-hemi mice two successive doses of 1B20, administered 14 days apart at 3 or 10 mpk, induced dose dependent reductions in LDL-cholesterol (≥ 25% for 7-14 days) that correlated well with the extent of PCSK9 occupancy by the antibody. In addition, 1B20 induces increases in total plasma antibody-bound PCSK9 levels and decreases in liver mRNA levels of SREBP-regulated genes PCSK9 and LDLR, with a time course that parallels decreases in plasma LDL-cholesterol (LDL-C). Consistent with this observation in mice, in statin-responsive human primary hepatocytes, 1B20 lowers PCSK9 and LDLR mRNA levels and raises serum steady-state levels of antibody-bound PCSK9. In addition, mRNA levels of several SREBP regulated genes involved in cholesterol and fatty-acid synthesis including ACSS2, FDPS, IDI1, MVD, HMGCR, and CYP51A1 were decreased significantly with antibody treatment of primary human hepatocytes. In rhesus monkeys, subcutaneous (SC) dosing of 1B20 dose-dependently induces robust LDL-C lowering (maximal ~70%), which is correlated with increases in target engagement and total antibody-bound PCSK9 levels. Importantly, a combination of 1B20 and Simvastatin in dyslipidemic rhesus monkeys reduced LDL-C more than either agent alone, consistent with a mechanism of action that predicts additive effects of anti-PCSK9 agents with statins. Our results suggest that antibodies targeting PCSK9 could provide patients powerful LDL lowering efficacy on top of statins, and lower cardiovascular risk.
Computing Reachable Sets as Capture-Viability Kernels in Reverse Time  [PDF]
No?l Bonneuil
Applied Mathematics (AM) , 2012, DOI: 10.4236/am.2012.311219
Abstract: The set SF(x0;T) of states y reachable from a given state x0 at time T under a set-valued dynamic x’(t)∈F(x (t)) and under constraints x(t)∈K where K is a closed set, is also the capture-viability kernel of x0 at T in reverse time of the target {x0} while remaining in K. In dimension up to three, Saint-Pierre’s viability algorithm is well-adapted; for higher dimensions, Bonneuil’s viability algorithm is better suited. It is used on a large-dimensional example.
Three Dimensional Evolution of SN 1987A in a Self-Gravitating Disk  [PDF]
L. Zaninetti
International Journal of Astronomy and Astrophysics (IJAA) , 2013, DOI: 10.4236/ijaa.2013.32010
Abstract:

The introduction of an exponential or power law gradient in the interstellar medium (ISM) allows to produce an asymmetric evolution of the supernova remnant (SNR) when the framework of the thin layer approximation is adopted. Unfortunately both the exponential and power law gradients for the ISM do not have a well defined physical meaning. The physics conversely is well represented by an isothermal self-gravitating disk of particles whose velocity is everywhere Maxwellian. We derived a law of motion in the framework of the thin layer approximation with a control parameter of the swept mass. The photon’s losses, which are often neglected in the thin layer approximation, are modeled trough velocity dependence. The developed framework is applied to SNR 1987A and the three observed rings are simulated.

The Luminosity Function of Galaxies as Modeled by a Left Truncated Beta Distribution  [PDF]
L. Zaninetti
International Journal of Astronomy and Astrophysics (IJAA) , 2014, DOI: 10.4236/ijaa.2014.41013
Abstract: A first new luminosity function of galaxies can be built starting from a left truncated beta probability density function, which is characterized by four parameters. In the astrophysical conversion, the number of parameters increases by one, due to the addition of the overall density of galaxies. A second new galaxy luminosity function is built starting from a left truncated beta probability for the mass of galaxies once a simple nonlinear relationship between mass and luminosity is assumed; in this case the number of parameters is six because the overall density of galaxies and a parameter that regulates mass and luminosity are added. The two new galaxy luminosity functions with finite boundaries were tested on the Sloan Digital Sky Survey (SDSS) in five different bands; the results produce a better fit than the Schechter luminosity function in two of the five bands considered. A modified Schechter luminosity function with four parameters has been also analyzed.
On the Dark Matter’s Halo Theoretical Description  [PDF]
L. M. L. M. Chechin
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.35052
Abstract: We argued that the standard field scalar potential couldn’t be widely used for getting the adequate galaxies’ curve lines and determining the profiles of dark matter their halo. For discovering the global properties of scalar fields that can describe the observable characteristics of dark matter on the cosmological space and time scales, we propose the simplest form of central symmetric potential celestial-mechanical type, i.e. U(φ) = –μ/φ. It was shown that this potential allows get rather satisfactorily dark matter profiles and rotational curves lines for dwarf galaxies. The good agreement with some previous results, based on the N-body simulation method, was pointed out. A new possibility of dwarf galaxies’ masses estimation was given, also.
Analytical Approximation to the Dynamics of a Binary Stars System with Time Depending Mass Variation  [PDF]
Gustavo V. López, Elkin L. López
Journal of Applied Mathematics and Physics (JAMP) , 2018, DOI: 10.4236/jamp.2018.63053
Abstract: We study the classical dynamics of binary stars when there is an interchange of mass between them. Assuming that one of the stars is more massive than others, the dynamics of the lighter one is analyzed as a function of its time depending mass variation. Within our approximations and models for mass transference, we obtain a general result which establishes that if the lightest star looses mass, its period increases. If the lightest star wins mass, its period decreases.
Quantization and Stable Attractors in a DissipativeOrbital Motion  [PDF]
Daniel L. Nascimento, Antonio L. A. Fonseca
Journal of Modern Physics (JMP) , 2011, DOI: 10.4236/jmp.2011.24030
Abstract: We present a method for determining the motion of an electron in a hydrogen atom, which starts from a field Lagrangean foundation for non-conservative systems that can exhibit chaotic behavior. As a consequence, the problem of the formation of the atom becomes the problem of finding the possible stable orbital attractors and the associated transition paths through which the electron mechanical energy varies continuously until a stable energy state is reached.
Genetic and dietary factors related to schizophrenia  [PDF]
Karl L. Reichelt, Michael L. G. Gardner
Open Journal of Psychiatry (OJPsych) , 2012, DOI: 10.4236/ojpsych.2012.21003
Abstract: Biochemical, immunological and epidemiological evidence increasingly support the suggestion that there is a causal relationship between gluten/gliadin and schizophrenia as originally proposed by F. C. Dohan. Furthermore the necessary physiological mechanisms exist to explain a mechanism involving bioactive peptides from these proteins, and these show that this mechanism is possible and probable in at least in a substantial subgroup of schizophrenic patients. Evidence shows a fairly strong genetic disposition, and it must be recognised that any genetic mechanism must implicate altered chemistry and function of proteins. Evidence supports the likelihood that dietary intervention is beneficial for some, and this demands further investigation. A similar conclusion may apply to autism spectrum conditions.
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