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Search Results: 1 - 10 of 488981 matches for " Peter A. DeRosa "
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Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest
Brad E. Zacharia,Zachary L. Hickman,Bartosz T. Grobelny,Peter A. DeRosa,Andrew F. Ducruet,E. Sander Connolly
Mediators of Inflammation , 2009, DOI: 10.1155/2009/124384
Abstract: Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.
Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy
Brian W. Cross,Timothy V. Johnson,Austin B. DeRosa,Kenneth Ogan,John G. Pattaras,Peter T. Nieh,Omer Kucuk,Wayne B. Harris,Viraj A. Master
International Journal of Surgical Oncology , 2012, DOI: 10.1155/2012/524981
Abstract: Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR) and overall survival in localized renal cell carcinoma (RCC) following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0?mm/hr), intermediate (20.1–50.0?mm/hr), and high risk (>50.0?mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI) survival was 44.1 (42.6–45.5) months, 35.5 (32.3–38.8) months, and 32.1 (25.5–38.6) months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228) increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC. 1. Introduction Over 50,000 Americans are diagnosed with renal cell carcinoma (RCC) each year, approximately 30% of whom will ultimately develop metastatic progression of their disease despite apparent curative nephrectomy for localized cancer at the time of clinical presentation [1, 2]. Metastatic RCC, untreated, has a dismal 5-year survival rate of <10% and a median overall survival of less than one year [3–6]. As such, there has been a long-standing interest in accurately identifying those patients most likely to suffer from postoperative disease progression, and much research in recent years has focused on the development of prognostic models to aid in surveillance strategies and patient counseling. Currently, the most commonly used tool to predict outcome in RCC is the TNM staging system. However, there is considerable overlap in survival between stages [5], and this has fostered the search for other prognostic markers to more clearly stratify those patients in whom a poor outcome can be expected. Recently, efforts at identifying markers of disease progression in RCC have focused
Complement Inhibition Promotes Endogenous Neurogenesis and Sustained Anti-Inflammatory Neuroprotection following Reperfused Stroke
Andrew F. Ducruet, Brad E. Zacharia, Sergey A. Sosunov, Paul R. Gigante, Mason L. Yeh, Justin W. Gorski, Marc L. Otten, Richard Y. Hwang, Peter A. DeRosa, Zachary L. Hickman, Paulina Sergot, E. Sander Connolly
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038664
Abstract: Background and Purpose The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points. Methods To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA). Results Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point. Conclusions Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke.
Solar Multi-Scale Convection and Rotation Gradients Studied in Shallow Spherical Shells
M. L. DeRosa,P. A. Gilman,J. Toomre
Physics , 2002, DOI: 10.1086/344295
Abstract: The differential rotation of the sun, as deduced from helioseismology, exhibits a prominent radial shear layer near the top of the convection zone wherein negative radial gradients of angular velocity are evident in the low- and mid-latitude regions spanning the outer 5% of the solar radius. Supergranulation and related scales of turbulent convection are likely to play a significant role in the maintenance of such radial gradients, and may influence dynamics on a global scale in ways that are not yet understood. To investigate such dynamics, we have constructed a series of three-dimensional numerical simulations of turbulent compressible convection within spherical shells, dealing with shallow domains to make such modeling computationally tractable. These simulations are the first models of solar convection in a spherical geometry that can explicitly resolve both the largest dynamical scales of the system (of order the solar radius) as well as smaller-scale convective overturning motions comparable in size to solar supergranulation (20--40 Mm). We find that convection within these simulations spans a large range of horizontal scales, and that the radial angular velocity gradient in these models is typically negative, especially in low- and mid-latitude regions. Analyses of the angular momentum transport indicates that such gradients are maintained by Reynolds stresses associated with the convection, transporting angular momentum inward to balance the outward transport achieved by viscous diffusion and large-scale flows in the meridional plane. We suggest that similar mechanisms associated with smaller-scale convection in the sun may contribute to the maintenance of the observed radial shear layer located immediately below the solar photosphere.
Using Coronal Loops to Reconstruct the Magnetic Field of an Active Region Before and After a Major Flare
A. Malanushenko,C. Schrijver,M. L. DeRosa,M. S. Wheatland
Physics , 2013, DOI: 10.1088/0004-637X/783/2/102
Abstract: The shapes of solar coronal loops are sensitive to the presence of electrical currents that are the carriers of the nonpotential energy available for impulsive activity. We use this information in a new method for modeling the coronal magnetic field of AR 11158 as a nonlinear force-free field (NLFFF). The observations used are coronal images around time of major flare activity on 2011/02/15, together with the surface line-of-sight magnetic field measurements. The data are from the Helioseismic and Magnetic Imager and Atmospheric Imaging Assembly (HMI and AIA, respectively) onboard the Solar Dynamics Observatory (SDO). The model fields are constrained to approximate the coronal loop configurations as closely as possible, while also subject to the force-free constraints. The method does not use transverse photospheric magnetic field components as input, and is thereby distinct from methods for modeling NLFFFs based on photospheric vector magnetograms. We validate the method using observations of AR 11158 at a time well before major flaring, and subsequently review the field evolution just prior to and following an X2.2 flare and associated eruption. The models indicate that the energy released during the instability is about $1\times10^{32}$ erg, consistent with what is needed to power such a large eruptive flare. Immediately prior to the eruption the model field contains a compact sigmoid bundle of twisted flux that is not present in the post-eruption models, which is consistent with the observations. The core of that model structure is twisted by $\approx0.9$ full turns about its axis.
Solar Magnetic Field Reversals and the Role of Dynamo Families
M. L. DeRosa,A. S. Brun,J. T. Hoeksema
Physics , 2012, DOI: 10.1088/0004-637X/757/1/96
Abstract: The variable magnetic field of the solar photosphere exhibits periodic reversals as a result of dynamo activity occurring within the solar interior. We decompose the surface field as observed by both the Wilcox Solar Observatory and the Michelson Doppler Imager into its harmonic constituents, and present the time evolution of the mode coefficients for the past three sunspot cycles. The interplay between the various modes is then interpreted from the perspective of general dynamo theory, where the coupling between the primary and secondary families of modes is found to correlate with large-scale polarity reversals for many examples of cyclic dynamos. Mean-field dynamos based on the solar parameter regime are then used to explore how such couplings may result in the various long-term trends in the surface magnetic field observed to occur in the solar case.
Advanced LIGO Two-Stage Twelve-Axis Vibration Isolation and Positioning Platform. Part 2: Experimental Investigation and Tests Results
Fabrice Matichard,Brian Lantz,Kenneth Mason,Richard Mittleman,Benjamin Abbott,Samuel Abbott,Eric Allwine,Samuel Barnum,Jeremy Birch,Sebastien Biscans,Daniel Clark,Dennis Coyne,Dan DeBra,Ryan DeRosa,Stephany Foley,Peter Fritschel,Joseph A Giaime,Corey Gray,Gregory Grabeel,Joe Hanson,Michael Hillard,Jeffrey Kissel,Christopher Kucharczyk,Adrien Le Roux,Vincent Lhuillier,Myron Macinnis,Brian OReilly,David Ottaway,Hugo Paris,Michael Puma,Hugh Radkins,Celine Ramet,Mitchell Robinson,Laurent Ruet,Pradeep Sareen,Daivid Shoemaker,Andy Stein,Jeremy Thomas,Michael Vargas,Jimmy Warner
Physics , 2014,
Abstract: This paper presents the results of the past seven years of experimental investigation and testing done on the two-stage twelve-axis vibration isolation platform for Advanced LIGO gravity waves observatories. This five-ton two-and-half-meter wide system supports more than a 1000 kg of very sensitive equipment. It provides positioning capability and seismic isolation in all directions of translation and rotation. To meet the very stringent requirements of Advanced LIGO, the system must provide more than three orders of magnitude of isolation over a very large bandwidth. It must bring the motion below 10^(-11) m/(Hz)^0.5 at 1 Hz and 10^(-12) m/(Hz)^0.5 at 10 Hz. A prototype of this system has been built in 2006. It has been extensively tested and analyzed during the following two years. This paper shows how the experimental results obtained with the prototype were used to engineer the final design. It highlights how the engineering solutions implemented not only improved the isolation performance but also greatly simplified the assembly, testing, and commissioning process. During the past two years, five units have been constructed, tested, installed and commissioned at each of the two LIGO observatories. Five other units are being built for an upcoming third observatory. The test results presented show that the system meets the motion requirements, and reach the sensor noise in the control bandwidth.
Advanced LIGO Two-Stage Twelve-Axis Vibration Isolation and Positioning Platform. Part 1: Design and Production Overview
Fabrice Matichard,Brian Lantz,Kenneth Mason,Richard Mittleman,Benjamin Abbott,Samuel Abbott,Eric Allwine,Samuel Barnum,Jeremy Birch,Sebastien Biscans,Daniel Clark,Dennis Coyne,Dan DeBra,Ryan DeRosa,Stephany Foley,Peter Fritschel,Joseph A Giaime,Corey Gray,Gregory Grabeel,Joe Hanson,Michael Hillard,Jeffrey Kissel,Christopher Kucharczyk,Adrien Le Roux,Vincent Lhuillier,Myron Macinnis,Brian OReilly,David Ottaway,Hugo Paris,Michael Puma,Hugh Radkins,Celine Ramet,Mitchell Robinson,Laurent Ruet,Pradeep Sareen,Daivid Shoemaker,Andy Stein,Jeremy Thomas,Michael Vargas,Jimmy Warner
Physics , 2014,
Abstract: New generations of gravity wave detectors require unprecedented levels of vibration isolation. This paper presents the final design of the vibration isolation and positioning platform used in Advanced LIGO to support the interferometers core optics. This five-ton two-and-half-meter wide system operates in ultra-high vacuum. It features two stages of isolation mounted in series. The stages are imbricated to reduce the overall height. Each stage provides isolation in all directions of translation and rotation. The system is instrumented with a unique combination of low noise relative and inertial sensors. The active control provides isolation from 0.1 Hz to 30 Hz. It brings the platform motion down to 10^(-11) m/Hz^(0.5) at 1 Hz. Active and passive isolation combine to bring the platform motion below 10^(-12) m/Hz^(0.5) at 10 Hz. The passive isolation lowers the motion below 10^(-13) m/Hz^(0.5) at 100 Hz. The paper describes how the platform has been engineered not only to meet the isolation requirements, but also to permit the construction, testing, and commissioning process of the fifteen units needed for Advanced LIGO observatories.
Implementation of a Simulation Model of the Controlled Release of Molecular Species from Halloysite Nanotubes  [PDF]
Divya Narayan Elumalai, Yuri Lvov, Pedro Derosa
Journal of Encapsulation and Adsorption Sciences (JEAS) , 2015, DOI: 10.4236/jeas.2015.51006
Abstract: In this work a three-dimensional, time-quantified Monte Carlo model that efficiently describes diffusion through and from nanotubes is implemented. Controlled delivery from Halloysite Nano-tubes (HNT) is modeled based on interactions between the HNT’s inner wall and the nanoparticles (NPs) and among NPs themselves. The model was validated using published experimental data. The validated model is then used to study the effect of multiples parameter like HNT diameter and length, particle charge, and ambient temperature on the release of encapsulated NPs. The results show that release profiles depend on the size distribution of the HNT batch used for the experiment, as delivery is sensitive to HNT lumen and length. A very good agreement with the experiment is observed when a weighted average release profile is compared to the experimental profile. Although the NP dynamics is temperature-dependent, the effect is minimum within the range of temperatures relevant to biomedical applications, but will be relevant for other applications at temperatures significantly different from room temperature. This model can be used to predict the best conditions for a particular delivery need.
Pathways of large-scale magnetic couplings between solar coronal events
C. J. Schrijver,A. M. Title,A. R. Yeates,M. L. DeRosa
Physics , 2013, DOI: 10.1088/0004-637X/773/2/93
Abstract: The high-cadence, comprehensive view of the solar corona by SDO/AIA shows many events that are widely separated in space while occurring close together in time. In some cases, sets of coronal events are evidently causally related, while in many other instances indirect evidence can be found. We present case studies to highlight a variety of coupling processes involved in coronal events. We find that physical linkages between events do occur, but concur with earlier studies that these couplings appear to be crucial to understanding the initiation of major eruptive or explosive phenomena relatively infrequently. We note that the post-eruption reconfiguration time scale of the large-scale corona, estimated from the EUV afterglow, is on average longer than the mean time between CMEs, so that many CMEs originate from a corona that is still adjusting from a previous event. We argue that the coronal field is intrinsically global: current systems build up over days to months, the relaxation after eruptions continues over many hours, and evolving connections easily span much of a hemisphere. This needs to be reflected in our modeling of the connections from the solar surface into the heliosphere to properly model the solar wind, its perturbations, and the generation and propagation of solar energetic particles. However, the large-scale field cannot be constructed reliably by currently available observational resources. We assess the potential of high-quality observations from beyond Earth's perspective and advanced global modeling to understand the couplings between coronal events in the context of CMEs and solar energetic particle events.
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