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Search Results: 1 - 10 of 305261 matches for " Matthew J. Maurer "
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The Ratios of CD8+ T Cells to CD4+CD25+ FOXP3+ and FOXP3- T Cells Correlate with Poor Clinical Outcome in Human Serous Ovarian Cancer
Claudia C. Preston, Matthew J. Maurer, Ann L. Oberg, Daniel W. Visscher, Kimberly R. Kalli, Lynn C. Hartmann, Ellen L. Goode, Keith L. Knutson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080063
Abstract: Ovarian cancer is an immune reactive malignancy with a complex immune suppressive network that blunts successful immune eradication. This suppressive microenvironment may be mediated by recruitment or induction of CD4+ regulatory T cells (Tregs). Our study sought to investigate the association of tumor-infiltrating CD4+CD25+FOXP3+ Tregs, and other immune factors, with clinical outcome in serous ovarian cancer patients. We performed immunofluorescence and quantification of intraepithelial tumor-infiltrating triple positive Tregs (CD4+CD25+FOXP3+), as well as CD4+CD25+FOXP3-, CD3+ and CD8+ T cells in tumor specimens from 52 patients with high stage serous ovarian carcinoma. Thirty-one of the patients had good survival (i.e. > 60 months) and 21 had poor survival of < 18 months. Total cell counts as well as cell ratios were compared among these two outcome groups. The total numbers of CD4+CD25+FOXP3+ Tregs, CD4+CD25+FOXP3-, CD3+ and CD8+ cells were not significantly different between the groups. However, higher ratios of CD8+/CD4+CD25+FOXP3+ Treg, CD8+/CD4+ and CD8/CD4+CD25+FOXP3- cells were seen in the good outcome group when compared to the patients with poor outcome. These data show for the first time that the ratios of CD8+ to both CD4+CD25+FOXP3+ Tregs and CD4+CD25+FOXP3- T cells are associated with disease outcome in ovarian cancer. The association being apparent in ratios rather than absolute count of T cells suggests that the effector/suppressor ratio may be a more important indicator of outcome than individual cell count. Thus, immunotherapy strategies that modify the ratio of CD4+CD25+FOXP3+ Tregs or CD4+CD25+FOXP3- T cells to CD8+ effector cells may be useful in improving outcomes in ovarian cancer.
A Kernel for Open Source Drug Discovery in Tropical Diseases
Leticia Ortí,Rodrigo J. Carbajo,Ursula Pieper,Narayanan Eswar,Stephen M. Maurer,Arti K. Rai,Ginger Taylor,Matthew H. Todd,Antonio Pineda-Lucena,Andrej Sali ,Marc A. Marti-Renom
PLOS Neglected Tropical Diseases , 2009, DOI: 10.1371/journal.pntd.0000418
Abstract: Background Conventional patent-based drug development incentives work badly for the developing world, where commercial markets are usually small to non-existent. For this reason, the past decade has seen extensive experimentation with alternative R&D institutions ranging from private–public partnerships to development prizes. Despite extensive discussion, however, one of the most promising avenues—open source drug discovery—has remained elusive. We argue that the stumbling block has been the absence of a critical mass of preexisting work that volunteers can improve through a series of granular contributions. Historically, open source software collaborations have almost never succeeded without such “kernels”. Methodology/Principal Findings Here, we use a computational pipeline for: (i) comparative structure modeling of target proteins, (ii) predicting the localization of ligand binding sites on their surfaces, and (iii) assessing the similarity of the predicted ligands to known drugs. Our kernel currently contains 143 and 297 protein targets from ten pathogen genomes that are predicted to bind a known drug or a molecule similar to a known drug, respectively. The kernel provides a source of potential drug targets and drug candidates around which an online open source community can nucleate. Using NMR spectroscopy, we have experimentally tested our predictions for two of these targets, confirming one and invalidating the other. Conclusions/Significance The TDI kernel, which is being offered under the Creative Commons attribution share-alike license for free and unrestricted use, can be accessed on the World Wide Web at http://www.tropicaldisease.org. We hope that the kernel will facilitate collaborative efforts towards the discovery of new drugs against parasites that cause tropical diseases.
Assessing computationally efficient isomerization dynamics: Delta-SCF density-functional theory study of azobenzene molecular switching
Reinhard J. Maurer,Karsten Reuter
Physics , 2012, DOI: 10.1063/1.3664305
Abstract: We present a detailed comparison of the S0, S1 (n -> \pi*) and S2 (\pi -> \pi*) potential energy surfaces (PESs) of the prototypical molecular switch azobenzene as obtained by Delta-self-consistent-field (Delta-SCF) Density-Functional Theory (DFT), time-dependent DFT (TD-DFT) and approximate Coupled Cluster Singles and Doubles (RI-CC2). All three methods unanimously agree in terms of the PES topologies, which are furthermore fully consistent with existing experimental data concerning the photo-isomerization mechanism. In particular, sum-method corrected Delta-SCF and TD-DFT yield very similar results for S1 and S2, when based on the same ground-state exchange-correlation (xc) functional. While these techniques yield the correct PES topology already on the level of semi-local xc functionals, reliable absolute excitation energies as compared to RI-CC2 or experiment require an xc treatment on the level of long-range corrected hybrids. Nevertheless, particularly the robustness of Delta-SCF with respect to state crossings as well as its numerical efficiency suggest this approach as a promising route to dynamical studies of larger azobenzene-containing systems.
Bistability loss as key feature in azobenzene (non-)switching on metal surfaces
Reinhard J. Maurer,Karsten Reuter
Physics , 2012, DOI: 10.1002/anie.201205718
Abstract: Coinage metal adsorbed azobenzene is investigated as prototypical molecular switch. It is shown that switching capabilities are not just lost due to excited state quenching, but already due to changes in the ground state energetics. Electron demanding coadsorbates are suggested as strategy to regain the switching function.
Excited-state potential-energy surfaces of metal-adsorbed organic molecules from Linear Expansion Δ-Self-Consistent Field Density-Functional Theory (ΔSCF-DFT)
Reinhard J. Maurer,Karsten Reuter
Physics , 2013, DOI: 10.1063/1.4812398
Abstract: Accurate and efficient simulation of excited state properties is an important and much aspired cornerstone in the study of adsorbate dynamics on metal surfaces. To this end, the recently proposed linear expansion \Delta Self-Consistent Field (le\Delta SCF) method by Gavnholt et al. [Phys. Rev. B 78, 075441 (2008)] presents an efficient alternative to time consuming quasi-particle calculations. In this method the standard Kohn-Sham equations of Density-Functional Theory are solved with the constraint of a non-equilibrium occupation in a region of Hilbert-space resembling gas-phase orbitals of the adsorbate. In this work we discuss the applicability of this method for the excited-state dynamics of metal-surface mounted organic adsorbates, specifically in the context of molecular switching. We present necessary advancements to allow for a consistent quality description of excited-state potential-energy surfaces (PESs), and illustrate the concept with the application to Azobenzene adsorbed on Ag(111) and Au(111) surfaces. We find that the explicit inclusion of substrate electronic states modifies the topologies of intra-molecular excited-state PESs of the molecule due to image charge and hybridization effects. While the molecule in gas phase shows a clear energetic separation of resonances that induce isomerization and backreaction, the surface-adsorbed molecule does not. The concomitant possibly simultaneous induction of both processes would lead to a significantly reduced switching efficiency of such a mechanism.
Economic Freedom, Migration and Income Change among U.S. Metropolitan Areas  [PDF]
J. Matthew Shumway
Current Urban Studies (CUS) , 2018, DOI: 10.4236/cus.2018.61001
Abstract:
Even though metropolitan area governments have no control over state level monetary, labor, or fiscal policies, they are able to enact policies designed to enhance local living conditions—however determined. Such policies include local taxes, labor and wage policies, and regulations that can differ substantially from other metropolitan areas even within the same state. Collectively such policies create differing levels of economic freedom, as measured by standardized indices. We examine differences in levels of economic freedom across United States metropolitan areas and explore how these differences affect migration patterns and local aggregate and per capita income changes. We find that those metropolitan areas with higher levels of economic freedom tend to experience net in-migration and positive changes in aggregate and per capita income, although the balance between in-state and out-of-state migration confounds these patterns.
O outro Nietzsche: justi a contra utopia moral
Reinhart Maurer,Oswaldo Giacóia Júnior
Trans/Form/A??o , 1995, DOI: 10.1590/s0101-31731995000100013
Abstract:
Akutes Koronarsyndrom bei Stenose des Hauptstammes der linken Herzkranzarterie
Auer J,Eber B,Maurer E
Journal für Kardiologie , 2004,
Abstract:
Iron Overdose during Pregnancy: Case and Treatment Review  [PDF]
Matthew J. Geraci, Haesuk Heagney
International Journal of Clinical Medicine (IJCM) , 2012, DOI: 10.4236/ijcm.2012.37A126
Abstract:

A 22-year-old pregnant female was transferred to the emergency department having ingested a bottle of iron-containing prenatal vitamins, ondansetron (Zofran?) tablets and alcohol. The patient was hemodynamically stable but suffered from intense bouts of brown, sandy emesis for the first few hours. Investigation revealed the patient ingested 13.57 mg/kg of elemental iron. Due to the initial iron level, history and presentation time whole bowel irrigation was initiated with polyethylene glycol solution. Acute iron toxicity in pregnancy is a medical emergency that can result in multisystem organ failure leading to maternal death and potential fetal demise. High maternal serum iron loads do not affect the developing fetus and are not associated with fetal malformations; however advanced poisoning can lead to maternal death, spontaneous abortions or preterm emergency deliveries. Initial treatment strategies may include whole bowel irrigation using polyethylene glycol electrolyte lavage solution and deferoxamine treatment along with necessary supportive care management. Despite concerns of teratogenicity deferoxamine does not cross the placenta and is regarded as safe for use during pregnancy. Maternal resuscitation must always be the primary objective in acute iron overdoses and, therefore such concern should not delay clinically indicated maternal treatment.

Have the Algae-Grazing Fish in the Back Reefs of Jamaica and Grand Cayman Changed in Size? A View across 36 Years  [PDF]
Matthew J. Draud, M. Itzkowitz
Open Journal of Marine Science (OJMS) , 2018, DOI: 10.4236/ojms.2018.82016
Abstract:
The island of Jamaica is often cited as an example of how overfishing has dramatically reduced the sizes of coral reef fishes. To examine the change in fish sizes over a 36-year period, we analyzed data from systematic surveys conducted in 1977 and 2013/14 of the sizes and relative abundances of four common algae-grazing fishes in the shallow backreef habitats of Jamaica and Grand Cayman. The four species are: striped parrotfish (Scarus iseri), stoplight parrotfish (Sparisoma viride), ocean surgeon (Acanthurus tractus) and the blue tang (Acanthurus coeruleus). We predicted that all four species would be larger in Grand Cayman than in Jamaica in 1977 as well as in 2013/14, because Grand Cayman has been cited as having less fishing pressure than Jamaica. For the same reason, we expected all four species would have declined in size over the 36 years in Jamaica but not in Grand Cayman. Furthermore, we predicted that the compressed body shape of the ocean surgeon and the blue tang would have made them especially vulnerable to net and trap fishing compared to the two parrotfishes, and that accordingly the effects of overfishing would be greater in these two species. We rejected this hypothesis. The size distributions of the laterally compressed species changed significantly on both islands over the 36-year time span, although not as predicted. At both islands, the blue tangs shifted toward smaller sizes and the ocean surgeons shifted toward larger sizes. There were no size distribution changes detected in the two fusiform species. There was also no support for the prediction that the sizes of these four species were larger in Grand Cayman than in Jamaica during either time period.
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