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Search Results: 1 - 10 of 427847 matches for " Thomas M Morgan "
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Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome
Thomas M Morgan, Lan Xiao, Patrick Lyons, Bethany Kassebaum, Harlan M Krumholz, John A Spertus
BMC Medical Genetics , 2008, DOI: 10.1186/1471-2350-9-66
Abstract: We examined the association of putative genetic risk factors with 3-year post-ACS mortality in 811 ACS survivors at university-affiliated hospitals in Kansas City, Missouri. Through a systematic literature search, we first identified genetic variants reported as susceptibility factors for atherosclerosis or ACS. Restricting our analysis to whites, so as to avoid confounding from racial admixture, we genotyped ACS cases for 89 genetic variants in 72 genes, and performed individual Kaplan-Meier survival analyses. We then performed Cox regression to create multivariate risk prediction models that further minimized potential confounding.Of 89 variants tested, 16 were potentially associated with mortality (P < 0.1 for all), of which 6 were significantly associated (P < 0.05) with mortality following ACS. While these findings are not more than what would be expected by chance (P = 0.28), even after Bonferroni correction and adjustment for traditional cardiac risk factors, the IRS1 972Arg variant association (P = 0.001) retained borderline statistical significance (P < 0.1).With the possible exception of IRS1, we conclude that multiple candidate genes were not associated with post-ACS mortality in our patient cohort. Because of power limitations, the 16 gene variants with P values < 0.1 may warrant further study. Our data do not support the hypothesis that the remaining 73 genes have substantial, clinically significant association with mortality after an ACS.Despite convincing evidence of heritable susceptibility to acute coronary syndromes (ACS), including unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI),[1] most common genetic variants have yet to be validated conclusively as ACS risk factors. [2-4] We recently reported an attempt to validate putative cardiac risk factors,[5] all of which had been previously published in significant association with ACS or atherosclerosis, finding that only one pre-spec
Method for non-invasively recording electrocardiograms in conscious mice
Victor Chu, Jose M Otero, Orlando Lopez, James P Morgan, Ivo Amende, Thomas G Hampton
BMC Physiology , 2001, DOI: 10.1186/1472-6793-1-6
Abstract: With this technique we demonstrated significantly reduced heart rate variability in neonates compared to adult mice. We also demonstrated that female mice exhibit significant ECG differences in comparison to age-matched males, both at baseline and in response to β-adrenergic stimulation.The technology we developed enables non-invasive screening of large numbers of mice for ECG changes resulting from genetic, pharmacological, or pathophysiological alterations. Data we obtained non-invasively are not only consistent with what have been reported using invasive and expensive methods, but also demonstrate new findings regarding gender-dependent and age-dependent variations in ECGs in mice.Although electrocardiograms (ECGs) have been obtained in conscious mice, currently reported techniques require restraint [1] or anesthesia and surgical implantation of telemetry devices [2,3,4]. Anesthesia, however, may depress cardiovascular function, and adequate recovery after transmitter implantation in mice is nearly 3 weeks [3,5]. Accordingly, we developed a non-invasive technique for obtaining ECGs in conscious mice by placing the animal on a platform embedded with paw-sized ECG electrodes connected to an amplifier. This method is much less traumatic, requires no anesthesia or surgery, and promotes rapid screening of large quantities of mice. ECG data we obtained non-invasively in conscious mice are comparable to those recently published using surgically implanted telemetry devices [2,4]. To test the efficacy of our system, we evaluated ECGs in mice of either sex, of several strains, and of different ages. Moreover, we tested whether our system could detect ECG alterations in response to pharmacological challenge by isoproterenol. The baseline heart rate data and responses to the β-adrenergic agonist isoproterenol we recorded non-invasively in mice are comparable to data published using invasive methods[6]. We developed an ECG signal processing, analyzing, and database Web portal
Impact of tunnel barrier strength on magnetoresistance in carbon nanotubes
Caitlin Morgan,Maciej Misiorny,Dominik Metten,Sebastian Heedt,Thomas Sch?pers,Claus M. Schneider,Carola Meyer
Physics , 2015,
Abstract: We investigate magnetoresistance in spin valves involving CoPd-contacted carbon nanotubes. Both temperature and bias voltage dependence clearly indicate tunneling magnetoresistance as the origin. We show that this effect is significantly affected by the tunnel barrier strength, which appears to be one reason for the variation between devices previously detected in similar structures. Modeling the data by means of the scattering matrix approach, we find a non-trivial dependence of the magnetoresistance on the barrier strength. Furthermore, analysis of the spin precession observed in a nonlocal Hanle measurement yields a spin lifetime of $\tau_s = 1.1\,$ns, a value comparable with those found in silicon- or graphene-based spin valve devices.
The meaning of acid–base abnormalities in the intensive care unit: Part III – effects of fluid administration
Thomas J Morgan
Critical Care , 2004, DOI: 10.1186/cc2946
Abstract: There is a persistent misconception among critical care personnel that the systemic acid–base properties of a fluid are dictated by its pH. Some even advocate 'pH-balanced' fluids, particularly when priming cardiopulmonary bypass pumps [1]. This is not to deny the merit of avoiding very high or very low pH in fluids intended for rapid administration. Extremes of pH can cause thrombophlebitis, and on extravasation tissue necrosis, and rapid administration is a hemolysis risk (specific data on this topic are sparse). However, these effects occur before equilibration. What must be understood is that fluids with widely disparate pH values can have exactly the same systemic acid–base effects. To illustrate, the acid–base properties of 'pure' 0.9% saline (pH 7.0 at 25°C) are identical to those of 0.9% saline equilibrated with atmospheric CO2 (pH 5.6 at 25°C).Until recently, the challenge was to find a logical basis for predicting the acid–base properties of intravenous fluids. In this review important concepts of quantitative physical chemistry are presented, concepts originally set out by the late Peter Stewart [2-5]. They provide the key to understanding fluid induced acid–base phenomena and allow a more informed approach to fluid design. On this background we consider the effects of intravenous fluids on acid–base balance.There are just three independent variables that, when imposed on the physical chemical milieu of body fluids, dictate their acid–base status. They are strong ion difference (SID), the total weak acid concentration (ATOT), and partial CO2 tension (PCO2). The interplay between SID, ATOT, and PCO2 is the sole determinant of pH, as well as of other dependent variables such as [HCO3 -]. All acid–base interventions, including fluid administration, act through SID, ATOT and PCO2, alone or in combination. The single exception is the addition of weak base (e.g. tris-hydroxymethyl aminomethane) [6], which is normally absent from body fluids.Elements such as Na+
Near-resonant optical forces beyond the two-level approximation for a continuous source of spin-polarized cold atoms
Thomas Vanderbruggen,Morgan Mitchell
Physics , 2013, DOI: 10.1103/PhysRevA.87.033410
Abstract: We propose a method to generate a source of spin-polarized cold atoms which are continuously extracted and guided from a magneto-optical trap using an atom-diode effect. We show that it is possible to create a pipe-like potential by overlapping two optical beams coupled with the two transitions of a three-level system in a ladder configuration. With alkali-metal atoms, and in particular with $^{87}$Rb, a proper choice of transitions enables both the potential generation and optical pumping, thus polarizing the sample in a given Zeeman state. We extend the Dalibard and Cohen-Tannoudji dressed-atom model of radiative forces to the case of a three-level system. We derive expressions for the average force and the different sources of momentum diffusion in the resonant, non-perturbative regime. We show using numerical simulations that a significant fraction of the atoms initially loaded can be guided over several centimeters with output velocities of a few meters per second. This would produce a collimated continuous source of slow spin-polarized atoms suitable for atom interferometry.
Consanguinity Mapping of Congenital Heart Disease in a South Indian Population
Tracy L. McGregor,Amit Misri,Jackie Bartlett,Guilherme Orabona,Richard D. Friedman,David Sexton,Sunita Maheshwari,Thomas M. Morgan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010286
Abstract: Parental consanguinity is a risk factor for congenital heart disease (CHD) worldwide, suggesting that a recessive inheritance model may contribute substantially to CHD. In Bangalore, India, uncle-niece and first cousin marriages are common, presenting the opportunity for an international study involving consanguinity mapping of structural CHD. We sought to explore the recessive model of CHD by conducting a genome-wide linkage analysis utilizing high-density oligonucleotide microarrays and enrolling 83 CHD probands born to unaffected consanguineous parents.
The Influence of Coral Reef Benthic Condition on Associated Fish Assemblages
Karen M. Chong-Seng, Thomas D. Mannering, Morgan S. Pratchett, David R. Bellwood, Nicholas A. J. Graham
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042167
Abstract: Accumulative disturbances can erode a coral reef’s resilience, often leading to replacement of scleractinian corals by macroalgae or other non-coral organisms. These degraded reef systems have been mostly described based on changes in the composition of the reef benthos, and there is little understanding of how such changes are influenced by, and in turn influence, other components of the reef ecosystem. This study investigated the spatial variation in benthic communities on fringing reefs around the inner Seychelles islands. Specifically, relationships between benthic composition and the underlying substrata, as well as the associated fish assemblages were assessed. High variability in benthic composition was found among reefs, with a gradient from high coral cover (up to 58%) and high structural complexity to high macroalgae cover (up to 95%) and low structural complexity at the extremes. This gradient was associated with declining species richness of fishes, reduced diversity of fish functional groups, and lower abundance of corallivorous fishes. There were no reciprocal increases in herbivorous fish abundances, and relationships with other fish functional groups and total fish abundance were weak. Reefs grouping at the extremes of complex coral habitats or low-complexity macroalgal habitats displayed markedly different fish communities, with only two species of benthic invertebrate feeding fishes in greater abundance in the macroalgal habitat. These results have negative implications for the continuation of many coral reef ecosystem processes and services if more reefs shift to extreme degraded conditions dominated by macroalgae.
Elucidating the CXCL12/CXCR4 Signaling Network in Chronic Lymphocytic Leukemia through Phosphoproteomics Analysis
Morgan O'Hayre,Catherina L. Salanga,Thomas J. Kipps,Davorka Messmer,Pieter C. Dorrestein,Tracy M. Handel
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011716
Abstract: Chronic Lymphocytic Leukemia (CLL) pathogenesis has been linked to the prolonged survival and/or apoptotic resistance of leukemic B cells in vivo, and is thought to be due to enhanced survival signaling responses to environmental factors that protect CLL cells from spontaneous and chemotherapy-induced death. Although normally associated with cell migration, the chemokine, CXCL12, is one of the factors known to support the survival of CLL cells. Thus, the signaling pathways activated by CXCL12 and its receptor, CXCR4, were investigated as components of these pathways and may represent targets that if inhibited, could render resistant CLL cells more susceptible to chemotherapy.
Crystal structures of Burkholderia cenocepacia dihydropteroate synthase in the apo-form and complexed with the product 7,8-dihydropteroate
Rachel E Morgan, Ga?lle O Batot, Jennifer M Dement, Vincenzo A Rao, Thomas C Eadsforth, William N Hunter
BMC Structural Biology , 2011, DOI: 10.1186/1472-6807-11-21
Abstract: An efficient recombinant protein expression system for DHPS from B. cenocepacia (BcDHPS) was prepared, the dimeric enzyme purified in high yield and crystallized. The structure of the apo-enzyme and the complex with the product 7,8-dihydropteroate have been determined to 2.35 ? and 1.95 ? resolution respectively in distinct orthorhombic crystal forms. The latter represents the first crystal structure of the DHPS-pterin product complex, reveals key interactions involved in ligand binding, and reinforces data generated by other structural studies. Comparisons with orthologues identify plasticity near the substrate-binding pocket and in particular a range of loop conformations that contribute to the architecture of the DHPS active site. These structural data provide a foundation for hit discovery. An intriguing observation, an artifact of the analysis, that of a potential sulfenamide bond within the ligand complex structure is mentioned.Structural similarities between BcDHPS and orthologues from other Gram-negative species are evident as expected on the basis of a high level of sequence identity. The presence of 7,8-dihydropteroate in the binding site provides details about ligand recognition by the enzyme and the different states of the enzyme allow us to visualize distinct conformational states of loops adjacent to the active site. Improved drugs to combat infections by Burkholderia sp. and related Gram-negative bacteria are sought and our study now provides templates to assist that process and allow us to discuss new ways of inhibiting DHPS.Dihydropteroate synthase (DHPS, EC: catalyses the reaction of 6-hydroxymethyl-7,8-dihydropterin-pyrophosphate with p-aminobenzoic acid (p-ABA) to yield 7,8-dihydropteroate and pyrophosphate (Figure 1). In so doing the enzyme supports the biosynthesis of folate, a key metabolite required to support the synthesis of DNA, and proteins. The provision of folates, either by synthesis in plants and microorganisms or as acquire
Unmeasured anions: the unknown unknowns
Bala Venkatesh, Thomas J Morgan
Critical Care , 2008, DOI: 10.1186/cc6768
Abstract: Unmeasured ions have long captured the imagination of intensivists. Potential candidates include L-lactate, β-hydroxybutyrate, D-lactate, salicylate, formate and oxalate in toxicological situations, pyroglutamate, semisynthetic penicillins, sulphate and hippurate in renal failure, and occasionally urate and amino acids with catabolic states and total parenteral nutrition. Reports of increased tricyclic acid (TCA) cycle anions in shock are now emerging [1,2].Their presence is often inferred from the anion gap (AG), calculated as [Na+] + [K+] - ([Cl-] + [HCO3-]). When its reference range is exceeded, a search for unmeasured anions should commence, irrespective of the overall metabolic acid-base status, because a competing metabolic alkalosis can mask their presence. Likely culprits vary with the clinical scenario, but the search usually starts with L-lactate and β-hydroxybutyrate. During this process, stoichiometry is tracked between ΔAG (measured AG – normal AG) and the summed concentrations of suspect anions (always in mEq/l, because we are dealing in electrical neutrality). If ΔAG – [suspect anions] exceeds 2 to 3 mEq/l, then the involvement of other unmeasured anions is likely.Unfortunately, the AG is a flawed instrument. Both sensitivity and specificity are reduced by perturbations of albumin (remembering that albumin negative charge forms the bulk of the normal AG), pH, [Ca2+], [Mg2+] and [phosphate] [3]. The most promising alternative is the strong ion gap (SIG) [4,5] Like the AG, the SIG quantifies unmeasured anions minus unmeasured cations, but unlike its predecessor it is insulated from variations in [albumin], [phosphate], pH, [L-lactate], [Ca2+] and [Mg2+] [6].In the previous issue of Critical Care, Bruegger and colleagues [1] combine SIG calculations with capillary electrophoresis, and report that anions associated with the TCA cycle, specifically citrate and acetate, contribute to the metabolic acidosis of canine haemorrhagic shock. Their data originate
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