1,965 research outputs found
Performance test of QU-fitting in cosmic magnetism study
QU-fitting is a standard model-fitting method to reconstruct distribution of
magnetic fields and polarized intensity along a line of sight (LOS) from an
observed polarization spectrum. In this paper, we examine the performance of
QU-fitting by simulating observations of two polarized sources located along
the same LOS, varying the widths of the sources and the gap between them in
Faraday depth space, systematically. Markov Chain Monte Carlo (MCMC) approach
is used to obtain the best-fit parameters for a fitting model, and Akaike and
Bayesian Information Criteria (AIC and BIC, respectively) are adopted to select
the best model from four fitting models. We find that the combination of MCMC
and AIC/BIC works fairly well in model selection and estimation of model
parameters in the cases where two sources have relatively small widths and a
larger gap in Faraday depth space. On the other hand, when two sources have
large width in Faraday depth space, MCMC chain tends to be trapped in a local
maximum so that AIC/BIC cannot select a correct model. We discuss the causes
and the tendency of the failure of QU-fitting and suggest a way to improve it.Comment: 8 pages, 9 figures, submitted to MNRA
Molecular dynamics simulations of human [Formula: see text]: the role of modified bases in mRNA recognition
Accuracy in translation of the genetic code into proteins depends upon correct tRNA–mRNA recognition in the context of the ribosome. In human [Formula: see text] three modified bases are present in the anticodon stem–loop—2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms(2)t(6)A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm(5)s(2)U34) and pseudouridine (ψ) at position 39—two of which, ms(2)t(6)A37 and mcm(5)s(2)U34, are required to achieve wild-type binding activity of wild-type human [Formula: see text] [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390–13395]. Molecular dynamics simulations of nine tRNA anticodon stem–loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms(2)t(6) modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms(2)t(6)A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to ψ39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps
Estrogens promote misfolded proinsulin degradation to protect insulin production and delay diabetes
Summary: Conjugated estrogens (CE) delay the onset of type 2 diabetes (T2D) in postmenopausal women, but the mechanism is unclear. In T2D, the endoplasmic reticulum (ER) fails to promote proinsulin folding and, in failing to do so, promotes ER stress and β cell dysfunction. We show that CE prevent insulin-deficient diabetes in male and in female Akita mice using a model of misfolded proinsulin. CE stabilize the ER-associated protein degradation (ERAD) system and promote misfolded proinsulin proteasomal degradation. This involves activation of nuclear and membrane estrogen receptor-α (ERα), promoting transcriptional repression and proteasomal degradation of the ubiquitin-conjugating enzyme and ERAD degrader, UBC6e. The selective ERα modulator bazedoxifene mimics CE protection of β cells in females but not in males. : Estrogens prevent diabetes in women, but the mechanism is poorly understood. Xu et al. report that estrogens activate the endoplasmic-reticulum-associated protein degradation pathway, which promotes misfolded proinsulin degradation, suppresses endoplasmic reticulum stress, and protects insulin secretion in mice and in human pancreatic β cells. Keywords: estrogens, beta cell, islet, endoplasmic reticulum stress, proinsulin misfolding, diabetes, bazedoxifene, sex dimorphism, ERAD, SER
Acute treatment with omecamtiv mecarbil to increase contractility in acute heart failure
Background:
Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that increases myocardial function in healthy volunteers and in patients with chronic heart failure.
Objectives:
This study evaluated the pharmacokinetics, pharmacodynamics, tolerability, safety, and efficacy of OM in patients with acute heart failure (AHF).
Methods:
Patients admitted for AHF with left ventricular ejection fraction ≤40%, dyspnea, and elevated plasma concentrations of natriuretic peptides were randomized to receive a double-blind, 48-h intravenous infusion of placebo or OM in 3 sequential, escalating-dose cohorts.
Results:
In 606 patients, OM did not improve the primary endpoint of dyspnea relief (3 OM dose groups and pooled placebo: placebo, 41%; OM cohort 1, 42%; cohort 2, 47%; cohort 3, 51%; p = 0.33) or any of the secondary outcomes studied. In supplemental, pre-specified analyses, OM resulted in greater dyspnea relief at 48 h (placebo, 37% vs. OM, 51%; p = 0.034) and through 5 days (p = 0.038) in the high-dose cohort. OM exerted plasma concentration-related increases in left ventricular systolic ejection time (p < 0.0001) and decreases in end-systolic dimension (p < 0.05). The adverse event profile and tolerability of OM were similar to those of placebo, without increases in ventricular or supraventricular tachyarrhythmias. Plasma troponin concentrations were higher in OM-treated patients compared with placebo (median difference at 48 h, 0.004 ng/ml), but with no obvious relationship with OM concentration (p = 0.95).
Conclusions:
In patients with AHF, intravenous OM did not meet the primary endpoint of dyspnea improvement, but it was generally well tolerated, it increased systolic ejection time, and it may have improved dyspnea in the high-dose group. (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure [ATOMIC-AHF]; NCT01300013)
Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis
Sepsis is commonly associated with brain dysfunction, but the underlying mechanisms remain unclear, although mitochondrial dysfunction and microvascular abnormalities have been implicated. We therefore assessed whether cerebral mitochondrial dysfunction during systemic endotoxemia in mice increased mitochondrial sensitivity to a further bioenergetic insult (hyoxemia), and whether hypothermia could improve outcome. Mice (C57bl/6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 85) or saline (0.01 ml/g; n = 47). Six, 24 and 48 h later, we used confocal imaging in vivo to assess cerebral mitochondrial redox potential and cortical oxygenation in response to changes in inspired oxygen. The fraction of inspired oxygen (FiO2) at which the cortical redox potential changed was compared between groups. In a subset of animals, spontaneous hypothermia was maintained or controlled hypothermia induced during imaging. Decreasing FiO2 resulted in a more reduced cerebral redox state around veins, but preserved oxidation around arteries. This pattern appeared at a higher FiO2 in LPS-injected animals, suggesting an increased sensitivity of cortical mitochondria to hypoxemia. This increased sensitivity was accompanied by a decrease in cortical oxygenation, but was attenuated by hypothermia. These results suggest that systemic endotoxemia influences cortical oxygenation and mitochondrial function, and that therapeutic hypothermia can be protective
A Review on Mechanics and Mechanical Properties of 2D Materials - Graphene and Beyond
Since the first successful synthesis of graphene just over a decade ago, a
variety of two-dimensional (2D) materials (e.g., transition
metal-dichalcogenides, hexagonal boron-nitride, etc.) have been discovered.
Among the many unique and attractive properties of 2D materials, mechanical
properties play important roles in manufacturing, integration and performance
for their potential applications. Mechanics is indispensable in the study of
mechanical properties, both experimentally and theoretically. The coupling
between the mechanical and other physical properties (thermal, electronic,
optical) is also of great interest in exploring novel applications, where
mechanics has to be combined with condensed matter physics to establish a
scalable theoretical framework. Moreover, mechanical interactions between 2D
materials and various substrate materials are essential for integrated device
applications of 2D materials, for which the mechanics of interfaces (adhesion
and friction) has to be developed for the 2D materials. Here we review recent
theoretical and experimental works related to mechanics and mechanical
properties of 2D materials. While graphene is the most studied 2D material to
date, we expect continual growth of interest in the mechanics of other 2D
materials beyond graphene
Demonstration of integrated microscale optics in surface-electrode ion traps
In ion trap quantum information processing, efficient fluorescence collection
is critical for fast, high-fidelity qubit detection and ion-photon
entanglement. The expected size of future many-ion processors require scalable
light collection systems. We report on the development and testing of a
microfabricated surface-electrode ion trap with an integrated high numerical
aperture (NA) micromirror for fluorescence collection. When coupled to a low NA
lens, the optical system is inherently scalable to large arrays of mirrors in a
single device. We demonstrate stable trapping and transport of 40Ca+ ions over
a 0.63 NA micromirror and observe a factor of 1.9 enhancement in photon
collection compared to the planar region of the trap.Comment: 15 pages, 8 figure
Stability of candida albicans over long and short term storage in a resource-limited setting
BACKGROUND: Candida albicans are widely isolated fungal yeast agents from clinical samples. Several storage methods for fungi have evolved overtime and they are not without setbacks. Preservation method is critical for research,training and teaching.In resource–poor setting,the method to employ must be cheap and easy to maintain with minimal risk of contamination as well as degeneration of the organisms.We thus,set out to study the stability of Candida albicans over long and short term storage in a resource-limited setting.METHODS: One hundred Candida albicans strains isolated from patients with vulvovaginal candidiasis and oral candidiasis were preserved in triplicates using sterile distilled water,Chromagar plate,mineral oil overlay and brain heart infusion broth plus 10% glycerol at -20OC.Recovery rates were determined at six months,12 months and 18 months by sub-culturing onto sabouraud dextrose agar.RESULT: The recovery rate of C. albicans was 100% for all the preservation methods used during the six months storage,mineral oil overlay and brain heart infusion broth plus 10% glycerol for the 12months storage,and only the brain heart infusion broth plus 10% glycerol during the 18months storage.CONCLUSION: Candida albicans can be preserved over long period of time in resource- limited setting where power supply is erratic using brain heart infusion broth plus 10% glycerol at -20OC and mineral oil overlay technique whereas for short term preservation, sterile distilled water and taped culture plates technique can be used. Preservation of Candida albicans isolates in resource- limited setting over short or long term period is possible and affordable depending on the technique employed.KEYWORDS: Candida albicans, preservation, sterile distilled water, Chromagar plate, mineral oil overlay, brain heart infusion broth
Development of a novel classification system for anatomical variants of the puboprostatic ligaments with expert validation
Introduction: We propose a novel classification system with a validation study to help clinicians identify and typify commonly seen variants of the puboprostatic ligaments (PPL). Methods: A preliminary dissection of 6 male cadavers and a prospective dataset of over 300 robotic-assisted laparoscopic radical prostatectomies (RARP) recorded on video were used to identify 4 distinct ligament types. Then the prospectively collected database of surgical videos was used to isolate images of the PPL from RARP. Over 300 surgical videos were reviewed and classified with 1 to 5 pictures saved for reference of the type of PPL. To validate the new classification system, we selected 5 independent, blinded expert robotic surgeons to classify 100 ligaments based on morphology into a 4-type system: parallel, V-shaped, inverted V-shape, and fused. One week later, a subset of 25 photographs was sent to the same experts and classified. Statistical analyses were performed to determine both the intra-rater and inter-rater reliability of the proposed system. Results: Inverted V-shaped ligaments were noted most frequently (29.97%), parallel and V-shaped ligaments were found at 19.19% and 11.11%, respectively and fused ligaments were noted less frequently (6.06%). There was good intra-rater agreement (ê = 0.66) and inter-rater agreement (ê = 0.67) for the classification system. Conclusions: This classification system provided standardized descriptions of ligament variations that could be adopted universally to help clinicians categorize the variants. The system, validated by several blinded expert surgeons, demonstrated that surgeons were able to learn and correctly classify the variants. The system may be useful in helping to predict peri- and postoperative outcomes; however, this will require further study
The Far-Infrared Spectral Energy Distributions of X-ray-selected Active Galaxies
[Abridged] We present ISO far-infrared (IR) observations of 21 hard X-ray
selected AGN from the HEAO-1 A2 sample. We compare the far-IR to X-ray spectral
energy distributions (SEDs) of this sample with various radio and optically
selected AGN samples. The hard-X-ray selected sample shows a wider range of
optical/UV shapes extending to redder near-IR colors. The bluer objects are
Seyfert 1s, while the redder AGN are mostly intermediate or type 2 Seyferts.
This is consistent with a modified unification model in which the amount of
obscuring material increases with viewing angle and may be clumpy. Such a
scenario, already suggested by differing optical/near-IR spectroscopic and
X-ray AGN classifications, allows for different amounts of obscuration of the
continuum emission in different wavebands and of the broad emission line region
which results in a mixture of behaviors for AGN with similar optical emission
line classifications. The resulting limits on the column density of obscuring
material through which we are viewing the redder AGN are 100 times lower than
for the standard optically thick torus models. The resulting decrease in
optical depth of the obscuring material allows the AGN to heat more dust at
larger radial distances. We show that an AGN-heated, flared, dusty disk with
mass 10^9 solar and size of few hundred pc is able to generate optical-far-IR
SEDs which reproduce the wide range of SEDs present in our sample with no need
for an additional starburst component to generate the long-wavelength, cooler
part of the IR continuum.Comment: 40 pages, 14 figures, accepted for publication in Astrophysical
Journal, V. 590, June 10, 200
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