711 research outputs found
Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis
Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base
Influence of Material Parameter Variability on the Predicted Coronary Artery Biomechanical Environment via Uncertainty Quantification
Central to the clinical adoption of patient-specific modeling strategies is
demonstrating that simulation results are reliable and safe. Simulation
frameworks must be robust to uncertainty in model input(s), and levels of
confidence should accompany results. In this study we applied a coupled
uncertainty quantification-finite element (FE) framework to understand the
impact of uncertainty in vascular material properties on variability in
predicted stresses. Univariate probability distributions were fit to material
parameters derived from layer-specific mechanical behavior testing of human
coronary tissue. Parameters were assumed to be probabilistically independent,
allowing for efficient parameter ensemble sampling. In an idealized coronary
artery geometry, a forward FE model for each parameter ensemble was created to
predict tissue stresses under physiologic loading. An emulator was constructed
within the UncertainSCI software using polynomial chaos techniques, and
statistics and sensitivities were directly computed. Results demonstrated that
material parameter uncertainty propagates to variability in predicted stresses
across the vessel wall, with the largest dispersions in stress within the
adventitial layer. Variability in stress was most sensitive to uncertainties in
the anisotropic component of the strain energy function. Unary and binary
interactions within the adventitial layer were the main contributors to stress
variance, and the leading factor in stress variability was uncertainty in the
stress-like material parameter summarizing contribution of the embedded fibers
to the overall artery stiffness. Results from a patient-specific coronary model
confirmed many of these findings. Collectively, this highlights the impact of
material property variation on predicted artery stresses and presents a
pipeline to explore and characterize uncertainty in computational biomechanics.Comment: To appear: Biomechanics and Modeling in Mechanobiolog
Some Like It Fat: Comparative Ultrastructure of the Embryo in Two Demosponges of the Genus Mycale (Order Poecilosclerida) from Antarctica and the Caribbean
0000-0002-7993-1523© 2015 Riesgo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article
Generation of Ultrastable Microwaves via Optical Frequency Division
There has been increased interest in the use and manipulation of optical
fields to address challenging problems that have traditionally been approached
with microwave electronics. Some examples that benefit from the low
transmission loss, agile modulation and large bandwidths accessible with
coherent optical systems include signal distribution, arbitrary waveform
generation, and novel imaging. We extend these advantages to demonstrate a
microwave generator based on a high-Q optical resonator and a frequency comb
functioning as an optical-to-microwave divider. This provides a 10 GHz
electrical signal with fractional frequency instability <8e-16 at 1 s, a value
comparable to that produced by the best microwave oscillators, but without the
need for cryogenic temperatures. Such a low-noise source can benefit radar
systems, improve the bandwidth and resolution of communications and digital
sampling systems, and be valuable for large baseline interferometry, precision
spectroscopy and the realization of atomic time
Quantum jumps induced by the center-of-mass motion of a trapped atom
We theoretically study the occurrence of quantum jumps in the resonance
fluorescence of a trapped atom. Here, the atom is laser cooled in a
configuration of level such that the occurrence of a quantum jump is associated
to a change of the vibrational center-of-mass motion by one phonon. The
statistics of the occurrence of the dark fluorescence period is studied as a
function of the physical parameters and the corresponding features in the
spectrum of resonance fluorescence are identified. We discuss the information
which can be extracted on the atomic motion from the observation of a quantum
jump in the considered setup
Narrow Spectral Feature In Resonance Fluorescence With A Single Monochromatic Laser Field
We describe the resonance fluorescence spectrum of an atomic three-level
system where two of the states are coupled by a single monochromatic laser
field. The influence of the third energy level, which interacts with the two
laser-coupled states only via radiative decays, is studied in detail. For a
suitable choice of parameters, this system gives rise to a very narrow
structure at the laser frequency in the fluorescence spectrum which is not
present in the spectrum of a two-level atom. We find those parameter ranges by
a numerical analysis and use the results to derive analytical expressions for
the additional narrow peak. We also derive an exact expression for the peak
intensity under the assumption that a random telegraph model is applicable to
the system. This model and a simple spring model are then used to describe the
physical origins of the additional peak. Using these results, we explain the
connection between our system, a three-level system in V-configuration where
both transitions are laser driven, and a related experiment which was recently
reported.Comment: 14 pages, 15 figures, extension of the spring mode
Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment
Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings
Theory and applications of atomic and ionic polarizabilities
Atomic polarization phenomena impinge upon a number of areas and processes in
physics. The dielectric constant and refractive index of any gas are examples
of macroscopic properties that are largely determined by the dipole
polarizability. When it comes to microscopic phenomena, the existence of
alkaline-earth anions and the recently discovered ability of positrons to bind
to many atoms are predominantly due to the polarization interaction. An
imperfect knowledge of atomic polarizabilities is presently looming as the
largest source of uncertainty in the new generation of optical frequency
standards. Accurate polarizabilities for the group I and II atoms and ions of
the periodic table have recently become available by a variety of techniques.
These include refined many-body perturbation theory and coupled-cluster
calculations sometimes combined with precise experimental data for selected
transitions, microwave spectroscopy of Rydberg atoms and ions, refractive index
measurements in microwave cavities, ab initio calculations of atomic structures
using explicitly correlated wave functions, interferometry with atom beams, and
velocity changes of laser cooled atoms induced by an electric field. This
review examines existing theoretical methods of determining atomic and ionic
polarizabilities, and discusses their relevance to various applications with
particular emphasis on cold-atom physics and the metrology of atomic frequency
standards.Comment: Review paper, 44 page
Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees
The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection
On the role of dust-deposited lithogenic particles for iron cycling in the tropical and subtropical Atlantic
Lithogenic material deposited as dust is one of the major sources of trace metals to the ocean, particularly in the tropical and subtropical Atlantic. On the other hand, it can also act as a scavenging surface for iron. Here we studied this double role of lithogenic material in the marine iron cycle by adding a new scheme for describing particle dynamics into a global biogeochemistry and ecosystem model including particle aggregation and disaggregation of two particle size classes and scavenging on both organic and lithogenic particles. Considering the additional scavenging of iron on lithogenic particles, the modeled dissolved iron concentration is reduced significantly in the tropical and subtropical Atlantic, bringing the model much closer to observations. This underlines the necessity to consider the double role of dust particles as iron source and sink in studies on the marine iron cycle in high dust regions and with changing dust fluxes
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