178 research outputs found
Effects of multiple-dose ponesimod, a selective SIP1 receptor modulator, on lymphocyte subsets in healthy humans
This study investigated the effects of ponesimod, a selective SIP1 receptor modulator, on T lymphocyte subsets in 16 healthy subjects. Lymphocyte subset proportions and absolute numbers were determined at baseline and on Day 10, after once-daily administration of ponesimod (10 mg, 20 mg, and 40 mg each consecutively for 3 days) or placebo (ratio 3: 1). The overall change from baseline in lymphocyte count was -1,292 +/- 340x10(6) cells/L and 275 +/- 486x10(6) cells/L in ponesimod- and placebo-treated subjects, respectively. This included a decrease in both T and B lymphocytes following ponesimod treatment. A decrease in naive CD4(+) T cells (CD45RA(+)CCR7(+)) from baseline was observed only after ponesimod treatment (-113 +/- 98x10(6) cells/L, placebo: 0 +/- 18x10(6) cells/L). The number of T-cytotoxic (CD3(+)CD8(+)) and T-helper (CD3(+)CD4(+)) cells was significantly altered following ponesimod treatment compared with placebo. Furthermore, ponesimod treatment resulted in marked decreases in CD4(+) T-central memory (CD45RA(-)CCR7(+)) cells (-437 +/- 164x10(6) cells/L) and CD4(+) T-effector memory (CD45RA(-)CCR7(-)) cells (-131 +/- 57x10(6) cells/L). In addition, ponesimod treatment led to a decrease of -228 +/- 90x10(6) cells/L of gut-homing T cells (CLA(-)integrin beta 7(+)). In contrast, when compared with placebo, CD8(+) T-effector memory and natural killer (NK) cells were not significantly reduced following multiple-dose administration of ponesimod. In summary, ponesimod treatment led to a marked reduction in overall T and B cells. Further investigations revealed that the number of CD4(+) cells was dramatically reduced, whereas CD8(+) and NK cells were less affected, allowing the body to preserve critical viral-clearing functions
Reconnaissance of Suspected Old Novae
Several of the \ blank fields\ in the novae atlas by Duerbeck were imaged at the WIYN 3.5 m telescope during technical engineering and commissioning activities in 1994-1995. Several old novae have been recovered utilizing CCD photometry. Multiobject spectroscopy with the Hydra/MOS instrumentation at WIYN was also used on random stars in the fields to search for a cataclysmic variable. The old novae candidates identified include SV Ari, V465 Cyg, SS LMi, V2104 Oph, GR Ori, V529 Ori, UW Per, and UW Tri
Exploring out-of-equilibrium quantum magnetism and thermalization in a spin-3 many-body dipolar lattice system
Understanding quantum thermalization through entanglement build-up in
isolated quantum systems addresses fundamental questions on how unitary
dynamics connects to statistical physics. Here, we study the spin dynamics and
approach towards local thermal equilibrium of a macroscopic ensemble of S = 3
spins prepared in a pure coherent spin state, tilted compared to the magnetic
field, under the effect of magnetic dipole-dipole interactions. The experiment
uses a unit filled array of 104 chromium atoms in a three dimensional optical
lattice, realizing the spin-3 XXZ Heisenberg model. The buildup of quantum
correlation during the dynamics, especially as the angle approaches pi/2, is
supported by comparison with an improved numerical quantum phase-space method
and further confirmed by the observation that our isolated system thermalizes
under its own dynamics, reaching a steady state consistent with the one
extracted from a thermal ensemble with a temperature dictated from the system's
energy. This indicates a scenario of quantum thermalization which is tied to
the growth of entanglement entropy. Although direct experimental measurements
of the Renyi entropy in our macroscopic system are unfeasible, the excellent
agreement with the theory, which can compute this entropy, does indicate
entanglement build-up.Comment: 12 figure
Regularized gene selection in cancer microarray meta-analysis
<p>Abstract</p> <p>Background</p> <p>In cancer studies, it is common that multiple microarray experiments are conducted to measure the same clinical outcome and expressions of the same set of genes. An important goal of such experiments is to identify a subset of genes that can potentially serve as predictive markers for cancer development and progression. Analyses of individual experiments may lead to unreliable gene selection results because of the small sample sizes. Meta analysis can be used to pool multiple experiments, increase statistical power, and achieve more reliable gene selection. The meta analysis of cancer microarray data is challenging because of the high dimensionality of gene expressions and the differences in experimental settings amongst different experiments.</p> <p>Results</p> <p>We propose a Meta Threshold Gradient Descent Regularization (MTGDR) approach for gene selection in the meta analysis of cancer microarray data. The MTGDR has many advantages over existing approaches. It allows different experiments to have different experimental settings. It can account for the joint effects of multiple genes on cancer, and it can select the same set of cancer-associated genes across multiple experiments. Simulation studies and analyses of multiple pancreatic and liver cancer experiments demonstrate the superior performance of the MTGDR.</p> <p>Conclusion</p> <p>The MTGDR provides an effective way of analyzing multiple cancer microarray studies and selecting reliable cancer-associated genes.</p
IL-2 Regulates Expression of C-MAF in Human CD4 T Cells
Blockade of IL-2R with humanized anti-CD25 Abs, such as daclizumab, inhibits Th2 responses in human T cells. Recent murine studies have shown that IL-2 also plays a significant role in regulating Th2 cell differentiation by activated STAT5. To explore the role of activated STAT5 in the Th2 differentiation of primary human T cells, we studied the mechanisms underlying IL-2 regulation of C-MAF expression. Chromatin immunoprecipitation studies revealed that IL-2 induced STAT5 binding to specific sites in the C-MAF promoter. These sites corresponded to regions enriched for markers of chromatin architectural features in both resting CD4 and differentiated Th2 cells. Unlike IL-6, IL-2 induced C-MAF expression in CD4 T cells with or without prior TCR stimulation. TCR-induced C-MAF expression was significantly inhibited by treatment with daclizumab or a JAK3 inhibitor, R333. Furthermore, IL-2 and IL-6 synergistically induced C-MAF expression in TCR-activated T cells, suggesting functional cooperation between these cytokines. Finally, both TCR-induced early IL4 mRNA expression and IL-4 cytokine expression in differentiated Th2 cells were significantly inhibited by IL-2R blockade. Thus, our findings demonstrate the importance of IL-2 in Th2 differentiation in human T cells and support the notion that IL-2R–directed therapies may have utility in the treatment of allergic disorders
Ambiguous loss and incomplete abduction narratives in Kosovo
Ten mothers of men and boys who were abducted and listed as missing during the war in Kosovo in 1998/1999 were interviewed in Kosovo in the spring of 2012. Although the missing are presumed dead by the authorities, the mothers continue to live in a state of emotional ambiguity where a presumption of death is balanced with the hope of being reunited. In the absence of absolute proof, finding the remains of their loved ones becomes a major preoccupation. Using a social phenomenological approach, this study explored the social and political complexities existing within the life-world of these women. The findings suggest that they live in a continual state of psychological distress, and even when remains are returned, the unknown elements of the narrative of their abduction and murder only add to their distress and force many into self-imposed emotional exile away from community and close family
Measuring multipartite entanglement via dynamic susceptibilities
Entanglement plays a central role in our understanding of quantum many body
physics, and is fundamental in characterising quantum phases and quantum phase
transitions. Developing protocols to detect and quantify entanglement of
many-particle quantum states is thus a key challenge for present experiments.
Here, we show that the quantum Fisher information, representing a witness for
genuinely multipartite entanglement, becomes measurable for thermal ensembles
via the dynamic susceptibility, i.e., with resources readily available in
present cold atomic gas and condensed-matter experiments. This moreover
establishes a fundamental connection between multipartite entanglement and
many-body correlations contained in response functions, with profound
implications close to quantum phase transitions. There, the quantum Fisher
information becomes universal, allowing us to identify strongly entangled phase
transitions with a divergent multipartiteness of entanglement. We illustrate
our framework using paradigmatic quantum Ising models, and point out potential
signatures in optical-lattice experiments.Comment: 5+5 pages, 3+2 figure
Many-body localization in a quantum simulator with programmable random disorder
When a system thermalizes it loses all local memory of its initial
conditions. This is a general feature of open systems and is well described by
equilibrium statistical mechanics. Even within a closed (or reversible) quantum
system, where unitary time evolution retains all information about its initial
state, subsystems can still thermalize using the rest of the system as an
effective heat bath. Exceptions to quantum thermalization have been predicted
and observed, but typically require inherent symmetries or noninteracting
particles in the presence of static disorder. The prediction of many-body
localization (MBL), in which disordered quantum systems can fail to thermalize
in spite of strong interactions and high excitation energy, was therefore
surprising and has attracted considerable theoretical attention. Here we
experimentally generate MBL states by applying an Ising Hamiltonian with
long-range interactions and programmably random disorder to ten spins
initialized far from equilibrium. We observe the essential signatures of MBL:
memory retention of the initial state, a Poissonian distribution of energy
level spacings, and entanglement growth in the system at long times. Our
platform can be scaled to higher numbers of spins, where detailed modeling of
MBL becomes impossible due to the complexity of representing such entangled
quantum states. Moreover, the high degree of control in our experiment may
guide the use of MBL states as potential quantum memories in naturally
disordered quantum systems.Comment: 9 pages, 9 figure
The Interspersed Spin Boson Lattice Model
We describe a family of lattice models that support a new class of quantum
magnetism characterized by correlated spin and bosonic ordering [Phys. Rev.
Lett. 112, 180405 (2014)]. We explore the full phase diagram of the model using
Matrix-Product-State methods. Guided by these numerical results, we describe a
modified variational ansatz to improve our analytic description of the
groundstate at low boson frequencies. Additionally, we introduce an
experimental protocol capable of inferring the low-energy excitations of the
system by means of Fano scattering spectroscopy. Finally, we discuss the
implementation and characterization of this model with current circuit-QED
technology.Comment: Submitted to EPJ ST issue on "Novel Quantum Phases and Mesoscopic
Physics in Quantum Gases
Muscle nonshivering thermogenesis in a feral mammal
Muscle nonshivering thermogenesis (NST) was recently suggested to play an important role in thermoregulation of species lacking brown adipose tissue (BAT). The mechanism, which is independent of muscle contractions, produces heat based on the activity of an ATPase pump in the sarcoplasmic reticulum (SERCA1a) and is controlled by the protein sarcolipin. To evaluate whether muscle NST could indeed play an important role in thermoregulation in species lacking BAT, we investigated the thermogenic capacities of newborn wild boar piglets. During cold exposure over the first 5 days of life, total heat production was improved while shivering intensity decreased, indicating an increasing contribution of NST. Sampling skeletal muscle tissue for analyses of SERCA activity as well as gene expression of SERCA1a and sarcolipin, we found an age-related increase in all three variables as well as in body temperature. Hence, the improved thermogenesis during the development of wild boars is not due to shivering but explained by the observed increase in SERCA activity. Our results suggest that muscle NST may be the primary mechanism of heat production during cold stress in large mammals lacking BAT, strengthening the hypothesis that muscle NST has likely played an important role in the evolution of endothermy
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