244 research outputs found
Three-dimensional finite-element elastic analysis of a thermally cycled single-edge wedge geometry specimen
An elastic stress analysis was performed on a wedge specimen (prismatic bar with single-wedge cross section) subjected to thermal cycles in fluidized beds. Seven different combinations consisting of three alloys (NASA TAZ-8A, 316 stainless steel, and A-286) and four thermal cycling conditions were analyzed. The analyses were performed as a joint effort of two laboratories using different models and computer programs (NASTRAN and ISO3DQ). Stress, strain, and temperature results are presented
Development of an Integrated Countermeasure Device for Long Duration Space Flight and Exploration Missions
Musculoskeletal, cardiovascular, and sensorimotor deconditioning have been observed consistently in astronauts and cosmonauts following long-duration spaceflight. Studies in bed rest, a spaceflight analog, have shown that high intensity resistive or aerobic exercise attenuates or prevents musculoskeletal and cardiovascular deconditioning, respectively, but complete protection has not been achieved during spaceflight. Exercise countermeasure hardware used during earlier International Space Station (ISS) missions included a cycle ergometer, a treadmill, and the interim resistive exercise device (iRED). Effectiveness of the countermeasures may have been diminished by limited loading characteristics of the iRED as well as speed restrictions and subject harness discomfort during treadmill exercise. The Advanced Resistive Exercise Device (ARED) and the second generation treadmill were designed to address many of the limitations of their predecessors, and anecdotal reports from ISS crews suggest that their conditioning is better preserved since the new hardware was delivered in 2009. However, several countermeasure devices to protect different physiologic systems will not be practical during exploration missions when the available volume and mass will be severely restricted. The combined countermeasure device (CCD) integrates a suite of hardware into one device intended to prevent spaceflight-induced musculoskeletal, cardiovascular, and sensorimotor deconditioning. The CCD includes pneumatic loading devices with attached cables for resistive exercise, a cycle for aerobic exercise, and a 6 degree of freedom motion platform for balance training. In a proof of concept test, ambulatory untrained subjects increased muscle strength (58%) as well as aerobic capacity (26%) after 12-weeks of exercise training with the CCD (without balance training), improvements comparable to those observed with traditional exercise training. These preliminary results suggest that this CCD can concurrently improve musculoskeletal and cardiovascular conditioning in ambulatory subjects, but further work is required to validate its use as countermeasure to spaceflight-induced deconditioning
Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice
Peer reviewedPublisher PD
A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology
The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named <i>TbOrg1</i>). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (<i>TbOrg2</i>). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits
Rapid Regulatory T-Cell Response Prevents Cytokine Storm in CD28 Superagonist Treated Mice
Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of regulatory T-cells (Treg cells) in rats, but a first-in-man trial of the human CD28SA TGN1412 resulted in an unexpected cytokine release syndrome. Using a novel mouse anti-mouse CD28SA, we re-investigate the relationship between Treg activation and systemic cytokine release. Treg activation by CD28SA was highly efficient but depended on paracrine IL-2 from CD28SA-stimulated conventional T-cells. Systemic cytokine levels were innocuous, but depletion of Treg cells prior to CD28SA stimulation led to systemic release of proinflammatory cytokines, indicating that in rodents, Treg cells effectively suppress the inflammatory response. Since the human volunteers of the TGN1412 study were not protected by this mechanism, we also tested whether corticosteroid prophylaxis would be compatible with CD28SA induced Treg activation. We show that neither the expansion nor the functional activation of Treg cells is affected by high-dose dexamethasone sufficient to control systemic cytokine release. Our findings warn that preclinical testing of activating biologicals in rodents may miss cytokine release syndromes due to the rapid and efficacious response of the rodent Treg compartment, and suggest that polyclonal Treg activation is feasible in the presence of antiphlogistic corticosteroid prophylaxis
Barrier Tissue Macrophages: Functional Adaptation to Environmental Challenges
Macrophages are found throughout the body, where they have crucial roles in tissue development, homeostasis and remodeling, as well as being sentinels of the innate immune system that can contribute to protective immunity and inflammation. Barrier tissues, such as the intestine, lung, skin and liver, are exposed constantly to the outside world, which places special demands on resident cell populations such as macrophages. Here we review the mounting evidence that although macrophages in different barrier tissues may be derived from distinct progenitors, their highly specific properties are shaped by the local environment, which allows them to adapt precisely to the needs of their anatomical niche. We discuss the properties of macrophages in steady-state barrier tissues, outline the factors that shape their differentiation and behavior and describe how macrophages change during protective immunity and inflammation
Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. I. Parasitological, Hematological and Pathological Parameters
African trypanosomiasis is a severe parasitic disease that affects both humans and livestock. Several different species may cause animal trypanosomosis and although Trypanosoma vivax (sub-genus Duttonella) is currently responsible for the vast majority of debilitating cases causing great economic hardship in West Africa and South America, little is known about its biology and interaction with its hosts. Relatively speaking, T. vivax has been more than neglected despite an urgent need to develop efficient control strategies. Some pioneering rodent models were developed to circumvent the difficulties of working with livestock, but disappointedly were for the most part discontinued decades ago. To gain more insight into the biology of T. vivax, its interactions with the host and consequently its pathogenesis, we have developed a number of reproducible murine models using a parasite isolate that is infectious for rodents. Firstly, we analyzed the parasitical characteristics of the infection using inbred and outbred mouse strains to compare the impact of host genetic background on the infection and on survival rates. Hematological studies showed that the infection gave rise to severe anemia, and histopathological investigations in various organs showed multifocal inflammatory infiltrates associated with extramedullary hematopoiesis in the liver, and cerebral edema. The models developed are consistent with field observations and pave the way for subsequent in-depth studies into the pathogenesis of T. vivax - trypanosomosis
Measurement of the branching fraction for the decay at Belle II
We report a measurement of the branching fraction of decays, where or
, using electron-positron collisions recorded at an energy at or near
the mass and corresponding to an integrated luminosity of
fb. The data was collected during 2019--2021 by the Belle II experiment
at the SuperKEKB asymmetric-energy collider. We reconstruct
candidates in the , , and
final states. The signal yields with statistical uncertainties are ,
, and for the decays , , and , respectively.
We measure the branching fractions of these decays for the entire range of the
dilepton mass, excluding the very low mass region to suppress the background and regions compatible with decays
of charmonium resonances, to be \begin{equation} {\cal B}(B \to
K^{\ast}(892)\mu^+\mu^-) = (1.19 \pm 0.31 ^{+0.08}_{-0.07}) \times 10^{-6},
{\cal B}(B \to K^{\ast}(892)e^+e^-) = (1.42 \pm 0.48 \pm 0.09)\times 10^{-6},
{\cal B}(B \to K^{\ast}(892)\ell^+\ell^-) = (1.25 \pm 0.30 ^{+0.08}_{-0.07})
\times 10^{-6}, \end{equation} where the first and second uncertainties are
statistical and systematic, respectively. These results, limited by sample
size, are the first measurements of branching
fractions from the Belle II experiment
Angular analysis of decays reconstructed in 2019, 2020, and 2021 Belle II data
We report on a Belle II measurement of the branching fraction
(), longitudinal polarization fraction (), and CP asymmetry
() of decays. We reconstruct decays in a
sample of SuperKEKB electron-positron collisions collected by the Belle II
experiment in 2019, 2020, and 2021 at the (4S) resonance and
corresponding to 190 fb of integrated luminosity. We fit the
distributions of the difference between expected and observed candidate
energy, continuum-suppression discriminant, dipion masses, and decay angles of
the selected samples, to determine a signal yield of events. The
signal yields are corrected for efficiencies determined from simulation and
control data samples to obtain $\mathcal{B}(B^+ \to \rho^+\rho^0) = [23.2^{+\
2.2}_{-\ 2.1} (\rm stat) \pm 2.7 (\rm syst)]\times 10^{-6}f_L = 0.943 ^{+\
0.035}_{-\ 0.033} (\rm stat)\pm 0.027(\rm syst)\mathcal{A}_{CP}=-0.069
\pm 0.068(\rm stat) \pm 0.060 (\rm syst)\mathcal{A}_{CP}B^+\to
\rho^+\rho^0$ decays reported by Belle II
Determination of from untagged decays using 2019-2021 Belle II data
We present an analysis of the charmless semileptonic decay , where , from 198.0 million pairs of
mesons recorded by the Belle II detector at the SuperKEKB
electron-positron collider. The decay is reconstructed without identifying the
partner meson. The partial branching fractions are measured independently
for and as functions of
(momentum transfer squared), using 3896 and
5466 decays. The total branching fraction is
found to be for decays, where the uncertainties are statistical and
systematic, respectively. By fitting the measured partial branching fractions
as functions of , together with constraints on the nonperturbative
hadronic contribution from lattice QCD calculations, the magnitude of the
Cabibbo-Kobayashi-Maskawa matrix element , , is extracted. Here, the first uncertainty is
statistical, the second is systematic and the third is theoretical
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