Study of instabilities and transition to turbulence in a linear hall accelerator

Magnetospheric instabilities and transition to plasma turbulence in Hall current accelerator

Regulatory activity revealed by dynamic correlations in gene expression noise

Gene regulatory interactions are context dependent, active in some cellular states but not in others. Stochastic fluctuations, or 'noise', in gene expression propagate through active, but not inactive, regulatory links^(1,2). Thus, correlations in gene expression noise could provide a noninvasive means to probe the activity states of regulatory links. However, global, 'extrinsic', noise sources generate correlations even without direct regulatory links. Here we show that single-cell time-lapse microscopy, by revealing time lags due to regulation, can discriminate between active regulatory connections and extrinsic noise. We demonstrate this principle mathematically, using stochastic modeling, and experimentally, using simple synthetic gene circuits. We then use this approach to analyze dynamic noise correlations in the galactose metabolism genes of Escherichia coli. We find that the CRP-GalS-GalE feed-forward loop is inactive in standard conditions but can become active in a GalR mutant. These results show how noise can help analyze the context dependence of regulatory interactions in endogenous gene circuits

T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4+ and CD8+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines. © 2013 de Melo et al

CRITICAL SPEED AND CRITICAL STROKE RATE COULD BE USEFUL PHYSIOLOGICAL AND TECHNICAL CRITERIA FOR COACHES TO MONITOR ENDURANCE PERFORMANCE IN COMPETITIVE SWIMMERS

The purposes of this study were to determine whether the concepts of critical swimming speed (CSS) and critical stroke rate (CSR) could be reliable and used by coaches in order to control and monitor endurance performance in competitive swimmers. The results of this study conducted with well-trained swimmers showed that CSS could be determined easily from two common distances and more accurately from 200- and 400-m tests after a correction of minus 1.4 %. Moreover, CSS was well correlated with swimming velocity corresponding to 4 mmol.l-1 of blood lactate concentration and could avoid using lactate testing. Furthermore, the concept of a critical stroke rate defined as ‘the stroke rate value, which can be theoretically maintained continuously indefinitely without exhaustion’ and expressed, as the slope of the regression line between the number of stroke cycles and time seemed to be reliable. Coaches, in order to set not only aerobic training loads but also to control swimming technique, could easily use CSS and CSR

Updated Information on the Local Group

The present note updates the information published in my recent monograph on \underline{The Galaxies of the Local Group}. Highlights include (1) the addition of the newly discovered Cetus dwarf spheroidal as a certain member of the Local Group, (2) an improved distance for SagDIG, which now places this object very close to the edge of the Local Group zero-velocity surface, (3) more information on the evolutionary histories of some individual Local Group members, and (4) improved distance determinations to, and luminosities for, a number of Local Group members. These data increase the number of certain (or probable) Local Group members to 36. The spatial distribution of these galaxies supports Hubble's claim that the Local Group ``is isolated in the general field.'' Presently available evidence suggests that star formation continued much longer in many dwarf spheroidals than it did in the main body of the Galactic halo. It is suggested that ``young'' globular clusters, such as Ruprecht 106, might have formed in now defunct dwarf spheroidals. Assuming SagDIG, which is the most remote Local Group galaxy, to lie on, or just inside, the zero-velocity surface of the Local Group yields a dynamical age \gtrsim 17.9 \pm 2.7 Gyr.Comment: 19 pages, 1 figure, to be published in the April 2000 issue of PAS

Three-dimensional shear in granular flow

The evolution of granular shear flow is investigated as a function of height in a split-bottom Couette cell. Using particle tracking, magnetic-resonance imaging, and large-scale simulations we find a transition in the nature of the shear as a characteristic height $H^*$ is exceeded. Below $H^*$ there is a central stationary core; above $H^*$ we observe the onset of additional axial shear associated with torsional failure. Radial and axial shear profiles are qualitatively different: the radial extent is wide and increases with height while the axial width remains narrow and fixed.Comment: 4 pages, 5 figure

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs

Deep Space Gateway Science Opportunities

The NASA Life Sciences Research Capabilities Team (LSRCT) has been discussing deep space research needs for the last two years. NASA's programs conducting life sciences studies - the Human Research Program, Space Biology, Astrobiology, and Planetary Protection - see the Deep Space Gateway (DSG) as affording enormous opportunities to investigate biological organisms in a unique environment that cannot be replicated in Earth-based laboratories or on Low Earth Orbit science platforms. These investigations may provide in many cases the definitive answers to risks associated with exploration and living outside Earth's protective magnetic field. Unlike Low Earth Orbit or terrestrial locations, the Gateway location will be subjected to the true deep space spectrum and influence of both galactic cosmic and solar particle radiation and thus presents an opportunity to investigate their long-term exposure effects. The question of how a community of biological organisms change over time within the harsh environment of space flight outside of the magnetic field protection can be investigated. The biological response to the absence of Earth's geomagnetic field can be studied for the first time. Will organisms change in new and unique ways under these new conditions? This may be specifically true on investigations of microbial communities. The Gateway provides a platform for microbiology experiments both inside, to improve understanding of interactions between microbes and human habitats, and outside, to improve understanding of microbe-hardware interactions exposed to the space environment

The Two Fluid Drop Snap-off Problem: Experiments and Theory

We address the dynamics of a drop with viscosity $\lambda \eta$ breaking up inside another fluid of viscosity $\eta$. For $\lambda=1$, a scaling theory predicts the time evolution of the drop shape near the point of snap-off which is in excellent agreement with experiment and previous simulations of Lister and Stone. We also investigate the $\lambda$ dependence of the shape and breaking rate.Comment: 4 pages, 3 figure

The Effect of Air on Granular Size Separation in a Vibrated Granular Bed

Using high-speed video and magnetic resonance imaging (MRI) we study the motion of a large sphere in a vertically vibrated bed of smaller grains. As previously reported we find a non-monotonic density dependence of the rise and sink time of the large sphere. We find that this density dependence is solely due to air drag. We investigate in detail how the motion of the intruder sphere is influenced by size of the background particles, initial vertical position in the bed, ambient pressure and convection. We explain our results in the framework of a simple model and find quantitative agreement in key aspects with numerical simulations to the model equations.Comment: 14 pages, 16 figures, submitted to PRE, corrected typos, slight change