133 research outputs found
Automated Test for NASA CFS
The core Flight System (cFS) is a flight software (FSW) product line developed by the Flight Software Systems Branch (FSSB) at NASA's Goddard Space Flight Center (GSFC). The cFS uses compile-time configuration parameters to implement variable requirements to enable portability across embedded computing platforms and to implement different end-user functional needs. The verification and validation of these requirements is proving to be a significant challenge. This paper describes the challenges facing the cFS and the results of a pilot effort to apply EXB Solution's testing approach to the cFS applications
A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release
Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. However, it is unknown whether EE and EC cells are directly mechanosensitive, and if so, what the molecular mechanism of their mechanosensitivity is. Consequently, the role of EE and EC cells in gastrointestinal mechanobiology is unclear. Piezo2 mechanosensitive ion channels are important for some specialized epithelial mechanosensors, and they are expressed in mouse and human EC cells. Here, we use EC and EE cell lineage tracing in multiple mouse models to show that Piezo2 is expressed in a subset of murine EE and EC cells, and it is distributed near serotonin vesicles by superresolution microscopy. Mechanical stimulation of a subset of isolated EE cells leads to a rapid inward ionic current, which is diminished by Piezo2 knockdown and channel inhibitors. In these mechanosensitive EE cells force leads to Piezo2-dependent intracellular Ca(2+) increase in isolated cells as well as in EE cells within intestinal organoids, and Piezo2-dependent mechanosensitive serotonin release in EC cells. Conditional knockout of intestinal epithelial Piezo2 results in a significant decrease in mechanically stimulated epithelial secretion. This study shows that a subset of primary EE and EC cells is mechanosensitive, uncovers Piezo2 as their primary mechanotransducer, defines the molecular mechanism of their mechanotransduction and mechanosensitive serotonin release, and establishes the role of epithelial Piezo2 mechanosensitive ion channels in regulation of intestinal physiology
The Higgs sector of the phenomenological MSSM in the light of the Higgs boson discovery
The long awaited discovery of a new light scalar at the LHC opens up a new
era of studies of the Higgs sector in the SM and its extensions. In this paper
we discuss the consequences of the observation of a light Higgs boson with the
mass and rates reported by the ATLAS and CMS collaborations on the parameter
space of the phenomenological MSSM, including also the so far unsuccessful LHC
searches for the heavier Higgs bosons and supersymmetric particle partners in
missing transverse momentum as well as the constraints from B physics and dark
matter. We explore the various regimes of the MSSM Higgs sector depending on
the parameters MA and tan beta and show that only two of them are still allowed
by all present experimental constraints: the decoupling regime where there is
only one light and standard--like Higgs boson and the supersymmetric regime in
which there are light supersymmetric particle partners affecting the decay
properties of the Higgs boson, in particular its di-photon and invisible
decays.Comment: 21 pages, 9 figures v2 - Discussion of the impact of LHC data
extended, scan statistics increased, a few figures added and typos correcte
Loss-of-function of the Voltage-gated Sodium Channel NaV1.5 (Channelopathies) in Patients with Irritable Bowel Syndrome.
Background & Aims SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5. Methods We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. Results Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P <.05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. Conclusions About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na V1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options
Revisiting the Higgs Mass and Dark Matter in the CMSSM
Taking into account the available accelerator and astrophysical constraints,
the mass of the lightest neutral Higgs boson h in the minimal supersymmetric
extension of the Standard Model with universal soft supersymmetry-breaking
masses (CMSSM) has been estimated to lie between 114 and ~ 130 GeV. Recent data
from ATLAS and CMS hint that m_h ~ 125 GeV, though m_h ~ 119 GeV may still be a
possibility. Here we study the consequences for the parameters of the CMSSM and
direct dark matter detection if the Higgs hint is confirmed, focusing on the
strips in the (m_1/2, m_0) planes for different tan beta and A_0 where the
relic density of the lightest neutralino chi falls within the range of the
cosmological cold dark matter density allowed by WMAP and other experiments. We
find that if m_h ~ 125 GeV focus-point strips would be disfavoured, as would
the low-tan beta stau-chi and stop -chi coannihilation strips, whereas the
stau-chi coannihilation strip at large tan beta and A_0 > 0 would be favoured,
together with its extension to a funnel where rapid annihilation via
direct-channel H/A poles dominates. On the other hand, if m_h ~ 119 GeV more
options would be open. We give parametrizations of WMAP strips with large tan
beta and fixed A_0/m_0 > 0 that include portions compatible with m_h = 125 GeV,
and present predictions for spin-independent elastic dark matter scattering
along these strips. These are generally low for models compatible with m_h =
125 GeV, whereas the XENON100 experiment already excludes some portions of
strips where m_h is smaller.Comment: 24 pages, 9 figure
Relating the CMSSM and SUGRA models with GUT scale and Super-GUT scale Supersymmetry Breaking
While the constrained minimal supersymmetric standard model (CMSSM) with
universal gaugino masses, m_{1/2}, scalar masses, m_0, and A-terms, A_0,
defined at some high energy scale (usually taken to be the GUT scale) is
motivated by general features of supergravity models, it does not carry all of
the constraints imposed by minimal supergravity (mSUGRA). In particular, the
CMSSM does not impose a relation between the trilinear and bilinear soft
supersymmetry breaking terms, B_0 = A_0 - m_0, nor does it impose the relation
between the soft scalar masses and the gravitino mass, m_0 = m_{3/2}. As a
consequence, tan(\beta) is computed given values of the other CMSSM input
parameters. By considering a Giudice-Masiero (GM) extension to mSUGRA, one can
introduce new parameters to the K\"ahler potential which are associated with
the Higgs sector and recover many of the standard CMSSM predictions. However,
depending on the value of A_0, one may have a gravitino or a neutralino dark
matter candidate. We also consider the consequences of imposing the
universality conditions above the GUT scale. This GM extension provides a
natural UV completion for the CMSSM.Comment: 16 pages, 11 figures; added erratum correcting several equations and
results in Sec.2, Sec.3 and 4 remain unaffected and conclusions unchange
Hydrophilic interaction liquid chromatography (HILIC) in proteomics
In proteomics, nanoflow multidimensional chromatography is now the gold standard for the separation of complex mixtures of peptides as generated by in-solution digestion of whole-cell lysates. Ideally, the different stationary phases used in multidimensional chromatography should provide orthogonal separation characteristics. For this reason, the combination of strong cation exchange chromatography (SCX) and reversed-phase (RP) chromatography is the most widely used combination for the separation of peptides. Here, we review the potential of hydrophilic interaction liquid chromatography (HILIC) as a separation tool in the multidimensional separation of peptides in proteomics applications. Recent work has revealed that HILIC may provide an excellent alternative to SCX, possessing several advantages in the area of separation power and targeted analysis of protein post-translational modifications
Hydrophilic interaction liquid chromatography (HILIC)—a powerful separation technique
Hydrophilic interaction liquid chromatography (HILIC) provides an alternative approach to effectively separate small polar compounds on polar stationary phases. The purpose of this work was to review the options for the characterization of HILIC stationary phases and their applications for separations of polar compounds in complex matrices. The characteristics of the hydrophilic stationary phase may affect and in some cases limit the choices of mobile phase composition, ion strength or buffer pH value available, since mechanisms other than hydrophilic partitioning could potentially occur. Enhancing our understanding of retention behavior in HILIC increases the scope of possible applications of liquid chromatography. One interesting option may also be to use HILIC in orthogonal and/or two-dimensional separations. Bioapplications of HILIC systems are also presented
Investigating Gamma-Ray Lines from Dark Matter with Future Observatories
We study the prospects for studying line features in gamma-ray spectra with
upcoming gamma-ray experiments, such as HESS-II, the Cherenkov Telescope Array
(CTA), and the GAMMA-400 satellite. As an example we use the narrow feature at
130 GeV seen in public data from the Fermi-LAT satellite. We found that all
three experiments should be able to confidently confirm or rule out the
presence of this 130 GeV feature. If it is real, it should be confirmed with a
confidence level higher than 5 sigma. Assuming it to be a spectral signature of
dark matter origin, GAMMA-400, thanks to a projected energy resolution of about
1.5% at 100 GeV, should also be able to resolve both the \gamma\gamma-line and
a corresponding Z\gamma- or H\gamma-feature, if the corresponding branching
ratio is comparable to that into two photons. It will also allow to distinguish
between a gamma-ray line and the similar feature resulting from internal
bremsstrahlung photons.Comment: 12 pages, 6 figures, 1 tabl
- …