811 research outputs found
Novel Biomarkers and the Future Potential of Biomarkers in Inflammatory Bowel Disease.
There is increasing importance placed upon noninvasive assessment of gut inflammation. These tools are likely to be the key in differentiating intestinal inflammatory disease from functional disorders and in monitoring the response to intervention in individuals with known inflammatory conditions. Although various noninvasive markers are currently available, they have limitations and do not provide ideal utility. This review focuses on emerging markers of gut inflammation, highlighting the potential of specific markers
Gravin orchestrates protein kinase A and 2-adrenergic receptor signaling critical for synaptic plasticity and memory
A kinase-anchoring proteins (AKAPs) organize compartmentalized pools of protein kinase A (PKA) to enable localized signaling events within neurons. However, it is unclear which of the many expressed AKAPs in neurons target PKA to signaling complexes important for long-lasting forms of synaptic plasticity and memory storage. In the forebrain, the anchoring protein gravin recruits a signaling complex containing PKA, PKC, calmodulin, and PDE4D (phosphodiesterase 4D) to the β2-adrenergic receptor. Here, we show that mice lacking the α-isoform of gravin have deficits in PKA-dependent long-lasting forms of hippocampal synaptic plasticity including β2-adrenergic receptor-mediated plasticity, and selective impairments of long-term memory storage. Furthermore, both hippocampal β2-adrenergic receptor phosphorylation by PKA, and learning-induced activation of ERK in the CA1 region of the hippocampus are attenuated in mice lacking gravin-α. We conclude that gravin compartmentalizes a significant pool of PKA that regulates learning-induced β2-adrenergic receptor signaling and ERK activation in the hippocampus in vivo, thereby organizing molecular interactions between glutamatergic and noradrenergic signaling pathways for long-lasting synaptic plasticity, and memory storage
A Quantitative Methodology for Identifying Evolvable Space Systems
1st AIAA Space Exploration Conference
January 2005, Orlando, FL.With the growing emphasis on spiral development, a system’s ability to evolve is
becoming increasingly critical. This is especially true in systems designed for the exploration
of space. While returning to the Moon is widely regarded as the next step in space
exploration, our journey does not end there. Therefore, the technologies, vehicles, and
systems created for near-term lunar missions should be selected and designed with the
future in mind. Intelligently selecting evolvable systems requires a method for quantitatively
measuring evolvability and a procedure for comparing these measurements. This paper
provides a brief discussion of a quantitative methodology for evaluating space system
evolvability and an in-depth application of this methodology to an example case study
Recommended from our members
Urban influence on the concentration and composition of submicron particulate matter in central Amazonia
An understanding of how anthropogenic emissions affect the concentrations and composition of airborne particulate matter (PM) is fundamental to quantifying the influence of human activities on climate and air quality. The central Amazon Basin, especially around the city of Manaus, Brazil, has experienced rapid changes in the past decades due to ongoing urbanization. Herein, changes in the concentration and composition of submicron PM due to pollution downwind of the Manaus metropolitan region are reported as part of the GoAmazon2014/5 experiment. A high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) and a suite of other gas- and particle-phase instruments were deployed at the T3 research site, 70 km downwind of Manaus, during the wet season. At this site, organic components represented 79±7 % of the non-refractory PM1 mass concentration on average, which was in the same range as several upwind sites. However, the organic PM1 was considerably more oxidized at T3 compared to upwind measurements. Positive-matrix factorization (PMF) was applied to the time series of organic mass spectra collected at the T3 site, yielding three factors representing secondary processes (73±15 % of total organic mass concentration) and three factors representing primary anthropogenic emissions (27±15 %). Fuzzy c-means clustering (FCM) was applied to the afternoon time series of concentrations of NOy, ozone, total particle number, black carbon, and sulfate. Four clusters were identified and characterized by distinct air mass origins and particle compositions. Two clusters, Bkgd-1 and Bkgd-2, were associated with background conditions. Bkgd-1 appeared to represent near-field atmospheric PM production and oxidation of a day or less. Bkgd-2 appeared to represent material transported and oxidized for two or more days, often with out-of-basin contributions. Two other clusters, Pol-1 and Pol-2, represented the Manaus influence, one apparently associated with the northern region of Manaus and the other with the southern region of the city. A composite of the PMF and FCM analyses provided insights into the anthropogenic effects on PM concentration and composition. The increase in mass concentration of submicron PM ranged from 25 % to 200 % under polluted compared with background conditions, including contributions from both primary and secondary PM. Furthermore, a comparison of PMF factor loadings for different clusters suggested a shift in the pathways of PM production under polluted conditions. Nitrogen oxides may have played a critical role in these shifts. Increased concentrations of nitrogen oxides can shift pathways of PM production from HO2-dominant to NO-dominant as well as increase the concentrations of oxidants in the atmosphere. Consequently, the oxidation of biogenic and anthropogenic precursor gases as well as the oxidative processing of preexisting atmospheric PM can be accelerated. This combined set of results demonstrates the susceptibility of atmospheric chemistry, air quality, and associated climate forcing to anthropogenic perturbations over tropical forests.</p
A Sawtooth-like Timeline for the First Billion Year of Lunar Bombardment
We revisit the early evolution of the Moon's bombardment. Our work combines
modeling (based on plausible projectile sources and their dynamical decay
rates) with constraints from the lunar crater record, radiometric ages of the
youngest lunar basins, and the abundance of highly siderophile elements in the
lunar crust and mantle. We deduce that the evolution of the impact flux did not
decline exponentially over the first billion years of lunar history, but also
there was no prominent and "narrow" impact spike some 3.9 Gy ago, unlike that
typically envisioned in the lunar cataclysm scenario. Instead, we show the
timeline of the lunar bombardment has a sawtooth-like profile, with an uptick
in the impact flux near 4.1 Gy ago. The impact flux at the beginning of this
weaker cataclysm was 5-10 times higher than the immediately preceding period.
The Nectaris basin should have been one of the first basins formed at the
sawtooth. We predict the bombardment rate since about 4.1Gy ago declined slowly
and adhered relatively close to classic crater chronology models (Neukum and
Ivanov (1994)). Overall we expect that the sawtooth event accounted for about
1/4 of the total bombardment suffered by the Moon since its formation.
Consequently, considering that about 12-14 basins formed during the sawtooth
event, we expect that the net number of basins formed on the Moon was about
45-50. From our expected bombardment timeline, we derived a new and improved
lunar chronology suitable for use on Pre-Nectarian surface units. According to
this chronology, a significant portion of the oldest lunar cratered terrains
has an age of 4.38-4.42 Gyr. Moreover, the largest lunar basin, South Pole
Aitken, is older than 4.3Gy, and therefore was not produced during the lunar
cataclysm.Comment: In press in EPS
A glassy contribution to the heat capacity of hcp He solids
We model the low-temperature specific heat of solid He in the hexagonal
closed packed structure by invoking two-level tunneling states in addition to
the usual phonon contribution of a Debye crystal for temperatures far below the
Debye temperature, . By introducing a cutoff energy in the
two-level tunneling density of states, we can describe the excess specific heat
observed in solid hcp He, as well as the low-temperature linear term in the
specific heat. Agreement is found with recent measurements of the temperature
behavior of both specific heat and pressure. These results suggest the presence
of a very small fraction, at the parts-per-million (ppm) level, of two-level
tunneling systems in solid He, irrespective of the existence of
supersolidity.Comment: 11 pages, 4 figure
Integration of genetics into a systems model of electrocardiographic traits using humanCVD BeadChip
<p>Background—Electrocardiographic traits are important, substantially heritable determinants of risk of arrhythmias and sudden cardiac death.</p>
<p>Methods and Results—In this study, 3 population-based cohorts (n=10 526) genotyped with the Illumina HumanCVD Beadchip and 4 quantitative electrocardiographic traits (PR interval, QRS axis, QRS duration, and QTc interval) were evaluated for single-nucleotide polymorphism associations. Six gene regions contained single nucleotide polymorphisms associated with these traits at P<10−6, including SCN5A (PR interval and QRS duration), CAV1-CAV2 locus (PR interval), CDKN1A (QRS duration), NOS1AP, KCNH2, and KCNQ1 (QTc interval). Expression quantitative trait loci analyses of top associated single-nucleotide polymorphisms were undertaken in human heart and aortic tissues. NOS1AP, SCN5A, IGFBP3, CYP2C9, and CAV1 showed evidence of differential allelic expression. We modeled the effects of ion channel activity on electrocardiographic parameters, estimating the change in gene expression that would account for our observed associations, thus relating epidemiological observations and expression quantitative trait loci data to a systems model of the ECG.</p>
<p>Conclusions—These association results replicate and refine the mapping of previous genome-wide association study findings for electrocardiographic traits, while the expression analysis and modeling approaches offer supporting evidence for a functional role of some of these loci in cardiac excitation/conduction.</p>
The glassy response of solid He-4 to torsional oscillations
We calculated the glassy response of solid He-4 to torsional oscillations
assuming a phenomenological glass model. Making only a few assumptions about
the distribution of glassy relaxation times in a small subsystem of otherwise
rigid solid He-4, we can account for the magnitude of the observed period shift
and concomitant dissipation peak in several torsion oscillator experiments. The
implications of the glass model for solid He-4 are threefold: (1) The dynamics
of solid He-4 is governed by glassy relaxation processes. (2) The distribution
of relaxation times varies significantly between different torsion oscillator
experiments. (3) The mechanical response of a torsion oscillator does not
require a supersolid component to account for the observed anomaly at low
temperatures, though we cannot rule out its existence.Comment: 9 pages, 4 figures, presented at QFS200
Defects and glassy dynamics in solid He-4: Perspectives and current status
We review the anomalous behavior of solid He-4 at low temperatures with
particular attention to the role of structural defects present in solid. The
discussion centers around the possible role of two level systems and structural
glassy components for inducing the observed anomalies. We propose that the
origin of glassy behavior is due to the dynamics of defects like dislocations
formed in He-4. Within the developed framework of glassy components in a solid,
we give a summary of the results and predictions for the effects that cover the
mechanical, thermodynamic, viscoelastic, and electro-elastic contributions of
the glassy response of solid He-4. Our proposed glass model for solid He-4 has
several implications: (1) The anomalous properties of He-4 can be accounted for
by allowing defects to freeze out at lowest temperatures. The dynamics of solid
He-4 is governed by glasslike (glassy) relaxation processes and the
distribution of relaxation times varies significantly between different
torsional oscillator, shear modulus, and dielectric function experiments. (2)
Any defect freeze-out will be accompanied by thermodynamic signatures
consistent with entropy contributions from defects. It follows that such
entropy contribution is much smaller than the required superfluid fraction, yet
it is sufficient to account for excess entropy at lowest temperatures. (3) We
predict a Cole-Cole type relation between the real and imaginary part of the
response functions for rotational and planar shear that is occurring due to the
dynamics of defects. Similar results apply for other response functions. (4)
Using the framework of glassy dynamics, we predict low-frequency yet to be
measured electro-elastic features in defect rich He-4 crystals. These
predictions allow one to directly test the ideas and very presence of glassy
contributions in He-4.Comment: 33 pages, 13 figure
- …