212 research outputs found
Bacterial metabolites and cardiovascular risk in children with chronic kidney disease
Cardiovascular complications are the major cause of the marked morbidity and mortality associated with chronic kidney disease (CKD). The classical cardiovascular risk factors such as diabetes and hypertension undoubtedly play a role in the development of cardiovascular disease (CVD) in adult CKD patients; however, CVD is just as prominent in children with CKD who do not have these risk factors. Hence, the CKD-specific pathophysiology of CVD remains incompletely understood. In light of this, studying children with CKD presents a unique opportunity to analyze CKD-associated mechanisms of CVD more specifically and could help to unveil novel therapeutic targets.Here, we comprehensively review the interaction of the human gut microbiome and the microbial metabolism of nutrients with host immunity and cardiovascular end-organ damage. The human gut microbiome is evolutionary conditioned and modified throughout life by endogenous factors as well as environmental factors. Chronic diseases, such as CKD, cause significant disruption to the composition and function of the gut microbiome and lead to disease-associated dysbiosis. This dysbiosis and the accompanying loss of biochemical homeostasis in the epithelial cells of the colon can be the result of poor diet (e.g., low-fiber intake), medications, and underlying disease. As a result of dysbiosis, bacteria promoting proteolytic fermentation increase and those for saccharolytic fermentation decrease and the integrity of the gut barrier is perturbed (leaky gut). These changes disrupt local metabolite homeostasis in the gut and decrease productions of the beneficial short-chain fatty acids (SCFAs). Moreover, the enhanced proteolytic fermentation generates unhealthy levels of microbially derived toxic metabolites, which further accumulate in the systemic circulation as a consequence of impaired kidney function. We describe possible mechanisms involved in the increased systemic inflammation in CKD that is associated with the combined effect of SCFA deficiency and accumulation of uremic toxins. In the future, a more comprehensive and mechanistic understanding of the gut-kidney-heart interaction, mediated largely by immune dysregulation and inflammation, might allow us to target the gut microbiome more specifically in order to attenuate CKD-associated comorbidities
The energy dependence of flow in Ni induced collisions from 400 to 1970A MeV
We study the energy dependence of collective (hydrodynamic-like) nuclear
matter flow in 400-1970 A MeV Ni+Au and 1000-1970 A MeV Ni+Cu reactions. The
flow increases with energy, reaches a maximum, and then gradually decreases at
higher energies. A way of comparing the energy dependence of flow values for
different projectile-target mass combinations is introduced, which demonstrates
a common scaling behaviour among flow values from different systems.Comment: 12 pages, 3 figures. Submitted to Physical Review Letter
Radial Flow in Au+Au Collisions at E=0.25-1.15 A GeV
A systematic study of energy spectra for light particles emitted at
midrapidity from Au+Au collisions at E=0.25-1.15 A GeV reveals a significant
non-thermal component consistent with a collective radial flow. This component
is evaluated as a function of bombarding energy and event centrality.
Comparisons to Quantum Molecular Dynamics (QMD) and Boltzmann-Uehling-Uhlenbeck
(BUU) models are made for different equations of state.Comment: 10 pages of text and 4 figures (all ps files in a uuencoded package)
Statistical signatures of critical behavior in small systems
The cluster distributions of different systems are examined to search for
signatures of a continuous phase transition. In a system known to possess such
a phase transition, both sensitive and insensitive signatures are present;
while in systems known not to possess such a phase transition, only insensitive
signatures are present. It is shown that nuclear multifragmentation results in
cluster distributions belonging to the former category, suggesting that the
fragments are the result of a continuous phase transition.Comment: 31 pages, two columns with 30 figure
?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH
Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA
The IceCube Neutrino Observatory: Instrumentation and Online Systems
The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy
neutrino detector built into the ice at the South Pole. Construction of
IceCube, the largest neutrino detector built to date, was completed in 2011 and
enabled the discovery of high-energy astrophysical neutrinos. We describe here
the design, production, and calibration of the IceCube digital optical module
(DOM), the cable systems, computing hardware, and our methodology for drilling
and deployment. We also describe the online triggering and data filtering
systems that select candidate neutrino and cosmic ray events for analysis. Due
to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are
operating and collecting data. IceCube routinely achieves a detector uptime of
99% by emphasizing software stability and monitoring. Detector operations have
been stable since construction was completed, and the detector is expected to
operate at least until the end of the next decade.Comment: 83 pages, 50 figures; updated with minor changes from journal review
and proofin
Detection of Atmospheric Muon Neutrinos with the IceCube 9-String Detector
The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino
detector under construction at the geographic South Pole. The dominant
population of neutrinos detected in IceCube is due to meson decay in cosmic-ray
air showers. These atmospheric neutrinos are relatively well-understood and
serve as a calibration and verification tool for the new detector. In 2006, the
detector was approximately 10% completed, and we report on data acquired from
the detector in this configuration. We observe an atmospheric neutrino signal
consistent with expectations, demonstrating that the IceCube detector is
capable of identifying neutrino events. In the first 137.4 days of livetime,
234 neutrino candidates were selected with an expectation of 211 +/-
76.1(syst.) +/- 14.5(stat.) events from atmospheric neutrinos
Middle Neolithic pits and a burial at West Amesbury, Wiltshire
Excavations on the south-eastern slopes of King Barrow Ridge, 1.5 km east of Stonehenge, revealed five pits, a grave and other features of Middle Neolithic date. Analysis of the pit assemblages and the partial inhumation interred in the grave has provided insights into lifeways in this landscape in the late fourth millennium cal BC. Evidence suggests that the area was visited by a pastoralist, mobile community on a semi-regular basis for a significant period, in late autumn or winter. Selected remnants of craft-working and consumption were deposited in pits, before deliberate infilling. These depositions repeatedly memorialised activity on the hillside at a time of contemporary activity elsewhere on King Barrow Ridge and at the future site of Stonehenge. Middle Neolithic pits are present in significant numbers across King Barrow Ridge, and alongside pits in the Durrington area, form one of the densest concentrations of such activity in the region. Long distance mobility is suggested by the possible Irish origins of the inhumation, the first Middle Neolithic individual excavated in the environs of Stonehenge. Whilst of significance for understanding the Middle Neolithic in the WHS and the region, this research also hints at the roots of Late Neolithic monumentalisation of this landscape
Limits on the high-energy gamma and neutrino fluxes from the SGR 1806-20 giant flare of December 27th, 2004 with the AMANDA-II detector
On December 27th 2004, a giant gamma flare from the Soft Gamma-ray Repeater
1806-20 saturated many satellite gamma-ray detectors. This event was by more
than two orders of magnitude the brightest cosmic transient ever observed. If
the gamma emission extends up to TeV energies with a hard power law energy
spectrum, photo-produced muons could be observed in surface and underground
arrays. Moreover, high-energy neutrinos could have been produced during the SGR
giant flare if there were substantial baryonic outflow from the magnetar. These
high-energy neutrinos would have also produced muons in an underground array.
AMANDA-II was used to search for downgoing muons indicative of high-energy
gammas and/or neutrinos. The data revealed no significant signal. The upper
limit on the gamma flux at 90% CL is dN/dE < 0.05 (0.5) TeV^-1 m^-2 s^-1 for
gamma=-1.47 (-2). Similarly, we set limits on the normalization constant of the
high-energy neutrino emission of 0.4 (6.1) TeV^-1 m^-2 s^-1 for gamma=-1.47
(-2).Comment: 14 pages, 3 figure
Thermal phase transition in nuclear multifragmentation: The role of Coulomb energy and finite size
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