Attributes of fault-tolerant distributed file systems

Fault tolerance in distributed file systems will be investigated by analyzing recovery techniques and concepts implemented within the following models of distributed systems: pool-processor model and user-server model. The research presented provides an overview of fault tolerance characteristics and mechanisms within current implementations and summarizes future directions for fault tolerant distributed file systems

TBX5 is required for embryonic cardiac cell cycle progression

Despite the critical importance of TBX5 in normal development and disease, relatively little is known about the mechanisms by which TBX5 functions in the embryonic heart. Our present studies demonstrate that TBX5 is necessary to control the length of the embryonic cardiac cell cycle, with depletion of TBX5 leading to cardiac cell cycle arrest in late G1- or early S-phase. Blocking cell cycle progression by TBX5 depletion leads to a decrease in cardiac cell number, an alteration in the timing of the cardiac differentiation program, defects in cardiac sarcomere formation, and ultimately, to cardiac programmed cell death. In these studies we have also established that terminally differentiated cardiomyocytes retain the capacity to undergo cell division. We further show that TBX5 is sufficient to determine the length of the embryonic cardiac cell cycle and the timing of the cardiac differentiation program. Thus, these studies establish a role for TBX5 in regulating the progression of the cardiac cell cycle

Cardiac Progenitors and the Embryonic Cell Cycle

Despite the critical importance of proper cell cycle regulation in establishing the correct morphology of organs and tissues during development, relatively little is known about how cell proliferation is regulated in a tissue-specific manner. The control of cell proliferation within the developing heart is of considerable interest, given the high prevalence of congenital cardiac abnormalities among humans, and recent interest in the isolation of cardiac progenitor populations. We therefore review studies exploring the contribution of cell proliferation to overall cardiac morphology and the molecular mechanisms regulating this process. In addition, we also review recent studies that have identified progenitor cell populations within the adult myocardium, as well as those exploring the capability of differentiated myocardial cells to proliferate post-natally. Thus, the exploration of cardiomyoctye cell cycle regulation, both during development as well as in the adult heart, promises to yield many exciting and important discoveries over the coming years

X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1)

BACKGROUND: Human Aortic Preferentially Expressed Protein-1 (APEG-1) is a novel specific smooth muscle differentiation marker thought to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). RESULTS: Good quality crystals that were suitable for X-ray crystallographic studies were obtained following the truncation of the 14 N-terminal amino acids of APEG-1, a region predicted to be disordered. The truncated protein (termed ΔAPEG-1) consists of a single immunoglobulin (Ig) like domain which includes an Arg-Gly-Asp (RGD) adhesion recognition motif. The RGD motif is crucial for the interaction of extracellular proteins and plays a role in cell adhesion. The X-ray structure of ΔAPEG-1 was determined and was refined to sub-atomic resolution (0.96 Å). This is the best resolution for an immunoglobulin domain structure so far. The structure adopts a Greek-key β-sandwich fold and belongs to the I (intermediate) set of the immunoglobulin superfamily. The residues lying between the β-sheets form a hydrophobic core. The RGD motif folds into a 3(10 )helix that is involved in the formation of a homodimer in the crystal which is mainly stabilized by salt bridges. Analytical ultracentrifugation studies revealed a moderate dissociation constant of 20 μM at physiological ionic strength, suggesting that APEG-1 dimerisation is only transient in the cell. The binding constant is strongly dependent on ionic strength. CONCLUSION: Our data suggests that the RGD motif might play a role not only in the adhesion of extracellular proteins but also in intracellular protein-protein interactions. However, it remains to be established whether the rather weak dimerisation of APEG-1 involving this motif is physiogically relevant

Comeback of epitaxial graphene for electronics: large-area growth of bilayer-free graphene on SiC

We present a new fabrication method for epitaxial graphene on SiC which enables the growth of ultra-smooth defect- and bilayer-free graphene sheets with an unprecedented reproducibility, a necessary prerequisite for wafer-scale fabrication of high quality graphene-based electronic devices. The inherent but unfavorable formation of high SiC surface terrace steps during high temperature sublimation growth is suppressed by rapid formation of the graphene buffer layer which stabilizes the SiC surface. The enhanced nucleation is enforced by decomposition of polymer adsorbates which act as a carbon source. With most of the steps well below 0.75 nm pure monolayer graphene without bilayer inclusions is formed with lateral dimensions only limited by the size of the substrate. This makes the polymer assisted sublimation growth technique the most promising method for commercial wafer scale epitaxial graphene fabrication. The extraordinary electronic quality is evidenced by quantum resistance metrology at 4.2 K with until now unreached precision and high electron mobilities on mm scale devices.Comment: 20 pages, 6 Figure

Metabolomic serum abnormalities in dogs with hepatopathies

Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.Peer reviewe

Membrane-Protein Interactions in a Generic Coarse-Grained Model for Lipid Bilayers

We study membrane-protein interactions and membrane-mediated protein-protein interactions by Monte Carlo simulations of a generic coarse-grained model for lipid bilayers with cylindrical hydrophobic inclusions. The strength of the hydrophobic force and the hydrophobic thickness of the proteins are systematically varied. The results are compared with analytical predictions of two popular analytical theories: The Landau-de Gennes theory and the elastic theory. The elastic theory provides an excellent description of the fluctuation spectra of pure membranes and successfully reproduces the deformation profiles of membranes around single proteins. However, its prediction for the potential of mean force between proteins is not compatible with the simulation data for large distances. The simulations show that the lipid-mediated interactions are governed by five competing factors: Direct interactions, lipid-induced depletion interactions, lipid bridging, lipid packing, and a smooth long-range contribution. The mechanisms leading to "hydrophobic mismatch" interactions are critically analyzed.Comment: 16 pages, 8 figures, accepted for publication in Biophysical Journa

Citizen-science data provides new insight into annual and seasonal variation in migration patterns

Current rates of global environmental and climate change pose potential challenges for migratory species that must cope with or adapt to new conditions and different rates of change across broad spatial scales throughout their annual life cycle. North American migratory hummingbirds may be especially sensitive to changes in environment and climate due to their extremely small body size, high metabolic rates, and dependence on nectar as a main resource. We used occurrence information from the eBird citizen-science database to track migratory movements of five North American hummingbird species (Archilochus alexandri, A. colubris, Selasphorus calliope, S. platycercus, and S. rufus) across 6 years (2008–2013) at a daily temporal resolution to describe annual and seasonal variation in migration patterns. Our findings suggest that the timing of the onset of spring migration generally varies less than the arrival on the wintering grounds. Species follow similar routes across years, but exhibit more variation in daily longitude than latitude. Long distance migrants generally had less annual variation in geographic location and timing than shorter distance migrants. Our study is among the first to examine variation in migration routes and timing for hummingbirds, but more work is needed to understand the capacity of these species to respond to different rates of environmental change along their migratory routes