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

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

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

Structural insights into human Kif7, a kinesin involved in Hedgehog signalling

The human Kif7 motor domain structure provides insights into a kinesin of medical significance

Semiresorbable biologic hybrid meshes for ventral abdominal hernia repair in potentially contaminated settings: lower risk of recurrence

In case of potential contamination, implantation of synthetic meshes in hernia and abdominal wall surgery is problematic due to a higher risk of mesh infection. As an alternative, a variety of different biologic meshes have been used. However, relevant data comparing outcome after implantation of these meshes are lacking. Between January 2012 and October 2021, biologic meshes were used for reconstruction of the abdominal wall in 71 patients with preoperative or intraoperative abdominal contamination. In this retrospective study, semiresorbable biologic hybrid meshes (BHM) and completely resorbable meshes (CRM) were compared and analyzed using a Castor EDC database. In 28 patients, semiresorbable biologic hybrid meshes were used; in 43 patients, completely resorbable meshes were used. Both groups showed no difference in age, gender, BMI, operation duration, hernia size and Charlson comorbidity index. The risk degree of surgical-site occurrences was graded according to the Ventral Hernia Working Group (VHWG) classification, and the median value was 3 (range 2–4) in the BHM group and 3 (range 2–4) in the CRM group. Hernia recurrence within 24 months after hernia repair was significantly lower in the BHM group (3.6% vs. 28.9%; p = 0.03), while postoperative complication rate, with respect to seromas in need of therapy (61.4% vs. 55.5%, p = 0.43) and operative revision (28.6% vs. 16.3%, p = 0.22) was not different in either group. Biologic hybrid meshes can be used safely in case of possible contamination. BHM seems to reduce the risk of hernia recurrence compared to completely resorbable biologic meshes, but this has to be investigated further

Heart failure therapy in diabetic patients-comparison with the recent ESC/EASD guideline

<p>Abstract</p> <p>Background</p> <p>To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function.</p> <p>Methods</p> <p>3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50%) and 994 patients in the whole cohort suffered from diabetes.</p> <p>Results</p> <p>The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function.</p> <p>Conclusions</p> <p>Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.</p