12 research outputs found
An efficient and principled method for detecting communities in networks
A fundamental problem in the analysis of network data is the detection of
network communities, groups of densely interconnected nodes, which may be
overlapping or disjoint. Here we describe a method for finding overlapping
communities based on a principled statistical approach using generative network
models. We show how the method can be implemented using a fast, closed-form
expectation-maximization algorithm that allows us to analyze networks of
millions of nodes in reasonable running times. We test the method both on
real-world networks and on synthetic benchmarks and find that it gives results
competitive with previous methods. We also show that the same approach can be
used to extract nonoverlapping community divisions via a relaxation method, and
demonstrate that the algorithm is competitively fast and accurate for the
nonoverlapping problem.Comment: 14 pages, 5 figures, 1 tabl
A comprehensive assessment of benign genetic variability for neurodegenerative disorders
Over the last few years, as more and more sequencing studies have been performed, it has become apparent that the identification of pathogenic mutations is, more often than not, a complex issue. Here, with a focus on neurodegenerative diseases, we have performed a survey of coding genetic variability that is unlikely to be pathogenic. We have performed whole-exome sequencing in 478 samples derived from several brain banks in the United Kingdom and the United States of America. Samples were included when subjects were, at death, over 60 years of age, had no signs of neurological disease and were subjected to a neuropathological examination, which revealed no evidence of neurodegeneration. This information will be valuable to studies of genetic variability as a causal factor for neurodegenerative syndromes. We envisage it will be particularly relevant for diagnostic laboratories as a filter step to the results being produced by either genome-wide or gene-panel sequencing. We have made this data publicly available at www.alzforum.org/exomes/hex
FLUSHING PORCINE DCD LIVERS WITH CYCLO-DEXTRIN COMPLEXED CURCUMIN DOES NOT REDUCE ISCHEMIA REPERFUSION INJURY
MULTIFACTORIAL BIOLOGICAL MODULATION OF WARM ISCHEMIA AND REPERFUSION INJURY IN LIVER TRANSPLANTATION FROM NON-HEART-BEATING-DONORS ELIMINATES PRIMARY GRAFT NON-FUNCTION AND REDUCES BILESALT TOXICITY
Isolation and structural characterization of novel sialylated oligosaccharide-alditols from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis
Isolation and Structural Characterization of Sialic Acid-Containing Glycopeptides of the O-GlycosidicType from the Urine of Two Patients with an Hereditary Deliciency in α-N-Acetylgalactosaminidase Activity
Multifactorial biological modulation of warm ischemia reperfusion injury in liver transplantation from non-heart-beating donors eliminates primary nonfunction and reduces bile salt toxicity
Objective: To design a multifactorial biological modulation approach targeting ischemia reperfusion injury to augment viability of porcine liver grafts from non-heart-beating donors (NHBD). Background Data: Liver Transplantation (LTx) from NHBD is associated with an increased risk of primary nonfunction (PNF) and biliary complications. In porcine NHBD-LTx, we previously reported a 50% risk of PNF and toxic bile formation in grafts exposed to >= 30' warm ischemia (WI). Methods: Porcine livers exposed to 45' WI were cold stored, transplanted and either modulated (n = 6) or not (controls, n = 9). In the modulation group, donor livers were flushed with warm Ringers (avoiding cold-induced vasoconstriction), streptokinase (eliminating stagnating thrombi), and epoprostenol (vasodilator, platelet aggregation inhibitor) prior to cold storage. In recipients, glycine (Kupffer cell stabilizer), alpha 1-acid-glycoprotein (anti-inflammatory protein), MAPKinase-inhibitor (pro-inflammatory cytokine generation inhibitor), alpha-tocopherol and glutathione (anti-oxidants), and apotransferrin (iron chelator) were administrated intravenously. PNF, survival, lactate, transaminase, TNF-alpha, redox-active iron, and biliary bile salt-to-phospholipid ratio were monitored. Results: No PNF was observed in modulated versus 55% in control pigs (P = 0.025). Survival was 83% in modulated versus 22% in control pigs (P = 0.02). At 180' postreperfusion, lactate was lower in modulated (5.4 +/- 1.9 mmol/L) versus control pigs (9.4 +/- 2.2 mmol/L; P = 0.011). At 60' postreperfusion, there was a trend for lower AST in modulated versus control pigs at 60' (939 +/- 578 vs. 1683 +/- 873 IU/L; P = 0.089). Postreperfusion, TNF-alpha remained stable in modulated pigs (49 +/- 27 pg/mL at 15' and 85 +/- 26 pg/mL at 180'; P = 0.399) but increased in control pigs (107 +/- 36pg/mL at 15' and 499 +/- 216 pg/mL at 180'; P = 0.023). At 180' postreperfusion, redox-active iron was higher in control pigs versus modulated pigs (0.21 +/- 0.18 vs. 0.042 +/- 0.062 mu m; P = 0.038). Biliary bile salt-to-phospholipid ratio post-LTx was lower in modulated versus control pigs (1128 +/- 447 vs. 4836 +/- 4619; P = 0.05). Conclusions: A multifactorial biological modulation eliminates PNF, improves liver function and increases survival. Biochemically, TNF-alpha and redox-active iron are suppressed and biliary bile salt toxicity is reduced. Translating this strategy clinically may lead to wider and safer use of NHBD. (Ann Surg 2009; 250: 808-817