Laplacian normalization and random walk on heterogeneous networks for disease-gene prioritization

© 2015 Elsevier Ltd. All rights reserved. Random walk on heterogeneous networks is a recently emerging approach to effective disease gene prioritization. Laplacian normalization is a technique capable of normalizing the weight of edges in a network. We use this technique to normalize the gene matrix and the phenotype matrix before the construction of the heterogeneous network, and also use this idea to define the transition matrices of the heterogeneous network. Our method has remarkably better performance than the existing methods for recovering known gene-phenotype relationships. The Shannon information entropy of the distribution of the transition probabilities in our networks is found to be smaller than the networks constructed by the existing methods, implying that a higher number of top-ranked genes can be verified as disease genes. In fact, the most probable gene-phenotype relationships ranked within top 3 or top 5 in our gene lists can be confirmed by the OMIM database for many cases. Our algorithms have shown remarkably superior performance over the state-of-the-art algorithms for recovering gene-phenotype relationships. All Matlab codes can be available upon email request

Content-aware photo collage using circle packing

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Antimony-doped graphene nanoplatelets

Heteroatom doping into the graphitic frameworks have been intensively studied for the development of metal-free electrocatalysts. However, the choice of heteroatoms is limited to non-metallic elements and heteroatom-doped graphitic materials do not satisfy commercial demands in terms of cost and stability. Here we realize doping semimetal antimony (Sb) at the edges of graphene nanoplatelets (GnPs) via a simple mechanochemical reaction between pristine graphite and solid Sb. The covalent bonding of the metalloid Sb with the graphitic carbon is visualized using atomic-resolution transmission electron microscopy. The Sb-doped GnPs display zero loss of electrocatalytic activity for oxygen reduction reaction even after 100,000 cycles. Density functional theory calculations indicate that the multiple oxidation states (Sb3+ and Sb5+) of Sb are responsible for the unusual electrochemical stability. Sb-doped GnPs may provide new insights and practical methods for designing stable carbon-based electrocatalystsclose0

An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

High power Q-switched thulium doped fibre laser using carbon nanotube polymer composite saturable absorber

We have proposed and demonstrated a Q-switched Thulium doped bre laser (TDFL) with a ‘Yin-Yang’ all- bre cavity scheme based on a combination of nonlinear optical loop mirror (NOLM) and nonlinear ampli ed loop mirror (NALM). Unidirectional lasing operation has been achieved without any intracavity isolator. By using a carbon nanotube polymer composite based saturable absorber (SA), we demonstrated the laser output power of ~197 mW and pulse energy of 1.7 μJ. To the best of our knowledge, this is the highest output power from a nanotube polymer composite SA based Q-switched Thulium doped bre laser

Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>The mainstay of pharmacologic therapy for rheumatoid arthritis includes the use of disease-modifying agents like sulfasalazine and methothrexate, and more recently, anti-tumor necrosis factor-α agents. Depression remains a major co-morbidity in patients with rheumatoid arthritis and is thought to contribute to disability and mortality in these patients. Evidence now suggests that a biologic link exists between substrates responsible for inflammatory conditions and mood disorders. Most of this evidence comes from preclinical studies. Nevertheless, more research into this area is helping us to understand the possible mechanisms through which these conditions interact with each other.</p> <p>Case presentation</p> <p>We describe a 60-year-old Indian man with rheumatoid arthritis diagnosed 15 years ago who had minimal response to multiple therapies with disease-modifying agents and whose arthritis symptoms surprisingly remitted when he was started on a specific serotonin reuptake inhibitor antidepressant, three years ago, for co-morbid major depression. This remission has been maintained with this medication, and the patient is currently not taking any antirheumatoid medications.</p> <p>Conclusion</p> <p>Possible mechanisms linking substrates of mood disorders and inflammation are reviewed in this case report, particularly the serotonergic system. Evidence seems to suggest a significant interaction between the serotonergic systems and inflammation. This interaction seems to be bidirectional. An understanding of this relation is most important to gain insight not only into pathophysiological mechanisms underlying this condition, but also into how treatments for these conditions may complement each other and possibly provide greater therapeutic options in both of these disabling conditions.</p

Finite element analysis and calculation method of residual flexural capacity of post-fire RC beams

Fire tests and subsequent bending tests of fourreinforced concrete (RC) beamswere performed. Based on these tests, the post-fire performance of RCbeams was further studied using finite element simulation through reasonable selection of suitable thermal and thermodynamic parameters of steel and concrete materials. A thermodynamic model of RC beams with three sides under fire was built using finite element analysis(FEA)software ABAQUS. The FEA model was validated with the results of fire tests. Different factors were taken into account for further parametric studies in fire using the proposed FE model.The results show that the main factors affecting the fire resistance of the beamsare the thickness of the concretecover, reinforcement ratio of longitudinal steel,the fire exposure timeandthe fire exposure sides. Based on the strength reduction formula at high temperature of steel and concrete, animproved section method was proposed to develop a calculation formula to calculate the flexural capacity of RC beams after fire. The theoretical calculation method proposed in this paper shows good agreement with FEA results, which can be used to calculate the flexuralcapacity of RC beams after fire

Gold nanocrystals with variable index facets as highly effective cathode catalysts for lithium-oxygen batteries

© 2015 Nature Publishing Group All rights reserved. Cathode catalysts are the key factor in improving the electrochemical performance of lithium-oxygen (Li-O2) batteries via their promotion of the oxygen reduction and oxygen evolution reactions (ORR and OER). Generally, the catalytic performance of nanocrystals (NCs) toward ORR and OER depends on both composition and shape. Herein, we report the synthesis of polyhedral Au NCs enclosed by a variety of index facets: cubic gold (Au) NCs enclosed by {100} facets; truncated octahedral Au NCs enclosed by {100} and {110} facets; and trisoctahedral (TOH) Au NCs enclosed by 24 high-index {441} facets, as effective cathode catalysts for Li-O2 batteries. All Au NCs can significantly reduce the charge potential and have high reversible capacities. In particular, TOH Au NC catalysts demonstrated the lowest charge-discharge overpotential and the highest capacity of ∼ 20 298 mA h g-1. The correlation between the different Au NC crystal planes and their electrochemical catalytic performances was revealed: high-index facets exhibit much higher catalytic activity than the low-index planes, as the high-index planes have a high surface energy because of their large density of atomic steps, ledges and kinks, which can provide a high density of reactive sites for catalytic reactions