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

Solving multi-scale low frequency electromagnetic problems

In this paper, we will discuss two methods to tackle the low-frequency, multi-scale electromagnetics problem. First we will discuss the augmented electric field integral equation (AEFIE), and then, we will discuss the equivalence principle algorithm (EPA). The AEFIE allows the solution of such problems without the need to perform a loop search of a complex structure. The EPA allows the separation of circuit physics from wave physics in a multiscale problem. Hybridization of these two methods will be discussed.published_or_final_versionThe 4th European Conference on Antennas and Propagation (EuCAP) 2010, Barcelona, Spain, 12-16 April 2010. In Proceedings of the 4th EuCAP, 2010, p. 1-

Phylogeny of Prokaryotes and Chloroplasts Revealed by a Simple Composition Approach on All Protein Sequences from Complete Genomes Without Sequence Alignment

The complete genomes of living organisms have provided much information on their phylogenetic relationships. Similarly, the complete genomes of chloroplasts have helped to resolve the evolution of this organelle in photosynthetic eukaryotes. In this paper we propose an alternative method of phylogenetic analysis using compositional statistics for all protein sequences from complete genomes. This new method is conceptually simpler than and computationally as fast as the one proposed by Qi et al. (2004b) and Chu et al. (2004). The same data sets used in Qi et al. (2004b) and Chu et al. (2004) are analyzed using the new method. Our distance-based phylogenic tree of the 109 prokaryotes and eukaryotes agrees with the biologists tree of life based on 16S rRNA comparison in a predominant majority of basic branching and most lower taxa. Our phylogenetic analysis also shows that the chloroplast genomes are separated to two major clades corresponding to chlorophytes s.l. and rhodophytes s.l. The interrelationships among the chloroplasts are largely in agreement with the current understanding on chloroplast evolution

Regulatory T cells in rheumatoid arthritis showed increased plasticity toward Th17 but retained suppressive function in peripheral blood

OBJECTIVE: Regulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim of this study was to investigate IL-17-producing Tregs from patients with rheumatoid arthritis (RA), and characterise their regulatory capacity and clinical significance. METHODS: Foxp3 and IL-17 coexpression were evaluated in CD4 T lymphocytes from RA patients. An in vitro T cell polarisation assay was performed to investigate the role of proinflammatory cytokines in IL-17-producing Treg polarisation. The suppressive function of IL-17-producing Tregs in RA was assessed by an in vitro suppression assay. The relationship between this Treg subset and clinical features in RA patients was analysed using Spearman's rank correlation test. RESULTS: A higher frequency of IL-17-producing Tregs was present in the peripheral blood of RA patients compared with healthy subjects. These cells from peripheral blood showed phenotypic characteristics of Th17 and Treg cells, and suppressed T cell proliferation in vitro. Tregs in RA synovial fluid lost suppressive function. The Th17 plasticity of Tregs could be induced by IL-6 and IL-23. An increased ratio of this Treg subset was associated with decreased levels of inflammatory markers, including the erythrocyte sedimentation rate and C-reactive protein level, in patients with RA. CONCLUSIONS: Increased levels of IL-17-producing Tregs were identified in RA patients. This Treg subset with Th17 plasticity in peripheral blood retained suppressive functions and was associated with milder inflammatory conditions, suggesting that this Treg population works as a negative regulator in RA, but in RA synovial site it may be pathogenic.postprin

Spin Hall effect in the kagome lattice with Rashba spin-orbit interaction

We study the spin Hall effect in the kagom\'{e} lattice with Rashba spin-orbit coupling. The conserved spin Hall conductance $\sigma_{xy}^{s}$ (see text) and its two components, i.e., the conventional term $\sigma_{xy}^{s0}$ and the spin-torque-dipole term $\sigma_{xy}^{s\tau}$, are numerically calculated, which show a series of plateaus as a function of the electron Fermi energy $\epsilon_{F}$. A consistent two-band analysis, as well as a Berry-phase interpretation, is also given. We show that these plateaus are a consequence of the various Fermi-surface topologies when tuning $\epsilon_{F}$. In particular, we predict that compared to the case with the Fermi surface encircling the $\mathbf{\Gamma}$ point in the Brillouin zone, the amplitude of the spin Hall conductance with the Fermi surface encircling the $\mathbf{K}$ points is twice enhanced, which makes it highly meaningful in the future to systematically carry out studies of the $\mathbf{K}$-valley spintronics.Comment: 7 pages, 3 figures. Phys. Rev. B (in press

Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca2+ handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca2+ transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca2+ transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca2+ concentration ([Ca 2+]o), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca2+ level and peak intracellular Ca 2+ concentration ([Ca2+]i), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca2+]i transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca2+]i transient was not normalized by increasing [Ca2+]o to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca2+ release. Blockade of sarcoplasmic reticulum (SR) Ca2+-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca2+]o, which was slowed in IL-2-treated myocytes when [Ca2+]o was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca 2+]o. The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na+-Ca2+ exchange activity, but not to any change in L-type Ca2+ channels. © 2003 Elsevier Ltd. All rights reserved.postprin

Kinetic frustration and the nature of the magnetic and paramagnetic states in iron pnictides and iron chalcogenides

The iron pnictide and chalcogenide compounds are a subject of intensive investigations due to their high temperature superconductivity.\cite{a-LaFeAsO} They all share the same structure, but there is significant variation in their physical properties, such as magnetic ordered moments, effective masses, superconducting gaps and T$_c$. Many theoretical techniques have been applied to individual compounds but no consistent description of the trends is available \cite{np-review}. We carry out a comparative theoretical study of a large number of iron-based compounds in both their magnetic and paramagnetic states. We show that the nature of both states is well described by our method and the trends in all the calculated physical properties such as the ordered moments, effective masses and Fermi surfaces are in good agreement with experiments across the compounds. The variation of these properties can be traced to variations in the key structural parameters, rather than changes in the screening of the Coulomb interactions. Our results provide a natural explanation of the strongly Fermi surface dependent superconducting gaps observed in experiments\cite{Ding}. We propose a specific optimization of the crystal structure to look for higher T$_c$ superconductors.Comment: 5 pages, 3 figures with a 5-page supplementary materia

SUMO-2 promotes mRNA translation by enhancing interaction between eIF4E and eIF4G

Small ubiquitin-like modifier (SUMO) proteins regulate many important eukaryotic cellular processes through reversible covalent conjugation to target proteins. In addition to its many well-known biological consequences, like subcellular translocation of protein, subnuclear structure formation, and modulation of transcriptional activity, we show here that SUMO-2 also plays a role in mRNA translation. SUMO-2 promoted formation of the active eukaryotic initiation factor 4F (eIF4F) complex by enhancing interaction between Eukaryotic Initiation Factor 4E (eIF4E) and Eukaryotic Initiation Factor 4G (eIF4G), and induced translation of a subset of proteins, such as cyclinD1 and c-myc, which essential for cell proliferation and apoptosis. As expected, overexpression of SUMO-2 can partially cancel out the disrupting effect of 4EGI-1, a small molecule inhibitor of eIF4E/eIF4G interaction, on formation of the eIF4F complex, translation of the cap-dependent protein, cell proliferation and apoptosis. On the other hand, SUMO-2 knockdown via shRNA partially impaired cap-dependent translation and cell proliferation and promoted apoptosis. These results collectively suggest that SUMO-2 conjugation plays a crucial regulatory role in protein synthesis. Thus, this report might contribute to the basic understanding of mammalian protein translation and sheds some new light on the role of SUMO in this process. © 2014 Chen et al

Antimicrobial activity of essential oil of Salvia officinalis L. collected in Syria

The essential oils of Salvia officinalis L. collected at two different altitudes in Syrian coastline were analyzed by gas chromatography. Plant’s development stage and the ecological factors had impact on the qualitative composition of S. officinalis essential oil. Although, the major components of the essential oils extracted from plants grown at both altitudes were 1,8-cineol, camphor, borneol, α-pinene, β-pinene, camphene, β-myrcene and caryophyllene, their percentage changed according to the altitude. S. officinalis essential oil was for its antibacterial activities by using Gram- positive and negative bacteria. Both Staphylococcus aureus and Streptococcus group D were efficiently inhibited after 10 min of contact at oil concentration of 20 μl/ml. The inhibitory effect of the essential oil on Candida albicans was total and definitive within a minimum of contact time and oil concentration. But the essential oil showed a temporary bacteriostatic effect on Escherichia coli, Salmonella typhi, as well as Pseudomonas aeruoginosa. In comparison with most known antibiotics, the efficiency of S. officinalis essential oil was much better, especially against bacteria resistant to antibiotic.Key words: Essential oil, Salvia officinalis L., antibacterial activities, inhibitory effect, bacteriostatic effect

Phase Separation and Magnetic Order in K-doped Iron Selenide Superconductor

Alkali-doped iron selenide is the latest member of high Tc superconductor family, and its peculiar characters have immediately attracted extensive attention. We prepared high-quality potassium-doped iron selenide (KxFe2-ySe2) thin films by molecular beam epitaxy and unambiguously demonstrated the existence of phase separation, which is currently under debate, in this material using scanning tunneling microscopy and spectroscopy. The stoichiometric superconducting phase KFe2Se2 contains no iron vacancies, while the insulating phase has a \surd5\times\surd5 vacancy order. The iron vacancies are shown always destructive to superconductivity in KFe2Se2. Our study on the subgap bound states induced by the iron vacancies further reveals a magnetically-related bipartite order in the superconducting phase. These findings not only solve the existing controversies in the atomic and electronic structures in KxFe2-ySe2, but also provide valuable information on understanding the superconductivity and its interplay with magnetism in iron-based superconductors