Spatially Resolved Distribution Function and the Medium-Range Order in Metallic Liquid and Glass

The structural description of disordered systems has been a longstanding challenge in physical science. We propose an atomic cluster alignment method to reveal the development of three-dimensional topological ordering in a metallic liquid as it undercools to form a glass. By analyzing molecular dynamic (MD) simulation trajectories of a Cu64.5Zr35.5 alloy, we show that medium-range order (MRO) develops in the liquid as it approaches the glass transition. Specifically, around Cu sites, we observe “Bergman triacontahedron” packing (icosahedron, dodecahedron and icosahedron) that extends out to the fourth shell, forming an interpenetrating backbone network in the glass. The discovery of Bergman-type MRO from our order-mining technique provides unique insights into the topological ordering near the glass transition and the relationship between metallic glasses and quasicrystals

The Escherichia coli transcriptome mostly consists of independently regulated modules

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome

A five-year review of burn injuries in Irrua

<p>Abstract</p> <p>Background</p> <p>The management of burns remains a challenge in developing countries. Few data exist to document the extent of the problem. This study provides data from a suburban setting by documenting the epidemiology of burn injury and ascertaining outcome of management. This will help in planning strategies for prevention of burns and reducing severity of complications.</p> <p>Methods</p> <p>A total of 72 patients admitted for burns between January 1st, 2002 and December 31st, 2006 at the Irrua specialist teaching hospital were studied retrospectively. Sources of information were the case notes and operation registers. Data extracted included demographics as well as treatment methods and outcome</p> <p>Results</p> <p>The results revealed male to female ratio of 2.1:1. Over 50% of the injuries occurred at home. There was a seasonal variation with over 40% of injuries occurring between November and January. The commonest etiologic agent was flame burn from kerosene explosion. There were 7 deaths in the series.</p> <p>Conclusion</p> <p>Burns are preventable. We recommend adequate supply of unadulterated petroleum products and establishment of burn centers.</p

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Methods and results: Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0–6 copies per diploid genome (pdg) in Peru, between 0–12 pdg in !Xhosa samples and between 0–10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). Conclusions: The case–control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations

Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structures

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Identification of Human IKK-2 Inhibitors of Natural Origin (Part I): Modeling of the IKK-2 Kinase Domain, Virtual Screening and Activity Assays

BACKGROUND: Their large scaffold diversity and properties, such as structural complexity and drug similarity, form the basis of claims that natural products are ideal starting points for drug design and development. Consequently, there has been great interest in determining whether such molecules show biological activity toward protein targets of pharmacological relevance. One target of particular interest is hIKK-2, a serine-threonine protein kinase belonging to the IKK complex that is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Indeed, this has led to the development of synthetic ATP-competitive inhibitors for hIKK-2. Therefore, the main goals of this study were (a) to use virtual screening to identify potential hIKK-2 inhibitors of natural origin that compete with ATP and (b) to evaluate the reliability of our virtual-screening protocol by experimentally testing the in vitro activity of selected natural-product hits. METHODOLOGY/PRINCIPAL FINDINGS: We thus predicted that 1,061 out of the 89,425 natural products present in the studied database would inhibit hIKK-2 with good ADMET properties. Notably, when these 1,061 molecules were merged with the 98 synthetic hIKK-2 inhibitors used in this study and the resulting set was classified into ten clusters according to chemical similarity, there were three clusters that contained only natural products. Five molecules from these three clusters (for which no anti-inflammatory activity has been previously described) were then selected for in vitro activity testing, in which three out of the five molecules were shown to inhibit hIKK-2. CONCLUSIONS/SIGNIFICANCE: We demonstrated that our virtual-screening protocol was successful in identifying lead compounds for developing new inhibitors for hIKK-2, a target of great interest in medicinal chemistry. Additionally, all the tools developed during the current study (i.e., the homology model for the hIKK-2 kinase domain and the pharmacophore) will be made available to interested readers upon request