Edge covering with budget constrains

We study two related problems: finding a set of k vertices and minimum number of edges (kmin) and finding a graph with at least m' edges and minimum number of vertices (mvms). Goldschmidt and Hochbaum \cite{GH97} show that the mvms problem is NP-hard and they give a 3-approximation algorithm for the problem. We improve \cite{GH97} by giving a ratio of 2. A 2(1+\epsilon)-approximation for the problem follows from the work of Carnes and Shmoys \cite{CS08}. We improve the approximation ratio to 2. algorithm for the problem. We show that the natural LP for \kmin has an integrality gap of 2-o(1). We improve the NP-completeness of \cite{GH97} by proving the pronlem are APX-hard unless a well-known instance of the dense k-subgraph admits a constant ratio. The best approximation guarantee known for this instance of dense k-subgraph is O(n^{2/9}) \cite{BCCFV}. We show that for any constant \rho>1, an approximation guarantee of \rho for the \kmin problem implies a \rho(1+o(1)) approximation for \mwms. Finally, we define we give an exact algorithm for the density version of kmin.Comment: 17 page

Electrical properties of metal/wse2structures

The formation of low resistance metal contacts on two-Dimensional layer (2-D) of WSe2 is a big challenge. In this research, a comparative study is presented on the electrical properties of metal/WSe2 Schottky barrier diodes with various metals such as Au, In, Al, and Ga in the temperature range of 80K to 400K well within the domain of thermionic emission theory. Topics covered here include the factors that determine the Schottky barrier height, the device capacitance, and its current-voltage (I-V) characteristics. I-V curves for different metals on WSe2 are analyzed as function of temperature. Barrier height is determined from Au-nWSe2 Schottky barrier diode. This study provides a theoretical background for the selection of favourable metals on monolayer WSe2

Fractures in the elderly: when is hip replacement a necessity?

As the world’s population ages, hip fractures pose a significant health care problem. Hip fractures in the elderly are associated with impaired mobility, and increased morbidity and mortality. Associated conditions, such as osteoporosis, medical comorbidity, and dementia, pose a significant concern and determine optimal treatment. One-year mortality rates currently range from 14% to 36%, and care for these patients represents a major global economic burden. The incidence of hip fractures is bimodal in its distribution. Young adult hip fractures are the result of high energy trauma, and the larger peak seen in the elderly population is secondary to low-energy injuries. The predilection for the site of fracture at the neck of femur falls into two major subgroups. Pertrochanteric fractures occur when the injury is extracapsular and the blood supply to the head of femur is unaffected. The management of this group involves internal fixation through a sliding hip screw device or intramedullary fixation device, both of which have good results. The other group of patients who sustain an intracapsular fracture at the femoral neck are at increased risk of nonunion and osteonecrosis. Recent papers in the literature have shown better functional outcomes with a primary hip replacement over other treatment modalities. This article reviews the current literature and indications for a primary total hip replacement in these patients

eModel-BDB: a database of comparative structure models of drug-target interactions from the Binding Database

Background: The structural information on proteins in their ligand-bound conformational state is invaluable for protein function studies and rational drug design. Compared to the number of available sequences, not only is the repertoire of the experimentally determined structures of holo-proteins limited, these structures do not always include pharmacologically relevant compounds at their binding sites. In addition, binding affinity databases provide vast quantities of information on interactions between drug-like molecules and their targets, however, often lacking structural data. On that account, there is a need for computational methods to complement existing repositories by constructing the atomic-level models of drug-protein assemblies that will not be determined experimentally in the near future. Results: We created eModel-BDB, a database of  200,005 comparative models of drug-bound proteins based on   1,391,403 interaction data obtained from the Binding Database and the PDB library of 31 January 2017. Complex models in eModel-BDB were generated with a collection of the state-of-the-art techniques, including protein meta-threading, template-based structure modeling, refinement and binding site detection, and ligand similarity-based docking. In addition to a rigorous quality control maintained during dataset generation, a subset of weakly homologous models was selected for the retrospective validation against experimental structural data recently deposited to the Protein Data Bank. Validation results indicate that eModel-BDB contains models that are accurate not only at the global protein structure level but also with respect to the atomic details of bound ligands. Conclusions: Freely available eModel-BDB can be used to support structure-based drug discovery and repositioning, drug target identification, and protein structure determination

Spectral characterizations, Hirshfeld surface analysis and molecular docking studies of new novel NLO 2-(3,4-Dimethoxyphenyl)-3-hydroxy-4H-chromen-4-one

The molecular structure of the compound, spectroscopic investigations (FT-IR, FT-Raman, and NMR) and the frontier energy level analysis of 2-(3,4-Dimethoxyphenyl)-3-hydroxy-4H-chromen-4-one (DMP3H), have been all examined using density functional theory (DFT) methods. Comparisons are made between predicted DFT geometrical parameters and experimental values and also the same performed between the theoretical vibrational wavenumbers and observed data. Chemical reactivity of DMP3H has been studied using DFT/PBEPBE approach that includes frontier orbital energies, optical characteristics and chemical descriptors. Additionally, the cytotoxic activity of the bioactive ligand has been checked against human cancer cell lines A549 and MCF-7 in vitro by the MTT assay. Hence, the docking and in vitro activity against cancer cell lines display positive results and the present ligand performance appears to be a promising way for anticancer agents with better efficacy

Formulation and Evaluation of Etoricoxib Niosomal Topical Gel.

The past decade, advanced drug delivery research and development has surged ahead of others in formulation research. The emergence of novel technology and the growing capabilities of proteomics, genomics and combinatorial chemistry have provided scientists with new technologies. The niosomal formulations were successfully prepared by thin film hydration technique using cholesterol and Span20, 40, 60, 80 Tween 60, 80 and Brij-52 as non-ionic surfactant. The presence of cholesterol made the niosomes more stable with high entrapment efficiency and retention properties. The highest entrapment efficiency was observed with span60 and it may be concluded that the entrapment efficiency may be improved using surfactant with decrease HLB value and highest phase transition temperature

eRepo-ORP: Exploring the Opportunity Space to Combat Orphan Diseases with Existing Drugs

© 2017 About 7000 rare, or orphan, diseases affect more than 350 million people worldwide. Although these conditions collectively pose significant health care problems, drug companies seldom develop drugs for orphan diseases due to extremely limited individual markets. Consequently, developing new treatments for often life-threatening orphan diseases is primarily contingent on financial incentives from governments, special research grants, and private philanthropy. Computer-aided drug repositioning is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Here, we present eRepo-ORP, a comprehensive resource constructed by a large-scale repositioning of existing drugs to orphan diseases with a collection of structural bioinformatics tools, including eThread, eFindSite, and eMatchSite. Specifically, a systematic exploration of 320,856 possible links between known drugs in DrugBank and orphan proteins obtained from Orphanet reveals as many as 18,145 candidates for repurposing. In order to illustrate how potential therapeutics for rare diseases can be identified with eRepo-ORP, we discuss the repositioning of a kinase inhibitor for Ras-associated autoimmune leukoproliferative disease. The eRepo-ORP data set is available through the Open Science Framework at https://osf.io/qdjup/

Comparative Analysis of Species-Specific Ligand Recognition in Toll-Like Receptor 8 Signaling: A Hypothesis

Toll-like receptors (TLRs) play a central role in the innate immune response by recognizing conserved structural patterns in a variety of microbes. TLRs are classified into six families, of which TLR7 family members include TLR7, 8, and 9, which are localized to endolysosomal compartments recognizing viral infection in the form of foreign nucleic acids. In our current study, we focused on TLR8, which has been shown to recognize different types of ligands such as viral or bacterial ssRNA as well as small synthetic molecules. The primary sequences of rodent and non-rodent TLR8s are similar, but the antiviral compound (R848) that activates the TLR8 pathway is species-specific. Moreover, the factors underlying the receptor's species-specificity remain unknown. To this end, comparative homology modeling, molecular dynamics simulations refinement, automated docking and computational mutagenesis studies were employed to probe the intermolecular interactions between this anti-viral compound and TLR8. Furthermore, comparative analyses of modeled TLR8 (rodent and non-rodent) structures have shown that the variation mainly occurs at LRR14-15 (undefined region); hence, we hypothesized that this variation may be the primary reason for the exhibited species-specificity. Our hypothesis was further bolstered by our docking studies, which clearly showed that this undefined region was in close proximity to the ligand-binding site and thus may play a key role in ligand recognition. In addition, the interface between the ligand and TLR8s varied depending upon the amino acid charges, free energy of binding, and interaction surface. Therefore, our current work provides a hypothesis for previous in vivo studies in the context of TLR signaling