Design and synthesis of a fragment set based on twisted bicyclic lactams

Current fragment sets tend to be dominated by flatter molecules, and their shape diversity does not reflect that of the fragments that are theoretically possible. The design and synthesis of a set of bridged fragments containing a bridgehead nitrogen is described. Many of these fragments contain twisted lactams whose modulated electronic properties may present unusual opportunities for interaction with target proteins. The demonstrated novelty, three-dimensionality and molecular properties of the set of 22 fragments may provide valuable, and highly distinctive, starting points for fragment-based drug discovery

Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions

To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales

Salidroside as a Novel Protective Agent to Improve Red Blood Cell Cryopreservation.

Glycerol and trehalose have been widely examined as protective agents in the cryopreservation of red blood cells (RBCs). However, the effectiveness of these reagents alone on cell viability is moderate. Here, the addition of salidroside attenuated oxidative damage of sheep RBCs prior to and post cryostorage. The supplementation of salidroside to the cryopreservation media containing 10% glycerol improved RBC survival by approximately 61.1±4.8% vs 37.9±4.6%. A smaller effect was seen in RBCs cryopreserved in 300 mM trehalose where the addition of salidroside improved survival by 7.6±0.3%. Furthermore, the addition of salidroside to cold storage solution demonstrated a significant reduction of haemolysis after 4 days for RBCs loaded with either glycerol or trehalose, compared to cells incubated without salidroside. RBCs survival was 2-fold greater following freezing in trehalose, compared with glycerol. After 10 days, salidroside enabled a lower haemolysis of 16.7±1.3% compared to 29.0±8.4% for cells incubated without salidroside. However, salidroside had no effect on RBCs which had been frozen in glycerol as the resulting haemolysis rate by day 10 was approximately 60%. Salidroside increased glutathione reductase activity and decreased lactate dehydrogenase activity. Furthermore, it led to reduced carbonylation of proteins in both glycerol and trehalose loaded cells. Finally, no effect on lipid peroxidation was found in the glycerol loaded RBCs although this was reduced in RBCs loaded with trehalose and salidroside. The present findings confirm the potential use of salidroside as a novel protective agent in cryopreservation and refrigerated storage of sheep RBCs.King AbdulAziz City for Science and Technology (KACST), NASAThis is the final version of the article. It first appeared from the Public Library of Science via https://doi.org/10.1371/journal.pone.016274

Carcass yield and characteristics of Karadi lambs as affected by dietary supplement of rumen undegradable nitrogen fed with Nigella sativa

The objective of this work was to investigate the effect of two levels of rumen undegradable nitrogen (7 and 10 g UDN/kg DM) fed with two levels of Nigella sativa (0 and 7.5 g NS/ kg DM) supplementation to rations of karadi lambs on carcass characteristics, using 2 x 2 factorial experiment. Sixteen individual Karadi male lambs were used (four lambs for each treatment). They were weighing approximately 34 kg live weight and 7 months old. The diets were formulated to be given a 40% NaOH-treated barley straw DM to 60% concentrates DM. At the end of feeding trial the lambs were slaughtered after over night with feeding draw. Differences in daily nutrients intake among treatments were not statistically significantly. The UDN and total N intake were followed the intended treatments composition (P < 0.01). Live weight gain was not significantly affected by levels of UDN and NS supplementation. Slaughter body weight, hot and cold carcass weights and killing out proportion were not significantly affected by both NS supplementation and levels of UDN. Moreover, no differences in leg cut tissue (lean, subcutaneous fat: intramuscular fat and bone) among treatments. The main wholesale cuts weights were not significantly different among treatments. The differences in fat-tail weights between the NS and UDN treatments were not statistically significant.Key words: Lambs, rumen undegredable nitrogen, Nigella sativa, carcass characteristic

Off-Diagonal Deformations of Kerr Metrics and Black Ellipsoids in Heterotic Supergravity

Geometric methods for constructing exact solutions of motion equations with first order $\alpha ^{\prime}$ corrections to the heterotic supergravity action implying a non-trivial Yang-Mills sector and six dimensional, 6-d, almost-K\"ahler internal spaces are studied. In 10-d spacetimes, general parametrizations for generic off-diagonal metrics, nonlinear and linear connections and matter sources, when the equations of motion decouple in very general forms are considered. This allows us to construct a variety of exact solutions when the coefficients of fundamental geometric/physical objects depend on all higher dimensional spacetime coordinates via corresponding classes of generating and integration functions, generalized effective sources and integration constants. Such generalized solutions are determined by generic off-diagonal metrics and nonlinear and/or linear connections. In particular, as configurations which are warped/compactified to lower dimensions and for Levi-Civita connections. The corresponding metrics can have (non) Killing and/or Lie algebra symmetries and/or describe (1+2)-d and/or (1+3)-d domain wall configurations, with possible warping nearly almost-K\"ahler manifolds, with gravitational and gauge instantons for nonlinear vacuum configurations and effective polarizations of cosmological and interaction constants encoding string gravity effects. A series of examples of exact solutions describing generic off-diagonal supergravity modifications to black hole/ ellipsoid and solitonic configurations are provided and analyzed. We prove that it is possible to reproduce the Kerr and other type black solutions in general relativity (with certain types of string corrections) in 4-d and to generalize the solutions to non-vacuum configurations in (super) gravity/ string theories.Comment: latex2e, 44 pages with table of content, v2 accepted to EJPC with minor typos modifications requested by editor and referee and up-dated reference

Rare parasitic copepods (Siphonostomatoida: Lernanthropidae) from Egyptian Red Sea fishes

© The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The attached file is the published version of the article

Reliability analysis of moment redistribution in reinforced concrete beams

Design codes allow a limited amount of moment redistribution in continuous reinforced concrete beams and often make use of lower bound values in the procedure for estimating the moment redistribution factors. Here, based on the concept of demand and capacity rotation, and by means of Monte Carlo simulation, a probabilistic model is derived for the evaluation of moment redistribution factors. Results show that in all considered cases, the evaluated mean and nominal values of moment redistribution factor are greater than the values provided by the ACI code. On the other hand, the 5th percentile value of moment redistribution factor could be lower than those specified by the code. Although the reduction of strength limit state reliability index attributable to uncertainty in moment redistribution factors is not large, it is comparable to the reduction in reliability index resulting from increasing the ratio of live to dead load

Anti-Inflammatory Activity of Crude Saponin Extracts from Five Nigerian Medicinal Plants

Crude saponin extracts of five medicinal plants used in the treatment of inflammatory diseases like rheumatoid arthritis, gout and haemorrhoids were screened for anti-inflammatory activity using carrageenan-induced rat paw oedema test. These plants were the whole plant of Schwenkia americana Linn (WSA), the rhizomes of Asparagus africanus Lam (RAA), the leaves of Dichrostachys cinerea Linn (LDC), the stem bark of Ficus iteophylla Miq (BFI) and the leaves of Indigofera pulchra Willd (LIP). A modify traditional method of crude saponins extraction was used to give the following percentage yields: WSA-2.74%, RAA-3.59%, LDC-1.62%, BFI-0.81% and LIP-1.57% respectively. Thin-layer chromatography was used to identify the type of saponins present in the extracts. The acute toxicity study of the crude saponin extracts in mice gave the following intraperitoneal LD50: WSA-471.2mg/kg, RAA- 1264.9mg/kg, LDC-1264.9mg/kg, BFI-118.3mg/kg and LIP-1264.9mg/kg respectively.  The antiinflammatory study of the extracts showed statistically significant (P<0.05) decreases in the rat paw-oedema as compared to the control. The percentage inhibitions of the extracts after four hours were as follow: WSA-61%, RAA-55%, LDC-72%, BFI-66% and LIP-40% respectively. These values were found to be comparable to that of ketoprofen-63%. The study showed that the antiinflammatory properties attributable to these plants may be due to their saponins contents.Keywords: - Asparagus africanus, Dichrostachys cinerea, Ficus iteophylla, Indigofera pulchra, Schwenkia americana, Saponin,Anti-inflammatory activity, Carrageenan, TLC

Seismic Performance of Exposed Column-Base Plate Connections with Ductile Anchor Rods

This paper presents full-scale experiments and computational analyses on exposed column-base plate connections with ductile anchors. The aim is to examine the seismic performance of these connections for their prospective use as weak bases, wherein steel moment frames are designed to concentrate inelastic rotations in the base connections rather than in the connected columns. The connections feature upset thread anchor rods in which the threads are milled to a smooth shank, providing a designated stretch length over which inelastic deformations may be concentrated. The shank is frictionally isolated from the footing using polyethylene tape. The four full-scale experiments investigate the effects of axial force, rod diameter, and rod material grade. The test specimens withstand (without anchor rod failure) the application of two Applied Technology Council-the Joint Venture partners of the Structural Engineers Association of California, the Applied Technology Council, and the Consortium of Universities for Research in Earthquake Engineering (ATC-SAC) protocols applied consecutively (each to drift amplitudes of 5%), followed by additional cycles to 6.5% drift amplitude. Complementary line element-based and continuum finite-element simulations are conducted to examine to what extent the experimentally observed response may be generalized to untested configurations. Implications for design are summarized, along with the limitations of the study

National Human Resource Policy Formulation and Implementation: A Fiduciary Trust and a Duty on Governments

The consequential effect of national policy formulation and implementation regarding human resource management (HRM) of private and public institutions have been presented in this research paper by analyzing samples taken from national policies on employment and environment in the context of Republic of Maldives. The analysis has been presented basically through two perspectives. From first perspective, the effect of national policies on HRM has been viewed through the external factors affecting HRM, rather than the internal factors of HRM. On the contrary, the second perspective involves the effects of national policies on HRM internally within the legislations related to employment as well as externally through environmental factors. The overall focus of the above said two perspectives is to analyze how national policy-making shortcomings related to human resource management (HRM) within any given country can be disruptive for HRM endeavours of not only private entities but public entities as well, especially when such policies are not in line with the respective HRM needs of such institutions. The findings would demonstrate the outcomes of shortcomings by governments to properly administer and implement national policies regarding human resource and how this could totally jeopardize the well-established human resource management procedures and endeavors of private and public institutions. The underlying reason for the effect of public policy on HRM of institutions has been identified and analyzed as the existence of the fiduciary relationship between governments and citizens whereby the institutions managed by the citizens are legally bound by any defective public policies