QSAR analysis of salicylamide isosteres with the use of quantum chemical molecular descriptors

Quantitative relationships between the molecular structure and the biological activity of 49 isosteric salicylamide derivatives as potential antituberculotics with a new mechanism of action against three Mycobacterial strains were investigated. The molecular structures were represented by quantum chemical B3LYP/6-31G* based molecular descriptors. A resulting set of 220 molecular descriptors, including especially electronic properties, was statistically analyzed using multiple linear regression, resulting in acceptable and robust QSAR models. The best QSAR model was found for Mycobacterium tuberculosis (r(2) = 0.92; q(2) = 0.89), and somewhat less good QSAR models were found for Mycobacterium avium (r(2) = 0.84; q(2) = 0.78) and Mycobacterium kansasii (r(2) = 0.80; q(2) = 0.56). All QSAR models were cross-validated using the leave-10-out procedure

The ASEAN community-based tourism standards: looking beyond certification

This paper reports findings from an opportunity study on the appropriateness of implementing community-based tourism standards (CBTS) certification through the Association of Southeast Asian Nations (ASEAN) criteria, as a way to improve sustainable tourism provision in the region. Framed by critical reflections on community-based tourism (CBT) literature and existing sustainable tourism standards (STS) practices, qualitative research consisting of interviews with six key industry experts provided core insights into a number of CBTS’ implementation challenges. Findings indicate the main hindering factors for the implementation of CBTS to be the lack of adequate governance, limited funding and insufficient community capacity. The study concluded that although at the moment the full implementation of CBTS as a certification programme would be premature, ASEAN-CBTS’ criteria are a useful benchmarking and strategic planning tool for local communities, which would eventually lead to improved CBT benefits, standards and performance in the region. At the same time, this paper argues that aspects including CBT competitiveness and service delivery need to be tackled first to create fruitful grounding for CBT certification

Structure of S. aureus HPPK and discovery of a new inhibitor

The first structural and biophysical data on the folate pathway enzyme and drug target, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), from the pathogenic bacterium Staphylococcus aureus is presented. HPPK is the second essential enzyme in the folate biosynthesis pathway, responsible for catalysing pyrophosphoryl transfer from cofactor (ATP) to the substrate (6-hydroxymethyl- 7,8-dihydropterin, HMDP). In-silico screening led to the discovery of a substrate competitive inhibitor, San1, which was subsequently co-crystallised with HPPK. A 1.65 Å resolution x-ray structure showed this to bind at the pterin site sharing many of the key intermolecular interactions of the substrate. ITC and SPR measurements yielded an equilibrium binding constant, Kd, of ~13 μM for San1. An IC50 of ~12 μM was determined by means of a new convenient tri-enzyme-coupled spectrophotometric assay. ITC and SPR further showed that the San1 inhibitor has no requirement for magnesium or ATP cofactor for competitive binding to the substrate site. According to 15N heteronuclear NMR measurements, the fast motion of the pterin loop (L2) is partially dampened in the ternary complex between SaHPPK, HMDP and , -methylene adenosine 5-triphosphate (AMPCPP), but the ATP loop (L3) remains mobile on the μs timescale. In contrast, for the SaHPPK/San1/AMPCPP ternary complex, loop L2 becomes rigid on the fast timescale and loop L3 becomes more ordered which are supported by a large entropic penalty associated with San1 binding as revealed by ITC. Backbone assignments and chemical shift perturbations implicate the sulphur in San1 as a likely important loop L2/L3 stabilizing mediato

Wound-on-tension for two drum winders

The two drum winder remains to be a high productivity winder for rewinding some paper and nonwoven webs at very high speeds. Winding models of varied capabilities exist for center winders, center winders with rider rollers, and surface winders. Winding models for two drum winders however are still in the introductory stages. Two drum winders are somewhat more complex than other winders due to the number of rollers, driven and undriven, which impinge the surface of the winding roll. The objectives of this paper are to show the influence of various winder operating parameters and thread path on the wound-on-tension in the outer layer (WOT).Mechanical and Aerospace Engineerin

Toward an integrative understanding of social behavior: new models and new opportunities.

Social interactions among conspecifics are a fundamental and adaptively significant component of the biology of numerous species. Such interactions give rise to group living as well as many of the complex forms of cooperation and conflict that occur within animal groups. Although previous conceptual models have focused on the ecological causes and fitness consequences of variation in social interactions, recent developments in endocrinology, neuroscience, and molecular genetics offer exciting opportunities to develop more integrated research programs that will facilitate new insights into the physiological causes and consequences of social variation. Here, we propose an integrative framework of social behavior that emphasizes relationships between ultimate-level function and proximate-level mechanism, thereby providing a foundation for exploring the full diversity of factors that underlie variation in social interactions, and ultimately sociality. In addition to identifying new model systems for the study of human psychopathologies, this framework provides a mechanistic basis for predicting how social behavior will change in response to environmental variation. We argue that the study of non-model organisms is essential for implementing this integrative model of social behavior because such species can be studied simultaneously in the lab and field, thereby allowing integration of rigorously controlled experimental manipulations with detailed observations of the ecological contexts in which interactions among conspecifics occur

Bovine chromosome 20: milk production QTL and candidate gene analysis in the Italian Holstein-Friesian breed

Bovine chromosome 20 (BTA20) was studied to identify QTL for milk yield and protein percentage in the Italian Holstein-Friesian breed using a selective milk DNA pooling strategy in a daughter design with sire haplotype analysis. Several QTL were identified. The effect of the known GHR F279Y and PRLR S18N mutations were in for the most part confirmed. However, it was also shown that these markers cannot explain all significant effects observed on BTA20 for the investigated traits

Temperature measurement and calibration in small punch creep testing machines and equipment

Serious lifetime estimation of machinery working in the power industry is conditioned by knowledge of an actual state of used construction materials. Determination of degradation degree by detection of mechanical properties of materials at machine parts used in operating conditions without the necessity of stopping operation of the apparatus and machine component disintegration in the past has led to the development of miniaturized test specimens associated with the emergence of special test procedures and methods. One of these methods is the small punch test (SPT) performed at room, low or elevated temperatures. Just testing temperature is one of the most important test parameters. The accuracy of measurement of this variable is a basic condition of repeatability, compatibility and comparability of the measured testing results. Very small specimen size, the way how it is stored in the heating system, the prescribed tolerance of measurement accuracy determines the way of measuring and controlling its temperature. One possible way of measuring specimen temperature is using a thermocouple directly touching its surface in the test process. However, this method is influenced by the unequal heat conduction between the specimen and the punch with the push pin in an upper direction and the cartridge sitting in the rod within the lower direction. How to determine the real specimen temperature in control systems of SPUTT500 testing machine is the subject of this paper