Evaluation of QSAR and ligand enzyme docking for the identification of ABCB1 substrates

P-glycoprotein (P-gp) is an efflux pump that belongs to ATP-binding cassette (ABC) transporter family embedded in the membrane bilayer. P-gp is a polyspecific protein that has demonstrated its function as a transporter of hydrophobic drugs as well as transporting lipids, steroids and metabolic products. Its role in multidrug resistance (MDR) and pharmacokinetic profile of clinically important drug molecules has been widely recognised. In this study, QSAR and enzyme-ligand docking methods were explored in order to classify substrates and non-substrates of P-glycoprotein. A set of 123 compounds designated as substrates (54) or non-substrates (69) by Matsson et al., 2009 was used for the investigation. For QSAR studies, molecular descriptors were calculated using ACD labs/LogD Suite and MOE (CCG Inc.). P-glycoprotein structures available in the Protein data bank were used for docking studies and determination of binding scores using MOE software. Binding sites were defined using co-crystallised ligand structures. Three classification algorithms which included classification and regression trees, boosted trees and support vector machine were examined. Models were developed using a training set of 98 compounds and were validated using the remaining compounds as the external test set. A model generated using BT was identified as the best of three models, with a prediction accuracy of 88%, Mathews correlation coefficient of 0.77 and Youden’s J index of 0.80 for the test set. Inclusion of various docking scores for different binding sites improved the models only marginally

Seed yam production at GoSeed

IITA GoSeed is a unit of the IITA Business Incubation Platform (BIP) and registered as a Limited Liability Company. The company saddled with the responsibility for the commercial promotion of the early generation seeds of the improved crop varieties generated by IITA and other CGIAR Centers across the glob

The impact of active workstations on workplace productivity and performance: a systematic review

Active workstations have been recommended for reducing sedentary behavior in the workplace. It is important to understand if the use of these workstations has an impact on worker productivity. The aim of this systematic review was to examine the effect of active workstations on workplace productivity and performance. A total of 3303 articles were initially identified by a systematic search and seven articles met eligibility criteria for inclusion. A quality appraisal was conducted to assess risk of bias, confounding, internal and external validity, and reporting. Most of the studies reported cognitive performance as opposed to productivity. Five studies assessed cognitive performance during use of an active workstation, usually in a single session. Sit-stand desks had no detrimental effect on performance, however, some studies with treadmill and cycling workstations identified potential decreases in performance. Many of the studies lacked the power required to achieve statistical significance. Three studies assessed workplace productivity after prolonged use of an active workstation for between 12 and 52 weeks. These studies reported no significant effect on productivity. Active workstations do not appear to decrease workplace performance

The Role of Central Banks and Competition Policies in the Rescue and Recapitalisation of Financial Institutions During (and in the Aftermath of) the Financial Crisis

Recent years have witnessed a change in focus from considerations of factors which could impede competition, for example over-regulation, to the need to strike a balance between over-regulation and insufficient regulation – in order to provide the right level of safety for consumers (such that they are protected from risky investments). A driving force behind the need for deregulation over the past two decades has been the objective and desire to foster competition. Re-regulation thereafter assumed centre stage in some jurisdictions in response to the need to manage cross sector services' risks more efficiently. Rescue cases involving guarantees (contrasted with restructuring cases) during the recent Financial Crisis, have illustrated the prominent position which the goal of promoting financial stability has assumed over that of the prevention or limitation of possible distortions of competition which may arise when granting State aid. The importance attached to maintaining and promoting financial stability - as well as the need to facilitate rescue and restructuring measures aimed at preventing systemically relevant financial institutions from failure, demonstrate how far authorities are willing to overlook certain competition policies. However increased government and central bank intervention also simultaneously trigger the usual concerns – which include moral hazard and the danger of serving as long term substitutes for market discipline. An interesting observation derives from the relationship between State aid grants, competition, and the potential to induce higher risk taking levels. Whilst the need to promote and maintain financial stability is paramount, safeguards need to be implemented and enforced to ensure that measures geared towards the aim of sustaining system stability (measures such as lender of last resort arrangements and State rescues) do not unduly distort competition as well as induce higher risk taking levels. This paper will draw attention to safeguards which have been provided by the Commission where approval is considered for the grant of State aid to financial institutions whose problems are attributable to inefficiencies, poor asset liability management or risky strategies. Whether the distinction drawn by the Commission – with regards to the preferential grant of recapitalisation packages to fundamentally sound banks (which require less restructuring measures)is justified, will also be considered. How far central banks and governments should intervene and how far distortions of competition should be permitted ultimately depends on how systemically relevant a financial institution is

Female infertility and patriarchy: A reflection on medical science and biblical position

Marriage traditionally has been based upon gender relations that prescribed authority of husband over wives. The rituals of throwing rice to symbolize fertility and the woman's obligation to bear and raise children also illustrate normative gender relations. In other words, in the home, infertile women feel and bear most the consequences of masculine power and privileges. In the main, the paper discussed the medical science aspects of female infertility which explain that both sexes are liable to infertility. This could be as a result of several factors like damage to fallopian tube, hormonal cause, age, smoking cigarettes, sexually transmitted infections, overweight and the likes. However, the study showed that infertility hinges on patriarchy in both the bible and Yoruba culture which was cited as example. In both cases, childlessness is viewed as female problems and the depression experience by such women areequivalent to suffering from terminal illness. The paper therefore argues for the exercising of “equal partner” model where the traditional marriage contract of shifting blame of infertility on women is completely disrupted. In other words, neither partner is more likely to perform provider roles. In practice, this might mean intentional sharing of blame, ridicule, abuse, segregation and violence associated with infertility.Keywords: Infertility, Patriarchy, Women, Medical Science, Violence

Effect of genotypes on soyabean seed quality development under West African Rainfed conditions

Effect of genotypes on soyabean seed quality development was monitored under rainfed conditions at Abeokuta between July and November, 1997. A consistent increase in rate of normal germination and seedling emergence occurred among early harvests. Greatest germination rate was detected in seeds harvested around physiological (functional) and harvest (full) maturity stages. Seedling emergence was significantly influenced by seed harvest date in all soyabean entries. Germination and emergence increased as soyaben seed development progressed and was greatest for seeds harvested between R7 and R8 in all soyabean cultivars. Enforced desiccation to 10% moisture content promoted germination of seeds harvested around physiological maturity stages. The onset of desiccation tolerance fell between physiological and harvest maturity stages in all the six soyabean cultivars. The rapid decline in seedling emergence of artifically dried seeds at 50d after mtff as against 60d after mtff for normal laboratory gemination indicated that seedlots of initial good germination may not necessarily produce high seedling emergence under good seeding condition due to differences in genotypes. Association of seed characters such as seed size, seed weight, germinability and emergence ability is essential in soyabean breeding to facilitate selection of genotypes with good seed quality, thereby reducing elaborate storage and screening methods

Beyond locutionary denotations: exploring trust between practitioners and policy

This study reports the findings of a research on the trust relationship between practitioners in the Skills for Life (SfL) area and the policy that informs their practice. The exploration of this relationship was premised on an extended notion of trust relationship which draws from the Speech Act theory of Austin (1962; Searle 1969; Kissine 2008), leading to the claim that the existence of different layers of imports in textual analysis makes it possible for a trust relationship to exist between the human/physical and the non human/non physical. The study found that the majority of practitioners in the SfL field trust policy to deliver its inherent policy only to a limited extent. Amongst others, the study identified the impact of the perlocutionary import of policy text on practitioners as a viable reason for this limited level of trust. Such perlocutionary imports, it also found, have adverse impact on practitioners who are considered to have drawn from previous experience to mediate the import of contemporary policies

In vitro characterization of cadmium and zinc uptake via the gastrointestinal tract of rainbow trout (Oncorhynchus mykiss): interactive effects and the influence of calcium

An in vitro gut sac technique was employed to study whether Cd and Zn uptake mechanisms in the gastro-intestinal tract of the rainbow trout are similar to those at the gills, where both metals are taken up via the Ca transport pathway. Metal accumulation in surface mucus, in the mucosal epithelium, and transport into the blood space were assayed using radiolabelled Cd or Zn concentrations of 50 mol L−1 in the luminal (internal) saline. Elevated luminal Ca (10 or 100 mmol L−1 versus 1 mmol L−1) reduced Cd uptake into all three phases by approximately 60% in the stomach, but had no effect in the anterior, mid, or posterior intestine. This finding is in accordance with recent in vivo evidence that Ca is taken up mainly via the stomach, and that high [Ca] diets inhibit Cd accumulation from the food specifically in this section of the tract. In contrast, 10 mmol L−1 luminal Ca had no effect on Zn transport in any section, whereas 100 mmol L−1 Ca stimulated Zn uptake, by approximately threefold, into all three phases in the stomach only. There was no influence of elevated luminal Zn (10 mmol L−1) on Cd uptake in the stomach or anterior intestine, or of high Cd (10 mmol L−1) on Zn uptake in these sections. However, high [Zn] stimulated Cd transport into the blood space but inhibited accumulation in the mucosal epithelium and/or mucus-binding in the mid and posterior intestine, whereas high [Cd] exerted a reciprocal effect in the mid-intestine only. We conclude that Cd uptake occurs via an important Ca-sensitive mechanism in the stomach which is different from that at the gills, while Cd transport mechanisms in the intestine are not directly Ca-sensitive. Zn uptake does not appear to involve Ca uptake pathways, in contrast to the gills. These results are discussed in the context of other possible Cd and Zn transport pathways, and the emerging role of the stomach as an organ of divalent metal uptake.Natural Sciences and Engineering Research Council of Canada CRD Program, the International Lead Zinc Research Organization, the International Zinc Association, the Nickel Producers Environmental Research Association, the International Copper Association, the Copper Development Association, Teck-Cominco, Xstrata (Noranda-Falconbridge), and Inc

Frequency and voltage control schemes for three-phase grid-forming inverters

Grid-forming inverters play an important role in supporting power systems with low rotational inertia. Their frequency and voltage control policies must guarantee a synchronised operation, accurate power sharing amongst inverters, and a good transient response. Simultaneously achieving the latter two requirements is in general a non-trivial problem and existing schemes in the literature often focus on one of these two aspects. In this paper, we propose a simple frequency controller that uses the inverter output current as feedback to adapt its frequency, and also propose controllers for the regulation of the DC and AC voltages. We show that the proposed control architectures achieve both power sharing without a communication link, and desirable passivity properties that can enhance the dynamic performance. Closed loop stability of the grid-forming inverter with a dynamic load is also proven and simulations on advanced models are carried out to validate the results.ERC starting grant 67977