The Effect of Different Chickpea Tissue Structures on Glycaemic Response and Gastrointestinal Digestion

Imperial Users onl

Function of Germline-specific Ribonucleoprotein granules-from germline to cancer

Male germ cells undergo complex differentiation from embryonic germ cells, through postnatal spermatogenesis to highly specialized spermatozoa. Precise regulation of gene expression is critical for meiosis and morphological changes in differentiating male germ cells. Large ribonucleoprotein (RNP) granules and germ granules, appear in the cytoplasm of germ cells to support the high requirement for posttranscriptional gene regulation. In this study, we elucidated the functions of two types of germ granules, the intermitochondrial cement (IMC) and chromatoid body (CB). We studied the protein composition of the IMC and verified its central role in the production of PIWI-interacting RNAs (piRNAs). We also identified two new IMC components, EXD1 and EXD2, and characterized their association with germ granules and the piRNA biogenesis machinery. In addition, we characterized the collaboration between EXD1 and the Tudor domain-containing protein TDRD12 in piRNA biogenesis in embryogenic testis and also revealed the essential role of this collaboration in male fertility. We further demonstrated that the functions associated with germ granules are utilized in cancer cells, as the germ granule protein DDX4 forms cytoplasmic granules in many tumor types. These DDX4 complexes contained various RNA-binding proteins, including splicing regulators and known germ granule proteins. Deletion of DDX4 in cancer cells led to transcriptome imbalance and impaired splicing landscape of genes that contribute to cancer growth and invasiveness, and consequently delayed tumor growth. Moreover, the presence of DDX4 granules in human cancer samples was shown to correlate with a poor prognosis for the patient. The results of this study highlight the importance of germ granules in the piRNA pathway during spermatogenesis and provide evidence for the novel role of germ granule components in transcriptome control in cancer cells that promote malignant properties

The Global Rise of Social Media: A Study of how Social Networking Sites influence Diffusion of Innovation

This paper explores the diffusion of innovation and behaviour of adopters towards the growth of social networks while understanding the role of innovative firms. The process by which innovation diffuses from its invention point to its adopter or end users can be defined as Diffusion of innovation (Robertson, 1967). The rise or growth of digital media has brought about intense competition for competitive firms in their quest for audience revenues while harnessing the potential of the internet through incremental and radical innovations. The growing literature on the contribution of innovative firms and new product development makes it unblemished that evidence about consumer behaviour on social networking platform to product innovation is a perilous input. Drawing on the present studies that explores consumer behaviour in light of motivational factors, home communication technology infrastructure, existing media use level and demographic attributes, research with digital media firms is drawn on to explore the overlapping twin logics of diffusion of innovation and behaviour of innovative firms towards product development. Over the last 60 years, researchers have studied the spread of new ideas and in thus explaining the factors in innovation processes and activities. Also, theory on the diffusion of innovations has been placed under scrutiny based on performance outcomes, adoption and diffusion patterns. The postulation underpinning this research is that, due to the recent global rise of digital media, it is however not arbitrary to take on that we might expect to see the diversity of attributes being patterned into distinct configurations. Drawing upon recent experience with internet start-ups and established internet social networking firms, the paper analyses the consumer behavioural constraints on the rapid diffusion of new innovations. Having examined processes and practices of product innovation in digital media, the article turns to some of the critical issues around firms and industry conventions towards how consumers adopt innovative product. This research stands to present a combinative methodology to the research of consumer behaviour founded on the adoption hypothesis of the innovation rather than the effects that it portrays. The task for innovative firms that this article intends to address is the ability to manage and balance the diffusion pattern of innovation, the elimination of waste of time when considering market segmentation of new products and the cultural imbalance that disrupts adoption of innovation while understanding how consumers of social media reacts to diffusion of innovation. This complex sorting of the understanding displays a stronger assessment of connection concerns between innovative firms, its consumers and the innovation

A two-dimensional simulation of atomic layer deposition process on substrate trenches

Abstract: In the cause of the increasing need for miniaturisation of devices, a more sophisticated nano-manufacturing technique of component was rummage around for, which has led to the adoption of atomic layer deposition (ALD) technique due to its competency of accomplishing superb uniformity, conformality, pinhole-free and ultra-thinness. In this dissertation, the ALD process within the cavity and surface of substrate trench was studied numerically with the intent to optimise the deposition process while formulating suitable ALD recipe. In the cause of optimising the process of an atomic layer deposition (ALD) for trenched substrate, a numerical model was presented, and two-dimensional simulations of the ALD process of substrate trenches in an arbitrary reactor were performed. Here, the deposition of aluminium oxide (Al2O3) was illustrated with trimethylaluminum (TMA) and ozone (O3) precursors as Aluminum (Al) and oxygen (O2) sources respectively while inert argon was used as purging gas in an arbitrary reactor. The flow is similar to a typical top-to-bottom type ALD reactor. The gases are assumed to enter at an inlet temperature of 150°C while the substrate, reactor walls and outlet temperature of 250°C is used. The TMA and O3 precursors are both pulsed separately, according to the sequence, into the reactor at 0.085 m/s for 0.2 and 1 second, respectively. While inert-purge gas (Ar) is used to purge the reactor domain at 0.17 m/s for 5 seconds between the pulse and exposure times. For this work the ALD sequence follows in a pulse-exposure-purge-exposure-pulse-exposure-purge manner to form a complete ALD cycle. After the reactive and inert-gases have flown and penetrated into the trenched substrate the excess and by-products are then exhausted past the edges of the trenched substrate towards the outlet of the reactor. The reactor flow domain is meshed into 67023 nodes. The ALD process within the arbitrary reactor is investigated by numerical simulating the reactor using computational fluid dynamics (CFD) within commercial software packages ANSYS FLUENT and CHEMKINPRO. This transient process is implemented by the coupled algorithm approach...M.Ing. (Mechanical Engineering

Isolation and Characterization of the Chemical Structure of Compound in Methanol Extract of Cochlospermum planchonii Hook.F (Cochlospermaceae)

Cochlospermum planchonii Hook.F (Cochlospermaceae) leaf is used by the Hausa/Fulani in the Northern Nigeria for the management of pain, inflammation and related diseases yet, its chemistry is poorly known. The present study is to isolate and characterize the structure (s) of compound (s) in methanol extract of Cochlospermum planchonii. Fractions of methanol samples were fractionated using TLC method into 80 fractions. Based on TLC-DPPH assay, similar fractions were pooled together by Preparative TLC. Aromatic singlet proton at δ 8.03 in the 'H NMR spectrum indicates that the compound might be an isoflavone. The final structure of the compound was confirmed by comparing the NMR data of the compound with the literature data. The NMR spectrum was obtained in methanol- δ4 and the literature values were obtained in DMSO. Keywords: Cochlospermum planchonii, Isolation, Characterization, Singlet proto

Use of statins and the development of incident diabetes mellitus : a retrospective cohort study

textStatins are pharmaceutical agents used in lowering blood cholesterols levels. Several landmark statin trials have demonstrated the beneficial effects of statins in both primary and secondary prevention of cardiovascular disease. Although statins are generally safe and well tolerated, several studies have suggested that statins are associated with a moderate increase in risk of new-onset diabetes. These observations prompted the FDA to revise statin labels to now include a warning of an increased risk of incident diabetes mellitus as a result of increases in glycosylated hemoglobin (A1C) and fasting plasma glucose (FPG). However, few studies have used US-based data to investigate this statin-associated increased risk of diabetes. Thus, the purpose of this study was to evaluate whether statin use was associated with an increased risk of new-onset diabetes. In addition, this study evaluated whether diabetes risk was increased when patients received intensive statin doses. This study was a retrospective cohort analysis that utilized data from the Thomson Reuters MarketScan® Commercial Claims Database for the period of 2003 - 2004. The study population included new statin users who were aged 20 - 63 years at index and who do not have a history of diabetes. Among the study population (N=116,224), 6.5% (or N=7,593) had incident diabetes. Compared to no statin use, statin use was significantly associated with increased risk of incident diabetes (HR=2.752; 99% C.I.=2.535 - 2.987; p<0.0001). In addition, each statin type (i.e., atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin) was associated with about a two-fold increase in risk of diabetes. Diabetes risk was highest among lovastatin users and lowest among rosuvastatin users. Furthermore, diabetes risk was higher among intensive-dose statin users compared to moderate-dose statin users (HR=1.540; 99% C.I.=1.393 – 1.704; p<0.0001). Because of the proven benefits of statins in both primary and secondary prevention of cardiovascular disease, and because the potential for diabetogenicity differs among statins, health care professionals should individualize statin therapy by identifying patients who would benefit from less diabetogenic statin types. This could help optimize treatment by providing the highest benefit achievable while reducing the number of patients developing diabetes under statin therapy.Pharmaceutical Science

Corporate Relationship Marketing in Developing Economies: Sustainability Tonic for Nigerian Banks

Banking is fundamentally characterized by systemic dynamism and industrialvolatility. Forward moving practitioners, therefore, are not relenting in theirresolve to be more sensitive, appreciative and proactive in the market place.This essentially challenges them to strategically leverage on contemporaryresearch outputs to blaze the trail in service innovation and overallcorporate profitability redefinition. This study critically showcases corporaterelationship marketing (CRM) as multi-auspicious and efficacious newsensation to drive Nigerian banks to topmost heights with utmostsustainability. This competition – friendly vantage pathway is conceptuallyprojected in this work as the relationship marketing – performance causality(REMPEC) diagnostic connect. Key Words: Bank profitability, Institutional sustainability, Nigerianeconomy, Relationship Marketin

Quasi-Newton Embedded Augmented Lagrangian Algorithm for Discretized Optimal Proportional Control Problems

In developing a robust algorithm for solving a class of optimal  control problems in which the control effort  is proportional to the state of the dynamic system, a typical model was studied which generates a constant feedback gain , an estimate of the Riccati for large values of the final time. Involving the third Simpson’s Rule, a discretized unconstrained non-linear problem via the Augmented Lagrangian Method was obtained. This problem was consequently subjected to the Broydon-Fletcher-Goldberg-Shannon(BFGS) based  on Quasi-Newton algorithm. The positive- definiteness of the estimated quadratic control operator was analyzed to guarantee its invertibility in the BFGS. Numerical examples were considered, tested and the results responded much more favourably to the analytical solution with linear convergence. Keywords: Proportional control, feedback gain, Augmented Lagrangian Method, Discretization, BFGS , Simpson’s Rule and Quasi-Newton Metho

Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.csbj.2022.12.040.Acknowledgment We would like to thank the Center for High-Performance Computing, Cape Town, South Africa for providing computational resources and Dr Nabil Hajji for his kind contributions in enhancing the staining protocol.The use of computer-aided methods have continued to propel accelerated drug discovery across various disease models, interestingly allowing the specific inhibition of pathogenic targets. Chloride Intracellular Channel Protein 4 (CLIC4) is a novel class of intracellular ion channel highly implicated in tumor and vascular biology. It regulates cell proliferation, apoptosis and angiogenesis; and is involved in multiple pathologic signaling pathways. Absence of specific inhibitors however impedes its advancement to translational research. Here, we integrate structural bioinformatics and experimental research approaches for the discovery and validation of small-molecule inhibitors of CLIC4. High-affinity allosteric binders were identified from a library of 1615 Food and Drug Administration (FDA)-approved drugs via a high-performance computing-powered blind-docking approach, resulting in the selection of amphotericin B and rapamycin. NMR assays confirmed the binding and conformational disruptive effects of both drugs while they also reversed stress-induced membrane translocation of CLIC4 and inhibited endothelial cell migration. Structural and dynamics simulation studies further revealed that the inhibitory mechanisms of these compounds were hinged on the allosteric modulation of the catalytic glutathione (GSH)-like site loop and the extended catalytic β loop which may elicit interference with the catalytic activities of CLIC4. Structurebased insights from this study provide the basis for the selective targeting of CLIC4 to treat the associated pathologies

On the Discretized Algorithm for Optimal Proportional Control Problems Constrained by Delay Differential Equation

This paper seeks to develop an algorithm for solving directly an optimal control problem whose solution is close to that of analytical solution. An optimal control problem with delay on the state variable was studied with the assumption that the control effort is proportional to the state of the dynamical system with a constant feedback gain, an estimate of the Riccati for large values of the final time. The performance index and delay constraint were discretized to transform the control problem into a large-scale nonlinear programming (NLP) problem using the augmented lagrangian method. The delay terms were consistently discretized over the entire delay interval to allow for its piecewise continuity at each grid point. The real, symmetric and positive-definite properties of the constructed control operator of the formulated unconstrained NLP were analyzed to guarantee its invertibility in the Broydon-Fletcher-Goldberg-Shanno (BFGS) based on Quasi-Newton algorithm. Numerical example was considered, tested and the results responded much more favourably to the analytical solution with linear convergence. Keywords: Simpson’s discretization method, proportional control constant, augmented Lagrangian, Quasi –Newton algorithm, BFGS update formula, delays on state variable, linear convergence