Search results for: B. Holloway

Authors: Syed Asif Hassan, Tabrej Khan

Abstract:

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: Lien T. H. Tran, David A. Holloway

Abstract:

Corporate governance practices have changed significantly across the world in the past three decades. Spectacular corporate failures during this period have acted as a catalyst for the development of codes and guidelines that have resulted in the global acceptance of a ‘best practice’ model. This study assesses the relevance of such a ‘one size fits all model’ for the developing nation state of Vietnam. The findings of this analytical paper is that there are three key elements (government, international institutions and the nature of business) that are pertinent and central to corporate governance developments in the country. We also find that the quality of corporate governance in Vietnam is at a medium level when compared to international practices. Vietnam still has a long way to go to construct and embed effective corporate governance policies and practices and promote ethical business behaviours and sound decision making at board level.

Keywords: corporate governance, government, international institutions, public companies, Vietnam

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Authors: N. Noroozian, M. Halim, B. Holloway

Abstract:

Computed Tomography (CT) has become the largest source of radiation exposure in modern countries however, recent technological advances have created new methods to reduce dose without negatively affecting image quality. SAFIRE has emerged as a new software package which utilizes full raw data projections for iterative reconstruction, thereby allowing for lower CT dose to be used. this audit was performed to compare CT doses in certain examinations before and after the introduction of SAFIRE at our Radiology department which showed CT doses were significantly lower using SAFIRE compared with pre-SAFIRE software at SAFIRE 3 setting for the following studies:CSKUH Unenhanced brain scans (-20.9%), CABPEC Abdomen and pelvis with contrast (-21.5%), CCHAPC Chest with contrast (-24.4%), CCHAPC Abdomen and pelvis with contrast (-16.1%), CCHAPC Total chest, abdomen and pelvis (-18.7%).

Keywords: dose reduction, iterative reconstruction, low dose CT techniques, SAFIRE

Procedia PDF Downloads 257

Authors: Manzurul Alam, John Griffiths, David Holloway, Megan Paull, Anne Clear

Abstract:

Background: This paper investigates the nature of risk management practices in non-profit organizations. It is argued here that the risk exposure of these organizations has increased as a result of their entrepreneurial activities. This study explores how a particular non-profit organization formulates its risk strategies in the face funding restrictions. Design/Method/Approach: The study adopts a case study approach to report the results on how a non-profit organization diversifies its activities, tackles risks arising from such activities and improves performance. Results: The findings show that the organization made structural adjustments and leadership changes which helped to adjust their risk strategies. It also reports the organizational processes to deal with risks arising from both related and unrelated diversification strategies. Implications: Any generalization from this case example needs to be taken with caution as there are significant differences between non-profit organizations operating in different sectors. Originality: The paper makes a significant contribution to the non-profit literature by highlighting the diversification strategies along with risk performance.

Keywords: risk management, performance management, non-profit organizations, financial management

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Authors: Alexander V. Spirov, David M. Holloway, Ekaterina M. Myasnikova

Abstract:

Segmentation of the early Drosophila embryo results from the dynamic establishment of spatial gene expression patterns. Patterning occurs on an embryo geometry which is a 'deformed' prolate ellipsoid, with anteroposterior and dorsal-ventral major and minor axes, respectively. Patterning is largely independent along each axis, but some interaction can be seen in the 'bending' of the segmental expression stripes. This interaction is not well understood. In this report, we investigate how 3D geometrical features of the early embryo affect the segmental expression patterning. Specifically, we study the effect of geometry on formation of the Bicoid primary morphogenetic gradient. Our computational results demonstrate that embryos with a much longer ventral than dorsal surface ('bellied') can produce curved Bicoid concentration contours which could activate curved stripes in the downstream pair-rule segmentation genes. In addition, we show that having an extended source for Bicoid in the anterior of the embryo may be necessary for producing the observed exponential form of the Bicoid gradient along the anteroposterior axis.

Keywords: Drosophila embryo, bicoid morphogenetic gradient, exponential expression profile, expression surface form, segmentation genes, 3D modelling

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Authors: Ehsan Javanmardemamgheisi, Javad Mehr, Jason Ali-Lavroff, Damien Holloway, Michael Davis

Abstract:

During the last decades, a growing interest in faster and more efficient waterborne transportation has led to the development of high-speed vessels for both commercial and military applications. To satisfy this global demand, a wide variety of arrangements of high-speed crafts have been proposed by designers. Among them, high-speed catamarans have proven themselves to be a suitable Roll-on/Roll-off configuration for carrying passengers and cargo due to widely spaced demi hulls, a wide deck zone, and a high ratio of deadweight to displacement. To improve passenger comfort and crew workability and enhance the operability and performance of high-speed catamarans, mitigating the severity of motions and structural loads using Ride Control Systems (RCS) is essential.In this paper, a set of towing tank tests was conducted on a 2.5 m scaled model of a 112 m Incat Tasmania high-speed catamaran in irregular head seas to investigate the effect of different ride control algorithms including linear and nonlinear versions of the heave control, pitch control, and local control on motion responses and passenger comfort of the full-scale ship. The RCS included a centre bow-fitted T-Foil and two transom-mounted stern tabs. All the experiments were conducted at the Australian Maritime College (AMC) towing tank at a model speed of 2.89 m/s (37 knots full scale), a modal period of 1.5 sec (10 sec full scale) and two significant wave heights of 60 mm and 90 mm, representing full-scale wave heights of 2.7 m and 4 m, respectively. Spectral analyses were performed using Welch’s power spectral density method on the vertical motion time records of the catamaran model to calculate heave and pitch Response Amplitude Operators (RAOs). Then, noting that passenger discomfort arises from vertical accelerations and that the vertical accelerations vary at different longitudinal locations within the passenger cabin due to the variations in amplitude and relative phase of the pitch and heave motions, the vertical accelerations were calculated at three longitudinal locations (LCG, T-Foil, and stern tabs). Finally, frequency-weighted Root Mean Square (RMS) vertical accelerations were calculated to estimate Motion Sickness Dose Value (MSDV) of the ship based on ISO 2631-recommendations. It was demonstrated that in small seas, implementing a nonlinear pitch control algorithm reduces the peak pitch motions by 41%, the vertical accelerations at the forward location by 46%, and motion sickness at the forward position by around 20% which provides great potential for further improvement in passenger comfort, crew workability, and operability of high-speed catamarans.

Keywords: high-speed catamarans, ride control system, response amplitude operators, vertical accelerations, motion sickness, irregular waves, towing tank tests.

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