Discovery of Human HMG-Coa Reductase Inhibitors Using Structure-Based Pharmacophore Modeling Combined with Molecular Dynamics Simulation Methodologies

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the conversion of HMG-CoA to mevalonate using NADPH and the enzyme is involved in rate-controlling step of mevalonate. Inhibition of HMGR is considered as effective way to lower cholesterol levels so it is drug target to treat hypercholesterolemia, major risk factor of cardiovascular disease. To discover novel HMGR inhibitor, we performed structure-based pharmacophore modeling combined with molecular dynamics (MD) simulation. Four HMGR inhibitors were used for MD simulation and representative structure of each simulation were selected by clustering analysis. Four structure-based pharmacophore models were generated using the representative structure. The generated models were validated used in virtual screening to find novel scaffolds for inhibiting HMGR. The screened compounds were filtered by applying drug-like properties and used in molecular docking. Finally, four hit compounds were obtained and these complexes were refined using energy minimization. These compounds might be potential leads to design novel HMGR inhibitor.

Health Care Ethics in Vulnerable Populations: Clinical Research through the Patient's Eyes

Chronic conditions carry with them strong emotions and often lead to charged relationships between patients and their health providers and, by extension, patients and health researchers. Persons are both autonomous and relational and a purely cognitive model of autonomy neglects the social and relational basis of chronic illness. Ensuring genuine informed consent in research requires a thorough understanding of how participants perceive a study and their reasons for participation. Surveys may not capture the complexities of reasoning that underlies study participation. Contradictory reasons for participation, for instance an initial claim of altruism as rationale and a subsequent claim of personal benefit (therapeutic misconception), affect the quality of informed consent. Individuals apply principles through the filter of personal values and lived experience. Authentic autonomy, and hence authentic consent to research, occurs within the context of patients- unique life narratives and illness experiences.

Blind Non-Minimum Phase Channel Identification Using 3rd and 4th Order Cumulants

In this paper we propose a family of algorithms based on 3rd and 4th order cumulants for blind single-input single-output (SISO) Non-Minimum Phase (NMP) Finite Impulse Response (FIR) channel estimation driven by non-Gaussian signal. The input signal represents the signal used in 10GBASE-T (or IEEE 802.3an-2006) as a Tomlinson-Harashima Precoded (THP) version of random Pulse-Amplitude Modulation with 16 discrete levels (PAM-16). The proposed algorithms are tested using three non-minimum phase channel for different Signal-to-Noise Ratios (SNR) and for different data input length. Numerical simulation results are presented to illustrate the performance of the proposed algorithms.

Mounting Time Reduction using Content-Based Block Management for NAND Flash File System

The flash memory has many advantages such as low power consumption, strong shock resistance, fast I/O and non-volatility. And it is increasingly used in the mobile storage device. The YAFFS, one of the NAND flash file system, is widely used in the embedded device. However, the existing YAFFS takes long time to mount the file system because it scans whole spare areas in all pages of NAND flash memory. In order to solve this problem, we propose a new content-based flash file system using a mounting time reduction technique. The proposed method only scans partial spare areas of some special pages by using content-based block management. The experimental results show that the proposed method reduces the average mounting time by 87.2% comparing with JFFS2 and 69.9% comparing with YAFFS.

Reduction of Chloride Dioxide in Paper Bleaching using Peroxide Activation

All around the world pulp and paper industries are the biggest plant production with the environmental pollution as the biggest challenge facing the pulp manufacturing operations. The concern among these industries is to produce a high volume of papers with the high quality standard and of low cost without affecting the environment. This result obtained from this bleaching study show that the activation of peroxide was an effective method of reducing the total applied charge of chlorine dioxide which is harmful to our environment and also show that softwood and hardwood Kraft pulps responded linearly to the peroxide treatments. During the bleaching process the production plant produce chlorines. Under the trial stages chloride dioxide has been reduced by 3 kg/ton to reduce the brightness from 65% ISO to 60% ISO of pulp and the dosing point returned to the E stage charges by pre-treating Kraft pulps with hydrogen peroxide. The pulp and paper industry has developed elemental chlorine free (ECF) and totally chlorine free (TCF) bleaching, in their quest for being environmental friendly, they have been looking at ways to turn their ECF process into a TCF process while still being competitive. This prompted the research to investigate the capability of the hydrogen peroxide as catalyst to reduce chloride dioxide.

Exploring the Application of Knowledge Management Factors in Esfahan University's Medical College

In this competitive age, one of the key tools of most successful organizations is knowledge management. Today some organizations measure their current knowledge and use it as an indicator for rating the organization on their reports. Noting that the universities and colleges of medical science have a great role in public health of societies, their access to newest scientific research and the establishment of organizational knowledge management systems is very important. In order to explore the Application of Knowledge Management Factors, a national study was undertaken. The main purpose of this study was to find the rate of the application of knowledge management factors and some ways to establish more application of knowledge management system in Esfahan University-s Medical College (EUMC). Esfahan is the second largest city after Tehran, the capital city of Iran, and the EUMC is the biggest medical college in Esfahan. To rate the application of knowledge management, this study uses a quantitative research methodology based on Probst, Raub and Romhardt model of knowledge management. A group of 267 faculty members and staff of the EUMC were asked via questionnaire. Finding showed that the rate of the application of knowledge management factors in EUMC have been lower than average. As a result, an interview with ten faculty members conducted to find the guidelines to establish more applications of knowledge management system in EUMC.

Estimating the Absorption of Volatile Organic Compounds in Four Biodiesels Using the UNIFAC Procedure

This work considered the thermodynamic feasibility of scrubbing volatile organic compounds into biodiesel in view of designing a gas treatment process with this absorbent. A detailed vapour – liquid equilibrium investigation was performed using the original UNIFAC group contribution method. The four biodiesels studied in this work are methyl oleate, methyl palmitate, methyl linolenate and ethyl stearate. The original UNIFAC procedure was used to estimate the infinite dilution activity coefficients of 13 selected volatile organic compounds in the biodiesels. The calculations were done at the VOC mole fraction of 9.213x10-8. Ethyl stearate gave the most favourable phase equilibrium. A close agreement was found between the infinite dilution activity coefficient of toluene found in this work and those reported in literature. Thermodynamic models can efficiently be used to calculate vast amount of phase equilibrium behaviour using limited number of experimental data.

Optimization Based Obstacle Avoidance

Based on a non-linear single track model which describes the dynamics of vehicle, an optimal path planning strategy is developed. Real time optimization is used to generate reference control values to allow leading the vehicle alongside a calculated lane which is optimal for different objectives such as energy consumption, run time, safety or comfort characteristics. Strict mathematic formulation of the autonomous driving allows taking decision on undefined situation such as lane change or obstacle avoidance. Based on position of the vehicle, lane situation and obstacle position, the optimization problem is reformulated in real-time to avoid the obstacle and any car crash.

Industrial Development, Environment And Occupational Problems: The Case Of Iran

There are three distinct stages in the evolution of economic thought, namely: 1. in the first stage, the major concern was to accelerate economic growth with increased availability of material goods, especially in developing economies with very low living standards, because poverty eradication meant faster economic growth. 2. in the second stage, economists made distinction between growth and development. Development was seen as going beyond economic growth, and bringing certain changes in the structure of the economy with more equitable distribution of the benefits of growth, with the growth coming automatic and sustained. 3. the third stage is now reached. Our concern is now with “sustainable development", that is, development not only for the present but also of the future. Thus the focus changed from “sustained growth" to “sustained development". Sustained development brings to the fore the long term relationship between the ecology and economic development. Since the creation of UNEP in 1972 it has worked for development without destruction for environmentally sound and sustained development. It was realised that the environment cannot be viewed in a vaccum, it is not separate from development, nor is it competing. It suggested for the integration of the environment with development whereby ecological factors enter development planning, socio-economic policies, cost-benefit analysis, trade, technology transfer, waste management, educational and other specific areas. Industrialisation has contributed to the growth of economy of several countries. It has improved the standards of living of its people and provided benefits to the society. It has also created in the process great environmental problems like climate change, forest destruction and denudation, soil erosion and desertification etc. On the other hand, industry has provided jobs and improved the prospects of wealth for the industrialists. The working class communities had to simply put up with the high levels of pollution in order to keep up their jobs and also to save their income. There are many roots of the environmental problem. They may be political, economic, cultural and technological conditions of the modern society. The experts concede that industrial growth lies somewhere close to the heart of the matter. Therefore, the objective of this paper is not to document all roots of an environmental crisis but rather to discuss the effects of industrial growth and development. We have come to the conclusion that although public intervention is often unnecessary to ensure that perfectly competitive markets will function in society-s best interests, such intervention is necessary when firms or consumers pollute.

Dependence of Virtual Subjects Reflection from the Features of Coping Behavior of Students

In the globalization process, when the struggle for minds and values of the people is taking place, the impact of the virtual space can cause unexpected effects and consequences in the process of adjustment of young people in this world. Their special significance is defined by unconscious influence on the underlying process of meaning and therefore the values preached by them are much more effective and affect both the personal characteristics and the peculiarities of adjustment process. Related to this the challenge is to identify factors influencing the reflection characteristics of virtual subjects and measures their impact on the personal characteristics of the students.

Serious Game for Autism Children: Review of Literature

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder which affects individuals with varying degrees of impairment. Currently, there has been ample research done in serious game for autism children. Although serious games are traditionally associated with software developments, developing them in the autism field involves studying the associated technology and paying attention to aspects related to interaction with the game. Serious Games for autism cover matters related to education, therapy for communication, psychomotor treatment and social behavior enhancement. In this paper, a systematic review sets out the lines of development and research currently being conducted into serious games which pursue some form of benefit in the field of autism. This paper includes a literature review of relevant serious game developments since in year 2007 and examines new trends.

Morpho-Phonological Modelling in Natural Language Processing

In this paper we propose a computational model for the representation and processing of morpho-phonological phenomena in a natural language, like Modern Greek. We aim at a unified treatment of inflection, compounding, and word-internal phonological changes, in a model that is used for both analysis and generation. After discussing certain difficulties cuase by well-known finitestate approaches, such as Koskenniemi-s two-level model [7] when applied to a computational treatment of compounding, we argue that a morphology-based model provides a more adequate account of word-internal phenomena. Contrary to the finite state approaches that cannot handle hierarchical word constituency in a satisfactory way, we propose a unification-based word grammar, as the nucleus of our strategy, which takes into consideration word representations that are based on affixation and [stem stem] or [stem word] compounds. In our formalism, feature-passing operations are formulated with the use of the unification device, and phonological rules modeling the correspondence between lexical and surface forms apply at morpheme boundaries. In the paper, examples from Modern Greek illustrate our approach. Morpheme structures, stress, and morphologically conditioned phoneme changes are analyzed and generated in a principled way.

Fluorescence Spectroscopy of Lysozyme-Silver Nanoparticles Complex

Identifying the nature of protein-nanoparticle interactions and favored binding sites is an important issue in functional characterization of biomolecules and their physiological responses. Herein, interaction of silver nanoparticles with lysozyme as a model protein has been monitored via fluorescence spectroscopy. Formation of complex between the biomolecule and silver nanoparticles (AgNPs) induced a steady state reduction in the fluorescence intensity of protein at different concentrations of nanoparticles. Tryptophan fluorescence quenching spectra suggested that silver nanoparticles act as a foreign quencher, approaching the protein via this residue. Analysis of the Stern-Volmer plot showed quenching constant of 3.73 μM−1. Moreover, a single binding site in lysozyme is suggested to play role during interaction with AgNPs, having low affinity of binding compared to gold nanoparticles. Unfolding studies of lysozyme showed that complex of lysozyme- AgNPs has not undergone structural perturbations compared to the bare protein. Results of this effort will pave the way for utilization of sensitive spectroscopic techniques for rational design of nanobiomaterials in biomedical applications.

Thermo-mechanical Behavior of Pressure Tube of Indian PHWR at 20 bar Pressure

In a nuclear reactor Loss of Coolant accident (LOCA) considers wide range of postulated damage or rupture of pipe in the heat transport piping system. In the case of LOCA with/without failure of emergency core cooling system in a Pressurised Heavy water Reactor, the Pressure Tube (PT) temperature could rise significantly due to fuel heat up and gross mismatch of the heat generation and heat removal in the affected channel. The extent and nature of deformation is important from reactor safety point of view. Experimental set-ups have been designed and fabricated to simulate ballooning (radial deformation) of PT for 220 MWe IPHWRs. Experiments have been conducted by covering the CT by ceramic fibers and then by submerging CT in water of voided PTs. In both the experiments, it is observed that ballooning initiates at a temperature around 665´┐¢C and complete contact between PT and Caldaria Tube (CT) occurs at around 700´┐¢C approximately. The strain rate is found to be 0.116% per second. The structural integrity of PT is retained (no breach) for all the experiments. The PT heatup is found to be arrested after the contact between PT and CT, thus establishing moderator acting as an efficient heat sink for IPHWRs.

Numerical Analysis and Experimental Validation of Detector Pressure Housing Subject to HPHT

Reservoirs with high pressures and temperatures (HPHT) that were considered to be atypical in the past are now frequent targets for exploration. For downhole oilfield drilling tools and components, the temperature and pressure affect the mechanical strength. To address this issue, a finite element analysis (FEA) for 206.84 MPa (30 ksi) pressure and 165°C has been performed on the pressure housing of the measurement-while-drilling/logging-whiledrilling (MWD/LWD) density tool. The density tool is a MWD/LWD sensor that measures the density of the formation. One of the components of the density tool is the pressure housing that is positioned in the tool. The FEA results are compared with the experimental test performed on the pressure housing of the density tool. Past results show a close match between the numerical results and the experimental test. This FEA model can be used for extreme HPHT and ultra HPHT analyses, and/or optimal design changes.

A Novel Approach of Route Choice in Stochastic Time-varying Networks

Many exist studies always use Markov decision processes (MDPs) in modeling optimal route choice in stochastic, time-varying networks. However, taking many variable traffic data and transforming them into optimal route decision is a computational challenge by employing MDPs in real transportation networks. In this paper we model finite horizon MDPs using directed hypergraphs. It is shown that the problem of route choice in stochastic, time-varying networks can be formulated as a minimum cost hyperpath problem, and it also can be solved in linear time. We finally demonstrate the significant computational advantages of the introduced methods.

Light Confinement in Low Index Nanometer Areas

In this work we numerically examine structures which could confine light in nanometer areas. A system consisting of two silicon disks with in plane separation of a few tens of nanometers has been studied first. The normalized unitless effective mode volume, Veff, has been calculated for the two lowest whispering gallery mode resonances. The effective mode volume is reduced significantly as the gap between the disks decreases. In addition, the effect of the substrate is also studied. In that case, Veff of approximately the same value as the non-substrate case for a similar two disk system can be obtained by using disks almost twice as thick. We also numerically examine a structure consisting of a circular slot waveguide which is formed into a silicon disk resonator. We show that the proposed structure could have high Q resonances thus raising the belief that it is a very promising candidate for optical interconnects applications. The study includes several numerical calculations for all the geometric parameters of the structure. It also includes numerical simulations of the coupling between a waveguide and the proposed disk resonator leading to a very promising conclusion about its applicability.

Automatic Clustering of Gene Ontology by Genetic Algorithm

Nowadays, Gene Ontology has been used widely by many researchers for biological data mining and information retrieval, integration of biological databases, finding genes, and incorporating knowledge in the Gene Ontology for gene clustering. However, the increase in size of the Gene Ontology has caused problems in maintaining and processing them. One way to obtain their accessibility is by clustering them into fragmented groups. Clustering the Gene Ontology is a difficult combinatorial problem and can be modeled as a graph partitioning problem. Additionally, deciding the number k of clusters to use is not easily perceived and is a hard algorithmic problem. Therefore, an approach for solving the automatic clustering of the Gene Ontology is proposed by incorporating cohesion-and-coupling metric into a hybrid algorithm consisting of a genetic algorithm and a split-and-merge algorithm. Experimental results and an example of modularized Gene Ontology in RDF/XML format are given to illustrate the effectiveness of the algorithm.

A Framework of the Factors Affecting the Adoption of ICT for Physical Education

Physical education (PE) is still neglected in schools despite its academic, social, psychological, and health benefits. Based on the assumption that Information and Communication Technologies (ICTs) can contribute to the development of PE in schools, this study aims to design a model of the factors affecting the adoption of ICTs for PE in schools. The proposed model is based on a sound theoretical framework. It was designed following a literature review of technology adoption theories and of ICT adoption factors for physical education. The technology adoption model that fitted to the best all ICT adoption factors was then chosen as the basis for the proposed model. It was found that the Unified Theory of Acceptance and Use of Technology (UTAUT) is the most adequate theoretical framework for the modeling of ICT adoption factors for physical education.

Location Update Cost Analysis of Mobile IPv6 Protocols

Mobile IP has been developed to provide the continuous information network access to mobile users. In IP-based mobile networks, location management is an important component of mobility management. This management enables the system to track the location of mobile node between consecutive communications. It includes two important tasks- location update and call delivery. Location update is associated with signaling load. Frequent updates lead to degradation in the overall performance of the network and the underutilization of the resources. It is, therefore, required to devise the mechanism to minimize the update rate. Mobile IPv6 (MIPv6) and Hierarchical MIPv6 (HMIPv6) have been the potential candidates for deployments in mobile IP networks for mobility management. HMIPv6 through studies has been shown with better performance as compared to MIPv6. It reduces the signaling overhead traffic by making registration process local. In this paper, we present performance analysis of MIPv6 and HMIPv6 using an analytical model. Location update cost function is formulated based on fluid flow mobility model. The impact of cell residence time, cell residence probability and user-s mobility is investigated. Numerical results are obtained and presented in graphical form. It is shown that HMIPv6 outperforms MIPv6 for high mobility users only and for low mobility users; performance of both the schemes is almost equivalent to each other.