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.

Combining Ant Colony Optimization and Dynamic Programming for Solving a Dynamic Facility Layout Problem

This paper presents an algorithm which combining ant colony optimization in the dynamic programming for solving a dynamic facility layout problem. The problem is separated into 2 phases, static and dynamic phase. In static phase, ant colony optimization is used to find the best ranked of layouts for each period. Then the dynamic programming (DP) procedure is performed in the dynamic phase to evaluate the layout set during multi-period planning horizon. The proposed algorithm is tested over many problems with size ranging from 9 to 49 departments, 2 and 4 periods. The experimental results show that the proposed method is an alternative way for the plant layout designer to determine the layouts during multi-period planning horizon.

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.

Alcoholic Extract of Terminalia Arjuna Protects Rabbit Heart against Ischemic-Reperfusion Injury: Role of Antioxidant Enzymes and Heat Shock Protein

The present study was designed to investigate the cardio protective role of chronic oral administration of alcoholic extract of Terminalia arjuna in in-vivo ischemic reperfusion injury and the induction of HSP72. Rabbits, divided into three groups, and were administered with the alcoholic extract of the bark powder of Terminalia arjuna (TAAE) by oral gavage [6.75mg/kg: (T1) and 9.75mg/kg: (T2), 6 days /week for 12 weeks]. In open-chest Ketamine pentobarbitone anaesthetized rabbits, the left anterior descending coronary artery was occluded for 15 min of ischemia followed by 60 min of reperfusion. In the vehicle-treated group, ischemic-reperfusion injury (IRI) was evidenced by depression of global hemodynamic function (MAP, HR, LVEDP, peak LV (+) & (- ) (dP/dt) along with depletion of HEP compounds. Oxidative stress in IRI was evidenced by, raised levels of myocardial TBARS and depletion of endogenous myocardial antioxidants GSH, SOD and catalase. Western blot analysis showed a single band corresponding to 72 kDa in homogenates of hearts from rabbits treated with both the doses. In the alcoholic extract of the bark powder of Terminalia arjuna treatment groups, both the doses had better recovery of myocardial hemodynamic function, with significant reduction in TBARS, and rise in SOD, GSH, catalase were observed. The results of the present study suggest that the alcoholic extract of the bark powder of Terminalia arjuna in rabbit induces myocardial HSP 72 and augments myocardial endogenous antioxidants, without causing any cellular injury and offered better cardioprotection against oxidative stress associated with myocardial IR injury.

Construction of Recombinant E.coli Expressing Fusion Protein to Produce 1,3-Propanediol

In this study, a synthetic pathway was created by assembling genes from Clostridium butyricum and Escherichia coli in different combinations. Among the genes were dhaB1 and dhaB2 from C. butyricum VPI1718 coding for glycerol dehydratase (GDHt) and its activator (GDHtAc), respectively, involved in the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA). The yqhD gene from E.coli BL21 was also included which codes for an NADPHdependent 1,3-propanediol oxidoreductase isoenzyme (PDORI) reducing 3-HPA to 1,3-propanediol (1,3-PD). Molecular modeling analysis indicated that the conformation of fusion protein of YQHD and DHAB1 was favorable for direct molecular channeling of the intermediate 3-HPA. According to the simulation results, the yqhD and dhaB1 gene were assembled in the upstream of dhaB2 to express a fusion protein, yielding the recombinant strain E. coliBL21 (DE3)//pET22b+::yqhD-dhaB1_dhaB2 (strain BP41Y3). Strain BP41Y3 gave 10-fold higher 1,3-PD concentration than E. coliBL21 (DE3)//pET22b+::yqhD-dhaB1_dhaB2 (strain BP31Y2) expressing the recombinant enzymes simultaneously but in a non-fusion mode. This is the first report using a gene fusion approach to enhance the biological conversion of glycerol to the value added compound 1,3- PD.

Structural Funds of Polish Agriculture

The research objective of the project and article “The impact of Structural Funds on the growth of competitiveness of Polish agriculture" is to assess competitiveness of regions in Poland from the perspective of Polish agriculture by analysing the efficiency of the use of Structural Funds, the economic procedure of their distribution and the regulatory and organisational framework under the Rural Development Programme (RDP). It must be stressed that defining the scope of research in the above manner limits the analysis only to the part of Structural Funds directed to support Polish agriculture.

Study of the Effect of Project Management on Manufacturing and Production Projects

In this article the accumulated results out of the effects and length of the manufacture and production projects in the university and research standard have been settled with the usefulness definition of the process of project management for the accessibility to the proportional pattern in the “time and action" stages. Studies show that many problems confronted by the researchers in these projects are connected to the non-profiting of: 1) autonomous timing for gathering the educational theme, 2) autonomous timing for planning and pattern, presenting before the construction, and 3) autonomous timing for manufacture and sample presentation from the output. The result of this study indicates the division of every manufacture and production projects into three smaller autonomous projects from its kind, budget and autonomous expenditure, shape and order of the stages for the management of these kinds of projects. In this case study real result are compared with theoretical results.

Feature Based Dense Stereo Matching using Dynamic Programming and Color

This paper presents a new feature based dense stereo matching algorithm to obtain the dense disparity map via dynamic programming. After extraction of some proper features, we use some matching constraints such as epipolar line, disparity limit, ordering and limit of directional derivative of disparity as well. Also, a coarseto- fine multiresolution strategy is used to decrease the search space and therefore increase the accuracy and processing speed. The proposed method links the detected feature points into the chains and compares some of the feature points from different chains, to increase the matching speed. We also employ color stereo matching to increase the accuracy of the algorithm. Then after feature matching, we use the dynamic programming to obtain the dense disparity map. It differs from the classical DP methods in the stereo vision, since it employs sparse disparity map obtained from the feature based matching stage. The DP is also performed further on a scan line, between any matched two feature points on that scan line. Thus our algorithm is truly an optimization method. Our algorithm offers a good trade off in terms of accuracy and computational efficiency. Regarding the results of our experiments, the proposed algorithm increases the accuracy from 20 to 70%, and reduces the running time of the algorithm almost 70%.

Digital Power Management Hardware Realization Using FPGA

This paper describes design of a digital feedback loop for a low switching frequency dc-dc switching converters. Low switching frequencies were selected in this design. A look up table for the digital PID (proportional integrator differentiator) compensator was implemented using Altera Stratix II with built-in ADC (analog-to-digital converter) to achieve this hardware realization. Design guidelines are given for the PID compensator, high frequency DPWM (digital pulse width modulator) and moving average filter.

The Establishment of Cause-System of Poor Construction Site Safety and Priority Analysis from Different Perspectives

Construction site safety in China has aroused comprehensive concern all over the world. It is imperative to investigate the main causes of poor construction site safety. This paper divides all the causes into four aspects, namely the factors of workers, object, environment and management and sets up the accident causes element system based on Delphi Method. This is followed by the application of structural equation modeling to examine the importance of each aspect of causes from the standpoints of different roles related to the construction respectively. The results indicate that all the four aspects of factors are in need of improvement, and different roles have different ideas considering the priority of those factors. The paper has instructive significance for the practitioners to take measures to improve construction site safety in China accordingly.

Application of Acidithiobacillus ferrooxidans in Desulfurization of US Coal: 10 L Batch Stirred Reactor Study

The desulfurization of coal using biological methods is an emerging technology. The biodesulfurization process uses the catalytic activity of chemolithotrophic acidpohiles in removing sulfur and pyrite from the coal. The present study was undertaken to examine the potential of Acidithiobacillus ferrooxidans in removing the pyritic sulfur and iron from high iron and sulfur containing US coal. The experiment was undertaken in 10 L batch stirred tank reactor having 10% pulp density of coal. The reactor was operated under mesophilic conditions and aerobic conditions were maintained by sparging the air into the reactor. After 35 days of experiment, about 64% of pyrite and 21% of pyritic sulfur was removed from the coal. The findings of the present study indicate that the biodesulfurization process does have potential in treating the high pyrite and sulfur containing coal. A good mass balance was also obtained with net loss of about 5% showing its feasibility for large scale application.

A Continuous Time Sigma Delta Modulators Using CMOS Current Conveyors

In this paper, a alternative structure method for continuous time sigma delta modulator is presented. In this modulator for implementation of integrators in loop filter second generation current conveyors are employed. The modulator is designed in CMOS technology and features low power consumption (65db), and with 180khZ bandwidth. Simulation results confirm that this design is suitable for data converters.

Dynamic Performances of Tubular Linear Induction Motor for Pneumatic Capsule Pipeline System

Tubular linear induction motor (TLIM) can be used as a capsule pump in a large pneumatic capsule pipeline (PCP) system. Parametric performance evaluation of the designed 1-meter diameter PCP-TLIM system yields encouraging results for practical implementation. The capsule thrust and speed inside the TLIM pump can be calculated from the combination of the PCP fluid mechanics and the TLIM equations. The TLIM equivalent circuits derived from those of the conventional three-phase induction motor are used as a model to predict the static test results of a small-scale PCP-TLIM system. In this paper, additional dynamic tests are performed on the same small-scale PCP-TLIM system with two capsules of different diameters. The behaviors of the capsule inside the pump are observed and analyzed. The dynamic performances from the dynamic tests are compared with the theoretical predictions based on the TLIM equivalent circuit model.

Interconnect Analysis of a Novel Multiplexer Based Full-Adder Cell for Power and Propagation Delay Optimizations

The proposed multiplexer-based novel 1-bit full adder cell is schematized by using DSCH2 and its layout is generated by using microwind VLSI CAD tool. The adder cell layout interconnect analysis is performed by using BSIM4 layout analyzer. The adder circuit is compared with other six existing adder circuits for parametric analysis. The proposed adder cell gives better performance than the other existing six adder circuits in terms of power, propagation delay and PDP. The proposed adder circuit is further analyzed for interconnect analysis, which gives better performance than other adder circuits in terms of layout thickness, width and height.

Tunable Photonic Microwave Bandpass Filter Based on EOPM and VPBS

A tunable photonic microwave bandpass filter with negative coefficient based on an electro-optic phase modulator (EOPM) and a variable polarization beamsplitter (VPBS) is demonstrated. A two-tap microwave bandpass filter with one negative coefficient is presented. The chromatic dispersion and optical coherence are not affected on this filter.

Hierarchies Based On the Number of Cooperating Systems of Finite Automata on Four-Dimensional Input Tapes

In theoretical computer science, the Turing machine has played a number of important roles in understanding and exploiting basic concepts and mechanisms in computing and information processing [20]. It is a simple mathematical model of computers [9]. After that, M.Blum and C.Hewitt first proposed two-dimensional automata as a computational model of two-dimensional pattern processing, and investigated their pattern recognition abilities in 1967 [7]. Since then, a lot of researchers in this field have been investigating many properties about automata on a two- or three-dimensional tape. On the other hand, the question of whether processing fourdimensional digital patterns is much more difficult than two- or threedimensional ones is of great interest from the theoretical and practical standpoints. Thus, the study of four-dimensional automata as a computasional model of four-dimensional pattern processing has been meaningful [8]-[19],[21]. This paper introduces a cooperating system of four-dimensional finite automata as one model of four-dimensional automata. A cooperating system of four-dimensional finite automata consists of a finite number of four-dimensional finite automata and a four-dimensional input tape where these finite automata work independently (in parallel). Those finite automata whose input heads scan the same cell of the input tape can communicate with each other, that is, every finite automaton is allowed to know the internal states of other finite automata on the same cell it is scanning at the moment. In this paper, we mainly investigate some accepting powers of a cooperating system of eight- or seven-way four-dimensional finite automata. The seven-way four-dimensional finite automaton is an eight-way four-dimensional finite automaton whose input head can move east, west, south, north, up, down, or in the fu-ture, but not in the past on a four-dimensional input tape.

Mining Frequent Patterns with Functional Programming

Frequent patterns are patterns such as sets of features or items that appear in data frequently. Finding such frequent patterns has become an important data mining task because it reveals associations, correlations, and many other interesting relationships hidden in a dataset. Most of the proposed frequent pattern mining algorithms have been implemented with imperative programming languages such as C, Cµ, Java. The imperative paradigm is significantly inefficient when itemset is large and the frequent pattern is long. We suggest a high-level declarative style of programming using a functional language. Our supposition is that the problem of frequent pattern discovery can be efficiently and concisely implemented via a functional paradigm since pattern matching is a fundamental feature supported by most functional languages. Our frequent pattern mining implementation using the Haskell language confirms our hypothesis about conciseness of the program. The performance studies on speed and memory usage support our intuition on efficiency of functional language.

New Triangle-Ring UWB Bandpass Filter with Sharp Roll-Off and Dual Notched Bands

This paper presents a new ultra-wideband (UWB) bandpass filter (BPF) with sharp roll-off and dual-notched bands. The filter consists of a triangle ring multi-mode resonator (MMR) with the stub-loaded resonator (SLR) for controlling the two transmission zeros at 2.8 / 11 GHz, the embedded open-circuited stub and the asymmetric tight coupled input/output (I/O) lines for introducing the dual notched bands at 5.2 / 6.8 GHz. The attenuation slope in the lower and higher passband edges of the proposed filter show 160- and 153-dB/GHz, respectively. This study mainly provides a simple method to design a UWB bandpass filter with high passband selectivity and dual-notched bands for satisfying the Federal Communications Commission (FCC-defined) indoor UWB specification

Mechanical and Morphological Properties of Polypropylene and High Density Polyethylene Matrix Composites Reinforced with Surface Modified Nano Sized TiO2 Particles

Plastics occupy wide place in the applications of automotive, electronics and house goods. Especially reinforced plastics become popular because of their high strength besides their advantages of low weight and easy manufacturability. In this study, mechanical and morphological properties of polypropylene (PP) and high density polyethylene (HDPE) matrix composites reinforced with surface modified nano titan dioxide (TiO2) particles were investigated. Surface modification was made by coating the nano powders with maleic anhydride grafted styrene ethylene butylene styrene (SEBS-g-MA) and silane, respectively. After surface modification, PP/TiO2 and HDPE/TiO2 composites were obtained by using twin screw extruder at titan dioxide loading of 1 wt.%, 3 wt.% and 5 wt.%. Effects of surface modification were determined by thermal and morphological analysis. SEBS-g-MA provided bridging effect between TiO2 particles and polymer matrix while silane was effective as a dispersant. Depending on that, homogenous structures without agglomeration were obtained. Mechanical tests were performed on the injection moldings of the composites for obtaining the impact strength, tensile strength, stress at break, elongation and elastic modulus. Reinforced HDPE and PP moldings gave higher tensile strength and elastic modulus due to the rigid structure of TiO2. Slight increment was seen in stress at break. Elongation and impact strength decreased due to the stiffness of the nano titan dioxide.

A New Analytical Approach for Free Vibration of Membrane from Wave Standpoint

In this paper, an analytical approach for free vibration analysis of rectangular and circular membranes is presented. The method is based on wave approach. From wave standpoint vibration propagate, reflect and transmit in a structure. Firstly, the propagation and reflection matrices for rectangular and circular membranes are derived. Then, these matrices are combined to provide a concise and systematic approach to free vibration analysis of membranes. Subsequently, the eigenvalue problem for free vibration of membrane is formulated and the equation of membrane natural frequencies is constructed. Finally, the effectiveness of the approach is shown by comparison of the results with existing classical solution.