Inhibition of the Interaction Between NS3 Protease and HCV IRES With a Small Peptide: A Novel Therapeutic Strategy

Recently, we have demonstrated that the protease domain of NS3 alone can bind specifically to hepatitis C virus (HCV) internal ribosome entry site (IRES) near the initiator AUG, dislodges human La protein and inhibits translation in favor of viral RNA replication. Here, by using a computational approach, the contact points of the protease on the HCV IRES were putatively mapped. A 30-mer NS3 peptide was designed from the predicted RNA-binding region that retained RNA-binding ability and also inhibited IRES-mediated translation. This peptide was truncated to 15 mer and this also demonstrated ability to inhibit HCV RNA-directed translation as well as replication. More importantly, its activity was tested in an in vivo mouse model by encapsulating the peptide in Sendai virus virosomes followed by intravenous delivery. The study demonstrates for the first time that the HCV NS3-IRES RNA interaction can be selectively inhibited using a small peptide and reports a strategy to deliver the peptide into the liver.

Thermal oxidation strategy for the synthesis of phase-controlled GeO2 and photoluminescence characterization

We report the synthesis of trigonal and tetragonal phase GeO2 films/microrods from a Ge wafer/powder by thermal oxidation. Both trigonal and tetragonal GeO2 exhibit excitation-dependent luminescence. Trigonal GeO2 exhibits strong green luminescence while tetragonal GeO2 exhibits strong blue luminescence when excited with ultra-violet light. Yellow-red luminescence is observed when both the phases are excited with green light. The emission wavelength varies almost linearly with the excitation wavelength both for trigonal and tetragonal GeO2. The variation is significant in the case of tetragonal GeO2, indicating a potential wavelength converter material.

Improving query focused summarization using look-ahead strategy

Query focused summarization is the task of producing a compressed text of original set of documents based on a query. Documents can be viewed as graph with sentences as nodes and edges can be added based on sentence similarity. Graph based ranking algorithms which use 'Biased random surfer model' like topic-sensitive LexRank have been successfully applied to query focused summarization. In these algorithms, random walk will be biased towards the sentences which contain query relevant words. Specifically, it is assumed that random surfer knows the query relevance score of the sentence to where he jumps. However, neighbourhood information of the sentence to where he jumps is completely ignored. In this paper, we propose look-ahead version of topic-sensitive LexRank. We assume that random surfer not only knows the query relevance of the sentence to where he jumps but he can also look N-step ahead from that sentence to find query relevance scores of future set of sentences. Using this look ahead information, we figure out the sentences which are indirectly related to the query by looking at number of hops to reach a sentence which has query relevant words. Then we make the random walk biased towards even to the indirect query relevant sentences along with the sentences which have query relevant words. Experimental results show 20.2% increase in ROUGE-2 score compared to topic-sensitive LexRank on DUC 2007 data set. Further, our system outperforms best systems in DUC 2006 and results are comparable to state of the art systems.

Linear programming approach for state estimation incorporating phasor measurements

This paper presents methodologies for incorporating phasor measurements into conventional state estimator. The angle measurements obtained from Phasor Measurement Units are handled as angle difference measurements rather than incorporating the angle measurements directly. Handling in such a manner overcomes the problems arising due to the choice of reference bus. Current measurements obtained from Phasor Measurement Units are treated as equivalent pseudo-voltage measurements at the neighboring buses. Two solution approaches namely normal equations approach and linear programming approach are presented to show how the Phasor Measurement Unit measurements can be handled. Comparative evaluation of both the approaches is also presented. Test results on IEEE 14 bus system are presented to validate both the approaches.

Automatic compilation of MATLAB programs for synergistic execution on heterogeneous processors

MATLAB is an array language, initially popular for rapid prototyping, but is now being increasingly used to develop production code for numerical and scientific applications. Typical MATLAB programs have abundant data parallelism. These programs also have control flow dominated scalar regions that have an impact on the program's execution time. Today's computer systems have tremendous computing power in the form of traditional CPU cores and throughput oriented accelerators such as graphics processing units(GPUs). Thus, an approach that maps the control flow dominated regions to the CPU and the data parallel regions to the GPU can significantly improve program performance. In this paper, we present the design and implementation of MEGHA, a compiler that automatically compiles MATLAB programs to enable synergistic execution on heterogeneous processors. Our solution is fully automated and does not require programmer input for identifying data parallel regions. We propose a set of compiler optimizations tailored for MATLAB. Our compiler identifies data parallel regions of the program and composes them into kernels. The problem of combining statements into kernels is formulated as a constrained graph clustering problem. Heuristics are presented to map identified kernels to either the CPU or GPU so that kernel execution on the CPU and the GPU happens synergistically and the amount of data transfer needed is minimized. In order to ensure required data movement for dependencies across basic blocks, we propose a data flow analysis and edge splitting strategy. Thus our compiler automatically handles composition of kernels, mapping of kernels to CPU and GPU, scheduling and insertion of required data transfer. The proposed compiler was implemented and experimental evaluation using a set of MATLAB benchmarks shows that our approach achieves a geometric mean speedup of 19.8X for data parallel benchmarks over native execution of MATLAB.

Noniterative inversion strategy for photoacoustic tomography: recovery of absorbed energy map from boundary pressure measurements

The inverse problem in photoacoustic tomography (PAT) seeks to obtain the absorbed energy map from the boundary pressure measurements for which computationally intensive iterative algorithms exist. The computational challenge is heightened when the reconstruction is done using boundary data split into its frequency spectrum to improve source localization and conditioning of the inverse problem. The key idea of this work is to modify the update equation wherein the Jacobian and the perturbation in data are summed over all wave numbers, k, and inverted only once to recover the absorbed energy map. This leads to a considerable reduction in the overall computation time. The results obtained using simulated data, demonstrates the efficiency of the proposed scheme without compromising the accuracy of reconstruction.

An Outward-Wave-Favouring Finite Element-Based Strategy for Exterior Acoustical Problems

This work presents a finite element-based strategy for exterior acoustical problems based on an assumed pressure form that favours outgoing waves. The resulting governing equation, weak formulation, and finite element formulation are developed both for coupled and uncoupled problems. The developed elements are very similar to conventional elements in that they are based on the standard Galerkin variational formulation and use standard Lagrange interpolation functions and standard Gaussian quadrature. In addition and in contrast to wave envelope formulations and their extensions, the developed elements can be used in the immediate vicinity of the radiator/scatterer. The method is similar to the perfectly matched layer (PML) method in the sense that each layer of elements added around the radiator absorbs acoustical waves so that no boundary condition needs to be applied at the outermost boundary where the domain is truncated. By comparing against strategies such as the PML and wave-envelope methods, we show that the relative accuracy, both in the near and far-field results, is considerably higher.

Gene expression programming-fuzzy logic method for crop type classification

Crop type classification using remote sensing data plays a vital role in planning cultivation activities and for optimal usage of the available fertile land. Thus a reliable and precise classification of agricultural crops can help improve agricultural productivity. Hence in this paper a gene expression programming based fuzzy logic approach for multiclass crop classification using Multispectral satellite image is proposed. The purpose of this work is to utilize the optimization capabilities of GEP for tuning the fuzzy membership functions. The capabilities of GEP as a classifier is also studied. The proposed method is compared to Bayesian and Maximum likelihood classifier in terms of performance evaluation. From the results we can conclude that the proposed method is effective for classification.

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation I as augmentation therapeutic strategy approaches in muscular dystrophy

Backgrond: Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods: In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results: The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

An integrated model for optimal reservoir operation for irrigation of multiple crops

An integratedm odel is developed,b asedo n seasonailn puts of reservoiri nflow and rainfall in the irrigated area, to determine the optimal reservoir release policies and irrigation allocationst o multiple crops.T he model is conceptuallym ade up of two modules. Module 1 is an intraseasonal allocation model to maximize the sum of relative yieldso f all crops,f or a givens tateo f the systemu, singl inear programming(L P). The module takes into account reservoir storage continuity, soil moisture balance, and crop root growthw ith time. Module 2 is a seasonaal llocationm odel to derive the steadys tate reservoiro peratingp olicyu sings tochastidc ynamicp rogramming(S DP). Reservoir storage, seasonal inflow, and seasonal rainfall are the state variables in the SDP. The objective in SDP is to maximize the expected sum of relative yields of all crops in a year.The resultso f module 1 and the transitionp robabilitieso f seasonailn flow and rainfall form the input for module 2. The use of seasonailn puts coupledw ith the LP-SDP solution strategy in the present formulation facilitates in relaxing the limitations of an earlier study,w hile affectinga dditionali mprovementsT. he model is applied to an existing reservoir in Karnataka State, India.

On Uniform Approximate Solutions in Bending of Symmetric Laminated Plates

A layer-wise theory with the analysis of face ply independent of lamination is used in the bending of symmetric laminates with anisotropic plies. More realistic and practical edge conditions as in Kirchhoff's theory are considered. An iterative procedure based on point-wise equilibrium equations is adapted. The necessity of a solution of an auxiliary problem in the interior plies is explained and used in the generation of proper sequence of two dimensional problems. Displacements are expanded in terms of polynomials in thickness coordinate such that continuity of transverse stresses across interfaces is assured. Solution of a fourth order system of a supplementary problem in the face ply is necessary to ensure the continuity of in-plane displacements across interfaces and to rectify inadequacies of these polynomial expansions in the interior distribution of approximate solutions. Vertical deflection does not play any role in obtaining all six stress components and two in-plane displacements. In overcoming lacuna in Kirchhoff's theory, widely used first order shear deformation theory and other sixth and higher order theories based on energy principles at laminate level in smeared laminate theories and at ply level in layer-wise theories are not useful in the generation of a proper sequence of 2-D problems converging to 3-D problems. Relevance of present analysis is demonstrated through solutions in a simple text book problem of simply supported square plate under doubly sinusoidal load.

A strategy-proof and budget-balanced mechanism for carbon footprint reduction by global companies

The problem addressed in this paper is concerned with an important issue faced by any green aware global company to keep its emissions within a prescribed cap. The specific problem is to allocate carbon reductions to its different divisions and supply chain partners in achieving a required target of reductions in its carbon reduction program. The problem becomes a challenging one since the divisions and supply chain partners, being autonomous, may exhibit strategic behavior. We use a standard mechanism design approach to solve this problem. While designing a mechanism for the emission reduction allocation problem, the key properties that need to be satisfied are dominant strategy incentive compatibility (DSIC) (also called strategy-proofness), strict budget balance (SBB), and allocative efficiency (AE). Mechanism design theory has shown that it is not possible to achieve the above three properties simultaneously. In the literature, a mechanism that satisfies DSIC and AE has recently been proposed in this context, keeping the budget imbalance minimal. Motivated by the observation that SBB is an important requirement, in this paper, we propose a mechanism that satisfies DSIC and SBB with slight compromise in allocative efficiency. Our experimentation with a stylized case study shows that the proposed mechanism performs satisfactorily and provides an attractive alternative mechanism for carbon footprint reduction by global companies.

A divide and conquer strategy for scaling weather simulations with multiple regions of interest

Accurate and timely prediction of weather phenomena, such as hurricanes and flash floods, require high-fidelity compute intensive simulations of multiple finer regions of interest within a coarse simulation domain. Current weather applications execute these nested simulations sequentially using all the available processors, which is sub-optimal due to their sub-linear scalability. In this work, we present a strategy for parallel execution of multiple nested domain simulations based on partitioning the 2-D processor grid into disjoint rectangular regions associated with each domain. We propose a novel combination of performance prediction, processor allocation methods and topology-aware mapping of the regions on torus interconnects. Experiments on IBM Blue Gene systems using WRF show that the proposed strategies result in performance improvement of up to 33% with topology-oblivious mapping and up to additional 7% with topology-aware mapping over the default sequential strategy.

Optimal synthesis of adjustable planar four-bar crank-rocker type mechanisms for approximate multi-path generation

This paper deals with an optimization based method for synthesis of adjustable planar four-bar, crank-rocker mechanisms. For multiple different and desired paths to be traced by a point on the coupler, a two stage method first determines the parameters of the possible driving dyads. Then the remaining mechanism parameters are determined in the second stage where a least-squares based circle-fitting procedure is used. Compared to existing formulations, the optimization method uses less number of design variables. Two numerical examples demonstrate the effectiveness of the proposed synthesis method. (C) 2013 Elsevier Ltd. All rights reserved.

Generalized model predictive static programming and its application to 3D impact angle constrained guidance of air-to-surface missiles

A new `generalized model predictive static programming (G-MPSP)' technique is presented in this paper in the continuous time framework for rapidly solving a class of finite-horizon nonlinear optimal control problems with hard terminal constraints. A key feature of the technique is backward propagation of a small-dimensional weight matrix dynamics, using which the control history gets updated. This feature, as well as the fact that it leads to a static optimization problem, are the reasons for its high computational efficiency. It has been shown that under Euler integration, it is equivalent to the existing model predictive static programming technique, which operates on a discrete-time approximation of the problem. Performance of the proposed technique is demonstrated by solving a challenging three-dimensional impact angle constrained missile guidance problem. The problem demands that the missile must meet constraints on both azimuth and elevation angles in addition to achieving near zero miss distance, while minimizing the lateral acceleration demand throughout its flight path. Both stationary and maneuvering ground targets are considered in the simulation studies. Effectiveness of the proposed guidance has been verified by considering first order autopilot lag as well as various target maneuvers.