The biology and pathogenesis of hepatitis viruses

Viral hepatitis is caused mainly by infection with one of the five hepatitis viruses, which use the liver as their primary site of replication. Each of these, known as hepatitis A through E viruses (HAV to HEV), belong to different virus families, have unique morphology, genomic organization and replication strategy. These viruses cause similar clinical manifestations during the acute phase of infection but vary in their ability to cause chronic infection. While HAV and HEV cause only acute disease with no chronic sequelae, HBV, HCV and HDV cause varying degrees of chronicity and liver injury, which can progress to cirrhosis and liver cancers. Though specific serological tests are available for the known hepatitis viruses, nearly 20% of all hepatitis cases show no markers. Antiviral therapy is also recommended for some hepatitis viruses and a preventive vaccine is available only for hepatitis B. More research and public awareness programmes are needed to control the disease. This review will provide an overview of the hepatitis viruses and the disease they cause.

A genetic algorithm with characteristic amplification through multiple geographically isolated populations and varied fitness landscapes

This paper proposes a new approach, wherein multiple populations are evolved on different landscapes. The problem statement is broken down, to describe discrete characteristics. Each landscape, described by its fitness landscape is used to optimize or amplify a certain characteristic or set of characteristics. Individuals from each of these populations are kept geographically isolated from each other Each population is evolved individually. After a predetermined number of evolutions, the system of populations is analysed against a normalized fitness function. Depending on this score and a predefined merging scheme, the populations are merged, one at a time, while continuing evolution. Merging continues until only one final population remains. This population is then evolved, following which the resulting population will contain the optimal solution. The final resulting population will contain individuals which have been optimized against all characteristics as desired by the problem statement. Each individual population is optimized for a local maxima. Thus when populations are merged, the effect is to produce a new population which is closer to the global maxima.

A genetic algorithm with characteristic amplification through multiple geographically isolated populations and varied fitness landscapes

This paper proposes a new approach, wherein multiple populations are evolved on different landscapes. The problem statement is broken down, to describe discrete characteristics. Each landscape, described by its fitness landscape is used to optimize or amplify a certain characteristic or set of characteristics. Individuals from each of these populations are kept geographically isolated from each other Each population is evolved individually. After a predetermined number of evolutions, the system of populations is analysed against a normalized fitness function. Depending on this score and a predefined merging scheme, the populations are merged, one at a time, while continuing evolution. Merging continues until only one final population remains. This population is then evolved, following which the resulting population will contain the optimal solution. The final resulting population will contain individuals which have been optimized against all characteristics as desired by the problem statement. Each individual population is optimized for a local maxima. Thus when populations are merged, the effect is to produce a new population which is closer to the global maxima.

Emerging trends at the interface of chemistry and biology: Applications to the design of human therapeutics

This article describes recent developments in the design and implementation of various strategies towards the development of novel therapeutics using first principles from biology and chemistry. Strategies for multi-target therapeutics and network analysis with a focus on cancer and HIV are discussed. Methods for gene and siRNA delivery are presented along with challenges and opportunities for siRNA therapeutics. Advances in protein design methodology and screening are described, with a focus on their application to the design of antibody based therapeutics. Future advances in this area relevant to vaccine design are also mentioned.

Framework for enabling highly available distributed applications for utility computing

The move towards IT outsourcing is the first step towards an environment where compute infrastructure is treated as a service. In utility computing this IT service has to honor Service Level Agreements (SLA) in order to meet the desired Quality of Service (QoS) guarantees. Such an environment requires reliable services in order to maximize the utilization of the resources and to decrease the Total Cost of Ownership (TCO). Such reliability cannot come at the cost of resource duplication, since it increases the TCO of the data center and hence the cost per compute unit. We, in this paper, look into aspects of projecting impact of hardware failures on the SLAs and techniques required to take proactive recovery steps in case of a predicted failure. By maintaining health vectors of all hardware and system resources, we predict the failure probability of resources based on observed hardware errors/failure events, at runtime. This inturn influences an availability aware middleware to take proactive action (even before the application is affected in case the system and the application have low recoverability). The proposed framework has been prototyped on a system running HP-UX. Our offline analysis of the prediction system on hardware error logs indicate no more than 10% false positives. This work to the best of our knowledge is the first of its kind to perform an end-to-end analysis of the impact of a hardware fault on application SLAs, in a live system.

Computing complete test graphs for hierarchical systems

Conformance testing focuses on checking whether an implementation. under test (IUT) behaves according to its specification. Typically, testers are interested it? performing targeted tests that exercise certain features of the IUT This intention is formalized as a test purpose. The tester needs a "strategy" to reach the goal specified by the test purpose. Also, for a particular test case, the strategy should tell the tester whether the IUT has passed, failed. or deviated front the test purpose. In [8] Jeron and Morel show how to compute, for a given finite state machine specification and a test purpose automaton, a complete test graph (CTG) which represents all test strategies. In this paper; we consider the case when the specification is a hierarchical state machine and show how to compute a hierarchical CTG which preserves the hierarchical structure of the specification. We also propose an algorithm for an online test oracle which avoids a space overhead associated with the CTG.

Specification-driven approach for protocol design of distributed computing systems

An important issue in the design of a distributed computing system (DCS) is the development of a suitable protocol. This paper presents an effort to systematize the protocol design procedure for a DCS. Protocol design and development can be divided into six phases: specification of the DCS, specification of protocol requirements, protocol design, specification and validation of the designed protocol, performance evaluation, and hardware/software implementation. This paper describes techniques for the second and third phases, while the first phase has been considered by the authors in their earlier work. Matrix and set theoretic based approaches are used for specification of a DCS and for specification of the protocol requirements. These two formal specification techniques form the basis of the development of a simple and straightforward procedure for the design of the protocol. The applicability of the above design procedure has been illustrated by considering an example of a computing system encountered on board a spacecraft. A Petri-net based approach has been adopted to model the protocol. The methodology developed in this paper can be used in other DCS applications.

Gas turbine diagnostics using a soft computing approach

A fuzzy system is developed using a linearized performance model of the gas turbine engine for performing gas turbine fault isolation from noisy measurements. By using a priori information about measurement uncertainties and through design variable linking, the design of the fuzzy system is posed as an optimization problem with low number of design variables which can be solved using the genetic algorithm in considerably low amount of computer time. The faults modeled are module faults in five modules: fan, low pressure compressor, high pressure compressor, high pressure turbine and low pressure turbine. The measurements used are deviations in exhaust gas temperature, low rotor speed, high rotor speed and fuel flow from a base line 'good engine'. The genetic fuzzy system (GFS) allows rapid development of the rule base if the fault signatures and measurement uncertainties change which happens for different engines and airlines. In addition, the genetic fuzzy system reduces the human effort needed in the trial and error process used to design the fuzzy system and makes the development of such a system easier and faster. A radial basis function neural network (RBFNN) is also used to preprocess the measurements before fault isolation. The RBFNN shows significant noise reduction and when combined with the GFS leads to a diagnostic system that is highly robust to the presence of noise in data. Showing the advantage of using a soft computing approach for gas turbine diagnostics.

Computing a matrix symmetrizer exactly using modified multiple modulus residue arithmetic

A symmetric solution X satisfying the matrix equation XA = AtX is called a symmetrizer of the matrix A. A general algorithm to compute a matrix symmetrizer is obtained. A new multiple-modulus residue arithmetic called floating-point modular arithmetic is described and implemented on the algorithm to compute an error-free matrix symmetrizer.

On computing an equivalent symmetric matrix for a nonsymmetric matrix

A real or a complex symmetric matrix is defined here as an equivalent symmetric matrix for a real nonsymmetric matrix if both have the same eigenvalues. An equivalent symmetric matrix is useful in computing the eigenvalues of a real nonsymmetric matrix. A procedure to compute equivalent symmetric matrices and its mathematical foundation are presented.

Functional linkages can reveal protein complexes for structure determination

The study of molecular machines, and protein complexes in general, is a growth area of biology. Is there a computational method for inferring which combinations of proteins in an organism are likely to form a crystallizable complex? We use the Protein Data Bank (PDB) to assess the usefulness of inferred functional protein linkages for this task. We find that of 242 nonredundant prokaryotic protein complexes (complexes excluding structural variants of the same protein) from organisms that are shared between the current PDB and the Prolinks functional linkage database, 44% (107/242) contain proteins that are linked at high-confidence by one or more methods of computed functional linkages. This suggests that computing functional linkages will be useful in defining protein complexes for structural studies. We offer a database of such inferred linkages corresponding to likely protein complexes for some 629,952 pairs of proteins in 154 prokaryotes and archea.

Visiting the cell biology of Salmonella infection

Salmonella, a Gram-negative facultative intracellular pathogen is capable of infecting vast array of hosts. The striking ability of Salmonella to overcome every hurdle encountered in the host proves that they are true survivors. In the host, Salmonella infects various cell types and needs to survive and replicate by countering the defense mechanism of the specific cell. In this review, we will summarize the recent insights into the cell biology of Salmonella infection. Here, we will focus on the findings that deal with the specific mechanism of various cell types to control Salmonella infection. Further, the survival strategies of the pathogen in response to the host immunity will also be discussed in detail. Better understanding of the mechanisms by which Salmonella evade the host defense system and establish pathogenesis will be critical in disease management. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

A geodesic constant method for computing high-frequency mutual coupling between antennas on general quadric cylinders

A Geodesic Constant Method (GCM) is outlined which provides a common approach to ray tracing on quadric cylinders in general, and yields all the surface ray-geometric parameters required in the UTD mutual coupling analysis of conformal antenna arrays in the closed form. The approach permits the incorporation of a shaping parameter which permits the modeling of quadric cylindrical surfaces of desired sharpness/flatness with a common set of equations. The mutual admittance between the slots on a general parabolic cylinder is obtained as an illustration of the applicability of the GCM.