Antibody-mediated catalysis: Induction and therapeutic relevance

Abzymes are immunoglobulins endowed with enzymatic activities. The catalytic activity of an abzyme resides in the variable domain of the antibody, which is constituted by the close spatial arrangement of amino acid residues involved in catalysis. The origin of abzymes is conferred by the innate diversity of the immunoglobulin gene repertoire. Under deregulated immune conditions, as in autoimmune diseases, the generation of abzymes to self-antigens could be deleterious. Technical advancement in the ability to generate monoclonal antibodies has been exploited in the generation of abzymes with defined specificities and activities. Therapeutic applications of abzymes are being investigated with the generation of monoclonal abzymes against several pathogenesis-associated antigens. Here, we review the different contexts in which abzymes are generated, and we discuss the relevance of monoclonal abzymes for the treatment of human diseases.

Mobile agent based node monitoring protocol for MANETs

Mobile ad-hoc network is a wireless ad-hoc network with dynamic network topology. The Dynamicity, due to the random node movement, and scarcity of resources lead to a challenge in monitoring the nodes in a MANET. Monitoring the lack of resources (bandwidth, buffer, and energy), misbehavior, and mobility at node level remains, a challenge. In a MANET the proposed protocol uses both static as well as mobile agents, where the mobile agents migrate to different clusters of the zones respectively, collect the node status information periodically, and provide a high level information to the static agent (which resides at the central node) by analyzing the raw information at the nodes. This, in turn, reduces the network traffic and conserves the workload of the central node, where a static agent is available with high level information and in coordination with other modules. The protocol has been tested in different size MANETs with variable number of nodes and applications. The results shown in the simulation indicates the effectiveness of the protocol.

SeaMo plus : a virtual real-time multimedia service framework on handhelds to enable remote real-time patient monitoring for mobile doctors

The key requirements for enabling real-time remote healthcare service on a mobile platform, in the present day heterogeneous wireless access network environment, are uninterrupted and continuous access to the online patient vital medical data, monitor the physical condition of the patient through video streaming, and so on. For an application, this continuity has to be sufficiently transparent both from a performance perspective as well as a Quality of Experience (QoE) perspective. While mobility protocols (MIPv6, HIP, SCTP, DSMIP, PMIP, and SIP) strive to provide both and do so, limited or non-availability (deployment) of these protocols on provider networks and server side infrastructure has impeded adoption of mobility on end user platforms. Add to this, the cumbersome OS configuration procedures required to enable mobility protocol support on end user devices and the user's enthusiasm to add this support is lost. Considering the lack of proper mobility implementations that meet the remote healthcare requirements above, we propose SeaMo+ that comprises a light-weight application layer framework, termed as the Virtual Real-time Multimedia Service (VRMS) for mobile devices to provide an uninterrupted real-time multimedia information access to the mobile user. VRMS is easy to configure, platform independent, and does not require additional network infrastructure unlike other existing schemes. We illustrate the working of SeaMo+ in two realistic remote patient monitoring application scenarios.

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.

Albumin-mediated incorporation of water-insoluble therapeutics in layer-by-layer assembled thin films and microcapsules

The present study demonstrates a method to deliver hydrophobic drugs by incorporation into thin films and microcapsules fabricated via a layer-by-layer assembly approach. The hydrophobic molecule binding properties of albumin have been exploited for solubilization of a water-insoluble molecule, pyrene (model drug), by preparation of non-covalent conjugates with bovine serum albumin (BSA). Conjugation with BSA renders a highly negative zeta potential to the previously uncharged pyrene which favors the assembly formation by electrostatic interaction with a positively charged polyelectrolyte, chitosan (at acidic pH). The growth of the assembly was followed by monitoring pyrene absorbance with successive layer deposition. The thin film assembly was demonstrated to be capable of releasing its hydrophobic cargo under physiological conditions. We demonstrated the applicability of this approach by encapsulating a water-insoluble drug, curcumin. These assemblies were further loaded with the anti-cancer drug Doxorubicin. Biocompatible calcium carbonate microparticles were used for capsule preparation. The porous nature of the microparticles allows for the pre-encapsulation of therapeutic macromolecules like protein. The fabrication of protein encapsulated stable microcapsules with hydrophobic molecules incorporated into the shell of the microcapsules has been demonstrated. The microcapsules were further capable of loading hydrophilic molecules like Rhodamine B. Thus, using the approach described, a multi-agent carrier for hydrophobic and hydrophilic drugs as well as therapeutic macromolecules can be envisioned.

Real time monitoring of petroleum leakage detection using etched fiber Bragg grating

Detection of petroleum leakages in pipelines and storage tanks is a very important as it may lead to significant pollution of the environment, accidental hazards, and also it is a very important fuel resource. Petroleum leakage detection sensor based on fiber optics was fabricated by etching the fiber Bragg grating (FBG) to a region where the total internal reflection is affected. The experiment shows that the reflected Bragg's wavelength and intensity goes to zero when etched FBG is in air and recovers Bragg's wavelength and intensity when it is comes in contact with petroleum or any external fluid. This acts as high sensitive, fast response fluid optical switch in liquid level sensing, petroleum leakage detection etc. In this paper we present our results on using this technique in petroleum leakage detection.

Compositional hierarchical monitoring automaton construction for LTL

In this paper we give a compositional (or inductive) construction of monitoring automata for LTL formulas. Our construction is similar in spirit to the compositional construction of Kesten and Pnueli [5]. We introduce the notion of hierarchical Büchi automata and phrase our constructions in the framework of these automata. We give detailed constructions for all the principal LTL operators including past operators, along with proofs of correctness of the constructions.

Resource usage monitoring for KVM based virtual machines

Realization of cloud computing has been possible due to availability of virtualization technologies on commodity platforms. Measuring resource usage on the virtualized servers is difficult because of the fact that the performance counters used for resource accounting are not virtualized. Hence, many of the prevalent virtualization technologies like Xen, VMware, KVM etc., use host specific CPU usage monitoring, which is coarse grained. In this paper, we present a performance monitoring tool for KVM based virtualized machines, which measures the CPU overhead incurred by the hypervisor on behalf of the virtual machine along-with the CPU usage of virtual machine itself. This fine-grained resource usage information, provided by the above tool, can be used for diverse situations like resource provisioning to support performance associated QoS requirements, identification of bottlenecks during VM placements, resource profiling of applications in cloud environments, etc. We demonstrate a use case of this tool by measuring the performance of web-servers hosted on a KVM based virtualized server.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

A method of developing an agent based ubiquitous node monitoring protocol

A ubiquitous network plays a critical role to provide rendered services to ubiquitous application running nodes. To provide appropriate resources the nodes are needed to be monitored continuously. Monitoring a node in ubiquitous network is challenging because of dynamicity and heterogeneity of the ubiquitous network. The network monitor has to monitor resource parameters, like data rate, delay and throughput, as well as events such as node failure, network failure and fault in the system to curb the system failure. In this paper, we propose a method to develop a ubiquitous system monitoring protocol using agents. Earlier works on network monitoring using agents consider that the agents are designed for particular network. While in our work the heterogeneity property of the network has been considered. We have shown that the nodes' behaviour can be easily monitored by using agents (both static and mobile agent). The past behavior of the application and network, and past history of the Unode and the predecessor are taken into consideration to help SA to take appropriate decision during the time of emergency situation like unavailability of resources at the local administration, and to predict the migration of the Unode based on the previous node history. The results obtained in the simulation reflects the effectiveness of the technique.

Hypersensitivity of hypoxia grown Mycobacterium smegmatis to DNA damaging agents: Implications of the DNA repair deficiencies in attenuation of mycobacteria

Mycobacteria are an important group of pathogenic bacteria. We generated a series of DNA repair deficient strains of Mycobacterium smegmatis, a model organism, to understand the importance of various DNA repair proteins (UvrB, Ung, UdgB, MutY and Fpg) in survival of the pathogenic strains. Here, we compared tolerance of the M. smegmatis strains to genotoxic stress (ROS and RNI) under aerobic, hypoxic and recovery conditions of growth by monitoring their survival. We show an increased susceptibility of mycobacteria to genotoxic stress under hypoxia. UvrB deficiency led to high susceptibility of M. smegmatis to the DNA damaging agents. Ung was second in importance in strains with single deficiencies. Interestingly, we observed that while deficiency of UdgB had only a minor impact on the strain's susceptibility, its combination with Ung deficiency resulted in severe consequences on the strain's survival under genotoxic stress suggesting a strong interdependence of different DNA repair pathways in safeguarding genomic integrity. Our observations reinforce the possibility of targeting DNA repair processes in mycobacteria for therapeutic intervention during active growth and latency phase of the pathogen. High susceptibility of the UvrB, or the Ung/UdgB deficient strains to genotoxic stress may be exploited in generation of attenuated strains of mycobacteria. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

6PANview: Application performance conscious network monitoring for 6LoWPAN based WSNs

6PANview[1] is a Wireless Sensor Network(WSN) monitoring system for 6LoWPAN/RPL networks which we developed as an overlay network for a WSN application. A monitoring system, while performing its operations for maintaining the health of the monitored network, must also be conscious of its impact on the application performance, and must strive to minimize this impact. To this end, we propose a centralized scheduling algorithm within 6PANview which non-intrusively analyzes application traffic arrival patterns at the base station, identifies network idle periods and schedules monitoring activities. The proposed algorithm finds those periodic sequences which are likely to have given rise to the pattern of arrivals seen at the base station. Parts of those sequences are then extended to coarsely predict future traffic and find epochs where low traffic is predicted, in order to schedule monitoring traffic or other activities at these times. We present simulation results for the proposed prediction and scheduling algorithm and its implementation as part of 6PANview. As an enhancement, we briefly talk about using 6PANview's overlay network architecture for distributed scheduling.

Structural health monitoring of aerospace structural components using wave propagation based diagnostics

The paper discusses a wave propagation based method for identifying the damages in an aircraft built up structural component such as delamination and skin-stiffener debonding. First, a spectral finite element mode l (SFEM) is developed for modeling wave propagation in general built-up structures by using the concept of assembling 2D spectral plate elements. The developed numerical model is validated using conventional 2-D FEM. Studies are performed to capture the mode coupling,that is, the flexural-axial coupling present in the wave responses. Lastly, the damages in these built up structures are then identified using the developed SFEM model and the measured responses using the concept Damage Force Indicator (DFI) technique.

Acoustic emission techniques for NDE & structural health monitoring of advanced composite materials

Structural Health Monitoring (SHM) is an effective extension of NDE to reduce down time and cost of Inspection of structural components. On – line monitoring is an essential part of SHM. Acoustic Emission Techniques have most of the desirable requirements of an effective SHM tool. With the kind of advancement seen in the last couple of decades in the field of electronics, computers and signal processing technologies it can only be more helpful in obtaining better and meaningful quantitative results which can further enhance the potential of AET for the purpose. Advanced Composite materials owing to their specific high performance characteristics are finding a wide range of engineering applications. Testing and Evaluation of this category of materials and SHM of composite structures have been very challenging problems due to the very nature of these materials. Mechanical behaviour of fiber composite materials under different loading conditions is complex and involves different types of failure mechanisms. This is where the potential of AET can be exploited effectively. This paper presents an over view of some relevant studies where AET has been utilised to test, evaluate and monitor health of composite structures.

Monitoring of ultraviolet pulse rate dependent photomechanical actuation in carbon nanotubes using fiber Bragg gratings

In this Letter, we present a non-contact method of controlling and monitoring photomechanical actuation in carbon nanotubes (CNT) by exposing it to ultra-violet radiation at different pulse rates (10 to 200 Hz). This is accomplished by imparting a reversible photo induced strain (5-330 mu epsilon) on CNT coated fibre Bragg gratings; CNT undergoes an internal reversible structural change due to cyclic photon absorption that leads to the development of mechanical strain, which in turn allows reversible switching of the Bragg wavelength. The results also reveal an interesting pulse rate dependent rise and fall times of photomechanical actuation in CNT. (C) 2014 AIP Publishing LLC.