Avian Influenza (H5N1) Virus of Clade 2.3.2 in Domestic Poultry in India

South Asia has experienced regular outbreaks of H5N1 avian influenza virus since its first detection in India and Pakistan in February, 2006. Till 2009, the outbreaks in this region were due to clade 2.2 H5N1 virus. In 2010, Nepal reported the first outbreak of clade 2.3.2 virus in South Asia. In February 2011, two outbreaks of H5N1 virus were reported in the State of Tripura in India. The antigenic and genetic analyses of seven H5N1 viruses isolated during these outbreaks were carried out. Antigenic analysis confirmed 64 to 256-fold reduction in cross reactivity compared with clade 2.2 viruses. The intravenous pathogenicity index of the isolates ranged from 2.80–2.95 indicating high pathogenicity to chickens. Sequencing of all the eight gene-segments of seven H5N1 viruses isolated in these outbreaks was carried out. The predicted amino acid sequence analysis revealed high pathogenicity to chickens and susceptibility to the antivirals, amantadine and oseltamivir. Phylogenetic analyses indicated that these viruses belong to clade 2.3.2.1 and were distinct to the clade 2.3.2.1 viruses isolated in Nepal. Identification of new clade 2.3.2 H5N1 viruses in South Asia is reminiscent of the introduction of clade 2.2 viruses in this region in 2006/7. It is now important to monitor whether the clade 2.3.2.1 is replacing clade 2.2 in this region or co-circulating with it. Continued co-circulation of various subclades of the H5N1 virus which are more adapted to land based poultry in a highly populated region such as South Asia increases the risk of evolution of pandemic H5N1 strains

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m(2) on days 1 and 2 of cycle 1; 27 mg/m(2) thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients

Control Growth Factor Release Using a Self-Assembled [polycation∶heparin] Complex

The importance of growth factors has been recognized for over five decades; however their utilization in medicine has yet to be fully realized. This is because free growth factors have short half-lives in plasma, making direct injection inefficient. Many growth factors are anchored and protected by sulfated glycosaminoglycans in the body. We set out to explore the use of heparin, a well-characterized sulfated glycosaminoglycan, for the controlled release of fibroblast growth factor-2 (FGF-2). Heparin binds a multitude of growth factors and maintains their bioactivity for an extended period of time. We used a biocompatible polycation to precipitate out the [heparin∶FGF-2] complex from neutral buffer to form a release matrix. We can control the release rate of FGF-2 from the resultant matrix by altering the molecular weight of the polycation. The FGF-2 released from the delivery complex maintained its bioactivity and initiated cellular responses that were at least as potent as fresh bolus FGF-2 and fresh heparin stabilized FGF-2. This new delivery platform is not limited to FGF-2 but applicable to the large family of heparin-binding growth factors

Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels

A novel enzyme-responsive hydrogel drug delivery system was developed with the potential to treat inflammation locally. Human neutrophil elastase (HNE) is a serine protease secreted by neutrophils which are the first cells recruited to inflammatory sites. We exploited this cell-secreted enzyme as a biological cue for controlled release. HNE sensitive peptide linkers were immobilized within poly(ethylene glycol) hydrogels using photopolymerization techniques. The kinetics of the enzyme reaction within the gel was tailored by varying the amino acid residues present in the P1 and P1 ′ substrate positions (immediately adjacent to cleavage location). A novel FRET-based hydrogel platform was designed to characterize the accessibility of the substrate within the cross-linked, macroscopic hydrogel. Lastly, a diffusion-reaction mathematical model with Michaelis-Menten kinetics was developed to predict the overall release profile and captured the initial 80 % of the experimentally observed release. The hydrogel platform presented shows highly controlled release kinetics with potential applications in cellular responsive drug delivery. 1

The Use of Biomaterials in Islet Transplantation

Pancreatic islet transplantation is a therapeutic option to replace destroyed β cells in autoimmune diabetes. Islets are transplanted into the liver via the portal vein; however, inflammation, the required immunosuppression, and lack of vasculature decrease early islet viability and function. Therefore, the use of accessory therapy and biomaterials to protect islets and improve islet function has definite therapeutic potential. Here we review the application of niche accessory cells and factors, as well as the use of biomaterials as carriers or capsules, for pancreatic islet transplantation

Enantiomeric and Diastereomeric Self-Assembled Multivalent Nanostructures : Understanding the Effects of Chirality on Binding to Polyanionic Heparin and DNA

A family of four self-assembling lipopeptides containing Ala-Lys peptides attached to a C16 aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C16-l-Ala-l-Lys/C16-d-Ala-d-Lys) and (C16-d-Ala-l-Lys/C16-l-Ala-d-Lys). These diastereomeric pairs have very different critical micelle concentrations (CMCs). The self-assembled multivalent (SAMul) systems bind biological polyanions as a result of the cationic lysine groups on their surfaces. For heparin binding, there was no significant enantioselectivity, but there was a binding preference for the diastereomeric assemblies with lower CMCs. Conversely, for DNA binding, there was significant enantioselectivity for systems displaying d-lysine ligands, with a further slight preference for attachment to l-alanine, with the CMC being irrelevant

FLIGHT INSTRUMENTATION TELEMETRY FOR AEROSPACE APPLICATION

International Telemetering Conference Proceedings / October 13-16, 1986 / Riviera Hotel, Las Vegas, NevadaIn Aerospace missions it is often required to have a flexible telemetry system for carrying out flight test on aircraft, in which the bit rate, sampling rate and the number of channels can be programmed. This enables the pilot of the aircraft to reconfigure the telemetry system to suit any particular test missions. An L-Band PCM/FM Telemetry System containing a Stored Programme Multiplexer, 12 bit ADC and other digital interfaces for carrying out the measurements on Speed, Events, etc has been developed as a flight instrumentation telemetry for HAL, India. This paper not only presents complete details of the system, which was qualified to meet MIL-5422 levels but also the performance of the system during actual aircraft missions.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

Data Handling System for IRS

International Telemetering Conference Proceedings / October 26-29, 1987 / Town and Country Hotel, San Diego, CaliforniaThe three axis stabilized Indian Remote Sensing Satellite will image the earth from a 904 Km polar - sun synchronous orbit. The payload is a set of CCD cameras which collect data in four bands visible and near infra-red region. This payload data from two cameras, each at 10.4 megabits per sec is transmitted in a balanced QPSK in X Band. The payload data before transmission is formatted by adopting Major and Minor frame synchronizing codes. The formatted two streams of data are differentially encoded to take care of 4-phase ambiguity due to QPSK transmission. This paper describes the design and development aspects related to such a Data Handling System. It also highlights the environmental qualification tests that were carried out to meet the requirement of three years operational life of the satellite.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

An Implementation of Concatenated Coding Scheme on Indian Spacecraft

International Telemetering Conference Proceedings / October 26-29, 1987 / Town and Country Hotel, San Diego, CaliforniaA Concatenated Coding Scheme to provide an extremely 'clean' channel is suggested for onboard spacecraft telemetry system by the Consultative Committee for Space Data Systems (CCSDS). The outer code is a Reed Solomon block code and the inner, a Viterbi or Convolutional Code. The Gaussian channel are corrected by the inner code. However, the Viterbi decoder may introduce some burst errors. These are then corrected by the Reed Solomon decoder. The inner Viterbi code (K=7, rate 1/2) was developed and implemented for the first time in RSD2 (Rohini series) satellite. The outer code has not yet been implemented onboard spacecraft since the decoder has not been fully developed. However, the onboard encoding system (255,223) has been developed and tested. This paper describes the development and implementation of Viterbi encoder in RSD2 satellite along with its inorbit performance.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection