ATP release and autocrine signaling through P2X4 receptors regulate gamma delta T cell activation

Purinergic signaling plays a key role in a variety of physiological functions, including regulation of immune responses. Conventional alpha beta T cells release ATP upon TCR cross-linking; ATP binds to purinergic receptors expressed by these cells and triggers T cell activation in an autocrine and paracrine manner. Here, we studied whether similar purinergic signaling pathways also operate in the ``unconventional'' gamma delta T lymphocytes. We observed that gamma delta T cells purified from peripheral human blood rapidly release ATP upon in vitro stimulation with anti-CD3/CD28-coated beads or IPP. Pretreatment of gamma delta T cells with (10)panx-1, CBX, or Bf A reversed the stimulation-induced increase in extracellular ATP concentration, indicating that panx-1, connexin hemichannels, and vesicular exocytosis contribute to the controlled release of cellular ATP. Blockade of ATP release with (10)panx-1 inhibited Ca2+ signaling in response to TCR stimulation. qPCR revealed that gamma delta T cells predominantly express purinergic receptor subtypes A2a, P2X1, P2X4, P2X7, and P2Y11. We found that pharmacological inhibition of P2X4 receptors with TNP-ATP inhibited transcriptional up-regulation of TNF-alpha and IFN-gamma in gamma delta T cells stimulated with anti-CD3/CD28-coated beads or IPP. Our data thus indicate that purinergic signaling via P2X4 receptors plays an important role in orchestrating the functional response of circulating human gamma delta T cells. J. Leukoc. Biol. 92: 787-794; 2012.

Formulation development and evaluation of lamivudine controlled release tablets using cross-linked sago starch

Objectives: Modified starches based polymeric substances find utmost applicability in pharmaceutical formulation development. Cross-linked starches showed very promising results in drug delivery application. The present investigation concerns with the development of controlled release tablets of lamivudine using cross-linked sago starch. Methods: The cross-linked derivative was synthesized with phosphorous oxychloride and native sago starch in basic pH medium. The cross-linked sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulated tablets were evaluated for various physical characteristics, in vitro dissolution release study and in vivo pharmacokinetic study in rabbit model. Results: In vitro release study showed that the optimized formulation exhibited highest correlation (R) in case of zero order kinetic model and the release mechanism followed a combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T-max, C-max, AUC, V-d, T-1/2, and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir (R). Conclusion: The cross-linked starch showed promising results in terms of controlling the release behavior of the active drug from the matrix. The hydrophilic matrix synthesized by cross-linking could be used with a variety of active pharmaceutical ingredients for making their controlled/sustained release formulations.

Advanced multifunctional inorganic nanostructured oxides for controlled release and sensing

ADVANCED MULTIFUNCTIONAL INORGANIC NANOSTRUCTURED OXIDES FOR CONTROLLED RELEASE AND SENSING. We demonstrate here certain examples of multifunctional nanostructured oxidematerials for biotechnological and environmental applications.Various in-house synthesized homogeneous nanostructured viz.mesoporous and nanotubes silica and titania have been employed for controlled drug delivery and electrochemical biosensing applications. Confinement of macromolecules such as proteins studied via electrochemical, thermal and spectroscopic methods showed no detrimental effect on native protein structure and function, thus suggesting effective utility of oxide nanostructures as bio-encapsulators. Multi-functionalitywas demonstrated via employing similar nanostructures for sensing organic water pollutants e.g. textile dyes.

Petri net based performance modeling for effective DVFS for multithreaded programs

Dynamic Voltage and Frequency Scaling (DVFS) is a very effective tool for designing trade-offs between energy and performance. In this paper, we use a formal Petri net based program performance model that directly captures both the application and system properties, to find energy efficient DVFS settings for CMP systems, that satisfy a given performance constraint, for SPMD multithreaded programs. Experimental evaluation shows that we achieve significant energy savings, while meeting the performance constraints.

Evaluation of dynamic voltage and frequency scaling for stream programs

Dynamic Voltage and Frequency Scaling (DVFS) offers a huge potential for designing trade-offs involving energy, power, temperature and performance of computing systems. In this paper, we evaluate three different DVFS schemes - our enhancement of a Petri net performance model based DVFS method for sequential programs to stream programs, a simple profile based Linear Scaling method, and an existing hardware based DVFS method for multithreaded applications - using multithreaded stream applications, in a full system Chip Multiprocessor (CMP) simulator. From our evaluation, we find that the software based methods achieve significant Energy/Throughput2(ET−2) improvements. The hardware based scheme degrades performance heavily and suffers ET−2 loss. Our results indicate that the simple profile based scheme achieves the benefits of the complex Petri net based scheme for stream programs, and present a strong case for the need for independent voltage/frequency control for different cores of CMPs, which is lacking in most of the state-of-the-art CMPs. This is in contrast to the conclusions of a recent evaluation of per-core DVFS schemes for multithreaded applications for CMPs.

Dataflow analysis for data-race free programs

Memory models for shared-memory concurrent programming languages typically guarantee sequential consistency (SC) semantics for datarace-free (DRF) programs, while providing very weak or no guarantees for non-DRF programs. In effect programmers are expected to write only DRF programs, which are then executed with SC semantics. With this in mind, we propose a novel scalable solution for dataflow analysis of concurrent programs, which is proved to be sound for DRF programs with SC semantics. We use the synchronization structure of the program to propagate dataflow information among threads without requiring to consider all interleavings explicitly. Given a dataflow analysis that is sound for sequential programs and meets certain criteria, our technique automatically converts it to an analysis for concurrent programs.

Trends and Variability of AVHRR-Derived NPP in India

In this paper, we estimate the trends and variability in Advanced Very High Resolution Radiometer (AVHRR)-derived terrestrial net primary productivity (NPP) over India for the period 1982-2006. We find an increasing trend of 3.9% per decade (r = 0.78, R-2 = 0.61) during the analysis period. A multivariate linear regression of NPP with temperature, precipitation, atmospheric CO2 concentration, soil water and surface solar radiation (r = 0.80, R-2 = 0.65) indicates that the increasing trend is partly driven by increasing atmospheric CO2 concentration and the consequent CO2 fertilization of the ecosystems. However, human interventions may have also played a key role in the NPP increase: non-forest NPP growth is largely driven by increases in irrigated area and fertilizer use, while forest NPP is influenced by plantation and forest conservation programs. A similar multivariate regression of interannual NPP anomalies with temperature, precipitation, soil water, solar radiation and CO2 anomalies suggests that the interannual variability in NPP is primarily driven by precipitation and temperature variability. Mean seasonal NPP is largest during post-monsoon and lowest during the pre-monsoon period, thereby indicating the importance of soil moisture for vegetation productivity.

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.

Size independent fracture energy from fracture energy release rate in plain concrete beams

Size independent fracture energy and size effect on fracture energy are the key concerns for characterization of concrete fracture. Although there have been inconsistencies in results, a consensual fact is that the fracture energy from a large specimen is size independent. The fracture energy is proportional to the size of the fracture process zone (FPZ). FPZ size increases with size of the specimen, but the rate of increase of FPZ size decreases with increase in specimen size 1] implying that rate of increase of fracture energy decreases with increase in specimen size, more appropriately with increase in un-cracked ligament length. The ratio of fracture energy to the un-cracked ligament length almost becomes a constant at larger un-cracked ligament lengths. In the present study an attempt is made to obtain size independent fracture energy from fracture energy release rate. (C) 2012 Elsevier Ltd. All rights reserved.

Ages and relative sizes of pre-2004 tsunamis in the Bay of Bengal inferred from geologic evidence in the Andaman and Nicobar Islands

Geologic evidence along the northern part of the 2004 Aceh-Andaman rupture suggests that this region generated as many as five tsunamis in the prior 2000years. We identify this evidence by drawing analogy with geologic records of land-level change and the tsunami in 2004 from the Andaman and Nicobar Islands (A&N). These analogs include subsided mangrove swamps, uplifted coral terraces, liquefaction, and organic soils coated by sand and coral rubble. The pre-2004 evidence varies in potency, and materials dated provide limiting ages on inferred tsunamis. The earliest tsunamis occurred between the second and sixth centuries A.D., evidenced by coral debris of the southern Car Nicobar Island. A subsequent tsunami, probably in the range A.D. 770-1040, is inferred from deposits both in A&N and on the Indian subcontinent. It is the strongest candidate for a 2004-caliber earthquake in the past 2000years. A&N also contain tsunami deposits from A.D. 1250 to 1450 that probably match those previously reported from Sumatra and Thailand, and which likely date to the 1390s or 1450s if correlated with well-dated coral uplift offshore Sumatra. Thus, age data from A&N suggest that within the uncertainties in estimating relative sizes of paleo-earthquakes and tsunamis, the 1000year interval can be divided in half by the earthquake or earthquakes of A.D. 1250-1450 of magnitude >8.0 and consequent tsunamis. Unlike the transoceanic tsunamis generated by full or partial rupture of the subduction interface, the A&N geology further provides evidence for the smaller-sized historical tsunamis of 1762 and 1881, which may have been damaging locally.

Role of Fly Ash Pozzolanic Reactions in Controlling Fluoride Release from Phosphogypsum

Phosphogypsum is added to building materials to accelerate fly ash pozzolanic reaction and contributes to early strength development of concrete. The release of unacceptable fluoride levels by phoshogypsum on contact with water is a major impediment in its usage to manufacture building products because excess fluoride consumption causes dental and skeletal fluorosis. This paper examines the efficacy of fly ash pozzolanic reactions in controlling fluoride release by phosphogypsum. Fly ash (FA), sand (S), lime (L), and phosphogypsum (G) (FA-S-L-G) slurries are cured for various periods, and the fluoride released by the mix is monitored as a function of time. A substantial reduction in fluoride release was observed and is attributed to entrapment of phosphogypsum particles in a cementious matrix formed by fly ash-lime pozzolanic reactions coupled with consumption of fluoride in formation of insoluble compounds. The compressive strength developed by compacted FA-S-L-G specimens with time was observed to be a three-stage process; maximum strength mobilization occurred during 14 and 28days of curing at room temperature. Exposure of the compacted FA-S-L-G specimens to acidic and alkaline environments for 9 days did not impact their compressive strengths. (C) 2013 American Society of Civil Engineers.

Cryogenically cured hydroxyapatite-gelatin nanobiocomposite for bovine serum albumin protein adsorption and release

This research paper presents the first results on the protein adsorption and release kinetics and in vitro biodegradability of cryogenically cured hydroxyapatite-gelatin based micro/macroporous scaffolds (CHAMPS). While the adsorption and release of bovine serum albumin (BSA) protein exhibits steady state behavior over an incubation period of up to 10 days, Fourier transform infrared (FT-IR) analysis importantly confirms the absence of any change in the secondary structure of BSA proteins due to interaction with the CHAMPS scaffold. The compression properties of the CHAMPS scaffold with interconnected porosity (pore size similar to 50-200 mm) is characterized by a non-linear stress-strain response with a strength close to 5 MPa and a maximum strain of up to 24%. The slow but systematic increase in weight loss over a period of 7 days as well as apatite layer formation indicates its good bioactivity. The extensive micro-computed tomography (micro-CT) analysis establishes cancellous bone-like highly interconnected and complex porous architecture of the CHAMPS scaffold. Importantly, the excellent adsorption (up to 50%) and release (up to 60% of adsorbed protein) of BSA has been uniquely attributed to the inherent porous microstructure of the CHAMPS scaffold. Overall, the present study provides an assessment of the interaction of protein with the gelatin-hydroxyapatite macroporous scaffold in vitro, as well as reporting for the first time the efficacy of such scaffolds to release 60% of BSA loaded onto the scaffold in vitro, which is significantly higher than earlier literature reports.

Microcracking and fracture process in cement mortar and concrete: a comparative study using acoustic emission technique

This article reports the acoustic emission (AE) study of precursory micro-cracking activity and fracture behaviour of quasi-brittle materials such as concrete and cement mortar. In the present study, notched three-point bend specimens (TPB) were tested under crack mouth opening displacement (CMOD) control at a rate of 0.0004 mm/sec and the accompanying AE were recorded using a 8 channel AE monitoring system. The various AE statistical parameters including AE event rate , AE energy release rate , amplitude distribution for computing the AE based b-value, cumulative energy (I E) pound and ring down count (RDC) were used for the analysis. The results show that the micro-cracks initiated and grew at an early stage in mortar in the pre peak regime. While in the case of concrete, the micro-crack growth occurred during the peak load regime. However, both concrete and mortar showed three distinct stages of micro-cracking activity, namely initiation, stable growth and nucleation prior to the final failure. The AE statistical behavior of each individual stage is dependent on the number and size distribution of micro-cracks. The results obtained in the laboratory are useful to understand the various stages of micro-cracking activity during the fracture process in quasi-brittle materials such as concrete & mortar and extend them for field applications.

Evaluation of microwave assisted grafted sago starch as controlled release polymeric carrier

In the present investigation an attempt has been made to develop a new co-polymeric material for controlled release tablet formulations. The acrylamide grafting was successfully performed on the backbone of sago starch. The modified starch was tested for acute toxicity and drug-excipient compatibility study. The grafted material was used in making of controlled release tablets of lamivudine. The formulations were evaluated for physical characteristics such as hardness, friability, %drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in case of Higuchi model and the release mechanism of the optimized formulation predominantly exhibited combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T-max, C-max, AUC, V-d, T-1/2 and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir (R) was observed. The pharmacokinetics parameters were showed controlled pattern and better bioavailability. The optimized formulation exhibited good stability and release profile at the accelerated stability conditions. (c) 2013 Elsevier B.V. All rights reserved.

TCP: thread contention predictor for parallel programs

With proliferation of chip multicores (CMPs) on desktops and embedded platforms, multi-threaded programs have become ubiquitous. Existence of multiple threads may cause resource contention, such as, in on-chip shared cache and interconnects, depending upon how they access resources. Hence, we propose a tool - Thread Contention Predictor (TCP) to help quantify the number of threads sharing data and their sharing pattern. We demonstrate its use to predict a more profitable shared, last level on-chip cache (LLC) access policy on CMPs. Our cache configuration predictor is 2.2 times faster compared to the cycle-accurate simulations. We also demonstrate its use for identifying hot data structures in a program which may cause performance degradation due to false data sharing. We fix layout of such data structures and show up-to 10% and 18% improvement in execution time and energy-delay product (EDP), respectively.