Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus

Background: Tuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug resistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of biomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the development of improved TB vaccines. Methods: Recombinant proteins (n = 7) and peptide pools (n = 14) from M. tuberculosis (M.tb) antigens associated with M.tb pathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune responses defined by IFN-gamma production using a whole blood assay (WBA) from i) patients with TB, ii) individuals recovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus. Results: We identified differences in M.tb target peptide recognition between the test groups, i.e. a frequent recognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The pattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as compared to individuals suffering from pulmonary TB. Detection of biologically relevant M.tb targets was confirmed by staining for intracellular cytokines (IL-2, TNF-alpha and IFN-gamma) in T cells from non-human primates (NHPs) after BCG vaccination. Conclusions: PBMCs from healthy individuals and those recovered from TB recognized a broader spectrum of M.tb antigens as compared to patients with TB. The nature of the pattern recognition of a broad panel of M.tb antigens will devise better strategies to identify improved diagnostics gauging previous exposure to M.tb; it may also guide the development of improved TB-vaccines.

RRI-GBT MULTI-BAND RECEIVER: MOTIVATION, DESIGN, AND DEVELOPMENT

We report the design and development of a self-contained multi-band receiver (MBR) system, intended for use with a single large aperture to facilitate sensitive and high time-resolution observations simultaneously in 10 discrete frequency bands sampling a wide spectral span (100-1500 MHz) in a nearly log-periodic fashion. The development of this system was primarily motivated by need for tomographic studies of pulsar polar emission regions. Although the system design is optimized for the primary goal, it is also suited for several other interesting astronomical investigations. The system consists of a dual-polarization multi-band feed (with discrete responses corresponding to the 10 bands pre-selected as relatively radio frequency interference free), a common wide-band radio frequency front-end, and independent back-end receiver chains for the 10 individual sub-bands. The raw voltage time sequences corresponding to 16 MHz bandwidth each for the two linear polarization channels and the 10 bands are recorded at the Nyquist rate simultaneously. We present the preliminary results from the tests and pulsar observations carried out with the Robert C. Byrd Green Bank Telescope using this receiver. The system performance implied by these results and possible improvements are also briefly discussed.

A channel-aware, fast sub-channel to user assignment algorithm in OFDMA systems

Channel-aware assignment of sub-channels to users in the downlink of an OFDMA system demands extensive feedback of channel state information (CSI) to the base station. Since the feedback bandwidth is often very scarce, schemes that limit feedback are necessary. We develop a novel, low feedback splitting-based algorithm for assigning each sub-channel to its best user, i.e., the user with the highest gain for that sub-channel among all users. The key idea behind the algorithm is that, at any time, each user contends for the sub-channel on which it has the largest channel gain among the unallocated sub-channels. Unlike other existing schemes, the algorithm explicitly handles multiple access control aspects associated with the feedback of CSI. A tractable asymptotic analysis of a system with a large number of users helps design the algorithm. It yields 50% to 65% throughput gains compared to an asymptotically optimal one-bit feedback scheme, when the number of users is as small as 10 or as large as 1000. The algorithm is fast and distributed, and scales with the number of users.

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-gamma and IL-17 production in blood from TB plus patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

Background: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-gamma and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results: M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-gamma production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions: The pattern of immune target recognition is different in regard to IFN-gamma and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Sub-band envelope approach to obtain instants of significant excitation in speech

In this paper, we propose a new sub-band approach to estimate the glottal activity. The method is based on the spectral harmonicity and the sub-band temporal properties of voiced speech. We propose a method to represent glottal excitation signal using sub-band temporal envelope. Instants of maximum glottal excitation or Glottal Closure Instants (GCI) are extracted from the estimated glottal excitation pattern and the result is compared with a standard GCI computation method, DYPSA [1]. The performance of the algorithm is also compared for the noisy signal and it is shown that the proposed method is less variant to GCI estimation under noisy conditions compared to DYPSA. The algorithm is evaluated on the CMU-ARCTIC database.

Microstructure and texture evolution during sub-transus thermomechanical processing of Ti-6Al-4V-0.1B alloy: part I. hot rolling in (alpha plus beta) phase field

In the current study, the evolution of microstructure and texture has been studied for Ti-6Al-4V-0.1B alloy during sub-transus thermomechanical processing. This part of the work deals with the deformation response of the alloy by rolling in the (alpha + beta) phase field. The (alpha + beta) annealing behavior of the rolled specimen is communicated in part II. Rolled microstructures of the alloys exhibit either kinked or straight alpha colonies depending on their orientations with respect to the principal rolling directions. The Ti-6Al-4V-0.1B alloy shows an improved rolling response compared with the alloy Ti-6Al-4V because of smaller alpha lamellae size, coherency of alpha/beta interfaces, and multiple slip due to orientation factors. Accelerated dynamic globularization for this alloy is similarly caused by the intralamellar transverse boundary formation via multiple slip and strain accumulation at TiB particles. The (0002)(alpha) pole figures of rolled Ti-6Al-4V alloy shows ``TD splitting'' at lower rolling temperatures because of strong initial texture. Substantial beta phase mitigates the effect of starting texture at higher temperature so that ``RD splitting'' characterizes the basal pole figure. Weak starting texture and easy slip transfer for Ti-6Al-4V-0.1B alloy produce simultaneous TD and RD splittings in basal pole figures at all rolling temperatures.

Microstructure and texture evolution during sub-transus thermo-mechanical processing of Ti-6Al-4V-0.1B alloy: part II. static annealing in (alpha plus beta) regime

The first part of this study describes the evolution of microstructure and texture in Ti-6Al-4V-0.1B alloy during sub-transus rolling vis-A -vis the control alloy Ti-6Al-4V. In the second part, the static annealing response of the two alloys at self-same conditions is compared and the principal micromechanisms are analyzed. Faster globularization kinetics has been observed in the Ti-6Al-4V-0.1B alloy for equivalent annealing conditions. This is primarily attributed to the alpha colonies, which leads to easy boundary splitting via multiple slip activation in this alloy. The other mechanisms facilitating lamellar to equiaxed morphological transformations, e.g., termination migration and cylinderization, also start early in the boron-modified alloy due to small alpha colony size, small aspect ratio of the alpha lamellae, and the presence of TiB particles in the microstructure. Both the alloys exhibit weakening of basal fiber (ND||aOE (c) 0001 >) and strengthening of prism fiber (RD||aOE (c) aOE(a)) upon annealing. A close proximity between the orientations of fully globularized primary alpha and secondary alpha phases during alpha -> beta -> alpha transformation has accounted for such a texture modification.

An approach for assessing the accuracy of accelerometer responses during axial impact tests

The primary objective of the present study is to show that for the most common configuration of an impactor system, the accelerometer cannot exactly reproduce the dynamic response of a specimen subjected to impact loading. An equivalent Lumped Parameter Model (LPM) of the given impactor set-up has been formulated for assessing the accuracy of an accelerometer mounted in a drop-weight impactor set-up for an axially loaded specimen. A specimen under the impact loading is represented by a non-linear spring of varying stiffness, while the accelerometer is assumed to behave in a linear manner due to its high stiffness. Specimens made of steel, aluminium and fibre-reinforced composite (FRC) are used in the present study. Assuming the force-displacement response obtained in an actual impact test to be the true behaviour of the test specimen, a suitable numerical approach has been used to solve the governing non-linear differential equations of a three degrees-of-freedom (DOF) system in a piece-wise linear manner. The numerical solution of the governing differential equations following an explicit time integration scheme yields an excellent reproduction of the mechanical behaviour of the specimen, consequently confirming the accuracy of the numerical approach. However, the spring representing the accelerometer predicts a response that qualitatively matches the assumed force-displacement response of the test specimen with a perceptibly lower magnitude of load.

Refining sub-solidus phase relations in the systems CaO-RuO2-SiO2 and CaO-RuO2-V2O5

Sub-solidus phase relations in the ternary systems CaO-RuO2-SiO2 and CaO-RuO2-V2O5 have been refined using thermodynamic data on calcium ruthenates, silicates and vanadates. Tie lines are established by considering Gibbs energy change for exchange reactions. Quaternary oxides have not been detected in these systems. Because of the relatively large entropy associated with phase transition of Ca2SiO4 from olivine to alpha' structure at 1120 K, reversal of one tie line is seen in the system CaO-RuO2-SiO2 between 950 and 1230 K. There is no change in sub-solidus phase relation as a function of temperature in the system CaO-RuO2-V2O5. Since vanadium can exist in several lower oxidation states, the computed sub-solidus phase relations are valid only at high oxygen partial pressures. There is fair agreement between the computed phase diagram and the limited experimental information available for CaO-deficient compositions in the literature. (C) 2013 Elsevier Ltd. All rights reserved.

Multiple sub-row buffers in DRAM: unlocking performance and energy improvement opportunities

The twin demands of energy-efficiency and higher performance on DRAM are highly emphasized in multicore architectures. A variety of schemes have been proposed to address either the latency or the energy consumption of DRAMs. These schemes typically require non-trivial hardware changes and end up improving latency at the cost of energy or vice-versa. One specific DRAM performance problem in multicores is that interleaved accesses from different cores can potentially degrade row-buffer locality. In this paper, based on the temporal and spatial locality characteristics of memory accesses, we propose a reorganization of the existing single large row-buffer in a DRAM bank into multiple sub-row buffers (MSRB). This re-organization not only improves row hit rates, and hence the average memory latency, but also brings down the energy consumed by the DRAM. The first major contribution of this work is proposing such a reorganization without requiring any significant changes to the existing widely accepted DRAM specifications. Our proposed reorganization improves weighted speedup by 35.8%, 14.5% and 21.6% in quad, eight and sixteen core workloads along with a 42%, 28% and 31% reduction in DRAM energy. The proposed MSRB organization enables opportunities for the management of multiple row-buffers at the memory controller level. As the memory controller is aware of the behaviour of individual cores it allows us to implement coordinated buffer allocation schemes for different cores that take into account program behaviour. We demonstrate two such schemes, namely Fairness Oriented Allocation and Performance Oriented Allocation, which show the flexibility that memory controllers can now exploit in our MSRB organization to improve overall performance and/or fairness. Further, the MSRB organization enables additional opportunities for DRAM intra-bank parallelism and selective early precharging of the LRU row-buffer to further improve memory access latencies. These two optimizations together provide an additional 5.9% performance improvement.

Group testing based spectrum hole search using a simple sub-nyquist sampling scheme

In this paper, we consider the problem of finding a spectrum hole of a specified bandwidth in a given wide band of interest. We propose a new, simple and easily implementable sub-Nyquist sampling scheme for signal acquisition and a spectrum hole search algorithm that exploits sparsity in the primary spectral occupancy in the frequency domain by testing a group of adjacent subbands in a single test. The sampling scheme deliberately introduces aliasing during signal acquisition, resulting in a signal that is the sum of signals from adjacent sub-bands. Energy-based hypothesis tests are used to provide an occupancy decision over the group of subbands, and this forms the basis of the proposed algorithm to find contiguous spectrum holes. We extend this framework to a multi-stage sensing algorithm that can be employed in a variety of spectrum sensing scenarios, including non-contiguous spectrum hole search. Further, we provide the analytical means to optimize the hypothesis tests with respect to the detection thresholds, number of samples and group size to minimize the detection delay under a given error rate constraint. Depending on the sparsity and SNR, the proposed algorithms can lead to significantly lower detection delays compared to a conventional bin-by-bin energy detection scheme; the latter is in fact a special case of the group test when the group size is set to 1. We validate our analytical results via Monte Carlo simulations.

NOD2-Nitric Oxide-responsive MicroRNA-146a Activates Sonic Hedgehog Signaling to Orchestrate Inflammatory Responses in Murine Model of Inflammatory Bowel Disease

Background: Genetic variants of NOD2 are linked to inflammatory bowel disease (IBD) etiology. Results: DSS model of colitis in wild-type and inducible nitric-oxide synthase (iNOS) null mice revealed that NOD2-iNOS/NO-responsive microRNA-146a targets NUMB gene facilitating Sonic hedgehog (SHH) signaling. Conclusion: miR-146a-mediated NOD2-SHH signaling regulates gut inflammation. Significance: Identification of novel regulators of IBD provides new insights into pathophysiology and development of new therapy concepts. Inflammatory bowel disease (IBD) is a debilitating chronic inflammatory disorder of the intestine. The interactions between enteric bacteria and genetic susceptibilities are major contributors of IBD etiology. Although genetic variants with loss or gain of NOD2 functions have been linked to IBD susceptibility, the mechanisms coordinating NOD2 downstream signaling, especially in macrophages, during IBD pathogenesis are not precisely identified. Here, studies utilizing the murine dextran sodium sulfate model of colitis revealed the crucial roles for inducible nitric-oxide synthase (iNOS) in regulating pathophysiology of IBDs. Importantly, stimulation of NOD2 failed to activate Sonic hedgehog (SHH) signaling in iNOS null macrophages, implicating NO mediated cross-talk between NOD2 and SHH signaling. NOD2 signaling up-regulated the expression of a NO-responsive microRNA, miR-146a, that targeted NUMB gene and alleviated the suppression of SHH signaling. In vivo and ex vivo studies confirmed the important roles for miR-146a in amplifying inflammatory responses. Collectively, we have identified new roles for miR-146a that established novel cross-talk between NOD2-SHH signaling during gut inflammation. Potential implications of these observations in therapeutics could increase the possibility of defining and developing better regimes to treat IBD pathophysiology.

Simulations and experiments in punching spring-steel devices with sub-millimeter features

This work demonstrates the feasibility of mesoscale (100 μm to mm) punching of multiple holes of intricate shapes in metals. Analytical modeling, finite element (FE)simulation, and experimentations are used in this work. Two dimensional FE simulations in ABAQUS were done with an assumed material modeling and plane-strain condition. A known analytical model was used and compared with the ABAQUS simulation results to understand the effects of clearance between the punch and the die. FE simulation in ABAQUS was done for different clearances and corner radii at punch, die, and holder. A set of punches and dies were used to punch out a miniature spring-steel gripper. Comparison of compliant grippers manufactured by wire-cut electro discharge machining(EDM) and punching shows that realizing sharp interior and re-entrant corners by punching is not easy to achieve. Punching of circular holes with 5 mm and 2.5 mm diameter is achieved. The possibility of realizing meso-scale parts with complicated shapes through punching is demonstrated in this work; and some strategies are suggested for improvement.

Micropillar and macropillar compression responses of magnesium single crystals oriented for single slip or extension twinning

Uniaxial compression experiments were conducted on two magnesium (Mg) single crystals whose crystallographic orientations facilitate the deformation either by basal slip or by extension twinning. Specimen size effects were examined by conducting experiments on mu m- and mm-sized samples. A marked specimen size effect was noticed, with micropillars exhibiting significantly higher flow stress than bulk samples. Further, it is observed that the twin nucleation stress exerts strong size dependence, with micropillars requiring substantially higher stress than the bulk samples. The flow curves obtained on the bulk samples are smooth whereas those obtained from micropillars exhibit intermittent and precipitous stress drops. Electron backscattered diffraction and microstructural analyses of the deformed samples reveal that the plastic deformation in basal slip oriented crystals occurs only by slip while twin oriented crystals deform by both slip and twinning modes. The twin oriented crystals exhibit a higher strain hardening during plastic deformation when compared to the single slip oriented crystals. The strain hardening rate, theta, of twin oriented crystals is considerably greater in micropillars compared to the bulk single crystals, suggesting the prevalence of different work hardening mechanisms at these different sample sizes. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.