Genome-wide transcription analysis of interaction between the human macrophage and Mycobacterium tuberculosis during concurrent drug administration by conventional and novel methods

Targeted drug delivery to alveolar macrophages harboring Mycobacterium tuberculosis (Mtb) holds promise of high efficacy against pulmonary tuberculosis (TB). It was investigated whether inhalable microparticles (MP) can rescue macrophages from ‘alternative’ activation induced by pathogenic Mtb in addition to achieving targeted drug delivery. A genome-wide transcription analysis (Affymetrix HG-U133 Plus 2.0 DNA microarray) of THP-1 cell line derived macrophages was undertaken after exposing them to infection with 10 MOI of MTB H37Rv at 0, 12 and 24 hours post infection. The Molecular markers of macrophage bactericidal activity were assayed in THP-1- and primary human peripheral blood mononuclear cell (PBMC)-derived macrophages, in the presence or absence of soluble anti-tuberculosis drugs, drug-containing MP and blank MP. About 1,500 genes were differentially upregulated and about 500 genes differentially downregulated in response to various modes of treatment. Variations were also observed in the kinetics of gene expression. Cluster analysis indicated activation of several pathways related to innate immune response (cytokines, chemokines, receptors and ligands), apoptosis, cytoskeleton and membrane remodeling, general metabolism and general housekeeping. Some of these results were validated at the functional level, by studying caspase activities, concentrations and time-courses of effector molecules , rates/extents of apoptosis and nitrite oxide induction. Production of cytokines and NO, apoptosis, and bacterial survival were studied as pharmacodynamic outcomes. Cytokine responses of THP-1 derived macrophages were estimated. MP reversed suppression of tumor necrosis factor (TNF) induced by infection, and transiently upregulated γ-interferon (IFN-γ). Drug-free MP surprisingly induced IFN-γ, but not TNF. Primary cells responded to MP, regardless of drug content, by upregulation of NO; but THP-1-derived cells did not respond to blank MP. About 19% of infected cells exposed to MP underwent apoptosis as compared to ~11% cells treated with soluble drugs or blank MP. Cell death induced by blank MP was caspase-independent. Only drug-containing MP induced apoptosis through caspase-8 and caspase-9. Bacterial survival after different treatments varied between individuals. In the best case, while untreated infection resulted in survival of 900±141 colony forming units (CFU), treatment with soluble drugs, drug-containing MP and blank MP respectively, reduced CFU counts to 8.5± 0.7, 3±1.4 and 102±138.6. The results suggest a role of the drug delivery system in macrophage activation as a component of therapeutic strategy against TB

Primordial Non-Gaussianity in the Cosmic Microwave Background

In the last few decades, advances in observational cosmology have given us a standard model of cosmology. We know the content of the universe to within a few percent. With more ambitious experiments on the way, we hope to move beyond the knowledge of what the universe is made of, to why the universe is the way it is. In this review paper we focus on primordial non-Gaussianity as a probe of the physics of the dynamics of the universe at the very earliest moments. We discuss 1) theoretical predictions from inflationary models and their observational consequences in the cosmic microwave background (CMB) anisotropies; 2) CMB--based estimators for constraining primordial non-Gaussianity with an emphasis on bispectrum templates; 3) current constraints on non-Gaussianity and what we can hope to achieve in the near future; and 4) non-primordial sources of non-Gaussianities in the CMB such as bispectrum due to second order effects, three way cross-correlation between primary-lensing-secondary CMB, and possible instrumental effects.Comment: 27 pages, 8 figures; Invited Review for the Journal "Advances in Astronomy"; references adde

Probing Primordial Magnetism with Off-Diagonal Correlators of CMB Polarization

Primordial magnetic fields (PMF) can create polarization $B$-modes in the cosmic microwave background (CMB) through Faraday rotation (FR), leading to non-trivial 2-point and 4-point correlators of the CMB temperature and polarization. We discuss the detectability of primordial magnetic fields using different correlators and evaluate their relative merits. We have fully accounted for the contamination by weak lensing, which contributes to the variance, but whose contribution to the 4-point correlations is orthogonal to that of FR. We show that a Planck-like experiment can detect scale-invariant PMF of nG strength using the FR diagnostic at 90GHz, while realistic future experiments at the same frequency can detect 10^{-10} G. Utilizing multiple frequencies will improve on these prospects, making FR of CMB a powerful probe of scale-invariant PMF.Comment: 11 pages, 4 figures; unit typos fixed in fig 1 and

Primordial B-mode Diagnostics and Self Calibrating the CMB Polarization

Distortions in the primordial cosmic microwave background (CMB) along the line-of-sight can be modeled and described using 11 fields. These distortion fields correspond to various cosmological signals such as weak gravitational lensing of the CMB by large-scale structure, screening from patchy reionization, rotation of the plane of polarization due to magnetic fields or parity violating physics. Various instrumental systematics such as gain fluctuations, pixel rotation, differential gain, pointing, differential ellipticity are also described by the same distortion model. All these distortions produce B-mode that contaminate the primordial tensor B-modes signal. In this paper we show that apart from generating B-modes, each distortion uniquely couples different modes (\bfl_1\ne \bfl_2) of the CMB anisotropies, generating $$ correlations which for the primordial CMB are zero. We describe and implement unbiased minimum variance quadratic estimators which using the off diagonal correlations in the CMB can extract the map of distortions. We perform Monte-Carlo simulations to characterize the estimators and illustrate the level of distortions that can be detected with current and future experiments. The estimators can be used to look for cosmological signals, or to check for any residual systematics in the data. As a specific example of primordial tensor B-mode diagnostics we compare the level of minimum detectable distortions using our method with maximum allowed distortion level for the B-modes detection. We show that for any experiment, the distortions will be detected at high significance using correlations before they would show up as spurious B-modes in the power spectrum.Comment: 14 pages, 4 figure

New generation light emitting diodes:fundamentals and applications

Light emitting diodes (LEDs) have made tremendous progress in last 15 years andhave reached to a point where they are reinventing and redefining artificial lighting.The efficiency and better control over light quality parameters have been the keyattributes of LEDs that makes them better than the existing lighting solutions.Nevertheless, in their own realm they suffer from decrease in efficiency at highercurrents, i.e. the “efficiency droop” phenomenon. Thus, a better understandingof the mechanisms leading to droop is of utmost importance. Moreover, the fullpotential in terms of light quality, i.e. colour rendering index (CRI) and correlatedcolour temperature (CCT) that can be offered by these devices can be furtherimproved with existing or alternative schemes and device configurations.In this thesis, a novel phosphor covered approach is investigated towards improvingthe CRI for indoor lighting applications. A monolithic di-chromatic LEDemitting at blue and cyan wavelengths is used to pump a green-red phosphor mixtureand a warm (CCT ∼ 3400 K) white light with a superior CRI of 98.6 is achieved.An alternate phosphor free solution to achieve warm white light emission is alsostudied. These monolithic di-chromatic QW devices emitting at blue and greenwavelengths under electrical pumping demonstrated tuneable emission from cool(CCT ∼ 22000 k) to warm (CCT ∼ 5500 K) white light. A maximum CRI of 67,which is the highest value demonstrated for such devices till date to the best of myknowledge, is also achieved.On the subject of efficiency of LEDs, temperature dependence of LEE andIQE of commercial InGaN/GaN based blue LED is studied in light of a step-wiseprocessing procedure based on the ABC-model to determine these quantities. Adecrease in both IQE and LEE with temperature is noted. On the other hand,efficiency decrease in the investigated AlGaInP based red LEDs under pulsed currentshows a shift in the onset of efficiency decrease towards higher current values withdecreasing pulse width with < 1% duty cycle. For sub-nanosecond pulses a linearrelation between applied peak current and peak output power is obtained. Theseobservations indicate device self-heatin

Histopathology and Molecular Pathology of Vitiligo

Vitiligo is a common skin disorder that manifests as whitish macules. There is no special geographic or sex predilection. Vitiligo is a multifactorial disorder. The various theories proposed include neutral theory, autoimmune theory, zinc-α2-glycoprotein theory, viral infection, intrinsic theory and melanocytorrhagy theory. However, the currently favored opinion is that there is a convergence of various theories known as the convergence theory. The basic defect is the absence of functional melanocytes from the epidermal melanin unit. This absence can be demonstrated by using special stains like Fontana-Masson, immunohistochemistry like HMB-45 and Melan-A and electron microscopy. Margins of lesions especially early lesions show inflammatory cells principally CD4+ and CD8+ T cells. The cornerstone of management in vitiligo is correct categorization of a case into stable and unstable vitiligo. This distinction is based mainly on clinical criteria. It is recommended that while evaluating biopsies, histopathological examination should be primarily concentrated on evaluating five histopathological variables—spongiosis, epidermal lymphocytes, basal cell vacuolation, dermal lymphocytes and melanophages. These parameters are then scored using a scoring system, and the recommended diagnoses based on these scores are given. Adoption of a systematic reporting system brings more consistency and objectivity in the diagnosis

An Advance Node Pairing Protocol for Wireless Sensor Networks

In the recent developments in the communication system, the role of Wireless sensor network (WSN) is remarkable. In WSN information is collected using sensors and then it is transmitted to sink node. For this collection and transmission, the nodes need power back up and hence the power back up of nodes is one of the most crucial factor which will influence the proper functioning of WSN. This is the reason behind why we focus on the less consumption of the power by the nodes while making any WSN algorithm. This paper presents a node pairing protocol along with clustering of nodes.&nbsp; Overall, field in which sensor node are deployed is divided into zones and in zone 1 simple clustering based mechanism is used for data transfer to BS, while in zone 2, node pairing concept is used, and in a round only one node remain active while other remains in sleep mode thus energy saving is ensured. Simulations results show that the proposed protocol improve stability period 142%, 85.37%, 100.4%, 69.8% 35.5% and 72.43% the improved network lifetime of 55%, 128.9%, and 113.2% , 96.42% 27.38% and 40.93% as compared to LEACH, DEEC, DDEEC, MAHEE, S-SEP and EECP-EI respectively