Effects of varying body forces on isothermal and non isothermal liquid jet impingement

Liquid jet impingement is often used to cool heated surfaces encountered in various industrial applications. Such applications include cooling of electronic components and annealing of metals. Liquid jet impingement investigations primarily involve submerged jets and less commonly free liquid jets. Most of the studies done on both submerged jet impingement and free liquid jet impingement are done under terrestrial gravity conditions. There have been few studies on liquid jet impingement under non terrestrial conditions in zero or non zero gravitational force or of electrical body forces. These conditions are expected to result in significantly different flow patterns and heat transfer compared to terrestrial gravity.;The relatively uncommon forces like the electric Kelvin force could significantly affect the heat transfer and flow characteristics of an impinging liquid jet. As per one of the objectives of this research, an electrode arrangement was designed to obtain a uniform electric Kelvin body force acting in a direction opposite to the impinging jet. Another objective was to assess the effects of varying gravity on heat transfer to an impinging jet. Simulation results involving liquid jet impingement with different body forces are presented in this dissertation. These results were obtained with the aid of a commercial multiphysics code called CFD-ACE+.;The isothermal set of simulations included the electric Kelvin force as the source term, while in the non isothermal cases gravity was varied from 0 to 1.5 g in the increments of 0.5 g. The transient effects of the electric Kelvin force were observed in the isothermal simulations while in the non isothermal simulations it was found that for low velocities the heat transfer from an impinging liquid jet was enhanced as the gravitational force was increased

Development of instrumentation for acoustic monitoring

This thesis describes a source/sink flow acoustic wave sensor for the identification of leaks in gas pipelines. One of the many type of signals associated with the high velocity gas flowing out of a hole in the pipeline is the ramp or step pressure drop.;A large 3-inch diameter diaphragm was installed in an attempt to detect the low frequency waves associated with a leak. This diaphragm with source or sink flow through a 17mm internal diameter pipe acts as a pressure signal amplifier.;The deflection of the diaphragm due to the amplified force can be measured with a strain gage whose voltage is proportional to this deflection. A microphone should be used to record high frequency sound generated by the fluid inside the transmission line. (Abstract shortened by UMI.)

Implications of traditional commercial practices on the current environmental status of River Yamuna in the Delhi-Mathura-Agra region, India

The River Yamuna is regarded as a holy river in Indian mythology. It originates in the Himalayas and several important cities, pilgrimage centres and temple towns are located along its banks. It is a source of water supply to these cities and also receives their wastewaters from domestic and industrial activities. This study aims to assess the environmental and human health implications of traditional commercial practices such as electroplating and jewellery making in the cottage industries along the banks of River Yamuna in the Delhi-Mathura-Agra region. Human exposure to contaminants from overbank soil and also through the food chain from crops grown on floodplains are considered through analyses of overbank and floodplain soils with special reference to toxic trace metals such as silver, cadmium, copper, and zinc. The findings of study show that the overbank and floodplain soils at the temple town of Mathura are highly contaminated with silver and cadmium, and are above normal background concentrations for copper and zinc. This leads to suggest that the traditional and cultural activities of jewellery-making and electroplating works at Mathura are contributing a high metal load to its overbank and floodplain soils and are a cause for concern for human health

The current state of animal models and genomic approaches towards identifying and validating molecular determinants of Mycobacterium tuberculosis infection and tuberculosis disease

Animal models are important in understanding both the pathogenesis of and immunity to tuberculosis (TB). Unfortunately, we are beginning to understand that no animal model perfectly recapitulates the human TB syndrome, which encompasses numerous different stages. Furthermore, Mycobacterium tuberculosis infection is a very heterogeneous event at both the levels of pathogenesis and immunity. This review seeks to establish the current understanding of TB pathogenesis and immunity, as validated in the animal models of TB in active use today. We especially focus on the use of modern genomic approaches in these models to determine the mechanism and the role of specific molecular pathways. Animal models have significantly enhanced our understanding of TB. Incorporation of contemporary technologies such as single cell transcriptomics, high-parameter flow cytometric immune profiling, proteomics, proteomic flow cytometry and immunocytometry into the animal models in use will further enhance our understanding of TB and facilitate the development of treatment and vaccination strategies

Development of transgenics in Indian oilseed mustard (Brassica juncea) resistant to herbicide phosphinothricin

Transgenic lines resistant to herbicide phosphinothricin (PPT) were developed in mustard (Brassica juncea), a major oilseed crop grown in more than 6 million hectares of land in North India. Seedling-derived hypocotyl explants were transformed with a disarmed Agrobacterium tumefaciens strain GV3101. The developed constructs contained the bar gene encoding the enzyme phosphinothricin-acetyl-transferase (PAT) which inactivates phosphinothricin (PPT) by acetylating it. The expression of the bar gene was controlled either by the double enhancer version of CaMV35S promoter (35Sdebar) or a CaMV35S promoter with a leader sequence from RNA4 of alfalfa mosaic virus introduced at the 5' end of the bar gene (35SAMVLbar) or without (35Sbar) it. Plant viral leader sequences have been shown to be translational enhancers. In vitro selections for transformed plants were carried out on a medium containing PPT. Transgenic shoots were recovered at a frequency of 23% with 35Sdebar gene construct and at a frequency of 16% with 35SAMVLbar containing construct. Transformation frequencies were low with 35Sbar construct. Individual transgenics with 35Sdebar and 35SAMVLbar constructs were tested for copy number on both the right and left border flanks of T-DNA by Southern hybridization. Single copy transgenic lines were further analysed for transcript levels of the bar gene by Northern blotting and for protein levels by PAT assays. Wide variation in expression levels were observed, particularly amongst the transgenics containing the 35Sdebar construct. Single copy transgenics were selfed to develop homozygous lines which could be used for the study of resistance to herbicide PPT at the field level and to correlate this protection with expression levels observed through molecular analysis. Herbicide- tolerant lines could be used for testing the possibility of low-till or no-till cultivation of mustard in the rain-fed areas where it is extensively grown

Myeloid-derived suppressor cells mediate T cell dysfunction in nonhuman primate TB granulomas

Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population comprised of immature myeloid cells and myeloid progenitors with very potent immunosuppressive potential. MDSCs are reported to be abundant in the lungs of active tuberculosis (TB) patients. We sought to perform an in-depth study of MDSCs during latent TB infection (LTBI) and active TB (ATB) using the nonhuman primate (NHP) model of pulmonary TB. We found a higher proportion of granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the lungs of ATB animals compared to those with LTBI or naive control animals. Active disease in the lung, but not LTBI, was furthermore associated with higher proliferation, expansion, and immunosuppressive capabilities of PMN-MDSCs, as shown by enhanced expression of Ki67, indoleamine 2,3-dioxygenase (IDO1), interleukin-10 (IL-10), matrix metallopeptidase 9 (MMP-9), inducible nitric oxide synthase (iNOS), and programmed death-ligand 1 (PD-L1). These immunosuppressive PMN-MDSCs specifically localized to the lymphocytic cuff at the periphery of the granulomas in animals with ATB. Conversely, these cells were scarcely distributed in interstitial lung tissue and the inner core of granulomas. This spatial regulation suggests an important immunomodulatory role of PMN-MDSCs by restricting T cell access to the TB granuloma core and can potentially explain dysfunctional anti-TB responses in active granuloma. Our results raise the possibility that the presence of MDSCs can serve as a biomarker for ATB, while their disappearance can indicate successful therapy. Furthermore, MDSCs may serve as a potential target cell for adjunctive TB therapy

Myeloid cell interferon responses correlate with clearance of SARS-CoV-2

Emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi; peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLAD

Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals

The Stress-Response Factor SigH Modulates the Interaction between Mycobacterium tuberculosis and Host Phagocytes

The Mycobacterium tuberculosis stress response factor SigH plays a crucial role in modulating the pathogen's response to heat, oxidative-stress, envelope damage and hypoxia. We hypothesized that the lack of this key stress response factor would alter the interaction between the pathogen and its host cells. We compared the interaction of Mtb, Mtb:Δ-sigH and a strain where the mutation had been genetically complemented (Mtb: Δ-sigH:CO) with primary rhesus macaque bone marrow derived macrophages (Rh-BMDMs). The expression of numerous inducible and homeostatic (CCL) β-chemokines and several apoptotic markers was induced to higher levels in the cells infected with Mtb:Δ-sigH, relative to Mtb or the complemented strain. The differential expression of these genes manifested into functional differences in chemotaxis and apoptosis in cells infected with these two strains. The mutant strain also exhibited reduced late-stage survival in Rh-BMDMs. We hypothesize that the product of one or more SigH-dependent genes may modulate the innate interaction of Mtb with host cells, effectively reducing the chemokine-mediated recruitment of immune effector cells, apoptosis of infected monocytes and enhancing the long-term survival and replication of the pathogen in this milieu The significantly higher induction of Prostaglandin Synthetase 2 (PTGS2 or COX2) in Rh-BMDMs infected with Mtb relative to Mtb: Δ-sigH may explain reduced apoptosis in Mtb-infected cells, as PTGS2 is known to inhibit p53-dependent apoptosis.The SigH-regulon modulates the innate interaction of Mtb with host phagocytes, perhaps as part of a strategy to limit its clearance and prolong its survival. The SigH regulon appears to be required to modulate innate immune responses directed against Mtb

Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses

BACKGROUND: The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib. PATIENTS AND METHODS: Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs. RESULTS: In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127]). CONCLUSION: Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC. CLINICALTRIALS.GOV IDENTIFIER: NCT0314879