93 research outputs found
The Nation and its citizens: Tales of Bondage and Belonging
No full textThe Nation and Its Citizens: Tales of Bondage and Belonging is about nationalism as a uniquely modern political doctrine, shaped by the lived experience of citizens. Nationalism has changed in its appeal through history, as have its manifestations. Getting to know these may be part of the challenge of negotiating the ongoing turmoil, both internal and external to the nation.
In addressing these issues, this book offers several propositions on how the construct of ‘identity’ is crafted, with all its power to influence modern politics. It then explores how well India’s practice of republican democracy has lived up to the competing dynamics of identity and equality.
As India celebrates 75 years of Independence, author Sukumar Muralidharan takes the readers on a journey into how the sense of fellow-feeling and mutual dependence of the nation are consolidated, and under what circumstances these could fray. The Nation and Its Citizens offers many fresh perspectives in understanding India’s unique political trajectory
PLoS Pathog
No full textMycobacterium tuberculosis (Mtb) remains a major public health problem, with an effective vaccine continuing to prove elusive. Progress in vaccination strategies has been hampered by a lack of appreciation of the bacterium's response to dynamic changes in the host immune environment. Here, we utilize reporter Mtb strains that respond to specific host immune stresses such as hypoxia and nitric oxide (hspX'::GFP), and phagosomal maturation (rv2390c'::GFP), to investigate vaccine-induced alterations in the environmental niche during experimental murine infections. While vaccination undoubtedly decreased bacterial burden, we found that it also appeared to accelerate Mtb's adoption of a phenotype better equipped to survive in its host. We subsequently utilized a novel replication reporter strain of Mtb to demonstrate that, in addition to these alterations in host stress response, there is a decreased percentage of actively replicating Mtb in vaccinated hosts. This observation was supported by the differential sensitivity of recovered bacteria to the front-line drug isoniazid. Our study documents the natural history of the impact that vaccination has on Mtb's physiology and replication and highlights the value of reporter Mtb strains for probing heterogeneous Mtb populations in the context of a complex, whole animal model.20141DP2LM011952-01/DP/NCCDPHP CDC HHS/United StatesAI067027/AI/NIAID NIH HHS/United StatesDP2 LM011952/LM/NLM NIH HHS/United StatesHL055936/HL/NHLBI NIH HHS/United StatesR01 AI067027/AI/NIAID NIH HHS/United StatesR01 HL055936/HL/NHLBI NIH HHS/United States25233380PMC41695031018
TRANSCRIPTIONAL REGULATION AND PROTECTIVE EFFICACY OF BORDETELLA COLONIZATION FACTOR A (BcfA) IN BORDETELLA INFECTIONS
No full textTo successfully colonize their mammalian hosts many bacteria produce multiple virulence factors that play essential roles in disease processes and pathogenesis. Some of these molecules are adhesins that allow efficient attachment to host cells, a prerequisite for successful host colonization. Bordetella spp. express a number of proteins which either play a direct role in attachment to the respiratory epithelia or exhibit similarity to previously known bacterial adhesins. One such recently identified protein is BipA. Despite similarity to intimins and invasins, its deletion from B. bronchiseptica did not result in any significant defect in respiratory tract colonization. We hypothesized the existence of a paralogous protein that could complement the function of BipA. In the studies described here, we report the identification and characterization of an ORF in B. bronchiseptica, designated as bcfA (Bordetella colonization factor A) that is similar to bipA. We show that in contrast to maximal expression of bipA in the Bvgi phase, bcfA is expressed at high levels in both the Bvg+ and the Bvgi phases. We have identified multiple sequence elements resembling the consensus BvgA binding site in the bcfA promoter region. Direct binding of purified BvgA to the bcfA promoter revealed differences in the DNA binding profiles of BvgA and BvgA-P to the promoter region. Utilizing an antibody raised against BcfA, we show that BcfA is localized in the outer membrane. Finally, we demonstrate that simultaneous deletion of both bipA and bcfA results in a defect in colonization of the rat trachea and that BcfA is expressed during Bordetella infectious cycle.
Based on our findings that BcfA is an outer membrane immunogenic protein and is critical for murine respiratory tract colonization, we examined its utility in inducing a protective immune response against B. bronchiseptica in a mouse model of intranasal infection. Mice vaccinated with BcfA demonstrated reduced pathology in the lungs and harbored lower bacterial burdens in the respiratory tract. Immunization with BcfA led to the generation of BcfA-specific antibodies in both the serum and the lungs and passive immunization led to the reduction of B. bronchiseptica in the trachea and the lungs. These results suggest that protection after immunization with BcfA is mediated in part by antibodies against BcfA. To further investigate the mechanism of BcfA-induced immune clearance, we examined the role of neutrophils and macrophages. Our results demonstrate that neutrophils are critical for anti-BcfA antibody-mediated clearance and that opsonization with anti-BcfA serum enhances phagocytosis of B. bronchiseptica by murine macrophages. We show that immunization with BcfA results in the production of IFN-γ and subclasses of IgG antibodies that are consistent with the induction of a Th1 type immune response. In combination, our findings suggest that mechanism of BcfA-mediated immunity involves humoral and cellular responses. Expression of BcfA is conserved among multiple clinical isolates of B. bronchiseptica. Our results demonstrate the striking protective efficacy of BcfA-mediated immunization thereby highlighting its utility as a potential vaccine candidate. These results also provide a model for the development of cell-free vaccines against B. bronchiseptica
Pharmacogenomic and mechanistic studies on dietary factors in chemoprevention of cancer
No full textPharmacogenomic profiling of cancer has recently seen much activity with the accessibility of the newest generation of high-throughput platforms and technologies. A myriad of mechanistic studies have been devoted to identifying dietary factors that can help prevent cancer, with evidence gleaned from epidemiologic studies revealing an inverse correlation between the intake of cruciferous vegetables and the risk of certain types of cancer. To develop a comprehensive understanding of cancer pathogenesis, and potential for chemopreventive intervention with dietary factors, an integrated approach that encompasses both pharmacogenomic and mechanistic aspects is desirable. Our transcriptomic profiling of butylated hydroxyanisole-induced Nuclear Factor-E2-related factor 2 (Nrf2)-dependent genes in Nrf2-deficient mice identified several germane molecular targets for prevention. Toxicogenomic analyses of endoplasmic reticulum stress inducer tunicamycin in Nrf2-deficient mice elucidated Nrf2-regulated unfolded protein response effects. Mechanistic studies on a combination of sulforaphane and (-) epigallocatechin-3-gallate in HT-29 AP-1 (Activator Protein-1) cells revealed a synergy in colon cancer chemoprevention. Pharmacogenomic studies of this combination in PC-3 AP-1 cells provided a discursive framework for understanding putative crosstalk between Nrf2 and AP-1 in prostate cancer chemoprevention. Regulatory potential for concerted modulation of Nrf2 and Nuclear Factor-κB (Nfκb1) in inflammation and carcinogenesis was delineated by bioinformatic analyses. Metabolomic approaches identified potential prognostic biomarkers in human prostate cancer. Differential biological networks in prostate cancer were elicited in androgen-dependent 22Rv1 cells, androgen- and estrogen-dependent LNCaP cells and androgen-independent DU 145 and PC-3 cells. Taken together, our identification of Nrf2-regulated molecular targets by expression profiling using dietary factors, synergistic effects in combinatorial use of dietary factors in colon cancer, regulatory studies on crosstalk between Nrf2 and AP-1 in prostate cancer, bioinformatic analyses of concerted modulation of Nrf2 and Nfkb1 in inflammation and carcinogenesis, metabolomic identification of biomarkers, and delineation of target hubs in differential prostate cancer biological networks, greatly enhance our understanding of the transcriptional circuitry in cancer and important master regulatory nodes including Nrf2 that might potentially be exploited for chemopreventive intervention with dietary factors.Ph.D.Includes bibliographical references (p. 311-331)
The Influence of the Increasing Penetration of Photovoltaic Generation on Integrated Transmission-Distribution Power Systems
No full textPower system simulations should be adapted to be applicable to the trends that are currently evoked by the energy transition. This transition is pushing our power system from a traditional hierarchical system to a modern interactive system. In order to keep the supply and transport of energy safe and reliant, we need to change the way we perform power system simulations. This requires a comprehensive framework in which both transmission and distribution systems are simultaneously analyzed. This chapter describes how transmission and distribution networks are modeled together as an integrated network and used to do steady-state operation analysis in order to assess the interaction of these two networks. Furthermore, we investigate the influence of the increasing amount of imbalance at distribution level on the transmission network that is evoked by the increase of highly variable resources and loads at distribution level. This influence is not taken into account in traditional power system simulations as power networks are analyzed on its own. We show that the hybrid network representation is a powerful tool to analyze modern power systems and that the effects of increased PV penetration under normal operating conditions are limitedGreen Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Numerical Analysi
Disparity in endoscopic localisation of early distal colorectal cancers: a retrospective cohort analysis from a single institution
No full textBACKGROUND: Accurate staging of distal colorectal cancers is paramount in guiding neoadjuvant therapy, peri-operative, and ostomy planning. Early colonic lesions can be difficult to visualise on computed tomography (CT) scans, with tumour location solely deduced via endoscopy with the potential for introducing error. We aimed to address the paucity in literature in this area and assessed the accuracy of radiological and endoscopic localisation of distal colorectal cancers. METHODS: Retrospective analysis of an electronic database of patients at a large District General Hospital (DGH) diagnosed with distal colorectal cancer between January 2014 to January 2023 was performed. Patient demographics, investigations, endoscopic, and operative findings were analysed. Outcomes were assessed to determine disparities between pre-operative endoscopy and final tumour location. RESULTS: A total of 212 patients were endoscopically diagnosed with distal sigmoid tumour. Of these, 207 (97.6%) had a CT scan performed with 25.1% (52/207) lesions not being identified on this imaging modality with the remainder (74.9%; 155/207) being reported as visible. 38.2% (79/207) of tumours were in the sigmoid colon, 17.4% (36/207) rectosigmoid, and 19.3% (40/207) in the rectum. Pre-operative magnetic resonance imaging (MRI) was performed in 42.5% (90/212) of cases showing 84 tumours: 6.0% (5/84) sigmoid colon, 9.5% (8/84) rectosigmoid and 83.3% (70/84) rectal cancers (upper: 34, mid-rectum: 26, low: 10), with one anal cancer. 42.3% (22/52) of patients with non-visible lesions on CT had MRI scans: 68.2% (15/22) had rectal cancer (upper: 10, mid-rectum: 4, low: 1). Of the 30 where MRI was not performed, 46.7% (14) had sigmoid cancer, 16.7% (5) rectosigmoid, and 33.3% (10) rectal intraoperatively. Overall, 30.7% (65/212) of patients reported as having a distal sigmoid lesion endoscopically in fact had rectal cancer intra-operatively (rectosigmoid lesions excluded). CONCLUSION: Endoscopic localisation of distal colorectal tumours can be unreliable for accurate staging and operative planning. A pre-operative MRI scan should be considered in such instances, and particularly for non-visible lesions on CT scan. This may improve peri-operative planning, staging accuracy and patient outcomes.Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.Not hel
Regulation of bone quality and calcium absorption in obesity and during caloric restriction in women
No full textWeight loss (WL) is associated with loss of bone loss due to several factors such as decrease in intake of calcium, true fractional calcium absorption (TFCA), serum insulin like growth factor -1 (IGF-1) , reduced weight bearing . The aim in this dissertation was to understand whether a higher intake of dietary protein and vitamin D can attenuate bone loss during caloric restriction (CR), and addresses bone quality and altered hormonal milieu in obesity. In the first trial, our goal was to examine how bone responds to CR during a 1 year randomized trial using 2 levels of protein intake with controlled calcium intake of 1.2 g/d in both groups. Forty seven women were randomized to either a normal (18%) or higher (24%) protein intake for 1 year. Our results showed greater loss of BMD at certain sites and lower IGF-1 in the NP compared to HP diet (p <0.05). The second trial hypothesized that a higher compared to normal vitamin D supplementation will attenuate the decrease in TFCA associated with CR. Eighty four women were supplemented with either 2500 IU/d or 400 IU/d of vitamin D3 for 6 weeks during WL or weight maintenance (WM). TFCA increased with 2500 IU/d D supplementation in the WM-D group by 3.7% (p <0.05) however did not attenuate the decrease in TFCA associated with CR, with the greatest increase in 25 hydroxy vitamin D (25OHD) in the WL-D group. These findings suggest that vitamin D supplementation does not attenuate the decrease in TFCA associated with CR. The cross sectional study in this dissertation aimed at evaluating bone quality in obesity using peripheral quantitative computed tomography (pQCT). Our results in 211 women showed that obesity is associated with higher trabecular bone and lower cortical BMD. A separate case control clinical study in 111 women shows that high serum PTH in obesity is also associated with higher monocyte chemoattractant protein (MCP-1). This unique effect of parathyroid hormone (PTH) on MCP-1 is independent of the level of adiposity. Together these studies evaluate nutrient supplementation in attenuating bone loss during CR and help better understand bone quality and higher serum PTH in obesity.Ph. D.Includes bibliographical referencesIncludes vitaby Deeptha Sukuma
Study of Mass Transfer Phenomena During Frying of Potato Slice
No full textThis Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page
Frying Studies of Potato Strips using Dry Coating Materials
No full textThis Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page
Studies on Physico-Chemical Properties of Fried Oils
No full textThis Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page
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