91 research outputs found
It's an Ad, Ad, Ad World - Strategies of tobacco industry in India to diffuse tobacco control efforts- An unholy nexus
No full textWorld Health Organization (WHO) recommends prohibition of advertisements, promotion and sponsorship of tobacco to reverse tobacco epidemic. Tobacco advertising, promotion and sponsorship (TAPS) is also banned under India's Cigarettes and Other Tobacco Products Act, 2003, with few exceptions. Despite the Act and increasing evidence of advertising linked with smoking behaviours, tobacco companies indulge in it brazenly to neutralise tobacco control efforts and normalize its use, making it seem like any other consumer product. The companies aim at creating a brand franchise for their product through advertisements. Point of sale promotion account for more than three-fourth of marketing spends by tobacco companies. Although India has been a frontrunner in tobacco control, it faced huge legal challenge from the tobacco industry. There is a need to regulate tobacco business by compulsory registration and licensing of tobacco vendors and also effective implementation of Indian Act. Besides, the gap in current research from developing countries on how restrictions on advertising impact tobacco use and its associated behaviour, monitor tobacco industry activity, map vendors and access of products, and economic impact of restrictions on tobacco promotions at POS needs to be fulfilled. Without these measures it will be challenging to counter nefarious, cash-rich and truant tobacco industry
Deletion of Nedd4-2 results in progressive kidney disease in mice
No full textNEDD4-2 (NEDD4L), a ubiquitin protein ligase of the Nedd4 family, is a key regulator of cell surface expression and activity of the amiloride-sensitive epithelial Na⁺ channel (ENaC). While hypomorphic alleles of Nedd4-2 in mice show salt-sensitive hypertension, complete knockout results in pulmonary distress and perinatal lethality due to increased cell surface levels of ENaC. We now show that Nedd4-2 deficiency in mice also results in an unexpected progressive kidney injury phenotype associated with elevated ENaC and Na⁺Cl⁻ cotransporter expression, increased Na⁺ reabsorption, hypertension and markedly reduced levels of aldosterone. The observed nephropathy is characterized by fibrosis, tubule epithelial cell apoptosis, dilated/cystic tubules, elevated expression of kidney injury markers and immune cell infiltration, characteristics reminiscent of human chronic kidney disease. Importantly, we demonstrate that the extent of kidney injury can be partially therapeutically ameliorated in mice with nephron-specific deletions of Nedd4-2 by blocking ENaC with amiloride. These results suggest that increased Na⁺ reabsorption via ENaC causes kidney injury and establish a novel role of NEDD4-2 in preventing Na⁺-induced nephropathy. Contrary to some recent reports, our data also indicate that ENaC is the primary in vivo target of NEDD4-2 and that Nedd4-2 deletion is associated with hypertension on a normal Na⁺ diet. These findings provide further insight into the critical function of NEDD4-2 in renal pathophysiology.Tanya L Henshall, Jantina A Manning, Omri S Alfassy, Pranay Goel, Natasha A Boase, Hiroshi Kawabe and Sharad Kuma
The Decisions To Make (In An Advertising Agency)
No full textThis case is about Mr. Pranay Bharadwaj who with his hard word rose to an entrepreneur and initiated Total Advertising after understanding the advertising trade. In the case author has made an effort to understand the need of customers in the changing times. At the time of this problem Mr. Pranay put emphasis on research parameters to use it as a tool of decision making thus leading to customer satisfaction
Efficient learning and planning using spatial side information
No full textThis thesis investigates the following question: how to efficiently integrate side information, available either a priori or online, with existing algorithms for learning and planning in environments with stochastic features? Side information in this context refers to any information that does not directly determine system parameters, but indicates a relationship between them. Such information can often be obtained from existing data, including that collected by onboard sensors. Algorithms that exploit side information are of interest in solving many real-world problems that can be modeled as stochastic control processes with unknown transition probabilities or unknown transition times. Specifically, we consider the problems of reward maximization in grid-world environments with unknown, stochastic dynamics and travel time minimization in urban transit routing problems with deterministic dynamics and stochastic travel times. Exploiting additional information available to solve these problems, when classical algorithms leave much to be desired in terms of performance and accuracy, is the main theme of this thesis.
The first part of the thesis proposes the idea of indirect sampling for accelerated learning in Markov decision processes when additional information is available in the form of bounds on the differences between the transition probabilities at different states. In addition, it proposes a greedy approximation algorithm that utilizes the additional side information to effectively balance exploration and exploitation. It also analyzes the performance of indirect sampling algorithms in different information settings and defines the notion of agent safety, a vital consideration for systems operating in the physical environment, in the context of our problem. Under certain assumptions, it provides guarantees on the safety of an agent exploring with our algorithm that exploits side information.
The second part proposes a methodology and a tool that, given an origin-destination pair, a travel time budget, and a measure of the passenger's tolerance for ambiguity, provide the optimal online route choice in a transit network by balancing the objectives of maximizing on-time arrival probability and minimizing expected travel time. This framework is a significant improvement over existing algorithms where the problem of optimal routing in urban transit networks is usually studied with only the least expected travel time as the performance criteria under the assumption of travel time independence on different road segments. The proposed algorithm utilizes side information, available in the form of historic travel time data and upstream real-time data, to build and update the underlying model online.
We demonstrate the utility and the performance of the proposed algorithms with the help of realistic numerical experiments conducted (i) on a fixed-route bus system that serves the residents of the Champaign-Urbana metropolitan area and, (ii) in the setting of a Mars rover navigating on unknown or partially known terrain. In both of these problems, data from onboard sensors and external sources acts as the side information.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2022-12-01The student, Pranay Thangeda, accepted the attached license on 2020-12-07 at 20:36.The student, Pranay Thangeda, submitted this Thesis for approval on 2020-12-07 at 21:47.This Thesis was approved for publication on 2020-12-09 at 15:15.DSpace SAF Submission Ingestion Package generated from Vireo submission #16086 on 2021-03-04 at 16:20:43Made available in DSpace on 2021-03-05T21:42:51Z (GMT). No. of bitstreams: 2
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Previous issue date: 2020-12-09Embargo set by: Seth Robbins for item 117236
Lift date: 2023-03-05T21:43:00Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Onl
Characterisation of pathophysiological function of NEDD4-2 in kidney
No full textNedd4-2 (NEDD4L, neural precursor cell expressed, developmentally down regulated 4-like) belongs to the Nedd4 family of ubiquitin ligases. These ligases aid in maintaining cellular homeostasis by binding to, and ubiquitinating a number of membrane proteins to initiate their internalization and turnover. Previous work from our laboratory has suggested that Nedd4-2 plays an essential role in regulating ion channels, especially the epithelial sodium channel and voltage gated sodium channels. The misregulation of these channels has been implicated in multiple channelopathies, including hypertension and cystic fibrosis like disease. This study characterises a previously unknown function of Nedd4-2 in the kidney. In order to understand this significance of Nedd4-2 in renal homeostasis, the previously generated Nedd4-2⁻ʹ⁻ (Nedd4-2 knockout) mice (Boase et al., 2011) were characterised. The initial histological examination of postnatal kidneys suggested renal cyst formation in Nedd4-2⁻ʹ⁻ animals. Further analysis revealed that Nedd4-2 loss results in renal dysplasia. Nedd4-2⁻ʹ⁻ mice showed variable renal cystic index, onset of cyst formation starting from postnatal day 2 and progressing until the Nedd4-2⁻ʹ⁻ animals die due to respiratory distress around day 19-21. To investigate the prevalence of the cystic phenotype in other tissues histological analysis was performed in pancreas, liver, spleen, colon, stomach and thymus with no significant pathological differences observed in the knockout mice. The Nedd4-2⁻ʹ⁻ kidneys showed increased cell proliferation, with no apoptotic differences in the cells lining the cystic epithelia suggesting an imbalance between cell proliferation and apoptosis in cyst formation. The cyst formation and kidney development disorders are associated with malformation in the kidney tissue leading to extracellular matrix modification with enhanced accumulation of collagens causing increased interstitial fibrosis. The Nedd4-2⁻ʹ⁻ kidneys showed increased interstitial fibrosis, collagen-1 accumulation and expression during progression of the disease. The renal tissue membrane is made up of polysaccharides, glycogen and mucin, the Nedd4-2⁻ʹ⁻ kidneys were found to have decreased accumulation of polysaccharides. The cysts in the Nedd4-2⁻ʹ⁻ kidneys originated from different parts within the nephron. The larger cysts originated from loop of Henle and with the smaller cysts from collecting ducts and distal convoluted tubules. The cystic progression is dependent on cAMP flux initiated by fluid secretion within the cyst. The postnatal day 19 cystic kidneys in Nedd4-2⁻ʹ⁻ animals showed increased cAMP levels suggesting cystic disease progression. As renal cystic disorders may arise from abnormal cilia, ciliary anomalies were found in the Nedd4-2⁻ʹ⁻ around the cysts suggesting importance of cilia in kidney cyst formation. Polycystins are known to be involved in renal cyst development with polycystin-1 and polycystin-2 together known to form calcium ion channel. To investigate the role of Nedd4-2 in the regulation of these polycystins, in vitro and in vivo studies were conducted. In vitro studies suggested that depletion of Nedd4-2 results in increased expression of polycystin-1 on the cell membrane with a decrease in polycystin-2 levels. Further, polycystin-1 was found to be ubiquitinated by Nedd4-2 in vitro providing the first evidence of Nedd4-2-mediated regulation of polycystins. In vivo Polycystin-1 was up-regulated in the Nedd4-2⁻ʹ⁻ kidneys suggesting an important role of Nedd4-2 in regulation of polycystins in cyst formation. To analyse the transcriptional signature of the phenotype seen in the knockout kidneys, postnatal day 19 kidneys from wild-type and Nedd4-2⁻ʹ⁻ mice were subjected to RNA sequencing highlighting 537 genes that were differentially expressed between wild-type and knockout kidneys, with 167 genes down-regulated and 370 genes significantly up-regulated in the absence of Nedd4-2. DAVID and Ingenuity pathway analyses was used to highlight the importance of genes involved in extracellular matrix modification, cell junction formation and cell-cell communication. The work presented in this thesis thus provides new information on the pathophysiological role of Nedd4-2 in kidney and identifies polycystin-1 as a Nedd4-2 target, along with transcriptional changes which may partially explain the cystic phenotype associated with renal dysplasia.Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2016
The Use of Maps in the Analysis of Networks of Coupled Neuronal Oscillators
No full textIn this thesis we study aspects of periodic activity in model mutually-coupled oscillators inspired by the nervous system. We define and use maps describing the timing of activity on successive cycles. The central theme here is to examine emergent behavior in networks through the properties of the individual oscillators.In the first chapter, we describe Phase Response Curves (PRCs), which map the changes in theperiod of an oscillator to perturbations at dierent phases along the cycle. We consider various networks of oscillators, pulse-coupled through their PRCs: rings, chains, arrays, and global coupling.We study conditions under which stable patterns, such as synchrony and waves, may be found.In the second and third chapters, we model beta (12-30 Hz) and gamma (30-80 Hz) rhythmsin the nervous system in reduced networks of excitatory and inhibitory neurons. We look at theintriguing results of experiments that show increases in beta band activity in human MEGs upon taking the sedative Diapam. We show that the model network is able to mimic the experimental data. The model then clarifies the inhibitory action of the drug in tissue.We look at another experiment that finds disruption of long-range synchrony of gamma oscillations in transgenic mice with altered excitatory kinetics. We study this behavior in a reduced network that encodes for conduction delays across spatially distal sites. The model provides an explanation of this phenomenon in terms of the properties of the cells involved in generating the rhythm.In our analyses, we use maps to study stability of the patterns of activity
Smoking trends among women in India: Analysis of nationally representative surveys (1993-2009)
No full textBackground: There is growing concern among policy makers with respect to alarming growth in smoking prevalence among women in the developing countries. Methods: Using disaggregated data from five nationally representative surveys: Global Adult Tobacco Survey 2010, National Family Health Survey-III (NFHS-III) 2004-2005, NFHS-II 1998-1999, National Sample Survey (NSS) 52 nd Round 1995-1996, NSS 50 th Round 1993-1994 we analysed female smoking trend from 1993-2009. Tobacco use among females was monitored for almost two decades focusing on gender, literacy, and state-specific trends among respondents aged >15 years. Results: Smoking use among women has doubled from 1.4% to 2.9% (P < 0.001) during the period 2005-2010. The prevalence of smoking increased with decrease in per capita State Gross Domestic Product and literacy status for both men and women. Conclusion: As the overall smoking prevalence grows, female smoking is growing at a faster rate than smoking among males, which is an emerging concern for tobacco control in India and requires the attention of policymakers
Learning theories reveal loss of pancreatic electrical connectivity in diabetes as an adaptive response.
No full textCells of almost all solid tissues are connected with gap junctions which permit the direct transfer of ions and small molecules, integral to regulating coordinated function in the tissue. The pancreatic islets of Langerhans are responsible for secreting the hormone insulin in response to glucose stimulation. Gap junctions are the only electrical contacts between the beta-cells in the tissue of these excitable islets. It is generally believed that they are responsible for synchrony of the membrane voltage oscillations among beta-cells, and thereby pulsatility of insulin secretion. Most attempts to understand connectivity in islets are often interpreted, bottom-up, in terms of measurements of gap junctional conductance. This does not, however, explain systematic changes, such as a diminished junctional conductance in type 2 diabetes. We attempt to address this deficit via the model presented here, which is a learning theory of gap junctional adaptation derived with analogy to neural systems. Here, gap junctions are modelled as bonds in a beta-cell network, that are altered according to homeostatic rules of plasticity. Our analysis reveals that it is nearly impossible to view gap junctions as homogeneous across a tissue. A modified view that accommodates heterogeneity of junction strengths in the islet can explain why, for example, a loss of gap junction conductance in diabetes is necessary for an increase in plasma insulin levels following hyperglycemia
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