Search results for: Pramod S. Kamath

Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

Abstract:

Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

Procedia PDF Downloads 159

Authors: Snehal D. Ganjave, Hardik Dodia, Avinash V. Sunder, Swati Madhu, Pramod P. Wangikar

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Batch cultivation of recombinant bacteria in shake flasks results in low cell density due to nutrient depletion. Previous protocols on high cell density cultivation in shake flasks have relied mainly on controlled release mechanisms and extended cultivation protocols. In the present work, we report an optimized fed-batch process for high cell density cultivation of recombinant E. coli BL21(DE3) for protein production. A cybernetic model-based, multi-objective optimization strategy was implemented to obtain the optimum operating variables to achieve maximum biomass and minimized substrate feed rate. A syringe pump was used to feed a mixture of glycerol and yeast extract into the shake flask. Preliminary experiments were conducted with online monitoring of dissolved oxygen (DO) and offline measurements of biomass and glycerol to estimate the model parameters. Multi-objective optimization was performed to obtain the pareto front surface. The selected optimized recipe was tested for a range of proteins that show different extent soluble expression in E. coli. These included eYFP and LkADH, which are largely expressed in soluble fractions, CbFDH and GcanADH , which are partially soluble, and human PDGF, which forms inclusion bodies. The biomass concentrations achieved in 24 h were in the range 19.9-21.5 g/L, while the model predicted value was 19.44 g/L. The process was successfully reproduced in a standard laboratory shake flask without online monitoring of DO and pH. The optimized fed-batch process showed significant improvement in both the biomass and protein production of the tested recombinant proteins compared to batch cultivation. The proposed process will have significant implications in the routine cultivation of E. coli for various applications.

Keywords: cybernetic model, E. coli, high cell density cultivation, multi-objective optimization

Procedia PDF Downloads 224

Authors: Anum Javed

Abstract:

This study identifies the dynamical image of human body that continues its metamorphosis in the virtual field of reality. It calls attention to the ways where humans start co-evolving with other life forms; technology in particular and are striving to establish a realm outside the physical framework of matter. The problem exceeds the area of technological ethics by explicably and explanatorily entering the space of literary texts and criticism. Textual analysis of Geek Love (1989) by Katherine Dunn is adjoined with posthumanist perspectives of Pramod K. Nayar to beget psycho-somatic changes in man’s nature of being. It uncovers the meaning people give to their experiences in this budding social and cultural phenomena of material representation tied up with personal practices and technological innovations. It also observes an ethical, physical and psychological reassessment of man within the context of technological evolutions. The study indicates the elements that have rendered morphological freedom and new materialism in man’s consciousness. Moreover this work is inquisitive of what it means to be a human in this time of accelerating change where surgeries, implants, extensions, cloning and robotics have shaped a new sense of being. It attempts to go beyond individual’s body image and explores how objectifying media and culture have influenced people’s judgement of others on new material grounds. It further argues a decentring of the glorified image of man as an independent entity because of his energetic partnership with intelligent machines and external agents. The history of the future progress of technology is also mentioned. The methodology adopted is posthumanist techno-ethical textual analysis. This work necessitates a negotiating relationship between man and technology in order to achieve harmonic and balanced interconnected existence. The study concludes by recommending a call for an ethical set of codes to be cultivated for the techno-human habituation. Posthumanism ushers a strong need of adopting new ethics within the terminology of neo-materialist humanism.

Keywords: corporeality, dematerialism, human ethos, posthumanism

Procedia PDF Downloads 123

Authors: Gayathri Pramod, Sheeja K. P.

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Urban flooding has been seen rising in cities for the past few years. This rise in urban flooding is the result of increasing urbanization and increasing climate change. A resilient city design focuses on 'living with water'. This means that the city is capable of accommodating the floodwaters without having to risk any loss of lives or properties. The resilient city design incorporates green infrastructure, river edge treatment, open space design, etc. to form a city that functions as a whole for resilience. Sponge urbanism is a recent method for building resilient cities and is founded by China in 2014. Sponge urbanism is the apt method for resilience building for a tropical town like Aluva of Kerala. Aluva is a tropical town that experiences rainfall of about 783 mm per month during the rainy season. Aluva is an urbanized town which faces the risk of urban flooding and riverine every year due to the presence of Periyar River in the town. Impervious surfaces and hard construction and developments contribute towards flood risk by posing as interference for a natural flow and natural filtration of water into the ground. This type of development is seen in Aluva also. Aluva is designed in this research as a town that have resilient strategies of sponge city and which focusses on natural methods of construction. The flood susceptibility of Aluva is taken into account to design the spaces for sponge urbanism and in turn, reduce the flood susceptibility for the town. Aluva is analyzed, and high-risk zones for development are identified through studies. These zones are designed to withstand the risk of flooding. Various catchment areas are identified according to the natural flow of water, and then these catchment areas are designed to act as a public open space and as detention ponds in case of heavy rainfall. Various development guidelines, according to land use, is also prescribed, which help in increasing the green cover of the town. Aluva is then designed to be a completely flood-adapted city or sponge city according to the guidelines and interventions.

Keywords: climate change, flooding, resilient city, sponge city, sponge urbanism, urbanization

Procedia PDF Downloads 131

Authors: Guna Raj Dhungana, Roshan Nepal, Apshara Parajuli, , Archana Maharjan, Shyam K. Mishra, Pramod Aryal, Rajani Malla

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Introduction: Klebsiella pneumoniae is a well-known opportunistic human pathogen, primarily causing healthcare-associated infections. The global emergence of carbapenemase-producing K. pneumoniaeis a major public health burden, which is often extensively multidrug resistant.Thus, because of the difficulty to treat these ‘superbug’ and menace and some term as ‘apocalypse’ of post antibiotics era, an alternative approach to controlling this pathogen is prudent and one of the approaches is phage mediated control and/or treatment. Objective: In this study, we aimed to isolate novel bacteriophage against carbapenemase-producing K. pneumoniaeand characterize for potential use inphage therapy. Material and Methods: Twenty lytic phages were isolated from river water using double layer agar assay and purified. Biological features, physiochemical characters, burst size, host specificity and activity spectrum of phages were determined. One most potent phage: Phage TU_Kle10O was selected and characterized by electron microscopy. Whole genome sequences of the phage were analyzed for presence/absence of virulent factors, and other lysin genes. Results: Novel phage TU_Kle10O showed multiple host range within own genus and did not induce any BIM up to 5th generation of host’s life cycle. Electron microscopy confirmed that the phage was tailed and belonged to Caudovirales family. Next generation sequencing revealed its genome to be 166.2 Kb. bioinformatical analysis further confirmed that the phage genome ‘did not’ contain any ‘bacterial genes’ within phage genome, which ruled out the concern for transfer of virulent genes. Specific 'lysin’ enzyme was identified phages which could be used as 'antibiotics'. Conclusion: Extensively multidrug resistant bacteria like carbapenemase-producing K. pneumoniaecould be treated efficiently by phages.Absence of ‘virulent’ genes of bacterial origin and presence of lysin proteins within phage genome makes phages an excellent candidate for therapeutics.

Keywords: bacteriophage, Klebsiella pneumoniae, MDR, phage therapy, carbapenemase,

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Authors: Sabyasachi Behera, Shiv Kumar, Pramod Gautam, Anisur Rahman, Pawan Pathak, Rahul Bhadouria

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Background: The increasing proportion of population especially urban poor and vulnerable groups or groups with specific needs, with health indicators worse than their rural counterparts in India face various issues related with availability and quality of health care. The reasons are myriad, starting from information and awareness of the community, especially, in a scenario wherein the needs and challenges of floating and migrant urban populations remain poorly understood. Weak linkages between health care facilities and slum dwellers and vulnerable populations hinder the improvement of health services for urban poor. Method: To address this issue, TCIHC program is helping health department of Indore city of Madhya Pradesh to establish a referral mechanism with a dual approach: at both community and facility level. The former is based on the premise of ‘building social capital’, i.e. norms and networks within a community facilitating collective action, helps improve the demand and supply of health services at appropriate levels of care (Minus 2: Accredited Social Health Activist and Community Health Groups; Minus 1: Urban Health Nutrition Days; Zero: Urban Primary Health Center; Plus 1: secondary facility with BEmONC services; Plus 2: secondary facilities with CEmONC services; Plus 3: tertiary level facility) for the urban poor. The latter focuses on encouraging the provision of all services at various levels of service delivery points and stakeholders to function in a coordinated manner to ensure better health service availability and coverage in underserved slum areas. Results: This initiative has enhanced the utilization of community based, primary and secondary level services through defined referral pathways that are clearly known to a community dweller. Conclusion: An ideal referral mechanism should begin with referral at the community level wherein services of a frontline health care provider are accessed by them at their door-step, causing no delay in both understanding and decision on the health issues faced by them.

Keywords: levels of care, linkages, referral mechanism, service delivery

Procedia PDF Downloads 121

Authors: Pramod Somvanshi, Manu Tomar, K. V. Venkatesh

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Insulin and glucagon are responsible for homeostasis of key plasma metabolites like glucose, amino acids and fatty acids in the blood plasma. These hormones act antagonistically to each other during the secretion and signaling stages. In the present work, we analyze the effect of macronutrients on the response from integrated insulin and glucagon signaling pathways. The insulin and glucagon pathways are connected by DAG (a calcium signaling component which is part of the glucagon signaling module) which activates PKC and inhibits IRS (insulin signaling component) constituting a crosstalk. AKT (insulin signaling component) inhibits cAMP (glucagon signaling component) through PDE3 forming the other crosstalk between the two signaling pathways. Physiological level of anabolism and catabolism is captured through a metric quantified by the activity levels of AKT and PKA in their phosphorylated states, which represent the insulin and glucagon signaling endpoints, respectively. Under resting and starving conditions, the phosphorylation metric represents homeostasis indicating a balance between the anabolic and catabolic activities in the tissues. The steady state analysis of the integrated network demonstrates the presence of a bistable response in the phosphorylation metric with respect to input plasma glucose levels. This indicates that two steady state conditions (one in the homeostatic zone and other in the anabolic zone) are possible for a given glucose concentration depending on the ON or OFF path. When glucose levels rise above normal, during post-meal conditions, the bistability is observed in the anabolic space denoting the dominance of the glycogenesis in liver. For glucose concentrations lower than the physiological levels, while exercising, metabolic response lies in the catabolic space denoting the prevalence of glycogenolysis in liver. The non-linear positive feedback of AKT on IRS in insulin signaling module of the network is the main cause of the bistable response. The span of bistability in the phosphorylation metric increases as plasma fatty acid and amino acid levels rise and eventually the response turns monostable and catabolic representing diabetic conditions. In the case of high fat or protein diet, fatty acids and amino acids have an inhibitory effect on the insulin signaling pathway by increasing the serine phosphorylation of IRS protein via the activation of PKC and S6K, respectively. Similar analysis was also performed with respect to input amino acid and fatty acid levels. This emergent property of bistability in the integrated network helps us understand why it becomes extremely difficult to treat obesity and diabetes when blood glucose level rises beyond a certain value.

Keywords: bistability, diabetes, feedback and crosstalk, obesity

Procedia PDF Downloads 245