Search results for: Mayank Sharma

Authors: Kalpana Adhikari, Mandip Subedi, Keshab Sharma, Indra P. Acharya

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The Gorkha Nepal earthquake of moment magnitude (Mw) 7.8 struck the central region of Nepal on April 25, 2015 with the epicenter about 77 km northwest of Kathmandu Valley . Peak ground acceleration observed during the earthquake was 0.18g. This motion induced several geotechnical effects such as landslides, foundation failures liquefaction, lateral spreading and settlement, and local amplification. An aftershock of moment magnitude (Mw) 7.3 hit northeast of Kathmandu on May 12 after 17 days of main shock caused additional damages. Kathmandu is the largest city in Nepal, have a population over four million. As the Kathmandu Valley deposits are composed mainly of sand, silt and clay layers with a shallow ground water table, liquefaction is highly anticipated. Extensive liquefaction was also observed in Kathmandu Valley during the 1934 Nepal-Bihar earthquake. Field investigations were carried out in Kathmandu Valley immediately after Mw 7.8, April 25 main shock and Mw 7.3, May 12 aftershock. Geotechnical investigation of both liquefied and non-liquefied sites were conducted after the earthquake. This paper presents observations of liquefaction and liquefaction induced damage, and the liquefaction potential assessment based on Standard Penetration Tests (SPT) for liquefied and non-liquefied sites. SPT based semi-empirical approach has been used for evaluating liquefaction potential of the soil and Liquefaction Potential Index (LPI) has been used to determine liquefaction probability. Recorded ground motions from the event are presented. Geological aspect of Kathmandu Valley and local site effect on the occurrence of liquefaction is described briefly. Observed liquefaction case studies are described briefly. Typically, these are sand boils formed by freshly ejected sand forced out of over-pressurized sub-strata. At most site, sand was ejected to agricultural fields forming deposits that varied from millimetres to a few centimeters thick. Liquefaction-induced damage to structures in these areas was not significant except buildings on some places tilted slightly. Boiled soils at liquefied sites were collected and the particle size distributions of ejected soils were analyzed. SPT blow counts and the soil profiles at ten liquefied and non-liquefied sites were obtained. The factors of safety against liquefaction with depth and liquefaction potential index of the ten sites were estimated and compared with observed liquefaction after 2015 Gorkha earthquake. The liquefaction potential indices obtained from the analysis were found to be consistent with the field observation. The field observations along with results from liquefaction assessment were compared with the existing liquefaction hazard map. It was found that the existing hazard maps are unrepresentative and underestimate the liquefaction susceptibility in Kathmandu Valley. The lessons learned from the liquefaction during this earthquake are also summarized in this paper. Some recommendations are also made to the seismic liquefaction mitigation in the Kathmandu Valley.

Keywords: factor of safety, geotechnical investigation, liquefaction, Nepal earthquake

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Authors: C. A. Sharma, Birendra P. Singh

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We recovered 40 well preserved ribbon-shaped, meandering specimens of S. ningqiangensis from the Earthy Dolomite Member (Krol Group) and calcareous siltstone beds of the Earthy Siltstone Member (Tal Group) showing closely spaced annulations that lacked branching. The beginning and terminal points are indistinguishable. In certain cases, individual specimens are characterized by irregular, low-angle to high-angle sinuosity. It has been variously described as body fossil, ichnofossil and algae. Detailed study of this enigmatic fossil is needed to resolve the long standing controversy regarding its phylogenetic and stratigraphic placements, which will be an important contribution to the evolutionary history of metazoans. S. ningqiangensis has been known from the late Neoproterozoic (Ediacaran) of southern and central China (Sichuan, Shaanxi, Quinghai and Guizhou provinces and Ningxia Hui Autonomous region), Siberian platform and across Pc/C Boundary from latest Neoprterozoic to earliest Cambrian of northern India. Shaanxilithes is considered an Ediacaran organism that spans the Precambrian–Cambrian boundary, an interval marked by significant taphonomic and ecological transformations that include not only innovation but also probable extinction. All the past well constrained finds of S. ningqiangensis are restricted to Ediacaran age. However, due to the new recoveries of the fossil from Nigalidhar Syncline, the stratigraphic status of S. ningqiangensis-bearing Earthy Siltstone Member of the Shaliyan Formation of the Tal Group (Cambrian) is rendered uncertain, though the overlying Chert Member in the adjoining Korgai Syncline has yielded definite early Cambrian acritarchs. The moot question is whether the Earthy Siltstone Member represents an Ediacaran or an early Cambrian age?. It would be interesting to find if Shaanxilithes, so far known from Ediacaran sequences, could it transgress to the early Cambrian or in simple words could it withstand the Pc/C Boundary event? GC-MS data shows the S. ningqiangensis structure is formed by hydrocarbon organic compounds which are filled with inorganic elements filler like silica, Calcium, phosphorus etc. The S. ningqiangensis structure is a mixture of organic compounds of high molecular weight, containing several saturated rings with hydrocarbon chains having an occasional isolated carbon-carbon double bond and also containing, in addition, to small amounts of nitrogen, sulfur and oxygen. Data also revealed that the presence of nitrogen which would be either in the form of peptide chains means amide/amine or chemical form i.e. nitrates/nitrites etc. The formula weight and the weight ratio of C/H shows that it would be expected for algae derived organics, since algae produce fatty acids as well as other hydrocarbons such as cartenoids.

Keywords: GC-MS Analysis, lesser himalaya, Pc/C Boundary, shaanxilithes

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Authors: Piyush Sharma, Laltu Chandra, P. S. Ghoshdastidar, Rajiv Shekhar

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Metals processing operations such as melting and heat treatment of metals are energy-intensive, requiring temperatures greater than 500oC. The desired temperature in these industrial furnaces is attained by circulating electrically-heated air. In most of these furnaces, electricity produced from captive coal-based thermal power plants is used. Solar thermal energy could be a viable heat source in these furnaces. A retrofitted solar convective furnace (SCF) concept, which uses solar thermal generated hot air, has been proposed. Critical to the success of a SCF is the design of an open volumetric air receiver (OVAR), which can heat air in excess of 800oC. The OVAR is placed on top of a tower and receives concentrated solar radiation from a heliostat field. Absorbers, mixer assembly, and the return air flow chamber (RAFC) are the major components of an OVAR. The absorber is a porous structure that transfers heat from concentrated solar radiation to ambient air, referred to as primary air. The mixer ensures uniform air temperature at the receiver exit. Flow of the relatively cooler return air in the RAFC ensures that the absorbers do not fail by overheating. In an earlier publication, the detailed design basis, fabrication, and characterization of a 2 kWth open volumetric air receiver (OVAR) based laboratory solar air tower simulator was presented. Development of an experimentally-validated, CFD based mathematical model which can ultimately be used for the design and scale-up of an OVAR has been the major objective of this investigation. In contrast to the published literature, where flow and heat transfer have been modeled primarily in a single absorber module, the present study has modeled the entire receiver assembly, including the RAFC. Flow and heat transfer calculations have been carried out in ANSYS using the LTNE model. The complex return air flow pattern in the RAFC requires complicated meshes and is computational and time intensive. Hence a simple, realistic 1-D mathematical model, which circumvents the need for carrying out detailed flow and heat transfer calculations, has also been proposed. Several important results have emerged from this investigation. Circumferential electrical heating of absorbers can mimic frontal heating by concentrated solar radiation reasonably well in testing and characterizing the performance of an OVAR. Circumferential heating, therefore, obviates the need for expensive high solar concentration simulators. Predictions suggest that the ratio of power on aperture (POA) and mass flow rate of air (MFR) is a normalizing parameter for characterizing the thermal performance of an OVAR. Increasing POA/MFR increases the maximum temperature of air, but decreases the thermal efficiency of an OVAR. Predictions of the 1-D mathematical are within 5% of ANSYS predictions and computation time is reduced from ~ 5 hours to a few seconds.

Keywords: absorbers, mixer assembly, open volumetric air receiver, return air flow chamber, solar thermal energy

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Authors: Chang Liu, Hanwen Zhang, Vikash Sharma, Don Eliseo Lucerno-Prisno III, Emmanuel Yujuico, Maulik Chokshi, Prashanthi Krishnakumar, Bach Xuan Tran, Giang Thu Vu, Kamilla Anna Pinter, Shenglan Tang

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Background and Aims: Globally, many health systems focus on hospital-based healthcare models targeting acute care and disease treatment, which are not effective in addressing the challenges of ageing populations, chronic conditions, multi-morbidities, and increasingly unhealthy lifestyles. Recently, integrated care programs on chronic diseases have been developed, piloted, and implemented to meet such challenges. However, integrated care programs in the Asia-Pacific region vary in the levels of integration from linkage to coordination to full integration. This study aims to identify and analyze existing cases of integrated care in the Asia-Pacific region and identify the facilitators and barriers in order to improve existing cases and inform future cases. Methods: The study is a comparative study, with a combination approach of desk-based research and key informant interviews. The selected countries included in this study represent a good mix of lower-middle income countries (the Philippines, India, Vietnam, and Fiji), upper-middle income country (China), and high-income country (Singapore) in the Asia-Pacific region. Existing integrated care programs were identified through the scoping review approach. Trigger, history, general design, beneficiaries, and objectors were summarized with barriers and facilitators of integrated care based on key informant interviews. Representative case(s) in each country were selected and comprehensively analyzed through deep-dive case studies. Results: A total of 87 existing integrated care programs on chronic diseases were found in all countries, with 44 in China, 21 in Singapore, 12 in India, 5 in Vietnam, 4 in the Philippines, and 1 in Fiji. 9 representative cases of integrated care were selected for in-depth description and analysis, with 2 in China, the Philippines, and Vietnam, and 1 in Singapore, India, and Fiji. Population aging and the rising chronic disease burden have been identified as key drivers for almost all the six countries. Among the six countries, Singapore has the longest history of integrated care, followed by Fiji, the Philippines, and China, while India and Vietnam have a shorter history of integrated care. Incentives, technologies, education, and performance evaluation would be crucial for developing strategies for implementing future programs and improve already existing programs. Conclusion: Integrated care is important for addressing challenges surrounding the delivery of long-term care. To date, there is an increasing trend of integrated care programs on chronic diseases in the Asia-Pacific region, and all six countries in our study set integrated care as a direction for their health systems transformation.

Keywords: integrated healthcare, integrated care delivery, chronic diseases, Asia-Pacific region

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Authors: Niraimathi Kesavan, Sangeeta Sharma, Deepa Jagan, Sridhar Sukumar, Mohan Ramachandran, Vidhubala Elangovan

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Background: Childhood is a dynamic period for growth and development. Optimum nutrition during this period forms a strong foundation for growth, development, resistance to infections, long-term good health, cognition, educational achievements, and work productivity in a later phase of life. Underprivileged children living in a resource constraint settings like shelter homes are at high risk of malnutrition due to poor quality diet and nutritional inadequacy. In low-income countries, underprivileged children are vulnerable to being deprived of nutritious food, which stands as a major challenge in the health sector. The present aims to assess the dietary intake, nutritional status, and nutritional inadequacy and their association with malnutrition among children residing in shelter homes in rural Tamil Nadu. Methods: The study was a descriptive survey conducted among all the children aged between 8-18 years residing in two selected shelter homes (Anbu illam, a home for female children, and Amaidhi illam, a home for male children), rural Tirunelveli, Tamil Nadu, India. A total of 57 children were recruited, including 18 boys and 39 girls, for the study. Dietary intake was measured using seven days 24 hours recall. The average nutrient intake was considered for further analysis. Results: Of the 57 children, about 60% (n=35) were undernutrition. The mean daily energy intake was 1298 (SD 180) kcal for boys and 952 (SD155) kcal for girls. The total calorie intake was 55-60% below the estimated average requirement (EAR) for adolescent boys and girls in the age group 13-15 years and 16-18 years. Carbohydrates were the major source of energy (boys 53% and girls 51%), followed by fat (boys 31.5% and girls 34.5%) and protein (boys 14% and girls 12.9%). Dairy intake (<200ml/day) was less than the recommendation (500ml/day). Micro-nutrient-rich foods such as fruits, vegetables, and green leafy vegetables in the diet were <200g/day, which was far less than the recommended dietary guidelines of 400g- 600g/day for the age group of 7-18 years. Nearly 26% of girls reported experiencing menstrual problems. The majority (76.9%) of the children exhibited nutrient deficiency-related signs and symptoms. Conclusion: The total energy, minerals, and micro-nutrient intake were inadequate and below the Recommended Dietary Allowance for children and adolescents. The diet predominantly consists of refined cereals, rice, semolina, and vermicelli. Consumption of whole grains, milk, fruits, vegetables, and leafy vegetables was far below the recommended dietary guidelines. Dietary inadequacies among these children pose a serious concern for their overall health status and its consequences in the later phase of life.

Keywords: adolescents, children, dietary intake, malnutrition, nutritional inadequacy, shelter home

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Authors: L. Raczynski, P. Moskal, P. Kowalski, W. Wislicki, T. Bednarski, P. Bialas, E. Czerwinski, A. Gajos, L. Kaplon, A. Kochanowski, G. Korcyl, J. Kowal, T. Kozik, W. Krzemien, E. Kubicz, Sz. Niedzwiecki, M. Palka, Z. Rudy, O. Rundel, P. Salabura, N.G. Sharma, M. Silarski, A. Slomski, J. Smyrski, A. Strzelecki, A. Wieczorek, M. Zielinski, N. Zon

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The J-PET scanner, which allows for single bed imaging of the whole human body, is currently under development at the Jagiellonian University. The J-PET detector improves the TOF resolution due to the use of fast plastic scintillators. Since registration of the waveform of signals with duration times of few nanoseconds is not feasible, a novel front-end electronics allowing for sampling in a voltage domain at four thresholds was developed. To take fully advantage of these fast signals a novel scheme of recovery of the waveform of the signal, based on ideas from the Tikhonov regularization (TR) and Compressive Sensing methods, is presented. The prior distribution of sparse representation is evaluated based on the linear transformation of the training set of waveform of the signals by using the Principal Component Analysis (PCA) decomposition. Beside the advantage of including the additional information from training signals, a further benefit of the TR approach is that the problem of signal recovery has an optimal solution which can be determined explicitly. Moreover, from the Bayes theory the properties of regularized solution, especially its covariance matrix, may be easily derived. This step is crucial to introduce and prove the formula for calculations of the signal recovery error. It has been proven that an average recovery error is approximately inversely proportional to the number of samples at voltage levels. The method is tested using signals registered by means of the single detection module of the J-PET detector built out from the 30 cm long BC-420 plastic scintillator strip. It is demonstrated that the experimental and theoretical functions describing the recovery errors in the J-PET scenario are largely consistent. The specificity and limitations of the signal recovery method in this application are discussed. It is shown that the PCA basis offers high level of information compression and an accurate recovery with just eight samples, from four voltage levels, for each signal waveform. Moreover, it is demonstrated that using the recovered waveform of the signals, instead of samples at four voltage levels alone, improves the spatial resolution of the hit position reconstruction. The experiment shows that spatial resolution evaluated based on information from four voltage levels, without a recovery of the waveform of the signal, is equal to 1.05 cm. After the application of an information from four voltage levels to the recovery of the signal waveform, the spatial resolution is improved to 0.94 cm. Moreover, the obtained result is only slightly worse than the one evaluated using the original raw-signal. The spatial resolution calculated under these conditions is equal to 0.93 cm. It is very important information since, limiting the number of threshold levels in the electronic devices to four, leads to significant reduction of the overall cost of the scanner. The developed recovery scheme is general and may be incorporated in any other investigation where a prior knowledge about the signals of interest may be utilized.

Keywords: plastic scintillators, positron emission tomography, statistical analysis, tikhonov regularization

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Authors: Kaveri Dutta, Ratna Sharma

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Indian traditional textile is a synthesis of various cultures. Art and crafts of a country showcases the rich cultural and artistic history of that nation. Prehistorically Indian handicrafts were basically made for day to day use; the yearning for aesthetic application soon saw the development of flooding designs and motifs. Similarly, Bagh print a traditional hand block Print with natural colours an Indian handicraft practiced in Bagh, Madhya Pradesh(India). Bagh print has its roots in Sindh, which is now a part of Pakistan. The present form of Bagh printing actually started in 1962 when the craftsmen migrated from Manavar to the neighboring town of Bagh situated in Madhya Pradesh and hence Bagh has always been associated with this printing style. Bagh printing basically involved blocks that are carved onto motifs that represent flora such as Jasmine, Mushroom leheriya and so on. There are some prints that were inspired by the jaali work that embellished the Taj Mahal and various other forts. Inspiration is also drawn from the landscapes and geometrical figures. The motifs evoke various moods in the serenity of the prints and that is the catchy element of Bagh prints. The development in this traditional textile is as essential as in another field. Nowadays fashion trends are fragile and innovative changes over existing fashion field in the short span is the demand of times. We must make efforts to preserve this cultural heritage of arts and crafts and this is done either by documenting the various ancient traditions or by making a blend of it. Since this craft is well known over the world, but the need is to document the original motif, fabric, technology and colors used in contemporary fashion. Hence keeping above points in mind this study on bagh print textiles of Madhya Pradesh work has been formulated. The information incorporated in the paper was based on secondary data taken from relevant books, journals, museum visit and articles. Besides for the demographic details and working profile of the artisans dealt with printing, an interview schedule was carried out in three regions of Madhya Pradesh. This work of art was expressed in Cotton fabric. For this study selected traditional motifs for Bang printing was used. Some of the popular traditional Bagh motifs are Jasmine, Mushroom leheriya, geometrical figures and jaali work. The Bagh printed cotton fabrics were developed into a range of men’s ethic wear in combination with embroideries from Rajasthan. Products developed were bandhgala jackets, kurtas, serwani and dupattas. From the present study, it can be observed that the embellished traditional Bang printed range of ethnic men’s wear resulted in the fresh and colourful pattern. The embroidered Bagh printed cotton fabric also created a huge change in a positive way among artisans of the three regions.

Keywords: art and craft of Madhya Pradesh, evolution of printing in India, history of Bagh printing, sources of inspiration

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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Authors: Makda Aamir, Sood Aayushi, Syed Omar, Nihan Khuld, Iskander Peter, Ijaz Naeem, Sharma Nishant

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Introduction:Glycogen Storage Disease Type-1 (GSD-1) is a rare phenomenon primarily affecting the liver and kidney. Excessive accumulation of glycogen and fat in liver, kidney, and intestinal mucosa is noted in patients with deficiency of Glucose-6-phosphatase deficiency. Patients with GSD-1 have a wide spectrum of symptoms, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Age of onset, rate of disease progression and its severity is variable in this disease.Case:An 18-year-old male with GSD-1a, Von Gierke’s disease, hyperuricemia, and hypertension presented to the hospital with nausea and vomiting. The patient followed an hourly cornstarch regimen during the day and overnight through infusion via a PEG tube. The complaints started at work, where he was unable to tolerate oral cornstarch. He washemodynamically stable on arrival. ABG showed pH 7.372, PaCO2 30.3, and PaO2 92.2. WBC 16.80, K+ 5.8, HCO3 13, BUN 28, Cr 2.2, Glucose 60, AST 115, ALT 128, Cholesterol 352, Triglycerides >1000, Uric Acid 10.6, Lactic Acid 11.8 which trended down to 8.0. CT abdomen showed hepatomegaly and fatty infiltration with the PEG tube in place.He was admitted to the ICU and started on D5NS for hypoglycemia and lactic acidosis. Per request by the patient’s pediatrician, he was transitioned to IV D10/0.45NS at 110mL/Hr to maintain blood glucose above 75 mg/L. Frequent accuchecks were done till he could tolerate his dietary regimen with cornstarch. Lactic acid downtrend to 2.9, and accuchecks ranged between 100-110. Cr improved to 1.3, and his home medications (Allopurinol and Lisinopril) were resumed. He was discharged in stable condition with plans for further genetic therapy work up.Discussion:Mainstay therapy for Von Gierke’s Disease is the prevention of metabolic derangements for which dietary and lifestyle changes are recommended. A low fructose and sucrose diet is recommended by limiting the intake of galactose and lactose to one serving per day. Hypoglycemia treatment in such patients is two-fold, utilizing both quick and stable release sources. Cornstarch has been one such therapy since the 1980s; its slow digestion provides a steady release of glucose over a longer period of time as compared with other sources of carbohydrates. Dosing guidelines vary from age to age and person to person, but it is highly recommended to check BG levels frequently to maintain a BG > 70 mg/dL. Associated high levels of triglycerides and cholesterol can be treated with statins, fibrates, etc. Conclusion:The management of hypoglycemia in GSD 1 disease presents various obstacles which could prove to be fatal. Due to the deficiency of G6P, treatment with a specialized hypoglycemic regimen is warranted. A D10 ½ NS infusion can be used to maintain blood sugar levels as well as correct metabolic or lactate imbalances. Infusion should be gradually weaned off after the patient can tolerate oral feeds as this can help prevent the risk of hypoglycemia and other derangements. Further research is needed in regards to these patients for more sustainable regimens.

Keywords: von gierke, glycogen storage disease, hypoglycemia, genetic disease

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Authors: Ashima Sharma

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Human Serum Albumin (HSA)- one of the most demanded therapeutic proteins with immense biotechnological applications- is a large multidomain protein containing 17 disulfide bonds. The current source of HSA is human blood plasma which is a limited and unsafe source. Thus, there exists an indispensable need to promote non-animal derived recombinant HSA (rHSA) production. Escherichia coli is one of the most convenient hosts which had contributed to the production of more than 30% of the FDA approved recombinant pharmaceuticals. It grows rapidly and reaches high cell density using inexpensive and simple substrates. E. coli derived recombinant products have more economic potential as fermentation processes are cheaper compared to the other expression hosts. The major bottleneck in exploiting E. coli as a host for a disulfide-rich multidomain protein is the formation of aggregates of overexpressed protein. The majority of the expressed HSA forms inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA from inclusion bodies is not preferred because it is difficult to obtain a large multidomain disulfide bond rich protein like rHSA in its functional native form. Purification is tedious, time-consuming, laborious and expensive. Because of such limitations, the E. coli host system was neglected for rHSA production for the past few decades despite its numerous advantages. In the present work, we have exploited the capabilities of E. coli as a host for the enhanced functional production of rHSA (~60% of the total expressed rHSA in the soluble fraction). Parameters like intracellular environment, temperature, induction type, duration of induction, cell lysis conditions etc. which play an important role in enhancing the level of production of the desired protein in its native form in vivo have been optimized. We have studied the effect of assistance of different types of exogenously employed chaperone systems on the functional expression of rHSA in the E. coli host system. Different aspects of cell growth parameters during the production of rHSA in presence and absence of molecular chaperones in E. coli have also been studied. Upon overcoming the difficulties to produce functional rHSA in E. coli, it has been possible to produce significant levels of functional protein through engineering the biological system of protein folding in the cell, the E. coli-derived rHSA has been purified to homogeneity. Its detailed physicochemical characterization has been performed by monitoring its conformational properties, secondary and tertiary structure elements, surface properties, ligand binding properties, stability issues etc. These parameters of the recombinant protein have been compared with the naturally occurring protein from the human source. The outcome of the comparison reveals that the recombinant protein resembles exactly the same as the natural one. Hence, we propose that the E. coli-derived rHSA is an ideal biosimilar for human blood plasma-derived serum albumin. Therefore, in the present study, we have introduced and promoted the E. coli- derived rHSA as an alternative to the preparation from a human source, pHSA.

Keywords: recombinant human serum albumin, Escherichia coli, biosimilar, chaperone assisted protein folding

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Authors: Monika Soni, Shovonlal Bhowmick, Chandra Bhattacharya, Jitendra Sharma, Prafulla Dutta, Jagadish Mahanta

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Aedes aegypti and Aedes albopictus are considered as two major vectors to transmit dengue virus. In North-east India, two states viz. Assam and Arunachal Pradesh are known to be high endemic zone for dengue and Chikungunya viral infection. The taxonomical classification of medically important vectors are important for mapping of actual evolutionary trends and epidemiological studies. However, misidentification of mosquito species in field-collected mosquito specimens could have a negative impact which may affect vector-borne disease control policy. DNA barcoding is a prominent method to record available species, differentiate from new addition and change of population structure. In this study, a combined approach of a morphological and molecular technique of DNA barcoding was adopted to explore sequence variation in mitochondrial cytochrome c oxidase subunit I (COI) gene within dengue vectors. The study has revealed the map distribution of the dengue vector from two states i.e. Assam and Arunachal Pradesh, India. Approximate five hundred mosquito specimens were collected from different parts of two states, and their morphological features were compared with the taxonomic keys. The analysis of detailed taxonomic study revealed identification of two species Aedes aegypti and Aedes albopictus. The species aegypti comprised of 66.6% of the specimen and represented as dominant dengue vector species. The sequences obtained through standard DNA barcoding protocol were compared with public databases, viz. GenBank and BOLD. The sequences of all Aedes albopictus have shown 100% similarity whereas sequence of Aedes aegypti has shown 99.77 - 100% similarity of COI gene with that of different geographically located same species based on BOLD database search. From dengue prevalent different geographical regions fifty-nine sequences were retrieved from NCBI and BOLD databases of the same and related taxa to determine the evolutionary distance model based on the phylogenetic analysis. Neighbor-Joining (NJ) and Maximum Likelihood (ML) phylogenetic tree was constructed in MEGA6.06 software with 1000 bootstrap replicates using Kimura-2-Parameter model. Data were analyzed for sequence divergence and found that intraspecific divergence ranged from 0.0 to 2.0% and interspecific divergence ranged from 11.0 to 12.0%. The transitional and transversional substitutions were tested individually. The sequences were deposited in NCBI: GenBank database. This observation claimed the first DNA barcoding analysis of Aedes mosquitoes from North-eastern states in India and also confirmed the range expansion of two important mosquito species. Overall, this study insight into the molecular ecology of the dengue vectors from North-eastern India which will enhance the understanding to improve the existing entomological surveillance and vector incrimination program.

Keywords: COI, dengue vectors, DNA barcoding, molecular identification, North-east India, phylogenetics

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Authors: Saurabh Sharma

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Introduction: The case study deals with the ground stabilisation of Nabi Karim Metro Station in Delhi, India, wherein an extremely complex geology was encountered while excavating the tunnelling shaft for launching Tunnel Boring Machine. The borelog investigation and the Seismic Refraction Technique (SRT) indicated towards the presence of an extremely hard rocky mass from a depth of 3-4 m itself, and accordingly, the Geotechnical Interpretation Report (GIR) concluded the presence of Grade-IV rock from 3m onwards and presence of Grade-III and better rock from 5-6m onwards. Accordingly, it was planned to retain the ground by providing secant piles all around the launching shaft and then excavating the shaft vertically after leaving a berm of 1.5m to prevent secant piles from getting exposed. To retain the side slopes, rock bolting with shotcreting and wire meshing were proposed, which is a normal practice in such strata. However, with the increase in depth of excavation, the rock quality kept on decreasing at an unexpected and surprising pace, with the Grade-III rock mass at 5-6 m converting to conglomerate formation at the depth of 15m. This worsening of geology from high grade rock to slushy conglomerate formation can never be predicted and came as a surprise to even the best geotechnical engineers. Since the excavation had already been cut down vertically to manage the shaft size, the execution was continued with enhanced cautions to stabilise the side slopes. But, when the shaft work was about to finish, a collapse was encountered on one side of the excavation shaft. This collapse was unexpected and surprising since all measures to stabilise the side slopes had been taken after face mapping, and the grid size, diameter, and depth of the rockbolts had already been readjusted to accommodate rock fractures. The above scenario was baffling even to the best geologists and geotechnical engineers, and it was decided that any further slope stabilisation scheme shall have to be designed in such a way to ensure safe completion of works. Accordingly, following revisions to excavation scheme were made: The excavation would be carried while maintaining a slope based on type of soil/rock. The rock bolt type was changed from SN rockbolts to Self Drilling type anchor. The grid size of the bolts changed on real time assessment. the excavation carried out by implementing a ‘Bench Release Approach’. Aggressive Real Time Instrumentation Scheme. Discussion: The above case Study again asserts vitality of correct interpretation of the geological strata and the need of real time revisions of the construction schemes based on the actual site data. The excavation is successfully being done with the above revised scheme, and further details of the Revised Slope Stabilisation Scheme, Instrumentation Schemes, Monitoring results, along with the actual site photographs, shall form the part of the final Paper.

Keywords: unconfined compressive strength (ucs), rock mass rating (rmr), rock bolts, self drilling anchors, face mapping of rock, secant pile, shotcrete

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Authors: Drishti Sharma, Mona Duggal

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Background: WhatsApp can serve as a cost-effective, scalable, convenient, and popular medium for public health management related communication in the developing world where the existing system of communication is top-down and slow. The product supports sending and receiving a variety of media: text, photos, videos, documents, and location, as well as voice/video calls. With growing number of users of smartphones and improving access and penetration of internet, the scope of information technology remains immense in resolving the hurdles faced by traditional public health system. Poor infrastructure, gap in digital literacy, faulty documentation, strict organizational hierarchy and slow movement of information across desks and offices- all these, make WhatsApp an efficient prospect to complement the existing system for communication, feedback and leadership for public health system in India. Objective: This study investigates the benefits, challenges and limitations associated with WhatsApp usage as a public health management tool. Methods: The study was conducted within the Chandigarh Union Territory. We used a qualitative approach and conducted individual semi-structured interviews and group interviews (n = 10). Participants included medical officers (n 20), Program managers (n = 4), academicians (n=2) and administrators (n=2). Thematic and content qualitative analyses were conducted. Message log of the WhatsApp group of one of the health program was assessed. Results: Medical Officers said that WhatsApp helped them remain in touch with the program officer. They could easily give feedback and highlight those challenges which needed immediate intervention from the program managers, hence they felt supported. Also, the application helped them share pictures of their activities (meetings and field activities) with the group which they thought inspired others and gave themselves immense satisfaction. Also, it helped build stronger relationships and better coordination among themselves, the same being important in team events. For program managers, it had become a portal for coordinating large scale campaigns. Its reach and the fact that the feedback is real-time make WhatsApp ideal for district level events. Though the easy informal connectivity made them answerable to their staff but it also provided them with flexibility in operations. It turned out to be an important portal for sharing outcome and goals related feedback (both positive and negative) to the team. To be sure, using WhatsApp for the purpose of public health program presents considerable challenges, including technological barriers, organizational challenges, gender issues, confidentiality concerns and unplanned aftereffects. Nevertheless, its advantages in a low-cost setting make it an efficient alternative. Conclusion: WhatsApp has become an integral part of our lives. Use of this app for public health program management within closed groups looks promising and useful. At the same time, addressing the challenges involved would make its usage safer.

Keywords: communication, mobile technology, public health management, WhatsApp

Procedia PDF Downloads 177

Authors: Mohamed Abouelresh, Subhajit Kumar, Lamidi Babalola, Septriandi Chan, Ali Al Musabeh A., Thadickal V. Joydas, Bruno Pulido

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Neom has a relatively long coastline on the Red Sea and the Gulf of Aqaba, which is about 300 kilometres long, in addition to many naturally formed bays along the Red Sea coast. Undoubtedly, these coasts provide an excellent opportunity for tourism and other activities; however, these coastal areas host a wide range of salinity-dependent ecosystems that need to be protected. The main objective of the study was to identify the coastal features, including tidal flats and salt flats, along the NEOM coast. A base map of the study area generated from the satellite images contained the main landform features and, in particular, the boundaries of the inland and coastal sabkhas. A field survey was conducted to map and characterize the intertidal and sabkha landforms. The coastal and inner coastal areas of NEOM are mainly covered by the quaternary sediments, which include gravel sheets, terraces, raised reef limestone, evaporite successions, eolian dunes, and undifferentiated sand/gravel deposits (alluvium, alluvial outwash, wind-blown sand beach). There are different landforms that characterizes the NEOM coast, including rocky coast, tidal zone, and sabkha. Sabkha area ranges between a few to tens of square kilometers. Coastal sabkha extended across the shoreline of NEOM, specifically at Gayal and Sharma areas, while the continental sabkha only existed at Gayal Town. The inland Sabkha at Gayal is mainly composed of a thin (15-25 cm) evaporite crust composed of a dark brown, cavernous, rugged, pitted, colloidal salty sand layer with salt-tolerant vegetation. The inland Sabkha is considered a groundwater-driven sedimentary system as indicated by syndepositional intra-sediment capillary evaporites, which precipitate in both marine and continental salt flats. Gayal coastal Sabkha is made up of tidal inlets, tidal creeks, and lagoons followed in a landward direction with well-developed sabkha layers. The surface sediments of the coastal Sabkha are composed of unlithified calcareous, gypsiferous, coarse to medium sands, and silt with bioclastic fragments underlain by several organic-rich layers. The coastal flat is graded landward into widespread, flat vegetated Sabkhas dissected by tributaries of the fluvial system, which debouches to the Red Sea. The coast from Gayal to Magna through Ras El-Sheikh Humaid is continuously subjected to tidal flows, which create an intertidal depositional system. The intertidal flats at NEOM are extensive, nearly horizontal land forming a very dynamic system in which several physical, chemical, geomorphological, and biological processes are acting simultaneously. The current work provides a field-based identification of the coastal sabkha and intertidal sites at NEOM. However, the mutual interaction between tidal flows and sabkha development, particularly at Gayal, needs to be well understood through comprehensive field and lab analysis.

Keywords: coast, intertidal, deposition, sabkha

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Authors: Aditya Sharma

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Profits earned from relative strength strategy of zero-cost portfolio i.e. taking long position in winner stocks and short position in loser stocks from recent past are termed as momentum profits. In recent times, there has been lot of controversy and concern about sources of momentum profits, since the existence of these profits acts as an evidence of earning non-normal returns from publicly available information directly contradicting Efficient Market Hypothesis. Literature review reveals conflicting theories and differing evidences on sources of momentum profits. This paper aims at re-examining the sources of momentum profits in Indian capital markets. The study focuses on assessing the effect of fundamental as well as behavioral sources in order to understand the role of investor behavior in stock returns and suggest (if any) improvements to existing behavioral asset pricing models. This Paper adopts calendar time methodology to calculate momentum profits for 6 different strategies with and without skipping a month between ranking and holding period. For each J/K strategy, under this methodology, at the beginning of each month t stocks are ranked on past j month’s average returns and sorted in descending order. Stocks in upper decile are termed winners and bottom decile as losers. After ranking long and short positions are taken in winner and loser stocks respectively and both portfolios are held for next k months, in such manner that at any given point of time we have K overlapping long and short portfolios each, ranked from t-1 month to t-K month. At the end of period, returns of both long and short portfolios are calculated by taking equally weighted average across all months. Long minus short returns (LMS) are momentum profits for each strategy. Post testing for momentum profits, to study the role market risk plays in momentum profits, CAPM and Fama French three factor model adjusted LMS returns are calculated. In the final phase of studying sources, decomposing methodology has been used for breaking up the profits into unconditional means, serial correlations, and cross-serial correlations. This methodology is unbiased, can be used with the decile-based methodology and helps to test the effect of behavioral and fundamental sources altogether. From all the analysis, it was found that momentum profits do exist in Indian capital markets with market risk playing little role in defining them. Also, it was observed that though momentum profits have multiple sources (risk, serial correlations, and cross-serial correlations), cross-serial correlations plays a major role in defining these profits. The study revealed that momentum profits do have multiple sources however, cross-serial correlations i.e. the effect of returns of other stocks play a major role. This means that in addition to studying the investors` reactions to the information of the same firm it is also important to study how they react to the information of other firms. The analysis confirms that investor behavior does play an important role in stock returns and incorporating both the aspects of investors’ reactions in behavioral asset pricing models help make then better.

Keywords: investor behavior, momentum effect, sources of momentum, stock returns

Procedia PDF Downloads 305

Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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Authors: Nisha Sharma, Mili Kaur, Ashutosh Halder, Seema Kaushal, Manoj Kumar, Manish Jain

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Purpose: To investigate microRNAs (miRNA) as an epigenomic etiological factor in idiopathic non-obstructive azoospermia (NOA). In order to achieve the same, an association was seen between occupational exposure to radiation, thermal, and chemical factors and idiopathic cases of non-obstructive azoospermia, and later, testicular differential miRNA expression profiling was done in exposure group NOA cases. Method: It is a prospective study in which 200 apparent idiopathic male factor infertility cases, who have been advised to undergo testicular fine needle aspiration (FNA) evaluation, are recruited. A detailed occupational history was taken to understand the possible type of exposure due to the nature and duration of work. A total of 26 patients were excluded upon XY-FISH and Yq microdeletion tests due to the presence of genetic causes of infertility, 6 hypospermatogeneis (HS), six Sertoli cell-only syndrome (SCOS), and six normospermatogeneis patients testicular FNA samples were used for RNA isolation followed by small RNA sequencing and nCounter miRNA expression analysis. Differential miRNA expression profile of HS and SCOS patients was done. A web-based tool, miRNet, was used to predict the interacting compounds or chemicals using the shortlisted miRNAs with high fold change. The major limitation encountered in this study was the insufficient quantity of testicular FNA sample used for total RNA isolation, which resulted in a low yield and RNA integrity number (RIN) value. Therefore, the number of RNA samples admissible for differential miRNA expression analysis was very small in comparison to the total number of patients recruited. Results: Differential expression analysis revealed 69 down-regulated and 40 up-regulated miRNAs in HS and 66 down-regulated and 33 up-regulated miRNAs in SCOS in comparison to normospermatogenesis controls. The miRNA interaction analysis using the miRNet tool showed that the differential expression profiles of HS and SCOS patients were associated with arsenic trioxide, bisphenol-A, calcium sulphate, lithium, and cadmium. These compounds are reproductive toxins and might be responsible for miRNA-mediated epigenetic deregulation leading to NOA. The association between occupational risk factor exposure and the non-exposure group of NOA patients was not statistically significant, with ꭓ2 (3, N= 178) = 6.70, p= 0.082. The association between individual exposure groups (radiation, thermal, and chemical) and various sub-types of NOA is also not significant, with ꭓ2 (9, N= 178) = 15.06, p= 0.089. Functional analysis of HS and SCOS patients' miRNA profiles revealed some important miR-family members in terms of male fertility. The miR-181 family plays a role in the differentiation of spermatogonia and spermatocytes, as well as the transcriptional regulation of haploid germ cells. The miR-34 family is expressed in spermatocytes and round spermatids and is involved in the regulation of SSCs differentiation. Conclusion: The reproductive toxins might adopt the miRNA-mediated mechanism of disease development in idiopathic cases of NOA. Chemical compound induced; miRNA-mediated epigenetic deregulation can give a future perspective on the etiopathogenesis of the disease.

Keywords: microRNA, non-obstructive azoospermia (NOA), occupational exposure, hypospermatogenesis (HS), Sertoli cell only syndrome (SCOS)

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Authors: Haresh Sharma, Jaimini Luharia

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The ecology in the Western Himalayan region transforms with the change in altitude. This change is observed in terms of topography, species of flora and fauna and the quality of the soil. The current study focuses on women of indigenous communities of Pangi Valley, which is located in the state of Himachal Pradesh, India. The valley is bifurcated into three different areas –Saichu, Hudan Bhatori, and Sural Bhatori valleys. It is one of the most remote, rugged and difficult to access tribal regions of Chamba district. The altitude of the valley ranges from 2,000 m to 6,000 m above sea level. The Pangi valley is inhabited by ‘Pangwals’ and ‘Bhots’ tribes of the Himalayas who speak their local tribal language called’ Pangwali’. The valley is cut-off from the mainland due to heavy snow and lack of proper roads during peak winters. Due to difficult geographical location, the daily lives of the people are constantly challenged, and they are most of the times deprived of benefits targeted through government programs. However, the indigenous communities earn their livelihood through livestock and forest-based produce while some of them migrate to nearby places for better work. The current study involves snowball sampling methodology for data collection along with in-depth interviews of women members of Self-Help Groups and women farmers. The findings reveal that the lives of these indigenous communities largely depend on forest-based products. So, it creates all the more significance of enhancing, maintaining, and consuming natural resources sustainably. Under such circumstances, the women of the community play a significant role of guardians in conservation and protection of the forests. They are the custodians of traditional knowledge of environment conservation practices that have been followed for many years in the region. The present study also sought to establish a relationship between some of the development initiatives undertaken by the women in the valley that stimulate sustainable mountain economy and conservation practices. These initiatives include cultivation of products like hazelnut, ‘Gucchi’ rare quality mushroom, medicinal plants exclusively found in the region, thereby promoting long term sustainable conservation of agro-biodiversity of the Western Himalayan region. The measures taken by the community women are commendable as they ensure access and distribution of natural resources as well as manage them for future generations. Apart from this, the tribal women have actively formed Self-Help Groups promoting financial inclusion through various activities that augment ownership and accountability towards the overall development of the communities. But, the results also suggest that there’s not enough recognition given to women’s role in forests conservation practices due to several local socio-political reasons. There are not enough research studies done on communities of Pangi Valley due to inaccessibility created out of lack of proper roads and other resources. Also, there emerged a need to concretize indigenous and traditional knowledge of conservation practices followed by women in the community.

Keywords: forest conservation, indigenous community women, sustainable livelihoods, sustainable development, poverty alleviation, Western Himalayas

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Authors: Sharma Aseem, Dhurat Rachita, Pawar Varsha, Khalse Manisha

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Introduction: Androgenetic alopecia (AGA) is a prevalent condition characterized by progressive hair thinning driven by genetic and androgen-related factors. The current FDA-approved treatments include oral finasteride and topical minoxidil, though many patients seek combination therapies to enhance results. This study aims to evaluate the effectiveness of a combination therapy involving Minoxidil, Finasteride, and Capixyl™ based on feedback from dermatologists. Methodology: A survey, validated by experts, was distributed to 29 leading dermatologists across India (in Tier 1 and 2 cities). The survey examined real-world clinical experiences, focusing on patient outcomes and the overall effectiveness of the mentioned formulation. Results: Among the surveyed dermatologists, 41.4% identified women aged 35-40 as the most frequently diagnosed with female pattern hair loss. The combination therapy with Minoxidil, Finasteride, and Capixyl™ was utilized by 34.5% of dermatologists for over 60 patients per month. The majority highlighted the benefits of this combination therapy, which acts via multiple mechanisms, such as vasodilation and dihydrotestosterone (DHT) receptor blockade, resulting in improved hair regrowth. Additionally, patients demonstrated better clinical outcomes, enhanced compliance, and fewer side effects. Demographically, younger patients, particularly those with AGA for less than 10 years, responded more positively to the treatment. Early intervention led to quicker and more significant results. Overall satisfaction among dermatologists was high, with 86.2% expressing positive feedback on the therapy. In terms of treatment outcomes, 51.7% of dermatologists observed visible results within 4-6 months, while 34.5% noticed a significant reduction in hair fall within 8-12 weeks. Improvements in scalp health were reported by 48.3%, and 51.7% saw an increased hair density within 3-4 months. Despite mild side effects such as scalp irritation, dryness, flaking, and occasional issues like folliculitis, headaches, itching, and redness, patient satisfaction remained high. Dermatologists reported that 93.1% of patients experienced faster and better hair regrowth with Capixyl™ compared to Minoxidil alone. Suggestions for improving the formulation included incorporating peptides like Saw Palmetto and enhancing product packaging to better meet patient needs. Discussion: The combination of Minoxidil, Finasteride, and Capixyl™ yielded positive clinical outcomes, especially in improving hair density, scalp health, and overall patient satisfaction. Dermatologists found that Capixyl™ peptides enhanced the therapeutic effect, promoting hair regrowth and improving compliance. While side effects were generally mild, there were suggestions to further improve the formulation by adding additional peptides like Saw Palmetto. Conclusion: The combination of Minoxidil and Finasteride fortified with Capixyl™ presents a promising therapeutic option for managing AGA. Dermatologists reported significant improvements in hair density, scalp health, and patient satisfaction. With its favorable efficacy and manageable side effects, this formulation proves to be a valuable addition to the treatment landscape for AGA.

Keywords: androgenetic alopecia, combination therapy, minoxidil, finasteride, capixyl

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Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

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Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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Authors: Priyanka Jain, Ashish K. Sharma, Esha Shukla, K. J. Mukherjee

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We propose a paradigm shift in our approach to design improved platforms for recombinant protein production, by addressing system level issues rather than the individual steps associated with recombinant protein synthesis like transcription, translation, etc. We demonstrate that by controlling and modulating the cellular stress response (CSR), which is responsible for feedback control of protein synthesis, we can generate hyper-producing strains. We did transcriptomic profiling of post-induction cultures, expressing different types of protein, to analyze the nature of this cellular stress response. We found significant down-regulation of substrate utilization, translation, and energy metabolism genes due to generation CSR inside the host cell. However, transcription profiling has also shown that many genes are up-regulated post induction and their role in modulating the CSR is unclear. We hypothesized that these up-regulated genes trigger signaling pathways, generating the CSR and concomitantly reduce the recombinant protein yield. To test this hypothesis, we knocked out the up-regulated genes, which did not have any downstream regulatees, and analyzed their impact on cellular health and recombinant protein expression. Two model proteins i.e., GFP and L-Asparaginase were chosen for this analysis. We observed a significant improvement in expression levels, with some knock-outs showing more than 7-fold higher expression compared to control. The 10 best single knock-outs were chosen to make 45 combinations of all possible double knock-outs. A further increase in expression was observed in some of these double knock- outs with GFP levels being highest in a double knock-out ΔyhbC + ΔelaA. However, for L-Asparaginase which is a secretory protein, the best results were obtained using a combination of ΔelaA+ΔcysW knock-outs. We then tested all the knock outs for their ability to enhance the expression of a 'difficult-to-express' protein. The Rubella virus E1 protein was chosen and tagged with sfGFP at the C-terminal using a linker peptide for easy online monitoring of expression of this fusion protein. Interestingly, the highest increase in Rubella-sGFP levels was obtained in the same double knock-out ΔelaA + ΔcysW (5.6 fold increase in expression yield compared to the control) which gave the highest expression for L-Asparaginase. However, for sfGFP alone, the ΔyhbC+ΔmarR knock-out gave the highest level of expression. These results indicate that there is a fair degree of commonality in the nature of the CSR generated by the induction of different proteins. Transcriptomic profiling of the double knock out showed that many genes associated with the translational machinery and energy biosynthesis did not get down-regulated post induction, unlike the control where these genes were significantly down-regulated. This confirmed our hypothesis of these genes playing an important role in the generation of the CSR and allowed us to design a strategy for making better expression hosts by simply knocking out key genes. This strategy is radically superior to the previous approach of individually up-regulating critical genes since it blocks the mounting of the CSR thus preventing the down-regulation of a very large number of genes responsible for sustaining the flux through the recombinant protein production pathway.

Keywords: cellular stress response, GFP, knock-outs, up-regulated genes

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Authors: Sonika Sharma, Mohan G. Vairale, Sibnarayan Datta, Soumya Chatterjee, Dharmendra Dubey, Rajesh Prasad, Raghvendra Budhauliya, Bidisha Das, Vijay Veer

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Bacteriophages are viruses that parasitize specific bacteria and multiply in metabolising host bacteria. Bacteriophages hunt for a single or a subset of bacterial species, making them potential antibacterial agents. Utilizing the ability of phages to control bacterial populations has several applications from medical to the fields of agriculture, aquaculture and the food industry. However, harnessing phage based techniques in wastewater treatments to improve quality of effluent and sludge release into the environment is a potential area for R&D application. Phage mediated bactericidal effect in any wastewater treatment process has many controlling factors that lead to treatment performance. In laboratory conditions, titer of bacteriophages (coliphages) isolated from effluent water of a specially designed anaerobic digester of human night soil (DRDO Biotoilet) was successfully increased with a modified protocol of the classical double layer agar technique. Enrichment of the same was carried out and efficacy of the phage enriched medium was evaluated at different conditions (specific media, temperature, storage conditions). Growth optimization study was carried out on different media like soybean casein digest medium (Tryptone soya medium), Luria-Bertani medium, phage deca broth medium and MNA medium (Modified nutrient medium). Further, temperature-phage yield relationship was also observed at three different temperatures 27˚C, 37˚C and 44˚C at laboratory condition. Results showed the higher activity of coliphage 27˚C and at 37˚C. Further, addition of divalent ions (10mM MgCl2, 5mM CaCl2) and 5% glycerol resulted in a significant increase in phage titer. Besides this, effect of antibiotics addition like ampicillin and kanamycin at different concentration on plaque formation was analysed and reported that ampicillin at a concentration of 1mg/ml ampicillin stimulates phage infection and results in more number of plaques. Experiments to test viability of phage showed that it can remain active for 6 months at 4˚C in fresh tryptone soya broth supplemented with fresh culture of coliforms (early log phase). The application of bacteriophages (especially coliphages) for treatment of effluent of human faecal matter contaminated effluent water is unique. This environment-friendly treatment system not only reduces the pathogenic coliforms, but also decreases the competition between nuisance bacteria and functionally important microbial populations. Therefore, the phage based cocktail to treat fecal pathogenic bacteria present in black water has many implication in wastewater treatment processes including ‘DRDO Biotoilet’, which is an ecofriendly appropriate and affordable human faecal matter treatment technology for different climates and situations.

Keywords: wastewater, microbes, virus, biotoilet, phage viability

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Authors: Alaa Fezai, Anuj Sharma, Wolfgang Mueller-Hirsch, André Zimmermann

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Viscoelastic materials have been widely used in the automotive industry over the last few decades with different functionalities. Besides their main application as a simple and efficient surface damping treatment, they may ensure optimal operating conditions for on-board electronics as thermal interface or sealing layers. The dynamic behavior of viscoelastic materials is generally dependent on many environmental factors, the most important being temperature and strain rate or frequency. Prior to the reliability analysis of systems including viscoelastic layers, it is, therefore, crucial to accurately predict the dynamic and lifetime behavior of these materials. This includes the identification of the dynamic material parameters under critical temperature and frequency conditions along with a precise damage localization and identification methodology. The goal of this work is twofold. The first part aims at applying an inverse viscoelastic material-characterization approach for a wide frequency range and under different temperature conditions. For this sake, dynamic measurements are carried on a single lap joint specimen using an electrodynamic shaker and an environmental chamber. The specimen consists of aluminum beams assembled to adapter plates through a viscoelastic adhesive layer. The experimental setup is reproduced in finite element (FE) simulations, and frequency response functions (FRF) are calculated. The parameters of both the generalized Maxwell model and the fractional derivatives model are identified through an optimization algorithm minimizing the difference between the simulated and the measured FRFs. The second goal of the current work is to guarantee an on-line detection of the damage, i.e., delamination in the viscoelastic bonding of the described specimen during frequency monitored end-of-life testing. For this purpose, an inverse technique, which determines the damage location and size based on the modal frequency shift and on the change of the mode shapes, is presented. This includes a preliminary FE model-based study correlating the delamination location and size to the change in the modal parameters and a subsequent experimental validation achieved through dynamic measurements of specimen with different, pre-generated crack scenarios and comparing it to the virgin specimen. The main advantage of the inverse characterization approach presented in the first part resides in the ability of adequately identifying the material damping and stiffness behavior of soft viscoelastic materials over a wide frequency range and under critical temperature conditions. Classic forward characterization techniques such as dynamic mechanical analysis are usually linked to limitations under critical temperature and frequency conditions due to the material behavior of soft viscoelastic materials. Furthermore, the inverse damage detection described in the second part guarantees an accurate prediction of not only the damage size but also its location using a simple test setup and outlines; therefore, the significance of inverse numerical-experimental approaches in predicting the dynamic behavior of soft bonding layers applied in automotive electronics.

Keywords: damage detection, dynamic characterization, inverse approaches, vibration testing, viscoelastic layers

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Priyanka Sharma, Ranjita Das, Mohan C. Kalita, Debajit Thakur

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Background: Actinomycetes are the richest source of novel bioactive secondary metabolites such as antibiotics, enzymes and other therapeutically useful metabolites with diverse biological activities. The present study aims at the antimicrobial potential and genetic diversity of culturable Actinomycetes isolated from protected forest ecosystems of Assam which includes Kaziranga National Park (26°30˝-26°45˝N and 93°08˝-93°36˝E), Pobitora Wildlife Sanctuary (26º12˝-26º16˝N and 91º58˝-92º05˝E) and Gibbon Wildlife Sanctuary (26˚40˝-26˚45˝N and 94˚20˝-94˚25˝E) which are located in the North-eastern part of India. Northeast India is a part of the Indo-Burma mega biodiversity hotspot and most of the protected forests of this region are still unexplored for the isolation of effective antibiotic-producing Actinomycetes. Thus, there is tremendous possibility that these virgin forests could be a potential storehouse of novel microorganisms, particularly Actinomycetes, exhibiting diverse biological properties. Methodology: Soil samples were collected from different ecological niches of the protected forest ecosystems of Assam and Actinomycetes were isolated by serial dilution spread plate technique using five selective isolation media. Preliminary screening of Actinomycetes for an antimicrobial activity was done by spot inoculation method and the secondary screening by disc diffusion method against several test pathogens, including multidrug resistant Staphylococcus aureus (MRSA). The strains were further screened for the presence of antibiotic synthetic genes such as type I polyketide synthases (PKS-I), type II polyketide synthases (PKS-II) and non-ribosomal peptide synthetases (NRPS) genes. Genetic diversity of the Actinomycetes producing antimicrobial metabolites was analyzed through 16S rDNA-RFLP using Hinf1 restriction endonuclease. Results: Based on the phenotypic characterization, a total of 172 morphologically distinct Actinomycetes were isolated and screened for antimicrobial activity by spot inoculation method on agar medium. Among the strains tested, 102 (59.3%) strains showed activity against Gram-positive bacteria, 98 (56.97%) against Gram-negative bacteria, 92 (53.48%) against Candida albicans MTCC 227 and 130 (75.58%) strains showed activity against at least one of the test pathogens. Twelve Actinomycetes exhibited broad spectrum antimicrobial activity in the secondary screening. The taxonomic identification of these twelve strains by 16S rDNA sequencing revealed that Streptomyces was found to be the predominant genus. The PKS-I, PKS-II and NRPS genes detection indicated diverse bioactive products of these twelve Actinomycetes. Genetic diversity by 16S rDNA-RFLP indicated that Streptomyces was the dominant genus amongst the antimicrobial metabolite producing Actinomycetes. Conclusion: These findings imply that Actinomycetes from the protected forest ecosystems of Assam, India, are a potential source of bioactive secondary metabolites. These areas are as yet poorly studied and represent diverse and largely unscreened ecosystem for the isolation of potent Actinomycetes producing antimicrobial secondary metabolites. Detailed characterization of the bioactive Actinomycetes as well as purification and structure elucidation of the bioactive compounds from the potent Actinomycetes is the subject of ongoing investigation. Thus, to exploit Actinomycetes from such unexplored forest ecosystems is a way to develop bioactive products.

Keywords: Actinomycetes, antimicrobial activity, forest ecosystems, RFLP

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Authors: Solanki Ravirajsinh, Kudo Kuniaki, Sharma Ankit, Devi Sherine, Kuboshima Misaki, Tachi Shuntaro

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In software development life cycles, the absence of scalable CI/CD significantly impacts organizations, leading to increased overall maintenance costs, prolonged release delivery times, heightened manual efforts, and difficulties in meeting tight deadlines. Implementing CI/CD with standard serverless technologies using cloud services overcomes all the above-mentioned issues and helps organizations improve efficiency and faster delivery without the need to manage server maintenance and capacity. By integrating scalable CI/CD with scalable automation testing, productivity, quality, and agility are enhanced while reducing the need for repetitive work and manual efforts. Implementing scalable CI/CD for development using cloud services like ECS (Container Management Service), AWS Fargate, ECR (to store Docker images with all dependencies), Serverless Computing (serverless virtual machines), Cloud Log (for monitoring errors and logs), Security Groups (for inside/outside access to the application), Docker Containerization (Docker-based images and container techniques), Jenkins (CI/CD build management tool), and code management tools (GitHub, Bitbucket, AWS CodeCommit) can efficiently handle the demands of diverse development environments and are capable of accommodating dynamic workloads, increasing efficiency for faster delivery with good quality. CI/CD pipelines encourage collaboration among development, operations, and quality assurance teams by providing a centralized platform for automated testing, deployment, and monitoring. Scalable CI/CD streamlines the development process by automatically fetching the latest code from the repository every time the process starts, building the application based on the branches, testing the application using a scalable automation testing framework, and deploying the builds. Developers can focus more on writing code and less on managing infrastructure as it scales based on the need. Serverless CI/CD eliminates the need to manage and maintain traditional CI/CD infrastructure, such as servers and build agents, reducing operational overhead and allowing teams to allocate resources more efficiently. Scalable CI/CD adjusts the application's scale according to usage, thereby alleviating concerns about scalability, maintenance costs, and resource needs. Creating scalable automation testing using cloud services (ECR, ECS Fargate, Docker, EFS, Serverless Computing) helps organizations run more than 500 test cases in parallel, aiding in the detection of race conditions, performance issues, and reducing execution time. Scalable CI/CD offers flexibility, dynamically adjusting to varying workloads and demands, allowing teams to scale resources up or down as needed. It optimizes costs by only paying for the resources as they are used and increases reliability. Scalable CI/CD pipelines employ automated testing and validation processes to detect and prevent errors early in the development cycle.

Keywords: achieve parallel execution, cloud services, scalable automation testing, scalable continuous integration and deployment

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Authors: Hari K. Adhikari, Keshab Sharma, K. C. Apil

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The Gorkha Nepal earthquake of moment magnitude (Mw) 7.8 hit the central region of Nepal on April 25, 2015; with the epicenter about 77 km northwest of Kathmandu Valley. This paper aims to explore challenges of reconstruction in the rural earthquake-stricken areas of Nepal. The Gorkha earthquake on April 25, 2015, has significantly affected the livelihood of people and overall economy in Nepal, causing severe damage and destruction in central Nepal including nation’s capital. A larger part of the earthquake affected area is difficult to access with rugged terrain and scattered settlements, which posed unique challenges and efforts on a massive scale reconstruction and rehabilitation. 800 thousand buildings were affected leaving 8 million people homeless. Challenge of reconstruction of optimum 800 thousand houses is arduous for Nepal in the background of its turmoil political scenario and weak governance. With significant actors involved in the reconstruction process, no appreciable relief has reached to the ground, which is reflected over the frustration of affected people. The 2015 Gorkha earthquake is one of most devastating disasters in the modern history of Nepal. Best of our knowledge, there is no comprehensive study on reconstruction after disasters in modern Nepal, which integrates the necessary information to deal with challenges and opportunities of reconstructions. The study was conducted using qualitative content analysis method. Thirty engineers and ten social mobilizes working for reconstruction and more than hundreds local social workers, local party leaders, and earthquake victims were selected arbitrarily. Information was collected through semi-structured interviews and open-ended questions, focus group discussions, and field notes, with no previous assumption. Author also reviewed literature and document reviews covering academic and practitioner studies on challenges of reconstruction after earthquake in developing countries such as 2001 Gujarat earthquake, 2005 Kashmir earthquake, 2003 Bam earthquake and 2010 Haiti earthquake; which have very similar building typologies, economic, political, geographical, and geological conditions with Nepal. Secondary data was collected from reports, action plans, and reflection papers of governmental entities, non-governmental organizations, private sector businesses, and the online news. This study concludes that inaccessibility, absence of local government, weak governance, weak infrastructures, lack of preparedness, knowledge gap and manpower shortage, etc. are the key challenges of the reconstruction after 2015 earthquake in Nepal. After scrutinizing different challenges and issues, study counsels that good governance, integrated information, addressing technical issues, public participation along with short term and long term strategies to tackle with technical issues are some crucial factors for timely and quality reconstruction in context of Nepal. Sample collected for this study is relatively small sample size and may not be fully representative of the stakeholders involved in reconstruction. However, the key findings of this study are ones that need to be recognized by academics, governments, and implementation agencies, and considered in the implementation of post-disaster reconstruction program in developing countries.

Keywords: Gorkha earthquake, reconstruction, challenges, policy

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Authors: K. C. Apil, Keshab Sharma, Bigul Pokharel

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Kathmandu Valley, capital city of Nepal houses numerous historical monuments as well as religious structures which are as old as from the 4th century A.D. The city alone is home to seven UNESCO’s world heritage sites including various public squares and religious sanctums which are often regarded as living heritages by various historians and archeological explorers. Recently on April 25, 2015, the capital city including other nearby locations was struck with Gorkha earthquake of moment magnitude (Mw) 7.8, followed by the strongest aftershock of moment magnitude (Mw) 7.3 on May 12. This study reports structural failures and collapse of heritage structures in Kathmandu Valley during the earthquake and presents preliminary findings as to the causes of failures and collapses. Field reconnaissance was carried immediately after the main shock and the aftershock, in major heritage sites: UNESCO world heritage sites, a number of temples and historic buildings in Kathmandu Durbar Square, Patan Durbar Square, and Bhaktapur Durbar Square. Despite such catastrophe, a significant number of heritage structures stood high, performing very well during the earthquake. Preliminary reports from archeological department suggest that 721 of such structures were severely affected, whereas numbers within the valley only were 444 including 76 structures which were completely collapsed. This study presents recorded accelerograms and geology of Kathmandu Valley. Structural typology and architecture of the heritage structures in Kathmandu Valley are briefly described. Case histories of damaged heritage structures, the patterns, and the failure mechanisms are also discussed in this paper. It was observed that performance of heritage structures was influenced by the multiple factors such as structural and architecture typology, configuration, and structural deficiency, local ground site effects and ground motion characteristics, age and maintenance level, material quality etc. Most of such heritage structures are of masonry type using bricks and earth-mortar as a bonding agent. The walls' resistance is mainly compressive, thus capable of withstanding vertical static gravitational load but not horizontal dynamic seismic load. There was no definitive pattern of damage to heritage structures as most of them behaved as a composite structure. Some structures were extensively damaged in some locations, while structures with similar configuration at nearby location had little or no damage. Out of major heritage structures, Dome, Pagoda (2, 3 or 5 tiered temples) and Shikhara structures were studied with similar variables. Studying varying degrees of damages in such structures, it was found that Shikhara structures were most vulnerable one where Dome structures were found to be the most stable one, followed by Pagoda structures. The seismic performance of the masonry-timber and stone masonry structures were slightly better than that of the masonry structures. Regular maintenance and periodic seismic retrofitting seems to have played pivotal role in strengthening seismic performance of the structure. The study also recommends some key functions to strengthen the seismic performance of such structures through study based on structural analysis, building material behavior and retrofitting details. The result also recognises the importance of documentation of traditional knowledge and its revised transformation in modern technology.

Keywords: Gorkha earthquake, field observation, heritage structure, seismic performance, masonry building

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Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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Authors: S. Sharma, Gaballa Aqeelah, Tawfig Alghbaili, Ali Elmessmari

Abstract:

There were abrupt discontinuities in the Brute Stack in the northernmost locations during the acquisition of 2D (2007) and 3D (2021) seismic data in the northwest region of the Ghadames Basin, Libya. In both campaigns, complete fluid circulation loss was seen in these regions during up-hole drilling. Geophysics, sedimentology and shallow subsurface geology were all integrated to look into what was causing the seismic signal to disappear at shallow depths. The Upper Cretaceous Nalut Formation is the near-surface or surface formation in the studied area. It is distinguished by abnormally high resistivity in all the neighboring wells. The Nalut Formation in all the nearby wells from the present study and previous outcrop study suggests lithology of dolomite and chert/flint in nodular or layered forms. There are also reports of karstic caverns, vugs, and thick cracks, which all work together to produce the high resistivity. Four up-hole samples that were analyzed for microfacies revealed a near-coastal to tidal environment. Algal (Chara) infested deposits up to 30 feet thick and monotonous, very porous, are seen in two up-hole sediments; these deposits are interpreted to be scattered, continental algal travertine mounds. Chert/flint, dolomite, and calcite in varying amounts are confirmed by XRD analysis. Regional tracking of the high resistivity of the Nalut Formation, which is thought to be connected to the sea level drop that created the paleokarst layer, is possible. It is abruptly overlain by a blanket marine transgressive deposit caused by rapid sea level rise, which is a regional, relatively high radioactive layer of argillaceous limestone. The examined area's close proximity to the mountainous, E-W trending ridges of northern Libya made it easier for recent freshwater circulation, which later enhanced cavern development and mineralization in the paleokarst layer. Seismic signal loss at shallow depth is caused by extremely heterogeneous mineralogy of pore- filling or lack thereof. Scattering effect of shallow karstic layer on seismic signal has been well documented. Higher velocity inflection points at shallower depths in the northern part and deeper intervals in the southern part, in both cases at Nalut level, demonstrate the layer's influence on the seismic signal. During the Permian-Carboniferous, the Ghadames Basin underwent uplift and extensive erosion, which resulted in this karstic layer of the Nalut Formation uplifted to a shallow depth in the northern part of the studied area weakening the acoustic signal, whereas in the southern part of the 3D acquisition area the Nalut Formation remained at the deeper interval without affecting the seismic signal. Results from actions taken during seismic processing to deal with this signal loss are visible and have improved. This study recommends using denser spacing or dynamite to circumvent the karst layer in a comparable geographic area in order to prevent signal loss at lesser depths.

Keywords: well logging, seismic data acquisition, sesimic data processing, up-holes

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