Search results for: V. K. Arora
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 55

Search results for: V. K. Arora

25 An Unusual Presentation of Plasmacytoid Urothelial Carcinoma of the Bladder - A Case Report and Literature Review

Authors: Bharti Arora, Michael Chen, Steven Lun

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Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare and aggressive subtype of urothelial carcinoma that usually presents at an advanced clinical stage, has a predilection for early metastatic potential and is associated with poor prognosis. The first reported case of PUC was in 1991 and approximately 100 cases were reported in the literature worldwide. We present a case of a 43 year old female presenting with a 3-month history of urgency and frequency. Failing medical management of her urinary symptoms with anticholinergic medication, she underwent a diagnostic cystoscopy which revealed an erythematous and indurated bladder. Bladder biopsies of these regions revealed plasmacytoid urothelial carcinoma. Pre-operative staging scans were clear of any metastatic disease and the patient subsequently underwent a radical cystectomy and pelvic clearance with the formation of ileal conduit for urinary diversion. Histology confirmed plasmacytoid urothelial carcinoma with involvement of right upper vagina and focally positive margins in soft tissue at right and left sides of bladder. She received adjuvant chemotherapy but passed away within a year from disease progression. PUC can present atypically and our case highlights the role of cystoscopy in patients with persistent urinary symptoms. By reviewing the literature on PUC, we aim to raise awareness and improve understanding of this rare bladder cancer subtype amongst urologists.

Keywords: urology, bladder cancer, plasmacytoid urothelial cancer, literature review

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24 Enhancement of Hydrophobicity of Thermally Evaporated Bi Thin Films by Oblique Angle Deposition

Authors: Ravish K. Jain, Jatinder Kaur, Shaira Arora, Arun Kumar, Amit K. Chawla, Atul Khanna

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Surface-dependent properties such as hydrophobicity can be modified significantly by oblique angle deposition technique. Bi thin films were studied for their hydrophobic nature. The effects of oblique angle deposition on structural, surface morphology, electrical and wettability properties of Bi thin films have been studied and a comparison of these physical properties of normally deposited and obliquely deposited Bi films has been carried out in this study. X-ray diffraction studies found that films have highly oriented hexagonal crystal structure and crystallite size is smaller for obliquely deposited (70 nm) film as compared to that of the normally deposited film (111 nm). Raman spectra of the films consist of peaks corresponding to E_g and A_1g first-order Raman modes of bismuth. The atomic force and scanning electron microscopy studies show that the surface roughness of obliquely deposited film is higher as compared to that of normally deposited film. Contact angle measurements revealed that both films are strongly hydrophobic in nature with the contact angles of 105ᵒ and 119ᵒ for normally and obliquely deposited films respectively. Oblique angle deposition enhances the hydrophobicity of the film. The electrical conductivity of the film is significantly reduced by oblique angle deposition. The activation energies for electrical conduction were determined by four-probe measurements and are 0.016 eV and 0.018 eV for normally and obliquely deposited films respectively.

Keywords: bi thin films, hydrophobicity, oblique angle deposition, surface morphology

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23 Sign Language Recognition of Static Gestures Using Kinect™ and Convolutional Neural Networks

Authors: Rohit Semwal, Shivam Arora, Saurav, Sangita Roy

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This work proposes a supervised framework with deep convolutional neural networks (CNNs) for vision-based sign language recognition of static gestures. Our approach addresses the acquisition and segmentation of correct inputs for the CNN-based classifier. Microsoft Kinect™ sensor, despite complex environmental conditions, can track hands efficiently. Skin Colour based segmentation is applied on cropped images of hands in different poses, used to depict different sign language gestures. The segmented hand images are used as an input for our classifier. The CNN classifier proposed in the paper is able to classify the input images with a high degree of accuracy. The system was trained and tested on 39 static sign language gestures, including 26 letters of the alphabet and 13 commonly used words. This paper includes a problem definition for building the proposed system, which acts as a sign language translator between deaf/mute and the rest of the society. It is then followed by a focus on reviewing existing knowledge in the area and work done by other researchers. It also describes the working principles behind different components of CNNs in brief. The architecture and system design specifications of the proposed system are discussed in the subsequent sections of the paper to give the reader a clear picture of the system in terms of the capability required. The design then gives the top-level details of how the proposed system meets the requirements.

Keywords: sign language, CNN, HCI, segmentation

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22 Correlation Analysis between the Corporate Governance and Financial Performance of Banking Sectors Using Parameter Estimation

Authors: Vishwa Nath Maurya, Rama Shanker Sharma, Saad Talib Hasson Aljebori, Avadhesh Kumar Maurya, Diwinder Kaur Arora

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Present paper deals with problems of determining the relationship between the variables of corporate governance and financial performance of Islamic banks. Here, we dealt with the corporate governance in the banking sector, where increasing the importance of corporate governance, due to their special nature, as the bankruptcy of banks affects not only the relevant parties from customers, depositors and lenders, but also affect financial stability and then the economy as a whole. Through this paper we dealt to the specificity of governance in Islamic banks, which face double governance: Anglo-Saxon governance system and Islamic governance system. In addition, we focused our attention to measure the impact of corporate governance variables on financial performance through an empirical study on a sample of Islamic banks during the period 2005-2012 in the GCC region. Our present study implies that there is a very strong relationship between the variables of governance and financial performance of Islamic banks, where there is a positive relationship between return on assets and the composition of the Board of Directors, the size of the Board of Directors, the number of committees in the Council, as well as the number of members of the Sharia Supervisory Board, while it is clear that there is a negative relationship between return on assets and concentration ownership.

Keywords: correlation analysis, parametric estimation, corporate governance, financial performance, financial stability, conventional banks, bankruptcy, Islamic governance system

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21 Equipment Donation: A Perspective from a Teaching Tertiary Care Hospital in North India

Authors: Jitender Sodhi, Shweta Talati, A. K. Gupta, Pankaj Arora

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Background:Equipment donation to hospitals in resource-limited settings can significantly benefit services in these settings albeit requires important ethical, practical and financial issues to be considered before accepting donations. Objective: To understand the decision making process leading to acceptance/ rejection/ deferment of equipment donation from the perspective of a public sector teaching tertiary care hospital. Design: Retrospective, record based study. Setting: 2000-bedded public sector teaching tertiary care hospital in North India. Methods: A total of 30 cases of equipment donation from March 2010-October 2013, were analysed for their decision process leading to acceptance/rejection/deferment.Each case was studied retrospectively and data pertaining to the agenda and decision taken was collected. Results: A total of 30 cases of equipment donation received from March 2010- October 2013 were screened, out of which 17 (56.6%) were for diagnostic purpose and 13 (43.3%) for therapeutic purpose. Out of 30 cases, 16 (53.3%) were accepted and 8 (26.6%) were rejected. The remaining 6 cases included 3 (10%) which required further clarification and other 3 (10%) which were out of the domain of committee. Conclusion: This study highlights the importance of equipment donation in resource limited settings and considerations involved while making decisions for acceptance/rejections/defermentof such donations.

Keywords: equipment donation, teaching hospital, decision-making, North India

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20 The Global Relationship between the Prevalence of Diabetes Mellitus and Incidence of Tuberculosis: 2000-2012

Authors: Alaa Badawi, Suzan Sayegh, Mohamed Sallam, Eman Sadoun, Mohamed Al-Thani, Muhammad W. Alam, Paul Arora

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Background: The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has increased over the past decade with DM prevalence increasing in countries already afflicted with a high burden of TB. The coexistence of the two conditions presents a serious threat to global public health. Objective: The present study examines the global relationship between the prevalence of DM and the incidence of TB to evaluate their coexistence worldwide and their contribution to one another. Methods: This is an ecological longitudinal study covering the period between years 2000 to 2012. We utilized data from the WHO and World Bank sources and International Diabetes Federation to estimate prevalence of DM (%) and the incidence of TB (per 100,000). Measures of central tendency and dispersion as well as the harmonic mean and linear regression were used for different WHO regions. The association between DM prevalence and TB incidence was examined by quartile of DM prevalence. Results: The worldwide average (±S.D.) prevalence of DM within the study period was 6.6±3.8% whereas TB incidence was 135.0±190.5 per 100,000. DM prevalence was highest in the Eastern Mediterranean (8.3±4.1) and West Pacific (8.2±5.6) regions and lowest in the Africa (3.5±2.6). TB incidence was highest in Africa (313.1±275.9 per 100,000) and South-East Asia (216.7±124.9) and lowest in the European (46.5±68.6) and American (47.2±52.9) regions. Only countries with high DM prevalence (>7.6%) showed a significant positive association with TB incidence (r=0.17, p=0.013). Conclusion: A positive association between DM and TB may exist in some – but not all – world regions, a dual burden that necessitates identifying the nature of this coexistence to assist in developing public health approaches that curb their rising burden.

Keywords: diabetes mellitus, tuberculosis, disease burden, global association

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19 The Application of Robotic Surgical Approaches in the Management of Midgut Neuroendocrine Tumours: A Systematic Review

Authors: Jatin Sridhar Naidu, Aryan Arora, Zainab Shafiq, Reza Mirnezami

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Background: Robotic-assisted surgery (RAS) promises good outcomes in midgut adenocarcinoma surgery. However, its effectiveness in midgut neuroendocrine tumours (MNETs) is unknown. This study aimed to assess the current use, user interface, and any emerging developments of RAS in MNET treatment using the literature available. Methods: This review was carried out using PRISMA guidelines. MEDLINE, EMBASE, and Web of Science were searched on 22nd October 2022. All studies reporting primary data on robotic surgery in midgut neuroendocrine tumours or carcinoid tumours were included. The midgut was defined to be from the duodenojejunal flexure to the splenic flexure. Methodological quality was assessed using the Joanna Briggs critical appraisal tool. Results: According to our systematic review protocol, nineteen studies were selected. A total of twenty-six patients were identified. RAS was used for right colectomies, right hemicolectomies, ileal resections, caecal resections, intracorporeal anastomoses, and complete mesocolic excisions. It offered an optimal user-interface with enhanced visuals, fine dexterity, and ergonomic work position. Innovative developments in tumour-healthy tissue boundary and vasculature visualisation were reported. Conclusion: RAS for MNETs is safe and feasible, although the evidence base is limited. We recommend large prospective-randomised controlled trials comparing it with laparoscopy and open surgery. Developments in intraoperative contrast dyes and tumour-specific probes are very promising.

Keywords: robotic surgery, colorectal surgery, neuroendocrine neoplasms, midgut neoplasms

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18 The Effect of an Abnormal Prefrontal Cortex on the Symptoms of Attention Deficit/Hyperactivity Disorder

Authors: Irene M. Arora

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Hypothesis: Attention Deficit Hyperactivity Disorder is the result of an underdeveloped prefrontal cortex which is the primary cause for the signs and symptoms seen as defining features of ADHD. Methods: Through ‘PubMed’, ‘Wiley’ and ‘Google Scholar’ studies published between 2011-2018 were evaluated, determining if a dysfunctional prefrontal cortex caused the characteristic symptoms associated with ADHD. The search terms "prefrontal cortex", "Attention-Deficit/Hyperactivity Disorder", "cognitive control", "frontostriatal tract" among others, were used to maximize the assortment of relevant studies. Excluded papers were systematic reviews, meta-analyses and publications published before 2010 to ensure clinical relevance. Results: Nine publications were analyzed in this review, all of which were non-randomized matched control studies. Three studies found a decrease in the functional integrity of the frontostriatal tract fibers in conjunction with four studies finding impaired frontal cortex stimulation. Prefrontal dysfunction, specifically medial and orbitofrontal areas, displayed abnormal functionality of reward processing in ADHD patients when compared to their normal counterparts. A total of 807 subjects were studied in this review, yielding that a little over half (54%) presented with remission of symptoms in adulthood. Conclusion: While the prefrontal cortex shows the highest consistency of impaired activity and thinner volumes in patients with ADHD, this is a heterogenous disorder implicating its pathophysiology to the dysfunction of other neural structures as well. However, remission of ADHD symptomatology in adulthood was found to be attributable to increased prefrontal functional connectivity and integration, suggesting a key role for the prefrontal cortex in the development of ADHD.

Keywords: prefrontal cortex, ADHD, inattentive, impulsivity, reward processing

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17 Gap Formation into Bulk InSb Crystals Grown by the VDS Technique Revealing Enhancement in the Transport Properties

Authors: Dattatray Gadkari, Dilip Maske, Manisha Joshi, Rashmi Choudhari, Brij Mohan Arora

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The vertical directional solidification (VDS) technique has been applied to the growth of bulk InSb crystals. The concept of practical stability is applied to the case of detached bulk crystal growth on earth in a simplified design. By optimization of the set up and growth parameters, 32 ingots of 65-75 mm in length and 10-22 mm in diameter have been grown. The results indicate that the wetting angle of the melt on the ampoule wall and the pressure difference across the interface are the crucial factors effecting the meniscus shape and stability. Taking into account both heat transfer and capillarity, it is demonstrated that the process is stable in case of convex menisci (seen from melt), provided that pressure fluctuations remain in a stable range. During the crystal growth process, it is necessary to keep a relationship between the rate of the difference pressure controls and the solidification to maintain the width of gas gap. It is concluded that practical stability gives valuable knowledge of the dynamics and could be usefully applied to other crystal growth processes, especially those involving capillary shaping. Optoelectronic properties were investigated in relation to the type of solidification attached and detached ingots growth. These samples, room temperature physical properties such as Hall mobility, FTIR, Raman spectroscopy and microhardness achieved for antimonide samples grown by VDS technique have shown the highest values gained till at this time. These results reveal that these crystals can be used to produce InSb with high mobility for device applications.

Keywords: alloys, electronic materials, semiconductors, crystal growth, solidification, etching, optical microscopy, crystal structure, defects, Hall effect

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16 Myomectomy and Blood Loss: A Quality Improvement Project

Authors: Ena Arora, Rong Fan, Aleksandr Fuks, Kolawole Felix Akinnawonu

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Introduction: Leiomyomas are benign tumors that are derived from the overgrowth of uterine smooth muscle cells. Women with symptomatic leiomyomas who desire future fertility, myomectomy should be the standard surgical treatment. Perioperative hemorrhage is a common complication in myomectomy. We performed the study to investigate blood transfusion rate in abdominal myomectomies, risk factors influencing blood loss and modalities to improve perioperative blood loss. Methods: Retrospective chart review was done for patients who underwent myomectomy from 2016 to 2022 at Queens hospital center, New York. We looked at preoperative patient demographics, clinical characteristics, intraoperative variables, and postoperative outcomes. Mann-Whitney U test were used for parametric and non-parametric continuous variable comparisons, respectively. Results: A total of 159 myomectomies were performed between 2016 and 2022, including 1 laparoscopic, 65 vaginal and 93 abdominal. 44 patients received blood transfusion during or within 72 hours of abdominal myomectomy. The blood transfusion rate was 47.3%. Blood transfusion rate was found to be twice higher than the average documented rate in literature which is 20%. Risk factors identified were black race, preoperative hematocrit<30%, preoperative blood transfusion within 72 hours, large fibroid burden, prolonged surgical time, and abdominal approach. Conclusion: Preoperative optimization with iron supplements or GnRH agonists is important for patients undergoing myomectomy. Interventions to decrease intra operative blood loss should include cell saver, tourniquet, vasopressin, misoprostol, tranexamic acid and gelatin-thrombin matrix hemostatic sealant.

Keywords: myomectomy, perioperative blood loss, cell saver, tranexamic acid

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15 The Nimbārka School of Vedānta and the Indian Classical Dance: The Philosophical Relevance through Rasa Theory

Authors: Shubham Arora

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This paper illustrates a relationship between the Dvaitādvaita (dualistic non-dualistic) doctrine of Nimbārka school of Vedānta and philosophy of Indian classical dance, through the Rasa theory. There would be a separate focus on the philosophies of both the disciplines and then analyzing Rasa theory as a connexion between them. The paper presents ideas regarding the similarity between the Brahman and the dancer, manifestation of enacting character and the Jīva (soul), the existence of the phenomenal world and the imaginary world classification of rasa on the basis of three modes of nature, and the feelings and expressions depicting the Dvaita and Advaita. The reason behind choosing such a topic is an intention to explore the relativity of the Vedantic philosophy of this school in real manner. It is really important to study the practical implications and relevance of the doctrine with other disciplines for perceiving it cogently. In our daily lives, we use various forms of facial expressions and bodily gestures in order to communicate, along with the oral and written means of communication. What if, when gestures and expressions mingle with the music beats, in order to present an idea? Indian Classical dance is highly rich in expressing the emotions using extraordinary expressions, unconventional bodily gestures and mesmerizing music beats. Ancient scriptures like Nāṭyaśāstra of Bharata Muni and Abhinava Bhārati by Abhinavaguptā recount aesthetics in a well-defined and structured way of acting and dancing and also reveal the grammar of rasa theory. Indian Classical dance is not only for entertainment but it is deeply in contact with divinity. During the period of Bhakti movement in India, this art form was used as a means to narrate the vignettes from epics like Rāmāyana and Mahābhārata and Purānas. Even in present era, this art has a deep rooted philosophy within.

Keywords: Advaita, Brahman, Dvaita, Jiva, Nimbarka, Rasa, Vedanta

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14 Study of Radiation Response in Lactobacillus Species

Authors: Kanika Arora, Madhu Bala

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The small intestine epithelium is highly sensitive and major targets of ionizing radiation. Radiation causes gastrointestinal toxicity either by direct deposition of energy or indirectly (inflammation or bystander effects) generating free radicals and reactive oxygen species. Oxidative stress generated as a result of radiation causes active inflammation within the intestinal mucosa leading to structural and functional impairment of gut epithelial barrier. As a result, there is a loss of tolerance to normal dietary antigens and commensal flora together with exaggerated response to pathogens. Dysbiosis may therefore thought to play a role in radiation enteropathy and can contribute towards radiation induced bowel toxicity. Lactobacilli residing in the gut shares a long conjoined evolutionary history with their hosts and by doing so these organisms have developed an intimate and complex symbiotic relationships. The objective behind this study was to look for the strains with varying resistance to ionizing radiation and to see whether the niche of the bacteria is playing any role in radiation resistance property of bacteria. In this study, we have isolated the Lactobacillus spp. from probiotic preparation and murine gastrointestinal tract, both of which were supposed to be the important source for its isolation. Biochemical characterization did not show a significant difference in the properties, while a significant preference was observed in carbohydrate utilization capacity by the isolates. Effect of ionizing radiations induced by Co60 gamma radiation (10 Gy) on lactobacilli cells was investigated. A cellular survival curve versus absorbed doses was determined. Radiation resistance studies showed that the response of isolates towards cobalt-60 gamma radiation differs from each other and significant decrease in survival was observed in a dose-dependent manner. Thus the present study revealed that the property of radioresistance in Lactobacillus depends upon the source from where they have been isolated.

Keywords: dysbiosis, lactobacillus, mitigation, radiation

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13 Structural and Functional Characterization of the Transcriptional Regulator Rv1176 of Mycobacterium tuberculosis H37Rv

Authors: Vikash Yadav, Ashish Arora

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Microorganisms have self-defense mechanisms to protect themselves from toxic environments. Phenolic acid decarboxylase(pad) is responsible for the defense against toxicity caused by phenolic acids, converting them into less toxic vinyl derivatives. The transcription of the pad gene is regulated by a negative transcription factor, phenolic acid decarboxylase regulators (PadR), in a substrate-inducible manner. The PadR family members share the conserved DNA-binding features and interact with the operator DNA using a winged helix-turn-helix (wHTH) motif, which contains a three-helix motif and a β-stranded wing. The members of this family function as transcriptional regulators that are involved in various cellular survival processes, such as toxin production, detoxification, multidrug resistance, antibiotic biosynthesis, and carbon catabolism. Rv1176 of Mycobacterium tuberculosis H37Rv has been assigned to the PadR family protein that remains to be structurally and functionally uncharacterized. To reveal the structural mechanism by which Rv1176 could regulates effector-responsive transcription, several experiments were performed, including Electrophoretic Mobility Shift Assay (EMSA) for DNA protein interaction, differential scanning calorimetry (DSC) and Differential Scanning Fluorimetry (DSF) for temperature and ligand-dependent protein stability, Circular Dichroism (CD) spectroscopy for secondary structure analysis. Further, to evaluate the functional role of Rv1176, the intracellular survival of recombinant M. smegmatis was examined in murine macrophage cell line J774A.1 and different stressed conditions like oxidative, pH, and nutritive stress. All these studies demonstrated that Rv1176 could behave as a transcription regulator and its expression in recombinant M. smegmatis increases intracellular survival.

Keywords: EMSA, Mycobacterium tuberculosis, PadR family protein, transcriptional regulator

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12 Pathogenic Effects of IgG and IgM Apoptotic Cell-Reactive Monoclonal Auto-Antibodies on Innate and Adaptive Immunity in Lupus

Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

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Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

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11 Age Estimation from Teeth among North Indian Population: Comparison and Reliability of Qualitative and Quantitative Methods

Authors: Jasbir Arora, Indu Talwar, Daisy Sahni, Vidya Rattan

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Introduction: Age estimation is a crucial step to build the identity of a person, both in case of deceased and alive. In adults, age can be estimated on the basis of six regressive (Attrition, Secondary dentine, Dentine transparency, Root resorption, Cementum apposition and Periodontal Disease) changes in teeth qualitatively using scoring system and quantitatively by micrometric method. The present research was designed to establish the reliability of qualitative (method 1) and quantitative (method 2) of age estimation among North Indians and to compare the efficacy of these two methods. Method: 250 single-rooted extracted teeth (18-75 yrs.) were collected from Department of Oral Health Sciences, PGIMER, Chandigarh. Before extraction, periodontal score of each tooth was noted. Labiolingual sections were prepared and examined under light microscope for regressive changes. Each parameter was scored using Gustafson’s 0-3 point score system (qualitative), and total score was calculated. For quantitative method, each regressive change was measured quantitatively in form of 18 micrometric parameters under microscope with the help of measuring eyepiece. Age was estimated using linear and multiple regression analysis in Gustafson’s method and Kedici’s method respectively. Estimated age was compared with actual age on the basis of absolute mean error. Results: In pooled data, by Gustafson’s method, significant correlation (r= 0.8) was observed between total score and actual age. Total score generated an absolute mean error of ±7.8 years. Whereas, for Kedici’s method, a value of correlation coefficient of r=0.5 (p<0.01) was observed between all the eighteen micrometric parameters and known age. Using multiple regression equation, age was estimated, and an absolute mean error of age was found to be ±12.18 years. Conclusion: Gustafson’s (qualitative) method was found to be a better predictor for age estimation among North Indians.

Keywords: forensic odontology, age estimation, North India, teeth

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10 One Pot Synthesis of Ultrasmall NiMo Catalysts Supported on Amorphous Alumina with Enhanced type 2 Sites for Hydrodesulfurization Reaction: A Combined Experimental and Theoretical Study

Authors: Shalini Arora, Sri Sivakumar

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The deep removal of high molecular weight sulphur compounds (e.g., 4,6, dimethyl dibenzothiophene) is challenging due to their steric hindrance. Hydrogenation desulfurization (HYD) pathway is the main pathway to remove these sulfur compounds, and it is mainly governed by the number of type 2 sites. The formation of type 2 sites can be enhanced by modulating the pore structure and the interaction between the active metal and support. To this end, we report the enhanced HDS catalytic activity of ultrasmall NiMo supported on amorphous alumina (A-Al₂O₃) catalysts by one pot colloidal synthesis method followed by calcination and sulfidation. The amorphous alumina (A-Al₂O₃) was chosen as the support due to its lower surface energy, better physicochemical properties, and enhanced acidic sites (due to the dominance of tetra and penta coordinated [Al] sites) than crystalline alumina phase. At 20% metal oxide composition, NiMo supported on A-Al₂O₃ catalyst showed 1.4 and 1.2 times more reaction rate constant and turn over frequency (TOF) respectively than the conventional catalyst (wet impregnated NiMo catalysts) for HDS reaction of dibenzothiophene reactant molecule. A-Al₂O₃ supported catalysts represented enhanced type 2 sites formation (because this catalystpossesses higher sulfidation degree (80%) and NiMoS sites (19.3 x 10¹⁷ sites/mg) with desired optimum stacking degree (2.5) than wet impregnated catalyst at same metal oxide composition 20%) along with higher active metal dispersion, Mo edge site fraction. The experimental observations were also supported by DFT simulations. Lower heat of adsorption (< 4.2 ev for MoS2 interaction and < 3.15 ev for Ni doped MoS2 interaction) values for A-Al₂O₃ confirmed the presence of weaker metal-support interaction in A-Al₂O₃ in contrast to crystalline ℽ-Al₂O3. The weak metal-support interaction for prepared catalysts clearly suggests the higher formation of type 2 sites which leads to higher catalytic activity for HDS reaction.

Keywords: amorphous alumina, colloidal, desulfurization, metal-support interaction

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9 Effect of Preoperative Single Dose Dexamethasone and Lignocaine on Post-Operative Quality of Recovery and Pain Relief after Laparoscopic Cholecystectomy

Authors: Gurjeet Khurana, Surender Singh, Poonam Arora, Praveendra K. Sachan

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Introduction: Post-operative quality of recovery is the key outcome in the perspective of anesthesiologist. It is directly related to patient satisfaction. This is unsurprising, considering most aspects of a poor quality recovery after surgery will impair satisfaction with care. This study was thus undertaken to evaluate effects of Dexamethasone and Lignocaine on Quality of Recovery using QoR- 40 questionnaire and compare their effects. Material and methods: After obtaining the ethical committee approval and written informed consent, 67 patients of 18-60 years, ASA grade I and II scheduled for elective laparoscopic cholecystectomy were randomly allocated into two groups. Group I of 34 patients received 2mg/kg lignocaine diluted to 10ml with normal saline. Group 2 of 33 patients received 0.1 mg/kg I/V Dexamethasone diluted to 10ml with normal saline. QoR-40 was assessed on pre-operative day, and again QoR-40 was assessed at 24 hr post-operative day-1. Postoperative pain scores, nausea and vomiting and shoulder pain were secondary outcomes. Results: The Global QoR-40 was more than 180 at 24 hr in both the groups. The Dexamethasone group had higher Global QoR-40 than lignocaine group 187.94 v/s 182.85. Amongst dimensions of QoR-40 Dexamethasone had statistically better physical comfort, physical independence, and pain relief as compared to Lignocaine. Positive items had excellent responses in Dexamethasone group. Headache, backache and sore throat were also less severe in Dexamethasone group as compared to Lignocaine group. Dexamethasone group had lower VAS compared to lignocaine group. Similarly, there was less fentanyl consumption in dexamethasone group (364.08 ± 127.31) in postoperative period when compared to the lignocaine group (412.31 ± 147.8). Group receiving dexamethasone had 36% increase in appetite compared to lignocaine group (17.6%), which facilitated early oral feeding. Frequency of PONV was less in group-2 at different time interval as compared to group 1. Total episode of PONV were 18 in group 1 and 7 in group 2. Statistically significant difference was seen among two groups (p value= 0.007). Use of antiemetic was more in group 1 as compared to group 2 at all the times, though it was not statistically significant at different time intervals. Antiemetics were administered to 18 patients in group 1 as compared to 5 patients in group 2 postoperatively. Statistically significant difference (p value= 0.011) was seen in total antiemetic consumption. Conclusion: Our study demonstrated that pre-operative administration of a single dose of dexamethasone enhanced the quality of recovery after laparoscopic cholecystectomy as compared to Lignocaine bolus dose.

Keywords: dexamethasone, lignocaine, QoR-40 questionnaire, quality of recovery

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8 Nutritional Status of Children in a Rural Food Environment, Haryana: A Paradox for the Policy Action

Authors: Neha Gupta, Sonika Verma, Seema Puri, Nikhil Tandon, Narendra K. Arora

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The concurrent increasing prevalence of underweight and overweight/obesity among children with changing lifestyle and the rapid transitioning society has necessitated the need for a unifying/multi-level approach to understand the determinants of the problem. The present community-based cross-sectional research study was conducted to assess the associations between lifestyle behavior and food environment of the child at household, neighborhood, and school with the BMI of children (6-12 year old) (n=612) residing in three rural clusters of Palwal district, Haryana. The study used innovative and robust methods for assessing the lifestyle and various components of food environment in the study. The three rural clusters selected for the study were located at three different locations according to their access to highways in the SOMAARTH surveillance site. These clusters were significantly different from each other in terms of their socio-demographic and socio-economic profile, living conditions, environmental hygiene, health seeking behavior and retail density. Despite of being different, the quality of living conditions and environmental hygiene was poor across three clusters. The children had higher intakes of dietary energy and sugars; one-fifth share of the energy being derived from unhealthy foods, engagement in high levels of physical activity and significantly different food environment at home, neighborhood and school level. However, despite having a high energy intake, 22.5% of the recruited children were thin/severe thin, and 3% were overweight/obese as per their BMI-for-age categories. The analysis was done using multi-variate logistic regression at three-tier hierarchy including individual, household and community level. The factors significantly explained the variability in governing the risk of getting thin/severe thin among children in rural area (p-value: 0.0001; Adjusted R2: 0.156) included age (>10years) (OR: 2.1; 95% CI: 1.0-4.4), the interaction between minority category and poor SES of the household (OR: 4.4; 95% CI: 1.6-12.1), availability of sweets (OR: 0.9; 95% CI: 0.8-0.99) and cereals (OR: 0.9; 95% CI: 0.8-1.0) in the household and poor street condition (proxy indicator of the hygiene and cleanliness in the neighborhood) (OR: 0.3; 95% CI: 0.1-1.1). The homogeneity of other factors at neighborhood and school level food environment diluted the heterogeneity in the lifestyles and home environment of the recruited children and their households. However, it is evident that when various individual factors interplay at multiple levels amplifies the risk of undernutrition in a rural community. Conclusion: These rural areas in Haryana are undergoing developmental, economic and societal transition. In correspondence, no improvements in the nutritional status of children have happened. Easy access to the unhealthy foods has become a paradox.

Keywords: transition, food environment, lifestyle, undernutrition, overnutrition

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7 The Toxic Effects of Kynurenine Metabolites on SH-SY5Y Neuroblastoma Cells

Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

Abstract:

Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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6 Biophysical and Structural Characterization of Transcription Factor Rv0047c of Mycobacterium Tuberculosis H37Rv

Authors: Md. Samsuddin Ansari, Ashish Arora

Abstract:

Every year 10 million people fall ill with one of the oldest diseases known as tuberculosis, caused by Mycobacterium tuberculosis. The success of M. tuberculosis as a pathogen is because of its ability to persist in host tissues. Multidrug resistance (MDR) mycobacteria cases increase every day, which is associated with efflux pumps controlled at the level of transcription. The transcription regulators of MDR transporters in bacteria belong to one of the following four regulatory protein families: AraC, MarR, MerR, and TetR. Phenolic acid decarboxylase repressor (PadR), like a family of transcription regulators, is closely related to the MarR family. Phenolic acid decarboxylase repressor (PadR) was first identified as a transcription factor involved in the regulation of phenolic acid stress response in various microorganisms (including Mycobacterium tuberculosis H37Rv). Recently research has shown that the PadR family transcription factors are global, multifunction transcription regulators. Rv0047c is a PadR subfamily-1 protein. We are exploring the biophysical and structural characterization of Rv0047c. The Rv0047 gene was amplified by PCR using the primers containing EcoRI and HindIII restriction enzyme sites cloned in pET-NH6 vector and overexpressed in DH5α and BL21 (λDE3) cells of E. coli following purification with Ni2+-NTA column and size exclusion chromatography. We did DSC to know the thermal stability; the Tm (transition temperature) of protein is 55.29ºC, and ΔH (enthalpy change) of 6.92 kcal/mol. Circular dichroism to know the secondary structure and conformation and fluorescence spectroscopy for tertiary structure study of protein. To understand the effect of pH on the structure, function, and stability of Rv0047c we employed spectroscopy techniques such as circular dichroism, fluorescence, and absorbance measurements in a wide range of pH (from pH-2.0 to pH-12). At low and high pH, it shows drastic changes in the secondary and tertiary structure of the protein. EMSA studies showed the specific binding of Rv0047c with its own 30-bp promoter region. To determine the effect of complex formation on the secondary structure of Rv0047c, we examined the CD spectra of the complex of Rv0047c with promoter DNA of rv0047. The functional role of Rv0047c was characterized by over-expressing the Rv0047c gene under the control of hsp60 promoter in Mycobacterium tuberculosis H37Rv. We have predicted the three-dimensional structure of Rv0047c using the Swiss Model and Modeller, with validity checked by the Ramachandra plot. We did molecular docking of Rv0047c with dnaA, through PatchDock following refinement through FireDock. Through this, it is possible to easily identify the binding hot-stop of the receptor molecule with that of the ligand, the nature of the interface itself, and the conformational change undergone by the protein pattern. We are using X-crystallography to unravel the structure of Rv0047c. Overall the studies show that Rv0047c may have transcription regulation along with providing an insight into the activity of Rv0047c in the pH range of subcellular environment and helps to understand the protein-protein interaction, a novel target to kill dormant bacteria and potential strategy for tuberculosis control.

Keywords: mycobacterium tuberculosis, phenolic acid decarboxylase repressor, Rv0047c, Circular dichroism, fluorescence spectroscopy, docking, protein-protein interaction

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5 Imaging Spectrum of Central Nervous System Tuberculosis on Magnetic Resonance Imaging: Correlation with Clinical and Microbiological Results

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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4 Low-carbon Footprint Diluents in Solvent Extraction for Lithium-ion Battery Recycling

Authors: Abdoulaye Maihatchi Ahamed, Zubin Arora, Benjamin Swobada, Jean-yves Lansot, Alexandre Chagnes

Abstract:

Lithium-ion battery (LiB) is the technology of choice in the development of electric vehicles. But there are still many challenges, including the development of positive electrode materials exhibiting high cycle ability, high energy density, and low environmental impact. For this latter, LiBs must be manufactured in a circular approach by developing the appropriate strategies to reuse and recycle them. Presently, the recycling of LiBs is carried out by the pyrometallurgical route, but more and more processes implement or will implement the hydrometallurgical route or a combination of pyrometallurgical and hydrometallurgical operations. After producing the black mass by mineral processing, the hydrometallurgical process consists in leaching the black mass in order to uptake the metals contained in the cathodic material. Then, these metals are extracted selectively by liquid-liquid extraction, solid-liquid extraction, and/or precipitation stages. However, liquid-liquid extraction combined with precipitation/crystallization steps is the most implemented operation in the LiB recycling process to selectively extract copper, aluminum, cobalt, nickel, manganese, and lithium from the leaching solution and precipitate these metals as high-grade sulfate or carbonate salts. Liquid-liquid extraction consists in contacting an organic solvent and an aqueous feed solution containing several metals, including the targeted metal(s) to extract. The organic phase is non-miscible with the aqueous phase. It is composed of an extractant to extract the target metals and a diluent, which is usually aliphatic kerosene produced from the petroleum industry. Sometimes, a phase modifier is added in the formulation of the extraction solvent to avoid the third phase formation. The extraction properties of the diluent do not depend only on the chemical structure of the extractant, but it may also depend on the nature of the diluent. Indeed, the interactions between the diluent can influence more or less the interactions between extractant molecules besides the extractant-diluent interactions. Only a few studies in the literature addressed the influence of the diluent on the extraction properties, while many studies focused on the effect of the extractants. Recently, new low-carbon footprint aliphatic diluents were produced by catalytic dearomatisation and distillation of bio-based oil. This study aims at investigating the influence of the nature of the diluent on the extraction properties of three extractants towards cobalt, nickel, manganese, copper, aluminum, and lithium: Cyanex®272 for nickel-cobalt separation, DEHPA for manganese extraction, and Acorga M5640 for copper extraction. The diluents used in the formulation of the extraction solvents are (i) low-odor aliphatic kerosene produced from the petroleum industry (ELIXORE 180, ELIXORE 230, ELIXORE 205, and ISANE IP 175) and (ii) bio-sourced aliphatic diluents (DEV 2138, DEV 2139, DEV 1763, DEV 2160, DEV 2161 and DEV 2063). After discussing the effect of the diluents on the extraction properties, this conference will address the development of a low carbon footprint process based on the use of the best bio-sourced diluent for the production of high-grade cobalt sulfate, nickel sulfate, manganese sulfate, and lithium carbonate, as well as metal copper.

Keywords: diluent, hydrometallurgy, lithium-ion battery, recycling

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3 Integrated Services Hub for Exploration and Production Industry: An Indian Narrative

Authors: Sunil Arora, Anitya Kumar Jena, S. A. Ravi

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India is at the cusp of major reforms in the hydrocarbon sector. Oil and gas sector is highly liberalised to attract private investment and to increase domestic production. Major hydrocarbon Exploration & Production (E&P) activity here have been undertaken by Government owned companies but with easing up and reworking of hydro carbon exploration licensing policies private players have also joined the fray towards achieving energy security for India. Government of India has come up with policy and administrative reforms including Hydrocarbon Exploration and Licensing Policy (HELP), Sagarmala (port-led development with coastal connectivity), and Development of Small Discovered Fields, etc. with the intention to make industry friendly conditions for investment, ease of doing business and reduce gestation period. To harness the potential resources of Deep water and Ultra deep water, High Pressure – High Temperature (HP-HT) regions, Coal Bed Methane (CBM), Shale Hydrocarbons besides Gas Hydrates, participation shall be required from both domestic and international players. Companies engaged in E&P activities in India have traditionally been managing through their captive supply base, but with crude prices under hammer, the need is being felt to outsource non-core activities. This necessitates establishment of a robust support services to cater to E&P Industry, which is currently non-existent to meet the bourgeon challenges. This paper outlines an agenda for creating an Integrated Services Hub (ISH) under Special Economic Zone (SEZ) to facilitate complete gamut of non-core support activities of E&P industry. This responsive and proficient multi-usage facility becomes viable with better resource utilization, economies of scale to offer cost effective services. The concept envisages companies to bring-in their core technical expertise leaving complete hardware peripherals outsourced to this ISH. The Integrated Services Hub, complying with the best in class global standards, shall typically provide following Services under Single Window Solution, but not limited to: a) Logistics including supply base operations, transport of manpower and material, helicopters, offshore supply vessels, warehousing, inventory management, sourcing and procurement activities, international freight forwarding, domestic trucking, customs clearance service etc. b) Trained/Experienced pool of competent Manpower (Technical, Security etc.) will be available for engagement by companies on either short or long term basis depending upon the requirements with provisions of meeting any training requirements. c) Specialized Services through tie-up with global best companies for Crisis Management, Mud/Cement, Fishing, Floating Dry-dock besides provision of Workshop, Repair and Testing facilities, etc. d) Tools and Tackles including drill strings, etc. A pre-established Integrated Services Hub shall facilitate an early start-up of activities with substantial savings in time lines. This model can be replicated at other parts of the world to expedite E&P activities.

Keywords: integrated service hub, India, oil gas, offshore supply base

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2 Fe Modified Tin Oxide Thin Film Based Matrix for Reagentless Uric Acid Biosensing

Authors: Kashima Arora, Monika Tomar, Vinay Gupta

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Biosensors have found potential applications ranging from environmental testing and biowarfare agent detection to clinical testing, health care, and cell analysis. This is driven in part by the desire to decrease the cost of health care and to obtain precise information more quickly about the health status of patient by the development of various biosensors, which has become increasingly prevalent in clinical testing and point of care testing for a wide range of biological elements. Uric acid is an important byproduct in human body and a number of pathological disorders are related to its high concentration in human body. In past few years, rapid growth in the development of new materials and improvements in sensing techniques have led to the evolution of advanced biosensors. In this context, metal oxide thin film based matrices due to their bio compatible nature, strong adsorption ability, high isoelectric point (IEP) and abundance in nature have become the materials of choice for recent technological advances in biotechnology. In the past few years, wide band-gap metal oxide semiconductors including ZnO, SnO₂ and CeO₂ have gained much attention as a matrix for immobilization of various biomolecules. Tin oxide (SnO₂), wide band gap semiconductor (Eg =3.87 eV), despite having multifunctional properties for broad range of applications including transparent electronics, gas sensors, acoustic devices, UV photodetectors, etc., it has not been explored much for biosensing purpose. To realize a high performance miniaturized biomolecular electronic device, rf sputtering technique is considered to be the most promising for the reproducible growth of good quality thin films, controlled surface morphology and desired film crystallization with improved electron transfer property. Recently, iron oxide and its composites have been widely used as matrix for biosensing application which exploits the electron communication feature of Fe, for the detection of various analytes using urea, hemoglobin, glucose, phenol, L-lactate, H₂O₂, etc. However, to the authors’ knowledge, no work is being reported on modifying the electronic properties of SnO₂ by implanting with suitable metal (Fe) to induce the redox couple in it and utilizing it for reagentless detection of uric acid. In present study, Fe implanted SnO₂ based matrix has been utilized for reagentless uric acid biosensor. Implantation of Fe into SnO₂ matrix is confirmed by energy-dispersive X-Ray spectroscopy (EDX) analysis. Electrochemical techniques have been used to study the response characteristics of Fe modified SnO₂ matrix before and after uricase immobilization. The developed uric acid biosensor exhibits a high sensitivity to about 0.21 mA/mM and a linear variation in current response over concentration range from 0.05 to 1.0 mM of uric acid besides high shelf life (~20 weeks). The Michaelis-Menten kinetic parameter (Km) is found to be relatively very low (0.23 mM), which indicates high affinity of the fabricated bioelectrode towards uric acid (analyte). Also, the presence of other interferents present in human serum has negligible effect on the performance of biosensor. Hence, obtained results highlight the importance of implanted Fe:SnO₂ thin film as an attractive matrix for realization of reagentless biosensors towards uric acid.

Keywords: Fe implanted tin oxide, reagentless uric acid biosensor, rf sputtering, thin film

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1 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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