Search results for: intra- and interbrain coupling
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1177

Search results for: intra- and interbrain coupling

187 NK Cells Expansion Model from PBMC Led to a Decrease of CD4+ and an Increase of CD8+ and CD25+CD127- T-Reg Lymphocytes in Patients with Ovarian Neoplasia

Authors: Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Paulo Cesar Martins Alves, Sophie Françoise Derchain, Fernando Guimarães

Abstract:

T-reg lymphocytes are important for the control of peripheral tolerance. They control the adaptive immune system and prevent autoimmunity through its suppressive action on CD4+ and CD8+ lymphocytes. The suppressive action also includes B lymphocytes, dendritic cells, monocytes/macrophages and recently, studies have shown that T-reg are also able to inhibit NK cells, therefore they exert their control of the immune response from innate to adaptive response. Most tumors express self-ligands, therefore it is believed that T-reg cells induce tolerance of the immune system, hindering the development of successful immunotherapies. T-reg cells have been linked to the suppression mechanisms of the immune response against tumors, including ovarian cancer. The goal of this study was to disclose the sub-population of the expanded CD3+ lymphocytes reported by previous studies, using the long-term culture model designed by Carlens et al 2001, to generate effector cell suspensions enriched with cytotoxic CD3-CD56+ NK cells, from PBMC of ovarian neoplasia patients. Methods and Results: Blood was collected from 12 patients with ovarian neoplasia after signed consent: 7 benign (Bng) and 5 malignant (Mlg). Mononuclear cells were separated by Ficoll-Paque gradient. Long-term culture was conducted by a 21 day culturing process with SCGM CellGro medium supplemented with anti-CD3 (10ng/ml, first 5 days), IL-2 (1000UI/ml) and FBS (10%). After 21 days of expansion, there was an increase in the population of CD3+ lymphocytes in the benign and malignant group. Within CD3+ population, there was a significant decrease in the population of CD4+ lymphocytes in the benign (median Bgn D-0=73.68%, D-21=21.05%) (p<0.05) and malignant (median Mlg D-0=64.00%, D-21=11.97%) (p < 0.01) group. Inversely, after 21 days of expansion, there was an increase in the population of CD8+ lymphocytes within the CD3+ population in the benign (median Bgn D-0=16.80%, D-21=38.56%) and malignant (median Mlg D-0=27.12%, D-21=72.58%) group. However, this increase was only significant on the malignant group (p<0.01). Within the CD3+CD4+ population, there was a significant increase (p < 0.05) in the population of T-reg lymphocytes in the benign (median Bgn D-0=9.84%, D-21=39.47%) and malignant (median Mlg D-0=3.56%, D-21=16.18%) group. Statistical analysis inter groups was performed by Kruskal-Wallis test and intra groups by Mann Whitney test. Conclusion: The CD4+ and CD8+ sub-population of CD3+ lymphocytes shifts with the culturing process. This might be due to the process of the immune system to produce a cytotoxic response. At the same time, T-reg lymphocytes increased within the CD4+ population, suggesting a modulation of the immune response towards cells of the immune system. The expansion of the T-reg population can hinder an immune response against cancer. Therefore, an immunotherapy using this expansion procedure should aim to halt the expansion of T-reg or its immunosuppresion capability.

Keywords: regulatory T cells, CD8+ T cells, CD4+ T cells, NK cell expansion

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186 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity

Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics

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185 Glycerol-Based Bio-Solvents for Organic Synthesis

Authors: Dorith Tavor, Adi Wolfson

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In the past two decades a variety of green solvents have been proposed, including water, ionic liquids, fluorous solvents, and supercritical fluids. However, their implementation in industrial processes is still limited due to their tedious and non-sustainable synthesis, lack of experimental data and familiarity, as well as operational restrictions and high cost. Several years ago we presented, for the first time, the use of glycerol-based solvents as alternative sustainable reaction mediums in both catalytic and non-catalytic organic synthesis. Glycerol is the main by-product from the conversion of oils and fats in oleochemical production. Moreover, in the past decade, its price has substantially decreased due to an increase in supply from the production and use of fatty acid derivatives in the food, cosmetics, and drugs industries and in biofuel synthesis, i.e., biodiesel. The renewable origin, beneficial physicochemical properties and reusability of glycerol-based solvents, enabled improved product yield and selectivity as well as easy product separation and catalyst recycling. Furthermore, their high boiling point and polarity make them perfect candidates for non-conventional heating and mixing techniques such as ultrasound- and microwave-assisted reactions. Finally, in some reactions, such as catalytic transfer-hydrogenation or transesterification, they can also be used simultaneously as both solvent and reactant. In our ongoing efforts to design a viable protocol that will facilitate the acceptance of glycerol and its derivatives as sustainable solvents, pure glycerol and glycerol triacetate (triacetin) as well as various glycerol-triacetin mixtures were tested as sustainable solvents in several representative organic reactions, such as nucleophilic substitution of benzyl chloride to benzyl acetate, Suzuki-Miyaura cross-coupling of iodobenzene and phenylboronic acid, baker’s yeast reduction of ketones, and transfer hydrogenation of olefins. It was found that reaction performance was affected by the glycerol to triacetin ratio, as the solubility of the substrates in the solvent determined product yield. Thereby, employing optimal glycerol to triacetin ratio resulted in maximum product yield. In addition, using glycerol-based solvents enabled easy and successful separation of the products and recycling of the catalysts.

Keywords: glycerol, green chemistry, sustainability, catalysis

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184 Pelvic Floor Training in Elite Athletes: Fact or Fiction

Authors: Maria Barbano Acevedo-Gomez, Elena Sonsoles Rodriguez-Lopez, Sofia Olivia Calvo-Moreno, Angel Basas-Garcia, Cristophe Ramirez

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Introduction: Urinary incontinence (UI) is defined as the involuntary leakage of urine. In persons who practice sport, its prevalence is 36.1% (95% CI 26.5%-46.8%) and varies as it seems to depend on the intensity of exercise, movements, and impact on the ground. Such high impact sports are likely to generate higher intra-abdominal pressures and leading to pelvic floor muscle weakness. Even though the emphasis of this research is on female athletes, all women should perform pelvic floor muscle exercises as a part of their general physical exercise. Pelvic floor exercises are generally considered the first treatment against urinary incontinence. Objective: The main objective of the present study was to determine the knowledge of the pelvic floor and of the UI in elite athletes and know if they incorporate pelvic floor strengthening in their training. Methods: This was an observational study conducted on 754 elite athletes. After collecting questions about the pelvic floor, UI, and sport-related data, participants completed the questionnaire International Consultation on Incontinence Questionnaire-UI Short-Form (ICIQ-SF). Results: 57.3% of the athletes reflect not having knowledge of their pelvic floor, 48.3% do not know what strengthening exercises are, and around 90% have never practiced them. 78.1% (n=589) of all elite athletes do not include pelvic floor exercises in their training. Of the elite athletes surveyed, 33% had UI according to ICIQ-SF (mean age 23.75 ± 7.74 years). In response to the question 'Do you think you have or have had UI?', Only 9% of the 754 elite athletes admitted they presently had UI, and 13.3% indicated they had had UI at some time. However, 22.7% (n=171) reported they had experienced urine leakage while training. Of the athletes who indicated they did not have UI in the ICIQ-SF, 25.7% stated they did experience urine leakage during training (χ² [1] = 265.56; p < 0.001). Further, 12.3% of the athletes who considered they did not have UI and 60% of those who admitted they had had UI on some occasion stated they had suffered some urine leakage in the past 3 months (χ² [1] = 287.59; p < 0.001). Conclusions: There is a lack of knowledge about UI in sport. Through the use of validated questionnaires, we observed a UI prevalence of 33%, and 22.7% reported they experienced urine leakage while training. These figures contrast with only 9% of athletes who reported they had or had in the past had UI. This discrepancy could reflect the great lack of knowledge about UI in sports and that sometimes an athlete may consider that urine leakage is normal and a consequence of the demands of training. These data support the idea that coaches, physiotherapists, and other professionals involved in maximizing the performance of athletes should include pelvic floor muscle exercises in their training programs. Measures such as this could help to prevent UI during training and could be a starting point for future studies designed to develop adequate prevention and treatment strategies for this embarrassing problem affecting young athletes, both male and female.

Keywords: athletes, pelvic floor, performance, prevalence, sport, training, urinary incontinence

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183 Effect of Pioglitazone on Intracellular Na+ Homeostasis in Metabolic Syndrome-Induced Cardiomyopathy in Male Rats

Authors: Ayca Bilginoglu, Belma Turan

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Metabolic syndrome, is associated impaired blood glucose level, insulin resistance, dyslipidemia caused by abdominal obesity. Also, it is related with cardiovascular risk accumulation and cardiomyopathy. The hypothesis of this study was to examine the effect of thiazolidinediones such as pioglitazone which is widely used insulin-sensitizing agents that improve glycemic control, on intracellular Na+ homeostasis in metabolic syndrome-induced cardiomyopathy in male rats. Male Wistar-Albino rats were randomly divided into three groups, namely control (Con, n=7), metabolic syndrome (MetS, n=7) and pioglitazone treated metabolic syndrome group (MetS+PGZ, n=7). Metabolic syndrome was induced by providing drinking water that was 32% sucrose, for 18 weeks. All of the animals were exposed to a 12 h light – 12 h dark cycle. Abdominal obesity and glucose intolerance had measured as a marker of metabolic syndrome. Intracellular Na+ ([Na+]i) is an important modulator of excitation–contraction coupling in heart. [Na+]i at rest and [Na+]i during pacing with electrical field stimulation in 0.2 Hz, 0.8 Hz, 2.0 Hz stimulation frequency were recorded in cardiomyocytes. Also, Na+ channel current (INa) density and I-V curve were measured to understand [Na+]i homeostasis. In results, high sucrose intake, as well as the normal daily diet, significantly increased body mass and blood glucose level of the rats in the metabolic syndrome group as compared with the non-treated control group. In MetS+PZG group, the blood glucose level and body inclined to decrease to the Con group. There was a decrease in INa density and there was a shift both activation and inactivation curve of INa. Pioglitazone reversed the shift to the control side. Basal [Na+]i either MetS and Con group were not significantly different, but there was a significantly increase in [Na+]i in stimulated cardiomyocytes in MetS group. Furthermore, pioglitazone had not effect on basal [Na+]i but it reversed the increase in [Na+]i in stimulated cardiomyocytes to the that of Con group. Results of the present study suggest that pioglitazone has a significant effect on the Na+ homeostasis in the metabolic syndrome induced cardiomyopathy in rats. All animal procedures and experiments were approved by the Animal Ethics Committee of Ankara University Faculty of Medicine (2015-2-37).

Keywords: insulin resistance, intracellular sodium, metabolic syndrome, sodium current

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182 Safety and Feasibility of Distal Radial Balloon Aortic Valvuloplasty - The DR-BAV Study

Authors: Alexandru Achim, Tamás Szűcsborus, Viktor Sasi, Ferenc Nagy, Zoltán Jambrik, Attila Nemes, Albert Varga, Călin Homorodean, Olivier F. Bertrand, Zoltán Ruzsa

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Aim: Our study aimed to establish the safety and the technical success of distal radial access for balloon aortic valvuloplasty (DR-BAV). The secondary objective was to determine the effectiveness and appropriate role of DR-BAV within half year follow-up. Methods: Clinical and angiographic data from 32 consecutive patients with symptomatic aortic stenosis were evaluated in a prospective pilot single-center study. Between 2020 and 2021, the patients were treated utilizing dual distal radial access with 6-10F compatible balloons. The efficacy endpoint was divided into technical success (successful valvuloplasty balloon inflation at the aortic valve and absence of intra- or periprocedural major complications), hemodynamic success (a reduction of the mean invasive gradient >30%), and clinical success (an improvement of at least one clinical category in the NYHA classification). The safety endpoints were vascular complications (major and minor Valve Academic Research Consortium (VARC)-2 bleeding, diminished or lost arterial pulse or the presence of any pseudo-aneurysm or arteriovenous fistula during the clinical follow-up) and major adverse events, MAEs (the composite of death, stroke, myocardial infarction, and urgent major aortic valve replacement or implantation during the hospital stay and or at one-month follow-up). Results: 32 patients (40 % male, mean age 80 ± 8,5) with severe aortic valve stenosis were included in the study and 4 patients were excluded. Technical success was achieved in all patients (100%). Hemodynamic success was achieved in 30 patients (93,75%). Invasive max and mean gradients were reduced from 73±22 mm Hg and 49±22 mm Hg to 49±19 mm Hg and 20±13 mm Hg, respectively (p = <.001). Clinical success was achieved in 29 patients (90,6%). In total, no major adverse cardiac or cerebrovascular event nor vascular complications (according to VARC 2 criteria) occurred during the intervention. All-cause death at 6 months was 12%. Conclusion: According to our study, dual distal radial artery access is a safe and effective option for balloon aortic valvuloplasty in patients with severe aortic valve stenosis and can be performed in all patients with sufficient lumen diameter. Future randomized studies are warranted to investigate whether this technique is superior to other approaches.

Keywords: mean invasive gradient, distal radial access for balloon aortic valvuloplasty (DR-BAV), aortic valve stenosis, pseudo-aneurysm, arteriovenous fistula, valve academic research consortium (VARC)-2

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181 Magnetoelastically Induced Perpendicular Magnetic Anisotropy and Perpendicular Exchange Bias of CoO/CoPt Multilayer Films

Authors: Guo Lei, Wang Yue, Nakamura Yoshio, Shi Ji

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Recently, perpendicular exchange bias (PEB) is introduced as an active topic attracting continuous efforts. Since its discovery, extrinsic control of PEB has been proposed, due to its scientific significance in spintronic devices and potential application in high density magnetic random access memory with perpendicular magnetic tunneling junction (p-MTJ). To our knowledge, the researches aiming to controlling PEB so far are focused mainly on enhancing the interfacial exchange coupling by adjusting the FM/AFM interface roughness, or optimizing the crystalline structures of FM or AFM layer by employing different seed layers. In present work, the effects of magnetoelastically induced PMA on PEB have been explored in [CoO5nm/CoPt5nm]5 multilayer films. We find the PMA strength of FM layer also plays an important role on PEB at the FM/AFM interface and it is effective to control PEB of [CoO5nm/CoPt5nm]5 multilayer films by changing the magnetoelastically induced PMA of CoPt layer. [CoO5nm/CoPt5nm]5 multilayer films were deposited by magnetron sputtering on fused quartz substrate at room temperature, then annealed at 100°C, 250°C, 300°C and 375°C for 3h, respectively. XRD results reveal that all the samples are well crystallized with preferred fcc CoPt (111) orientation. The continuous multilayer structure with sharp component transition at the CoO5nm/CoPt5nm interface are identified clearly by transmission electron microscopy (TEM), x-ray reflectivity (XRR) and atomic force microscope (AFM). CoPt layer in-plane tensile stress is calculated by sin2φ method, and we find it increases gradually upon annealing from 0.99 GPa (as-deposited) up to 3.02 GPa (300oC-annealed). As to the magnetic property, significant enhancement of PMA is achieved in [CoO5nm/CoPt5nm]5 multilayer films after annealing due to the increase of CoPt layer in-plane tensile stress. With the enhancement of magnetoelastically induced PMA, great improvement of PEB is also achieved in [CoO5nm/CoPt5nm]5 multilayer films, which increases from 130 Oe (as-deposited) up to 1060 Oe (300oC-annealed), showing the same change tendency as PMA and the strong correlation with CoPt layer in-plane tensile stress. We consider it is the increase of CoPt layer in-plane tensile stress that leads to the enhancement of PMA, and thus the enhancement of magnetoelastically induced PMA results in the improvement of PEB in [CoO5nm/CoPt5nm]5 multilayer films.

Keywords: perpendicular exchange bias, magnetoelastically induced perpendicular magnetic anisotropy, CoO5nm/CoPt5nm]5 multilayer film with in-plane stress, perpendicular magnetic tunneling junction

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180 Integration of a Microbial Electrolysis Cell and an Oxy-Combustion Boiler

Authors: Ruth Diego, Luis M. Romeo, Antonio Morán

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In the present work, a study of the coupling of a Bioelectrochemical System together with an oxy-combustion boiler is carried out; specifically, it proposes to connect the combustion gas outlet of a boiler with a microbial electrolysis cell (MEC) where the CO2 from the gases are transformed into methane in the cathode chamber, and the oxygen produced in the anode chamber is recirculated to the oxy-combustion boiler. The MEC mainly consists of two electrodes (anode and cathode) immersed in an aqueous electrolyte; these electrodes are separated by a proton exchange membrane (PEM). In this case, the anode is abiotic (where oxygen is produced), and it is at the cathode that an electroactive biofilm is formed with microorganisms that catalyze the CO2 reduction reactions. Real data from an oxy-combustion process in a boiler of around 20 thermal MW have been used for this study and are combined with data obtained on a smaller scale (laboratory-pilot scale) to determine the yields that could be obtained considering the system as environmentally sustainable energy storage. In this way, an attempt is made to integrate a relatively conventional energy production system (oxy-combustion) with a biological system (microbial electrolysis cell), which is a challenge to be addressed in this type of new hybrid scheme. In this way, a novel concept is presented with the basic dimensioning of the necessary equipment and the efficiency of the global process. In this work, it has been calculated that the efficiency of this power-to-gas system based on MEC cells when coupled to industrial processes is of the same order of magnitude as the most promising equivalent routes. The proposed process has two main limitations, the overpotentials in the electrodes that penalize the overall efficiency and the need for storage tanks for the process gases. The results of the calculations carried out in this work show that certain real potentials achieve an acceptable performance. Regarding the tanks, with adequate dimensioning, it is possible to achieve complete autonomy. The proposed system called OxyMES provides energy storage without energetically penalizing the process when compared to an oxy-combustion plant with conventional CO2 capture. According to the results obtained, this system can be applied as a measure to decarbonize an industry, changing the original fuel of the oxy-combustion boiler to the biogas generated in the MEC cell. It could also be used to neutralize CO2 emissions from industry by converting it to methane and then injecting it into the natural gas grid.

Keywords: microbial electrolysis cells, oxy-combustion, co2, power-to-gas

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179 Urinary Incontinence and Performance in Elite Athletes

Authors: María Barbaño Acevedo Gómez, Elena Sonsoles Rodríguez López, Sofía Olivia Calvo Moreno, Ángel Basas García, Christophe RamíRez Parenteau

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Introduction: Urinary incontinence (UI) is defined as the involuntary leakage of urine. In persons who practice sport, its prevalence is 36.1% (95% CI 26.5% –46.8%) and varies as it seems to depend on the intensity of exercise, movements and impact on the ground. Such high impact sports are likely to generate higher intra-abdominal pressures and leading to pelvic floor muscle weakness. Although physical exercise reduces the risk of suffering from many diseases the mentality of an elite athlete is not to optimize their health, achieving their goals can put their health at risk. Furthermore, feeling or suffering from any discomfort during training seems to be normal within the elite sport demands. Objective: The main objective of the present study was to know the effects of UI in sports performance in athletes. Methods: This was an observational study conducted in 754 elite athletes. After collecting questions about pelvic floor, UI and sport-related data, participants completed the questionnaire International Consultation on Incontinence Questionnaire-UI Short- Form (ICIQ-SF) and ISI (index of incontinence severity). Results: 48.8% of the athletes declare having losses also in rest, preseason and / or competition (χ2 [3] = 3.64; p = 0.302), being the competition period (29.1%) the most frequent where suffer from urine leakage. Of the elite athletes surveyed, 33% had UI according ICIQ-SF (mean age 23.75 ± 7.74 years). Elite athletes with UI (5.31 ± 1.07 days) dedicate significantly more days per week to training [M = 0.28; 95% CI = 0.08-0.48; t (752) = 2.78; p = 0.005] than those without UI. Regarding frequency, 59.7% lose urine once a week, 25.6% lose urine more than 3 times a week, and 14.7% daily. Based on the amount, approximately 15% claim to lose a moderate and abundant. Athletes with the highest number of urine leaks during their training, the UI affects them more in their daily life (r = 0.259; p = 0.001), they present a greater number of losses in their day to day (r = 0.341; p <0.001 ) and greater severity of UI (r = 0.341; p <0.001). Conclusions: Athletes consider that UI affects them negatively in their daily routine, 30.9% affirm having a severity between moderate and severe in their daily routine, and 29.1% loss urine in competition period. An interesting fact is that more than half of the samples collected were elite athletes who compete at the highest level (Olympic Games, World and European Championship), the dedication to sport occupies a big piece in their life. The most frequent period where athletes suffers urine leakage is in competition and there are many emotions that athletes manage to get their best performance, if we add urine losses in that moments it is possible that their performance could be affected.

Keywords: athletes, performance, prevalence, sport, training, urinary incontinence

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178 A New Second Tier Screening for Congenital Adrenal Hyperplasia Utilizing One Dried Blood Spot

Authors: Engy Shokry, Giancarlo La Marca, Maria Luisa Della Bona

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Newborn screening for Congenital Adrenal Hyperplasia (CAH) relies on quantification of 17α-hydroxyprogesterone using enzyme immunoassays. These assays, in spite of being rapid, readily available and easy to perform, its reliability was found questionable due to lack of selectivity and specificity resulting in large number of false-positives, consequently family anxiety and associated hospitalization costs. To improve specificity of conventional 17α-hydroxyprogesterone screening which may experience false transient elevation in preterm, low birth weight or acutely ill neonates, steroid profiling by LC-MS/MS as a second-tier test was implemented. Unlike the previously applied LC-MS/MS methods, with the disadvantage of requiring a relatively high number of blood drops. Since newborn screening tests are increasing, it is necessary to minimize the sample volume requirement to make the maximum use of blood samples collected on filter paper. The proposed new method requires just one 3.2 mm dried blood spot (DBS) punch. Extraction was done using methanol: water: formic acid (90:10:0.1, v/v/v) containing deuterium labelled internal standards. Extracts were evaporated and reconstituted in 10 % acetone in water. Column switching strategy for on-line sample clean-up was applied to improve the chromatographic run. The first separative step retained the investigated steroids and passed through the majority of high molecular weight impurities. After the valve switching, the investigated steroids are back flushed from the POROS® column onto the analytical column and separated using gradient elution. Found quantitation limits were 5, 10 and 50 nmol/L for 17α-hydroxyprogesterone, androstenedione and cortisol respectively with mean recoveries of between 98.31-103.24 % and intra-/ inter-assay CV% < 10 % except at LLOQ. The method was validated using standard addition calibration and isotope dilution strategies. Reference ranges were determined by analysing samples from 896 infants of various ages at the time of sample collection. The method was also applied on patients with confirmed CAH. Our method represents an attractive combination of low sample volume requirement, minimal sample preparation time without derivatization and quick chromatography (5 min). The three steroid profile and the concentration ratios (17OHP + androstenedione/cortisol) allowed better screening outcomes of CAH reducing false positives, associated costs and anxiety.

Keywords: congenital adrenal hyperplasia (CAH), 17α-hydroxyprogesterone, androstenedione, cortisol, LC-MS/MS

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177 Observation of Inverse Blech Length Effect during Electromigration of Cu Thin Film

Authors: Nalla Somaiah, Praveen Kumar

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Scaling of transistors and, hence, interconnects is very important for the enhanced performance of microelectronic devices. Scaling of devices creates significant complexity, especially in the multilevel interconnect architectures, wherein current crowding occurs at the corners of interconnects. Such a current crowding creates hot-spots at the respective corners, resulting in non-uniform temperature distribution in the interconnect as well. This non-uniform temperature distribution, which is exuberated with continued scaling of devices, creates a temperature gradient in the interconnect. In particular, the increased current density at corners and the associated temperature rise due to Joule heating accelerate the electromigration induced failures in interconnects, especially at corners. This has been the classic reliability issue associated with metallic interconnects. Herein, it is generally understood that electromigration induced damages can be avoided if the length of interconnect is smaller than a critical length, often termed as Blech length. Interestingly, the effect of non-negligible temperature gradients generated at these corners in terms of thermomigration and electromigration-thermomigration coupling has not attracted enough attention. Accordingly, in this work, the interplay between the electromigration and temperature gradient induced mass transport was studied using standard Blech structure. In this particular sample structure, the majority of the current is forcefully directed into the low resistivity metallic film from a high resistivity underlayer film, resulting in current crowding at the edges of the metallic film. In this study, 150 nm thick Cu metallic film was deposited on 30 nm thick W underlayer film in the configuration of Blech structure. Series of Cu thin strips, with lengths of 10, 20, 50, 100, 150 and 200 μm, were fabricated. Current density of ≈ 4 × 1010 A/m² was passed through Cu and W films at a temperature of 250ºC. Herein, along with expected forward migration of Cu atoms from the cathode to the anode at the cathode end of the Cu film, backward migration from the anode towards the center of Cu film was also observed. Interestingly, smaller length samples consistently showed enhanced migration at the cathode end, thus indicating the existence of inverse Blech length effect in presence of temperature gradient. A finite element based model showing the interplay between electromigration and thermomigration driving forces has been developed to explain this observation.

Keywords: Blech structure, electromigration, temperature gradient, thin films

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176 Synthesis and Preparation of Carbon Ferromagnetic Nanocontainers for Cancer Therapy

Authors: L. Szymanski, Z. Kolacinski, Z. Kamiński, G. Raniszewski, J. Fraczyk, L. Pietrzak

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In the article the development and demonstration of method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nano containers. Methodology of the production carbon - ferromagnetic nanocontainers includes: the synthesis of carbon nanotubes, chemical and physical characterization, increasing the content of ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Folic acid is ligand of folate receptors which is overexpresion in tumor cells. The presence of ligand should ensure the specificity of the interaction between ferromagnetic nanocontainers and tumor cells. The chemical functionalization contains several step: oxidation reaction, transformation of carboxyl groups into more reactive ester or amide groups, incorporation of spacer molecule (linker), attaching folic acid. Activation of carboxylic groups was prepared with triazine coupling reagent (preparation of superactive ester attached on the nanocontainers). The spacer molecules were designed and synthesized. In order to ensure biocompatibillity of linkers they were built from amino acids or peptides. Spacer molecules were synthesized using the SPPS method. Synthesis was performed on 2-Chlorotrityl resin. The linker important feature is its length. Due to that fact synthesis of peptide linkers containing from 2 to 4 -Ala- residues was carried out. Independent synthesis of the conjugate of foilic acid with 6-aminocaproic acid was made. Final step of synthesis was connecting conjugat with spacer molecules and attaching it on the ferromagnetic nanocontainer surface. This article contains also information about special CVD and microvave plasma system to produce nanotubes and ferromagnetic nanocontainers. The first tests in the device for hyperthermal RF generator will be presented. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz.

Keywords: synthesis of carbon nanotubes, hyperthermia, ligands, carbon nanotubes

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175 The Effect of Green Power Trading Mechanism on Interregional Power Generation and Transmission in China

Authors: Yan-Shen Yang, Bai-Chen Xie

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Background and significance of the study: Both green power trading schemes and interregional power transmission are effective ways to increase green power absorption and achieve renewable power development goals. China accelerates the construction of interregional power transmission lines and the green power market. A critical issue focusing on the close interaction between these two approaches arises, which can heavily affect the green power quota allocation and renewable power development. Existing studies have not discussed this issue adequately, so it is urgent to figure out their relationship to achieve a suitable power market design and a more reasonable power grid construction.Basic methodologies: We develop an equilibrium model of the power market in China to analyze the coupling effect of these two approaches as well as their influence on power generation and interregional transmission in China. Our model considers both the Tradable green certificate (TGC) and green power market, which consists of producers, consumers in the market, and an independent system operator (ISO) minimizing the total system cost. Our equilibrium model includes the decision optimization process of each participant. To reformulate the models presented as a single-level one, we replace the producer, consumer, ISO, and market equilibrium problems with their Karush-Kuhn-Tucker (KKT) conditions, which is further reformulated as a mixed-integer linear programming (MILP) and solved in Gurobi solver. Major findings: The result shows that: (1) the green power market can significantly promote renewable power absorption while the TGC market provides a more flexible way for green power trading. (2) The phenomena of inefficient occupation and no available transmission lines appear simultaneously. The existing interregional transmission lines cannot fully meet the demand for wind and solar PV power trading in some areas while the situation is vice versa in other areas. (3) Synchronous implementation of green power and TGC trading mechanism can benefit the development of green power as well as interregional power transmission. (4) The green power transaction exacerbates the unfair distribution of carbon emissions. The Carbon Gini Coefficient is up to 0.323 under the green power market which shows a high Carbon inequality. The eastern coastal region will benefit the most due to its huge demand for external power.

Keywords: green power market, tradable green certificate, interregional power transmission, power market equilibrium model

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174 A Collaborative Approach to Improving Mental and Physical Health-Related Outcomes for a Heart Transplant Patient Through Music and Art Therapy Treatment

Authors: Elizabeth Laguaite, Alexandria Purdy

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Heart transplant recipients face psycho-physiological stressors, including pain, lengthy hospitalizations, delirium, and existential crises. They pose an increased risk for Post Traumatic Stress Disorder (PTSD) and can be a predictor of poorer mental and physical Health-Related Quality of Life (HRQOL) outcomes and increased mortality. There is limited research on the prevention of Post Traumatic Stress Symptoms (PTSS) in transplant patients. This case report focuses on a collaborative Music and Art Therapy intervention used to improve outcomes for HMH transplant recipient John (Alias). John, a 58-year-old man with congestive heart failure, was admitted to HMH in February of 2021 with cardiogenic shock, cannulated with an Intra-aortic Balloon Pump, Impella 5.5, and Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) as a bridge to heart and kidney transplant. He was listed as status 1 for transplant. Music Therapy and Art Therapy (MT and AT) were ordered by the physician for mood regulation, trauma processing and anxiety management. During MT/AT sessions, John reported a history of anxiety and depression exacerbated by medical acuity, shortness of breath, and lengthy hospitalizations. He expressed difficulty sleeping, pain, and existential questions. Initially seen individually by MT/AT, it was determined he could benefit from a collaborative approach due to similar thematic content within sessions. A Life Review intervention was developed by MT/AT. The purpose was for him to creatively express, reflect and process his medical narrative, including the identification of positive and negative events leading up to admission at HMH, the journey to transplant, and his hope for the future. Through this intervention, he created artworks that symbolized each event and paired them with songs, two of which were composed with the MT during treatment. As of September 2023, John has not been readmitted to the hospital and expressed that this treatment is what “got him through transplant”. MT and AT can provide opportunities for a patient to reminisce through creative expression, leading to a shift in the personal meaning of these experiences, promoting resolution, and ameliorating associated trauma. The closer to trauma it is processed, the less likely to develop PTSD. This collaborative MT/AT approach could improve long-term outcomes by reducing mortality and readmission rates for transplant patients.

Keywords: art therapy, music therapy, critical care, PTSD, trauma, transplant

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173 Study on Spatial Structure and Evolvement Process of Traditional Villages’ Courtyard Based on Clannism

Authors: Liang Sun, Yi He

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The origination and development of Chinese traditional villages have a strong link with clan society. Thousands of traditional villages are constituted by one big family who have the same surname. Villages’ basic social relationships are built on the basis of family kinship. Clan power controls family courtyards’ spatial structure and influences their evolvement process. Compared with other countries, research from perspective of clanism is a particular and universally applicable manner to recognize Chinese traditional villages’ space features. This paper takes traditional villages in astern Zhejiang province as examples, especially a single-clan village named Zoumatang. Through combining rural sociology with architecture, it clarifies the coupling relationship between clan structure and village space, reveals spatial composition and evolvement logic of family courtyards. Clan society pays much attention to the patrilineal kinship and genealogy. In astern Zhejiang province, clan is usually divided to ‘clan-branches-families’ three levels. Its structural relationship looks like pyramid, which results in ‘center-margin’ structure when projecting to villages’ space. Due to the cultural tradition of ancestor worship, family courtyards’ space exist similar ‘center-margin’ structure. Ancestor hall and family temple are respectively the space core of village and courtyard. Other parts of courtyard also shows order of superiority and inferiority. Elder and men must be the first. However, along with the disintegration of clan society, family courtyard gradually appears fragmentation trend. Its spatial structure becomes more and more flexible and its scale becomes smaller and smaller. Living conditions rather than ancestor worship turn out to be primary consideration. As a result, there are different courtyard historical prototype in different historic period. To some extent, Chinese present traditional villages’ conservation ignore the impact of clan society. This paper discovers the social significance of courtyard’s spatial texture and rebuilds the connection between society and space. It is expected to promote Chinese traditional villages’ conservation paying more attention to authenticity which defined in the historical process and integrity which built on the basis of social meaning.

Keywords: China, clanism, courtyard, evolvement process, spatial structure, traditional village

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172 Impact of the Oxygen Content on the Optoelectronic Properties of the Indium-Tin-Oxide Based Transparent Electrodes for Silicon Heterojunction Solar Cells

Authors: Brahim Aissa

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Transparent conductive oxides (TCOs) used as front electrodes in solar cells must feature simultaneously high electrical conductivity, low contact resistance with the adjacent layers, and an appropriate refractive index for maximal light in-coupling into the device. However, these properties may conflict with each other, motivating thereby the search for TCOs with high performance. Additionally, due to the presence of temperature sensitive layers in many solar cell designs (for example, in thin-film silicon and silicon heterojunction (SHJ)), low-temperature deposition processes are more suitable. Several deposition techniques have been already explored to fabricate high-mobility TCOs at low temperatures, including sputter deposition, chemical vapor deposition, and atomic layer deposition. Among this variety of methods, to the best of our knowledge, magnetron sputtering deposition is the most established technique, despite the fact that it can lead to damage of underlying layers. The Sn doped In₂O₃ (ITO) is the most commonly used transparent electrode-contact in SHJ technology. In this work, we studied the properties of ITO thin films grown by RF sputtering. Using different oxygen fraction in the argon/oxygen plasma, we prepared ITO films deposited on glass substrates, on one hand, and on a-Si (p and n-types):H/intrinsic a-Si/glass substrates, on the other hand. Hall Effect measurements were systematically conducted together with total-transmittance (TT) and total-reflectance (TR) spectrometry. The electrical properties were drastically affected whereas the TT and TR were found to be slightly impacted by the oxygen variation. Furthermore, the time of flight-secondary ion mass spectrometry (TOF-SIMS) technique was used to determine the distribution of various species throughout the thickness of the ITO and at various interfaces. The depth profiling of indium, oxygen, tin, silicon, phosphorous, boron and hydrogen was investigated throughout the various thicknesses and interfaces, and obtained results are discussed accordingly. Finally, the extreme conditions were selected to fabricate rear emitter SHJ devices, and the photovoltaic performance was evaluated; the lower oxygen flow ratio was found to yield the best performance attributed to lower series resistance.

Keywords: solar cell, silicon heterojunction, oxygen content, optoelectronic properties

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171 Relative Importance of Different Mitochondrial Components in Maintaining the Barrier Integrity of Retinal Endothelial Cells: Implications for Vascular-associated Retinal Diseases

Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

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Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

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170 Assessing the Recycling Potential of Cupriavidus Necator for Space Travel: Production of Single Cell Proteins and Polyhydroxyalkanoates From Organic Waste

Authors: P. Joris, E. Lombard, X. Cameleyre, G. Navarro, A. Paillet, N. Gorret, S. E. Guillouet

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Today, on the international space station, multiple supplies are needed per year to supply food and spare parts and to take out waste. But as it is planned to go longer and further into space these supplies will no longer be possible. The astronaut life support system must be able of continuously transform waste into valuable compounds. Two types of production were identified as critical and could be be supplemented by microorganisms. On the one hand, since microgravity causes rapid muscle loss, single cell proteins (SCPs) could be used as protein rich feed or food. On the other hand, having enough building materials to build an advanced habitat will not be possible only by transporting space goods from earth to mars for example. The bacterium Cupriavidus. necator is well known for its ability to produce a large amount of proteins or of polyhydroxyalkanoate biopolymers (PHAs) depending on its implementation. By coupling the life support system to a 3D-printer, astronauts could be supplied with an unlimited amount of building materials. Additionally, based on the design of the life support system, waste streams have been identified: urea from the crew urine and volatile fatty acids (VFAs) from a first stage of organic waste (excrement and food waste) treatment through anaerobic digestion. Thus, the objective of this, within the Spaceship.Fr project, was to demonstrate the feasibility of producing SCPs and PHAs from VFAs and urea in bioreactor. Because life support systems operate continuously as loops, continuous culture experiments were chosen and the effect of the bioreactor dilution rate on biomass composition was investigated. Total transformation of the carbon source into biomass with high SCP or PHA content was achieved in all cases. We will present the transformation performances of VFAs and urea by the bacteria in bioreactor in terms of titers, yields and productivities but also in terms of the quality of SCP and PHA produced, nucleic acid content. We will further discuss the envisioned integration of our process within life support systems.

Keywords: life support system, space travel, waste treatment, single cell proteins, polyhydroxyalkanoates, bioreactor

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169 Cognitive Performance Post Stroke Is Affected by the Timing of Evaluation

Authors: Ayelet Hersch, Corrine Serfaty, Sigal Portnoy

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Stroke survivors commonly report persistent fatigue and sleep disruptions during rehabilitation and post-recovery. While limited research has explored the impact of stroke on a patient's chronotype, there is a gap in understanding the differences in cognitive performance based on treatment timing. Study objectives: (a) To characterize the sleep chronotype in sub-acute post-stroke individuals. (b) Explore cognitive task performance differences during preferred and non-preferred hours. (c) Examine the relationships between sleep quality and cognitive performance. For this intra-subject study, twenty participants (mean age 60.2±8.6) post-first stroke (6-12 weeks post stroke) underwent assessments at preferred and non-preferred chronotypic times. The assessment included demographic surveys, the Munich Chronotype Questionnaire, Montreal Cognitive Assessment (MoCA), Rivermead Behavioral Memory Test (RBMT), a fatigue questionnaire, and 4-5 days of actigraphy (wrist-worn wGT3X-BT, ActiGraph) to record sleep characteristics. Four sleep quality indices were extracted from actigraphy wristwatch recordings: The average of total sleep time per day (minutes), the average number of awakenings during the sleep period per day, the efficiency of sleep (total hours of sleep per day divided by hours spent in bed per day, averaged across the days and presented as percentage), and the Wake after Sleep Onset (WASO) index, indicating the average number of minutes elapsed from the onset of sleep to the first awakening. Stroke survivors exhibited an earlier sleep chronotype post-injury compared to pre-injury. Enhanced attention, as indicated by higher RBMT scores, occurred during preferred hours. Specifically, 30% of the study participants demonstrated an elevation in their final scores during their preferred hours, transitioning from the category of "mild memory impairment" to "normal memory." However, no significant differences emerged in executive functions, attention tasks, and MoCA scores between preferred and non-preferred hours. The Wake After Sleep Onset (WASO) index correlated with MoCA/RBMT scores during preferred hours (r=0.53/0.51, p=0.021/0.027, respectively). The number of awakenings correlated with MoCA letter task performance during non-preferred hours (r=0.45, p=0.044). Enhanced attention during preferred hours suggests a potential relationship between chronotype and cognitive performance, highlighting the importance of personalized rehabilitation strategies in stroke care. Further exploration of these relationships could contribute to optimizing the timing of cognitive interventions for stroke survivors.

Keywords: sleep chronotype, chronobiology, circadian rhythm, rehabilitation timing

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168 Refractory Visceral Leishmaniasis Responding to Second-Line Therapy

Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

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167 Understanding Magnetic Properties of Cd1-xSnxCr2Se4 Using Local Structure Probes

Authors: P. Suchismita Behera, V. G. Sathe, A. K. Nigam, P. A. Bhobe

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Co-existence of long-range ferromagnetism and semi-conductivity with correlated behavior of structural, magnetic, optical and electrical properties in various sites doping at CdCr2Se4 makes it a most promising candidate for spin-based electronic applications and magnetic devices. It orders ferromagnetically below TC = 130 K with a direct band gap of ~ 1.5 eV. The magnetic ordering is believed to result from strong competition between the direct antiferromagnetic Cr-Cr spin couplings and the ferromagnetic Cr-Se-Cr exchange interactions. With an aim of understanding the influence of crystal structure on its magnetic properties without disturbing the magnetic site, we investigated four compositions with 3%, 5%, 7% and 10% of Sn-substitution at Cd-site. Partial substitution of Cd2+ (0.78Å) by small sized nonmagnetic ion, Sn4+ (0.55Å), is expected to bring about local lattice distortion as well as a change in electronic charge distribution. The structural disorder would affect the Cd/Sn – Se bonds thus affecting the Cr-Cr and Cr-Se-Cr bonds. Whereas, the charge imbalance created due to Sn4+ substitution at Cd2+ leads to the possibility of Cr mixed valence state. Our investigation of the local crystal structure using the EXAFS, Raman spectroscopy and magnetic properties using SQUID magnetometry of the Cd1-xSnxCr2Se4 series reflects this premise. All compositions maintain the Fd3m cubic symmetry with tetrahedral distribution of Sn at Cd-site, as confirmed by XRD analysis. Lattice parameters were determined from the Rietveld refinement technique of the XRD data and further confirmed from the EXAFS spectra recorded at Cr K-edge. Presence of five Raman-active phonon vibrational modes viz. (T2g (1), T2g (2), T2g (3), Eg, A1g) in the Raman spectra further confirms the crystal symmetry. Temperature dependence of the Raman data provides interesting insight to the spin– phonon coupling, known to dominate the magneto-capacitive properties in the parent compound. Below the magnetic ordering temperature, the longitudinal damping of Eg mode associated with Se-Cd/Sn-Se bending and T2g (2) mode associated to Cr-Se-Cr interaction, show interesting deviations with respect to increase in Sn substitution. Besides providing the estimate of TC, the magnetic measurements recorded as a function of field provide the values of total magnetic moment for all the studied compositions indicative of formation of multiple Cr valences.

Keywords: exchange interactions, EXAFS, ferromagnetism, Raman spectroscopy, spinel chalcogenides

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166 A Stepwise Approach for Piezoresistive Microcantilever Biosensor Optimization

Authors: Amal E. Ahmed, Levent Trabzon

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Due to the low concentration of the analytes in biological samples, the use of Biological Microelectromechanical System (Bio-MEMS) biosensors for biomolecules detection results in a minuscule output signal that is not good enough for practical applications. In response to this, a need has arisen for an optimized biosensor capable of giving high output signal in response the detection of few analytes in the sample; the ultimate goal is being able to convert the attachment of a single biomolecule into a measurable quantity. For this purpose, MEMS microcantilevers based biosensors emerged as a promising sensing solution because it is simple, cheap, very sensitive and more importantly does not need analytes optical labeling (Label-free). Among the different microcantilever transducing techniques, piezoresistive based microcantilever biosensors became more prominent because it works well in liquid environments and has an integrated readout system. However, the design of piezoresistive microcantilevers is not a straightforward problem due to coupling between the design parameters, constraints, process conditions, and performance. It was found that the parameters that can be optimized to enhance the sensitivity of Piezoresistive microcantilever-based sensors are: cantilever dimensions, cantilever material, cantilever shape, piezoresistor material, piezoresistor doping level, piezoresistor dimensions, piezoresistor position, Stress Concentration Region's (SCR) shape and position. After a systematic analyzation of the effect of each design and process parameters on the sensitivity, a step-wise optimization approach was developed in which almost all these parameters were variated one at each step while fixing the others to get the maximum possible sensitivity at the end. At each step, the goal was to optimize the parameter in a way that it maximizes and concentrates the stress in the piezoresistor region for the same applied force thus get the higher sensitivity. Using this approach, an optimized sensor that has 73.5x times higher electrical sensitivity (ΔR⁄R) than the starting sensor was obtained. In addition to that, this piezoresistive microcantilever biosensor it is more sensitive than the other similar sensors previously reported in the open literature. The mechanical sensitivity of the final senior is -1.5×10-8 Ω/Ω ⁄pN; which means that for each 1pN (10-10 g) biomolecules attach to this biosensor; the piezoresistor resistivity will decrease by 1.5×10-8 Ω. Throughout this work COMSOL Multiphysics 5.0, a commercial Finite Element Analysis (FEA) tool, has been used to simulate the sensor performance.

Keywords: biosensor, microcantilever, piezoresistive, stress concentration region (SCR)

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165 A Conceptual Framework of the Individual and Organizational Antecedents to Knowledge Sharing

Authors: Muhammad Abdul Basit Memon

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The importance of organizational knowledge sharing and knowledge management has been documented in numerous research studies in available literature, since knowledge sharing has been recognized as a founding pillar for superior organizational performance and a source of gaining competitive advantage. Built on this, most of the successful organizations perceive knowledge management and knowledge sharing as a concern of high strategic importance and spend huge amounts on the effective management and sharing of organizational knowledge. However, despite some very serious endeavors, many firms fail to capitalize on the benefits of knowledge sharing because of being unaware of the individual characteristics, interpersonal, organizational and contextual factors that influence knowledge sharing; simply the antecedent to knowledge sharing. The extant literature on antecedents to knowledge sharing, offers a range of antecedents mentioned in a number of research articles and research studies. Some of the previous studies about antecedents to knowledge sharing, studied antecedents to knowledge sharing regarding inter-organizational knowledge transfer; others focused on inter and intra organizational knowledge sharing and still others investigated organizational factors. Some of the organizational antecedents to KS can relate to the characteristics and underlying aspects of knowledge being shared e.g., specificity and complexity of the underlying knowledge to be transferred; others relate to specific organizational characteristics e.g., age and size of the organization, decentralization and absorptive capacity of the firm and still others relate to the social relations and networks of organizations such as social ties, trusting relationships, and value systems. In the same way some researchers have highlighted on only one aspect like organizational commitment, transformational leadership, knowledge-centred culture, learning and performance orientation and social network-based relationships in the organizations. A bulk of the existing research articles on antecedents to knowledge sharing has mainly discussed organizational or environmental factors affecting knowledge sharing. However, the focus, later on, shifted towards the analysis of individuals or personal determinants as antecedents for the individual’s engagement in knowledge sharing activities, like personality traits, attitude and self efficacy etc. For example, employees’ goal orientations (i.e. learning orientation or performance orientation is an important individual antecedent of knowledge sharing behaviour. While being consistent with the existing literature therefore, the antecedents to knowledge sharing can be classified as being individual and organizational. This paper is an endeavor to discuss a conceptual framework of the individual and organizational antecedents to knowledge sharing in the light of the available literature and empirical evidence. This model not only can help in getting familiarity and comprehension on the subject matter by presenting a holistic view of the antecedents to knowledge sharing as discussed in the literature, but can also help the business managers and especially human resource managers to find insights about the salient features of organizational knowledge sharing. Moreover, this paper can help provide a ground for research students and academicians to conduct both qualitative as well and quantitative research and design an instrument for conducting survey on the topic of individual and organizational antecedents to knowledge sharing.

Keywords: antecedents to knowledge sharing, knowledge management, individual and organizational, organizational knowledge sharing

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164 Microalgae Hydrothermal Liquefaction Process Optimization and Comprehension to Produce High Quality Biofuel

Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet

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Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.

Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass

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163 Molecular Characterization of Arginine Sensing Response in Unravelling Host-Pathogen Interactions in Leishmania

Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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162 No-Par Shares Working in European LLCs

Authors: Agnieszka P. Regiec

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Capital companies are based on monetary capital. In the traditional model, the capital is the sum of the nominal values of all shares issued. For a few years within the European countries, the limited liability companies’ (LLC) regulations are leaning towards liberalization of the capital structure in order to provide higher degree of autonomy regarding the intra-corporate governance. Reforms were based primarily on the legal system of the USA. In the USA, the tradition of no-par shares is well-established. Thus, as a point of reference, the American legal system is being chosen. Regulations of Germany, Great Britain, France, Netherlands, Finland, Poland and the USA will be taken into consideration. The analysis of the share capital is important for the development of science not only because the capital structure of the corporation has significant impact on the shareholders’ rights, but also it reflects on relationships between creditors of the company and the company itself. Multi-level comparative approach towards the problem will allow to present a wide range of the possible outcomes stemming from the novelization. The dogmatic method was applied. The analysis was based on the statutes, secondary sources and judicial awards. Both the substantive and the procedural aspects of the capital structure were considered. In Germany, as a result of the regulatory competition, typical for the EU, the structure of LLCs was reshaped. New LLC – Unternehmergesellschaft, which does not require a minimum share capital, was introduced. The minimum share capital for Gesellschaft mit beschrankter Haftung was lowered from 25 000 to 10 000 euro. In France the capital structure of corporations was also altered. In 2003, the minimum share capital of société à responsabilité limitée (S.A.R.L.) was repealed. In 2009, the minimum share capital of société par actions simplifiée – in the “simple” version of S.A.R.L. was also changed – there is no minimum share capital required by a statute. The company has to, however, indicate a share capital without the legislator imposing the minimum value of said capital. In Netherlands the reform of the Besloten Vennootschap met beperkte aansprakelijkheid (B.V.) was planned with the following change: repeal of the minimum share capital as the answer to the need for higher degree of autonomy for shareholders. It, however, preserved shares with nominal value. In Finland the novelization of yksityinen osakeyhtiö took place in 2006 and as a result the no-par shares were introduced. Despite the fact that the statute allows shares without face value, it still requires the minimum share capital in the amount of 2 500 euro. In Poland the proposal for the restructuration of the capital structure of the LLC has been introduced. The proposal provides among others: devaluation of the capital to 1 PLN or complete liquidation of the minimum share capital, allowing the no-par shares to be issued. In conclusion: American solutions, in particular, balance sheet test and solvency test provide better protection for creditors; European no-par shares are not the same as American and the existence of share capital in Poland is crucial.

Keywords: balance sheet test, limited liability company, nominal value of shares, no-par shares, share capital, solvency test

Procedia PDF Downloads 161
161 The Renewed Constitutional Roots of Agricultural Law in Hungary in Line with Sustainability

Authors: Gergely Horvath

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The study analyzes the special provisions of the highest level of national agricultural legislation in the Fundamental Law of Hungary (25 April 2011) with descriptive, analytic and comparative methods. The agriculturally relevant articles of the constitution are very important, because –in spite of their high level of abstraction– they can determine and serve the practice comprehensively and effectively. That is why the objective of the research is to interpret the concrete sentences and phrases in connection with agriculture compared with the methods of some other relevant constitutions (historical-grammatical interpretation). The major findings of the study focus on searching for the appropriate provisions and approach capable of solving the problems of sustainable food production. The real challenge agricultural law must face with in the future is protecting or conserving its background and subjects: the environment, the ecosystem services and all the 'roots' of food production. In effect, agricultural law is the legal aspect of the production of 'our daily bread' from farm to table. However, it also must guarantee the safe daily food for our children and for all our descendants. In connection with sustainability, this unique, value-oriented constitution of an agrarian country even deals with uncustomary questions in this level of legislation like GMOs (by banning the production of genetically modified crops). The starting point is that the principle of public good (principium boni communis) must be the leading notion of the norm, which is an idea partly outside the law. The public interest is reflected by the agricultural law mainly in the concept of public health (in connection with food security) and the security of supply with healthy food. The construed Article P claims the general protection of our natural resources as a requirement. The enumeration of the specific natural resources 'which all form part of the common national heritage' also means the conservation of the grounds of sustainable agriculture. The reference of the arable land represents the subfield of law of the protection of land (and soil conservation), that of the water resources represents the subfield of water protection, the reference of forests and the biological diversity visualize the specialty of nature conservation, which is an essential support for agrobiodiversity. The mentioned protected objects constituting the nation's common heritage metonymically melt with their protective regimes, strengthening them and forming constitutional references of law. This regimes also mean the protection of the natural foundations of the life of the living and also the future generations, in the name of intra- and intergenerational equity.

Keywords: agricultural law, constitutional values, natural resources, sustainability

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160 Synthesis of Porphyrin-Functionalized Beads for Flow Cytometry

Authors: William E. Bauta, Jennifer Rebeles, Reggie Jacob

Abstract:

Porphyrins are noteworthy in biomedical science for their cancer tissue accumulation and photophysical properties. The preferential accumulation of some porphyrins in cancerous tissue has been known for many years. This, combined with their characteristic photophysical and photochemical properties, including their strong fluorescence and their ability to generate reactive oxygen species in vivo upon laser irradiation, has led to much research into the application of porphyrins as cancer diagnostic and therapeutic agents. Porphyrins have been used as dyes to detect cancer cells both in vivo and, less commonly, in vitro. In one example, human sputum samples from lung cancer patients and patients without the disease were dissociated and stained with the porphyrin TCPP (5,10,15,20-tetrakis-(4-carboxyphenyl)-porphine). Cells were analyzed by flow cytometry. Cancer samples were identified by their higher TCPP fluorescence intensity relative to the no-cancer controls. However, quantitative analysis of fluorescence in cell suspensions stained with multiple fluorophores requires particles stained with each of the individual fluorophores as controls. Fluorescent control particles must be compatible in size with flow cytometer fluidics and have favorable hydrodynamic properties in suspension. They must also display fluorescence comparable to the cells of interest and be stable upon storage amine-functionalized spherical polystyrene beads in the 5 to 20-micron diameter range that was reacted with TCPP and EDC in aqueous pH six buffer overnight to form amide bonds. Beads were isolated by centrifugation and tested by flow cytometry. The 10-micron amine-functionalized beads displayed the best combination of fluorescence intensity and hydrodynamic properties, such as lack of clumping and remaining in suspension during the experiment. These beads were further optimized by varying the stoichiometry of EDC and TCPP relative to the amine. The reaction was accompanied by the formation of a TCPP-related particulate, which was removed, after bead centrifugation, using a microfiltration process. The resultant TCPP-functionalized beads were compatible with flow cytometry conditions and displayed a fluorescence comparable to that of stained cells, which allowed their use as fluorescence standards. The beads were stable in refrigerated storage in the dark for more than eight months. This work demonstrates the first preparation of porphyrin-functionalized flow cytometry control beads.

Keywords: tetraaryl porphyrin, polystyrene beads, flow cytometry, peptide coupling

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159 A Study on Computational Fluid Dynamics (CFD)-Based Design Optimization Techniques Using Multi-Objective Evolutionary Algorithms (MOEA)

Authors: Ahmed E. Hodaib, Mohamed A. Hashem

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In engineering applications, a design has to be as fully perfect as possible in some defined case. The designer has to overcome many challenges in order to reach the optimal solution to a specific problem. This process is called optimization. Generally, there is always a function called “objective function” that is required to be maximized or minimized by choosing input parameters called “degrees of freedom” within an allowed domain called “search space” and computing the values of the objective function for these input values. It becomes more complex when we have more than one objective for our design. As an example for Multi-Objective Optimization Problem (MOP): A structural design that aims to minimize weight and maximize strength. In such case, the Pareto Optimal Frontier (POF) is used, which is a curve plotting two objective functions for the best cases. At this point, a designer should make a decision to choose the point on the curve. Engineers use algorithms or iterative methods for optimization. In this paper, we will discuss the Evolutionary Algorithms (EA) which are widely used with Multi-objective Optimization Problems due to their robustness, simplicity, suitability to be coupled and to be parallelized. Evolutionary algorithms are developed to guarantee the convergence to an optimal solution. An EA uses mechanisms inspired by Darwinian evolution principles. Technically, they belong to the family of trial and error problem solvers and can be considered global optimization methods with a stochastic optimization character. The optimization is initialized by picking random solutions from the search space and then the solution progresses towards the optimal point by using operators such as Selection, Combination, Cross-over and/or Mutation. These operators are applied to the old solutions “parents” so that new sets of design variables called “children” appear. The process is repeated until the optimal solution to the problem is reached. Reliable and robust computational fluid dynamics solvers are nowadays commonly utilized in the design and analyses of various engineering systems, such as aircraft, turbo-machinery, and auto-motives. Coupling of Computational Fluid Dynamics “CFD” and Multi-Objective Evolutionary Algorithms “MOEA” has become substantial in aerospace engineering applications, such as in aerodynamic shape optimization and advanced turbo-machinery design.

Keywords: mathematical optimization, multi-objective evolutionary algorithms "MOEA", computational fluid dynamics "CFD", aerodynamic shape optimization

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158 Anti-Apoptotic Effect of Pueraria tuberosa in Rats with Streptozotocin Induced Diabetic Nephropathy

Authors: Rashmi Shukla, Yamini Bhusan Tripathi

Abstract:

Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

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