Search results for: cell morphology

Authors: Mustafa Metin Donma, Orkide Donma

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Obesity in children particularly draws attention because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases, including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. The liver is at the center of the metabolic pathways network. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and two major hepatokines, cytokines produced predominantly by the liver, fibroblast growth factor-21 (FGF-21) and fetuin A were investigated in pediatric obesity. Two groups were constituted from seventy-six obese children based on World Health Organization criteria. Group 1 was composed of children whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children who are above the 99ᵗʰ percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by an automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by the SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and the platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p<0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p<0.01) in MO group. Both hepatokines were increased in the same group; however, increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r=0.425; p<0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.

Keywords: childhood obesity, fetuin A , fibroblast growth factor-21, hematologic markers, red cell distribution width

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Authors: Alhaji Musa Abdullahi, Usman Abdullahi, Adamu Adamu, Aminu Maidala

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One hundred and fifty (150) day old chicks were randomly allocated into five dietary treatments birds and each treatment where replicated twice in groups of fifteen birds in each replicate. Camel rumen content (CRC) was included in the diets of broiler at 0, 5, 10, 15, and 20% to replace maize and groundnut cake to evaluate the effect on the performance and hematological parameters at the starter and finisher phase. A completely randomized design was used and 600g of feed was given daily and water was given ad libitum. At the starter phase, the daily weight gain and feed conversion ratio were significantly affected by the test ingredients, although T1(0% CRC) which serve as a control, were similar with T2(5% CRC), T3(10% CRC), and T4(15% CRC), while the lowest value was recorded in T5(20% CRC). The result indicates that up to 15% (CRC) level can be included in the starter diet to replace maize and groundnut cake without any effect on the performance. However, at the finisher phase, the daily feed intake, daily weight gain and feed conversion ratio show no significant (F>0.05) difference among the dietary treatments. Similarly, Packed cell volume (PCV), Red Blood Cell (RBC), White Blood Cell (WBC), Mean Corpuscular Volume (MCV), and Mean Corpuscular Haemoglobin (MCH) also did not differ significantly (F>0.05) among the dietary treatments while hemoglobin (Hb) and Mean Corpuscular Haemoglobin Concentration (MCHC) differs significantly. The differential counts of eosinophils, heterophils, and lymphocytes differ significantly among the treatment groups, while that of basophils and monocytes shows no significant difference among the treatment groups. This means up to 20% CRC inclusion level can be used to replaced maize and groundnut cake in the finisher diet without any adverse effect on the performance and hematological parameters of the chickens.

Keywords: camel, rumen content, growth, hematology

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Authors: Gabriel Wosiak, Felipe Staciaki, Eryka Nobrega, Ernesto Pereira

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Hydrogen is an energy carrier with potential applications in various industries. Alkaline electrolysis is a commonly used method for hydrogen production; however, its energy cost remains relatively high compared to other methods. This is due in part to interfacial pH changes that occur during the electrolysis process. Interfacial pH changes refer to the changes in pH that occur at the interface between the cathode electrode and the electrolyte solution. These changes are caused by the electrochemical reactions at both electrodes, which consume or produces hydroxide ions (OH-) from the electrolyte solution. This results in an important change in the local pH at the electrode surface, which can have several impacts on the energy consumption and durability of electrolysers. One impact of interfacial pH changes is an increase in the overpotential required for hydrogen production. Overpotential is the difference between the theoretical potential required for a reaction to occur and the actual potential that is applied to the electrodes. In the case of water electrolysis, the overpotential is caused by a number of factors, including the mass transport of reactants and products to and from the electrodes, the kinetics of the electrochemical reactions, and the interfacial pH. An increase in the interfacial pH at the anode surface in alkaline conditions can lead to an increase in the overpotential for hydrogen production. This is because the lower local pH makes it more difficult for the hydroxide ions to be oxidized. As a result, there is an increase in the required energy to the process occur. In addition to increasing the overpotential, interfacial pH changes can also lead to the degradation of the electrodes. This is because the lower pH can make the electrode more susceptible to corrosion. As a result, the electrodes may need to be replaced more frequently, which can increase the overall cost of water electrolysis. The method presented in the paper addresses the issue of interfacial pH changes by using a cell design with a different cell design, introducing the electrode asymmetry. This design helps to mitigate the pH gradient at the anode/electrolyte interface, which reduces the overpotential and improves the energy efficiency of the electrolyser. The method was tested using a multivariate approach in both laboratory and industrial current density conditions and validated the results with numerical simulations. The results demonstrated a clear improvement (11.6%) in energy efficiency, providing an important contribution to the field of sustainable energy production. The findings of the paper have important implications for the development of cost-effective and sustainable hydrogen production methods. By mitigating interfacial pH changes, it is possible to improve the energy efficiency of alkaline electrolysis and make it a more competitive option for hydrogen production.

Keywords: electrolyser, interfacial pH, numerical simulation, optimization, asymmetric cell

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Authors: Merry Meryam Martgrita, Marselina Irasonia Tan

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One of several aggresive cancer is cancer that overexpress c-erbB2 receptor along with the expression of estrogen receptor. Components of extracellular matrix play an important role to increase cancer cells proliferation, migration and invasion. Both components can affect cancer development by regulating the signal transduction pathways in cancer cells. In recent research, SKOV-3 ovarian cancer cell line, that overexpress c-erbB2 receptor was cultured on type IV collagen and treated with estradiol-17β, to reveal the role of both components on RNA and protein level of c-erbB2 receptor. In this research we found a modulation phenomena of increasing and decreasing of c-erbB2 RNA level and a stabilisation phenomena of c-erbB2 protein expression due to estradiol-17β and type IV collagen. It seemed that estradiol-17β has an important role to increase c-erbB2 transcription and the stability of c-erbB2 protein expression. Type IV collagen has an opposite role. It blocked c-erbB2 transcription when it bound to integrin receptor in SKOV-3 cells.

Keywords: c-erbB2, estradiol-17β, SKOV-3, type IV collagen

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Authors: Ainoa Guinart, Maria Korpidou, Daniel Doellerer, Cornelia Palivan, Ben L. Feringa

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Stimuli responsive systems arise from the need to meet unsolved needs of current molecular drugs. Our study presents the design of a delivery system with high spatiotemporal control and tuneable release profiles. We study the incorporation of a hydrophobic synthetic molecular motor into PDMS-b-PMOXA block copolymer vesicles to create a self-assembled system. We prove their successful incorporation and selective activation by low powered visible light (λ 430 nm, 6.9 mW). We trigger the release of a fluorescent dye with high release efficiencies over sequential cycles (up to 75%) with the ability to turn on and off the release behaviour on demand by light irradiation. Low concentrations of photo-responsive units are proven to trigger release down to 1 mol% of molecular motor. Finally, we test our system in relevant physiological conditions using a lung cancer cell line and the encapsulation of an approved drug. Similar levels of cell viability are observed compared to the free-given drugshowing the potential of our platform to deliver functional drugs on demand with the same efficiency and lower toxicity.

Keywords: molecular motor, polymer, drug delivery, light-responsive, cancer, selfassembly

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Authors: Elena Petersen, Inna Kornienko, Svetlana Guryeva, Sergey Simakov

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In vitro organoid cultivation requires the simultaneous provision of necessary vascularization and nutrients perfusion of cells during organoid development. However, many aspects of this problem are still unsolved. The functionality of vascular network intergrowth is limited during early stages of organoid development since a function of the vascular network initiated on final stages of in vitro organoid cultivation. Therefore, a microchannel network should be created in early stages of organoid cultivation in hydrogel matrix aimed to conduct and maintain minimally required the level of nutrients perfusion for all cells in the expanding organoid. The network configuration should be designed properly in order to exclude hypoxic and necrotic zones in expanding organoid at all stages of its cultivation. In vitro vascularization is currently the main issue within the field of tissue engineering. As perfusion and oxygen transport have direct effects on cell viability and differentiation, researchers are currently limited only to tissues of few millimeters in thickness. These limitations are imposed by mass transfer and are defined by the balance between the metabolic demand of the cellular components in the system and the size of the scaffold. Current approaches include growth factor delivery, channeled scaffolds, perfusion bioreactors, microfluidics, cell co-cultures, cell functionalization, modular assembly, and in vivo systems. These approaches may improve cell viability or generate capillary-like structures within a tissue construct. Thus, there is a fundamental disconnect between defining the metabolic needs of tissue through quantitative measurements of oxygen and nutrient diffusion and the potential ease of integration into host vasculature for future in vivo implantation. A model is proposed for growth prognosis of the organoid perfusion based on joint simulations of general nutrient diffusion, nutrient diffusion to the hydrogel matrix through the contact surfaces and microchannels walls, nutrient consumption by the cells of expanding organoid, including biomatrix contraction during tissue development, which is associated with changed consumption rate of growing organoid cells. The model allows computing effective microchannel network design giving minimally required the level of nutrients concentration in all parts of growing organoid. It can be used for preliminary planning of microchannel network design and simulations of nutrients supply rate depending on the stage of organoid development.

Keywords: 3D model, consumption model, diffusion, spheroid, tissue organoid

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Authors: H. Bouaziz, M. Sefi, J. de Lapuente, M. Borras, N. Zeghal

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Although arsenic trioxide has been the subject of toxicological research, in vitro cytotoxicity and genotoxicity studies using relevant cell models and uniform methodology are not well elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by arsenic trioxide in human keratinocytes (HaCaT) using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and alkaline single cell gel electrophoresis (Comet) assays, respectively. Human keratinocytes were treated with different doses of arsenic trioxide for 4 h prior to cytogenetic assessment. Data obtained from the MTT assay indicated that arsenic trioxide significantly reduced the viability of HaCaT cells in a dose-dependent manner, showing a IC50 value of 34.18 ± 0.6 µM. Data generated from the comet assay also indicated a significant dose-dependent increase in DNA damage in HaCaT cells associated with arsenic trioxide exposure. We observed a significant increase in comet tail length and tail moment, showing an evidence of arsenic trioxide -induced genotoxic damage in HaCaT cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by arsenic.

Keywords: arsenic trioxide, cytotoxixity, genotoxicity, HaCaT

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

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Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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Authors: Lindy Adoma Dampare, Marina Aferiba Tandoh

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Sickle cell disease (SCD) is an inherited blood disorder that mostly affects individuals in sub-Saharan Africa. Nutritional deficiencies have been well established in SCD patients. In Ghana, studies have revealed the prevalence of malnutrition, especially amongst children with SCD and hence the need to develop an evidence-based comprehensive nutritional therapy for SCD to improve their nutritional status. The aim of the study was to develop and assess the effect of a nutrition education material on the nutritional status of SCD patients in Ghana. This was a pre-post interventional study. Patients between the ages of 2 to 60 years were recruited from the Tema General Hospital. Following a baseline nutrition knowledge (NK), beliefs, sanitary practice and dietary consumption pattern assessment, a twice-monthly nutrition education was carried out for 3 months, followed by a post-intervention assessment. Nutritional status of SCD patients was assessed using a 3-days dietary recall and anthropometric measurements. Nutrition education (NE) was given to SCD adults and caregivers of SCD children. Majority of the caregivers (69%) and SCD adult (82%) at baseline had low NK. The level of NK improved significantly in SCD adults (4.18±1.83 vs. 10.00±1.00, p<0.001) and caregivers (5.58 ± 2.25 vs.10.44± 0.846, p<0.001) after NE. Increase in NK improved dietary intake and dietary consumption pattern of SCD patients. Significant increase in weight (23.2±11.6 vs. 25.9±12.1, p=0.036) and height (118.5±21.9 vs. 123.5±22.2, p=0.011) was observed in SCD children at post intervention. Stunting (10.5% vs. 8.6%, p=0.62) and wasting (22.1% vs. 14.4%, p=0.30) reduced in SCD children after NE although not statistically significant. Reduction (18.2% vs. 9.1%) in underweight and an increase (18.2% vs. 27.3%) in overweight SCD adults was recorded at post intervention. Fat mass remained the same while high muscle mass increased (18.2% vs. 27.3%) at post intervention in SCD adult. Anaemic status of SCD patients improved at post intervention and the improvement was statistically significant amongst SCD children. Nutrition education improved the NK of SCD caregivers and adults hence, improving the dietary consumption pattern and nutrient intake of SCD patients. Overall, NE improved the nutritional status of SCD patients. This study shows the potential of nutrition education in improving the nutritional knowledge, dietary consumption pattern, dietary intake and nutritional status of SCD patients, and should be further explored.

Keywords: sickle cell disease, nutrition education, dietary intake, nutritional status

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Authors: Paul Hernandez-Herrera, Fernando Montoya, Juan Manuel Rendon, Alberto Darszon, Gabriel Corkidi

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Intracellular calcium ([Ca2+]i) regulates sperm motility. The analysis of [Ca2+]i has been traditionally achieved in two dimensions while the real movement of the cell takes place in three spatial dimensions. Due to optical limitations (high speed cell movement and low light emission) important data concerning the three dimensional movement of these flagellated cells had been neglected. Visualizing [Ca2+]i in 3D is not a simple matter since it requires complex fluorescence microscopy techniques where the resulting images have very low intensity and consequently low SNR (Signal to Noise Ratio). In 4D sequences, this problem is magnified since the flagellum oscillates (for human sperm) at least at an average frequency of 15 Hz. In this paper, a novel approach to extract the flagellum’s center-line in 4D stacks is presented. For this purpose, an iterative algorithm based on the fast-marching method is proposed to extract the flagellum’s center-line. Quantitative and qualitative results are presented in a 4D stack to demonstrate the ability of the proposed algorithm to trace the flagellum’s center-line. The method reached a precision and recall of 0.96 as compared with a semi-manual method.

Keywords: flagellum, minimal path, segmentation, sperm

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Authors: Ivna Mororó, Lise P. Labéjof, Stephanie Ribeiro, Kely Almeida

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Lipid droplets (LDs) are normally presented in greater or lesser number in the cytoplasm of almost all eukaryotic and some prokaryotic cells. They are independent organelles composed of a lipid ester core and a surface phospholipid monolayer. As a lipid storage form, they provide an available source of energy for the cell. Recently it was demonstrated that they play an important role in other many cellular processes. Among the many unresolved questions about them, it is not even known how LDs is formed, how lipids are recruited to LDs and how they interact with the other organelles. Excess fat in the organism is pathological and often associated with the development of some genetic, hormonal or behavioral diseases. The formation and accumulation of lipid droplets in the cytoplasm can be increased by exogenous physical or chemical agents. It is well known that ionizing radiation affects lipid metabolism resulting in increased lipogenesis in cells, but the details of this process are unknown. To better understand the mode of formation of LDs in liver cells, we investigate their ultrastructural morphology after irradiation. For that, Wistar rats were exposed to whole body gamma radiation from 60-cobalt at various single doses. Samples of the livers were processed for analysis under a conventional transmission electron microscope. We found that when compared to controls, morphological changes in liver cells were evident at the higher doses of radiation used. It was detected a great number of lipid droplets of different sizes and homogeneous content and some of them merged each other. In some cells, it was observed diffused LDs, not limited by a monolayer of phospholipids. This finding suggests that the phospholipid monolayer of the LDs was disrupted by ionizing radiation exposure that promotes lipid peroxydation of endo membranes. Thus the absence of the phospholipid monolayer may prevent the realization of some cellular activities as follow: - lipid exocytosis which requires the merging of LDs membrane with the plasma membrane; - the interaction of LDs with other membrane-bound organelles such as the endoplasmic reticulum (ER), the golgi and mitochondria and; - lipolysis of lipid esters contained in the LDs which requires the presence of enzymes located in membrane-bound organelles as ER. All these impediments can contribute to lipid accumulation in the cytoplasm and the development of diseases such as liver steatosis, cirrhosis and cancer.

Keywords: radiobiology, hepatocytes, lipid metabolism, transmission electron microscopy

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Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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Authors: Saman Khan, Imrana Naseem

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Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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Authors: Fahimeh Palizban, Farshad Noravesh, Amir Hossein Saeidian, Mahya Mehrmohamadi

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In the recent decade, the emergence of liquid biopsy has significantly improved cancer monitoring and detection. Dying cells, including those originating from tumors, shed their DNA into the blood and contribute to a pool of circulating fragments called cell-free DNA. Accordingly, identifying the tissue origin of these DNA fragments from the plasma can result in more accurate and fast disease diagnosis and precise treatment protocols. Open chromatin regions are important epigenetic features of DNA that reflect cell types of origin. Profiling these features by DNase-seq, ATAC-seq, and histone ChIP-seq provides insights into tissue-specific and disease-specific regulatory mechanisms. There have been several studies in the area of cancer liquid biopsy that integrate distinct genomic and epigenomic features for early cancer detection along with tissue of origin detection. However, multimodal analysis requires several types of experiments to cover the genomic and epigenomic aspects of a single sample, which will lead to a huge amount of cost and time. To overcome these limitations, the idea of predicting OCRs from WGS is of particular importance. In this regard, we proposed a computational approach to target the prediction of open chromatin regions as an important epigenetic feature from cell-free DNA whole genome sequence data. To fulfill this objective, local sequencing depth will be fed to our proposed algorithm and the prediction of the most probable open chromatin regions from whole genome sequencing data can be carried out. Our method integrates the signal processing method with sequencing depth data and includes count normalization, Discrete Fourie Transform conversion, graph construction, graph cut optimization by linear programming, and clustering. To validate the proposed method, we compared the output of the clustering (open chromatin region+, open chromatin region-) with previously validated open chromatin regions related to human blood samples of the ATAC-DB database. The percentage of overlap between predicted open chromatin regions and the experimentally validated regions obtained by ATAC-seq in ATAC-DB is greater than 67%, which indicates meaningful prediction. As it is evident, OCRs are mostly located in the transcription start sites (TSS) of the genes. In this regard, we compared the concordance between the predicted OCRs and the human genes TSS regions obtained from refTSS and it showed proper accordance around 52.04% and ~78% with all and the housekeeping genes, respectively. Accurately detecting open chromatin regions from plasma cell-free DNA-seq data is a very challenging computational problem due to the existence of several confounding factors, such as technical and biological variations. Although this approach is in its infancy, there has already been an attempt to apply it, which leads to a tool named OCRDetector with some restrictions like the need for highly depth cfDNA WGS data, prior information about OCRs distribution, and considering multiple features. However, we implemented a graph signal clustering based on a single depth feature in an unsupervised learning manner that resulted in faster performance and decent accuracy. Overall, we tried to investigate the epigenomic pattern of a cell-free DNA sample from a new computational perspective that can be used along with other tools to investigate genetic and epigenetic aspects of a single whole genome sequencing data for efficient liquid biopsy-related analysis.

Keywords: open chromatin regions, cancer, cell-free DNA, epigenomics, graph signal processing, correlation clustering

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Authors: Sang-Myung Jung, Jeong Hyun Ju, Gwang Heum Yoon, Hwa Sung Shin

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Central nervous system (CNS) consists of neuronal cell and supporting cells. Astrocytes are the most common supporting cells and play roles in metabolism between neurons and blood vessel. For this function, engineered astrocytes have been studied as a therapeutic source for CNS injury. In neural tissue engineering, nanofiber has been suggested as an effective scaffold for providing structure and mechanical properties influencing physiology. Cellulose acetate (CA) has been investigated for material to fabricate scaffold because of its biocompatibility, biodegradability and fine thermal stability. In this research, CA nanofiber was modified via heat treatment and its effect on astrocyte activity was evaluated. Adhesion and viability of astrocyte were increased in proportion to stiffness. Additionally, expression of GFAP, a marker of astrocyte activation, was increased via stiffness of scaffold. This research suggests a simple modification method to change stiffness of CA nanofiber and shows cellular behavior affecting stiffness of three-dimensional scaffold independently. For the results, we highlight that the stiffness is a factor to regulate astrocyte activity.

Keywords: astrocyte, cellulose acetate, cell therapy, stiffness of scaffold

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Authors: M. Yadegari, M. Nourbakhsh, N. Arbabzadeh

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The skeletal system injuries are of major importance. In addition, it is recommended to use materials for hard tissue repair in open or closed fractures. It is important to use complex minerals with a beneficial effect on hard tissue repair, stimulating cell growth in the bone. Materials that could help avoid bone fracture inflammatory reaction and speed up bone fracture repair are of utmost importance in the treatment of bone fractures. Similar to minerals, the inner eggshell membrane consists of carbohydrates, lipids, proteins with the high pH, high calcium absorptive capacity and with faster bone fracture repair ability. In the present radiographic survey, eggshell-derived bone graft substitutes were used for bone defect repair in 8 dog tibia, measuring bone density on the day of implant placement and 30 and 60 days after placement. In fact, the result of this study shows the difference in bone growth and misshapen bones between treatment and control sites. Cell growth was adequate in treatment sites and misshapen bones were less frequent here than in control sites.

Keywords: bone repair, eggshell powder, implant, radiography

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Authors: Lucky Malise, Hilary Rutto, Tumisang Seodigeng

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Heavy metal contamination in waste water is a very serious issue affecting a lot of industrialized countries due to the health and environmental impact of these heavy metals on human life and the ecosystem. Adsorption using activated carbon is the most promising method for the removal of heavy metals from waste water but commercial activated carbon is expensive which gives rise to the need for alternatively activated carbon derived from cheap precursors, agricultural wastes, or byproducts from other processes. In this study activated bio-carbon derived from the carbonaceous material obtained from the pyrolysis of Marula nut shells was chemically activated and used as an adsorbent for the removal of lead (II) and copper (II) ions from aqueous solution. The surface morphology and chemistry of the adsorbent before and after chemical activation with zinc chloride impregnation were studied using SEM and FTIR analysis respectively and the results obtained indicate that chemical activation with zinc chloride improves the surface morphology of the adsorbent and enhances the intensity of the surface oxygen complexes on the surface of the adsorbent. The effect of process parameters such as adsorbent dosage, pH value of the solution, initial metal concentration, contact time, and temperature on the adsorption of lead (II) and copper (II) ions onto Marula nut activated carbon were investigated, and their optimum operating conditions were also determined. The experimental data was fitted to both the Langmuir and Freundlich isotherm models, and the data fitted best on the Freundlich isotherm model for both metal ions. The adsorption kinetics were also evaluated, and the experimental data fitted the pseudo-first order kinetic model better than the pseudo second-order kinetic model. The adsorption thermodynamics were also studied and the results indicate that the adsorption of lead and copper ions is spontaneous and exothermic in nature, feasible, and also involves a dissociative mechanism in the temperature range of 25-45 °C.

Keywords: adsorption, isotherms, kinetics, marula nut shells activated carbon, thermodynamics

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Authors: Gabriella Notarianni Burk

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The present study investigates the Aspect Hypothesis (AH) in Italian child language in the production of frog story narratives from the CHILDES database. The AH is based on the assumption that children initially encode aspectual and lexical distinctions rather than temporal relations. Children from a variety of first languages have been shown to mark past initially with achievements and accomplishments (telic predicates) and in later stages with states and activities (atelic predicates). Aspectual distinctions in Romance languages are obligatorily and overtly encoded in the inflectional morphology. In Italian the perfective viewpoint is realized by the passato prossimo, which expresses a temporal and aspectual meaning of pastness and perfectivity, whereas the imperfective viewpoint in the past tense is realized by the imperfetto. The aim of this study is to assess the role of lexical aspect in the acquisition of tense and aspect morphology and to understand if Italian children’s mapping of aspectual and temporal distinctions follows consistent developmental patterns across languages. The research methodology aligns with the cross-linguistic designs, tasks and coding procedures previously developed in the frog story literature. Results from two-factor ANOVA show that Italian children (age range: 4-6) exhibited a statistically significant distinction between foregrounded perfective and backgrounded imperfective marking. However, a closer examination of the sixty narratives reveals an idiosyncratic production pattern for Italian children, whereby the marking of imperfetto deviates from the tenets of AH and emerges as deictic tense to entail completed and bounded events in foreground clauses. Instances of ‘perfective’ uses of imperfetto were predominantly found in the four-year old narratives (25%). Furthermore, the analysis of the perfective marking suggests that morphological articulation and diatopic variation may influence the child production of formal linguistic devices in discourse.

Keywords: actionality, aspect, grounding, temporal reference

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Authors: Edgar Ochoa, G. Torres-Villasenor

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Superplastic deformation is shown by materials with a fine grain size, usually less than 10 μm, when they are deformed within the strain rate range 10-5 10-1 s-1 at temperatures greater than 0.5Tm, where Tm is the melting point in Kelvin. According to the constitutive equation for superplastic flow, refinement of the grain size would be expected to increase the optimum strain rate and decrease the temperature required for superplastic flow. Ribbons of eutectic Ag-Cu and Bi-Cd alloys were manufactured by using a single roller melt-spinning technique to obtain a fine grain structure for later test in superplastic regime. The eutectics ribbons were examined by scanning electron microscopy and X-Ray diffraction, and the grain size was determined using the image analysis software ImageJ. The average grain size was less than 1 μm. Tensile tests were carried out from 10-4 to 10-1 s-1, at room temperature, to evaluate the superplastic behavior. The largest deformation was shown by the Bi-Cd eutectic ribbons, Ɛ=140 %, despite that these ribbons have a hexagonal unit cell. On the other hand, Ag-Cu eutectic ribbons have a minor grain size and cube unit cell, however they showed a lower deformation in tensile test under the same conditions than Bi-Cd ribbons. This is because the Ag-Cu grew in a strong cube-cube orientation relationship.

Keywords: eutectic ribbon, fine grain, superplastic deformation, cube-cube orientation

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Authors: Yi Sun, George Ed Rainger, Steve P. Watson

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Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.

Keywords: membrane proteins, large-scale screening, platelets, recombinant expression

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Authors: Victor U. Odoemelam, Ihemdirim C. Unamba-Opara, Martins C. Anyanwuocha

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Antibiotics used as growth promoters in animal feeds have been criticized and banned in many nations due to possible development of both drug resistance, cross resistance and multiple resistances by consumers. Numerous additives are now being used or proposed as alternatives. A study to compare the effects of Ocimum gratissimum (Scent leaf) and antibiotic growth promoter (Oxytetracycline HCl) on growth performance and intestinal morphology of starter broiler birds was conducted using ninety six (96) days old broiler birds. The birds were randomly assigned to four treatments with each treatment comprising 24 birds replicated three times with 8 birds per replicate in a completely randomized design experiment. Four diets (T1 control diet without Oxytetracycline HCl and Ocimum gratissimum; T2 had Oxytetracycline HCl; T3 had 1% Ocimum gratissimum; T4 had 1.5% Ocimum gratissimum) were formulated and offered ad libitum to the respective birds. Data was collected on feed intake, body weight gain and feed conversion ratio (FCR) also Jejenal sections of the intestine were collected for examination of Villi length and Crypt depth at the end of starter phase. Results show that there were no significant difference (P>0.05) observed in feed intake and final body weight. However, feed conversion ratio (FCR) and daily weight gain significantly differed (P<0.05). T1, T2, and T4 were similar, however T2 differed (P<0.05) from T3. FCR followed the same pattern. Dietary treatment significantly (P<0.05) affected Villi length, Crypt depth and Villi length/crypt depth ratio. Birds fed OG containing diets, had significantly higher (P<0.05) villi length/crypt depth ratio. However, this did not translate to a significantly higher body weight gain or feed conversion ratio. It can be concluded that O. gratissimum can replace antibiotic growth promoter (Oxytetracycline HCl) since their effect on performance were similar.

Keywords: antibiotics, body weight, feed additives, intestinal morphology, phytogenics

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Authors: Ishani D. Goonasekara, Erio Camporesi, Timur Bulgakov, Rungtiwa Phookamsak, Kevin D. Hyde

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Phaeosphaeriaceae comprises a large number of species occurring mainly on grasses and cereal crops as endophytes, saprobes and especially pathogens. Parastagonospora is an important genus in Phaeosphaeriaceae that includes pathogens causing leaf and glume blotch on cereal crops. Currently, there are fifteen Parastagonospora species described, including both pathogens and saprobes. In this study, one sexual morph species and an asexual morph species, occurring as saprobes on members of Poaceae are introduced based on morphology and a combined molecular analysis of the LSU, SSU, ITS, and RPB2 gene sequence data. The sexual morph species Parastagonospora elymi was isolated from a Russian sample of Elymus repens, a grass commonly known as couch grass, and important for grazing animals, as a weed and used in traditional Austrian medicine. P. elymi is similar to the sexual morph of P. avenae in having cylindrical asci, bearing 8, overlapping biseriate, fusiform ascospores but can be distinguished by its subglobose to conical shaped, wider ascomata. In addition, no sheath was observed surrounding the ascospores. The asexual morph species was isolated from a specimen from Italy, on Dactylis glomerata, a commonly found grass distributed in temperate regions. It is introduced as Parastagonospora macrouniseptata, a coelomycete, and bears a close resemblance to P. allouniseptata and P. uniseptata in having globose to subglobose, pycnidial conidiomata and hyaline, cylindrical, 1-septate conidia. However, the new species could be distinguished in having much larger conidiomata. In the phylogenetic analysis which consisted of a maximum likelihood and Bayesian analysis P. elymi showed low bootstrap support, but well segregated from other strains within the Parastagonospora clade. P. neoallouniseptata formed a sister clade with P. allouniseptata with high statistical support.

Keywords: dothideomycetes, multi-gene analysis, Poaceae, saprobes, taxonomy

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Authors: Ali Bayram, Remzi Yiğiter

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Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.

Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR

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Authors: Hyunjung Lim, Jeonghun Nam, Hyuk Choi

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High-throughput separation is an essential technique for cancer research and diagnosis. Here, we propose a viscoelastic microfluidic device for sheathless, high-throughput isolation of circulating tumor cells (CTCs) from white blood cells. Here, we demonstrate a viscoelastic method for separation and concentration of CTCs using closed-loop microfluidics. Our device is a rectangular straight channel with a low aspect ratio. Also, to achieve high-efficiency, high-throughput processing, we used a polymer solution with low viscosity. At the inlet, CTCs and white blood cells (WBCs) were randomly injected into the microchannel. Due to the viscoelasticity-induced lateral migration to the equilibrium positions, large CTCs could be collected from the side outlet while small WBCs were removed at the center outlet. By recirculating the collected CTCs from the side outlet back to the sample reservoir, continuous separation and concentration of CTCs could be achieved with high separation efficiency (~ 99%). We believe that our device has the potential to be applied in resource-limited clinical settings.

Keywords: circulating tumor cell, closed-loop microfluidics, concentration, separation, viscoelastic fluid

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Authors: Dimitriya A. Mihaylova, Zlatka V. Valkova-Jarvis, Georgi L. Iliev

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One possible approach for maintaining the security of communication systems relies on Physical Layer Security mechanisms. However, in wireless time division duplex systems, where uplink and downlink channels are reciprocal, the channel estimate procedure is exposed to attacks known as pilot contamination, with the aim of having an enhanced data signal sent to the malicious user. The Shifted 2-N-PSK method involves two random legitimate pilots in the training phase, each of which belongs to a constellation, shifted from the original N-PSK symbols by certain degrees. In this paper, legitimate pilots’ offset values and their influence on the detection capabilities of the Shifted 2-N-PSK method are investigated. As the implementation of the technique depends on the relation between the shift angles rather than their specific values, the optimal interconnection between the two legitimate constellations is investigated. The results show that no regularity exists in the relation between the pilot contamination attacks (PCA) detection probability and the choice of offset values. Therefore, an adversary who aims to obtain the exact offset values can only employ a brute-force attack but the large number of possible combinations for the shifted constellations makes such a type of attack difficult to successfully mount. For this reason, the number of optimal shift value pairs is also studied for both 100% and 98% probabilities of detecting pilot contamination attacks. Although the Shifted 2-N-PSK method has been broadly studied in different signal-to-noise ratio scenarios, in multi-cell systems the interference from the signals in other cells should be also taken into account. Therefore, the inter-cell interference impact on the performance of the method is investigated by means of a large number of simulations. The results show that the detection probability of the Shifted 2-N-PSK decreases inversely to the signal-to-interference-plus-noise ratio.

Keywords: channel estimation, inter-cell interference, pilot contamination attacks, wireless communications

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Authors: K. J. Keerthi, Vasundhara Kamineni, A. Ravi Shanker, T. Rammurthy, A. Vijaya Lakshmi, Q. Hasan

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Pancreatic β-cells are the predominant insulin-producing cell types within the Islets of Langerhans and insulin is the primary hormone which regulates carbohydrate and fat metabolism. Apoptosis of β-cells or insufficient insulin production leads to Diabetes Mellitus (DM). Current therapy for diabetes includes either medical management or insulin replacement and regular monitoring. Replacement of β- cells is an attractive treatment option for both Type-1 and Type-2 DM in view of the recent paper which indicates that β-cells apoptosis is the common underlying cause for both the Types of DM. With the development of Edmonton protocol, pancreatic β-cells allo-transplantation became possible, but this is still not considered as standard of care due to subsequent requirement of lifelong immunosuppression and the scarcity of suitable healthy organs to retrieve pancreatic β-cell. Fetal pancreatic cells from abortuses were developed as a possible therapeutic option for Diabetes, however, this posed several ethical issues. Hence, in the present study Mesenchymal stem cells (MSCs) were differentiated into insulin producing cells which were isolated from Human Umbilical cord (HUC) tissue. MSCs have already made their mark in the growing field of regenerative medicine, and their therapeutic worth has already been validated for a number of conditions. HUC samples were collected with prior informed consent as approved by the Institutional ethical committee. HUC (n=26) were processed using a combination of both mechanical and enzymatic (collagenase-II, 100 U/ml, Gibco ) methods to obtain MSCs which were cultured in-vitro in L-DMEM (Low glucose Dulbecco's Modified Eagle's Medium, Sigma, 4.5 mM glucose/L), 10% FBS in 5% CO2 incubator at 37°C. After reaching 80-90% confluency, MSCs were characterized with Flowcytometry and Immunocytochemistry for specific cell surface antigens. Cells expressed CD90+, CD73+, CD105+, CD34-, CD45-, HLA-DR-/Low and Vimentin+. These cells were differentiated to β-cells by using H-DMEM (High glucose Dulbecco's Modified Eagle's Medium,25 mM glucose/L, Gibco), β-Mercaptoethanol (0.1mM, Hi-Media), basic Fibroblast growth factor (10 µg /L,Gibco), and Nicotinamide (10 mmol/L, Hi-Media). Pancreatic β-cells were confirmed by positive Dithizone staining and were found to be functionally active as they released 8 IU/ml insulin on glucose stimulation. Isolating MSCs from usually discarded, abundantly available HUC tissue, expanding and differentiating to β-cells may be the most feasible cell therapy option for the millions of people suffering from DM globally.

Keywords: diabetes mellitus, human umbilical cord, mesenchymal stem cells, differentiation

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Authors: Mohanad Alhabo, Li Zhang, Naveed Nawaz

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In this paper, a non-cooperative game method is formulated where all players compete to transmit at higher power. Every base station represents a player in the game. The game is solved by obtaining the Nash equilibrium (NE) where the game converges to optimality. The proposed method, named Power Efficient Handover Game Theoretic (PEHO-GT) approach, aims to control the handover in dense small cell networks. Players optimize their payoff by adjusting the transmission power to improve the performance in terms of throughput, handover, power consumption and load balancing. To select the desired transmission power for a player, the payoff function considers the gain of increasing the transmission power. Then, the cell selection takes place by deploying Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS). A game theoretical method is implemented for heterogeneous networks to validate the improvement obtained. Results reveal that the proposed method gives a throughput improvement while reducing the power consumption and minimizing the frequent handover.

Keywords: energy efficiency, game theory, handover, HetNets, small cells

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Authors: Mohammad Arif, Soumen Chatterjee, Krishnendu Gupta

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The peri-urban interface is an area of transition where the urban and rural areas meet and interact. So the peri-urban areas, which is characterized by strong urban influence, easy access to markets, services and other inputs, are ready supplies of labour but distant from the land paucity and pollution related to urban growth. Hence, the present study is primarily aimed at quantifying the spatio-temporal pattern of land use/land cover change during the last three decades (i.e., 1987 to 2016) in the peri-urban area of Burdwan city. In the recent past, the morphology of the study region has rapid change due to high growth of population and establishment of industries. The change has predominantly taken place along the State and National Highway 2 (NH-2) and around the Burdwan Municipality for meeting both residential and commercial purposes. To ascertain the degree of change in land use and land cover, over the specified time, satellite imageries and topographical sheets are employed. The data is processed through appropriate software packages to arrive at a deduction that most of the land use changes have occurred by obliterating agricultural land & water bodies and substituting them by built area and industrial spaces. Geospatial analysis of study area showed that this area has experienced a steep increase (30%) of built-up areas and excessive decrease (15%) in croplands between 1987 and 2016. Increase in built-up areas is attributed to the increase of out-migration during this period from the core city. This study also examined social, economic and institutional factors that lead to this rapid land use change in peri-urban areas of the Burdwan city by carrying out a field survey of 250 households in peri-urban areas. The research concludes with an urgency for regulating land subdivisions in peri-urban areas to prevent haphazard land use development. It is expected that the findings of the study would go a long way in facilitating better policy making.

Keywords: growth, land use land cover, morphology, peri-urban, policy making

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Authors: Ahmed M. Hjazi, Bader M. Hjazi

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Protein 4.1 is a crucial component of complex interactions between the cytoskeleton and other junctional complex proteins. When the gene encoding this protein is altered, resulting in reduced expression, or when the protein is absent, the red cell undergoes a significant structural change. This research aims to achieve a deeper comprehension of the biochemical effects of red cell protein deficiency. A Tandem Mass Spectrometry Analysis (TMT-MS/MS) of patient cells lacking protein 4.1 compared to three healthy controls was achieved by the Proteomics Institute of the University of Bristol. The SDS-PAGE and Western blotting were utilized on the original patient sample and controls to partially confirm TMT MS/MS data analysis of the protein-4.1-deficient cells. Compared to healthy controls, protein levels in samples lacking protein 4.1 had a significantly higher concentration of proteins that probably originated from reticulocytes. This could occur if the patient has an elevated reticulocyte count. The increase in chaperone and reticulocyte-associated proteins was most notable in this study. This may result from elevated quantities of reticulocytes in patients with hereditary elliptocytosis.

Keywords: hereditary elliptocytosis, protein 4.1, red cells, tandem mass spectrometry data.

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Authors: Yang Liu, Mathias Agmell, Aylin Ahadi, Jan-Eric Stahl, Jinming Zhou

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Tool wear and tool geometry have significant effects on the residual stresses in the component produced by high-speed machining. In this paper, Coupled Eulerian and Lagrangian (CEL) model is adopted to investigate the residual stress in high-speed machining of Inconel718 with a CBN170 cutting tool. The result shows that the mesh with the smallest size of 5 um yields cutting forces and chip morphology in close agreement with the experimental data. The analysis of thermal loading and mechanical loading are performed to study the effect of segmented chip morphology on the machined surface topography and residual stress distribution. The effects of cutting edge radius and flank wear on residual stresses formation and distribution on the workpiece were also investigated. It is found that the temperature within 100um depth of the machined surface increases drastically due to the more friction heat generation with the contact area of tool and workpiece increasing when a larger edge radius and flank wear are used. With the depth further increasing, the temperature drops rapidly for all cases due to the low conductivity of Inconel718. Consequently, higher and deeper tensile residual stress is generated on the superficial. Furthermore, an increased depth of plastic deformation and compressive residual stress is noticed in the subsurface, which is attributed to the reduction of the yield strength under the thermal effect. Besides, the ploughing effect produced by a larger tool edge radius contributes more than flank wear. The magnitude variation of the compressive residual stress caused by various edge radius and flank wear have a totally opposite trend, which depends on the magnitude of the ploughing and friction pressure acting on the machined surface.

Keywords: Coupled Eulerian Lagrangian, segmented chip, residual stress, tool wear, edge radius, Inconel718

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