Search results for: limbal stem cell deficiency

Authors: Muhammad Umar Hassan

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Renal cell carcinoma is a subset of kidney cancer that arises in the lining of DCT and is present in parenchymal tissue. Diagnosis is based on lab reports, including urinalysis, renal function tests (RFTs), and electrolyte balance, along with imaging techniques. Organ failure and other complications have been commonly observed in these cases. Over the years, the presentation of patients has varied, so carcinoma was classified on the basis of site, shape, and consistency for detailed analysis. Lifestyle patterns and occupational history were inquired about and recorded. Methods: Data from 100 patients presenting to the oncology and nephrology department of Mayo Hospital in the year 2015-2020 were included in this retrospective study on a random basis. The study was specifically focused on three risk factors. Smoking, occupational exposures, and Hakim medicine are taken by the patient for any cause. After procurement of data, follow-up contacts of these patients were established, resulting in a detailed analysis of lifestyle. Conclusion: The inference drawn is a direct causal link between smoking, industrial workplace exposure, and Hakim medicine with the development of Renal Cell Carcinoma. It was shown in the majority of the patients and hence confirmed our hypothesis.

Keywords: renal cell carcinoma, kidney cancer, clear cell carcinoma

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Authors: Sadık Ata, Kevser Dincer

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In this study, performance of proton exchange membrane (PEM) fuel cell was experimentally investigated and modelled with Rule-Based Mamdani-Type Fuzzy (RBMTF) modelling technique. Coating on the anode side of the PEM fuel cell was accomplished with the spin method by using Yttria-stabilized zirconia (YSZ). Input parameters voltage density (V/cm2), and current density (A/cm2), temperature (°C), time (s); output parameter power density (W/cm2) were described by RBMTF if-then rules. Numerical parameters of input and output variables were fuzzificated as linguistic variables: Very Very Low (L1), Very Low (L2), Low (L3), Negative Medium (L4), Medium (L5), Positive Medium (L6), High (L7), Very High (L8) and Very Very High (L9) linguistic classes. The comparison between experimental data and RBMTF is done by using statistical methods like absolute fraction of variance (R2). The actual values and RBMTF results indicated that RBMTF can be successfully used for the analysis of performance of PEM fuel cell.

Keywords: proton exchange membrane (PEM), fuel cell, rule-based Mamdani-type fuzzy (RMBTF) modeling, yttria-stabilized zirconia (YSZ)

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Authors: Astghik R. Sukiasyan

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Under the drought stress condition, the plants would grow slower. Temperature is one of the most important abiotic factors which suppress the germination processes. However, the processes of transpiration are regulated directly by the cell water, which followed to an increase in volume of vacuoles. During stretching under the influence of water pressure, the cell goes into the state of turgor. In our experiments, lines of the semi-dental sweet maize of Armenian population from various zones of growth under mild and severe drought stress were tested. According to results, the value of the water balance of the plant cells may reflect the ability of plants to adapt to drought stress. It can be assumed that the turgor allows evaluating the number of received dissolved substance in cell.

Keywords: turgor, drought stress, plant growth, Armenian Zea Maize Semidentata

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Authors: Miguel Contreras, David Long, Will Bachman

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Background: Microscopy plays a central role in cell and developmental biology. In particular, fluorescence microscopy can be used to visualize specific cellular components and subsequently quantify their morphology through development of virtual-cell models for study of effects of mechanical forces on cells. However, there are challenges with these imaging experiments, which can make it difficult to quantify cell morphology: inconsistent results, time-consuming and potentially costly protocols, and limitation on number of labels due to spectral overlap. To address these challenges, the objective of this project is to develop an automatic computational machine learning pipeline to predict cellular components morphology for virtual-cell generation based on fluorescence cell membrane confocal z-stacks. Methods: Registered confocal z-stacks of nuclei and cell membrane of endothelial cells, consisting of 20 images each, were obtained from fluorescence confocal microscopy and normalized through software pipeline for each image to have a mean pixel intensity value of 0.5. An open source machine learning algorithm, originally developed to predict fluorescence labels on unlabeled transmitted light microscopy cell images, was trained using this set of normalized z-stacks on a single CPU machine. Through transfer learning, the algorithm used knowledge acquired from its previous training sessions to learn the new task. Once trained, the algorithm was used to predict morphology of nuclei using normalized cell membrane fluorescence images as input. Predictions were compared to the ground truth fluorescence nuclei images. Results: After one week of training, using one cell membrane z-stack (20 images) and corresponding nuclei label, results showed qualitatively good predictions on training set. The algorithm was able to accurately predict nuclei locations as well as shape when fed only fluorescence membrane images. Similar training sessions with improved membrane image quality, including clear lining and shape of the membrane, clearly showing the boundaries of each cell, proportionally improved nuclei predictions, reducing errors relative to ground truth. Discussion: These results show the potential of pre-trained machine learning algorithms to predict cell morphology using relatively small amounts of data and training time, eliminating the need of using multiple labels in immunofluorescence experiments. With further training, the algorithm is expected to predict different labels (e.g., focal-adhesion sites, cytoskeleton), which can be added to the automatic machine learning pipeline for direct input into Principal Component Analysis (PCA) for generation of virtual-cell mechanical models.

Keywords: cell morphology prediction, computational machine learning, fluorescence microscopy, virtual-cell models

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Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

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Authors: Benjaporn Buranrat, Nootchanat Mairuae

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Cratoxylum formosum (Jack) Dyer (CF) has been used for the traditional medicines in South East Asian and Thailand. Normally, northeast Thai vegetables have proven cytotoxic to many cancer cells. Therefore, the present study aims to explore the molecular mechanisms underlying CF-induced cancer cell death and apoptosis on breast and liver cancer cells. The cytotoxicity and antiproliferative effects of CF on the human breast MCF-7 and liver HepG2 cancer cell lines were evaluated using sulforhodamine B assay and colony formation assay. Cell migration assay was measured using wound healing assay. The apoptosis induction mechanisms were investigated through reactive oxygen species formation, caspase 3 activity, and JC-1 activity. Gene expression by real-time PCR and apoptosis related protein levels by Western blot analysis. CF induced MCF-7 and HepG2 cell death by time- and dose-dependent manner. Furthermore, CF had the greater cytotoxic potency on MCF-7 more than HepG2 cells with IC50 values of 85.70+4.52 μM and 219.03±9.96 μM respectively, at 24 h. Treatment with CF also caused a dose-dependent decrease in colony forming ability and cell migration, especially on MCF-7 cells. CF induced ROS formation, increased caspase 3 activities, and decreased the mitochondrial membrane potential, and causing apoptotic body production and DNA fragmentation. CF significantly decreased expression of the cell cycle regulatory protein RAC1 and downstream proteins, cdk6. Additionally, CF enhanced p21 and reduced cyclin D1 protein levels. CF leaf extract induced cell death, apoptosis, antimigration in both of MCF-7 and HepG2 cells. CF could be useful for developing to anticancer drug candidate for breast and liver cancer therapy.

Keywords: cratoxylum formosum (jack) dyer, breast cancer, liver cancer, cell death

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Authors: Wedad Azhar

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Vitamin D is an essential fat-soluble vitamin that is required for the maintenance of good health. It is obtained either through exposure to sunlight (ultraviolet B radiation) or through dietary sources. The role of vitamin D is beyond bone health. Indeed, it plays a critical role in the immune system and a broad range of organ functions such as the cardiovascular system. Moreover, vitamin D plays a critical role in the endothelial function, which is one of the main indicators of atherosclerosis. This study is investigating the correlation between vitamin D status and endothelial function in preventing and treating atherosclerosis especially in country that has ample of sunshine but yet, Saudis from suffering from this issue vitamin D deficiency and insufficiency. Ninety participants from both genders and aged 40 to 60will be involved. The participants will be categorised into three groups: the control group will be healthy persons, patients at risk of developing atherosclerosis, patients formally diagnosed atherosclerosis. Half of the participants in each group should already have been taking vitamin D supplementations. Fasting blood samples will be taken from the participants for biochemical assays. Endothelial function will be assist by flow-mediated dilation of the brachial artery. Participants will be asked to complete a questionnaire on their social and economic status, education level, daily exposure to sunlight, smoking status, consumption of supplements and medication, and a food frequency of vitamin D intake. The data will be analysed using SPSS.

Keywords: atherosclerosis, endothelial function, nutrition, vitamin D

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Authors: Kejal Joshi Reddy, Sirimavo Nair

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Micronutrient malnutrition affects pregnant women and children extremely with reference to growth manifestations in gestation as well as after birth. Early fetal development affected by iodine and iron deficiency leads to poor life quality. Various researchers have found interesting interrelations between iron and iodine. A few studies on impact assessment of DFS supplementation during pregnancy have been reported in India. Aim To provide meaningful contribution by assessing the efficacy of DFS supplementation on iodine and iron status of pregnant women. Design An interventional study. Setting A semi government hospital of urban Vadodara. Subjects Pregnant women (n=150) enrolled during first trimester (< 12 weeks) and followed up till the end of gestation, n=75 were divided in experimental (DFS supplemented) and control (Non supplemented) group. Results Impact on iron and iodine status was assessed by Hb concentration and UIE respectively. Mean Hb improved significantly (p < 0.001) (+0.42 g/dl) in experimental group and reduced non significantly (-0.20 g/dl) in control group at the end, since DFS provided additional 93 mg of iron within 6 months. Median UIE improved non significantly (278.6 to 299.01µg/L) in experimental group and decreased significantly (p < 0.05) (376.59 to 288.66 µg/L) in control group. Conclusion DFS could improve iron and iodine status of experimental group compared to control group. It is an effective measure to control two essential micronutrient deficiencies together.

Keywords: DFS supplementation, anemia, pregnancy, iodine deficiency, iron

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Authors: Jinyoung Park, Eun Joo Song

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Introduction: Deubiquitinating enzymes (DUBs) are proteases that cleave ubiquitin or ubiquitin-like modifications on substrates. Deubiquitination could regulate cellular physiology, such as signal transduction, DNA damage and repair, and cell cycle progression. Although more than 100 DUBs are encoded in the human and the importance of DUBs has been realized, the functions of most DUBs are unknown. This study aims to identify the molecular mechanism by which deubiquitinating enzyme USP35 regulates cell cycle progression for the first time. Methods: USP35 RNAi was mainly used to identify the function of USP35 in cell cycle progression. To find substrates of USP35, we analyzed protein-protein interaction using LC-MS. Several biological methods, such as ubiquitination assay, cell synchronization, immunofluorescence, and immunoprecipitation assay were used to investigate the exact mechanism by which USP35 affects successful completion of mitosis. Results: USP35 knockdown caused not only reduction of mitotic cell number but also induction of mitotic cells with abnormal spindle formation. Actually, cell proliferation was decreased by USP35 knockdown. Interestingly, we found that loss of USP35 decreased the stability and expression of Aurora B, a member of chromosomal passenger complex (CPC), and the phosphorylation of its substrate. Indeed, USP35 interacted with Aurora B and deubiquitinated it. In addition, USP35 knockdown induced abnormal localization of Aurora B in mitotic cells. Finally, CDH1-mediated ubiquitination of Aurora B level was rescued by USP35 overexpression, but not inactive form of USP35, USP35 C450A. Discussion: Our findings suggest that USP35 regulates Aurora B-mediated mitotic spindle assembly and G2-M transition by blocking CDH1-induced degradation of Aurora B.

Keywords: USP35, HSP90, Aurora B, cell cycle progression

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Authors: Joshua Teo, Leo Phan

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Signet cell carcinoma of the appendix is the rarest and the most aggressive subtype of appendiceal malignancy, typically with non-specific presentations. We describe a case of a 62-year-old male with large bowel obstruction and CT demonstrating dilated large bowels from caecum to proximal sigmoid colon with pneumoperitoneum. Intra-operatively, closed-loop obstruction caused by dense adherence of sigmoid colon to caecum was noted, which had resulted in caecal perforation. Histopathology study indicated primary appendiceal malignancy of signet cell morphology with intra-peritoneal spread to the sigmoid colon. Large bowel obstruction from appendiceal malignancy has rarely been reported, and a similar presentation has not been described in the existing literature. When left-sided large bowel obstruction is suspected to be caused by a malignant stricture, it is essential to consider transperitoneal spread of appendiceal malignancy as potential aetiology, particularly in the elderly.

Keywords: appendiceal carcinoma, large bowel obstruction, signet ring cell cancer, caecal perforation

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Authors: Sadık Ata, Kevser Dincer

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In this study, the performance of proton exchange membrane (PEM) fuel cell was experimentally investigated and modelled with Rule-Based Mamdani-Type Fuzzy (RBMTF) modelling technique. Coating on the anode side of the PEM fuel cell was accomplished with the spin method by using Yttria-stabilized zirconia (YSZ). Input-output parameters were described by RBMTF if-then rules. Numerical parameters of input and output variables were fuzzificated as linguistic variables: Very Very Low (L1), Very Low (L2), Low (L3), Negative Medium (L4), Medium (L5), Positive Medium (L6),High (L7), Very High (L8) and Very Very High (L9) linguistic classes. The comparison between experimental data and RBMTF is done by using statistical methods like absolute fraction of variance (R2). The actual values and RBMTF results indicated that RBMTF can be successfully used for the analysis of performance PEM fuel cell.

Keywords: proton exchange membrane (PEM), fuel cell, rule-based mamdani-type fuzzy (RMBTF) modelling, Yttria-stabilized zirconia (YSZ)

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Authors: Kwangho Lee, Joongmyeon Bae

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Fuel cells are spotlighted in the world for being highly efficient and environmentally friendly. A hydrogen fuel for a fuel cell is obtained from a number of sources. Most of fuel cell for APU(Auxiliary power unit) system using diesel fuel as a hydrogen source. Diesel fuel has many advantages, such as high hydrogen storage density, easy to transport and also well-infra structure. However, conventional diesel reforming system for PEMFC(Proton exchange membrane fuel cell) requires a large volume and complex CO removal system for the lower the CO level to less than 10ppm. In addition, the PROX(Preferential Oxidation) reaction cooling load is needed because of the strong exothermic reaction. However, the hydrogen separation membrane that we propose can be eliminated many disadvantages, because the volume is small and permeates only pure hydrogen. In this study, we were conducted to the pressurized diesel reforming and water-gas shift reaction experiment for the hydrogen permeable membrane application.

Keywords: hydrogen, diesel, reforming, ATR, WGS, PROX, membrane, pressure

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Authors: Liza Meutia Sari, Gus Permana Subita, Elza Ibrahim Auerkari

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Background: Many herbs have been discovered to be potential sources of anticancer drugs. Biji Pinang or areca nut (Areca catechu Linn.) has a high content of phenolics and flavonoids, and which is related to antioxidant activity. However, data on its effects on oral squamous cell carcinoma is not available. Objectives: Identification of the cytotoxicity and apoptosis activity in HSC-2 and HSC-3. Methods: The areca nut was extracted by ethanol 96%, MTS assay and apoptosis activity with flow cytometry. Results: The extract of areca nut showed higher toxicity on HSC-3 cell compared to HSC-2. The IC₅₀ of HSC-3 was 164.06 μg/ml vs. 629.50 μg/ml in HSC-2. There was an increase in late apoptosis percentage after 24 and 48 hours in HSC-2. There was a significant increase in early apoptosis percentage after 24 hours and late in 48 hours in HSC-3. Conclusion: The antioxidant activity of the extract of areca nut might be associated with the selective cytotoxicity on HSC-2 and HSC-3. Apoptosis is the major cell death mechanism involved. The areca nut may play an important role in anticancer herb medicine.

Keywords: areca nut, cytotoxicity, apoptosis, oral carcinoma

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Authors: Adenike Boyo Olasunkanmi Kesinro, Henry Boyo, Surukite Oluwole

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Utilizing solar energy in producing electricity can minimize environmental pollution generated by fossil fuel in producing electricity. Our research was base on the extraction of dye from Roystonea regia fruit by using methanol as solvent. The dye extracts were used as sensitizers in Dye-sensitized solar cell (DSSCs). Study was done on the electrical properties from the extracts of Roystonea regia fruit as Dye-sensitized solar cell (DSSCs). The absorptions of the extracts and extracts with dye were determined at different wavelengths (350-1000nm). Absorption peak was observed at 1.339 at wavelength 400nm. The obtained values for methanol extract Roystonea regia extract are, Imp = 0.015mA, Vmp = 12.0mV, fill factor = 0.763, Isc= 0.018 mA and Voc = 13.1 mV and efficiency of 0.32%. .The phytochemical screening was taken and it was observed that Roystonea regia extract contained less of anthocyanin compared to flavonoids. The nanostructured dye sensitized solar cell (DSSC) will provide economically credible alternative to present day silicon p–n junction photovoltaic.

Keywords: methanol, ethanol, titanium dioxide, roystonea regia fruit, dye-sensitized solar cell

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: Lan Cheng, Harry Qin, Yang Wang

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Background: COVID-19 has induced the largest digital learning experiment in history. There is also emerging research evidence that students have paid a high cost of learning loss from virtual learning. University-wide survey results demonstrate that digital learning remains difficult for students who struggle with learning challenges, isolation, or a lack of resources. Large-scale efforts are therefore increasingly utilized for digital education. To better prepare students in higher education for this grand scientific and technological transformation, STEM education has been prioritized and promoted as a strategic imperative in the ongoing curriculum reform essential for unfinished learning needs and whole-person development. Building upon five key elements identified in the STEM education literature: Problem-based Learning, Community and Belonging, Technology Skills, Personalization of Learning, Connection to the External Community, this case study explores the potential of pedagogical innovation that integrates computational and experimental methodologies to support, enrich, and navigate STEM education. Objectives: The goal of this case study is to create a high-fidelity prototype design for STEM education with knowledge transfer technology that contains a Cooperative Multi-Agent System (CMAS), which has the objectives of (1) conduct assessment to reveal a virtual learning mechanism and establish strategies to facilitate scientific learning engagement, accessibility, and connection within and beyond university setting, (2) explore and validate an interactional co-creation approach embedded in project-based learning activities under the STEM learning context, which is being transformed by both digital technology and student behavior change,(3) formulate and implement the STEM-oriented campaign to guide learning network mapping, mitigate the loss of learning, enhance the learning experience, scale-up inclusive participation. Methods: This study applied a case study strategy and a methodology informed by Social Network Analysis Theory within a cross-disciplinary communication paradigm (students, peers, educators). Knowledge transfer technology is introduced to address learning challenges and to increase the efficiency of Reinforcement Learning (RL) algorithms. A co-creation learning framework was identified and investigated in a context-specific way with a learning analytic tool designed in this study. Findings: The result shows that (1) CMAS-empowered learning support reduced students’ confusion, difficulties, and gaps during problem-solving scenarios while increasing learner capacity empowerment, (2) The co-creation learning phenomenon have examined through the lens of the campaign and reveals that an interactive virtual learning environment fosters students to navigate scientific challenge independently and collaboratively, (3) The deliverables brought from the STEM educational campaign provide a methodological framework both within the context of the curriculum design and external community engagement application. Conclusion: This study brings a holistic and coherent pedagogy to cultivates students’ interest in STEM and develop them a knowledge base to integrate and apply knowledge across different STEM disciplines. Through the co-designing and cross-disciplinary educational content and campaign promotion, findings suggest factors to empower evidence-based learning practice while also piloting and tracking the impact of the scholastic value of co-creation under the dynamic learning environment. The data nested under the knowledge transfer technology situates learners’ scientific journey and could pave the way for theoretical advancement and broader scientific enervators within larger datasets, projects, and communities.

Keywords: co-creation, cross-disciplinary, knowledge transfer, STEM education, social network analysis

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Authors: Matthew F. Gibson, Narasimha D. Rao, Raphael B. Slade, Joana Portugal Pereira, Joeri Rogelj

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Globally, India’s population is among the most severely impacted by nutrient deficiency, yet millions of tonnes of food are lost before reaching consumers. Across food groups, grains represent the largest share of daily calories and overall losses by mass in India. If current losses remain unresolved and follow projected population rates, we estimate, by 2030, losses from grains for human consumption could increase by 1.3-1.8 million tonnes (Mt) per year against current levels of ~10 Mt per year. This study quantifies energy input to minimise storage losses across India, responsible for a quarter of grain supply chain losses. In doing so, we identify and explore a Sustainable Development Goal (SDG) triplet between SDG₂, SDG₇, and SDG₁₂ and provide insight for development of joined up agriculture and health policy in the country. Analyzing rice, wheat, maize, bajra, and sorghum, we quantify one route to reduce losses in supply chains, by modelling the energy input to maintain favorable climatic conditions in modern silo storage. We quantify key nutrients (calories, protein, zinc, iron, vitamin A) contained within these losses and calculate roughly how much deficiency in these dietary components could be reduced if grain losses were eliminated. Our modelling indicates, with appropriate uncertainty, maize has the highest energy input intensity for storage, at 110 kWh per tonne of grain (kWh/t), and wheat the lowest (72 kWh/t). This energy trade-off represents 8%-16% of the energy input required in grain production. We estimate if grain losses across the supply chain were saved and targeted to India’s nutritionally deficient population, average protein deficiency could reduce by 46%, calorie by 27%, zinc by 26%, and iron by 11%. This study offers insight for development of Indian agriculture, food, and health policy by first quantifying and then presenting benefits and trade-offs of tackling food grain losses.

Keywords: energy, food loss, grain storage, hunger, India, sustainable development goal, SDG

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Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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Authors: Helan Satish, M. Ramasubba Reddy

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The simulation of an endocardial cell for gene mutation in the cardiac sodium ion channel NaV1.5, encoded by SCN5A gene, is discussed. The characterization of Brugada Syndrome by loss of function effect on SCN5A mutation due to L812Q mutant present in the DII-S4 transmembrane region of the NaV1.5 channel protein and its effect in an endocardial cell is studied. Ten Tusscher model of human ventricular action potential is modified to incorporate the changes contributed by L812Q mutant in the endocardial cells. Results show that BrS-associated SCN5A mutation causes reduction in the inward sodium current by modifications in the channel gating dynamics such as delayed activation, enhanced inactivation, and slowed recovery from inactivation in the endocardial cell. A decrease in the inward sodium current was also observed, which affects depolarization phase (Phase 0) that leads to reduction in the spike amplitude of the cardiac action potential.

Keywords: SCN5A gene mutation, sodium channel, Brugada syndrome, cardiac arrhythmia, action potential

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Authors: Aminu Muhammad, Mustapha Ya’u, Hasnah Mohd Sirat

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An investigation of the chemical constituents into the stem bark of Ficus platyphylla (Moraceae) has resulted in the isolation of hordenine, epicatechin, lupeol, lupeol acetate and α-amyrin acetate. Their structures were determined using spectroscopic data as well as comparison with literature data. The antibacterial assay has been tested against Gram positive and Gram negative bacteria, while the tyrosinase inhibition assay was examined using L-Dopa as a substrate of mushroom tyrosinase enzyme. hordenine, epicatechin, lupeol, lupeol acetate and α-amyrin acetate showed minimum inhibition concentration (MIC) values in the range of 225-900 µg/mL against the bacterial strains. Lupeol, lupeol acetate and α-amyrin acetate showed significant antityrosinase activity against mushroom tyrosinase enzyme with percent inhibition of 67.7%, 66.2% and 62.2%, respectively.

Keywords: antibacterial, antityrosinase, chemical constituents, Ficus platyphylla

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Authors: Melissa Chavez Portillo, Mauricio Pacio Castillo, Hector Juarez Santiesteban, Oscar Portillo Moreno

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Chemical bath deposited PbS:Bi3+ as an electron collection layer is introduced between the silicon wafer and the Ag electrode the performance of the PbS heterojunction thin film solar thin film solar cells with 1 cm2 active area. We employed Bi-doping to transform it into an n-type semiconductor. The experimental results reveal that the cell response parameters depend critically on the deposition procedures in terms of bath temperature, deposition time. The device achieves an open-circuit voltage of 0.4 V. The simple and low-cost deposition method of PbS:Bi3+ films is promising for the fabrication.

Keywords: Bi doping, PbS, thin films, solar cell

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Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Yung-Gi Chen, Pei-Leun Kang, Yu-Hsin Lin, Shwu-Jen Chang

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Myocardial tissue has limited self-repair ability due to its loss of differentiation characteristic for most mature cardiomyocytes. Therefore, the effective use of stem cell technology in regenerative medicine is an important development to alleviate the current difficulties in cardiac disease treatment. The main purpose of this project was to develop a 3-D hydrogel electrical stimulating system for promoting the differentiation of stem cells into myocardial cells, and the patch will be used to repair damaged myocardial tissue. This project was focused on the preparation of the electrical stimulation system with carbon/CaCl₂ electrodes covered with carbon nanotube-hydrogel. In this study, we utilized screen imprinting techniques and used Poly(lactic-co-glycolic acid)(PLGA) membranes as printing substrates to fabricate a carbon/CaCl₂ interdigitated electrode that covered with alginate/carbon nanotube hydrogels. The single-walled carbon nanotube was added in the hydrogel to enhance the mechanical strength and conductivity of hydrogel. In this study, we used PLGA (85:15) as electrode preparing substrate. The CaCl₂/ EtOH solution (80% w/v) was mixed into carbon paste to prepare various concentration calcium-containing carbon paste (2.5%, 5%, 7.5%, 10% v/v). Different concentrations of alginate (1%, 1.5%, 2% v/v) and SWCNT(Diameter < 2nm, length between 5-15μm) (1, 1.5, 3 mg/ml) are gently immobilized on the electrode by cross-linking with calcium chloride. The three-dimensional hydrogel electrode was tested for its redox efficiency by cyclic voltammetry to determine the optimal parameters for the hydrogel electrode preparation. From the result of the final electrodes, it indicated that the electrode was not easy to maintain the pattern of the interdigitated electrode when the concentration of calcium of chloride was more than 10%. According to the gel rate test and cyclic voltammetry experiment results showed the SWCNT could increase the electron conduction of hydrogel electrodes significantly. So far the 3D electrode system has been completed, 2% alginate mixed with 3mg SWCNT is the optimal condition to construct the most complete structure for the hydrogel preparation.

Keywords: myocardial tissue engineering, screen printing technology, poly (lactic-co-glycolic acid), alginate, single walled carbon nanotube

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Authors: Eric Bang

Abstract:

Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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Authors: Zuzana Poborilova, Anna B. Ohlsson, Torkel Berglund, Anna Vildova, Petr Babula

Abstract:

Lawsone is a pigment that occurs naturally in plants. It has been used as a skin and hair dye for a long time. Moreover, its different biological activities have been reported. The present study focused on the effect of lawsone on a plant cell model represented by tobacco BY-2 cell suspension culture, which is used as a model comparable with the HeLa cells. It has been shown that lawsone inhibits the cell growth in the concentration-dependent manner. In addition, changes in DNA methylation level have been determined. We observed decreasing level of DNA methylation in the presence of increasing concentrations of lawsone. These results were accompanied with overproduction of reactive oxygen species (ROS). Since epigenetic modifications can be caused by different stress factors, there could be a connection between the changes in the level of DNA methylation and ROS production caused by lawsone.

Keywords: DNA methylation, lawsone, naphthoquinone, reactive oxygen species

Procedia PDF Downloads 421

Authors: M. Javadzadeh, H. Khoshsima

Abstract:

In this article, we present a layout printing way for producing Fresnel zone on 1294-1b doped liquid crystal with Methyl-Red azo dye. We made a Fresnel zone mask with 25 zones and radius of 5 mm using lithography technique. With layout printing way, we recorded mask’s pattern on cell with λ=532 nm solid-state diode pump laser. By recording Fresnel zone pattern on cell and making Fresnel pattern on the surface of cell, odd and even zones, will form. The printed pattern, because of Azo dye’s photoisomerization, was permanent. Experimentally, we saw focal length tunability from 32 cm to 43 cm.

Keywords: liquid crystal, lens, Fresnel zone, diffraction, Fresnel lens

Procedia PDF Downloads 199

Authors: Rajesh P.P., Md. Tabish Noori, Makarand M. Ghangrekar

Abstract:

Methanogenic substrate loss is reported to be a major bottleneck in microbial fuel cell which significantly reduces the power production capacity and coulombic efficiency (CE) of microbial fuel cell (MFC). Nitroethane is found to be a potent inhibitor of hydrogenotrophic methanogens in rumen fermentation process. Influence of nitroethane pre-treated sewage sludge inoculum on suppressing the methanogenic activity and enhancing the electrogenesis in MFC was evaluated. MFC inoculated with nitroethane pre-treated anodic inoculum demonstrated a maximum operating voltage of 541 mV, with coulombic efficiency and sustainable volumetric power density of 39.85 % and 14.63 W/m3 respectively. Linear sweep voltammetry indicated a higher electron discharge on the anode surface due to enhancement of electrogenic activity while suppressing methanogenic activity. A 63 % reduction in specific methanogenic activity was observed in anaerobic sludge pre-treated with nitroethane; emphasizing significance of this pretreatment for suppressing methanogenesis and its utility for enhancing electricity generation in MFC.

Keywords: coulombic efficiency, methanogenesis inhibition, microbial fuel cell, nitroethane

Procedia PDF Downloads 311

Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

Abstract:

Background: It is clearly that phytochemical constituents of plants in relation exhibit free radical scavenging, antioxidant and glycosylation properties. This study investigated the in vitro antioxidant and free radical scavenging, inhibited activities against α-amylase and invertase enzymes of stem bark extracts C. edulis (Olacaceae). Methods: Four extracts (hexane, dichloromethane, ethanol and aqueous) from the barks of C. edulis were used in this study. Colorimetric in vitro methods were using for evaluate free radical scavenging activity DPPH, ABTS, NO, OH, antioxidant capacity, glycosylation activity, inhibition of α-amylase and invertase activities, phenolic, flavonoid and alkaloid contents. Results: C. edulis extracts (CEE) had a higher scavenging potential on the 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), nitrite oxide (NO), 2, 2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals and glucose scavenging with the IC50 varied between 41.95 and 36694.43 µg/ml depending on the solvent of extraction. The ethanol extract of C. edulis stem bark (CE EtOH) showed the highest polyphenolic (289.10 + 30.32), flavonoid (1.12 + 0.09) and alkaloids (18.47 + 0.16) content. All the tested extracts demonstrated a relative high inhibition potential against α-amylase and invertase digestive enzymes activities. Conclusion: This study suggests that CEE exhibited higher antioxidant potential and significant inhibition potential against digestive enzymes.

Keywords: Coula edulis, antioxidant, scavenging activity, amylase, invertase

Procedia PDF Downloads 344

Authors: Omar M. Al Aufi, Abdulwahab Noorwali, Ahmed Al Abd, Safia Alattas, Fathya Zahran, Fahd Almutairi

Abstract:

Cisplatin (CDDP) is a potent anticancer agent used for several tumor types. Thymoquinone (TQ) is a naturally occurring compound drawing great attention as an anticancer and chemomodulator for chemotherapies. Herein, we studied the potential cytotoxicity of thymoquinone, CDDP and their combination against human oral squamous cell carcinoma cells in contrast to normal oral epithelial cells. CDDP similarly killed both head and neck squamous cell carcinoma cells (UMSCC-14C) and normal oral epithelial cells (OEC). TQ alone exerted considerable cytotoxicity against UMSCC-14C cells, while it induced a weaker killing effect against normal oral epithelial cells (OEC). The equitoxic combination of TQ and CDDP showed additive to synergistic interaction against both UMSCC-14C and OEC cells. TQ alone increased apoptotic cell fraction in UMSCC-14C cells as early as after 6 hours. In addition, prolonged exposure of UMSCC-14C to TQ alone resulted in 96.7±1.6% total apoptosis, which was increased after combination with CDDP to 99.3±1.2% in UMSCC-14C cells. On the other hand, TQ induced a marginal increase in the apoptosis in OEC and even decreased the apoptosis induced by CDDP alone. Finally, apoptosis induction results were confirmed by the change in the expression levels of p53, Bcl-2 and Caspase-9 proteins in both UMSCC-14c and OEC cells.

Keywords: thymoquinone, cisplatin, apoptosis, oral squamous cell carcinoma, P53, Caspase-9, Bcl-2

Procedia PDF Downloads 55

Authors: Mahmoud Fouad, Mervat Badr, Marwa Ibrahim

Abstract:

Micro-grid system is presently considered a reliable solution for the expected deficiency in the power required from future power systems. Renewable power sources such as wind, solar and hydro offer high potential of benign power for future micro-grid systems. Micro-Grid (MG) is basically a low voltage (LV) or medium voltage (MV) distribution network which consists of a number of called distributed generators (DG’s); micro-sources such as photovoltaic array, fuel cell, wind turbine etc. energy storage systems and loads; operating as a single controllable system, that could be operated in both grid-connected and islanded mode. The capacity of the DG’s is sufficient to support all; or most, of the load connected to the micro-grid. This paper presents a micro-grid system based on wind and solar power sources and addresses issues related to operation, control, and stability of the system. Using Matlab/Simulink, the system is modeled and simulated to identify the relevant technical issues involved in the operation of a micro-grid system based on renewable power generation units.

Keywords: micro-grid system, photovoltaic, wind turbine, energy storage, distributed generation, modeling

Procedia PDF Downloads 425