Search results for: Paraptosis-like program cell death

Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

Abstract:

Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

Procedia PDF Downloads 120

Authors: Şule Yanık, Emel Ertürk-Mustul, Zerrin Turan, Hasan Gürgür

Abstract:

It is known that there are policies that will support the early special education (ESE) for children requiring special care including the children with hearing loss (CHL) in many countries that give importance to early childhood (0-6 years) education, accordingly ESE services have been gradually increasing and these services provide positive contributions to the child and family. These services begin with medical diagnostics, provision of the use of assistive technologies for hearing and the orientation of children towards early education program (EEP) for the CHL. In 0-3 years of age EEP, education and support services are provided to the children and their families. In 3-6 years of age, children are supported in a pre-school education program (PSE) in which their peers and teachers are present. Therefore, the children with hearing loss and their families are going through a series of medical, educational and social transition process after diagnosed with hearing loss. Depending on their age and development, CHL also go through a transition period from hospital to home, from home to EEP and from EEP to PSE. It is seen that there is no legal regulation regarding the transition process in Turkey and hence different processes have been carried out in the transition process from EEP to PSE. The aim of this study is to reveal the problems confronted by the CHL during the transition period from EEP to PSE and the solution proposals for these problems. In this study, a document review was made by reviewing the national and international studies about transition processes of the CHL in Turkey from EEP to PSE. Accordingly, in the study carried out in two stages, firstly, a review of the body of literature was performed by creating key words related to the subject. Secondly, the problems confronted by the CHL in Turkey during the transition period from EEP to PSE and the solution proposals for these problems were demonstrated by analyzing the obtained data. According to the body of literature, it is seen that there are no laws concerning the transition processes of the children who require special care including the CHL in Turkey from EEP (sending) to PSE (receiving), and correspondingly numerous problems have been experienced during the transition period. It seems that the EEP adopts family-centered approaches for strengthening the families of the CHL. However, PSE program aims to prepare the children to school life by focusing on their social and academical development rather with the adoption of children-centered approaches. Therefore, while the families feel an inseparable part of the team in EEP, they indicated that they felt like a stranger in the school team after their children have started to PSE. Therefore, families find the transition processes worrisome and state that they are not satisfied with the process. We discovered that in the process of transition from EEP to PSE, families are not informed, there is a limited number of PSE options available, children cannot adapt to the new educational environment and cannot benefit from the existing PSE.

Keywords: early education program, early special education, children with hearing loss, transition

Procedia PDF Downloads 135

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

Abstract:

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

Procedia PDF Downloads 210

Authors: Shuaa A. Mutawally, Budor H. Saigh, Ebtehal A. Mutawally

Abstract:

This study aims to analyze and compare the success factors of play-based intervention programs for children with different abilities in Canada. Children with disabilities often face limited participation in play and physical activities, leading to increased health risks. Understanding the specific features of these interventions that contribute to positive outcomes is crucial to promoting holistic development in these children. A comparative case study approach was used, selecting three similar successful intervention programs through purposive sampling. Data were collected through interviews and program documents, with 40 participants purposively chosen. Thematic analysis was conducted to identify key themes, including Quality Program, Meeting the Needs of Participants, and Lessons Learned from Experts and Practitioners. These programs play a vital role in addressing the gap in community programming for children with different abilities. The results of this study contribute to the generalization of success factors derived from best practices in play-based intervention programs for children with different abilities.

Keywords: children with different abilities, physical activity, play, play-based intervention programs

Procedia PDF Downloads 68

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

Abstract:

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

Procedia PDF Downloads 65

Authors: Merry Meryam Martgrita, Marselina Irasonia Tan

Abstract:

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

Procedia PDF Downloads 279

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

Abstract:

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

Procedia PDF Downloads 128

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

Abstract:

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

Procedia PDF Downloads 307

Authors: O. Gsib, U. Peirera, C. Egles, S. A. Bencherif

Abstract:

In skin regenerative medicine, one of the critical issues is to produce a three-dimensional scaffold with optimized porosity for dermal fibroblast infiltration and neovascularization, which exhibits high mechanical properties and displays sufficient wound healing characteristics. In this study, we report on the synthesis and characterization of macroporous sequential interpenetrating polymer networks (IPNs) combining skin wound healing properties of fibrin with the excellent physical properties of polyethylene glycol (PEG). Fibrin fibers serve as a provisional biologically active network to promote cell adhesion and proliferation while PEG provides the mechanical stability to maintain the entire 3D construct. After having modified both PEG and Serum Albumin (used for promoting enzymatic degradability) by adding methacrylate residues (PEGDM and SAM, respectively), Fibrin/PEGDM-SAM sequential IPNs were synthesized as follows: Macroporous sponges were first produced from PEGDM-SAM hydrogels by a freeze-drying technique and then rehydrated by adding the fibrin precursors. Environmental Scanning Electron Microscopy (ESEM) and Confocal Laser Scanning Microscopy (CLSM) were used to characterize their microstructure. Human dermal fibroblasts were cultivated during one week in the constructs and different cell culture parameters (viability, morphology, proliferation) were evaluated. Subcutaneous implantations of the scaffolds were conducted on five-week old male nude mice to investigate their biocompatibility in vivo. We successfully synthesized interconnected and macroporous Fibrin/PEGDM-SAM sequential IPNs. The viability of primary dermal fibroblasts was well maintained (above 90%) after 2 days of culture. Cells were able to adhere, spread and proliferate in the scaffolds suggesting the suitable porosity and intrinsic biologic properties of the constructs. The fibrin network adopted a spider web shape that covered partially the pores allowing easier cell infiltration into the macroporous structure. To further characterize the in vitro cell behavior, cell proliferation (EdU incorporation, MTS assay) is being studied. Preliminary histological analysis of animal studies indicated the persistence of hydrogels even after one-month post implantation and confirmed the absence of inflammation response, good biocompatibility and biointegration of our scaffolds within the surrounding tissues. These results suggest that our Fibrin/PEGDM-SAM IPNs could be considered as potential candidates for dermis regenerative medicine. Histological analysis will be completed to further assess scaffold remodeling including de novo extracellular matrix protein synthesis and early stage angiogenesis analysis. Compression measurements will be conducted to investigate the mechanical properties.

Keywords: fibrin, hydrogels for dermal reconstruction, polyethylene glycol, semi-interpenetrating polymer network

Procedia PDF Downloads 231

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

Abstract:

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

Procedia PDF Downloads 254

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

Abstract:

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

Procedia PDF Downloads 454

Authors: Miguel A. Jimenez Barros, Elyn L. Solano Charris, Luis E. Ramirez, Lauren Castro Bolano, Carlos Torres Barreto, Juliana Morales Cubillo

Abstract:

This project sought to mitigate the high levels of water consumption in industrial processes in accordance with the water-rationing plan promoted at national and international level due to the water consumption projections published by the United Nations. Water consumption has three main uses, municipal (common use), agricultural and industrial where the latter consumes a minimum percentage (around 20% of the total consumption). Awareness on world water scarcity, a Colombian company responsible for generation of massive consumption products, decided to implement politics and techniques for water treatment, recycling, and reuse. The project consisted in a business technology program that permits a better use of wastewater caused by production operations. This approach reduces the potable water consumption, generates better conditions of water in the sewage dumps, generates a positive environmental impact for the region, and is a reference model in national and international levels. In order to achieve the objective, a process flow diagram was used in order to define the industrial processes that required potable water. This strategy allowed the industry to determine a water reuse plan at the operational level without affecting the requirements associated with the manufacturing process and even more, to support the activities developed in administrative buildings. Afterwards, the company made an evaluation and selection of the chemical and biological processes required for water reuse, in compliance with the Colombian Law. The implementation of the business technology program optimized the water use and recirculation rate up to 70%, accomplishing an important reduction of the regional environmental impact.

Keywords: bio-reactor, potable water, reverse osmosis, water treatment

Procedia PDF Downloads 230

Authors: Lindy Adoma Dampare, Marina Aferiba Tandoh

Abstract:

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

Procedia PDF Downloads 95

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

Abstract:

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

Procedia PDF Downloads 277

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

Abstract:

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

Procedia PDF Downloads 312

Authors: U.-B. Schaer, M. Wehr, R. Hodler

Abstract:

Background: Most nursing students require more training time for necessary nursing skills than defined by nursing schools curriculum to acquire basic nursing skills. Given skills training lessons are too brief to enable effective student learning, meaning in-depth skills practice and repetition various learning steps. This increases stress levels and the pressure to succeed for a nursing student with slower learning capabilities. Another possible consequence is that nursing students are less prepared in the required skills for future clinical practice. Intervention: The Bern College of Higher Education of Nursing, Switzerland, started the independent peer practice learning program in 2012. A concept was developed which defines specific aims and content as well as student’s rights and obligations. Students enlist beforehand and order the required materials. They organize themselves and train in small groups in allocated training location in the area of Learning Training and Transfer (LTT). During the peer practice, skills and knowledge can be repeatedly trained and reflected in the peer groups without the presence of a tutor. All invasive skills are practiced only on teaching dummies. This allows students to use all their potential. The students may access learning materials as literature and their own student notes. This allows nursing students to practice their skills and to deepen their knowledge on corresponding with their own learning rate. Results: Peer group discussions during the independent peer practice learning support the students in gaining certainty and confidence in their knowledge and skills. This may improve patient safety in future daily care practice. Descriptive statics show that the number of students who take advantage of the independent peer practice learning increased continuously (2012-2018). It has to be mentioned that in 2012, solely students of the first semester attended the independent peer practice learning program, while in 2018 over one-third of the participating students were in their fifth semester and final study year. It is clearly visible that the demand for independent peer practice learning is increasing. This has to be considered in the development of future teaching curricula.

Keywords: learning program, nursing students, peer learning, skill training

Procedia PDF Downloads 117

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

Abstract:

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

Procedia PDF Downloads 143

Authors: Piyawan Sunasuan, Thiranan Pansuppawat, Mananya Manaratchasak, Maream Nillapun

Abstract:

This research aims to guide the development of the intensive English program for graduate students. The objectives are 1) to study the English skills in which needed for the graduate students and 2) to study the potential of the current course with the expected proficiency level. The samples are 46 graduate students enrolled in the ENG 102 and ENG 103 courses of the school year of 2019/2020 in semester one from the Silpakorn University, Sanamchandra Palace Campus, and two teachers. The researchers use 1) student survey, 2) teacher interview, and 3) focus group discussion among selected students. The data is analyzed by calculating the mean (x̅), the standard deviation, and document analysis. The findings show that nine skills are in the need of the course development; 1) academic writing 2) occupational purpose writing 3) communicative reading 4) occupational purpose reading 5) academic speaking 6) occupational purpose speaking 7) occupational purpose listening 8) academic listening and 9) communicative listening. The current course does not meet the expectation on a high level but has potential.

Keywords: English for academic purposes, English for communication, English for occupational purposes, intensive English

Procedia PDF Downloads 143

Authors: Keerthi S. Shetty, Annappa Basava

Abstract:

In recent years, modelling of biological systems represented by biochemical reactions has become increasingly important in Systems Biology. Biological systems represented by biochemical reactions are highly stochastic in nature. Probabilistic model is often used to describe such systems. One of the main challenges in Systems biology is to combine absolute experimental data into probabilistic model. This challenge arises because (1) some molecules may be present in relatively small quantities, (2) there is a switching between individual elements present in the system, and (3) the process is inherently stochastic on the level at which observations are made. In this paper, we describe a novel idea of combining absolute experimental data into probabilistic model using tool R2. Through a case study of the Transcription Process in Prokaryotes we explain how biological systems can be written as probabilistic program to combine experimental data into the model. The model developed is then analysed in terms of intrinsic noise and exact sampling of switching times between individual elements in the system. We have mainly concentrated on inferring number of genes in ON and OFF states from experimental data.

Keywords: systems biology, probabilistic model, inference, biology, model

Procedia PDF Downloads 343

Authors: Ibrahim Alshalan

Abstract:

The Islamic Republic of Iran is one of the greatest and most powerful countries, not only in the Arabian Gulf but in the entire Middle East region. However, the Iranian regime, which came to power as a result of the 1979 revolution that resulted in overthrowing the Shah Mohammad Reza Pahlavi, has been the biggest source of threat to the stability of the Middle East since the revolution until this day. It has ambitions to dominate the neighboring Arab countries, especially Iraq, Syria, Lebanon, Yemen and Bahrain. Iran has bad relationships with countries of the Gulf Cooperation Council (GCC), which includes Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman and Bahrain. The main objective of this paper is to shed light on the deteriorating political relations between the Iranian regime on one hand and the GCC on the other, especially Saudi Arabia which is witnessing more challenges as a result of Iran's determination to develop its nuclear program. Another important objective of this paper is to identify the Iranian role in the creation of the hotbeds of conflict in addition to its responsibility for some of the region's problems. It also aims to answer the question; why does Iran insist on developing its controversial nuclear program?

Keywords: Iran, GCC, Gulf, Saudi Arabia

Procedia PDF Downloads 567

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

Abstract:

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

Procedia PDF Downloads 474

Authors: Caroline M. Spagnol, Vera L. B. Isaac, Marcos A. Corrêa, Hérida R. N. Salgado

Abstract:

Phenolic compounds are abundant in the Brazilian plant kingdom and they are part of a large and complex group of organic substances. Cinnamic acids are part of this group of organic compounds, and caffeic acid (CA) is one of its representatives. Antioxidants are compounds which act as free radical scavengers and, in other cases, such as metal chelators, both in the initiation stage and the propagation of oxidative process. The tyrosinase, polyphenol oxidase, is an enzyme that acts at various stages of melanin biosynthesis within the melanocytes and is considered a key molecule in this process. Some phenolic compounds exhibit inhibitory effects on melanogenesis by inhibiting the tyrosinase enzymatic activity and therefore has been the subject of studies. However, few studies have reported the effectiveness of these products and their safety. Objectives: To assess the inhibitory activity of tyrosinase, the antioxidant activity of CA and its cytotoxic potential. The method to evaluate the inhibitory activity of tyrosinase aims to assess the reduction transformation of L-dopa into dopaquinone reactions catalyzed by the enzyme. For evaluating the antioxidant activity was used the analytical methodology of DPPH radical inhibition. The cytotoxicity evaluation was carried out using the MTT method (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide), a colorimetric assay which determines the amount of insoluble violet crystals formed by the reduction of MTT in the mitochondria of living cells. Based on the results obtained during the study, CA has low activity as a depigmenting agent. However, it is a more potent antioxidant than ascorbic acid (AA), since a lower amount of CA is sufficient to inhibit 50% of DPPH radical. The results are promising since CA concentration that promoted 50% toxicity in HepG2 cells (IC50=781.8 μg/mL) is approximately 330 to 400 times greater than the concentration required to inhibit 50% of DPPH (IC50 DPPH= 2.39 μg/mL) and ABTS (IC50 ABTS= 1.96 μg/mL) radicals scavenging activity, respectively. The maximum concentration of caffeic acid tested (1140 mg /mL) did not reach 50% of cell death in HaCat cells. Thus, it was concluded that the caffeic acid does not cause toxicity in HepG2 and HaCat cells in the concentrations required to promote antioxidant activity in vitro, and it can be applied in topical products.

Keywords: caffeic acid, antioxidant, cytotoxicity, cosmetic

Procedia PDF Downloads 372

Authors: A. Alvaredo , R. Guzman De Villoria, P. Castell, Juan P. Fernandez-Blazquez

Abstract:

Since graphene was discovered in 2004, has been considered as superb material, due to its outstanding mechanical, electrical and thermal properties. Graphene has been incorporated as reinforcement in several high performance polymers in order to obtain a good balance of properties and to get new properties as thermal or electric conductivity. As well known, the properties of semicrystalline polymer and its composites depends heavily on degree of crystallinity. In this context, our research group has studied the crystallization behavior from amorphous state of PEEK/GNP composites. The monitoring of cold crystallization processes studied by time-resolved simultaneous wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS). These techniques allowed to get an extremely relevant information about the evolution of the morphology of the PEEK/GNP composites. In addition, the thermal evolution of cold crystallization was followed by differential scanning calorimetry (DSC) as well. The experimental results showed changes in crystallization kinetics and c parameter unit cell when adding graphene. The main aim of this work is to produce PEEK/GNP composites and characterize their morphology, unit cell parameters and crystallization kinetic.

Keywords: PEEK, graphene, synchrotron, cold crystallization

Procedia PDF Downloads 342

Authors: M. Fernanda Salgado, Alfonso Tierra, Wilbert Aguilar

Abstract:

The present project consists in applying the informed search algorithm A star (A*) to solve traveler problems, applying it by urban public transportation routes. The digitization of the information allowed to identify 26% of the total of routes that are registered within the Metropolitan District of Quito. For the validation of this information, data were taken in field on the travel times and the difference with respect to the times estimated by the program, resulting in that the difference between them was not greater than 2:20 minutes. We validate A* algorithm with the Dijkstra algorithm, comparing nodes vectors based on the public transport stops, the validation was established through the student t-test hypothesis. Then we verified that the times estimated by the program using the A* algorithm are similar to those registered on field. Furthermore, we review the performance of the algorithm generating iterations in both algorithms. Finally, with these iterations, a hypothesis test was carried out again with student t-test where it was concluded that the iterations of the base algorithm Dijsktra are greater than those generated by the algorithm A*.

Keywords: algorithm A*, graph, mobility, public transport, travel planning, routes

Procedia PDF Downloads 230

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

Abstract:

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

Procedia PDF Downloads 314

Authors: Odaleia de O. Farias, Suzelene C. Marinho, Ecleidson B. Fragoso, Daniel S. Lima, Francisco R. S. Lira, Lara S. Araújo, Gabriel dos S. D. Soares

Abstract:

In populous cities, prehospital care services that use vehicles alternative to ambulances are needed in order to reduce costs and improve response time to occurrences in areas with large concentration of people, such as leisure and tourism spaces. In this context, it was implanted a program called BIKE VIDA, that is innovative quick access and assistance program. The aim of this study is to describe the implantation and initial profile of occurrences performed by an urgency/emergency pre-hospital care service through paramedics on bicycles. It is a cross-sectional, descriptive study carried out in the city of Fortaleza, Ceara, Brazil. The data included service records from July to August 2017. Ethical aspects were respected. The service covers a perimeter of 4.5 km, divided into three areas with perimeter of 1.5 km for each paramedic, attending from 5 am to 9 pm. Materials transported by bicycles include External Automated Defibrillator - DEA, portable oxygen, oximeter, cervical collar, stethoscope, sphygmomanometer, dressing and immobilization materials and personal protective equipment. Occurrences are requested directly by calling the emergency number 192 or through direct approach to the professional. In the first month of the program, there were 93 emergencies/urgencies, mainly in the daytime period (71,0%), in males (59,7%), in the age range of 26 to 45 years (46,2%). The main nature was traumatic incidents (53.3%). Most of the cases (88,2%) did not require ambulance transport to the hospital, and there were two deaths. Pre-hospital service through bicycles is an innovative strategy in Brazil and has shown to be promising in terms of reducing costs and improving the quality of the services offered.

Keywords: emergency, response time, prehospital care, urgency

Procedia PDF Downloads 192

Authors: Uma U. Uma, Uzoechi Laz

Abstract:

Protection of equipment insulation against lightning over voltages and selection of lightning arrester that will discharge at lower voltage level than the voltage required to breakdown the electrical equipment insulation is examined. The objectives of this paper are to design a computer based model using standard equations for the selection of appropriate lightning arrester with the lowest rated surge arrester that will provide adequate protection of equipment insulation and equally have a satisfactory service life when connected to a specified line voltage in power system network. The effectiveness and non-effectiveness of the earthing system of substation determine arrester properties. MATLAB program with GUI (graphic user interphase) its subprogram is used in the development of the model for the determination of required parameters like voltage rating, impulse spark over voltage, power frequency spark over voltage, discharge current, current rating and protection level of lightning arrester of a specified voltage level of a particular line.

Keywords: lightning arrester, GUIs, MatLab program, computer based model

Procedia PDF Downloads 411

Authors: Edgar Ochoa, G. Torres-Villasenor

Abstract:

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

Procedia PDF Downloads 162

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

Abstract:

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

Procedia PDF Downloads 148

Authors: Sara Zadehomidi

Abstract:

Iran, a geographically arid and semi-arid country, experiences varying levels of rainfall across its territory. Five major and important rivers, namely Karun, Dez, Karkheh, Jarrahi, and Hendijan, are valuable assets of the Khuzestan province. To address various needs, including those of farmers (especially during hot seasons with no rainfall), drinking water requirements, industrial and environmental, and most importantly, electricity production, dams have been constructed on several of these rivers, with some dams still under construction. The outflow of water from dam reservoirs must be managed in a way that not only preserves the reservoir's potential effectively but also ensures the maximum revenue from electricity generation. Furthermore, it should meet the other mentioned requirements. In this study, scientific methods such as optimization using Lingo software were employed to achieve these objectives. The results, when executed and adhering to the proposed electricity production program with Lingo software, indicate a 35.7% increase in electricity sales revenue over a one-year examination period. Considering that several electricity plants are currently under construction, the importance and necessity of utilizing computer systems for expediting and optimizing the electricity generation program planning from electricity plants will become evident in the future.

Keywords: Ahvaz, electricity generation programs, Iran, optimizing

Procedia PDF Downloads 54