Search results for: alloy target
697 In vitro Modeling of Aniridia-Related Keratopathy by the Use of Crispr/Cas9 on Limbal Epithelial Cells and Rescue
Authors: Daniel Aberdam
Abstract:
Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy
Procedia PDF Downloads 207696 Evaluation of Important Transcription Factors and Kinases in Regulating the Signaling Pathways of Cancer Stem Cells With Low and High Proliferation Rate Derived From Colorectal Cancer
Authors: Mohammad Hossein Habibi, Atena Sadat Hosseini
Abstract:
Colorectal cancer is the third leading cause of cancer-related death in the world. Colorectal cancer screening, early detection, and treatment programs could benefit from the most up-to-date information on the disease's burden, given the present worldwide trend of increasing colorectal cancer incidence. Tumor recurrence and resistance are exacerbated by the presence of chemotherapy-resistant cancer stem cells that can generate rapidly proliferating tumor cells. In addition, tumor cells can evolve chemoresistance through adaptation mechanisms. In this work, we used in silico analysis to select suitable GEO datasets. In this study, we compared slow-growing cancer stem cells with high-growth colorectal cancer-derived cancer stem cells. We then evaluated the signal pathways, transcription factors, and kinases associated with these two types of cancer stem cells. A total of 980 upregulated genes and 870 downregulated genes were clustered. MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Fc gamma R-mediated phagocytosis, and Steroid biosynthesis signaling pathways were observed in upregulated genes. Also, caffeine metabolism, amino sugar and nucleotide sugar metabolism, TNF signaling pathway, and cytosolic DNA-sensing pathway were involved in downregulated genes. In the next step, we evaluated the best transcription factors and kinases in two types of cancer stem cells. In this regard, NR2F2, ZEB2, HEY1, and HDGF as transcription factors and PRDM5, SMAD, CBP, and KDM2B as critical kinases in upregulated genes. On the other hand, IRF1, SPDEF, NCOA1, and STAT1 transcription factors and CTNNB1 and CDH7 kinases were regulated low expression genes. Using bioinformatics analysis in the present study, we conducted an in-depth study of colorectal cancer stem cells at low and high growth rates so that we could take further steps to detect and even target these cells. Naturally, more additional tests are needed in this direction.Keywords: colorectal cancer, bioinformatics analysis, transcription factor, kinases, cancer stem cells
Procedia PDF Downloads 126695 Online Bakery Management System Proposal
Authors: Alexander Musyoki, Collins Odour
Abstract:
Over the past few years, the bakery industry in Kenya has experienced significant growth largely in part to the increased adoption of technology and automation in their processes; more specifically due to the adoption of bakery management systems to help in running bakeries. While they have been largely responsible for the improved productivity and efficiency in bakeries, most of them are now outdated and pose more challenges than benefits. The proposed online bakery management system mentioned in this paper aims to address this by allowing bakery owners to track inventory, budget, job progress, and data analytics on each job and in doing so, promote the Sustainable Development Goals 3 and 12, which aim to ensure healthy lives and promote sustainable economic growth as the proposed benefits of these features include scalability, easy accessibility, reduced acquisition costs, better reliability, and improved functionality that will allow bakeries to become more competitive, reduce waste and track inventory more efficiently. To better understand the challenges, a comprehensive study has been performed to assess these traditional systems and try to understand if an online bakery management system can prove to be advantageous to bakery owners. The study conducted gathered feedback from bakery owners and employees in Nairobi County, Kenya using an online survey with a response rate of about 86% from the target population. The responses cited complex and hard to use bakery management systems (59.7%), lack of portability from one device to the other (58.1%) and high acquisition costs (51.6%) as the top challenges of traditional bakery management systems. On the other hand, some of the top benefits that most of the respondents would realize from the online bakery management system was better reliability (58.1%) and reduced acquisition costs (58.1%). Overall, the findings suggest that an online bakery management system has a lot of advantages over traditional systems and is likely to be well-received in the market. In conclusion, the proposed online bakery management system has the potential to improve the efficiency and competitiveness of small-sized bakeries in Nairobi County. Further research is recommended to expand the sample size and diversity of respondents and to conduct more in-depth analyses of the data collected.Keywords: ICT, technology and automation, bakery management systems, food innovation
Procedia PDF Downloads 80694 Early Transcriptome Responses to Piscine orthoreovirus-1 in Atlantic salmon Erythrocytes Compared to Salmonid Kidney Cell Lines
Authors: Thomais Tsoulia, Arvind Y. M. Sundaram, Stine Braaen, Øyvind Haugland, Espen Rimstad, Øystein Wessel, Maria K. Dahle
Abstract:
Fish red blood cells (RBC) are nucleated, and in addition to their function in gas exchange, they have been characterized as mediators of immune responses. Salmonid RBC are the major target cells of Piscineorthoreovirus (PRV), a virus associated with heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. The activation of antiviral response genesin RBChas previously been described in ex vivo and in vivo PRV-infection models, but not explored in the initial virus encounter phase. In the present study, mRNA transcriptome responses were explored in erythrocytes from individual fish, kept ex vivo, and exposed to purified PRV for 24 hours. The responses were compared to responses in macrophage-like salmon head kidney (SHK-1) and endothelial-like Atlantic salmon kidney (ASK) cells, none of which support PRV replication. The comparative analysis showed that the antiviral response to PRV was strongest in the SHK-1 cells, with a set of 80 significantly induced genes (≥ 2-fold upregulation). In RBC, 46 genes were significantly upregulated, while ASK cells were not significantly responsive. In particular, the transcriptome analysis of RBC revealed that PRV significantly induced interferon regulatory factor 1 (IRF1) and interferon-induced protein with tetratricopeptide repeats 5-like (IFIT9). However, several interferon-regulated antiviral genes which have previously been reported upregulated in PRV infected RBC in vivo (myxovirus resistance (Mx), interferon-stimulated gene 15 (ISG15), toll-like receptor 3 (TLR3)), were not significantly induced after 24h of virus stimulation. In contrast to RBC, these antiviral response genes were significantly upregulated in SHK-1. These results confirm that RBC are involved in the innate immune response to viruses, but with a delayed antiviral response compared to SHK-1. A notable difference is that interferon regulatory factor 1 (IRF-1) is the most strongly induced gene in RBC, but not among the significantly induced genes in SHK-1. Putative differences in the binding, recognition, and response to PRV, and any link to effects on the ability of PRV to replicate remains to be explored.Keywords: antiviral responses, atlantic salmon, piscine orthoreovirus-1, red blood cells, RNA-seq
Procedia PDF Downloads 190693 Neuroprotective Effect of Vildagliptin against Cerebral Ischemia in Rats
Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam
Abstract:
The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin
Procedia PDF Downloads 156692 Open Fields' Dosimetric Verification for a Commercially-Used 3D Treatment Planning System
Authors: Nashaat A. Deiab, Aida Radwan, Mohamed Elnagdy, Mohamed S. Yahiya, Rasha Moustafa
Abstract:
This study is to evaluate and investigate the dosimetric performance of our institution's 3D treatment planning system, Elekta PrecisePLAN, for open 6MV fields including square, rectangular, variation in SSD, centrally blocked, missing tissue, square MLC and MLC shaped fields guided by the recommended QA tests prescribed in AAPM TG53, NCS report 15 test packages, IAEA TRS 430 and ESTRO booklet no.7. The study was performed for Elekta Precise linear accelerator designed for clinical range of 4, 6 and 15 MV photon beams with asymmetric jaws and fully integrated multileaf collimator that enables high conformance to target with sharp field edges. Seven different tests were done applied on solid water equivalent phantom along with 2D array dose detection system, the calculated doses using 3D treatment planning system PrecisePLAN, compared with measured doses to make sure that the dose calculations are accurate for open fields including square, rectangular, variation in SSD, centrally blocked, missing tissue, square MLC and MLC shaped fields. The QA results showed dosimetric accuracy of the TPS for open fields within the specified tolerance limits. However large square (25cm x 25cm) and rectangular fields (20cm x 5cm) some points were out of tolerance in penumbra region (11.38 % and 10.9 %, respectively). For the test of SSD variation, the large field resulted from SSD 125 cm for 10cm x 10cm filed the results recorded an error of 0.2% at the central axis and 1.01% in penumbra. The results yielded differences within the accepted tolerance level as recommended. Large fields showed variations in penumbra. These differences between dose values predicted by the TPS and the measured values at the same point may result from limitations of the dose calculation, uncertainties in the measurement procedure, or fluctuations in the output of the accelerator.Keywords: quality assurance, dose calculation, 3D treatment planning system, photon beam
Procedia PDF Downloads 517691 Effects of Kolavironon Liver Oxidative Stress and Beta-Cell Damage in Streptozotocin-Induced Diabetic Rats
Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju
Abstract:
The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis
Procedia PDF Downloads 387690 Nanopack: A Nanotechnology-Based Antimicrobial Packaging Solution for Extension of Shelf Life and Food Safety
Authors: Andy Sand, Naama Massad – Ivanir, Nadav Nitzan, Elisa Valderrama, Alfred Wegenberger, Koranit Shlosman, Rotem Shemesh, Ester Segal
Abstract:
Microbial spoilage of food products is of great concern in the food industry due to the direct impact on the shelf life of foods and the risk of foodborne illness. Therefore, food packaging may serve as a crucial contribution to keep the food fresh and suitable for consumption. Active packaging solutions that have the ability to inhibit the development of microorganism in food products attract a lot of interest, and many efforts have been made to engineer and assimilate such solutions on various food products. NanoPack is an EU-funded international project aiming to develop state-of-the-art antimicrobial packaging systems for perishable foods. The project is based on natural essential oils which possess significant antimicrobial activity against many bacteria, yeasts and molds. The essential oils are encapsulated in natural aluminosilicate clays, halloysite nanotubes (HNT's), that serves as a carrier for the volatile essential oils and enable their incorporation into polymer films. During the course of the project, several polyethylene films with diverse essential oils combinations were designed based on the characteristics of their target food products. The antimicrobial activity of the produced films was examined in vitro on a broad spectrum of microorganisms including gram-positive and gram-negative bacteria, aerobic and anaerobic bacteria, yeasts and molds. The films that showed promising in vitro results were successfully assimilated on in vivo active packaging of several food products such as cheese, bread, fruits and raw meat. The results of the in vivo analyses showed significant inhibition of the microbial spoilage, indicating the strong contribution of the NanoPack packaging solutions on the extension of shelf life and reduction of food waste caused by early spoilage throughout the supply chain.Keywords: food safety, food packaging, essential oils, nanotechnology
Procedia PDF Downloads 138689 Evaluating the Needs of PhD Students in Preparation of a Genre-Based English for Academic Purposes Course
Authors: Heba I. Bakry
Abstract:
Academic writing in the tertiary education has always been a challenge to EFL learners. This proposed study aims at investigating the academic English language needs for PhD students and candidates studying humanities and social sciences at Cairo University. The research problem arises from the fact that most of them study English as a Foreign Language (EFL) or for specific purposes (ESP) in their undergraduate years. They are hardly familiarized with the different academic genres, despite the fact that they use academic resources written in English, and they are required to publish a paper internationally. Upon understanding the conventions and constraints of academic writing, postgraduates will have the opportunity to interact with the international academic spheres conveniently. There is, thus, a need to be acquainted with the generally accepted features of the academic genres, such as academic papers and their part-genres, such as writing abstracts, in addition to other occluded genres, such as personal statements and recommendation letters. The lack of practicing many of these genres is caused by the fact that there are clear differences between the rhetoric and conventions of the students' native language, i.e., Arabic, and the target language they are learning in the academic context, i.e., English. Moreover, apart from the general culture represented ethno-linguistically, the learners' 'small' culture represented in a national setting like Cairo University is more defining than their general cultural affiliations that are associated with their nationality, race, or religion, for instance. The main research question of this proposed study is: What is the effect of teaching a genre-based EAP course on the research writing competence of PhD candidates? To reach an answer to this question, the study will attempt to answer the following sub-questions: 1. What are the Egyptian PhD candidates' EAP perceived needs? 2. What are the requisite academic research skills for Egyptian scholars? The study intends to assess the students’ needs, as a step to design and evaluate an EAP course that is based on explaining and scrutinizing a variety of academic genres. Adopting a diagnostic approach, the needs assessment uses quantitative data collected through questionnaires, and qualitative data assembled from semi-structured interviews with the students and their teachers, in addition to non-participant observations of a convenience sample.Keywords: course design, English for academic purposes, genre-based, needs assessment
Procedia PDF Downloads 244688 Malignant Ovarian Cancer Ascites Confers Platinum Chemoresistance to Ovarian Cancer Cells: A Combination Treatment with Crizotinib and 2 Hydroxyestradiol Restore Platinum Sensitivity
Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna
Abstract:
Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib
Procedia PDF Downloads 71687 Current Situation and Need in Learning Management for Developing the Analytical Thinking of Teachers in Basic Education of Thailand
Authors: S. Art-in
Abstract:
This research was a survey research. The objective of this study was to study current situation and need in learning management for developing the analytical thinking of teachers in basic education of Thailand. The target group consisted of 400 teachers teaching in basic education level. They were selected by multi-stage random sampling. The instrument used in this study was the questionnaire asking current situation and need in learning management for developing the analytical thinking, 5 level rating scale. Data were analyzed by calculating the frequency, mean, standard deviation, percentage and content analysis. The research found that: 1) For current situation, the teachers provided learning management for developing analytical thinking, in overall, in “high” level. The issue with lowest level of practice: the teachers had competency in designing and establishing the learning management plan for developing the students’ analytical thinking. Considering each aspect it was found that: 1.1) the teacher aspect; the issue with lowest level of practice was: the teachers had competency in designing and establishing the learning management plan for developing the students’ analytical thinking, and 1.2) the learning management aspect for developing the students’ analytical thinking, the issue with lowest level of practice was: the learning activities provided opportunity for students to evaluate their analytical thinking process in each learning session. 2) The teachers showed their need in learning management for developing the analytical thinking, in overall, in “the highest” level. The issue with highest level of the need was: to obtain knowledge and competency in model, technique, and method for learning management or steps of learning management for developing the students’ analytical thinking. Considering each aspect it was found that: 2.1) teacher aspect; the issue with highest level of the need was: to obtain knowledge and comprehension in model, technique, and method for learning management or steps of learning management for developing the students’ analytical thinking, and 2.2) learning management aspect for developing the analytical thinking, the issue with highest level of need consisted of the determination of learning activities as problem situation, and the opportunity for students to comprehend the problem situation as well as practice their analytical thinking in order to find the answer.Keywords: current situation and need, learning management, analytical thinking, teachers in basic education level, Thailand
Procedia PDF Downloads 352686 The Understanding of Biochemical and Molecular Analysis of Diabetic Rats Treated with Andrographis paniculata and Erythrina indica Methanol Extract
Authors: Chakrapani Pullagummi, Arun Jyothi Bheemagani, B. Chandra Sekhar Singh, Prem Kumar, A. Roja Rani
Abstract:
Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and its action. The objective of present study was alloxan induced diabetes in S.D (Sprague Dawley) rats, treated with leaf extract of Andrographis paniculata and bark extract of Erythrina indica. Plant extract treated rats were analyzed biochemically and molecularly. on normal and diabetic rats. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with methanolic extracts of Andrographis paniculata leaf and Erythrina indica bark which are of medicinal importance. Later after inducing diabetes the rats were treated with medicinal plant extracts, Andrographis paniculata leaf and Erythrina indica bark which are well known for their anti diabetic and antioxidative property in order to control the glucose and MDA levels. The blood plasma of diabetic and normal rats was analyzed for the levels of MDA (lipid peroxidation) and glucose levels. Results of this study suggested that the Andrographis paniculata leaf and Erythrina indica can be used as a potential natural antidiabetic agent for treating and postponing the appearance of complications that arise due to Diabetes. Molecular study deals with the analysis of binding mechanism of 2 selected natural compounds from Andrographis and Erythrina extracts against the novel target for type T2D namely PPAR-γ compared with Rosiglitazone (standard compound). The results revealed that most of the selected herbal lead compounds were effective targets against the receptors. These compounds showed favorable interactions with the amino acid residues thereby substantiating their proven efficacy as anti-diabetic compounds.Keywords: andrographis paniculata, erythrina indica, alloxan, lipid peroxidation, blood glucose level, PPAR-γ
Procedia PDF Downloads 477685 Identification of New Familial Breast Cancer Susceptibility Genes: Are We There Yet?
Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson
Abstract:
The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.Keywords: predisposition, familial, exome sequencing, breast cancer
Procedia PDF Downloads 494684 Effect of Classroom Acoustic Factors on Language and Cognition in Bilinguals and Children with Mild to Moderate Hearing Loss
Authors: Douglas MacCutcheon, Florian Pausch, Robert Ljung, Lorna Halliday, Stuart Rosen
Abstract:
Contemporary classrooms are increasingly inclusive of children with mild to moderate disabilities and children from different language backgrounds (bilinguals, multilinguals), but classroom environments and standards have not yet been adapted adequately to meet these challenges brought about by this inclusivity. Additionally, classrooms are becoming noisier as a learner-centered as opposed to teacher-centered teaching paradigm is adopted, which prioritizes group work and peer-to-peer learning. Challenging listening conditions with distracting sound sources and background noise are known to have potentially negative effects on children, particularly those that are prone to struggle with speech perception in noise. Therefore, this research investigates two groups vulnerable to these environmental effects, namely children with a mild to moderate hearing loss (MMHLs) and sequential bilinguals learning in their second language. In the MMHL study, this group was assessed on speech-in-noise perception, and a number of receptive language and cognitive measures (auditory working memory, auditory attention) and correlations were evaluated. Speech reception thresholds were found to be predictive of language and cognitive ability, and the nature of correlations is discussed. In the bilinguals study, sequential bilingual children’s listening comprehension, speech-in-noise perception, listening effort and release from masking was evaluated under a number of different ecologically valid acoustic scenarios in order to pinpoint the extent of the ‘native language benefit’ for Swedish children learning in English, their second language. Scene manipulations included target-to-distractor ratios and introducing spatially separated noise. This research will contribute to the body of findings from which educational institutions can draw when designing or adapting educational environments in inclusive schools.Keywords: sequential bilinguals, classroom acoustics, mild to moderate hearing loss, speech-in-noise, release from masking
Procedia PDF Downloads 327683 FMCW Doppler Radar Measurements with Microstrip Tx-Rx Antennas
Authors: Yusuf Ulaş Kabukçu, Si̇nan Çeli̇k, Onur Salan, Mai̇de Altuntaş, Mert Can Dalkiran, Gökseni̇n Bozdağ, Metehan Bulut, Fati̇h Yaman
Abstract:
This study presents a more compact implementation of the 2.4GHz MIT Coffee Can Doppler Radar for 2.6GHz operating frequency. The main difference of our prototype depends on the use of microstrip antennas which makes it possible to transport with a small robotic vehicle. We have designed our radar system with two different channels: Tx and Rx. The system mainly consists of Voltage Controlled Oscillator (VCO) source, low noise amplifiers, microstrip antennas, splitter, mixer, low pass filter, and necessary RF connectors with cables. The two microstrip antennas, one is element for transmitter and the other one is array for receiver channel, was designed, fabricated and verified by experiments. The system has two operation modes: speed detection and range detection. If the switch of the operation mode is ‘Off’, only CW signal transmitted for speed measurement. When the switch is ‘On’, CW is frequency-modulated and range detection is possible. In speed detection mode, high frequency (2.6 GHz) is generated by a VCO, and then amplified to reach a reasonable level of transmit power. Before transmitting the amplified signal through a microstrip patch antenna, a splitter used in order to compare the frequencies of transmitted and received signals. Half of amplified signal (LO) is forwarded to a mixer, which helps us to compare the frequencies of transmitted and received (RF) and has the IF output, or in other words information of Doppler frequency. Then, IF output is filtered and amplified to process the signal digitally. Filtered and amplified signal showing Doppler frequency is used as an input of audio input of a computer. After getting this data Doppler frequency is shown as a speed change on a figure via Matlab script. According to experimental field measurements the accuracy of speed measurement is approximately %90. In range detection mode, a chirp signal is used to form a FM chirp. This FM chirp helps to determine the range of the target since only Doppler frequency measured with CW is not enough for range detection. Such a FMCW Doppler radar may be used in border security of the countries since it is capable of both speed and range detection.Keywords: doppler radar, FMCW, range detection, speed detection
Procedia PDF Downloads 399682 The Effects of Leadership on the Claim of Responsibility
Authors: Katalin Kovacs
Abstract:
In most forms of violence the perpetrators intend to hide their identities. Terrorism is different. Terrorist groups often take responsibility for their attacks, and consequently they reveal their identities. This unique characteristic of terrorism has been largely overlooked, and scholars are still puzzled as to why terrorist groups claim responsibility for their attacks. Certainly, the claim of responsibility is worth analysing. It would help to have a clearer picture of what terrorist groups try to achieve and how, but also to develop an understanding of the strategic planning of terrorist attacks and the message the terrorists intend to deliver. The research aims to answer the question why terrorist groups choose to claim responsibility for some of their attacks and not for others. In order to do so the claim of responsibility is considered to be a tactical choice, based on the assumption that terrorists weigh the costs and benefits of claiming responsibility. The main argument is that terrorist groups do not claim responsibility in cases when there is no tactical advantage gained from claiming responsibility. The idea that the claim of responsibility has tactical value offers the opportunity to test these assertions using a large scale empirical analysis. The claim of responsibility as a tactical choice depends on other tactical choices, such as the choice of target, the internationality of the attack, the number of victims and whether the group occupies territory or operates as an underground group. The structure of the terrorist groups and the level of decision making also affects the claim of responsibility. Terrorists on the lower level are less disciplined than the leaders. This means that the terrorists on lower levels pay less attention to the strategic objectives and engage easier in indiscriminate violence, and consequently they would less like to claim responsibility. Therefore, the research argues that terrorists, who are on a highest level of decision making would claim responsibility for the attacks as those are who takes into account the strategic objectives. As most studies on terrorism fail to provide definitions; therefore the researches are fragmented and incomparable. Separate, isolated researches do not support comprehensive thinking. It is also very important to note that there are only a few researches using quantitative methods. The aim of the research is to develop a new and comprehensive overview of the claim of responsibility based on strong quantitative evidence. By using well-established definitions and operationalisation the current research focuses on a broad range of attributes that can have tactical values in order to determine circumstances when terrorists are more likely to claim responsibility.Keywords: claim of responsibility, leadership, tactical choice, terrorist group
Procedia PDF Downloads 313681 Enhancing Animal Protection: Topical RNAi with Polymer Carriers for Sustainable Animal Health in Australian Sheep Flystrike
Authors: Yunjia Yang, Yakun Yan, Peng Li, Gordon Xu, Timothy Mahony, Neena Mitter, Karishma Mody
Abstract:
Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls and the parasite has developed resistance to nearly all control chemicals used in the past. It is therefore critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi and insects. However, the environmental instability of dsRNA is a major bottleneck with a protection window only lasting 5-7 days. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for controlled release of the dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. We have investigated four different BenPol carriers for their dsRNA loading capabilities of which three of them were able to afford dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in the sheep serum. Based on stability results, we further tested dsRNA from potential targeted genes loaded with BenPol carrier in larvae feeding assay, and get three knockdowns. Our results, establish that the dsRNA when loaded on BenPol particles is stable unlike naked dsRNA which is rapidly degraded in the sheep serum. A stable nanoparticles delivery system that can protect and increase the inherent stability of the dsRNA molecules at higher temperatures in a complex biological fluid like serum, offers a great deal of promise for the future use of this approach for enhancing animal protection.Keywords: RNA interference, Lucillia cuprina, polymer carriers, polymer stability
Procedia PDF Downloads 82680 An Empirical Study of Performance Management System: Implementation of Performance Management Cycle to Achieve High-Performance Culture at Pertamina Company, Indonesia
Authors: Arif Budiman
Abstract:
Any organization or company that wishes to achieve vision, mission, and goals of the organization is required to implement a performance management system or known as the Performance Management System (PMS) in every part of the whole organization. PMS is a tool to help visualize the direction and work program of the organization to achieve the goal. The challenge is PMS should not stop merely as a visualization tool to achieve the vision and mission of the organization, but PMS should also be able to create a high-performance culture that is inherent in each individual of the organization. Establishment of a culture within an organization requires the support of top leaders and also requires a system or governance that encourages every individual in the organization to be involved in any work program of the organization. Keywords of creating a high-performance culture are the formation of communication pattern involving the whole individual, either vertically or horizontally, and performed consistently and persistently by all individuals in each line of the organization. PT Pertamina (Persero) as the state-owned national energy company holds a system to internalize the culture of high performance through a system called Performance Management System Cycle (PMS Cycle). This system has 7 stages of the cycle, those are: (1) defining vision, mission and strategic plan of the company, (2) defining key performance indicator of each line and the individual (‘expectation setting conversation’), (3) defining performance target and performance agreement, (4) monitoring performance on a monthly regular basis (‘pulse check’), (5) implementing performance dialogue between leaders and staffs periodically every 3 months (‘performance dialogue’), (6) defining rewards and consequences based on the achievement of the performance of each line and the individual, and (7) calculating the final performance value achieved by each line and individual from one period of the current year. Perform PMS is a continual communication running throughout the year, that is why any three performance discussion that should be performed, include expectation setting conversations, pulse check and performance dialogue. In addition, another significant point and necessary undertaken to complete the assessment of individual performance assessment is soft competencies through 360-degree assessment by leaders, staffs, and peers.Keywords: 360-degree assessment, expectation setting conversation, performance management system cycle, performance dialogue, pulse check
Procedia PDF Downloads 442679 Recent Legal Changes in Turkish Commercial Law to Be a Part of International Markets and Their Results
Authors: Ibrahim Arslan
Abstract:
Since 1984, Turkey has experienced a significant transformation in legal and economic matters. The most consequential examples of this transformation in recent years are the renewal of the Commercial Code and the Check Act. Nowadays, the commercial activity is not limited within the boundaries of the country; on the contrary, as required by the global economy, it has an international dimension. For this reason, unlike some other legal principles, the rules regulating the commercial life should be compatible with the international standards as much as possible. Otherwise the development possibility in the global markets will be limited. The Check Act has been adopted in 2009 and the Commercial Code has been adopted in 2011. The Commercial Code has been entered into force on 1 July 2012. The international dimension of check is in-disputable for it is based on the Geneva Convention. However, the Turkish business life has created a unique application of this legal tool. This application is called “post-date” checks. Indeed the majority of the checks being used in the market are post-dated checks. The holders of these checks have waited the date written on the check for presentation and collection. Thus, the actual situation has occurred. This actual situation has been legitimized via Check Act No. 5941 and post dated checks have gained a legal status. In the preparation of the new the Turkish Commercial Code one of the goals is "to ensure that the Turkish commercial law becomes a part of the international market". To achieve this goal, significant changes have been made especially concerning the independent external audition of the corporations, the board structure and public disclosure regulations. These changes aim to facilitate the internationalization of Turkish corporations as well as intensification of foreign direct investments through foreign capital. Although the target has been determined this way, after the adoption but five days before the entry into force of the Turkish Commercial Code No. 6102, a law made backward going alterations concerning independent external audition and public disclosure regulations. Turkish Commercial Code has been currently in force with its altered status. Both the regulations in the Check Act as well as the changes in the Commercial Code are not compatible with the goals introduced by rationale “to ensure Turkish commercial law to be a part of the international market” as such.Keywords: Turkish Commercial Code No. 6102, Turkish Check Act, “post-date” checks, legal changes
Procedia PDF Downloads 295678 Critical Appraisal, Smart City Initiative: China vs. India
Authors: Suneet Jagdev, Siddharth Singhal, Dhrubajyoti Bordoloi, Peesari Vamshidhar Reddy
Abstract:
There is no universally accepted definition of what constitutes a Smart City. It means different things to different people. The definition varies from place to place depending on the level of development and the willingness of people to change and reform. It tries to improve the quality of resource management and service provisions for the people living in the cities. Smart city is an urban development vision to integrate multiple information and communication technology (ICT) solutions in a secure fashion to manage the assets of a city. But most of these projects are misinterpreted as being technology projects only. Due to urbanization, a lot of informal as well government funded settlements have come up during the last few decades, thus increasing the consumption of the limited resources available. The people of each city have their own definition of Smart City. In the imagination of any city dweller in India is the picture of a Smart City which contains a wish list of infrastructure and services that describe his or her level of aspiration. The research involved a comparative study of the Smart City models in India and in China. Behavioral changes experienced by the people living in the pilot/first ever smart cities have been identified and compared. This paper discussed what is the target of the quality of life for the people in India and in China and how well could that be realized with the facilities being included in these Smart City projects. Logical and comparative analyses of important data have been done, collected from government sources, government papers and research papers by various experts on the topic. Existing cities with historically grown infrastructure and administration systems will require a more moderate step-by-step approach to modernization. The models were compared using many different motivators and the data is collected from past journals, interacting with the people involved, videos and past submissions. In conclusion, we have identified how these projects could be combined with the ongoing small scale initiatives by the local people/ small group of individuals and what might be the outcome if these existing practices were implemented on a bigger scale.Keywords: behavior change, mission monitoring, pilot smart cities, social capital
Procedia PDF Downloads 290677 Arabicization and Terminology with Reference to Social Media Terms
Authors: Ahmed Al-Awthan
Abstract:
This study addresses the prevalence of English terminology in published Arabic documentation on social media. Although the problem of using English terms in translation instead of existing native ones has been addressed in general by researchers around the world, to the best of the author’s knowledge the attitude of the translators as professionals to this phenomenon in Qatar and Yemen has not received a detailed study. This study examines the impact of the use of English, social media terms in the Arab world on aspiring and professional translators; it explores the benefits and drawbacks of linguistic borrowing as identified by the translators and investigates whether translators consider any means of resisting linguistic borrowing and prioritizing Arabic. It also aims to answer the following questions: i. Is there any prevalence of English, social media terms in Arabic translation? Why or why not? ii. Do Arabic translators prefer using English, social media terms to their equivalents in Arabic? If so, why? iii. Which measures could be adopted to help reduce the frequently observed borrowing of English terms? In particular, how do translators see the role of the Arabic Language Academies in preserving Arabic? iv. This research is descriptive, comparative and analytical in nature. It is both qualitative and quantitative. To validate the problem, the researcher will analyze articles published by Al-Jazeera in 2016-2018 that refer to the use of social media in diplomacy. It will be examined whether the increased international discussion of political events in social media increased the amount of transliterated English terminology referring to this mode of communication.To investigate whether the translators recognize the phenomenon of borrowing, the researcher proposes to use a survey. This survey will use multiple choice questions. It will target 20 aspiring translators from Yemen and 20 participants from Qatar. It will offer 15 English, social media terms used in discourse in 15 sentences. For each sentence, the researcher will provide three different translations and will ask the translators to rate them and offer their rendition. After collecting all the answers online, the researcher will analyze the data. The results are expected to confirm whether there is a prevalence of English terms in translating into Arabic. It is also expected to show what measures the translators used to render the English, social media terms, and it raises awareness of borrowing English terms. It will guide the translator toward using Arabicization methods in order to contribute to preserving Arabic.Keywords: Arabicization, trans lingual borrowing, social media terms, terminology
Procedia PDF Downloads 151676 Alteration of Placental Development and Vascular Dysfunction in Gestational Diabetes Mellitus Has Impact on Maternal and Infant Health
Authors: Sadia Munir
Abstract:
The aim of this study is to investigate changes in placental development and vascular dysfunction which subsequently affect feto-maternal health in pregnancies complicated by gestational diabetes mellitus (GDM). Fetal and postnatal adverse health outcomes of GDM are shown to be associated with disturbances in placental structure and function. Children of women with GDM are more likely to be obese and diabetic in childhood and adulthood. GDM also increases the risk of adverse pregnancy outcomes, including preeclampsia, birth injuries, macrosomia and neonatal hypoglycemia, respiratory distress syndrome, neonatal cardiac dysfunction and stillbirth. Incidences of type 2 diabetes in the MENA region are growing at an alarming rate which is estimated to become more than double by 2030. Five of the top 10 countries for diabetes prevalence in 2010 were in the Gulf region. GDM also increases the risk of development of type 2 diabetes. Interestingly, more than half of the women with GDM develop diabetes later in their life. The human placenta is a temporary organ located at the interface between mother and fetal blood circulation. Placenta has a central role as both a producer as well as a target of several molecules that are involved in placental development and function. We have investigated performed a Pubmed search with key words placenta, GDM, placental villi, vascularization, cytokines, growth factors, inflammation, hypoxia, oxidative stress and pathophysiology. We have investigated differences in the development and vascularization of placenta, their underlying causes and impact on feto-maternal health through literature review. We have also identified gaps in the literature and research questions that need to be answered to completely understand the central role of placenta in the GDM. This study is important in understanding the pathophysiology of placenta due to changes in the vascularization of villi, surface area and diameter of villous capillaries in pregnancies complicated by GDM. It is necessary to understand these mechanisms in order to develop treatments to reverse their effects on placental malfunctioning, which in turn, will result in improved mother and child health.Keywords: gestational diabetes mellitus, placenta, vasculature, villi
Procedia PDF Downloads 318675 Microalgae for Plant Biostimulants on Whey and Dairy Wastewaters
Authors: Sergejs Kolesovs, Pavels Semjonovs
Abstract:
Whey and dairy wastewaters if disposed in the environment without proper treatment, cause serious environmental risks contributing to overall and particular environmental pollution and climate change. Biological treatment of wastewater is considered to be most eco-friendly approach, as compared to the chemical treatment methods. Research shows, that dairy wastewater can potentially be remediated by use of microalgae thussignificantly reducing the content of carbohydrates, P, N, K and other pollutants. Moreover, it has been shown, that use of dairy wastewaters results in higher microalgae biomass production. In recent decades microalgal biomass has entailed a big interest for its potential applications in pharmaceuticals, biomedicine, health supplementation, cosmetics, animal feed, plant protection, bioremediation and biofuels. It was shown, that lipids productivity on whey and dairy wastewater is higher as compared with standard cultivation media and occurred without the necessity of inducing specific stress conditions such as N starvation. Moreover, microalgae biomass production as usually associated with high production costs may benefit from perspective of both reasons – enhanced microalgae biomass or target substances productivity on cheap growth substrate and effective management of whey and dairy wastewaters, which issignificant for decrease of total production costs in both processes. Obviously, it became especially important when large volume and low cost industrial microalgal biomass production is anticipated for further use in agriculture of crops as plant growth stimulants, biopesticides soil fertilisers or remediating solutions. Environmental load of dairy wastewaters can be significantly decreased when microalgae are grown in coculture with other microorganisms. This enhances the utilisation of lactose, which is main C source in whey and dairy wastewaters when it is not metabolised easily by most microalgal species chosen. Our study showsthat certain microalgae strains can be used in treatment of residual sugars containing industrial wastewaters and decrease of their concentration thus approving that further extensive research on dairy wastewaters pre-treatment optionsfor effective cultivation of microalgae, carbon uptake and metabolism, strain selection and choice of coculture candidates is needed for further optimisation of the process.Keywords: microalgae, whey, dairy wastewaters, sustainability, plant biostimulants
Procedia PDF Downloads 96674 Evaluation of the Effectiveness of Barriers for the Control of Rats in Rice Plantation Field
Authors: Melina, Jumardi Jumardi, Erwin Erwin, Sri Nuraminah, Andi Nasruddin
Abstract:
The rice field rat (Rattus argentiventer Robinson and Kloss) is a pest causing the greatest yield loss of rice plants, especially in lowland agroecosystems with intensive cropping patterns (2-3 plantings per year). Field mice damage rice plants at all stages of growth, from seedling to harvest, even in storage warehouses. Severe damage with yield loss of up to 100% occurs if rats attack rice at the generative stage because the plants are no longer able to recover by forming new tillers. Farmers mainly use rodenticides in the form of poisoned baits or as fumigants, which are applied to rat burrow holes. This practice is generally less effective because mice are able to avoid the poison or become resistant after several exposures to it. In addition, excessive use of rodenticides can have negative impacts on the environment and non-target organisms. For this reason, this research was conducted to evaluate the effectiveness of fences as an environmentally friendly mechanical control method in reducing rice yield losses due to rat attacks. This study used a factorial randomized block design. The first factor was the fence material, namely galvanized zinc plate and plastic. The second factor was the height of the fence, namely 25, 50, 75, and 100 cm from the ground level. Each treatment combination was repeated five times. Data shows that zinc fences with a height of 75 and 100 cm are able to provide full protection to plants from rat infestations throughout the planting season. However, zinc fences with a height of 25 and 50 cm failed to prevent rat attacks. Plastic fences with a height of 25 and 50 cm failed to prevent rat attacks during the planting season, whereas 75 and 100 cm were able to prevent rat attacks until all the crops outside of the fence had been eaten by rats. The rat managed to get into the fence by biting the plastic fence close to the ground. Thus, the research results show that fences made of zinc plate with a height of at least 75 cm from the ground surface are effective in preventing plant damage caused by rats. To our knowledge, this research is the first to quantify the effectiveness of fences as a control of field rodents.Keywords: rice field rat, Rattus argentiventer, fence, rice
Procedia PDF Downloads 42673 One-Step Synthesis and Characterization of Biodegradable ‘Click-Able’ Polyester Polymer for Biomedical Applications
Authors: Wadha Alqahtani
Abstract:
In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer
Procedia PDF Downloads 117672 PTOP Expression Correlates with Telomerase Activity and Grades of Malignancy in Human Glioma Tissues
Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz
Abstract:
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.Keywords: glioblastoma, PTOP, telomere, brain tumors
Procedia PDF Downloads 346671 Perceptions of Mothers on Their Role in the Prevention of the Spread of Human Immunodeficiency Virus to Their Children and Childcare Received in the Healthcare Facility in a Rural Area
Authors: Sibusiso Buthelezi, Rugira Regis Marie-Modeste, Deliwe Rene Phetlhu
Abstract:
Introduction: Mother-to-child transmission persists owing to inadequate implementation of prevention of mother-to-child transmission programmes, particularly in rural areas. To achieve a target of zero new HIV infection in children born from women living with HIV, the involvement of mothers and caregivers is undeniable. Therefore, there is a need to explore the views of the mothers because of the role they play in their own right when it comes to preventing their children from contracting HIV by consistently adhering to the guidelines of the prevention of mother-to-child transmission programme. Thus, this study sought to explore and describe the perceptions of mothers on their role in the prevention of HIV to their children exposed to HIV and further explore their perceptions of the childcare received in the healthcare facility. Methods: The study was conducted in November-December 2019 in Ngaka Modiri Molema in North West Province in South Africa. A qualitative exploratory, descriptive research design was used. Purposive sampling was used to select the mothers of children exposed to HIV during the mother`s clinic attendance. Data collection was done through semi-structured individual interviews with mothers of children exposed to HIV. Colaizzi`s method of data analysis was used to analyse data in this study. Results: Seven themes emerged from data analysis, namely: health benefits from coming to the healthcare facility, communication, information needs, attitude of healthcare workers, healthcare administration system, the role of a mother, and disclosure of HIV status. Conclusion: This study revealed systematic gaps that exist in the programme, which hinder the childcare services of children exposed to HIV and socio-economically related hindrances. Mothers’ roles, such as exclusive breastfeeding, taking their own medication, and child follow-up visits, remain inadequate. The study findings show that there is a need to develop a contextual-tailored intervention strategy that would improve the implementation of prevention of mother-to-child transmission in rural areas.Keywords: children exposed to HIV, mothers’ role to prevent MTCT, mothers’ perceptions on childcare, PMTCT in rural areas
Procedia PDF Downloads 101670 The Identification of Instructional Approach for Enhancing Competency of Autism, Attention Deficit Hyperactivity Disorder and Learning Disability Groups
Authors: P. Srisuruk, P. Narot
Abstract:
The purpose of this research were 1) to develop the curriculum and instructional approach that are suitable for children with autism, attention deficit hyperactivity disorder and learning disability as well as to arrange the instructional approach that can be integrated into inclusive classroom 2) to increase the competency of the children in these group. The research processes were to a) study related documents, b) arrange workshops to clarify fundamental issues in developing core curriculum among the researchers and experts in curriculum development, c) arrange workshops to develop the curriculum, submit it to the experts for criticism and editing, d) implement the instructional approach to examine its effectiveness, e) select the schools to participate in the project and arrange training programs for teachers in the selected school, f) implement the instruction approach in the selected schools in different regions. The research results were 1) the core curriculum to enhance the competency of children with autism, attention deficit hyperactivity disorder and learning disability , and to be used as a guideline for teachers, and these group of children in order to arrange classrooms for students with special needs to study with normal students, 2) teaching and learning methods arranged for students with autism, attention deficit, hyperactivity disorder and learning disability to study with normal students can be used as a framework for writing plans to help students with parallel problems by developing teaching materials as part of the instructional approach. However, the details of how to help the students in each skill or content differ according to the demand of development as well as the problems of individual students or group of students. Furthermore; it was found that most of target teacher could implement the instructional approach based on the guideline model developed by the research team. School in each region does not have much difference in their implementation. The good point of the developed instructional model is that teacher can construct a parallel lesson plan. So teacher did not fell that they have to do extra work it was also shown that students in regular classroom enjoyed studying with the developed instructional model as well.Keywords: instructional approach, autism, attention deficit hyperactivity disorder, learning disability
Procedia PDF Downloads 333669 Lessons Learned in Implementing Programs to Delay Diabetic Nephropathy Management in Primary Health Care: Case Study in Sakon Nakhon Province
Authors: Sasiwan Tassana-iem, Sumattana Glangkarn
Abstract:
Diabetic nephropathy is a major complication in diabetic patients whom as the glomerular filtration rate falls. The affects their quality of life and results in loss of money for kidney replacement therapy costs. There is an existing intervention, but the prevalence remains high, thus this research aims to study lessons learned in implementing programs to delay diabetic nephropathy management in primary health care. Method: The target settings are, 24 sub-district health promoting hospital in Sakon Nakhon province. Participants included the health care professionals, head of the sub-district health promoting hospital and the person responsible for managing diabetic nephropathy in each hospital (n= 50). There are 400 patients with diabetes mellitus in an area. Data were collected using questionnaires, patient records data, interviews and focus groups and analyzed by statistics and content analysis. Result: Reflection of participants that the interventions to delay diabetic nephropathy management in each area, the Ministry of Public Health has a policy to screen and manage this disease. The implementing programs aimed to provide health education, innovative teaching media used in communication to educate. Patients and caregivers had misunderstanding about the actual causes and prevention of this disease and how to apply knowledge suitable for daily life. Conclusion: The obstacles to the success of the implementing programs to delay diabetic nephropathy management in primary health care were most importantly, the patient needs self-care and should be evaluated for health literacy. This is crucial to promote health literacy; to access and understand health information as well to decide their health-related choices based on health information which will promote and maintain a good health. This preliminary research confirms that situation of diabetic nephropathy still exists. The results of this study will lead to the development of delay in diabetic nephropathy implementation among patients in the province studied.Keywords: diabetic nephropathy, chronic kidney disease, primary health care, implementation
Procedia PDF Downloads 201668 Canthin-6-One Alkaloid Inhibits NF-κB and AP-1 Activity: An Inhibitory Action At Transcriptional Level
Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin
Abstract:
Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.
Procedia PDF Downloads 458