Search results for: biomolecular sequence synthesis

Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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Authors: Shaun G. Abbott, Rebecca C. Reynolds, James B. Etter, John B. F. de Wit

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The benefits of physical activity (PA) on health are well documented. Low socioeconomic status (SES) is associated with poor health, with PA a suggested mediator. Pedometers and accelerometers offer an effective behavior change tool to increase PA levels. While the role of pedometer and accelerometer use in increasing PA is recognized in many populations, little is known in low-SES groups. We are aiming to assess the effectiveness of pedometer- and accelerometer-based interventions for increasing PA step count and improving subsequent health outcomes among low-SES groups of high-income countries. Medline, Embase, PsycINFO, CENTRAL and SportDiscus databases were searched to identify articles published before 10th July, 2015; using search terms developed from previous systematic reviews. Inclusion criteria are: low-SES participants classified by income, geography, education, occupation or ethnicity; study duration minimum 4 weeks; an intervention and control group; wearing of an unsealed pedometer or accelerometer to objectively measure PA as step counts per day for the duration of the study. We retrieved 2,142 articles from our database searches, after removal of duplicates. Two investigators independently reviewed titles and abstracts of these articles (50% each) and a combined 20% sample were reviewed to account for inter-assessor variation. We are currently verifying the full texts of 430 articles. Included studies will be critically appraised for risk of bias using guidelines suggested by the Cochrane Public Health Group. Two investigators will extract data concerning the intervention; study design; comparators; steps per day; participants; context and presence or absence of obesity and/or chronic disease. Heterogeneity amongst studies is anticipated, thus a narrative synthesis of data will be conducted with the simplification of selected results into percentage increases from baseline to allow for between-study comparison. Results will be presented at the conference in December if selected.

Keywords: accelerometer, pedometer, physical activity, socioeconomic, step count

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Authors: Yew Mun Yip, Dawei Zhang

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Proteins are the biological machinery that executes specific vital functions in every cell of the human body by folding into their 3D structures. When a protein misfolds from its native structure, the machinery will malfunction and lead to misfolding diseases. Although in vitro experiments are able to conclude that the mutations of the amino acid sequence lead to incorrectly folded protein structures, these experiments are unable to decipher the folding process. Therefore, molecular dynamic (MD) simulations are employed to simulate the folding process so that our improved understanding of the folding process will enable us to contemplate better treatments for misfolding diseases. MD simulations make use of force fields to simulate the folding process of peptides. Secondary structures are formed via the hydrogen bonds formed between the backbone atoms (C, O, N, H). It is important that the hydrogen bond energy computed during the MD simulation is accurate in order to direct the folding process to the native structure. Since the atoms involved in a hydrogen bond possess very dissimilar electronegativities, the more electronegative atom will attract greater electron density from the less electronegative atom towards itself. This is known as the polarization effect. Since the polarization effect changes the electron density of the two atoms in close proximity, the atomic charges of the two atoms should also vary based on the strength of the polarization effect. However, the fixed atomic charge scheme in force fields does not account for the polarization effect. In this study, we introduce the polarized structure-specific backbone charge (PSBC) model. The PSBC model accounts for the polarization effect in MD simulation by updating the atomic charges of the backbone hydrogen bond atoms according to equations derived between the amount of charge transferred to the atom and the length of the hydrogen bond, which are calculated from quantum-mechanical calculations. Compared to other polarizable models, the PSBC model does not require quantum-mechanical calculations of the peptide simulated at every time-step of the simulation and maintains the dynamic update of atomic charges, thereby reducing the computational cost and time while accounting for the polarization effect dynamically at the same time. The PSBC model is applied to two different β-peptides, namely the Beta3s/GS peptide, a de novo designed three-stranded β-sheet whose structure is folded in vitro and studied by NMR, and the trpzip peptides, a double-stranded β-sheet where a correlation is found between the type of amino acids that constitute the β-turn and the β-propensity.

Keywords: hydrogen bond, polarization effect, protein folding, PSBC

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Authors: Farahnaz Amini, Woo Yun Kin, Lazwani Kolandaiveloo

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Availability of different genetic tests after completion of Human Genome Project increases the physicians’ responsibility to keep themselves update on the potential implementation of these genetic tests in their daily practice. However, due to numbers of barriers, still many of physicians are not either aware of these tests or are not willing to offer or refer their patients for genetic tests. This study was conducted an anonymous, cross-sectional, mailed-based survey to develop a primary data of Malaysian physicians’ level of knowledge and perception of gene profiling. Questionnaire had 29 questions. Total scores on selected questions were used to assess the level of knowledge. The highest possible score was 11. Descriptive statistics, one way ANOVA and chi-squared test was used for statistical analysis. Sixty three completed questionnaires was returned by 27 general practitioners (GPs) and 36 medical specialists. Responders’ age range from 24 to 55 years old (mean 30.2 ± 6.4). About 40% of the participants rated themselves as having poor level of knowledge in genetics in general whilst 60% believed that they have fair level of knowledge. However, almost half (46%) of the respondents felt that they were not knowledgeable about available genetic tests. A majority (94%) of the responders were not aware of any lab or company which is offering gene profiling services in Malaysia. Only 4% of participants were aware of using gene profiling for detection of dosage of some drugs. Respondents perceived greater utility of gene profiling for breast cancer (38%) compared to the colorectal familial cancer (3%). The score of knowledge ranged from 2 to 8 (mean 4.38 ± 1.67). Non-significant differences between score of knowledge of GPs and specialists were observed, with score of 4.19 and 4.58 respectively. There was no significant association between any demographic factors and level of knowledge. However, those who graduated between years 2001 to 2005 had higher level of knowledge. Overall, 83% of participants showed relatively high level of perception on value of gene profiling to detect patient’s risk of disease. However, low perception was observed for both statements of using gene profiling for general population in order to alter their lifestyle (25%) as well as having the full sequence of a patient genome for the purpose of determining a patient’s best match for treatment (18%). The lack of clinical guidelines, limited provider knowledge and awareness, lack of time and resources to educate patients, lack of evidence-based clinical information and cost of tests were the most barriers of ordering gene profiling mentioned by physicians. In conclusion Malaysian physicians who participate in this study had mediocre level of knowledge and awareness in gene profiling. The low exposure to the genetic questions and problems might be a key predictor of lack of awareness and knowledge on available genetic tests. Educational and training workshop might be useful in helping Malaysian physicians incorporate genetic profiling into practice for eligible patients.

Keywords: gene profiling, knowledge, Malaysia, physician

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Authors: Man Fung Ho, Lap So, Jiaqi Zhang, Yuheng Zhao, Huiyang Lu, Tat Shing Choi, K. Y. Michael Wong

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Nowadays, a tremendous amount of data is available in the transportation system, enabling the development of various machine learning approaches to make short-term latency predictions. A natural question is then the choice of relevant information to enable accurate predictions. Using traffic data collected from the Taiwan Freeway System, we consider the prediction of short-term latency of a freeway segment with a length of 17 km covering 5 measurement points, each collecting vehicle-by-vehicle data through the electronic toll collection system. The processed data include the past latencies of the freeway segment with different time lags, the traffic conditions of the individual segments (the accumulations, the traffic fluxes, the entrance and exit rates), the total accumulations, and the weekday latency profiles obtained by Gaussian process regression of past data. We arrive at several important conclusions about how data should be refined to obtain accurate predictions, which have implications for future system-wide latency predictions. (1) We find that the prediction of median latency is much more accurate and meaningful than the prediction of average latency, as the latter is plagued by outliers. This is verified by machine-learning prediction using XGBoost that yields a 35% improvement in the mean square error of the 5-minute averaged latencies. (2) We find that the median latency of the segment 15 minutes ago is a very good baseline for performance comparison, and we have evidence that further improvement is achieved by machine learning approaches such as XGBoost and Long Short-Term Memory (LSTM). (3) By analyzing the feature importance score in XGBoost and calculating the mutual information between the inputs and the latencies to be predicted, we identify a sequence of inputs ranked in importance. It confirms that the past latencies are most informative of the predicted latencies, followed by the total accumulation, whereas inputs such as the entrance and exit rates are uninformative. It also confirms that the inputs are much less informative of the average latencies than the median latencies. (4) For predicting the latencies of segments composed of two or three sub-segments, summing up the predicted latencies of each sub-segment is more accurate than the one-step prediction of the whole segment, especially with the latency prediction of the downstream sub-segments trained to anticipate latencies several minutes ahead. The duration of the anticipation time is an increasing function of the traveling time of the upstream segment. The above findings have important implications to predicting the full set of latencies among the various locations in the freeway system.

Keywords: data refinement, machine learning, mutual information, short-term latency prediction

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Authors: Hamza I. Isa, Gezina C. H. Ferreira, Jan E. Crafford, Christoffel J. Botha

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Moraea pallida Bak. (yellow tulip) poisoning is the most important plant-induced cardiac glycoside toxicosis in South Africa. Cardiac glycoside poisonings collectively account for about 33 and 10 % mortalities due to plants, in large and small stock respectively, in South Africa. The toxic principle is 1α, 2α-epoxyscillirosidine, a bufadienolide. The aim of the study was to investigate the potential to develop a vaccine against epoxyscillirosidine. Epoxyscillirosidine and the related bufadienolides proscillaridin and bufalin, which are commercially available, were conjugated to the carrier proteins [Hen ovalbumin (OVA), bovine serum albumin (BSA) and keyhole limpet haemocyanin (KLH)], rendering them immunogenic. Adult male New Zealand White rabbits were immunized. In Trials 1 and 2, rabbits (n=6) were, each assigned to two groups. Experimental animals (n=3; n=4) were vaccinated with epoxyscillirosidine-OVA conjugate, while the control (n=3; n=2) were vaccinated with OVA, using Freund’s complete and incomplete and Montanide adjuvants, for Trials 1 and 2, respectively. In Trial 3, rabbits (n=15), randomly allocated to 5 equal groups (I, II, III, IV and V), were vaccinated with proscillaridin-BSA, bufalin-BSA, epoxyscillirosidine-KLH, epoxyscillirosidine-BSA conjugates, and BSA respectively, using Montanide as adjuvant. Vaccination was on Days 0, 21 and 42. Additional vaccinations were done on Day 56 and 63 for Trial 1. Vaccination was by intradermal injection of 0.4 ml of the immunogen (4 mg/ml [Trial 1] and 8 mg/ml for Trials 2 and Trial 3, respectively). Blood was collected pre-vaccination and at 3 week intervals following each vaccination. Antibody response was determined using an indirect ELISA. There was poor immune response associated with the dose (0.4 mg per rabbit) and adjuvant used in Trial 1. Antibodies were synthesized against the conjugate administered in Trial 2. For Trail 3, antibodies against the immunogens were successfully raised in rabbits with epoxyscillirosidine-KLH inducing the highest immune response. The antibodies raised against proscillaridin and bufalin cross-reacted with epoxyscillirosidine when used as antigen in the ELISA. The study successfully demonstrated the synthesis of antibodies against the bufadienolide conjugates administered. The cross-reactivity of proscillaridin and bufalin with epoxyscillirosidine could potentially be utilized as alternative to epoxyscillirosidine in future studies to prevent yellow tulp poisoning by vaccination.

Keywords: antibodies , bufadienolides, cross-reactivity, epoxyscillirosidine, Moraea pallida, poisoning

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Authors: Michelle Rippy

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Medicolegal death investigation historically is a field that does not receive much research attention or advancement, as all of the subjects are deceased. Public health threats, drug epidemics and contagious diseases are typically recognized in decedents first, with thorough and accurate death investigations able to assist in epidemiology research and prevention programs. One vital component of medicolegal death investigation is determining the decedent’s time of death. An accurate time of death can assist in corroborating alibies, determining sequence of death in multiple casualty circumstances and provide vital facts in civil situations. Popular television portrays an unrealistic forensic ability to provide the exact time of death to the minute for someone found deceased with no witnesses present. The actuality of unattended decedent time of death determination can generally only be narrowed to a 4-6 hour window. In the mid- to late-20th century, liver temperatures were an invasive action taken by death investigators to determine the decedent’s core temperature. The core temperature was programmed into an equation to determine an approximate time of death. Due to many inconsistencies with the placement of the thermometer and other variables, the accuracy of the liver temperatures was dispelled and this once common place action lost scientific support. Currently, medicolegal death investigators utilize three major after death or post-mortem changes at a death scene. Many factors are considered in the subjective determination as to the time of death, including the cooling of the decedent, stiffness of the muscles, release of blood internally, clothing, ambient temperature, disease and recent exercise. Current research is utilizing non-invasive hospital grade tympanic thermometers to measure the temperature in the each of the decedent’s ears. This tool can be used at the scene and in conjunction with scene indicators may provide a more accurate time of death. The research is significant and important to investigations and can provide an area of accuracy to a historically inaccurate area, considerably improving criminal and civil death investigations. The goal of the research is to provide a scientific basis to unwitnessed deaths, instead of the art that the determination currently is. The research is currently in progress with expected termination in December 2018. There are currently 15 completed case studies with vital information including the ambient temperature, decedent height/weight/sex/age, layers of clothing, found position, if medical intervention occurred and if the death was witnessed. This data will be analyzed with the multiple variables studied and available for presentation in January 2019.

Keywords: algor mortis, forensic pathology, investigations, medicolegal, time of death, tympanic

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Authors: Fuad Abdullah Alatawi

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Microbial infections-based diseases are a significant public health issue around the world, mainly when antibiotic-resistant bacterium types evolve. In this research, we explored the anti-bacterial and anti-cancer potency of iron-oxide (Fe₂O₃) nanoparticles prepared from F. macrocarpa fruit extract. The chemical composition of F. macrocarpa fruit extract was used as a reducing and capping agent for nanoparticles’ synthesis was examined by GC-MS/MS analysis. Then, the prepared nanoparticles were confirmed by various biophysical techniques, including X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), UV-Vis Spectroscopy, and Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDAX), and Dynamic Light Scattering (DLS). Also, the antioxidant capacity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Fluorescence Recovery After Photobleaching (FRAP), Superoxide Dismutase (SOD) assays. Furthermore, the cytotoxicity activities of Fe₂O₃ NPs were determined using the (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) test on MCF-7 cells. In the antibacterial assay, lethal doses of the Fe₂O₃NPs effectively inhibited the growth of gram-negative and gram-positive bacteria. The surface damage, ROS production, and protein leakage are the antibacterial mechanisms of Fe₂O₃NPs. Concerning antioxidant activity, the fruit extracts of F. macrocarpa had strong antioxidant properties, which were confirmed by DPPH, ABTS, FRAP, and SOD assays. In addition, the F. microcarpa-derived iron oxide nanomaterials greatly reduced the cell viability of (MCF-7). The GC-MS/MS analysis revealed the presence of 25 main bioactive compounds in the F. microcarpa extract. Overall, the finding of this research revealed that F. microcarpa-derived Fe₂O₃ nanoparticles could be employed as an alternative therapeutic agent to cure microbial infection and breast cancer in humans.

Keywords: ficus microcarpa, iron oxide, antibacterial activity, cytotoxicity

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Authors: Pelin Balcik Ercin

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Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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Authors: Rachel Fanelwa Ajayi, Anovuyo Jonnas, Emmanuel I. Iwuoha

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Tuberculosis (TB) is an infectious disease caused by the bacterium (Mycobacterium tuberculosis) which has a predilection for lung tissue due to its rich oxygen supply. The mycobacterial cell has a unique innate characteristic which allows it to resist human immune systems and drug treatments; hence, it is one of the most difficult of all bacterial infections to treat, let alone to cure. At the same time, multi-drug resistance TB (MDR-TB) caused by poorly managed TB treatment, is a growing problem and requires the administration of expensive and less effective second line drugs which take much longer treatment duration than fist line drugs. Therefore, to acknowledge the issues of patients falling ill as a result of inappropriate dosing of treatment and inadequate treatment administration, a device with a fast response time coupled with enhanced performance and increased sensitivity is essential. This study involved the synthesis of electroactive platforms for application in the development of nano-biosensors suitable for the appropriate dosing of clinically diagnosed patients by promptly quantifying the levels of the TB drug; Isonaizid. These nano-biosensors systems were developed on gold surfaces using the enzyme N-acetyletransferase 2 coupled to the cysteamine modified poly(8-anilino-1-napthalene sulphonic acid)/zinc oxide nanocomposites. The morphology of ZnO nanoparticles, PANSA/ZnO nano-composite and nano-biosensors platforms were characterized using High-Resolution Transmission Electron Microscopy (HRTEM) and High-Resolution Scanning Electron Microscopy (HRSEM). On the other hand, the elemental composition of the developed nanocomposites and nano-biosensors were studied using Fourier Transform Infra-Red Spectroscopy (FTIR) and Energy Dispersive X-Ray (EDX). The electrochemical studies showed an increase in electron conductivity for the PANSA/ZnO nanocomposite which was an indication that it was suitable as a platform towards biosensor development.

Keywords: N-acetyletransferase 2, isonaizid, tuberculosis, zinc oxide

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Authors: Yi-Chiang Huang, Hsu-Feng Lee, Yu-Chao Tseng, Wen-Yao Huang

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Proton exchange membranes as a key component in fuel cells have been widely studying over the past few decades. As proton exchange, membranes should have some main characteristics, such as good mechanical properties, low oxidative stability and high proton conductivity. In this work, trifluoromethyl groups had been introduced on polymer backbone and phenyl side chain which can provide densely located sulfonic acid group substitution and also promotes solubility, thermal and oxidative stability. Herein, a series of novel sulfonated aromatic hydrocarbon polyelectrolytes was synthesized by polycondensation of 4,4''''-difluoro-3,3''''- bis(trifluoromethyl)-2'',3''-bis(3-(trifluoromethyl)phenyl)-1,1':4',1'':4'',1''':4''',1''''-quinquephenyl with 2'',3''',5'',6''-tetraphenyl-[1,1':4',1'': 4'',1''':4''',1''''-quinquephenyl]-4,4''''-diol and post-sulfonated was through chlorosulfonic acid to given sulfonated polymers (SFC3-X) possessing ion exchange capacities ranging from 1.93, 1.91 and 2.53 mmol/g. ¹H NMR and FT-IR spectroscopy were applied to confirm the structure and composition of sulfonated polymers. The membranes exhibited considerably dimension stability (10-27.8% in length change; 24-56.5% in thickness change) and excellent oxidative stability (weight remain higher than 97%). The mechanical properties of membranes demonstrated good tensile strength on account of the high rigidity multi-phenylated backbone. Young's modulus were ranged 0.65-0.77GPa which is much larger than that of Nafion 211 (0.10GPa). Proton conductivities of membranes ranged from 130 to 240 mS/cm at 80 °C under fully humidified which were comparable or higher than that of Nafion 211 (150 mS/cm). The morphology of membranes was investigated by transmission electron microscopy which demonstrated a clear hydrophilic/hydrophobic phase separation with spherical ionic clusters in the size range of 5-20 nm. The SFC3-1.97 single fuel cell performance demonstrates the maximum power density at 1.08W/cm², and Nafion 211 was 1.24W/cm² as a reference in this work. The result indicated that SFC3-X are good candidates for proton exchange membranes in fuel cell applications. Fuel cell of other membranes is under testing.

Keywords: fuel cells, polyelectrolyte, proton exchange membrane, sulfonated polymers

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Authors: Wadha Alqahtani

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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

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Authors: Ekaterina G. Lipatova

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The developing potential of a video task in teaching foreign languages involves the opportunities to improve four aspects of speech production process: listening, reading, speaking and writing. A video represents the sequence of actions, realized in the pictures logically connected and verbalized speech flow that simplifies and stimulates the process of perception. In this connection listening skills of students are developed effectively as well as their intellectual properties such as synthesizing, analyzing and generalizing the information. In terms of teaching capacity, a video task, in our opinion, is more stimulating than a traditional listening, since it involves the student into the plot of the communicative situation, emotional background and potentially makes them react to the gist in the cognitive and communicative ways. To be an effective method of teaching the video task should be structured in the way of psycho-linguistic characteristics of speech production process, in other words, should include three phases: before-watching, while-watching and after-watching. The system of tasks provided to each phase might involve the situations on reflecting to the video content in the forms of filling-the-gap tasks, multiple choice, True-or-False tasks (reading skills), exercises on expressing the opinion, project fulfilling (writing and speaking skills). In the before-watching phase we offer the students to adjust their perception mechanism to the topic and the problem of the chosen video by such task as “what do you know about such a problem?”, “is it new for you?”, “have you ever faced the situation of…?”. Then we proceed with the lexical and grammatical analysis of language units that form the body of a speech sample to lessen the perception and develop the student’s lexicon. The goal of while-watching phase is to build the student’s awareness about the problem presented in the video and challenge their inner attitude towards what they have seen by identifying the mistakes in the statements about the video content or making the summary, justifying their understanding. Finally, we move on to development of their speech skills within the communicative situation they observed and learnt by stimulating them to search the similar ideas in their backgrounds and represent them orally or in the written form or express their own opinion on the problem. It is compulsory to highlight, that a video task should contain the urgent, valid and interesting event related to the future profession of the student, since it will help to activate cognitive, emotional, verbal and ethic capacity of students. Also, logically structured video tasks are easily integrated into the system of e-learning and can provide the opportunity for the students to work with the foreign language on their own.

Keywords: communicative situation, perception mechanism, speech production process, speech skills

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Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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Authors: Daniel Todorov, Anton Hinkov, Petya Angelova, Kalina Shishkova, Venelin Tsvetkov, Stoyan Shishkov

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Human herpes viruses (HHV) are ubiquitous pathogens with a pandemic spread across the globe. HHV type 1 is the main causative agent of cold sores and fever blisters around the mouth and on the face, whereas HHV type 2 is generally responsible for genital herpes outbreaks. The treatment of both viruses is more or less successful with antivirals from the nucleoside analogues group. Their wide application increasingly leads to the emergence of resistant mutants In the past, medicinal plants have been used to treat a number of infectious and non-infectious diseases. Their diversity and ability to produce the vast variety of secondary metabolites according to the characteristics of the environment give them the potential to help us in our warfare with viral infections. The variable chemical characteristics and complex composition is an advantage in the treatment of herpes since the emergence of resistant mutants is significantly complicated. The screening process is difficult due to the lack of standardization. That is why it is especially important to follow the mechanism of antiviral action of plants. On the one hand, it may be expected to interact with its compounds, resulting in enhanced antiviral effects, and the most appropriate environmental conditions can be chosen to maximize the amount of active secondary metabolites. During our study, we followed the activity of various plant extracts on the viral replication cycle as well as their effect on the extracellular virion. We obtained our results following the logical sequence of the experimental settings - determining the cytotoxicity of the extracts, evaluating the overall effect on viral replication and extracellular virion.During our research, we have screened a variety of plant extracts for their antiviral activity against both virus replication and the virion itself. We investigated the effect of the extracts on the individual stages of the viral replication cycle - viral adsorption, penetration and the effect on replication depending on the time of addition. If there are positive results in the later experiments, we had studied the activity over viral adsorption, penetration and the effect of replication according to the time of addition. Our results indicate that some of the extracts from the Lamium album have several targets. The first stages of the viral life cycle are most affected. Several of our active antiviral agents have shown an effect on extracellular virion and adsorption and penetration processes. Our research over the last decade has shown several curative antiviral plants - some of which are from the Lamiacea family. The rich set of active ingredients of the plants in this family makes them a good source of antiviral preparation.

Keywords: human herpes virus, antiviral activity, Lamium album, Nepeta nuda

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Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

Procedia PDF Downloads 67

Authors: Alsu F. Saifitdinova, Alexey S. Komissarov, Svetlana A. Galkina, Elena I. Koshel, Maria M. Kulak, Stephen J. O'Brien, Elena R. Gaginskaya

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The mystery of sex determination is one of the most ancient and still not solved until the end so far. In many species, sex determination is genetic and often accompanied by the presence of dimorphic sex chromosomes in the karyotype. Genomic sequencing gave the information about the gene content of sex chromosomes which allowed to reveal their origin from ordinary autosomes and to trace their evolutionary history. Female-specific W chromosome in birds as well as mammalian male-specific Y chromosome is characterized by the degeneration of gene content and the accumulation of repetitive DNA. Tandem repeats complicate the analysis of genomic data. Despite the best efforts chicken W chromosome assembly includes only 1.2 Mb from expected 55 Mb. Supplementing the information on the sex chromosome composition not only helps to complete the assembly of genomes but also moves us in the direction of understanding of the sex-determination systems evolution. A whole-genome survey to the assembly Gallus_gallus WASHUC 2.60 was applied for repeats search in assembled genome and performed search and assembly of high copy number repeats in unassembled reads of SRR867748 short reads datasets. For cytogenetic analysis conventional methods of fluorescent in situ hybridization was used for previously cloned W specific satellites and specifically designed directly labeled synthetic oligonucleotide DNA probe was used for bioinformatically identified repetitive sequence. Hybridization was performed with mitotic chicken chromosomes and manually isolated giant meiotic lampbrush chromosomes from growing oocytes. A novel chicken W specific satellite (GGAAA)n which is not co-localizes with any previously described classes of W specific repeats was identified and mapped with high resolution. In the composition of autosomes this repeat units was found as a part of upstream regions of gonad specific protein coding sequences. These findings may contribute to the understanding of the role of tandem repeats in sex specific differentiation regulation in birds and sex chromosome evolution. This work was supported by the postdoctoral fellowships from St. Petersburg State University (#1.50.1623.2013 and #1.50.1043.2014), the grant for Leading Scientific Schools (#3553.2014.4) and the grant from Russian foundation for basic researches (#15-04-05684). The equipment and software of Research Resource Center “Chromas” and Theodosius Dobzhansky Center for Genome Bioinformatics of Saint Petersburg State University were used.

Keywords: birds, lampbrush chromosomes, sex chromosomes, tandem repeats

Procedia PDF Downloads 369

Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

Procedia PDF Downloads 256

Authors: Nadwah Onwi, Puspa Maniam, Azmawanie A. Aziz, Fairus Mukhtar, Nor Azrita Mohamed Zin, Nurul Haslina Mohd Zin, Nurul Fatehah Ismail, Mohamad Safwan Yusoff, Susilidianamanalu Abd Rahman, Siti Munirah Harris, Maryam Aizuddin

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Objective: Malaysia has a growing number of individuals with complex communication needs (CCN). The initiation of augmentative and alternative communication (AAC) intervention may facilitate individuals with CCN to understand and express themselves optimally and actively participate in activities in their daily life. AAC is defined as multimodal use of communication ability to allow individuals to use every mode possible to communicate with others using a set of symbols or systems that may include the symbols, aids, techniques, and strategies. It is consequently critical to evaluate the deficits to inform treatment for AAC intervention. However, no known measurement tools are available to evaluate the user with CCN available locally. Design: A systematic review (SR) is designed to analyze the psychometric properties of AAC assessment for adolescents with CCN published in peer-reviewed journals. Tools are rated by the methodological quality of studies and the psychometric measurement qualities of each tool. Method: A literature search identifying AAC assessment tools with psychometrically robust properties and conceptual framework was considered. Two independent reviewers screened the abstracts and full-text articles and review bibliographies for further references. Data were extracted using standardized forms and study risk of bias was assessed. Result: The review highlights the psychometric properties of AAC assessment tools that can be used by speech-language therapists applicable to be used in the Malaysian context. The work outlines how systematic review methods may be applied to the consideration of published material that provides valuable data to initiate the development of Malay Language AAC assessment tools. Conclusion: The synthesis of evidence has provided a framework for Malaysia Speech-Language therapists in making an informed decision for AAC intervention in our standard operating procedure in the Ministry of Health, Malaysia.

Keywords: augmentative and alternative communication, assessment, adolescents, complex communication needs

Procedia PDF Downloads 132

Authors: Xi Wang, Yoshio Bando

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Lithium-ion batteries (LIBs) can deliver high levels of energy storage density and offer long operating lifetimes, but their power density is too low for many important applications. Therefore, we developed some new strategies and fabricated novel electrodes for fast Li transport and its facile synthesis including N-doped graphene-SnO2 sandwich papers, bicontinuous nanoporous Cu/Li4Ti5O12 electrode, and binder-free N-doped graphene papers. In addition, by using advanced in-TEM, STEM techniques and the theoretical simulations, we systematically studied and understood their storage mechanisms at the atomic scale, which shed a new light on the reasons of the ultrafast lithium storage property and high capacity for these advanced anodes. For example, by using advanced in-situ TEM, we directly investigated these processes using an individual CuO nanowire anode and constructed a LIB prototype within a TEM. Being promising candidates for anodes in lithium-ion batteries (LIBs), transition metal oxide anodes utilizing the so-called conversion mechanism principle typically suffer from the severe capacity fading during the 1st cycle of lithiation–delithiation. Also we report on the atomistic insights of the GN energy storage as revealed by in situ TEM. The lithiation process on edges and basal planes is directly visualized, the pyrrolic N "hole" defect and the perturbed solid-electrolyte-interface (SEI) configurations are observed, and charge transfer states for three N-existing forms are also investigated. In situ HRTEM experiments together with theoretical calculations provide a solid evidence that enlarged edge {0001} spacings and surface "hole" defects result in improved surface capacitive effects and thus high rate capability and the high capacity is owing to short-distance orderings at the edges during discharging and numerous surface defects; the phenomena cannot be understood previously by standard electron or X-ray diffraction analyses.

Keywords: in-situ TEM, STEM, advanced anode, lithium-ion batteries, storage mechanism

Procedia PDF Downloads 334

Authors: Muhammad Ather Nadeem, Bilal Ahmad Khan, Tasawer Abbas

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Nanoherbicides utilize nanotechnology to enhance the delivery of biological or chemical herbicides using combinations of nanomaterials. The aim of this research was to examine the efficacy of chitosan nanoparticles containing MCPA herbicide as a potential eco-friendly alternative for weed control in wheat crops. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet absorbance were used to analyze the developed nanoparticles. The SEM analysis indicated that the average size of the particles was 35 nm, forming clusters with a porous structure. Both nanoparticles of fluroxyper + MCPA exhibited maximal absorption peaks at a wavelength of 320 nm. The compound fluroxyper +MCPA has a strong peak at a 2θ value of 30.55°, which correlates to the 78 plane of the anatase phase. The weeds, including Chenopodium album, Lathyrus aphaca, Angalis arvensis, and Melilotus indica, were sprayed with the nanoparticles while they were in the third or fourth leaf stage. There were seven distinct dosages used: doses (D0 (Check weeds), D1 (Recommended dose of traditional herbicide, D2 (Recommended dose of Nano-herbicide (NPs-H)), D3 (NPs-H with 05-fold lower dose), D4 ((NPs-H) with 10-fold lower dose), D5 (NPs-H with 15-fold lower dose), and D6 (NPs-H with 20-fold lower dose)). The chitosan-based nanoparticles of MCPA at the prescribed dosage of conventional herbicide resulted in complete death and visual damage, with a 100% fatality rate. The dosage that was 5-fold lower exhibited the lowest levels of plant height (3.95 cm), chlorophyll content (5.63%), dry biomass (0.10 g), and fresh biomass (0.33 g) in the broad-leaved weed of wheat. The herbicide nanoparticles, when used at a dosage 10-fold lower than that of conventional herbicides, had a comparable impact on the prescribed dosage. Nano-herbicides have the potential to improve the efficiency of standard herbicides by increasing stability and lowering toxicity.

Keywords: mortality, visual injury, chlorophyl contents, chitosan-based nanoparticles

Procedia PDF Downloads 45

Authors: Christofas Stergianos, Jason Atkin, Herve Morvan

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As air traffic increases, more airports are interested in utilizing optimization methods. Many processes happen in parallel at an airport, and complex models are needed in order to have a reliable solution that can be implemented for ground movement operations. The ground movement for aircraft in an airport, allocating a path to each aircraft to follow in order to reach their destination (e.g. runway or gate), is one process that could be optimized. The Quickest Path Problem with Time Windows (QPPTW) algorithm has been developed to provide a conflict-free routing of vehicles and has been applied to routing aircraft around an airport. It was subsequently modified to increase the accuracy for airport applications. These modifications take into consideration specific characteristics of the problem, such as: the pushback process, which considers the extra time that is needed for pushing back an aircraft and turning its engines on; stand holding where any waiting should be allocated to the stand; and runway sequencing, where the sequence of the aircraft that take off is optimized and has to be respected. QPPTW involves searching for the quickest path by expanding the search in all directions, similarly to Dijkstra’s algorithm. Finding a way to direct the expansion can potentially assist the search and achieve a better performance. We have further modified the QPPTW algorithm to use a heuristic approach in order to guide the search. This new algorithm is based on the A-star search method but estimates the remaining time (instead of distance) in order to assess how far the target is. It is important to consider the remaining time that it is needed to reach the target, so that delays that are caused by other aircraft can be part of the optimization method. All of the other characteristics are still considered and time windows are still used in order to route multiple aircraft rather than a single aircraft. In this way the quickest path is found for each aircraft while taking into account the movements of the previously routed aircraft. After running experiments using a week of real aircraft data from Zurich Airport, the new algorithm (A-star QPPTW) was found to route aircraft much more quickly, being especially fast in routing the departing aircraft where pushback delays are significant. On average A-star QPPTW could route a full day (755 to 837 aircraft movements) 56% faster than the original algorithm. In total the routing of a full week of aircraft took only 12 seconds with the new algorithm, 15 seconds faster than the original algorithm. For real time application, the algorithm needs to be very fast, and this speed increase will allow us to add additional features and complexity, allowing further integration with other processes in airports and leading to more optimized and environmentally friendly airports.

Keywords: a-star search, airport operations, ground movement optimization, routing and scheduling

Procedia PDF Downloads 208

Authors: Nazish Badar

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In early 2009, Pandemic type A (H1N1) Influenza virus emerged globally. Since then, it has continued circulation causing considerable morbidity and mortality. The purpose of this study was to evaluate the evolutionary changes in Influenza A (H1N1) pdm09 viruses from 2009-15 and their relevance with the current vaccine viruses. Methods: Respiratory specimens were collected with influenza-like illness and Severe Acute Respiratory Illness. Samples were processed according to CDC protocol. Sequencing and phylogenetic analysis of Haemagglutinin (HA) and neuraminidase (NA) genes was carried out comparing representative isolates from Pakistan viruses. Results: Between Jan2009 - Feb 2016, 1870 (13.2%) samples were positive for influenza A out of 14086. During the pandemic period (2009–10), Influenza A/ H1N1pdm 09 was the dominant strain with 366 (45%) of total influenza positives. In the post-pandemic period (2011–2016), a total of 1066 (59.6%) cases were positive Influenza A/ H1N1pdm 09 with co-circulation of different Influenza A subtypes. Overall, the Pakistan A(H1N1) pdm09 viruses grouped in two genetic clades. Influenza A(H1N1)pdm09 viruses only ascribed to Clade 7 during the pandemic period whereas viruses belong to clade 7 (2011) and clade 6B (2015) during the post-pandemic years. Amino acid analysis of the HA gene revealed mutations at positions S220T, I338V and P100S specially associated with outbreaks in all the analyzed strains. Sequence analyses of post-pandemic A(H1N1)pdm09 viruses showed additional substitutions at antigenic sites; S179N,K180Q (SA), D185N, D239G (CA), S202A (SB) and at receptor binding sites; A13T, S200P when compared with pandemic period. Substitution at Genetic markers; A273T (69%), S200P/T (15%) and D239G (7.6%) associated with severity and E391K (69%) associated with virulence was identified in viruses isolated during 2015. Analysis of NA gene revealed outbreak markers; V106I (23%) among pandemic and N248D (100%) during post-pandemic Pakistan viruses. Additional N-Glycosylation site; HA S179N (23%), NA I23T(7.6%) and N44S (77%) in place of N386K(77%) were only found in post-pandemic viruses. All isolates showed histidine (H) at position 275 in NA indicating sensitivity to neuraminidase inhibitors. Conclusion: This study shows that the Influenza A(H1N1)pdm09 viruses from Pakistan clustered into two genetic clades, with co-circulation of some variants. Certain key substitutions in the receptor binding site and few changes indicative of virulence were also detected in post-pandemic strains. Therefore, it is imperative to continue monitoring of the viruses for early identification of potential variants of high virulence or emergence of drug-resistant variants.

Keywords: Influenza A (H1N1) pdm09, evolutionary analysis, post pandemic period, Pakistan

Procedia PDF Downloads 183

Authors: Zhe Li, Tao Ju, Liguo Zhang, Zehong Zhang, Baoshun Zhang

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In-grow stacking-faults (IGSFs) in 4H-SiC epilayers can cause increased leakage current and reduce the blocking voltage of 4H-SiC power devices. Double Shockley stacking fault (2SSF) is a common type of IGSF with double slips on the basal planes. In this study, a 2SSF in the 4H-SiC epilayer grown by chemical vaper deposition (CVD) is characterized. The nucleation site of the 2SSF is discussed, and a model for the 2SSF nucleation is proposed. Homo-epitaxial 4H-SiC is grown on a commercial 4 degrees off-cut substrate by a home-built hot-wall CVD. Defect-selected-etching (DSE) is conducted with melted KOH at 500 degrees Celsius for 1-2 min. Room temperature cathodoluminescence (CL) is conducted at a 20 kV acceleration voltage. Low-temperature photoluminescence (LTPL) is conducted at 3.6 K with the 325 nm He-Cd laser line. In the CL image, a triangular area with bright contrast is observed. Two partial dislocations (PDs) with a 20-degree angle in between show linear dark contrast on the edges of the IGSF. CL and LTPL spectrums are conducted to verify the IGSF’s type. The CL spectrum shows the maximum photoemission at 2.431 eV and negligible bandgap emission. In the LTPL spectrum, four phonon replicas are found at 2.468 eV, 2.438 eV, 2.420 eV and 2.410 eV, respectively. The Egx is estimated to be 2.512 eV. A shoulder with a red-shift to the main peak in CL, and a slight protrude at the same wavelength in LTPL are verified as the so called Egx- lines. Based on the CL and LTPL results, the IGSF is identified as a 2SSF. Back etching by neutral loop discharge and DSE are conducted to track the origin of the 2SSF, and the nucleation site is found to be a threading screw dislocation (TSD) in this sample. A nucleation mechanism model is proposed for the formation of the 2SSF. Steps introduced by the off-cut and the TSD on the surface are both suggested to be two C-Si bilayers height. The intersections of such two types of steps are along [11-20] direction from the TSD, while a four-bilayer step at each intersection. The nucleation of the 2SSF in the growth is proposed as follows. Firstly, the upper two bilayers of the four-bilayer step grow down and block the lower two at one intersection, and an IGSF is generated. Secondly, the step-flow grows over the IGSF successively, and forms an AC/ABCABC/BA/BC stacking sequence. Then a 2SSF is formed and extends by the step-flow growth. In conclusion, a triangular IGSF is characterized by CL approach. Base on the CL and LTPL spectrums, the estimated Egx is 2.512 eV and the IGSF is identified to be a 2SSF. By back etching, the 2SSF nucleation site is found to be a TSD. A model for the 2SSF nucleation from an intersection of off-cut- and TSD- introduced steps is proposed.

Keywords: cathodoluminescence, defect-selected-etching, double Shockley stacking fault, low-temperature photoluminescence, nucleation model, silicon carbide

Procedia PDF Downloads 293

Authors: Abduladim Maitieg, Kevin Lynch, Mark Johnson

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The goal of the Libyan Environmental General Authority (EGA) and National Oil Corporation (Department of Health, Safety & Environment) during the last 5 years has been to adopt a common approach to coastal and marine spatial planning. Protection and planning of the coastal zone is a significant for Libya, due to the length of coast and, the high rate of oil export, and spills’ potential negative impacts on coastal and marine habitats. Coastal resource scenarios constitute an important tool for exploring the long-term and short-term consequences of oil spill impact and available response options that would provide an integrated perspective on mitigation. To investigate that, this paper reviews the Misratah coastal parameters to present the physical and human controls and attributes of coastal habitats as the first step in understanding how they may be damaged by an oil spill. This paper also investigates costal resources, providing a better understanding of the resources and factors that impact the integrity of the ecosystem. Therefore, the study described the potential spatial distribution of oil spill risk and the coastal resources value, and also created spatial maps of coastal resources and their vulnerability to oil spills along the coast. This study proposes an analysis of coastal resources condition at a local level in the Misratah region of the Mediterranean Sea, considering the implementation of coastal and marine spatial planning over time as an indication of the will to manage urban development. Oil spill contamination analysis and their impact on the coastal resources depend on (1) oil spill sequence, (2) oil spill location, (3) oil spill movement near the coastal area. The resulting maps show natural, socio-economic activity, environmental resources along of the coast, and oil spill location. Moreover, the study provides significant geodatabase information which is required for coastal sensitivity index mapping and coastal management studies. The outcome of study provides the information necessary to set an Environmental Sensitivity Index (ESI) for the Misratah shoreline, which can be used for management of coastal resources and setting boundaries for each coastal sensitivity sectors, as well as to help planners measure the impact of oil spills on coastal resources. Geographic Information System (GIS) tools were used in order to store and illustrate the spatial convergence of existing socio-economic activities such as fishing, tourism, and the salt industry, and ecosystem components such as sea turtle nesting area, Sabkha habitats, and migratory birds feeding sites. These geodatabases help planners investigate the vulnerability of coastal resources to an oil spill.

Keywords: coastal and marine spatial planning advancement training, GIS mapping, human uses, ecosystem components, Misratah coast, Libyan, oil spill

Procedia PDF Downloads 346

Authors: Christin Koch, Andreas Winkel, Martin Kahlmeyer, Stefan Böhm

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Due to environmental regulations on greenhouse gas emissions and the depletion of fossil fuels, there is an increasing interest in electric vehicles.To maximize their driving range, batteries with high storage capacities are needed. In most electric cars, rechargeable lithium-ion batteries are used because of their high energy density. However, it has to be taken into account that these batteries generate a large amount of heat during the charge and discharge processes. This leads to a decrease in a lifetime and damage to the battery cells when the temperature exceeds the defined operating range. To ensure an efficient performance of the battery cells, reliable thermal management is required. Currently, the cooling is achieved by heat sinks (e.g., cooling plates) bonded to the battery cells with a thermally conductive adhesive (TCA) that directs the heat away from the components. Especially when large amounts of heat have to be dissipated spontaneously due to peak loads, the principle of heat conduction is not sufficient, so attention must be paid to the mechanism of heat storage. An efficient method to store thermal energy is the use of phase change materials (PCM). Through an isothermal phase change, PCM can briefly absorb or release thermal energy at a constant temperature. If the phase change takes place in the transition from solid to liquid, heat is stored during melting and is released to the ambient during the freezing process upon cooling. The presented work displays the great potential of thermally conductive adhesives filled with microencapsulated PCM to limit peak temperatures in battery systems. The encapsulation of the PCM avoids the effects of aging (e.g., migration) and chemical reactions between the PCM and the adhesive matrix components. In this study, microencapsulation has been carried out by in situ polymerization. The microencapsulated PCM was characterized by FT-IR spectroscopy, and the thermal properties were measured by DSC and laser flash method. The mechanical properties, electrical and thermal conductivity, and adhesive toughness of the TCA/PCM composite were also investigated.

Keywords: phase change material, microencapsulation, adhesive bonding, thermal management

Procedia PDF Downloads 51

Authors: E. Zafeiraki, P. Nisianakis, K. Machera

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Cannabis plant contains 113 cannabinoids and it is commonly known for its psychoactive substance tetrahydrocannabinol or as a source of narcotic substances. The recent years’ cannabis cultivation also increases due to its wide use both for medical and industrial purposes as well as for uses as para-pharmaceuticals, cosmetics and food commodities. Depending on the final product, different parts of the plant are utilized, with the leaves and bud (seeds) being the most frequently used. Cannabis can accumulate various contaminants, including heavy metals, both from the soil and the water in which the plant grows. More specifically, metals may occur naturally in the soil and water, or they can enter into the environment through fertilizers, pesticides and fungicides that are commonly applied to crops. The high probability of metals accumulation in cannabis, combined with the latter growing use, raise concerns about the potential health effects in humans and consequently lead to the need for the implementation of safety measures for cannabis products, such as guidelines for regulating contaminants, including metals, and especially the ones characterized by high toxicity in cannabis. Acknowledging the above, the aim of the current study was first to investigate metals contamination in cannabis samples collected from Greece, and secondly to examine potential differences in metals accumulation among the different parts of the plant. To our best knowledge, this is the first study presenting information on elements in cannabis cultivated in Greece, and also on the distribution pattern of the former in the plant body. To this end, the leaves and the seeds of all the samples were initially separated and dried and then digested with Nitric acid (HNO₃) and Hydrochloric acid (HCl). For the analysis of these samples, an Inductive Coupled Plasma-Mass Spectrometry (ICP-MS) method was developed, able to quantify 28 elements. Internal standards were added at a constant rate and concentration to all calibration standards and unknown samples, while two certified reference materials were analyzed in every batch to ensure the accuracy of the measurements. The repeatability of the method and the background contamination were controlled by the analysis of quality control (QC) standards and blank samples in every sequence, respectively. According to the results, essential metals, such as Ca, Zn and Mg, were detected at high levels. On the contrary, the concentration of high toxicity metals, like As (average: 0.10ppm), Pb (average: 0.36ppm), Cd (average: 0.04ppm), and Hg (average: 0.012ppm) were very low in all the samples, indicating that no harmful effects on human health can be caused by the analyzed samples. Moreover, it appears that the pattern of contamination of metals is very similar in all the analyzed samples, which could be attributed to the same origin of the analyzed cannabis, i.e., the common soil composition, use of fertilizers, pesticides, etc. Finally, as far as the distribution pattern between the different parts of the plant is concerned, it was revealed that leaves present a higher concentration in comparison to seeds for all metals examined.

Keywords: cannabis, heavy metals, ICP-MS, leaves and seeds, elements

Procedia PDF Downloads 82

Authors: Nick Woodier, Iain Moppett

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Background: It is estimated that one in ten patients admitted to hospital will suffer an adverse event in their care. While the majority of these will result in low harm, patients are being significantly harmed by the processes meant to help them. Healthcare, therefore, seeks to make improvements in patient safety by taking learning from other industries that are perceived to be more mature in their management of safety events. Of particular interest to healthcare are ‘near misses,’ those events that almost happened but for an intervention. Healthcare does not have any guidance as to how best to manage and learn from near misses to reduce the chances of harm to patients. The authors, as part of a larger study of near-miss management in healthcare, sought to learn from the UK nuclear sector to develop principles for how healthcare can identify, report, and learn from near misses to improve patient safety. The nuclear sector was chosen as an exemplar due to its status as an ultra-safe industry. Methods: A Grounded Theory (GT) methodology, augmented by a scoping review, was used. Data collection included interviews, scenario discussion, field notes, and the literature. The review protocol is accessible online. The GT aimed to develop theories about how nuclear manages near misses with a focus on defining them and clarifying how best to support reporting and analysis to extract learning. Near misses related to radiation release or exposure were focused on. Results: Eightnuclear interviews contributed to the GT across nuclear power, decommissioning, weapons, and propulsion. The scoping review identified 83 articles across a range of safety-critical industries, with only six focused on nuclear. The GT identified that nuclear has a particular focus on precursors and low-level events, with regulation supporting their management. Exploration of definitions led to the recognition of the importance of several interventions in a sequence of events, but that do not solely rely on humans as these cannot be assumed to be robust barriers. Regarding reporting and analysis, no consistent methods were identified, but for learning, the role of operating experience learning groups was identified as an exemplar. The safety culture across nuclear, however, was heard to vary, which undermined reporting of near misses and other safety events. Some parts of the industry described that their focus on near misses is new and that despite potential risks existing, progress to mitigate hazards is slow. Conclusions: Healthcare often sees ‘nuclear,’ as well as other ultra-safe industries such as ‘aviation,’ as homogenous. However, the findings here suggest significant differences in safety culture and maturity across various parts of the nuclear sector. Healthcare can take learning from some aspects of management of near misses in nuclear, such as how they are defined and how learning is shared through operating experience networks. However, healthcare also needs to recognise that variability exists across industries, and comparably, it may be more mature in some areas of safety.

Keywords: culture, definitions, near miss, nuclear safety, patient safety

Procedia PDF Downloads 86

Authors: Hami Ashraf, Mohammad Heydarnejad

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Introduction: The landscape of cancer treatment has been revolutionized by immunotherapy, offering novel therapeutic avenues for diverse cancer types. Animal models play a pivotal role in the development and elucidation of these therapeutic modalities. Nevertheless, the manifestation of Graft-versus-Host Disease (GVHD) in such models poses significant challenges, muddling the interpretation of experimental data within the ambit of cancer immunotherapy. This study is dedicated to scrutinizing the role of GVHD as a confounding factor in animal models used for cancer immunotherapy, alongside proposing viable strategies to mitigate this complication. Method: Employing a systematic review framework, this study undertakes a comprehensive literature survey including academic journals in PubMed, Embase, and Web of Science databases and conference proceedings to collate pertinent research that delves into the impact of GVHD on animal models in cancer immunotherapy. The acquired studies undergo rigorous analysis and synthesis, aiming to assess the influence of GVHD on experimental results while identifying strategies to alleviate its confounding effects. Results: Findings indicate that GVHD incidence significantly skews the reliability and applicability of experimental outcomes, occasionally leading to erroneous interpretations. The literature surveyed also sheds light on various methodologies under exploration to counteract the GVHD dilemma, thereby bolstering the experimental integrity in this domain. Conclusion: GVHD's presence critically affects both the interpretation and validity of experimental findings, underscoring the imperative for strategies to curtail its confounding impacts. Current research endeavors are oriented towards devising solutions to this issue, aiming to augment the dependability and pertinence of experimental results. It is incumbent upon researchers to diligently consider and adjust for GVHD's effects, thereby enhancing the translational potential of animal model findings to clinical applications and propelling progress in the arena of cancer immunotherapy.

Keywords: graft-versus-host disease, cancer immunotherapy, animal models, preclinical model

Procedia PDF Downloads 39

Authors: Epaminondas G. Kyriakidis, Theodosis D. Dimitrakos, Constantinos C. Karamatsoukis

Abstract:

The vehicle routing problem (VRP) is a well-known problem in Operations Research and has been widely studied during the last fifty-five years. The context of the VRP is that of delivering or collecting products to or from customers who are scattered in a geographical area and have placed orders for these products. A vehicle or a fleet of vehicles start their routes from a depot and visit the customers in order to satisfy their demands. Special attention has been given to the capacitated VRP in which the vehicles have limited carrying capacity for the goods that are delivered or collected. In the present work, we present a specific capacitated stochastic vehicle routing problem which has many realistic applications. We develop and analyze a mathematical model for a specific vehicle routing problem in which a vehicle starts its route from a depot and visits N customers according to a particular sequence in order to collect from them two similar but not identical products. We name these products, product 1 and product 2. Each customer possesses items either of product 1 or product 2 with known probabilities. The number of the items of product 1 or product 2 that each customer possesses is a discrete random variable with known distribution. The actual quantity and the actual type of product that each customer possesses are revealed only when the vehicle arrives at the customer’s site. It is assumed that the vehicle has two compartments. We name these compartments, compartment 1 and compartment 2. It is assumed that compartment 1 is suitable for loading product 1 and compartment 2 is suitable for loading product 2. However, it is permitted to load items of product 1 into compartment 2 and items of product 2 into compartment 1. These actions cause costs that are due to extra labor. The vehicle is allowed during its route to return to the depot to unload the items of both products. The travel costs between consecutive customers and the travel costs between the customers and the depot are known. The objective is to find the optimal routing strategy, i.e. the routing strategy that minimizes the total expected cost among all possible strategies for servicing all customers. It is possible to develop a suitable dynamic programming algorithm for the determination of the optimal routing strategy. It is also possible to prove that the optimal routing strategy has a specific threshold-type strategy. Specifically, it is shown that for each customer the optimal actions are characterized by some critical integers. This structural result enables us to design a special-purpose dynamic programming algorithm that operates only over these strategies having this structural property. Extensive numerical results provide strong evidence that the special-purpose dynamic programming algorithm is considerably more efficient than the initial dynamic programming algorithm. Furthermore, if we consider the same problem without the assumption that the customers are ordered, numerical experiments indicate that the optimal routing strategy can be computed if N is smaller or equal to eight.

Keywords: dynamic programming, similar products, stochastic demands, stochastic preferences, vehicle routing problem

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