Search results for: hotspot mutation

Authors: Alieh Farshbaf, Tayyeb Bahrami

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Introduction: Cc-chemokine receptor-5 (CCR5) is known as a main co-receptor in human immunodeficiency virus type-1 (HIV-1) infection. Many studies showed 32bp deletion (Δ32) in CCR5 gene, provide natural resistance to HIV-1 infection in homozygous individuals. Inducing the resistance mechanism by CCR5 in HIV-1 infected patients eliminated many problems of highly-active-anti retroviral therapy (HAART) drugs like as low safety, side-effects and virus rebounding from latent reservoirs. New treatments solved some restrictions that are based on gene modification and cell therapy. Literature review: The stories of the “Berlin and Boston patients” showed autologous hematopoietic stem cells transplantation (HSCT) could provide effective cure of HIV-1 infected patients. Furthermore, gene modification by zinc finger nuclease (ZFN) demonstrated another successful result again. Despite the other studies for gene therapy by ∆32 genotype, there is another mutation -CCR5 ∆32/m303- that provides HIV-1 resistant. It is a heterozygote genotype for ∆32 and T→A point mutation at nucleotide 303. These results approved the key role of CCR5 gene. Conclusion: Recent studies showed immune gene therapy and cell therapy could provide effective cure for refractory disease like as HIV. Eradication of HIV-1 from immune system was not observed by HAART, because of reloading virus genome from latent reservoirs after stopping them. It is showed that CCR5 could induce natural resistant to HIV-1 infection by the new approaches based on stem cell transplantation and gene modifying.

Keywords: CCR5, HIV-1, stem cell, immune gene therapy, gene modification

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Authors: Kendouci Khedidja, Mazari Benyounes, Benhadria Mohamed Rachid, Dadi Rachida

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In recent years, direct torque control (DTC) has become an alternative to the well-known vector control especially for permanent magnet synchronous motor (PMSM). However, it presents a problem of field linkage and torque ripple. In order to solve this problem, the conventional DTC is combined with space vector pulse width modulation (SVPWM). This control theory has achieved great success in the control of PMSM. That has become a hotspot for resolving. The main objective of this paper gives us an introduction of the DTC and SVPWM-DTC control theory of PMSM which has been simulating on each part of the system via Matlab/Simulink based on the mathematical modeling. Moreover, the outcome of the simulation proved that the improved SVPWM- DTC of PMSM has a good dynamic and static performance.

Keywords: PMSM, DTC, SVM, speed control

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Authors: Aminah Muchdar

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To increase the genetic diversity of soybean in order to adapt to agroecology in Indonesia conducted ways including introduction, cross, mutation and genetic transformation. The purpose of this research is to obtain early maturity soybean mutant lines, large seed tolerant to drought with high yield potential. This study consisted of two stages: the first is sensitivity of gamma rays carried out in the Laboratory BATAN. The genetic variety used is Anjasmoro. The method seeds irradiated with gamma rays at a rate of activity with the old ci 1046.16976 irradiation 0-71 minutes. Irradiation doses of 0, 100, 200, 300, 400, 500, 600, 700, 800, 900 and 1000gy. The results indicated all seeds irradiated with doses of 0 - 1000gy, just a dose of 200 and 300gy are able to show the percentage of germination, plant height, number of leaves, number of normal sprouts and green leaves of the best and can be continued for a second trial in order to assemble and to get mutants which is expected. The result of second stage of soybean M2 Population irradiated with diversity Gamma Irradiation performed that in the form of soybean planting, the seed planted is the first derivative of the M2 irradiated seeds. The result after the age of 30ADP has already showing growth and development of plants that vary when compared to its parent, both in terms of plant height, number of leaves, leaf shape and leaf forage level. In the generative phase, a plant that has been irradiated 200 and 300 gy seen some plants flower form packs, but not formed pods, there is also a form packs of flowers, but few pods produce soybean morphological characters such as plant height, number of branches, pods, days to flowering, harvesting, seed weight and seed number.

Keywords: gamma ray, genetic mutation, irradiation, soybean

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Authors: Yasser O. Abualnaja1, Alexandra Pavlidou2, Taha Boksmati3, Ahmad Alharbi3, Hammad Alsulmi3, Saleh Omar Maghrabi3, Hassan Mowalad3, Rayan Mutwalli3, James H. Churchill4, Afroditi Androni2, Dionysios Ballas2, Ioannis Hatzianestis2, Harilaos Kontoyiannis2, Angeliki Konstantinopoulou2, Georgios Krokkos1, 5, Georgios Pappas2, Vassilis P. Papadopoulos2, Konstantinos Parinos2, Elvira Plakidi2, Eleni Rousselaki2, Dimitris Velaoras2, Panagiota Zachioti2, Theodore Zoulias2, Ibrahim Hoteit5.

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The coastal areas along the Kingdom of Saudi Arabia on both the Red Sea and Arabian Gulf have been witnessing in the past decades an unprecedented economic growth and a rapid increase in anthropogenic activities. Therefore, the Saudi Arabian government has decided to frame a strategy for sustainable development of the coastal and marine environments, which comes in the context of the Vision 2030, aimed at providing the first comprehensive ‘Status Quo Assessment’ of the Kingdom’s coastal and marine environments. This strategy will serve as a baseline assessment for future monitoring activities; this baseline is relied on scientific evidence of the drivers, pressures, and their impact on the environments of the Red Sea and Arabian Gulf. A key element of the assessment was the cumulative pressures of the hotspots analysis, which was developed following the principles of the Driver-Pressure-State-Impact-Response (DPSIR) framework and using the cumulative pressure and impact assessment methodology. Ten hotspot sites were identified, eight in the Red Sea and two in the Arabian Gulf. Thus, multidisciplinary research cruises were conducted throughout the Red Sea and the Arabian Gulf coastal and marine environments in June/July 2021 and September 2021, respectively, in order to understand the relative impact of hydrography and the various pressures on the quality of seawater and sediments. The main objective was to record the physical and biogeochemical parameters along the coastal waters of the Kingdom, tracing the dispersion of contaminants related to specific pressures. The assessment revealed the effect of hydrography on the trophic status of the southern marine coastal areas of the Red Sea. Jeddah Lagoon system seems to face significant eutrophication and pollution challenges, whereas sediments are enriched in some heavy metals in many areas of the Red Sea and the Arabian Gulf. This multidisciplinary research in the Red Sea and the Arabian Gulf coastal waters will pave the way for future detailed environmental monitoring strategies for the Saudi Arabian marine environment.

Keywords: arabian gulf, contaminants, hotspot, red sea

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Authors: G. Ultanbekova, Zh. Suleimenova, Zh. Rakhmetova, G. Mombekova, S. Mantieva

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Plant Growth Promoting Rhizobacteria (PGPR) are a group of free-living bacteria that colonize the rhizosphere, enhance plant growth of many cereals and other important agricultural crops and protect plants from disease and abiotic stresses through a wide variety of mechanisms. The use of PGPR has been proven to be an environmentally sound way of increasing crop yields by facilitating plant growth. In the present study, strain improvement of PGPR isolates were carried out by chemical mutagenesis for the improvement of growth and yield of lima bean. Induced mutagenesis is widely used for the selection of microorganisms producing biologically active substances and further improving their activities. Strain improvement is usually done by classical mutagenesis which involves exposing the microbes to chemical or physical mutagens. The strains of Pseudomonas putida 4/1, Azotobacter chroococcum Р-29 and Bacillus subtilis were subjected to mutation process for strain improvement by treatment with a chemical agent (sodium nitrite) to cause mutation and were observed for its consequent action on the seeds germination and plant growth of lima bean (Phaseolus lunatus). Bacterial mutant strains of Pseudomonas putida M-1, Azotobacter chroococcum M-1 and Bacillus subtilis M-1, treated with sodium nitrite in the concentration of 5 mg/ml for 120 min, were found effective to enhance the germination of lima bean seeds compared to parent strains. Moreover, treatment of the lima bean seeds with a mutant strain of Bacillus subtilis M-1 had a significant stimulation effect on plant growth. The length of the stems and roots of lima bean treated with Bacillus subtilis M-1 increased significantly in comparison with parent strain in 1.6 and 1.3 times, respectively.

Keywords: chemical mutagenesis, germination, kidney bean, plant growth promoting rhizobacteria (PGPR)

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Authors: Julien Caudeville, Muriel Ismert

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Analyzing the relationship between environment and health has become a major preoccupation for public health as evidenced by the emergence of the French national plans for health and environment. These plans have identified the following two priorities: (1) to identify and manage geographic areas, where hotspot exposures are suspected to generate a potential hazard to human health; (2) to reduce exposure inequalities. At a regional scale and fine resolution of exposure outcome prerequisite, environmental monitoring networks are not sufficient to characterize the multidimensionality of the exposure concept. In an attempt to increase representativeness of spatial exposure assessment approaches, risk composite indicators could be built using additional available databases and theoretical framework approaches to combine factor risks. To achieve those objectives, combining data process and transfer modeling with a spatial approach is a fundamental prerequisite that implies the need to first overcome different scientific limitations: to define interest variables and indicators that could be built to associate and describe the global source-effect chain; to link and process data from different sources and different spatial supports; to develop adapted methods in order to improve spatial data representativeness and resolution. A GIS-based modeling platform for quantifying human exposure to chemical substances (PLAINE: environmental inequalities analysis platform) was used to build health risk indicators within the Lorraine region (France). Those indicators combined chemical substances (in soil, air and water) and noise risk factors. Tools have been developed using modeling, spatial analysis and geostatistic methods to build and discretize interest variables from different supports and resolutions on a 1 km2 regular grid within the Lorraine region. By example, surface soil concentrations have been estimated by developing a Kriging method able to integrate surface and point spatial supports. Then, an exposure model developed by INERIS was used to assess the transfer from soil to individual exposure through ingestion pathways. We used distance from polluted soil site to build a proxy for contaminated site. Air indicator combined modeled concentrations and estimated emissions to take in account 30 polluants in the analysis. For water, drinking water concentrations were compared to drinking water standards to build a score spatialized using a distribution unit serve map. The Lden (day-evening-night) indicator was used to map noise around road infrastructures. Aggregation of the different factor risks was made using different methodologies to discuss weighting and aggregation procedures impact on the effectiveness of risk maps to take decisions for safeguarding citizen health. Results permit to identify pollutant sources, determinants of exposure, and potential hotspots areas. A diagnostic tool was developed for stakeholders to visualize and analyze the composite indicators in an operational and accurate manner. The designed support system will be used in many applications and contexts: (1) mapping environmental disparities throughout the Lorraine region; (2) identifying vulnerable population and determinants of exposure to set priorities and target for pollution prevention, regulation and remediation; (3) providing exposure database to quantify relationships between environmental indicators and cancer mortality data provided by French Regional Health Observatories.

Keywords: health risk, environment, composite indicator, hotspot areas

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Authors: Bindu I. Somarajan, Viney Gupta, Gagandeep Kaur Walia, Jasbir Kaur, Sunil Kumar, Shikha Gupta, Abadh K. Chaurasia, Dinesh Gupa, Abhinav Kaushik, Aditi Mehta, Vipin Gupta, Arundhati Sharma

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Background: Juvenile onset primary open angle glaucoma (JOAG), affects individuals under the age of 40 years. Studies on a few families of JOAG, that led to the discovery of the Myocilin gene, reported the disease to have an autosomal dominant pattern of inheritance. However, sporadic forms of JOAG been seen to be more common in some populations. Most pathological homozygous mutations in the CYP1B1 gene associated with JOAG have been seen among sporadic cases. Given the higher prevalence of sporadic JOAG cases in our population, we aimed to look for common mutations E229K and R368H, the two most common variants in the CYP1B1 gene associated with glaucoma. Objective: To determine the frequency and evaluate genotype phenotype correlation of CYP1B1 E229K and R368H mutations in a cohort of 120 sporadic Juvenile open angle glaucoma patients.Methods: Unrelated JOAG patients whose first degree relatives had been examined and found to be unaffected were included in the study. The patients and their parents were screened for E229K and R368H mutations. The phenotypic characteristics were compared between probands with and with out these mutations by SPSS v16. Results: Out of 120 JOAG patients included in the study, the E229K mutation was seen in 9 probands (7.5%) and R368H in 7 (5.8%). The average age of onset of the disease (p=0.3) and the highest untreated IOP (p=0.4) among those carrying mutations was not significantly different from those who did not have these mutations. The proportion of probands with angle dysgenesis among those with E229K and R368H mutations was 70% (11 out of 16) in comparison to 65% (67 out of 104) of those who did not harbour these mutations (p=0.56). Similarly the probands with moderate to high myopia among those with E229K and R368H mutations was 20% (3 out of 16) in comparison to 18% (18 out of 104) of those who did not harbour these mutations(p=0.59). Conclusion: The frequency of E229K and R368H mutations of the CYP1B1 gene is low even among sporadic JOAG patients. Moreover there is no clinical correlation between the presence of these mutations and disease severity

Keywords: CYP1B1, gene, IOP, JOAG, mutation

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Authors: Wang Zhenzhen, Wang Xu, Hong Liangping

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The construction of thematic commercial streets has been on the hotspot with the rapid development of cities. In order to improve the image and competitiveness of cities, many cities are building or rebuilding thematic commercial streets. However, many contradictions and problems have emerged during this process. Therefore, it is significant, for both the practice and the research, to analyse the development of thematic commercial streets and provide some useful suggestions. Through the deep research and comparative study of the eight typical thematic commercial streets in Harbin, this paper summarize the current situations, laws and influencing factors of the development of these streets, and then put forward some suggestions about the plan, constructions and developments of the thematic commercial streets.

Keywords: thematic commercial streets, laws of the development, influence factors, the constructions and developments, degrees of aggregation

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Authors: Xiaobing Liu, Bo Zhang, Xiaolong Zhao

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The square-dancing is one of the most popular new physical activities in China in recent years, which has become a hotspot of Chinese landscape research. This paper collects 749 news reports from four authoritative newspapers in Harbin for 3 years, and probes into the space use needs of participants and non-participants of square-dancing. In this paper, the research results are compared with the contents of three related planning and design codes in China, and some modification or supplementary suggestions are proposed from three aspects, such as decision-making process, total-quantity control, and site design. Different from the traditional research, this research does not use the data from interviews and the questionnaires, but uses the traditional media report content for analyzing. To some extent, it avoids the research result being excessively subjective, enhances objectivity and the authority.

Keywords: China, landscape, space design, square-dancing

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Authors: Syed Beenish Rufai, Sarman Singh

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Background: Performance of Genotype MTBDRsl (Hain Life science GmbH Germany) for detection of mutations associated with second-line drug resistance is well known. However, less evidence regarding the association of mutations and genetic background of strains is known which, in the future, is essential for clinical management of anti-tuberculosis drugs in those settings where the probability of particular genotype is predominant. Material and Methods: During this retrospective study, a total of 259 MDR-TB isolates obtained from pulmonary TB patients were tested for second-line drug susceptibility testing (DST) using Genotype MTBDRsl VER 1.0 and compared with BACTEC MGIT-960 as a reference standard. All isolates were further characterized using spoligotyping. The spoligo patterns obtained were compared and analyzed using SITVIT_WEB. Results: Of total 259 MDR-TB isolates which were screened for second-line DST by Genotype MTBDRsl, mutations were found to be associated with gyrA, rrs and emb genes in 82 (31.6%), 2 (0.8%) and 90 (34.7%) isolates respectively. 16 (6.1%) isolates detected mutations associated with both FQ as well as to AG/CP drugs (XDR-TB). No mutations were detected in 159 (61.4%) isolates for corresponding gyrA and rrs genes. Genotype MTBDRsl showed a concordance of 96.4% for detection of sensitive isolates in comparison with second-line DST by BACTEC MGIT-960 and 94.1%, 93.5%, 60.5% and 50% for detection of XDR-TB, FQ, EMB, and AMK/CAP respectively. D94G was the most prevalent mutation found among (38 (46.4%)) OFXR isolates (37 FQ mono-resistant and 1 XDR-TB) followed by A90V (23 (28.1%)) (17 FQ mono-resistant and 6 XDR-TB). Among AG/CP resistant isolates A1401G was the most frequent mutation observed among (11 (61.1%)) isolates (2 AG/CP mono-resistant isolates and 9 XDR-TB isolates) followed by WT+A1401G (6 (33.3%)) and G1484T (1 (5.5%)) respectively. On spoligotyping analysis, Beijing strain (46%) was found to be the most predominant strain among pre-XDR and XDR TB isolates followed by CAS (30%), X (6%), Unique (5%), EAI and T each of 4%, Manu (3%) and Ural (2%) respectively. Beijing strain was found to be strongly associated with D94G (47.3%) and A90V mutations by (47.3%) and 34.8% followed by CAS strain by (31.6%) and 30.4% respectively. However, among AG/CP resistant isolates, only Beijing strain was found to be strongly associated with A1401G and WT+A1401G mutations by 54.5% and 50% respectively. Conclusion: Beijing strain was found to be strongly associated with the most prevalent mutations among pre-XDR and XDR TB isolates. Acknowledgments: Study was supported with Grant by All India Institute of Medical Sciences, New Delhi reference No. P-2012/12452.

Keywords: tuberculosis, line probe assay, XDR TB, drug susceptibility

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Authors: Gilbert O. Osayemwenre, Meyer L. Edson

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Ethylene vinyl acetate (EVA) encapsulation degradation affects the performance of photovoltaic (PV) module. Hotspot formation causes the EVA encapsulation to undergo photothermal deterioration and molecular breakdown by UV radiation. This leads to diffusion of chemical particles into other layers. During outdoor deployment, the EVA encapsulation in the affect region loses its adhesive strength, when this happen the affected region layer undergoes rapid delamination. The presence of photo-thermal degradation is detrimental to PV modules as it causes both optical and thermal degradation. Also, it enables the encapsulant to be more susceptible to chemicals substance and moisture. Our findings show a high concentration of Sodium, Phosphorus and Aluminium which originate from the glass substrate, cell emitter and back contact respectively.

Keywords: ethylene vinyl acetate (EVA), encapsulation, photo-thermal degradation, thermogravimetric analysis (TGA), scanning probe microscope (SPM)

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Authors: Dalu Zhang, Xiang Jin, Dejiang Zhou, Jianpeng Wang, Haiying Jiang

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Traditional TCP/IP network is showing lots of shortages and research for future networks is becoming a hotspot. FIA (Future Internet Architecture) and FIA-NP (Next Phase) are supported by US NSF for future Internet designing. Moreover, virtual machine migration is a significant technique in cloud computing. As a network application, it should also be supported in XIA (expressive Internet Architecture), which is in both FIA and FIA-NP projects. This paper is an experimental study aims at verifying the feasibility of VM migration over XIA. We present three ways to maintain VM connectivity and communication states concerning DAG design and routing table modification. VM migration experiments are conducted intra-AD and inter-AD with KVM instances. The procedure is achieved by a migration control protocol which is suitable for the characters of XIA. Evaluation results show that our solutions can well supports full live VM migration over XIA network respectively, keeping services seamless.

Keywords: DAG, downtime, virtual machine migration, XIA

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Authors: Hassan Abubakar

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This paper will serve as a guide to good design and implementation of wireless networking for campus institutions in Nigeria. It can be implemented throughout the primary, secondary and tertiary institutions. This paper describe the some technical functions, standard configurations and layouts of the 802.11 wireless LAN(Local Area Network) that can be implemented across the campus network. The paper also touches upon the wireless infrastructure standards involved with enhanced services, such as voice over wireless and wireless guest hotspot. The paper also touch the benefits derived from implementing campus wireless network and share some lights on how to arrive at the success in increasing the performance of wireless and using the campus wireless to share resources like software applications, printer and documents.

Keywords: networking, standards, wireless local area network (WLAN), radio frequency (RF), campus

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Authors: Saima Saleem, Zubair Abbasi, Abdul Hameed, Mansoor Ahmed Khan, Navid Rashid Qureshi, Abid Azhar

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Oral Squamous Cell Carcinoma (OSCC) is the leading cause of death in the developing countries like Pakistan. This problem aggravates because of the excessive use of available chewing products. In spite of widespread information on their use and purported legislations against their use the Pakistani markets are classical examples of selling chewable carcinogenic mutagens. Reported studies indicated that these products are rich in reactive oxygen species (ROS) and polyphenols. TP53 gene is involved in the suppression of tumor. It has been reported that somatic mutations caused by TP53 gene are the foundation of the cancer. This study aims to find the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients. Total 260 tissues and blood specimens were collected from OSCC patients and compared with age and sex matched controls. Mutations in exons 2-11 of TP53 were examined by PCR-SSCP. Samples showing mobility shift were directly sequenced. Two mutations were found in exon 4 at nucleotide position 108 and 215 and one in exon 7 at nucleotide position 719 of the coding sequences in patient’s tumor samples. These results show that substitution of proline with arginine at codon 72 and serine with threonine at codon 240 of p53 protein. These polymorphic changes, found in tumor samples of OSCC, could be involved in loss of heterozygocity and apoptotic activity in the binding domain of TP53. The model of the mutated TP53 gene elaborated a nonfunctional unfolded p53 protein, suggesting an important role of these mutations in p53 protein inactivation and malfunction. This nonfunctional 3D model also indicates that exogenous tobacco related carcinogens may act as DNA-damaging agents affecting the structure of DNA. The interpretations could be helpful in establishing the pathways responsible for tumor formation in OSCC patients.

Keywords: TP53 mutation/polymorphism, OSCC, PCR-SSCP, direct DNA sequencing, 3D structure

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Authors: Hamza Zidoum

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This paper investigates the impact of human genetic variation on the function of human proteins using machine-learning algorithms. Single-Nucleotide Polymorphism represents the most common form of human genome variation. We focus on the single amino-acid polymorphism located in the coding region as they can affect the protein function leading to pathologic phenotypic change. We use several supervised Machine Learning methods to identify structural properties correlated with increased risk of the missense mutation being damaging. SVM associated with Principal Component Analysis give the best performance.

Keywords: single-nucleotide polymorphism, machine learning, feature selection, SVM

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Authors: Abiodun Amusan, Olugbenga Akinola, Kazeem Akano, María Hernández-Castañeda, Jenna Dick, Akintunde Sowunmi, Geoffrey Hart, Grace Gbotosho

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Introduction: Artemisinin-based Combination Therapy (ACTs) is the cornerstone malaria treatment option in most malaria-endemic countries. Unfortunately, the malaria control effort is constantly being threatened by resistance of Plasmodium falciparum to ACTs. The recent evidence of artemisinin resistance in East Africa and its possibility of spreading to other African regions portends an imminent health catastrophe. This study aimed at evaluating the occurrence, prevalence, and influence of artemisinin-resistance markers on treatment outcomes in Ibadan before and after post-adoption of artemisinin combination therapy (ACTs) in Nigeria in 2005. Method: The study involved day zero dry blood spot (DBS) obtained from malaria patients during retrospective (2000-2005) and prospective (2021) studies. A cohort in the prospective study received oral dihydroartemisinin-piperaquine and underwent a 42-day follow-up to observe treatment outcomes. Genomic DNA was extracted from the DBS samples using a QIAamp blood extraction kit. Fragments of P. falciparum kelch13 (Pfkelch13), P. falciparum coronin (Pfcoronin), P. falciparum multidrug resistance 2 (PfMDR2), and P. falciparum chloroquine resistance transporter (PfCRT) genes were amplified and sequenced on a sanger sequencing platform to identify artemisinin resistance-associated mutations. Mutations were identified by aligning sequenced data with reference sequences obtained from the National Center for Biotechnology Information. Data were analyzed using descriptive statistics and student t-tests. Results: Mean parasite clearance time (PCT) and fever clearance time (FCT) were 2.1 ± 0.6 days (95% CI: 1.97-2.24) and 1.3 ± 0.7 days (95% CI: 1.1-1.6) respectively. Four mutations, K189T [34/53(64.2%)], R255K [2/53(3.8%)], K189N [1/53(1.9%)] and N217H [1/53(1.9%)] were identified within the N-terminal (Coiled-coil containing) domain of Pfkelch13. No artemisinin resistance-associated mutation usually found within the β-propeller domain of the Pfkelch13 gene was found in these analyzed samples. However, K189T and R255K mutations showed a significant correlation with longer parasite clearance time in the patients (P<0.002). The observed Pfkelch13 gene changes did not influence the baseline mean parasitemia (P = 0.44). P76S [17/100 (17%)] and V62M [1/100 (1%)] changes were identified in the Pfcoronin gene fragment without any influence on the parasitological parameters. No change was observed in the PfMDR2 gene, while no artemisinin resistance-associated mutation was found in the PfCRT gene. Furthermore, a sample each in the retrospective study contained the Pfkelch13 K189T and Pfcoronin P76S mutations. Conclusion: The study revealed absence of genetic-based evidence of artemisinin resistance in the study population at the time of study. The high frequency of K189T Pfkelch13 mutation and its correlation with increased parasite clearance time in this study may depict geographical variation of resistance mediators and imminent artemisinin resistance, respectively. The study also revealed an inherent potential of parasites to harbour drug-resistant genotypes before the introduction of ACTs in Nigeria.

Keywords: artemisinin resistance, plasmodium falciparum, Pfkelch13 mutations, Pfcoronin

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Authors: Zoltan Horvath, Dora Nagy

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In this research, it was examined whether individual COVID variants cause differences in the lactate curve of cyclists. After all, the virus variants attacked different organs in our body during the infections. During our tests, we used a traditional lactate step test, the results of which were compared with the values before the infection. In the tests, it has been proven that different virus variants show unique lactate curves. In this way, based on the lactate curve, it is possible to identify which variant caused the disease. Thanks to this, it has been shorten the return time, because we can apply the best return protocol after infection to the competitors.

Keywords: COVID-Sars19, lactate, virus mutation, lactate profile

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Authors: Till Fehlauer, Blanche Collin, Bernard Angeletti, Andrea Somogyi, Claire Lallemand, Perrine Chaurand, Cédric Dentant, Clement Levard, Jerome Rose

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Over the last decades, yttrium (Y) has gained importance in high-tech applications. It is an essential part of alloys and compounds used for lasers, displays, or cell phones, for example. Due to its chemical similarities with the lanthanides, Y is often considered a rare earth element (REE). Despite their increased usage, the environmental behavior of REEs remains poorly understood. Especially regarding their interactions with plants, many uncertainties exist. On the one hand, Y is known to have a negative effect on root development and germination, but on the other hand, it appears to promote plant growth at low concentrations. In order to understand these phenomena, a precise knowledge is necessary about how Y is absorbed by the plant and how it is handled once inside the organism. Contradictory studies exist, stating that due to a similar ionic radius, Y and the other REEs might be absorbed through Ca²⁺-channels, while others suspect that Y has a shared pathway with Al³⁺. In this study, laser ablation coupled ICP-MS, and synchrotron-based micro-X-ray fluorescence (µXRF, beamline Nanoscopium, SOLEIL, France) have been used in order to localize Y within the plant tissue and identify associated elements. The plant used in this study is Saxifraga paniculata, a rugged alpine plant that has shown an affinity for Y in previous studies (in prep.). Furthermore, Saxifraga paniculata performs guttation, which means that it possesses phloem sap secreting openings on the leaf surface that serve to regulate root pressure. These so-called hydathodes could provide special insights in elemental transport in plants. The plants have been grown on Y doped soil (500mg/kg DW) for four months. The results showed that Y was mainly concentrated in the roots of Saxifraga paniculata (260 ± 85mg/kg), and only a small amount was translocated to the leaves (10 ± 7.8mg/kg). µXRF analysis indicated that within the root transects, the majority of Y remained in the epidermis and hardly penetrated the stele. Laser ablation coupled ICP-MS confirmed this finding and showed a positive correlation in the roots between Y, Fe, Al, and to a lesser extent Ca. In the stem transect, Y was mainly detected in a hotspot of approximately 40µm in diameter situated in the endodermis area. Within the stem and especially in the hotspot, Y was highly colocalized with Al and Fe. Similar-sized Y hotspots have been detected in/on the leaves. All of them were strongly colocalized with Al and Fe, except for those situated within the hydathodes, which showed no colocalization with any of the measured elements. Accordingly, a relation between Y and Ca during root uptake remains possible, whereas a correlation to Fe and Al appears to be dominant in the aerial parts, suggesting common storage compartments, the formation of complexes, or a shared pathway during translocation.

Keywords: laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), Phytoaccumulation, Rare earth elements, Saxifraga paniculata, Synchrotron-based micro-X-ray fluorescence, Yttrium

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Authors: Debamitra Chakravorty, Pratap K. Parida

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Cold-adapted proteases enhance wash performance in low-temperature laundry resulting in a reduction in energy consumption and wear of textiles and are also used in the dehairing process in leather industries. Unfortunately, the possible drawbacks of using cold-adapted proteases are their instability at higher temperatures. Therefore, proteases with broad temperature stability are required. Unfortunately, wild-type cold-adapted proteases exhibit instability at higher temperatures and thus have low shelf lives. Therefore, attempts to engineer cold-adapted proteases by protein engineering were made previously by directed evolution and random mutagenesis. The lacuna is the time, capital, and labour involved to obtain these variants are very demanding and challenging. Therefore, rational engineering for cold stability without compromising an enzyme's optimum pH and temperature for activity is the current requirement. In this work, mutations were rationally designed with the aid of high throughput computational methodology of network analysis, evolutionary conservation scores, and molecular dynamics simulations for Savinase from Bacillus lentus with the intention of rendering the mutants cold stable without affecting their temperature and pH optimum for activity. Further, an attempt was made to incorporate a mutation in the most stable mutant rationally obtained by this method to introduce oxidative stability in the mutant. Such enzymes are desired in detergents with bleaching agents. In silico analysis by performing 300 ns molecular dynamics simulations at 5 different temperatures revealed that these three mutants were found to be better in cold stability compared to the wild type Savinase from Bacillus lentus. Conclusively, this work shows that cold adaptation without losing optimum temperature and pH stability and additionally stability from oxidative damage can be rationally designed by in silico enzyme engineering. The key findings of this work were first, the in silico data of H5 (cold stable savinase) used as a control in this work, corroborated with its reported wet lab temperature stability data. Secondly, three cold stable mutants of Savinase from Bacillus lentus were rationally identified. Lastly, a mutation which will stabilize savinase against oxidative damage was additionally identified.

Keywords: cold stability, molecular dynamics simulations, protein engineering, rational design

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Authors: Darren Camilleri, Robert Rolston

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Rotor radial vents make use of the pumping effect to increase airflow through the active material thus reduce hotspot temperatures. The effect of rotor radial pumping in synchronous machines has been studied previously. This paper presents the findings of previous studies and builds upon their theories using a parametric numerical approach to investigate the rotor radial pumping effect. The pressure head generated by the poles and radial vent flow-rate were identified as important factors in maximizing the benefits of the pumping effect. The use of Minitab and ANSYS Workbench to investigate the key performance characteristics of radial pumping through a Design of Experiments (DOE) was described. CFD results were compared with theoretical calculations. A correlation for each response variable was derived through a statistical analysis. Findings confirmed the strong dependence of radial vent length on vent pressure head, and radial vent cross-sectional area was proved to be significant in maximising radial vent flow rate.

Keywords: CFD, cooling, electrical machines, regression analysis

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Authors: Simangele Dlamini

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Smart city development is seen as a way of facing the challenges brought about by the growing urban population the world over. Research indicates that cities have a role to play in combating urban challenges like crime, waste disposal, greenhouse gas emissions, and resource efficiency. These solutions should be such that they do not make city management less sustainable but should be solutions-driven, cost and resource-efficient, and smart. This study explores opportunities on how the City of Johannesburg, South Africa, can use Geographic Information Systems, Big Data and the Internet of Things (IoT) in identifying opportune areas to initiate smart city initiatives such as smart safety, smart utilities, smart mobility, and smart infrastructure in an integrated manner. The study will combine Big Data, using real-time data sources to identify hotspot areas that will benefit from ICT interventions. The GIS intervention will assist the city in avoiding a silo approach in its smart city development initiatives, an approach that has led to the failure of smart city development in other countries.

Keywords: smart cities, internet of things, geographic information systems, johannesburg

Procedia PDF Downloads 91

Authors: Zhou Hong, Gu Xiao-Qing, Lıu Hong-Jiao, Leng Jing

Abstract:

Seamless learning is becoming a research hotspot in recent years, and the emerging of micro-lectures, flipped classroom has strengthened the development of seamless learning. Based on the characteristics of the seamless learning across time and space and the course structure of the flipped classroom, and the theories of language learning, we put forward the language learning model which can support ‘seamless flipped’ environment (abbreviated as ‘S-F’). Meanwhile, the characteristics of the ‘S-F’ learning environment, the corresponding framework construction and the activity design of diversified corpora were introduced. Moreover, a language learning app named ‘Daily Speaking’ was developed to facilitate the practice of the language learning model in ‘S-F’ environment. In virtue of the learning case of Shanghai language, the rationality and feasibility of this framework were examined, expecting to provide a reference for the design of ‘S-F’ learning in different situations.

Keywords: seamless learning, flipped classroom, seamless-flipped environment, language learning model

Procedia PDF Downloads 152

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

Abstract:

Objective: Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioural deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani pomegranate extract on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). Methods: The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analysed. Results: APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Conclusion: Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioural impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, pomegranates, oman, cognitive decline, memory loss, anxiety, inflammation

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Authors: Abishek Rajkumar

Abstract:

Antibiotic resistance can occur naturally given the selective pressure placed on antibiotics. Within a large population of bacteria, there is a significant chance that some of those bacteria can develop resistance via mutations or genetic recombination. However, a growing public health concern has arisen over the fact that antibiotic resistance has increased significantly over the past few decades. This is because humans have been over-consuming and producing antibiotics, which has ultimately accelerated the antibiotic resistance seen in these bacteria. The product of all of this is an ongoing race between scientists and the bacteria as bacteria continue to develop resistance, which creates even more demand for an antibiotic that can still terminate the newly resistant strain of bacteria. This paper will focus on a myriad of aspects of antibiotic resistance in bacteria starting with how it occurs on a molecular level and then focusing on the antibiotic concentrations and how they affect the resistance and fitness seen in bacteria.

Keywords: antibiotic, molecular, mutation, resistance

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

Abstract:

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

Procedia PDF Downloads 290

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

Abstract:

Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

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Authors: Xiao Yihong, Yu Kexin, Burra Venkata Durga Kumar

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With the accelerating process of urbanization, the problem of urban road congestion is becoming more and more serious. Intelligent transportation system combining distributed and artificial intelligence has become a research hotspot. As the core development direction of the intelligent transportation system, Cooperative Intelligent Transportation System (C-ITS) integrates advanced information technology and communication methods and realizes the integration of humans, vehicle, roadside infrastructure, and other elements through the multi-agent distributed system. By analyzing the system architecture and technical characteristics of C-ITS, the report proposes a distributed multi-agent C-ITS. The system consists of Roadside Sub-system, Vehicle Sub-system, and Personal Sub-system. At the same time, we explore the scalability of the C-ITS and put forward incorporating local rewards in the centralized training decentralized execution paradigm, hoping to add a scalable value decomposition method. In addition, we also suggest introducing blockchain to improve the safety of the traffic information transmission process. The system is expected to improve vehicle capacity and traffic safety.

Keywords: distributed system, artificial intelligence, multi-agent, cooperative intelligent transportation system

Procedia PDF Downloads 178

Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Salina Y. Saddick

Abstract:

Mild gestational hyperglycemia (MGH) is a very common complication of pregnancy that is characterized by intolerance to glucose. The association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism to MGH has been previously reported. In this study, we evaluated the association between ACE polymorphism and the risk of MGH in a Saudi population. We conducted a case-control study in a population of 100 MGH patients and 100 control subjects. ACE gene polymorphism was analyzed by the novel approach of tetraprimer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR). The frequency of ACE polymorphism was not associated with either alleles or genotypes in MGH patients. Glucose concentration was found to be significantly associated with the MGH group. Our study suggests that ACE genotypes were not associated with ACE polymorphism in a Saudi population.

Keywords: MGH, ACE, insertion polymorphism, deletion polymorphism

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Authors: Khaleel Saleh Al-Rababah

Abstract:

Amyloid fibril forming regions, which are known as protein aggregates, in sequences of some protein families are associated with a number of diseases known as amyloidosis. Mutations play a role in forming fibrils by accelerating the fibril formation process. In this paper we want to extract diseases that caused by those mutations as a result of the impact of the mutations on structural and functional properties of the aggregated protein. We propose a text mining system, to automatically extract mutations, diseases and relations between mutations and diseases. We presented an algorithm based on finite state to cluster mutations found in the same sentence as a sentence could contain different mutation cause different diseases. Also, we presented a co reference algorithm that enables cross-link sentences.

Keywords: amyloid, amyloidosis, co reference, protein, text mining

Procedia PDF Downloads 497