Search results for: viral mutation

Authors: Gabriela C. Caldas, Fernanda C. Jacome, Arthur da C. Rasinhas, Ortrud M. Barth, Flavia B. dos Santos, Priscila C. G. Nunes, Yuli R. M. de Souza, Pedro Paulo de A. Manso, Marcelo P. Machado, Debora F. Barreto-Vieira

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The establishment of animal models for studies of DENV infections has been challenging, since circulating epidemic viruses do not naturally infect nonhuman species. Such studies are of great relevance to the various areas of dengue research, including immunopathogenesis, drug development and vaccines. In this scenario, the main objective of this study is to verify possible morphological changes, as well as the presence of antigens and viral RNA in lung samples from BALB/c mice experimentally infected with an epidemic and non-neuroadapted DENV-3 strain. Male BALB/c mice, 2 months old, were inoculated with DENV-3 by intravenous route. After 72 hours of infection, the animals were euthanized and the lungs were collected. Part of the samples was processed by standard technique for analysis by light and transmission electronic microscopies and another part was processed for real-time PCR analysis. Morphological analyzes of lungs from uninfected mice showed preserved tissue areas. In mice infected with DENV-3, the analyzes revealed interalveolar septum thickening with presence of inflammatory infiltrate, foci of alveolar atelectasis and hyperventilation, bleeding foci in the interalveolar septum and bronchioles, peripheral capillary congestion, accumulation of fluid in the blood capillary, signs of interstitial cell necrosis presence of platelets and mononuclear inflammatory cells circulating in the capillaries and/or adhered to the endothelium. In addition, activation of endothelial cells, platelets, mononuclear inflammatory cell and neutrophil-type polymorphonuclear inflammatory cell evidenced by the emission of cytoplasmic membrane prolongation was observed. DEN-like particles were seen in the cytoplasm of endothelial cells. The viral genome was recovered from 3 in 12 lung samples. These results demonstrate that the BALB / c mouse represents a suitable model for the study of the histopathological changes induced by DENV infection in the lung, with tissue alterations similar to those observed in human cases of DEN.

Keywords: BALB/c mice, dengue, histopathology, lung, ultrastructure

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Authors: Alexandru-Ion Marinescu

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There exist a plethora of methods in the scientific literature which tackle the well-established task of credit score evaluation. In its most abstract form, a credit scoring algorithm takes as input several credit applicant properties, such as age, marital status, employment status, loan duration, etc. and must output a binary response variable (i.e. “GOOD” or “BAD”) stating whether the client is susceptible to payment return delays. Data imbalance is a common occurrence among financial institution databases, with the majority being classified as “GOOD” clients (clients that respect the loan return calendar) alongside a small percentage of “BAD” clients. But it is the “BAD” clients we are interested in since accurately predicting their behavior is crucial in preventing unwanted loss for loan providers. We add to this whole context the constraint that the algorithm must yield an actual, tractable mathematical formula, which is friendlier towards financial analysts. To this end, we have turned to genetic algorithms and genetic programming, aiming to evolve actual mathematical expressions using specially tailored mutation and crossover operators. As far as data representation is concerned, we employ a very flexible mechanism – LINQ expression trees, readily available in the C# programming language, enabling us to construct executable pieces of code at runtime. As the title implies, they model trees, with intermediate nodes being operators (addition, subtraction, multiplication, division) or mathematical functions (sin, cos, abs, round, etc.) and leaf nodes storing either constants or variables. There is a one-to-one correspondence between the client properties and the formula variables. The mutation and crossover operators work on a flattened version of the tree, obtained via a pre-order traversal. A consequence of our chosen technique is that we can identify and discard client properties which do not take part in the final score evaluation, effectively acting as a dimensionality reduction scheme. We compare ourselves with state of the art approaches, such as support vector machines, Bayesian networks, and extreme learning machines, to name a few. The data sets we benchmark against amount to a total of 8, of which we mention the well-known Australian credit and German credit data sets, and the performance indicators are the following: percentage correctly classified, area under curve, partial Gini index, H-measure, Brier score and Kolmogorov-Smirnov statistic, respectively. Finally, we obtain encouraging results, which, although placing us in the lower half of the hierarchy, drive us to further refine the algorithm.

Keywords: expression trees, financial credit scoring, genetic algorithm, genetic programming, symbolic evolution

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Authors: Amit Chaudhary, B. S. Yadav, P. K. Maurya, A. M., S. Srivastava, S. Singh, A. Mani

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Cold shock protein A (CspA) is major cold inducible protein present in Escherichia coli. The protein is involved in stabilizing secondary structure of RNA by working as chaperone during cold temperature. Two RNA binding motifs play key role in the stabilizing activity. This study aimed to investigate implications of low temperature on structure and RNA binding activity of E. coli CspA. Molecular dynamics simulations were performed to compare the stability of the protein at 37°C and 10 °C. The protein was mutated at RNA binding motifs and docked with RNA to assess the stability of both complexes. Results suggest that CspA as well as CspA-RNA complex is more stable at low temperature. It was also confirmed that RNP1 and RNP2 play key role in RNA binding.

Keywords: CspA, homology modelling, mutation, molecular dynamics simulation

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Authors: Nino Damenia

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The paper discusses the risks arising in agriculture in Georgia, the possibilities of their acceptance and prevention, the threat created by the pandemic crisis, and the state programs for overcoming them. The share of agriculture in the country's GDP is 8.3%. Over the past five years, Georgia has imported $ 5.9 billion worth of agri-food products. Despite these figures, agriculture has become an important sector for the Georgian government since 2012, as evidenced by the more than 1.5 billion GEL spent from the 2012-2020 budget for agricultural development. Any field of agriculture, be it poultry, livestock, cereals, fruits, or vegetables, is very sensitive to various climatic and viral risks. Avoiding these risks requires additional investment. It is noteworthy that small farms are mainly affected by the risks, while relatively large farms face fewer problems because they are relatively prepared to face the problems and can avoid them more easily. An example of viral risk in the article is the export of hazelnuts, which has quite a lot of potential. Due to the spoilage of the crop caused by Brown Marmorated Stink Bug (BMSB), hazelnut exports have declined considerably over the years. If the volume of hazelnuts exported in 2016 was 179 378 thousand USD, due to the deficit caused by Brown Marmorated Stink Bug (BMSB) in 2018, it became 57 124 thousand USD. And after the situation was relatively settled, hazelnut seedlings were poisoned. By 2020, this figure improved to 91,088 thousand US dollars. The development of the agricultural sector and the reduction of risks require technological development, investor interest, and even more state support to enable more small farms to have the potential for greater production and sustainable development. The aim of the study is to identify the risks arising in the agricultural sector of Georgia before and after the pandemic, to evaluate them, compare them with the agriculture of some European countries, and to develop the necessary recommendations to avoid the emerging risks. The research uses methods of analysis and synthesis, observation, induction, deduction, and analysis of statistics. The paper is based on both Georgian and foreign scientific research, as well as state-published documentation on agricultural assistance programs. The research is based on the analysis of data published by the European Statistics Office, the National Statistics Office of Georgia, and many other organizations. The results of the study and the recommendations will help reduce the risks in agriculture in Georgia and, in general, to identify the existing potential and the development of the sector as a whole.

Keywords: risk, agriculture, pandemi, brown marmorated stink bug (BMSB)

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Authors: Wafa’ Alma'Aitah, Khaled Almakadmeh

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this study presents an information retrieval system of using genetic algorithm to increase information retrieval efficiency. Using vector space model, information retrieval is based on the similarity measurement between query and documents. Documents with high similarity to query are judge more relevant to the query and should be retrieved first. Using genetic algorithms, each query is represented by a chromosome; these chromosomes are fed into genetic operator process: selection, crossover, and mutation until an optimized query chromosome is obtained for document retrieval. Results show that information retrieval with adaptive crossover probability and single point type crossover and roulette wheel as selection type give the highest recall. The proposed approach is verified using (242) proceedings abstracts collected from the Saudi Arabian national conference.

Keywords: genetic algorithm, information retrieval, optimal queries, crossover

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Authors: Marina Kljaković-Gašpić Batinjan, Tea Petrović, Frano Vučković, Irzal Hadžibegović, Barbara Radovani, Ivana Jurin, Lovorka Đerek, Eva Huljev, Alemka Markotić, Ivica Lukšić, Irena Trbojević-Akmačić, Gordan Lauc, Ivan Gudelj, Rok Čivljak

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Immunoglobulin G has essential role in defense against infectious diseases, but its role cannot be fully recognized without understanding of changes in its N-glycans attached to the Fc domain. We analyzed and compared total IgG glycome in plasma samples of patients with influenza, patients with COVID-19 and healthy controls. We found similarities in IgG glycosylation changes in COVID-19 survivors and influenza patients that could be the consequence of adequate immune response to enveloped viruses, while observed changes in deceased COVID-19 patients may indicate its deviation.

Keywords: COVID-19, glycosylation, immunoglobulin G, influenza, pneumonia, viral infection

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Authors: P. Suparada, D. Eakapotch

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This research’s objectives were to analyze the using of new media in the form of set up candid clip that affects the product and presenter, to study the effectiveness of using new media in the form of set up candid clip in order to increase the circulation and audience satisfaction and to use the earned information and knowledge to develop the communication for publicizing and advertising via new media. This research is qualitative research based on questionnaire from 50 random sampling representative samples and in-depth interview from experts in publicizing and advertising fields. The findings indicated the positive and negative effects to the brands’ image and presenters’ image of product named “Scotch 100” and “Snickers” that used set up candid clips via new media for publicizing and advertising in Thailand. It will be useful for fields of publicizing and advertising in the new media forms.

Keywords: candid clip, effect, new media, social network

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Authors: Wafa' Alsharafat, Suhila Farhan Abu-Owida

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Genetic algorithm (GA) is a powerful evolutionary searching technique that is used successfully to solve and optimize problems in different research areas. Genetic Algorithm (GA) considered as one of optimization methods used to solve Travel salesman Problem (TSP). The feasibility of GA in finding a TSP solution is dependent on GA operators; encoding method, population size, termination criteria, in general. In specific, crossover and its probability play a significant role in finding possible solutions for Symmetric TSP (STSP). In addition, the crossover should be determined and enhanced in term reaching optimal or at least near optimal. In this paper, we spot the light on using a modified crossover method called modified sequential constructive crossover and its impact on reaching optimal solution. To justify the relevance of a parameter value in solving the TSP, a set comparative analysis conducted on different crossover methods values.

Keywords: genetic algorithm, crossover, mutation, TSP

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Authors: H. Kishor, G. Prabhuling, D. S. Ambika, D. P. Prakash

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The chemical mutagens have become important tool to enhance agronomic traits of banana crop. It is being used to develop fusarium resistance lines in various susceptible banana cultivars. There are several mutagens like EMS and NaN3 available for banana crop improvement and each mutagen has its own important role as positive or negative effects on growth and development of banana plants. Explants from shoot tip culture were treated with various EMS (0.30, 0.60, 0.90 and 0.12%) and NaN3 (0.01, 0.02 and 0.03%) concentrations. The putative mutants obtained after in vitro rooting were subjected for artificial inoculation of Fusarium oxysporum f.sp. cubense. Screening putative mutants resistance to Panama disease was carried out by using syringe method of inoculation. It was observed that, EMS treated mutants were more susceptible compared to NaN3 treatment. Among the NaN3 doses 0.01% found to produce 3 resistant lines during preliminary screening under greenhouse conditions.

Keywords: Nanjangud rasabale, EMS, NaN3, putative mutants

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Authors: Mafalda Moreira, Diana Alba, Inês Paiva Ferreira, Rita Calejo, Ana Rita Soares, Leonilde Machado

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Intellectual disability (ID) is characterized by deficits in intellectualfunctioningassociatedwithalterations in the adaptive behaviour, whose onset is inthedevelopmentalperiod. Itaffects 3% of the population, ofwhich 10% have a geneticaetiology. One of those causes isAlwadeiSyndrome, with 3 cases describedworldwide. It results from a homozygous nonsense mutation in theRUSC2 gene andisassociatedwithintellectualdisabilityanddysmorphic facialfeatures. Theauthorsreportthe case of a 5-year-old-boy, born to a healthymotherafter a full-termuneventfulpregnancy, thatwasreferred to Neurodevelopmentalconsultationdue toglobal developmentaldelay. Familyhistoryrevealedlearningdifficulties in the paternal brotherhood. Milddismorphicfeatureswereevidentsuch as darkinfraorbitalregion, low-set ears, beakednose, retrognathism, high-archedpalateandjointhyperlaxity. WechslerIntelligenceScale for Children III fullscaleIQ quoted 61. Karyotypeandchromosomalmicroarrayanalysiswerenormal, as well as the fragile X molecular study. DNA sequencingwasthenperformedandallowedtheidentificationof amutation in the RUSC2 gene. Theetiologicaldiagnosisof ID remains unknown in up to 80% of cases, creatinguncertainty in children’sfamilies. Theadvances in DNA sequencingtechnologieshaveincreasedourknowledgeofthegeneticdiseasesinvolved, as theAlwadeisyndromewasonlydescribedsince 2016. Thegeneticdiagnosisof ID allowsfamilygeneticcounselingandenablesthedevelopmentof target therapeutic approaches.

Keywords: intellectual disability, genetic aetiology, alwadei syndrome, RUSC2

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Authors: Jamileh Ahmed, Helena Hernandez, Gabriel De Erausquin

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H1N1 virus susceptibility of iPSC-derived DA neurons from schizophrenia patients and controls will compared. C57/BL-6 fibroblasts were reprogrammed into iPSCs using a lenti-viral vector containing SOKM genes. Pluripotency verification with the AP assay and immunocytochemistry ensured iPSC presence. The experimental outcome of ISPCs from DA neuron differentiation will be discussed in the Results section. Fibroblasts from patients and controls will be reprogrammed into iPSCs using a sendai-virus vector containing SOKM. IPSCs will be characterized using the AP assay, immunocytochemistry and RT-PCR. IPSCs will then be differentiated into DA neurons. Gene methylation will be compared for both groups with custom-designed microarrays.

Keywords: schizophrenia, iPSCs, stem cells, neuroscience

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Authors: M. C. O. Ezeibe, F. I. O. Ezeibe

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Reasons viral diseases (including AI, HIV/AIDS, and COVID-19), tumors (including Cancers and Prostrate enlargement), and antimicrobial-resistant infections (AMR) are difficult to cure are features of the pathogens which normal cells do not have or need (biomedical markers) have not been identified; medicines that can counter the markers have not been invented; strategies and mechanisms for their treatments have not been developed. When cells become abnormal, they acquire negative electrical charges, and viruses are either positively charged or negatively charged, while normal cells remain neutral (without electrical charges). So, opposite charges' electrostatic attraction is a treatment mechanism for viral diseases and tumors. Medicines that have positive electrical charges would mop abnormal (infected and tumor) cells and DNA viruses (negatively charged), while negatively charged medicines would mop RNA viruses (positively charged). Molecules of Aluminum-magnesium silicate [AMS: Al₂Mg₃ (SiO₄)₃], an approved medicine and pharmaceutical stabilizing agent, consist of nanoparticles which have both positive electrically charged ends and negative electrically charged ends. The very small size (0.96 nm) of the nanoparticles allows them to reach all cells in every organ. By stabilizing antimicrobials, AMS reduces the rate at which the body metabolizes them so that they remain at high concentrations for extended periods. When drugs remain at high concentrations for longer periods, their efficacies improve. Again, nanoparticles enhance the delivery of medicines to effect targets. Both remaining at high concentrations for longer periods and better delivery to effect targets improve efficacy and make lower doses achieve desired effects so that side effects of medicines are reduced to allow the immunity of patients to be enhanced. Silicates also enhance the immune responses of treated patients. Improving antimicrobial efficacies and enhancing patients` immunity terminate infections so that none remains that could develop resistance. Some countries do not have natural deposits of AMS, but they may have Aluminum silicate (AS: Al₄ (SiO₄)₃) and Magnesium silicate (MS: Mg₂SiO₄), which are also approved medicines. So, AS and MS were used to formulate an AMS-brand, named Medicinal synthetic AMS {Al₄ (SiO₄)₃ + 3Mg₂SiO₄ → 2Al₂Mg₃ (SiO₄)₃}. To overcome the challenge of AMS, AS, and MS being un-absorbable, Dextrose monohydrate is incorporated in MSAMS-formulations for the simple sugar to convey the electrically charged nanoparticles into blood circulation by the principle of active transport so that MSAMS-antimicrobial formulations function systemically. In vitro, MSAMS reduced (P≤0.05) titers of viruses, including Avian influenza virus and HIV. When used to treat virus-infected animals, it cured Newcastle disease and Infectious bursa disease of chickens, Parvovirus disease of dogs, and Peste des petits ruminants disease of sheep and goats. A number of HIV/AIDS patients treated with it have been reported to become HIV-negative (antibody and antigen). COVID-19 patients are also reported to recover and test virus negative when treated with MSAMS. PSA titers of prostate cancer/enlargement patients normalize (≤4) following treatment with MSAMS. MSAMS has also potentiated ampicillin trihydrate, sulfadimidin, cotrimoxazole, piparazine citrate and chloroquine phosphate to achieve ≥ 95 % infection-load reductions (AMR-prevention). At 75 % of doses of ampicillin, cotrimoxazole, and streptomycin, supporting MSAMS-formulations' treatments with antioxidants led to the termination of even already resistant infections.

Keywords: electrical charges, viruses, abnormal cells, aluminum-magnesium silicate

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Authors: Athini Ntloko

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Mycobacterium bovis and other species of Mycobacterium tuberculosis complex (MTBC) can result to a zoonotic infection known as Bovine tuberculosis (bTB). MTBC has members that may contaminate an extensive range of hosts, including wildlife. Diverse wild species are known to cause disease in domestic livestock and are acknowledged as TB reservoirs. It has been a main study worldwide to deliberate on bTB risk factors as a result and some studies focused on particular parts of risk factors such as wildlife and herd management. The significance of the study was to determine the incidence of Mycobacterium tuberculosis complex that is associated with soil, hayfeed and water. Questionnaires were administered to thirty (30) smallholding farm owners in the two villages (kwaMasele and Qungqwala) and three (3) three commercial farms (Fort Hare dairy farm, Middledrift dairy farm and Seven star dairy farm). Detection of M. tuberculosis complex was achieved by Polymerase Chain Reaction using primers for IS6110; whereas a genotypic drug resistance mutation was detected using Genotype MTBDRplus assays. Nine percent (9%) of respondents had more than 40 cows in their herd, while 60% reported between 10 and 20 cows in their herd. Relationship between farm size and vaccination for TB differed from forty one percent (41%) being the highest to the least five percent (5%). The highest number of respondents who knew about relationship between TB cases and cattle location was ninety one percent (91%). Approximately fifty one percent (51%) of respondents had knowledge about wild life access to the farms. Relationship between import of cattle and farm size ranged from nine percent (9%) to thirty five percent (35%). Cattle sickness in relation to farm size differed from forty three (43%) being the highest to the least three percent (3%); while thirty three percent (33%) of respondents had knowledge about health management. Respondents with knowledge about the occurrence of TB infections in farms were forty-eight percent (48%). The frequency of DNA isolation from samples ranged from the highest forty-five percent (45%) from water to the least twenty two percent (22%) from soil. Fort Hare dairy farm had the highest number of positive samples, forty four percent (44%) from water samples; whereas Middledrift dairy farm had the lowest positive from water, seventeen percent (17%). Twelve (22%) out of 55 isolates showed resistance to INH and RIF that is, multi-drug resistance (MDR) and nine percent (9%) were sensitive to either INH or RIF. The mutations at rpoB gene differed from 58% being the highest to the least (23%). Fifty seven percent (57%) of samples showed a S315T1 mutation while only 14% possessed a S531L in the katG gene. The highest inhA mutations were detected in T8A (80 %) and the least was observed in A16G (17%). The results of this study reveal that risk factors for bTB in cattle and dairy farm workers are a serious issue abound in the Eastern Cape of South Africa; with the possibility of widespread dissemination of multidrug resistant determinants in MTBC from the environment.

Keywords: hayfeed, isoniazid, multi-drug resistance, mycobacterium tuberculosis complex, polymerase chain reaction, rifampicin, soil, water

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Authors: Rasime Kalkan, Emine Ikbal Atli, Ali Arslantaş, Muhsin Özdemir, Sevilhan Artan

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Glioblastoma (WHO grade IV), is the malignant form of brain tumor, the genetic background of the GBM is highly variable. The tumor mass of a GBM is multilayered and every tumor layer shows distinct characteristics with a different cell population. The treatment planning of GBM should be focused on the tumor genetic characteristics. We screened primary glioblastoma multiforme (GBM) in a population-based study for MGMT and RARβ methylation and IDH1 mutation correlated them with clinical data and treatment. There was no correlation between MGMT-promoter methylation and overall survival. The overall survival time of the patients with methylated RARβ was statically (OS;p<0,05) significance between the patients who were treated with chemotherapy and radiotherapy. Here we showed the status of IDH1 gene associatied with younger age. We demonstrated that the together with MGMT gene the RARβ gene should be used as a potantial treatment decision marker for GBMs.

Keywords: RARβ, primary glioblastoma multiforme, methylation, MGMT

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Authors: Yu Pu, Chien-Ping Hsiao, Chien-Chang Huang, Chieh-Lun Cheng

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Free radicals can accelerate aging on human skin by causing lipid oxidation, protein denaturation, and even DNA mutation. Substances with the ability of anti-free radicals can be used as functional components in cosmetic products. Research are attracted to develop new anti-free radical components for cosmetic application. This study was aimed to evaluate the microbial metabolites on free radical scavenging ability. Two microorganisms, PU-01 and PU-02, were isolated from soil of hot spring environment and grew in LB agar at 50°C for 24 h. The suspension was collected by centrifugation at 4800 g for 3 min, The anti-free radical activity was determined by DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging assay. The result showed that the growth medium of PU-01 presented a higher DPPH scavenging effect than that of PU-02. This study presented potential anti-free radical components from microbial metabolites that might be applied in anti-aging cosmetics.

Keywords: anti-ageing, anti-free radical, biotechnology, microorganism

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Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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Authors: Danielle A. Walker, Kyle L. Johnson, Patrick J. Fox, Jacen S. Moore

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The HIV Continuum of Care has become a universal model to provide context for the process of HIV testing, linkage to care, treatment, and viral suppression. HIV testing is the first step in moving toward community viral suppression. Countries with a lower socioeconomic status experience the lowest rates of testing and access to care. The Democratic Republic of the Congo is located in the heart of sub-Saharan Africa, where testing and access to care are low and women experience higher HIV prevalence compared to men. In the Democratic Republic of the Congo there is only a 21.6% HIV testing rate among women. Because a critical gap exists between a woman’s risk of contracting HIV and the decision to be tested, this study was conducted to obtain a better understanding of the relationship between factors that could influence HIV testing among women. The datasets analyzed were from the 2013-14 Democratic Republic of the Congo Demographic and Health Survey Program. The data was subset for women with an age range of 18-49 years. All missing cases were removed and one variable was recoded. The total sample size analyzed was 14,982 women. The results showed that there did not seem to be a difference in HIV testing by mean age. Out of 11 religious categories (Catholic, Protestant, Armee de salut, Kimbanguiste, Other Christians, Muslim, Bundu dia kongo, Vuvamu, Animist, no religion, and other), those who identified as Other Christians had the highest testing rate of 25.9% and those identified as Vuvamu had a 0% testing rate (p<0.001). There was a significant difference in testing by religion. Only 0.7% of women surveyed identified as having no religious affiliation. This suggests partnerships with key community and religious leaders could be a tool to increase testing. Over 60% of women who had never been tested for HIV did not know where to be tested. This highlights the need to educate communities on where testing facilities can be located. Almost 80% of women who believed HIV could be transmitted by supernatural means and/or witchcraft had never been tested before (p=0.08). Cultural beliefs could influence risk perception and testing decisions. Consequently, misconceptions need to be considered when implementing HIV testing and prevention programs. Location by province, years of education, and wealth index were also analyzed to control for socioeconomic status. Kinshasa had the highest testing rate of 54.2% of women living there, and both Equateur and Kasai-Occidental had less than a 10% testing rate (p<0.001). As the education level increased up to 12 years, testing increased (p<0.001). Women within the highest quintile of the wealth index had a 56.1% testing rate, and women within the lowest quintile had a 6.5% testing rate (p<0.001). This study concludes that further research is needed to identify culturally competent methods to increase HIV education programs, build partnerships with key community leaders, and improve knowledge on access to care.

Keywords: Democratic Republic of the Congo, cultural beliefs, education, HIV testing

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Authors: Aydin Teymourifar, Gurkan Ozturk, Ozan Bahadir

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NSGA-II is one of the most well-known and most widely used evolutionary algorithms. In addition to its new versions, such as NSGA-III, there are several modified types of this algorithm in the literature. In this paper, a hybrid NSGA-II algorithm has been suggested for solving the multi-objective flexible job shop scheduling problem. For a better search, new neighborhood-based crossover and mutation operators are defined. To create new generations, the neighbors of the selected individuals by the tournament selection are constructed. Also, at the end of each iteration, before sorting, neighbors of a certain number of good solutions are derived, except for solutions protected by elitism. The neighbors are generated using a constraint-based neural network that uses various constructs. The non-dominated sorting and crowding distance operators are same as the classic NSGA-II. A comparison based on some multi-objective benchmarks from the literature shows the efficiency of the algorithm.

Keywords: flexible job shop scheduling problem, multi-objective optimization, NSGA-II algorithm, neighborhood structures

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Authors: Sirous Eydivandi

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Diacylglycerol-O-acyltransferase (DGAT1) gene encodes diacylglycerol transferase enzyme that plays an important role in glycerol lipid metabolism. DGAT1 is considered to be the key enzyme in controlling the synthesis of triglycerides in adipocytes. This enzyme catalyzes the final step of triglyceride synthesis (transform triacylglycerol (DAG) into triacylglycerol (TAG). A total of 20 DGAT1 gene sequences and corresponding amino acids belonging to 4 species include cattle, goats, sheep and yaks were analyzed, and the differentiation within and among the species was also studied. The length of the DGAT1 gene varies greatly, from 1527 to 1785 bp, due to deletion, insertion, and stop codon mutation resulting in elongation. Observed genetic diversity was higher among species than within species, and Goat had more polymorphisms than any other species. Novel amino acid variation sites were detected within several species which might be used to illustrate the functional variation. Differentiation of the DGAT1 gene was obvious among species, and the clustering result was consistent with the taxonomy in the National Center for Biotechnology Information.

Keywords: DGAT1gene, bioinformatic, ruminnants, biotechnology information

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Authors: Syed Talib Abbas Raza, Tahseen Ahmed Jilani, Saleem Abdullah

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This paper presents interval-valued intuitionistic fuzzy soft sets based TOPSIS method for group decision making. The interval-valued intuitionistic fuzzy soft set is a mutation of an interval-valued intuitionistic fuzzy set and soft set. In group decision making problems IVIFSS makes the process much more algebraically elegant. We have used weighted arithmetic averaging operator for aggregating the information and define a new Hybrid Score Function as metric tool for comparison between interval-valued intuitionistic fuzzy values. In an illustrative example we have applied the developed method to a criminological problem. We have developed a group decision making model for integrating the imprecise and hesitant evaluations of multiple law enforcement agencies working on target killing cases in the country.

Keywords: group decision making, interval-valued intuitionistic fuzzy soft set, TOPSIS, score function, criminology

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Authors: Imbesat Daudi

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Islamophobia, which is a billion-dollar industry, is widespread, especially in the United States, Europe, India, Israel, and countries that have Muslim minorities at odds with their governmental policies. Hatred of Islam in the West did not evolve spontaneously; it was methodically created. Islamophobia's current format has been designed to spread on its own, find a space in the Western psyche, and resist its eradication. Hatred has been sustained by neoconservative ideologues and their allies, which are supported by the mainstream media. Social scientists have evaluated how ideas spread, why any idea can go viral, and where new ideas find space in our brains. This was possible because of the advances in the computational power of software and computers. Spreading of ideas, including Islamophobia, follows a sine curve; it has three phases: An initial exploratory phase with a long lag period, an explosive phase if ideas go viral, and the final phase when ideas find space in the human psyche. In the initial phase, the ideas are quickly examined in a center in the prefrontal lobe. When it is deemed relevant, it is sent for evaluation to another center of the prefrontal lobe; there, it is critically examined. Once it takes a final shape, the idea is sent as a final product to a center in the occipital lobe. This center cannot critically evaluate ideas; it can only defend them from its critics. Counterarguments, no matter how scientific, are automatically rejected. Therefore, arguments that could be highly effective in the early phases are counterproductive once they are stored in the occipital lobe. Anti-Islamophobic intellectuals have done a very good job of countering Islamophobic arguments. However, they have not been as effective as neoconservative ideologues who have promoted anti-Muslim rhetoric that was based on half-truths, misinformation, or outright lies. The failure is partly due to the support pro-war activists receive from the mainstream media, state institutions, mega-corporations engaged in violent conflicts, and think tanks that provide Islamophobic arguments. However, there are also scientific reasons why anti-Islamophobic thinkers have been less effective. There are different dynamics of spreading ideas once they are stored in the occipital lobe. The human brain is incapable of evaluating further once it accepts ideas as its own; therefore, a different strategy is required to be effective. This paper examines 1) why anti-Islamophobic intellectuals have failed in changing the minds of non-Muslims and 2) the steps of countering hatred. Simply put, a new strategy is needed that can effectively counteract hatred of Islam and Muslims. Islamophobia is a disease that requires strong measures. Fighting hatred is always a challenge, but if we understand why Islamophobia is taking root in the twenty-first century, one can succeed in challenging Islamophobic arguments. That will need a coordinated effort of Intellectuals, writers and the media.

Keywords: islamophobia, Islam and violence, anti-islamophobia, demonization of Islam

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Authors: Biswabandhu Bankura, Srikanta Guria, Madhusudan Das

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Purpose: Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones. We aimed to identify the spectrum of mutations in the TPO gene leading to hypothyroidism in the population of West Bengal to establish the genetic etiology of the disease. Methods: 200 hypothyroid patients (case) and their corresponding sex and age matched 200 normal individuals (control) were screened depending on their clinical manifestations. Genomic DNA was isolated from peripheral blood samples and TPO gene (Exon 7 to Exon 14) was amplified by PCR. The PCR products were subjected to sequencing to identify mutations. Results: Single nucleotide changes such as Glu 641 Lys, Asp 668 Asn, Thr 725 Pro, Asp 620 Asn, Ser 398 Thr, and Ala 373 Ser were found. Changes in the TPO were assayed in vitro to compare mutant and wild-type activities. Five mutants were enzymatically inactive in the guaiacol and iodide assays. This is a strong indication that the mutations are present at crucial positions of the TPO gene, resulting in inactivated TPO. Key Findings: The results of this study may help to develop a genetic screening protocol for goiter and hypothyroidism in the population of West Bengal.

Keywords: thyroid peroxidase, hypothyroidism, mutation, in vitro assay, transfection

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Authors: Biswabandhu Bankura, Srikanta Guria, Madhusudan Das

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Purpose: Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones. We aimed to identify the spectrum of mutations in the TPO gene leading to hypothyroidism in the population of West Bengal to establish the genetic etiology of the disease. Methods: 200 hypothyroid patients (case) and their corresponding sex and age matched 200 normal individuals (control) were screened depending on their clinical manifestations. Genomic DNA was isolated from peripheral blood samples and TPO gene (Exon 7 to Exon 14) was amplified by PCR. The PCR products were subjected to sequencing to identify mutations. Results: Single nucleotide changes such as Glu 641 Lys, Asp 668 Asn, Thr 725 Pro, Asp 620 Asn, Ser 398 Thr, and Ala 373 Ser were found. Changes in the TPO were assayed in vitro to compare mutant and wild-type activities. Five mutants were enzymatically inactive in the guaiacol and iodide assays. This is a strong indication that the mutations are present at crucial positions of the TPO gene, resulting in inactivated TPO. Key Findings: The results of this study may help to develop a genetic screening protocol for goiter and hypothyroidism in the population of West Bengal.

Keywords: thyroid peroxidase, hypothyroidism, mutation, in vitro assay, transfection

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Authors: Negin Parsamanesh, Saman Ameri-Mahabadi, Ali Nikfar, Mojdeh Mansouri, Hossein Chiti, Gita Fatemi Abhari

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Duchenne muscular dystrophy (DMD) is a severe progressive X-linked neuromuscular illness that affects movement through mutations in dystrophin gene. The mutation leads to insufficient, lack of or dysfunction of dystrophin. The cause of DMD was determined in an Iranian family. Exome sequencing was carried out along with a complete physical examination of the family. In silico methods were applied to find the alteration in the protein structure. The homozygous variant in DMD gene (NM-004006.2) was defined as c.2732-2733delTT (p.Phe911CysfsX8) in exon 21. In addition, phylogenetic conservation study of the human dystrophin protein sequence revealed that phenylalanine 911 is one of the evolutionarily conserved amino acids. In conclusion, our study indicated a new deletion in the DMD gene in the affected family. This deletion with an X-linked inheritance pattern is new in Iran. These findings could facilitate genetic counseling for this family and other patients in the future.

Keywords: duchenne muscular dystrophy, whole exome sequencing, iran, metabolic syndrome

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Authors: Abdelhadi Adel, Kadri Ouahab

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This paper proposes an improved approach based on MAS Architecture and Heuristic Algorithm for systematic maintenance to minimize makespan. We have implemented a problem-solving approach for optimizing the processing time, methods based on metaheuristics. The proposed approach is inspired by the behavior of the human body. This hybridization is between a multi-agent system and inspirations of the human body, especially genetics. The effectiveness of our approach has been demonstrated repeatedly in this paper. To solve such a complex problem, we proposed an approach which we have used advanced operators such as uniform crossover set and single point mutation. The proposed approach is applied to three preventive maintenance policies. These policies are intended to maximize the availability or to maintain a minimum level of reliability during the production chain. The results show that our algorithm outperforms existing algorithms. We assumed that the machines might be unavailable periodically during the production scheduling.

Keywords: multi-agent systems, emergence, genetic algorithm, makespan, systematic maintenance, scheduling, hybrid flow shop scheduling

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Authors: Abiodun Ladanu Ajala, Wuyi Oke

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Mathematical simulation and optimization models packaged within interactive computer programs provide a common way for planners and managers to predict the behaviour of any proposed water resources system design or management policy before it is implemented. Modeling presents a principal technique of predicting the behaviour of the proposed infrastructural designs or management policies. Models can be developed and used to help identify specific alternative plans that best meet those objectives. This study discusses various types of models, their development, architecture, data requirements, and applications in the field of engineering. It also outlines the advantages and limitations of each the optimization and simulation models presented. The techniques explored in this review include; dynamic programming, linear programming, fuzzy optimization, evolutionary algorithms and finally artificial intelligence techniques. Previous studies carried out using some of the techniques mentioned above were reviewed, and most of the results from different researches showed that indeed optimization and simulation provides viable alternatives and predictions which form a basis for decision making in building engineering structures and also in engineering planning and management.

Keywords: linear programming, mutation, optimization, simulation

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Authors: Malik SS, Masood N, Mubarik S, Khadim TM

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Introduction: Xeroderma pigmentosum group G (XPG) gene plays a crucial role in the correction of UV-induced DNA damage through nucleotide excision repair pathway. Single nucleotide polymorphisms in XPG gene have been reported to be associated with different cancers. Current case-control study was designed to evaluate the relationship between one of the most frequently found XPG (rs1047768 T>C) polymorphism and breast cancer risk. Methodology: A total of 200 individuals were screened for this polymorphism including 100 pathologically confirmed breast cancer cases and age-matched 100 controls. Genotyping was carried out using Tetra amplification-refractory mutation system (ARMS) PCR and results were confirmed by gel electrophoresis. Results: Conditional logistic regression analysis showed significant association between TC genotype (OR: 8.9, CI: 2.0 – 38.7) and increased breast cancer risk. Although homozygous CC genotype was more frequent in patients as compared to controls, but it was statistically non-significant (OR: 3.9, CI: 0.4 – 35.7). Conclusion: In conclusion, XPG (rs1047768 T>C) polymorphism may contribute towards increased risk of breast cancer but other polymorphisms may also be evaluated to elucidate their role in breast cancer.

Keywords: XPG, breast cancer, NER, ARMS-PCR

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Authors: B. B. S. Pereira, M. O. Souza, L. P. Zanetti, L. C. S. Oliveira, J. R. P. Moreno, M. P. Souza, V. R. Colturato, C. M. Machado

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Background: The introduction of prophylactic or preemptive therapies has effectively decreased the CMV mortality rates after hematopoietic stem cell transplantation (HSCT). CMV antigenemia (pp65) or quantitative PCR are methods currently approved for CMV surveillance in pre-emptive strategies. Commercial assays are preferred as cut-off levels defined by in-house assays may vary among different protocols and in general show low reproducibility. Moreover, comparison of published data among different centers is only possible if international standards of quantification are included in the assays. Recently, the World Health Organization (WHO) established the first international standard for CMV detection. The real time PCR COBAS Ampliprep/ CobasTaqMan (CAP/CTM) (Roche®) was developed using the WHO standard for CMV quantification. However, the cut-off for the introduction of antiviral has not been determined yet. Methods: We conducted a retrospective study to determine: 1) the sensitivity and specificity of the new CMV CAP/CTM test in comparison with pp65 antigenemia to detect episodes of CMV infection/reactivation, and 2) the cut-off of viral load for introduction of ganciclovir (GCV). Pp65 antigenemia was performed and the corresponding plasma samples were stored at -20°C for further CMV detection by CAP/CTM. Comparison of tests was performed by kappa index. The appearance of positive antigenemia was considered the state variable to determine the cut-off of CMV viral load by ROC curve. Statistical analysis was performed using SPSS software version 19 (SPSS, Chicago, IL, USA.). Results: Thirty-eight patients were included and followed from August 2014 through May 2015. The antigenemia test detected 53 episodes of CMV infection in 34 patients (89.5%), while CAP/CTM detected 37 episodes in 33 patients (86.8%). AG and PCR results were compared in 431 samples and Kappa index was 30.9%. The median time for first AG detection was 42 (28-140) days, while CAP/CTM detected at a median of 7 days earlier (34 days, ranging from 7 to 110 days). The optimum cut-off value of CMV DNA was 34.25 IU/mL to detect positive antigenemia with 88.2% of sensibility, 100% of specificity and AUC of 0.91. This cut-off value is below the limit of detection and quantification of the equipment which is 56 IU/mL. According to CMV recurrence definition, 16 episodes of CMV recurrence were detected by antigenemia (47.1%) and 4 (12.1%) by CAP/CTM. The duration of viremia as detected by antigenemia was shorter (60.5% of the episodes lasted ≤ 7 days) in comparison to CAP/CTM (57.9% of the episodes lasting 15 days or more). This data suggests that the use of antigenemia to define the duration of GCV therapy might prompt early interruption of antiviral, which may favor CMV reactivation. The CAP/CTM PCR could possibly provide a safer information concerning the duration of GCV therapy. As prolonged treatment may increase the risk of toxicity, this hypothesis should be confirmed in prospective trials. Conclusions: Even though CAP/CTM by ROCHE showed great qualitative correlation with the antigenemia technique, the fully automated CAP/CTM did not demonstrate increased sensitivity. The cut-off value below the limit of detection and quantification may result in delayed introduction of pre-emptive therapy.

Keywords: antigenemia, CMV COBAS/TAQMAN, cytomegalovirus, antiviral cut-off

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Salma M. Wakil

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Advances in the field of genetics overwhelmed detecting large number of inherited disorders at the molecular level and directed to the development of innovative technologies. These innovations have led to gene sequencing, prenatal mutation detection, pre-implantation genetic diagnosis; population based carrier screening and genome wide analyses using microarrays. Microarrays are widely used in establishing clinical and diagnostic setup for genetic anomalies at a massive level, with the advent of cytoscan molecular karyotyping as a clinical utility card for detecting chromosomal aberrations with high coverage across the entire human genome. Unlike a regular karyotype that relies on the microscopic inspection of chromosomes, molecular karyotyping with cytoscan constructs virtual chromosomes based on the copy number analysis of DNA which improves its resolution by 100-fold. We have been investigating a large number of patients with Developmental Delay and Intellectual disability with this platform for establishing micro syndrome deletions and have detected number of novel CNV’s in the Arabian population with the clinical relevance.

Keywords: microarrays, molecular karyotyping, developmental delay, genetics

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