Search results for: Hepatitis C virus (HCV) CAD (Computer Aided Design)
14582 Programmed Cell Death in Datura and Defensive Plant Response toward Tomato Mosaic Virus
Authors: Asma Alhuqail, Nagwa Aref
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Programmed cell death resembles a real nature active defense in Datura metel against TMV after three days of virus infection. Physiological plant response was assessed for asymptomatic healthy and symptomatic infected detached leaves. The results indicated H2O2 and Chlorophyll-a as the most potential parameters. Chlorophyll-a was considered the only significant predictor variant for the H2O2 dependent variant with a P value of 0.001 and R-square of 0.900. The plant immune response was measured within three days of virus infection using the cutoff value of H2O2 (61.095 lmol/100 mg) and (63.201 units) for the tail moment in the Comet Assay. Their percentage changes were 255.12% and 522.40% respectively which reflects the stress of virus infection in the plant. Moreover, H2O2 showed 100% specificity and sensitivity in the symptomatic infected group using the receiver-operating characteristic (ROC). All tested parameters in the symptomatic infected group had significant correlations with twenty-five positive and thirty-one negative correlations where the P value was <0.05 and 0.01. Chlorophyll-a parameter had a crucial role of highly significant correlation between total protein and salicylic acid. Contrarily, this correlation with tail moment unit was (r = _0.930, P <0.01) where the P value was < 0.01. The strongest significant negative correlation was between Chlorophyll-a and H2O2 at P < 0.01, while moderate negative significant correlation was seen for Chlorophyll-b where the P value < 0.05. The present study discloses the secret of the three days of rapid transient production of activated oxygen species (AOS) that was enough for having potential quantitative physiological parameters for defensive plant response toward the virus.Keywords: programmed cell death, plant–adaptive immune response, hydrogen peroxide (H2O2), physiological parameters
Procedia PDF Downloads 24214581 Balancing Aesthetics, Sustainability, and Safety in Handmade Fabric Face Masks: A Testimony of Creativity and Adaptability
Authors: Anne Mastamet-Mason, Oluwatosin Onakoya, Karla Tissiman
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The COVID-19 pandemic that ravaged the world in 2020 brought about the need for handmade fabric face masks in South Africa and beyond. These masks showcased individuality and environmental responsibility and effectively aided our battle against the virus. These practical masks held significant meaning, representing human creativity, resilience, and commitment to sustainability in adversity. This paper examines how aesthetics, sustainability, and safety were achieved in the Handmade Fabric Face Masks. It analyses how their integration signified human agility and resilience to the pandemic while promoting dignity and environmental welfare. The research conducted a qualitative analysis to choose handmade fabric face masks and assess their aesthetic, sustainable, and safety features. The study involved interviewing a group of mask designers and users who evaluated the masks' efficacy in providing protection, aesthetics, and environmental sustainability. Although the designers demonstrated a high level of knowledge in the design aspects, the results indicated a need for more information regarding the functional safety measures and some environmental factors in mask selection and production. The mask analysis also revealed that the masks available in the market combined aesthetics and environmental protection but had limited safety measures. Despite the lack of balance of aesthetics, sustainability, and safety among the designers and the users of hand-fabric masks, functional aspects of fabrics and sustainability literacy are essentialKeywords: sustainable fashion, fabric mask, aesthetics, safety measures
Procedia PDF Downloads 5414580 Parental Awareness and Willingness to Vaccinate Adolescent Daughters against Human Papilloma Virus for Cervical Cancer Prevention in Eastern Region of Kenya: Towards Affirmative Action
Authors: Jacinta Musyoka, Wesley Too
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Cervical cancer is the second leading cause of cancer-related deaths in Kenya and the second most common cancer among women, yet preventable following prevention strategies put in place, which includes vaccination with Human Papilloma Virus Vaccine (HPPV) among the young adolescent girls. Kenya has the highest burden of cervical cancer and the leading cause of death among women of reproductive age and is a known frequent type of cancer amongst women. This is expected to double by 2025 if the necessary steps are not taken, which include vaccinating girls between the ages of 9 and 14 and screening women. Parental decision is critical in ensuring that their daughters receive this vaccine. Hence this study sought to establish parental willingness and factors associate with the acceptability to vaccine adolescent daughters against the human papilloma virus for cervical cancer prevention in Machakos County, Eastern Region of Kenya. Method: Cross-sectional study design utilizing a mixed methods approach was used to collect data from Nguluni Health Centre in Machakos County; Matungulu sub-county, Kenya. This study targeted all parents of adolescent girls seeking health care services in the Matungulu sub-county area who were aged 18 years and above. A total of 220 parents with adolescent girls aged 10-14 years were enrolled into the study after informed consent were sought. All ethical considerations were observed. Quantitative data were analyzed using Multivariate regression analysis, and thematic analysis was used for qualitative data related to perceptions of parents on HPVV. Results, conclusions, and recommendations- ongoing. We expect to report findings and articulate contributions based on the study findings in due course before October 2022Keywords: adolescents, human papilloma virus, kenya, parents
Procedia PDF Downloads 10614579 The Origin, Diffusion and a Comparison of Ordinary Differential Equations Numerical Solutions Used by SIR Model in Order to Predict SARS-CoV-2 in Nordic Countries
Authors: Gleda Kutrolli, Maksi Kutrolli, Etjon Meco
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SARS-CoV-2 virus is currently one of the most infectious pathogens for humans. It started in China at the end of 2019 and now it is spread in all over the world. The origin and diffusion of the SARS-CoV-2 epidemic, is analysed based on the discussion of viral phylogeny theory. With the aim of understanding the spread of infection in the affected countries, it is crucial to modelize the spread of the virus and simulate its activity. In this paper, the prediction of coronavirus outbreak is done by using SIR model without vital dynamics, applying different numerical technique solving ordinary differential equations (ODEs). We find out that ABM and MRT methods perform better than other techniques and that the activity of the virus will decrease in April but it never cease (for some time the activity will remain low) and the next cycle will start in the middle July 2020 for Norway and Denmark, and October 2020 for Sweden, and September for Finland.Keywords: forecasting, ordinary differential equations, SARS-COV-2 epidemic, SIR model
Procedia PDF Downloads 14514578 Epstein, Barr Virus Alters ATM-Dependent DNA Damage Responses in Germinal Centre B-Cells during Early Infection
Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic
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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.Keywords: EBV, ATM, DNA damage, germinal center cells
Procedia PDF Downloads 34214577 Anterior Uveitis Caused by Infection with Cytomegalovirus and Herpes Simplex Virus Type I at Cicendo Eye Hospital Bandung
Authors: Shinta Stri Ayuda Nur Setyaningsih
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Anterior uveitis is often triggered by viral infections such as herpes simplex virus (HSV) and cytomegalovirus (CMV). This study aims to provide an overview of the demographic and clinical characteristics of patients with anterior uveitis caused by CMV and HSV infection at PMN Cicendo Eye Hospital Bandung. This study used a retrospective observational method. Data were collected from the medical records of patients who visited the PMN Infection and Immunology Polyclinic at Cicendo Eye Hospital between February and July 2023. The results showed that anterior uveitis associated with HSV and CMV viruses often occurs in the elderly and more in women. The most common clinical symptoms are red eyes and decreased visual acuity, with a gradual onset of symptoms. Complications that often arise are cataracts and glaucoma. This study provides a deeper understanding of anterior uveitis caused by infection with HSV and CMV viruses.Keywords: uveitis anterior, cytomegavirus, herpes simplex virus type I ELISA
Procedia PDF Downloads 6914576 Detection of Viral-Plant Interaction Using Some Pathogenesis Related Protein Genes to Identify Resistant Genes against Potato LeafRoll Virus and Potato Virus Y in Egyptian Isolates
Authors: Dalia. G. Aseel, E. E. Hafez, S. M. Hammad
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Viral RNAs of both potato leaf roll virus (PLRV) and potato virus Y (PVY) were extracted from infected potato leaves collected from different Egyptian regions. Differential Display Polymerase Chain Reaction (DD-PCR) using (Endogluconase, β-1,3-glucanases, Chitinase, Peroxidase and Polyphenol oxidase) primers (forward strand) for was performed. The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, a 58 up regulated and 19 down regulated genes were detected, while, 31 up regulated and 14 down regulated genes were observed in case of PVY. Based on the nucleotide sequencing, variable phylogenetic relationships were reported for the three sequenced genes coding for: Induced stolen tip protein, Disease resistance RPP-like protein and non-specific lipid-transfer protein. In a complementary approach, using the quantitative Real-time PCR, the expressions of PRs genes understudy were estimated in the infected leaves by PLRV and PVY of three potato cultivars (Spunta, Diamont and Cara). The infection with both viruses inhibited the expressions of the five PRs genes. On the contrary, infected leaves by PLRV or PVY elevated the expression of some defense genes. This interaction also may be enhanced and/or inhibited the expression of some genes responsible for the plant defense mechanisms.Keywords: PLRV, PVY, PR genes, DD-PCR, qRT-PCR, sequencing
Procedia PDF Downloads 33214575 A Small-Molecular Inhibitor of Influenza Virus via Disrupting the PA and PB1 Interaction of the Viral Polymerase
Authors: Shuofeng Yuan, Bojian Zheng
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Assembly of the heterotrimeric polymerase complex of influenza virus from the individual subunits PB1, PA, and PB2 is a prerequisite for viral replication, in which the interaction between the N-terminal of PB1 (PB1N) and the C terminal of PA (PAC) may be a desired target for antiviral development. In this study, we first compared the feasibility of high throughput screening by enzyme-linked immunosorbent assay (ELISA) and fluorescence polarization (FP) assay. Among the two, ELISA was demonstrated to own broader dynamic range so that it was used for screening inhibitors, which blocked PA and PB1 interaction. Several binding inhibitors of PAC-PB1N were identified and subsequently tested for the antiviral efficacy. Apparently, 3-(2-chlorophenyl)-6-ethyl-7-methyl[1,2,4]triazolo[4,3-a]pyrimidin-5-ol, designated ANA-1, was found to be a strong inhibitor of PAC-PB1N interaction and act as a potent antiviral agent against the infections of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 subtypes, in cell cultures. Intranasal administration of ANA-1 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted that ANA-1 bound to an allosteric site of PAC, which would cause conformational changes thereby disrupting the PAC-PB1N interaction. Overall, our study has identified a novel compound with potential to be developed as an anti-influenza drug.Keywords: influenza, antiviral, viral polymerase, compounds
Procedia PDF Downloads 34314574 Evaluation of Existence of Antithyroid Antibodies, Anti-Thyroid Peroxidase and Anti-Thyroglobulin in Patients with Hepatitis C Viral Infections
Authors: Junaid Mahmood Alam, Sana Anwar, Sarah Sughra Asghar
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Chronic hepatitis or Hepatitis C viral (HCV) infection has been identified as one of the factors that could elicit autoimmune disease resulting in the development of auto-antibodies. Furthermore, HCV is implicated in contravening of forbearance to antigens, therefore, inciting auto-reactivity. In this regard, several near and past studies noted the prevalence of thyroid dysfunction and production of anti-thyroid antibodies (ATAb) such as anti-thyroid peroxidase (AntiTPO) and anti-thyroglobulin (AntiTG) in patients with HCV. Likewise, one of the etiologies of augmentation of thyroid disease is basically interferon therapy for HCV infections, for which a number of autoimmune diseases have been noted including Grave’s disease, Hishimoto thyroiditis. A prospectively case-control study was therefore carried out at department of clinical biochemistry lab services and chemical pathology in collaboration with department of clinical microbiology, at Liaquat National Hospital and Medical College, Karachi Pakistan for the period January 2015 to December 2017. Two control groups were inducted for comparison purpose, control group 1 = without HCV infection and with thyroid disorders (n = 20), control group 2 = with HCV infection and without thyroid disorders (n = 20), whereas HCV infected were n = 40 where more than half were noted to be positive for either of HCV IgG and Ag. In HCV group, patients with existing sub-clinical hypothyroidism and clinical hyperthyroidism were less than 5%. Analysis showed the presence of AntiTG in 12 HCV patients (30%), AntiTPO in 15 (37.5%) and both AntiTG and antiTPO in 10 patients (25%). Only 3 patients were found with the history of anti-thyroid auto-antibodies (7.5%) and one with parents and relatives with auto-immune disorders (2.5%). Patients that remained untreated were 12 (30%), under treatment 18 (45%) and with complete-course of treatment 10 (25%). As per review of the literature, meta-analysis of evident data and cross-sectional studies of selective cohorts (as studied in presented research), thyroid connection is designated as one of the most recurrent endocrine ailment associated with chronic HCV infection. Moreover, it also represents an extrahepatic disease in the continuum of HCV syndrome. In conclusion, HCV patients were more likely to encompass thyroid disorders especially related to development of either of ATAb or both antiTG and AntiTPO.Keywords: Hepatitis C viral (HCV) infection, anti-thyroid antibodies, anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies
Procedia PDF Downloads 15014573 Modeling of Hydraulic Networking of Water Supply Subsystem Case of Addis Ababa
Authors: Solomon Weldegebriel Gebrelibanos
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Water is one of the most important substances in human life that can give a human liberality with its cost and availability. Water comes from rainfall and runoff and reaches the ground as runoff that is stored in a river, ponds, and big water bodies, including sea and ocean and the remaining water portion is infiltrated into the ground to store in the aquifer. Water can serve human beings in various ways, including irrigation, water supply, hydropower and soon. Water supply is the main pillar of the water service to the human being. Water supply distribution in Addis Ababa arises from Legedadi, Akakai, and Gefersa. The objective of the study is to measure the performance of the water supply distribution in Addis Ababa city. The water supply distribution model is developed by computer-aided design software. The model can analyze the operational change, loss of water, and performance of the network. The two design criteria that have been employed to analyze the network system are velocity and pressure. The result shows that the customers are using the water at high pressure with low demand. The water distribution system is older than the expected service life with more leakage. Hence the study recommended that fixing Pressure valves and new distribution facilities can resolve the performance of the water supply systemKeywords: distribution, model, pressure, velocity
Procedia PDF Downloads 12114572 Detection of Respiratory Syncytial Virus (hRSV) by PCR Technique in Lower Respiratory Tract Infection (LRTI) in Babylon City
Authors: Amal Raqib Shameran, Ghanim Aboud Al-Mola
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Respiratory syncytial virus (hRSV) is the major pathogens of respiratory tract infections (RTI) among infants and children in the world. They are classified in family Paramyxoviridae and sub-family Pneumovirinae. The current work aimed to detect the role of RSV in the lower respiratory tract infection (LRTI) in Hilla, Iraq. The samples were collected from 50 children who were admitted to hospital suffering from lower respiratory tract infections (LRTI). 50 nasal and pharyngeal swabs were taken from patients at the period from January 2010 till April 2011, hospitalized in Hilla Maternity and Children Hospital. The results showed that the proportion of children infected with hRSV accounted for 24% 12/50 with lower respiratory tract infections (LRTI) when they tested by polymerase chain reaction (RT-PCR).Keywords: respiratory syncytial virus, respiratory tract infections, infants, polymerase chain reaction (PCR)
Procedia PDF Downloads 33214571 Analysis of Peoples' Adherence to Safety Measures that Curb Ebola Virus Diseases in Nigeria (A Case Study of State of Osun)
Authors: Shittu Bisi Agnes
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Ebola virus Diseases outbreak in Nigeria caused a lot of concerns considering the mode of transmission and no known cure discovered. Therefore a lot of safety measures were taken which eventually led to the eradication of the virus in Nigeria. This therefore attempted to determine the various safety measures, how socio-economic characteristic of the people affected adherence to safety measures. And provide reasonable recommendations for total eradication of the virus, future outbreak and general environmental safety Data were collected with the aid of well structured questionnaires and administered 180 randomly selected of the state and oral interview was also utilize. Data collected were analysed using both descriptive tools and inferential statistics vis-a-vis regression analysis. Finding showed that 70.5% was strongly adhere to almost all the measures, 15.2% was fairly advent, 3% was poorly observing the selected measures while 1.3% was in different. 65% of the respondents was strongly aware of the advent of ebola virus diseases, 20% was fairly in awareness, 8.5% was poorly in awareness while 6.55% was in aware of any disease outbreak. Safety measures put forwards were; hand washing, use of hand sanitize-rs, no shaking of hands non-consumption of wildlife games(Bush Meat) and general health and environmental safety measures. It was recommended that policy instrument to increase peoples income will accelerate eradication of diseases as this will enable households to pay for monetary safety measures, health and environmental education, in form of talk shop, workshop, lectures could be organised at the political ward levels, schools, market women, religious bodies functional unions and mass media.Keywords: ebola diseases, pay, safety, outbreak
Procedia PDF Downloads 59114570 A DNA-Based Nano-biosensor for the Rapid Detection of the Dengue Virus in Mosquito
Authors: Lilia M. Fernando, Matthew K. Vasher, Evangelyn C. Alocilja
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This paper describes the development of a DNA-based nanobiosensor to detect the dengue virus in mosquito using electrically active magnetic (EAM) nanoparticles as the concentrator and electrochemical transducer. The biosensor detection encompasses two sets of oligonucleotide probes that are specific to the dengue virus: the detector probe labeled with the EAM nanoparticles and the biotinylated capture probe. The DNA targets are double hybridized to the detector and the capture probes and concentrated from nonspecific DNA fragments by applying a magnetic field. Subsequently, the DNA sandwiched targets (EAM-detector probe–DNA target–capture probe-biotin) are captured on streptavidin modified screen printed carbon electrodes through the biotinylated capture probes. Detection is achieved electrochemically by measuring the oxidation–reduction signal of the EAM nanoparticles. Results indicate that the biosensor is able to detect the redox signal of the EAM nanoparticles at dengue DNA concentrations as low as 10 ng/ul.Keywords: dengue, magnetic nanoparticles, mosquito, nanobiosensor
Procedia PDF Downloads 35714569 The Effect of the Epstein-Barr Virus on the Development of Multiple Sclerosis
Authors: Sina Mahdavi
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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs
Procedia PDF Downloads 8614568 Marker-Controlled Level-Set for Segmenting Breast Tumor from Thermal Images
Authors: Swathi Gopakumar, Sruthi Krishna, Shivasubramani Krishnamoorthy
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Contactless, painless and radiation-free thermal imaging technology is one of the preferred screening modalities for detection of breast cancer. However, poor signal to noise ratio and the inexorable need to preserve edges defining cancer cells and normal cells, make the segmentation process difficult and hence unsuitable for computer-aided diagnosis of breast cancer. This paper presents key findings from a research conducted on the appraisal of two promising techniques, for the detection of breast cancer: (I) marker-controlled, Level-set segmentation of anisotropic diffusion filtered preprocessed image versus (II) Segmentation using marker-controlled level-set on a Gaussian-filtered image. Gaussian-filtering processes the image uniformly, whereas anisotropic filtering processes only in specific areas of a thermographic image. The pre-processed (Gaussian-filtered and anisotropic-filtered) images of breast samples were then applied for segmentation. The segmentation of breast starts with initial level-set function. In this study, marker refers to the position of the image to which initial level-set function is applied. The markers are generally placed on the left and right side of the breast, which may vary with the breast size. The proposed method was carried out on images from an online database with samples collected from women of varying breast characteristics. It was observed that the breast was able to be segmented out from the background by adjustment of the markers. From the results, it was observed that as a pre-processing technique, anisotropic filtering with level-set segmentation, preserved the edges more effectively than Gaussian filtering. Segmented image, by application of anisotropic filtering was found to be more suitable for feature extraction, enabling automated computer-aided diagnosis of breast cancer.Keywords: anisotropic diffusion, breast, Gaussian, level-set, thermograms
Procedia PDF Downloads 37014567 Development of Transgenic Tomato Immunity to Pepino Mosaic Virus and Tomato Yellow Leaf Curl Virus by Gene Silencing Approach
Authors: D. Leibman, D. Wolf, A. Gal-On
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Viral diseases of tomato crops result in heavy yield losses and may even jeopardize the production of these crops. Classical tomato breeding for disease resistance against Tomato yellow leaf curl virus (TYLCV), leads to partial resistance associated with a number of recessive genes. To author’s best knowledge Pepino mosaic virus (PepMV) genetic resistance is not yet available. The generation of viral resistance by means of genetic engineering was reported and implemented for many crops, including tomato. Transgenic resistance against viruses is based, in most cases, on Post Transcriptional Gene Silencing (PTGS), an endogenous mechanism which destroys the virus genome. In this work, we developed immunity against PepMV and TYLCV in a tomato based on a PTGS mechanism. Tomato plants were transformed with a hairpin-construct-expressed transgene-derived double-strand-RNA (tr-dsRNA). In the case of PepMV, the binary construct harbored three consecutive fragments of the replicase gene from three different PepMV strains (Italian, Spanish and American), to provide resistance against a range of virus strains. In the case of TYLCV, the binary vector included three consecutive fragments of the IR, V2 and C2 viral genes constructed in a hairpin configuration. Selected transgenic lines (T0) showed a high accumulation of transgene siRNA of 21-24 bases, and T1 transgenic lines showed complete immunity to PepMV and TYLCV. Graft inoculation displayed immunity of the transgenic scion against PepMV and TYLCV. The study presents the engineering of resistance in tomato against two serious diseases, which will help in the production of high-quality tomato. However, unfortunately, these resistant plants have not been implemented due to public ignorance and opposition against breeding by genetic engineering.Keywords: PepMV, PTGS, TYLCV, tr-dsRNA
Procedia PDF Downloads 12114566 Study of Non-hodgkin’s Lymphoma
Authors: Zidani Abla
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Lymphoma is a common type of cancer that affects the lymphatic system, including the lymph nodes, spleen and other associated organs. There are two main types of lymphoma: Hodgkin's lymphoma and non-Hodgkin's lymphoma. The epidemiological, clinical and biological features of lymphoma are poorly studied in Algeria. The main objective of our study is to investigate the epidemiological, clinical, paraclinical, etiological, evolutionary and biological characteristics of non-Hodgkin's lymphoma (NHL) in the hematology department of the University Hospital Center (HUC) of Batna. This is a study of 10 patients diagnosed at Batna University Hospital. 70% were male and 30% female (sex ratio M/F= 2.33). Median age was 51.7 years. Pain, especially abdominal pain, was the main reason for consultation. Stage IV predominated (40%), followed by stage III (20%). Abdominal adenopathies (34%) were the most abundant. Secondary hepatic localization was predominant. Large B-cell NHL predominated, accounting for 60% of cases, followed by small B-cell NHL (30%). Serology for hepatitis B and C, and human immunodeficiency virus (HIV) was negative. Biologically, a predominance of hyperleukocytosis, polynuclear neutrophilic leukocytosis, lymphopenia and hypoalbuminemia were present in the majority of cases. In summary, our results remain to be compared with other works for other periods and other regions in order to generalize lymphoma percentages for the entire Algerian population.Keywords: non Hodgkin's lymphoma, epidemiology, clinic, biology
Procedia PDF Downloads 1214565 A Novel Small-Molecule Inhibitor of Influenza a Virus Acts by Suppressing PA Endonuclease Activity of the Viral Polymerase
Authors: Shuafeng Yuan, Bojian Zheng
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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA
Procedia PDF Downloads 23714564 Households’ Willingness to Pay for Environmental and General Health Safety during the Advent of Ebola Virus Diseases in Nigeria
Authors: Shittu Bisi Agnes
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Studies on households’ willingness to pay for environmental and general health safety in the advent of Ebola virus Diseases in Nigeria was carried out. This is aimed at revealing the means by which the virus was eventually eradicated in Nigeria as widely claimed in the media. This study therefore attempted to determine the environmental and general health condition in the State Of Osun, how socio-economic characteristics of the people affected willingness to pay. And also provide platform for the reduction of environmental and general health problems. Data were collected with the aid of well-structured questionnaire and administer 150 randomly selected people of study area, and oral interview was also utilized. Data collected were analyzed using both descriptive tools and inferential statistics vis-a-viz regression analysis. Findings showed 92.5% of respondents was aware of ebola virus diseases outbreak in Nigeria, 8.5% was unaware of any disease outbreak. And 65.7% of respondents was strongly willing to pay for environmental and general health safety 27.1% was fairly willing, 5.7% was indifferent and 1.7% was unwilling to pay. 5% rated the level of environmental and general health condition in the area has been good, 53.6% rated theirs has been fair, 33.6% as been poor. The average willingness to pay per household per month were #500.00, #250.00, #150.00 and #100.00 respectively for the four categories. It was recommended that policy instruments to increase peoples' income will accelerate eradication of environmental and general health problems, environmental health education in form of talk shop, workshop, lectures and seminars could be organized at the political ward levels, churches, mosque, and at schools. Environmental and general health safety related information could be disseminated through mass media, market women, and functional unions.Keywords: ebola virus diseases (EVD), socio-economic, safety, pay, Osun
Procedia PDF Downloads 40714563 Prevalent Features of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017
Authors: Lei Zhou, Dan Li, Ruiqi Ren, Chao Li, Yali Wang, Daxin Ni, Zijian Feng, Timothy M. Uyeki, Qun Li
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Since the first human infections with avian influenza A(H7N9) virus were identified in early 2013, 1533 cases of laboratory-confirmed A(H7N9) virus infections were reported and confirmed as of September 13, 2017. The fifth epidemic was defined as starting from September 1, 2016, and the number of A(H7N9) cases has surged since the end of December in 2016. On February 18, 2017, the A(H7N9) cases who were infected with highly pathogenic avian influenza (HPAI) virus was reported from Southern China. The HPAI A(H7N9) cases were identified and then an investigation and analyses were conducted to assess whether disease severity in humans has changed with HPAI A(H7N9) compared with low pathogenic avian influenza (LPAI) A(H7N9) virus infection. Methods: All confirmed cases with A(H7N9) virus infections reported throughout mainland China from September 1, 2016, to September 13, 2017, were included. Cases' information was extracted from field investigation reports and the notifiable infectious surveillance system to describe the demographic, clinical, and epidemiologic characteristics. Descriptive statistics were used to compare HPAI A(H7N9) cases with all LPAI A(H7N9) cases reported during the fifth epidemic. Results: A total of 27 cases of HPAI A(H7N9) virus were identified infection from five provinces, including Guangxi (44%), Guangdong (33%), Hunan (15%), Hebei (4%) and Shangxi (4%). The median age of cases of HPAI A(H7N9) virus infection was 60 years (range, 15 to 80) and most of them were male (59%) and lived in rural areas (78%). All 27 cases had live poultry related exposures within 10 days before their illness onset. In comparison with LPAI A(H7N9) case-patients, HPAI A(H7N9) case-patients were significantly more likely to live in rural areas (78% vs. 51%; p = 0.006), have exposure to the sick or dead poultry (56% vs. 19%; p = 0.000), and be hospitalized earlier (median 3 vs. 4 days; p = 0.007). No significant differences were observed in median age, sex, prevalence of underlying chronic medical conditions, median time from illness onset to first medical service seeking, starting antiviral treatment, and diagnosis. Although the median time from illness onset to death (9 vs. 13 days) was shorter and the overall case-fatality proportion (48% vs. 38%) was higher for HPAI A(H7N9) case-patients than for LPAI A(H7N9) case-patients, these differences were not statistically significant. Conclusions: Our findings indicate that HPAI A(H7N9) virus infection was associated with exposure to sick and dead poultry in rural areas when visited live poultry market or in the backyard. In the fifth epidemic in mainland China, HPAI A (H7N9) case-patients were hospitalized earlier than LPAI A(H7N9) case-patients. Although the difference was not statistically significant, the mortality of HPAI A (H7N9) case-patients was obviously higher than that of LPAI A(H7N9) case-patients, indicating a potential severity change of HPAI A(H7N9) virus infection.Keywords: Avian influenza A (H7N9) virus, highly pathogenic avian influenza (HPAI), case-patients, poultry
Procedia PDF Downloads 15514562 Oncolytic Efficacy of Thymidine Kinase-Deleted Vaccinia Virus Strain Tiantan (oncoVV-TT) in Glioma
Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi
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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus
Procedia PDF Downloads 6814561 Epidemiological Survey of Feline Leukemia Virus in Domestic Cats on Tsushima Island, Japan: Tsushima Leopard Cats Are at Risk
Authors: Isaac Makundi, Kazuo Nishigaki
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The Tsushima leopard cat (TLC) Prionailurus bengalensis euptilurus, designated a National Natural Monument of Japan, inhabits Tsushima Island, Nagasaki Prefecture, Japan. TLC is considered a subspecies of P. bengalensis, and lives only on Tsushima Island. TLCs are threatened by various infectious diseases. Feline leukemia virus (FeLV) causes a serious infectious disease with a poor prognosis in cats. Therefore, the transmission of FeLV from Tsushima domestic cats (TDCs) to TLCs may threaten the TLC population. We investigated the FeLV infection status of both TDCs and TLCs on Tsushima Island by screening blood samples for FeLV p27 antigen and using PCR to amplify the full-length FeLV env gene. The prevalence of FeLV was 6.4% in TDCs and 0% in TLCs. We also demonstrated that the virus can replicate in the cells of TLCs, suggesting its potential cross-species transmission. The viruses in TDCs were classified as genotype I/clade 3, which is prevalent on a nearby island, based on previous studies of FeLV genotypes and FeLV epidemiology. The FeLV viruses identified on Tsushima Island can be further divided into two lineages within genotype I/clade 3, which are geographically separated in Kamijima and Shimojima, indicating that FeLV may have been transmitted to Tsushima Island at least twice. Monitoring FeLV infection in the TDC and TLC populations is highly recommended as part of the TLC surveillance and management strategy.Keywords: epidemiology, Feline leukemia virus, Tsushima Island, wildlife management
Procedia PDF Downloads 20114560 The Reality of the Digital Inequality and Its Negative Impact on Virtual Learning during the COVID-19 Pandemic: The South African Perspective
Authors: Jacob Medupe
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Life as we know it has changed since the global outbreak of Coronavirus Disease 2019 (COVID-19) and business as usual will not continue. The human impact of the COVID-19 crisis is already immeasurable. Moreover, COVID-19 has already negatively impacted economies, livelihoods and disrupted food systems around the world. The disruptive nature of the Corona virus has affected every sphere of life including the culture and teaching and learning. Right now the majority of education research is based around classroom management techniques that are no longer necessary with digital delivery. Instead there is a great need for new data about how to make the best use of the one-on-one attention that is now becoming possible (Diamandis & Kotler, 2014). The COVID-19 pandemic has necessitated an environment where the South African learners are focused to adhere to social distancing in order to minimise the wild spread of the Corona virus. This arrangement forces the student to utilise the online classroom technologies to continue with the lessons. The historical reality is that the country has not made much strides on the closing of the digital divide and this is particularly a common status quo in the deep rural areas. This will prove to be a toll order for most of the learners affected by the Corona Virus to be able to have a seamless access to the online learning facilities. The paper will seek to look deeply into this reality and how the Corona virus has brought us to the reality that South Africa remains a deeply unequal society in every sphere of life. The study will also explore the state of readiness for education system around the online classroom environment.Keywords: virtual learning, virtual classroom, COVID-19, Corona virus, internet connectivity, blended learning, online learning, distance education, e-learning, self-regulated Learning, pedagogy, digital literacy
Procedia PDF Downloads 12114559 Development of Dye Sensitized Solar Window by Physical Parameters Optimization
Authors: Tahsin Shameem, Chowdhury Sadman Jahan, Mohammad Alam
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Interest about Net Zero Energy Buildings have gained traction in recent years following the need to sustain energy consumption with generations on site and to reduce dependence on grid supplied energy from large plants using fossil fuel. With this end in view, building integrated photovoltaics are being studied attempting to utilize all exterior facades of a building to generate power. In this paper, we have looked at the physical parameters defining a dye sensitized solar cell (DSSC) and discussed their impact on energy harvest. Following our discussion and experimental data obtained from literature, we have attempted to optimize these physical parameters accordingly so as to allow maximum light absorption for a given active layer thickness. We then modified a planer DSSC design with our optimized properties to allow adequate light transmission which demonstrated a high fill factor and an External Quantum Efficiency (EQE) of greater than 9% by computer aided design and simulation. In conclusion, a DSSC based solar window with such high output values even after such high light transmission through it definitely flags a promising future for this technology and our work elicits the need for further study and practical experimentation.Keywords: net zero energy building, integrated photovoltaics, dye sensitized solar cell, fill factor, External Quantum Efficiency
Procedia PDF Downloads 13314558 Exploring Emerging Viruses From a Protected Reserve
Authors: Nemat Sokhandan Bashir
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Threats from viruses to agricultural crops could be even larger than the losses caused by the other pathogens because, in many cases, the viral infection is latent but crucial from an epidemic point of view. Wild vegetation can be a source of many viruses that eventually find their destiny in crop plants. Although often asymptomatic in wild plants due to adaptation, they can potentially cause serious losses in crops. Therefore, exploring viruses in wild vegetation is very important. Recently, omics have been quite useful for exploring plant viruses from various plant sources, especially wild vegetation. For instance, we have discovered viruses such as Ambrossia asymptomatic virus I (AAV-1) through the application of metagenomics from Oklahoma Prairie Reserve. Accordingly, extracts from randomly-sampled plants are subjected to high speed and ultracentrifugation to separated virus-like particles (VLP), then nucleic acids in the form of DNA or RNA are extracted from such VLPs by treatment with phenol—chloroform and subsequent precipitation by ethanol. The nucleic acid preparations are separately treated with RNAse or DNAse in order to determine the genome component of VLPs. In the case of RNAs, the complementary cDNAs are synthesized before submitting to DNA sequencing. However, for VLPs with DNA contents, the procedure would be relatively straightforward without making cDNA. Because the length of the nucleic acid content of VPLs can be different, various strategies are employed to achieve sequencing. Techniques similar to so-called "chromosome walking" may be used to achieve sequences of long segments. When the nucleotide sequence data were obtained, they were subjected to BLAST analysis to determine the most related previously reported virus sequences. In one case, we determined that the novel virus was AAV-l because the sequence comparison and analysis revealed that the reads were the closest to the Indian citrus ringspot virus (ICRSV). AAV—l had an RNA genome with 7408 nucleotides in length and contained six open reading frames (ORFs). Based on phylogenies inferred from the replicase and coat protein ORFs of the virus, it was placed in the genus Mandarivirus.Keywords: wild, plant, novel, metagenomics
Procedia PDF Downloads 6914557 Simulation Aided Life Cycle Sustainability Assessment Framework for Manufacturing Design and Management
Authors: Mijoh A. Gbededo, Kapila Liyanage, Ilias Oraifige
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Decision making for sustainable manufacturing design and management requires critical considerations due to the complexity and partly conflicting issues of economic, social and environmental factors. Although there are tools capable of assessing the combination of one or two of the sustainability factors, the frameworks have not adequately integrated all the three factors. Case study and review of existing simulation applications also shows the approach lacks integration of the sustainability factors. In this paper we discussed the development of a simulation based framework for support of a holistic assessment of sustainable manufacturing design and management. To achieve this, a strategic approach is introduced to investigate the strengths and weaknesses of the existing decision supporting tools. Investigation reveals that Discrete Event Simulation (DES) can serve as a rock base for other Life Cycle Analysis frameworks. Simio-DES application optimizes systems for both economic and competitive advantage, Granta CES EduPack and SimaPro collate data for Material Flow Analysis and environmental Life Cycle Assessment, while social and stakeholders’ analysis is supported by Analytical Hierarchy Process, a Multi-Criteria Decision Analysis method. Such a common and integrated framework creates a platform for companies to build a computer simulation model of a real system and assess the impact of alternative solutions before implementing a chosen solution.Keywords: discrete event simulation, life cycle sustainability analysis, manufacturing, sustainability
Procedia PDF Downloads 27214556 Addressing Factors Associated with Vertical HIV Transmission among Pregnant Women in Rwanda
Authors: Murorunkwere Marie Claire
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Introduction: In Sub-Saharan Africa and specifically in Rwandan rural areas, mother-to-Child human immunodeficiency virus transmission remains a big challenge. This is mainly due to lack of awareness and ignorance among pregnant rural women, leading to neglect regular taking of prophylactic antiretroviral treatment and to persistently beliefs in traditional healers and home deliveries. This paper explores the factors associated with stagnant reduction in human immunodeficiency virus vertical transmission among pregnant rural women and provides solutions to tackle it. Methodology: The first phase of this research will be a qualitative survey was conducted to assess the knowledge, attitudes and practices towards vertical human immunodeficiency virus transmission among pregnant women in one rural district in Rwanda. The data generated from phase one of this research will be used to address the main factors revealed through community mobilization and motivation on attending required antenatal consultations and hospital deliveries, proper and regular antiretroviral treatment taking, and discouraging beliefs in traditional healers and home deliveries. Refresher training seminars will also be organized for healthcare providers qualified on conducting deliveries about current measures to maximize the reduction of chances that can lead to mother -child contamination (to avoid early rupture of membranes and to prevent any source of contamination). Results: This paper is expected to contribute in a significant reduction of the vertical human immunodeficiency virus transmission burden among pregnant rural women. Conclusion: Strong campaigns on prevention of mother- to-child human immunodeficiency virus transmission and community mobilization of pregnant rural women, and house to house education and continuous reminders as well as training seminars to health care personnel on updated measures is, key in addressing vertical human immunodeficiency virus transmission.Keywords: attitudes transformation, community mobilisation, pregnant rural women, vertical HIV transmission
Procedia PDF Downloads 7614555 Design and in Slico Study of the Truncated Spike-M-N SARS-CoV-2 as a Novel Effective Vaccine Candidate
Authors: Aghasadeghi MR., Bahramali G., Sadat SM., Sadeghi SA., Yousefi M., Khodaei K., Ghorbani M., Sadat Larijani M.
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Background:The emerging COVID-19 pandemic is a serious concernfor the public health worldwide. Despite the many mutations in the virus genome, it is important to find an effective vaccine against viral mutations. Therefore, in current study, we aimed at immunoinformatic evaluation of the virus proteins immunogenicity to design a preventive vaccine candidate, which could elicit humoral and cellular immune responses as well. Methods:Three antigenic regions are included;Spike, Membrane, and Nucleocapsid amino acid sequences were obtained, and possible fusion proteins were assessed andcompared by immunogenicity, structural features, and population coverage. The best fusion protein was also evaluated for MHC-I and MHC-II T-cell epitopes and the linear and conformational B-cell epitopes. Results: Among the four predicted models, the truncated Spike protein in fusion with M and N proteins is composed of 24 highly immunogenic human MHC class I and 29 MHC class II, along with 14 B-cell linear and 61 discontinues epitopes. Also, the selected protein has high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. Conclusion: The data indicate that the truncated Spike-M-N SARS-CoV-2form which could be potential targets of neutralizing antibodies. The protein also has the ability to stimulate humoral and cellular immunity. The in silico study provided the fusion protein as a potential preventive vaccine candidate for further in vivo evaluation.Keywords: SARS-CoV-2, immunoinformatic, protein, vaccine
Procedia PDF Downloads 21414554 Design Optimization of Miniature Mechanical Drive Systems Using Tolerance Analysis Approach
Authors: Eric Mxolisi Mkhondo
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Geometrical deviations and interaction of mechanical parts influences the performance of miniature systems.These deviations tend to cause costly problems during assembly due to imperfections of components, which are invisible to a naked eye.They also tend to cause unsatisfactory performance during operation due to deformation cause by environmental conditions.One of the effective tools to manage the deviations and interaction of parts in the system is tolerance analysis.This is a quantitative tool for predicting the tolerance variations which are defined during the design process.Traditional tolerance analysis assumes that the assembly is static and the deviations come from the manufacturing discrepancies, overlooking the functionality of the whole system and deformation of parts due to effect of environmental conditions. This paper presents an integrated tolerance analysis approach for miniature system in operation.In this approach, a computer-aided design (CAD) model is developed from system’s specification.The CAD model is then used to specify the geometrical and dimensional tolerance limits (upper and lower limits) that vary component’s geometries and sizes while conforming to functional requirements.Worst-case tolerances are analyzed to determine the influenced of dimensional changes due to effects of operating temperatures.The method is used to evaluate the nominal conditions, and worse case conditions in maximum and minimum dimensions of assembled components.These three conditions will be evaluated under specific operating temperatures (-40°C,-18°C, 4°C, 26°C, 48°C, and 70°C). A case study on the mechanism of a zoom lens system is used to illustrate the effectiveness of the methodology.Keywords: geometric dimensioning, tolerance analysis, worst-case analysis, zoom lens mechanism
Procedia PDF Downloads 15914553 Tenofovir-Amino Acid Conjugates Act as Polymerase Substrates: Implications for Avoiding Cellular Phosphorylation in the Discovery of Nucleotide Analogs
Authors: Weijie Gu, Sergio Martinez, Hoai Nguyen, Hongtao Xu, Piet Herdewijn, Steven De Jonghe, Kalyan Das
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Nucleotide analogs are used for treating viral infections such as HIV, hepatitis B, hepatitis C, influenza, and SARS-CoV-2. To become polymerase substrates, a nucleotide analog must be phosphorylated by cellular kinases, which are rate-limiting. The goal of this study is to develop dNTP/NTP analogs directly from nucleotides. Tenofovir (TFV) analogs were synthesized by conjugating with natural or unnatural amino acids. It demonstrates that some conjugates act as dNTP analogs, and HIV-1 reverse transcriptase (RT) catalytically incorporates the TFV part as the chain terminator. X-ray structures in complex with HIV-1 RT/dsDNA showed binding of the conjugates at the polymerase active site, however, in different modes in the presence of Mg²⁺ vs. Mn²⁺ ions. The adaptability of the compounds is seemingly essential for catalytic incorporation of TFV by RT. 4d with a carboxyl sidechain demonstrated the highest incorporation. 4e showed weak incorporation and rather behaved as a dNTP-competitive inhibitor. This result advocates the feasibility of designing NTP/dNTP analogs by chemical substitutions to nucleotide analogs.Keywords: dNTP analogs, nucleotide analogs, polymerase, tenofovir, X-ray structure
Procedia PDF Downloads 147