Search results for: vaccine candidate
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 902

Search results for: vaccine candidate

752 A Mixed Expert Evaluation System and Dynamic Interval-Valued Hesitant Fuzzy Selection Approach

Authors: Hossein Gitinavard, Mohammad Hossein Fazel Zarandi

Abstract:

In the last decades, concerns about the environmental issues lead to professional and academic efforts on green supplier selection problems. In this sake, one of the main issues in evaluating the green supplier selection problems, which could increase the uncertainty, is the preferences of the experts' judgments about the candidate green suppliers. Therefore, preparing an expert system to evaluate the problem based on the historical data and the experts' knowledge can be sensible. This study provides an expert evaluation system to assess the candidate green suppliers under selected criteria in a multi-period approach. In addition, a ranking approach under interval-valued hesitant fuzzy set (IVHFS) environment is proposed to select the most appropriate green supplier in planning horizon. In the proposed ranking approach, the IVHFS and the last aggregation approach are considered to margin the errors and to prevent data loss, respectively. Hence, a comparative analysis is provided based on an illustrative example to show the feasibility of the proposed approach.

Keywords: green supplier selection, expert system, ranking approach, interval-valued hesitant fuzzy setting

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751 Molecular Characterisation and Expression of Glutathione S-Transferase of Fasciola Gigantica

Authors: J. Adeppa, S. Samanta, O. K. Raina

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Fasciolosis is a widespread economically important parasitic infection throughout the world caused by Fasciola hepatica and F. gigantica. In order to identify novel immunogen conferring significant protection against fasciolosis, currently, research has been focused on the defined antigens viz. glutathione S-transferase, fatty acid binding protein, cathepsin-L, fluke hemoglobin, paramyosin, myosin and F. hepatica- Kunitz Type Molecule. Among various antigens, GST which plays a crucial role in detoxification processes, i.e. phase II defense mechanism of this parasite, has a unique position as a novel vaccine candidate and a drug target in the control of this disease. For producing the antigens in large quantities and their purification to complete homogeneity, the recombinant DNA technology has become an important tool to achieve this milestone. RT- PCR was carried out using F. gigantica total RNA as template, and an amplicon of 657 bp GST gene was obtained. TA cloning vector was used for cloning of this gene, and the presence of insert was confirmed by blue-white selection for recombinant colonies. Sequence analysis of the present isolate showed 99.1% sequence homology with the published sequence of the F. gigantica GST gene of cattle origin (accession no. AF112657), with six nucleotide changes at 72, 74, 423, 513, 549 and 627th bp found in the present isolate, causing an overall change of 4 amino acids. The 657 bp GST gene was cloned at BamH1 and HindIII restriction sites of the prokaryotic expression vector pPROEXHTb in frame with six histidine residues and expressed in E. coli DH5α. Recombinant protein was purified from the bacterial lysate under non-denaturing conditions by the process of sonication after lysozyme treatment and subjecting the soluble fraction of the bacterial lysate to Ni-NTA affinity chromatography. Western blotting with rabbit hyper-immune serum showed immuno-reactivity with 25 kDa recombinant GST. Recombinant protein detected F. gigantica experimental as well as field infection in buffaloes by dot-ELISA. However, cross-reactivity studies on Fasciola gigantica GST antigen are needed to evaluate the utility of this protein in the serodiagnosis of fasciolosis.

Keywords: fasciola gigantic, fasciola hepatica, GST, RT- PCR

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750 Midwives’ Perceptions and Experiences of Recommending and Delivering Vaccines to Pregnant Women Following the COVID-19 Pandemic

Authors: Cath Grimley, Debra Bick, Sarah Hillman, Louise Clarke, Helen Atherton, Jo Parsons

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The problem: Women in the UK are offered influenza (flu), pertussis (whooping cough) and COVID-19 vaccinations during their pregnancy but uptake of all three vaccines is below the desired rate. These vaccines are offered during pregnancy as pregnant women are at an increased risk of hospitalisation, morbidity, and mortality from these illnesses. Exposure to these diseases during pregnancy can also have a negative impact on the unborn baby with an increased risk of serious complications both while in utero and following birth. The research aims to explore perceptions about the vaccinations offered in pregnancy both from the perspectives of pregnant women and midwives. To determine factors that influence pregnant women’s decisions about whether or not to accept the vaccines following the Covid-19 pandemic and to explore midwives’ experiences of recommending and delivering vaccines. The approach: This research follows a qualitative design involving semi-structured interviews with pregnant women and midwives in the UK. Interviews with midwives explored vaccination discussions they routinely have with pregnant women and identified some of the barriers to vaccination that pregnant women discuss with them. Interviews with pregnant women explored their views since the COVID-19 pandemic about vaccinations offered during pregnancy, and whether the pandemic has influenced perceptions of vulnerability to illness in pregnant women. Midwives were recruited via participating hospitals and midwife specific social media groups. Pregnant women were recruited via participating hospitals and community groups. All interviews were conducted remotely (using telephone or Microsoft Teams) and analysed using thematic analysis. Findings: 43 pregnant women and 16 midwives were recruited and interviewed. The findings presented here will focus on data from midwives. Topics identified included three key themes for midwives. These were 1) Delivery of vaccinations which includes the convenience of offering vaccinations while attending standard antenatal appointments and practical barriers faced in delivering these vaccinations at hospital. 2) Messages and guidance included the importance of up-to-date informational needs for midwives to deliver vaccines and that uncertainty and conflicting messages about the COVID-19 vaccine during pregnancy were a barrier to delivery. 3) Recommendations to have vaccines look at all aspects of recommendations such as how recommendations are communicated, the contents of the recommendation, the importance of the vaccine and the impact of those recommendations on whether women accept the vaccine. Implications: Findings highlight the importance for midwives to receive clear and consistent information so they can feel confident in relaying this information while recommending and delivering vaccines to pregnant women. Emphasising why vaccines are important when recommending vaccinations to pregnant women in addition to standard information on the availability and timing will add to the strength and impact of that recommendation in helping women to make informed decisions about accepting vaccines. The findings of this study will inform the development of an intervention to increase vaccination uptake amongst pregnant women.

Keywords: vaccination, pregnancy, qualitative, interviews, Covid-19, midwives

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749 An Analytical Metric and Process for Critical Infrastructure Architecture System Availability Determination in Distributed Computing Environments under Infrastructure Attack

Authors: Vincent Andrew Cappellano

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In the early phases of critical infrastructure system design, translating distributed computing requirements to an architecture has risk given the multitude of approaches (e.g., cloud, edge, fog). In many systems, a single requirement for system uptime / availability is used to encompass the system’s intended operations. However, when architected systems may perform to those availability requirements only during normal operations and not during component failure, or during outages caused by adversary attacks on critical infrastructure (e.g., physical, cyber). System designers lack a structured method to evaluate availability requirements against candidate system architectures through deep degradation scenarios (i.e., normal ops all the way down to significant damage of communications or physical nodes). This increases risk of poor selection of a candidate architecture due to the absence of insight into true performance for systems that must operate as a piece of critical infrastructure. This research effort proposes a process to analyze critical infrastructure system availability requirements and a candidate set of systems architectures, producing a metric assessing these architectures over a spectrum of degradations to aid in selecting appropriate resilient architectures. To accomplish this effort, a set of simulation and evaluation efforts are undertaken that will process, in an automated way, a set of sample requirements into a set of potential architectures where system functions and capabilities are distributed across nodes. Nodes and links will have specific characteristics and based on sampled requirements, contribute to the overall system functionality, such that as they are impacted/degraded, the impacted functional availability of a system can be determined. A machine learning reinforcement-based agent will structurally impact the nodes, links, and characteristics (e.g., bandwidth, latency) of a given architecture to provide an assessment of system functional uptime/availability under these scenarios. By varying the intensity of the attack and related aspects, we can create a structured method of evaluating the performance of candidate architectures against each other to create a metric rating its resilience to these attack types/strategies. Through multiple simulation iterations, sufficient data will exist to compare this availability metric, and an architectural recommendation against the baseline requirements, in comparison to existing multi-factor computing architectural selection processes. It is intended that this additional data will create an improvement in the matching of resilient critical infrastructure system requirements to the correct architectures and implementations that will support improved operation during times of system degradation due to failures and infrastructure attacks.

Keywords: architecture, resiliency, availability, cyber-attack

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748 Qualitative and Quantitative Analysis of Motivation Letters to Model Turnover in Non-Governmental Organization

Authors: A. Porshnev, A. Zaporozhtchuk

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Motivation regarded as a key factor of labor turnover, is especially important for volunteers working on an altruistic basis in NGO. Despite the motivational letter, candidate selection depends on the impression of the selection committee, which can be subject to human bias. We expect that structured and unstructured information provided in motivation letters could be used to improve candidate selection procedures. In our paper, we perform qualitative and quantitative analysis of 2280 motivation letters, create logistic regression, and build a decision tree to improve selection procedures. Our analysis showed that motivation factors are significant and enable human resources department to forecast labor turnover and provide extra information to demographic, professional and timing questions. In spite of the average level of accuracy the model demonstrates the selection procedures of company of under consideration can be improved. We also discuss interrelation between answers to open and closed motivation questions, recommend changes in motivational letter templates to ensure more relevant information about applicants and further steps to create more accurate model.

Keywords: decision trees, logistic regression, model, motivational letter, non-governmental organization, retention, turnover

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747 Selecting Answers for Questions with Multiple Answer Choices in Arabic Question Answering Based on Textual Entailment Recognition

Authors: Anes Enakoa, Yawei Liang

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Question Answering (QA) system is one of the most important and demanding tasks in the field of Natural Language Processing (NLP). In QA systems, the answer generation task generates a list of candidate answers to the user's question, in which only one answer is correct. Answer selection is one of the main components of the QA, which is concerned with selecting the best answer choice from the candidate answers suggested by the system. However, the selection process can be very challenging especially in Arabic due to its particularities. To address this challenge, an approach is proposed to answer questions with multiple answer choices for Arabic QA systems based on Textual Entailment (TE) recognition. The developed approach employs a Support Vector Machine that considers lexical, semantic and syntactic features in order to recognize the entailment between the generated hypotheses (H) and the text (T). A set of experiments has been conducted for performance evaluation and the overall performance of the proposed method reached an accuracy of 67.5% with C@1 score of 80.46%. The obtained results are promising and demonstrate that the proposed method is effective for TE recognition task.

Keywords: information retrieval, machine learning, natural language processing, question answering, textual entailment

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746 Phage Display-Derived Vaccine Candidates for Control of Bovine Anaplasmosis

Authors: Itzel Amaro-Estrada, Eduardo Vergara-Rivera, Virginia Juarez-Flores, Mayra Cobaxin-Cardenas, Rosa Estela Quiroz, Jesus F. Preciado, Sergio Rodriguez-Camarillo

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Bovine anaplasmosis is an infectious, tick-borne disease caused mainly by Anaplasma marginale; typical signs include anemia, fever, abortion, weight loss, decreased milk production, jaundice, and potentially death. Sick bovine can recover when antibiotics are administered; however, it usually remains as carrier for life, being a risk of infection for susceptible cattle. Anaplasma marginale is an obligate intracellular Gram-negative bacterium with genetic composition highly diverse among geographical isolates. There are currently no vaccines fully effective against bovine anaplasmosis; therefore, the economic losses due to disease are present. Vaccine formulation became a hard task for several pathogens as Anaplasma marginale, but peptide-based vaccines are an interesting proposal way to induce specific responses. Phage-displayed peptide libraries have been proved one of the most powerful technologies for identifying specific ligands. Screening of these peptides libraries is also a tool for studying interactions between proteins or peptides. Thus, it has allowed the identification of ligands recognized by polyclonal antiserums, and it has been successful for the identification of relevant epitopes in chronic diseases and toxicological conditions. Protective immune response to bovine anaplasmosis includes high levels of immunoglobulins subclass G2 (IgG2) but not subclass IgG1. Therefore, IgG2 from the serum of protected bovine can be useful to identify ligands, which can be part of an immunogen for cattle. In this work, phage display random peptide library Ph.D. ™ -12 was incubating with IgG2 or blood sera of immunized bovines against A. marginale as targets. After three rounds of biopanning, several candidates were selected for additional analysis. Subsequently, their reactivity with sera immunized against A. marginale, as well as with positive and negative sera to A. marginale was evaluated by immunoassays. A collection of recognized peptides tested by ELISA was generated. More than three hundred phage-peptides were separately evaluated against molecules which were used during panning. At least ten different peptides sequences were determined from their nucleotide composition. In this approach, three phage-peptides were selected by their binding and affinity properties. In the case of the development of vaccines or diagnostic reagents, it is important to evaluate the immunogenic and antigenic properties of the peptides. Immunogenic in vitro and in vivo behavior of peptides will be assayed as synthetic and as phage-peptide for to determinate their vaccine potential. Acknowledgment: This work was supported by grant SEP-CONACYT 252577 given to I. Amaro-Estrada.

Keywords: bovine anaplasmosis, peptides, phage display, veterinary vaccines

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745 Bacterial Flora of the Anopheles Fluviatilis S. L. in an Endemic Malaria Area in Southeastern Iran for Candidate Paraterasgenesis Strains

Authors: Seyed Hassan Moosa-kazemi, Jalal Mohammadi Soleimani, Hassan Vatandoost, Mohammad Hassan Shirazi, Sara Hajikhani, Roonak Bakhtiari, Morteza Akbari, Siamak Hydarzadeh

Abstract:

Malaria is an infectious disease and considered most important health problems in the southeast of Iran. Iran is elimination malaria phase and new tool need to vector control. Paraterasgenesis is a new way to cut of life cycle of the malaria parasite. In this study, the microflora of the surface and gut of various stages of Anopheles fluviatilis James as one of the important malaria vector was studied using biochemical and molecular techniques during 2013-2014. Twelve bacteria species were found including; Providencia rettgeri, Morganella morganii, Enterobacter aerogenes, Pseudomonas oryzihabitans, Citrobacter braakii، Citrobacter freundii، Aeromonas hydrophila، Klebsiella oxytoca, Citrobacter koseri, Serratia fonticola، Enterobacter sakazakii and Yersinia pseudotuberculosis. The species of Alcaligenes faecalis, Providencia vermicola and Enterobacter hormaechei were identified in various stages of the vector and confirmed by biochemical and molecular techniques. We found Providencia rettgeri proper candidate for paratransgenesis.

Keywords: Anopheles fluviatilis, bacteria, malaria, Paraterasgenesis, Southern Iran

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744 A Functional Analysis of the 2016 United States Presidential Debates through the Application of the Functional Theory of Political Campaign Discourse

Authors: Maryam Vaezi

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In this study, the Functional Theory of Political Campaign Discourse has been applied in order to investigate the 2016 Clinton-Trump presidential debates. All three kinds of utterances (acclaims, attacks, and defenses) were produced by the candidates supporting the usefulness of the Functional Theory of Political Campaign Discourse for the analysis of the presidential debates as a type of political discourse. Attacks comprised 45% of the candidates’ utterances, followed by acclaims at 33%; defenses were the least common function at 22%. The candidate from the Democratic Party, Hillary Clinton, acclaimed more, whereas the Republican Party presidential candidate, Donald Trump, attacked more. Simple denial was the most common form of defense used by the candidates. Both candidates directed more of their utterances to policy (past deeds, future plans, and general goals) than character (personal qualities, leadership abilities, and ideals). Analyzing debates in terms of the functions performed by the candidates to increase their desirability and chance of winning the election, can lead to a better understanding of these significant political events as well as other forms of political discourse.

Keywords: acclaim, attack, defend, character, Democratic Party, Donald Trump, Hillary Clinton, policy, presidential debates, Republican Party

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743 THRAP2 Gene Identified as a Candidate Susceptibility Gene of Thyroid Autoimmune Diseases Pedigree in Tunisian Population

Authors: Ghazi Chabchoub, Mouna Feki, Mohamed Abid, Hammadi Ayadi

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Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are inherited as complex traits. Genetic factors associated with AITDs have been tentatively identified by candidate gene and genome scanning approaches. We analysed three intragenic microsatellite markers in the thyroid hormone receptor associated protein 2 gene (THRAP2), mapped near D12S79 marker, which have a potential role in immune function and inflammation [THRAP2-1(TG)n, THRAP2-2 (AC)n and THRAP2-3 (AC)n]. Our study population concerned 12 patients affected with AITDs belonging to a multiplex Tunisian family with high prevalence of AITDs. Fluorescent genotyping was carried out on ABI 3100 sequencers (Applied Biosystems USA) with the use of GENESCAN for semi-automated fragment sizing and GENOTYPER peak-calling software. Statistical analysis was performed using the non parametric Lod score (NPL) by Merlin software. Merlin outputs non-parametric NPLall (Z) and LOD scores and their corresponding asymptotic P values. The analysis for three intragenic markers in the THRAP2 gene revealed strong evidence for linkage (NPL=3.68, P=0.00012). Our results suggested the possible role of THRAP2 gene in AITDs susceptibility in this family.

Keywords: autoimmunity, autoimmune disease, genetic, linkage analysis

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742 Quantitative Evaluation of Endogenous Reference Genes for ddPCR under Salt Stress Using a Moderate Halophile

Authors: Qinghua Xing, Noha M. Mesbah, Haisheng Wang, Jun Li, Baisuo Zhao

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Droplet digital PCR (ddPCR) is being increasingly adopted for gene detection and quantification because of its higher sensitivity and specificity. According to previous observations and our lab data, it is essential to use endogenous reference genes (RGs) when investigating gene expression at the mRNA level under salt stress. This study aimed to select and validate suitable RGs for gene expression under salt stress using ddPCR. Six candidate RGs were selected based on the tandem mass tag (TMT)-labeled quantitative proteomics of Alkalicoccus halolimnae at four salinities. The expression stability of these candidate genes was evaluated using statistical algorithms (geNorm, NormFinder, BestKeeper and RefFinder). There was a small fluctuation in cycle threshold (Ct) value and copy number of the pdp gene. Its expression stability was ranked in the vanguard of all algorithms, and was the most suitable RG for quantification of expression by both qPCR and ddPCR of A. halolimnae under salt stress. Single RG pdp and RG combinations were used to normalize the expression of ectA, ectB, ectC, and ectD under four salinities. The present study constitutes the first systematic analysis of endogenous RG selection for halophiles responding to salt stress. This work provides a valuable theory and an approach reference of internal control identification for ddPCR-based stress response models.

Keywords: endogenous reference gene, salt stress, ddPCR, RT-qPCR, Alkalicoccus halolimnae

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741 Trigonella foenum-graecum Seeds Extract as Therapeutic Candidate for Treatment of Alzheimer's Disease

Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Yuna Inada, Chihiro Tohda

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Intro: Trigonella foenum-graecum (Fenugreek), from Fabaceae family is a well-known plant traditionally used as food and medicine. Many pharmacological effects of Trigonella foenum- graecum seeds extract (TF extract) were evaluated such as anti-diabetic, anti-tumor and anti-dementia effects using in vivo models. Regarding the anti-dementia effects of TF extract, diabetic rats, aluminum chloride-induced amnesia rats and scopolamine-injected mice were used previously for evaluation, which are not well established as Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. Method: This study aimed to clarify the effect of TF extract on Alzheimer’s disease model, 5XFAD mouse that overexpresses mutated APP and PS1 genes and determine the major active constituent in the brain after oral intake of TF extract. Results: Trigonelline was detected in the cerebral cortex of 5XFAD mice after 24 hours of oral administration of TF extract by LC-MS/MS. Oral administration of TF extract for 17 days improved object location memory in 5XFAD mice. Conclusion: These results suggest that TF extract and its active constituents could be an expected therapeutic candidate for Alzheimer’s disease.

Keywords: Alzheimer's disease, LC-MS/MS, memory recovery, Trigonella foenum-graecum Seeds, 5XFAD mice

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740 Familial Exome Sequencing to Decipher the Complex Genetic Basis of Holoprosencephaly

Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

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Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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739 Ground Motion Modeling Using the Least Absolute Shrinkage and Selection Operator

Authors: Yildiz Stella Dak, Jale Tezcan

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Ground motion models that relate a strong motion parameter of interest to a set of predictive seismological variables describing the earthquake source, the propagation path of the seismic wave, and the local site conditions constitute a critical component of seismic hazard analyses. When a sufficient number of strong motion records are available, ground motion relations are developed using statistical analysis of the recorded ground motion data. In regions lacking a sufficient number of recordings, a synthetic database is developed using stochastic, theoretical or hybrid approaches. Regardless of the manner the database was developed, ground motion relations are developed using regression analysis. Development of a ground motion relation is a challenging process which inevitably requires the modeler to make subjective decisions regarding the inclusion criteria of the recordings, the functional form of the model and the set of seismological variables to be included in the model. Because these decisions are critically important to the validity and the applicability of the model, there is a continuous interest on procedures that will facilitate the development of ground motion models. This paper proposes the use of the Least Absolute Shrinkage and Selection Operator (LASSO) in selecting the set predictive seismological variables to be used in developing a ground motion relation. The LASSO can be described as a penalized regression technique with a built-in capability of variable selection. Similar to the ridge regression, the LASSO is based on the idea of shrinking the regression coefficients to reduce the variance of the model. Unlike ridge regression, where the coefficients are shrunk but never set equal to zero, the LASSO sets some of the coefficients exactly to zero, effectively performing variable selection. Given a set of candidate input variables and the output variable of interest, LASSO allows ranking the input variables in terms of their relative importance, thereby facilitating the selection of the set of variables to be included in the model. Because the risk of overfitting increases as the ratio of the number of predictors to the number of recordings increases, selection of a compact set of variables is important in cases where a small number of recordings are available. In addition, identification of a small set of variables can improve the interpretability of the resulting model, especially when there is a large number of candidate predictors. A practical application of the proposed approach is presented, using more than 600 recordings from the National Geospatial-Intelligence Agency (NGA) database, where the effect of a set of seismological predictors on the 5% damped maximum direction spectral acceleration is investigated. The set of candidate predictors considered are Magnitude, Rrup, Vs30. Using LASSO, the relative importance of the candidate predictors has been ranked. Regression models with increasing levels of complexity were constructed using one, two, three, and four best predictors, and the models’ ability to explain the observed variance in the target variable have been compared. The bias-variance trade-off in the context of model selection is discussed.

Keywords: ground motion modeling, least absolute shrinkage and selection operator, penalized regression, variable selection

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738 Going Viral: Expanding a Student-Run COVID-19 Journal Club to Social Media

Authors: Joseph Dodson, Robert Roth, Alexander Hodakowski, Leah Greenfield, Melissa Porterhouse, Natalie Maltby, Rachel Sadowsky

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Introduction: Throughout the COVID-19 pandemic, countless research publications were released regarding SARS-CoV-2 and its variants, suggested treatments, and vaccine safety and efficacy. Daily publication of research became overwhelming for health professionals and the general public to stay informed. To address this problem, a group of 70 students across the four colleges at Rush University created the “Rush University COVID-19 Journal Club.” To broaden the available audience, the journal club then expanded to social media. Methods: Easily accessible and understandable summaries of the research were written by students and sent to faculty sponsors for feedback. Following the revision, summaries were published weekly on the Rush University COVID-19 Journal Club website for clinicians and students to use for reference. An Instagram page was then created, and information was further condensed into succinct posts to address COVID-19 “FAQs.” Next, a survey was distributed to followers of the Instagram page with questions meant to assess the effectiveness of the platform and gain feedback. A 5-point Likert scale was used as the primary question format. Results: The Instagram page accrued 749 followers and posted 52 unique posts over a 2 year period. Preliminary results from the surveys demonstrate that over 80% of respondents strongly agree that the Instagram posts 1) are an effective platform for the public presentation of factual COVID-19-related information; 2) provide relevant and valuable information; 3) provide information that is clear, concise, and can be easily understood. Conclusion: These results suggest that the Rush COVID-19 Journal Club was able to successfully create a social media presence and convey information without sacrificing scholarly integrity. Other academic institutions may benefit from the application of this model to help students and clinicians with the interpretation and evaluation of research topics with large bodies of evidence.

Keywords: SARS-CoV-2, COVID-19, public health, social media, SARS-CoV-2 vaccine, SARS-CoV-2 variants

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737 Mobile Traffic Management in Congested Cells using Fuzzy Logic

Authors: A. A. Balkhi, G. M. Mir, Javid A. Sheikh

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To cater the demands of increasing traffic with new applications the cellular mobile networks face new changes in deployment in infrastructure for making cellular networks heterogeneous. To reduce overhead processing the densely deployed cells require smart behavior with self-organizing capabilities with high adaptation to the neighborhood. We propose self-organization of unused resources usually excessive unused channels of neighbouring cells with densely populated cells to reduce handover failure rates. The neighboring cells share unused channels after fulfilling some conditional candidature criterion using threshold values so that they are not suffered themselves for starvation of channels in case of any abrupt change in traffic pattern. The cells are classified as ‘red’, ‘yellow’, or ‘green’, as per the available channels in cell which is governed by traffic pattern and thresholds. To combat the deficiency of channels in red cell, migration of unused channels from under-loaded cells, hierarchically from the qualified candidate neighboring cells is explored. The resources are returned back when the congested cell is capable of self-contained traffic management. In either of the cases conditional sharing of resources is executed for enhanced traffic management so that User Equipment (UE) is provided uninterrupted services with high Quality of Service (QoS). The fuzzy logic-based simulation results show that the proposed algorithm is efficiently in coincidence with improved successful handoffs.

Keywords: candidate cell, channel sharing, fuzzy logic, handover, small cells

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736 The Effects of Different Sowing Times on Seed Yield and Quality of Fenugreek (Trigonella foenum graecum L.) in East Mediterranean Region of Turkey

Authors: Lale Efe, Zeynep Gokce

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In this study carried out in 2013-14 growing season in East Mediterranean Region of Turkey, it was aimed to investigate the effects of different sowing times on the seed yield and quality of fenugreek (Trigonella foenum graceum L.). Three fenugreek genotypes (Gürarslan, Candidate Line-1 and Genotype-1) were sown on 13.11.2013 and 07.03.2014 according to factorial randomized block design with 3 replications. Plant height (cm), branch number per plant, first pod height (cm), pod length (mm), seed number per pod (g), seed yield per plant (g), seed yield per decar (kg), thousand seed weight (g), mucilage rate (%), seed protein ratio (%), seed oil ratio (%), oleic acid (%), linoleic acid (%), palmitic acid (%) and stearic acid (%) were investigated. Among genotypes, while the highest seed yield per plant was obtained from Genotype-1 (5 g/plant), the lowest seed yield per plant was obtained from cv. Gürarslan (3.4 g/plant). According to genotype x sowing date interactions, it can be said that the highest seed yield per plant was taken in autumn sowing from Genotype-1 (6.6 g/plant) and the lowest seed yield per plant was taken in spring sowing from cv. Gürarslan (2.9 g/plant). Genotype-1 had the highest linoleic acid ratio (41.6 %). Cv. Gürarslan and Candidate Line-1 had the highest oleic acid ratio (respectively 17.8 % and 17.6%).

Keywords: fenugreek, seed yield and quality, sowing times, Trigonella foenum graecum L.

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735 Absolute Quantification of the Bexsero Vaccine Component Factor H Binding Protein (fHbp) by Selected Reaction Monitoring: The Contribution of Mass Spectrometry in Vaccinology

Authors: Massimiliano Biagini, Marco Spinsanti, Gabriella De Angelis, Sara Tomei, Ilaria Ferlenghi, Maria Scarselli, Alessia Biolchi, Alessandro Muzzi, Brunella Brunelli, Silvana Savino, Marzia M. Giuliani, Isabel Delany, Paolo Costantino, Rino Rappuoli, Vega Masignani, Nathalie Norais

Abstract:

The gram-negative bacterium Neisseria meningitidis serogroup B (MenB) is an exclusively human pathogen representing the major cause of meningitides and severe sepsis in infants and children but also in young adults. This pathogen is usually present in the 30% of healthy population that act as a reservoir, spreading it through saliva and respiratory fluids during coughing, sneezing, kissing. Among surface-exposed protein components of this diplococcus, factor H binding protein is a lipoprotein proved to be a protective antigen used as a component of the recently licensed Bexsero vaccine. fHbp is a highly variable meningococcal protein: to reflect its remarkable sequence variability, it has been classified in three variants (or two subfamilies), and with poor cross-protection among the different variants. Furthermore, the level of fHbp expression varies significantly among strains, and this has also been considered an important factor for predicting MenB strain susceptibility to anti-fHbp antisera. Different methods have been used to assess fHbp expression on meningococcal strains, however, all these methods use anti-fHbp antibodies, and for this reason, the results are affected by the different affinity that antibodies can have to different antigenic variants. To overcome the limitations of an antibody-based quantification, we developed a quantitative Mass Spectrometry (MS) approach. Selected Reaction Monitoring (SRM) recently emerged as a powerful MS tool for detecting and quantifying proteins in complex mixtures. SRM is based on the targeted detection of ProteoTypicPeptides (PTPs), which are unique signatures of a protein that can be easily detected and quantified by MS. This approach, proven to be highly sensitive, quantitatively accurate and highly reproducible, was used to quantify the absolute amount of fHbp antigen in total extracts derived from 105 clinical isolates, evenly distributed among the three main variant groups and selected to be representative of the fHbp circulating subvariants around the world. We extended the study at the genetic level investigating the correlation between the differential level of expression and polymorphisms present within the genes and their promoter sequences. The implications of fHbp expression on the susceptibility of the strain to killing by anti-fHbp antisera are also presented. To date this is the first comprehensive fHbp expression profiling in a large panel of Neisseria meningitidis clinical isolates driven by an antibody-independent MS-based methodology, opening the door to new applications in vaccine coverage prediction and reinforcing the molecular understanding of released vaccines.

Keywords: quantitative mass spectrometry, Neisseria meningitidis, vaccines, bexsero, molecular epidemiology

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734 Optimal Wind Based DG Placement Considering Monthly Changes Modeling in Wind Speed

Authors: Belal Mohamadi Kalesar, Raouf Hasanpour

Abstract:

Proper placement of Distributed Generation (DG) units such as wind turbine generators in distribution system are still very challenging issue for obtaining their maximum potential benefits because inappropriate placement may increase the system losses. This paper proposes Particle Swarm Optimization (PSO) technique for optimal placement of wind based DG (WDG) in the primary distribution system to reduce energy losses and voltage profile improvement with four different wind levels modeling in year duration. Also, wind turbine is modeled as a DFIG that will be operated at unity power factor and only one wind turbine tower will be considered to install at each bus of network. Finally, proposed method will be implemented on widely used 69 bus power distribution system in MATLAB software environment under four scenario (without, one, two and three WDG units) and for capability test of implemented program it is supposed that all buses of standard system can be candidate for WDG installing (large search space), though this program can consider predetermined number of candidate location in WDG placement to model financial limitation of project. Obtained results illustrate that wind speed increasing in some months will increase output power generated but this can increase / decrease power loss in some wind level, also results show that it is required about 3MW WDG capacity to install in different buses but when this is distributed in overall network (more number of WDG) it can cause better solution from point of view of power loss and voltage profile.

Keywords: wind turbine, DG placement, wind levels effect, PSO algorithm

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733 The Opinions of Counselor Candidates' regarding Universal Values in Marriage Relationship

Authors: Seval Kizildag, Ozge Can Aran

Abstract:

The effective intervention of counselors’ in conflict between spouses may be effective in increasing the quality of marital relationship. At this point, it is necessary for counselors to consider their own value systems at first and then reflect this correctly to the counseling process. For this reason, it is primarily important to determine the needs of counselors. Starting from this point of view, in this study, it is aimed to reveal the perspective of counselor candidates about the universal values in marriage relation. The study group of the survey was formed by sampling, which is one of the prospective sampling methods. As a criterion being a candidate for counseling area and having knowledge of the concepts of the Marriage and Family Counseling course is based, because, that candidate students have a comprehensive knowledge of the field and that students have mastered the concepts of marriage and family counseling will strengthen the findings of this study. For this reason, 61 counselor candidates, 32 (52%) female and 29 (48%) male counselor candidates, who were about to graduate from a university in south-east Turkey and who took a Marriage and Family Counseling course, voluntarily participated in the study. The average age of counselor candidates’ is 23. At the same time, 70 % of the parents of these candidates brought about their marriage through arranged marriage, 13% through flirting, 8% by relative marriage, 7% through friend circles and 2% by custom. The data were collected through Demographic Information Form and a form titled ‘Universal Values Form in Marriage’ which consists of six questions prepared by researchers. After the data were transferred to the computer, necessary statistical evaluations were made on the data. The qualitative data analysis was used on the data which was obtained in the study. The universal values which include six basic values covering trustworthiness, respect, responsibility, fairness, caring, citizenship, determined under the name as ‘six pillar of character’ are used as base and frequency values of the data were calculated trough content analysis. According to the findings of the study, while the value which most students find the most important value in marriage relation is being reliable, the value which they find the least important is to have citizenship consciousness. Also in this study, it is found out that counselor candidates associate the value of being trustworthiness ‘loyalty’ with (33%) as the highest in terms of frequency, the value of being respect ‘No violence’ with (23%), the value of responsibility ‘in the context of gender roles and spouses doing their owns’ with (35%) the value of being fairness ‘impartiality’ with (25%), the value of being caring ‘ being helpful’ with (25%) and finally as to the value of citizenship ‘love of country’ with (14%) and’ respect for the laws ‘ with (14%). It is believed that these results of the study will contribute to the arrangements for the development of counseling skills for counselor candidates regarding value in marriage and family counseling curricula.

Keywords: caring, citizenship, counselor candidate, fairness, marriage relationship, respect, responsibility, trustworthiness, value system

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732 Using Deep Learning for the Detection of Faulty RJ45 Connectors on a Radio Base Station

Authors: Djamel Fawzi Hadj Sadok, Marrone Silvério Melo Dantas Pedro Henrique Dreyer, Gabriel Fonseca Reis de Souza, Daniel Bezerra, Ricardo Souza, Silvia Lins, Judith Kelner

Abstract:

A radio base station (RBS), part of the radio access network, is a particular type of equipment that supports the connection between a wide range of cellular user devices and an operator network access infrastructure. Nowadays, most of the RBS maintenance is carried out manually, resulting in a time consuming and costly task. A suitable candidate for RBS maintenance automation is repairing faulty links between devices caused by missing or unplugged connectors. A suitable candidate for RBS maintenance automation is repairing faulty links between devices caused by missing or unplugged connectors. This paper proposes and compares two deep learning solutions to identify attached RJ45 connectors on network ports. We named connector detection, the solution based on object detection, and connector classification, the one based on object classification. With the connector detection, we get an accuracy of 0:934, mean average precision 0:903. Connector classification, get a maximum accuracy of 0:981 and an AUC of 0:989. Although connector detection was outperformed in this study, this should not be viewed as an overall result as connector detection is more flexible for scenarios where there is no precise information about the environment and the possible devices. At the same time, the connector classification requires that information to be well-defined.

Keywords: radio base station, maintenance, classification, detection, deep learning, automation

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731 Memristor-A Promising Candidate for Neural Circuits in Neuromorphic Computing Systems

Authors: Juhi Faridi, Mohd. Ajmal Kafeel

Abstract:

The advancements in the field of Artificial Intelligence (AI) and technology has led to an evolution of an intelligent era. Neural networks, having the computational power and learning ability similar to the brain is one of the key AI technologies. Neuromorphic computing system (NCS) consists of the synaptic device, neuronal circuit, and neuromorphic architecture. Memristor are a promising candidate for neuromorphic computing systems, but when it comes to neuromorphic computing, the conductance behavior of the synaptic memristor or neuronal memristor needs to be studied thoroughly in order to fathom the neuroscience or computer science. Furthermore, there is a need of more simulation work for utilizing the existing device properties and providing guidance to the development of future devices for different performance requirements. Hence, development of NCS needs more simulation work to make use of existing device properties. This work aims to provide an insight to build neuronal circuits using memristors to achieve a Memristor based NCS.  Here we throw a light on the research conducted in the field of memristors for building analog and digital circuits in order to motivate the research in the field of NCS by building memristor based neural circuits for advanced AI applications. This literature is a step in the direction where we describe the various Key findings about memristors and its analog and digital circuits implemented over the years which can be further utilized in implementing the neuronal circuits in the NCS. This work aims to help the electronic circuit designers to understand how the research progressed in memristors and how these findings can be used in implementing the neuronal circuits meant for the recent progress in the NCS.

Keywords: analog circuits, digital circuits, memristors, neuromorphic computing systems

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730 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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729 hsa-miR-1204 and hsa-miR-639 Prominent Role in Tamoxifen's Molecular Mechanisms on the EMT Phenomenon in Breast Cancer Patients

Authors: Mahsa Taghavi

Abstract:

In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

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728 Sheep Pox Virus Recombinant Proteins To Develop Subunit Vaccines

Authors: Olga V. Chervyakova, Elmira T. Tailakova, Vitaliy M. Strochkov, Kulyaisan T. Sultankulova, Nurlan T. Sandybayev, Lev G. Nemchinov, Rosemarie W. Hammond

Abstract:

Sheep pox is a highly contagious infection that OIE regards to be one of the most dangerous animal diseases. It causes enormous economic losses because of death and slaughter of infected animals, lower productivity, cost of veterinary and sanitary as well as quarantine measures. To control spread of sheep pox infection the attenuated vaccines are widely used in the Republic of Kazakhstan and other Former Soviet Union countries. In spite of high efficiency of live vaccines, the possible presence of the residual virulence, potential genetic instability restricts their use in disease-free areas that leads to necessity to exploit new approaches in vaccine development involving recombinant DNA technology. Vaccines on the basis of recombinant proteins are the newest generation of prophylactic preparations. The main advantage of these vaccines is their low reactogenicity and this fact makes them widely used in medical and veterinary practice for vaccination of humans and farm animals. The objective of the study is to produce recombinant immunogenic proteins for development of the high-performance means for sheep pox prophylaxis. The SPV proteins were chosen for their homology with the known immunogenic vaccinia virus proteins. Assay of nucleotide and amino acid sequences of the target SPV protein genes. It has been shown that four proteins SPPV060 (ortholog L1), SPPV074 (ortholog H3), SPPV122 (ortholog A33) and SPPV141 (ortholog B5) possess transmembrane domains at N- or C-terminus while in amino acid sequences of SPPV095 (ortholog А 4) and SPPV117 (ortholog А 27) proteins these domains were absent. On the basis of these findings the primers were constructed. Target genes were amplified and subsequently cloned into the expression vector рЕТ26b(+) or рЕТ28b(+). Six constructions (pSPPV060ΔТМ, pSPPV074ΔТМ, pSPPV095, pSPPV117, pSPPV122ΔТМ and pSPPV141ΔТМ) were obtained for expression of the SPV genes under control of T7 promoter in Escherichia coli. To purify and detect recombinant proteins the amino acid sequences were modified by adding six histidine molecules at C-terminus. Induction of gene expression by IPTG was resulted in production of the proteins with molecular weights corresponding to the estimated values for SPPV060, SPPV074, SPPV095, SPPV117, SPPV122 and SPPV141, i.e. 22, 30, 20, 19, 17 and 22 kDa respectively. Optimal protocol of expression for each gene that ensures high yield of the recombinant protein was identified. Assay of cellular lysates by western blotting confirmed expression of the target proteins. Recombinant proteins bind specifically with antibodies to polyhistidine. Moreover all produced proteins are specifically recognized by the serum from experimentally SPV-infected sheep. The recombinant proteins SPPV060, SPPV074, SPPV117, SPPV122 and SPPV141 were also shown to induce formation of antibodies with virus-neutralizing activity. The results of the research will help to develop a new-generation high-performance means for specific sheep pox prophylaxis that is one of key moments in animal health protection. The research was conducted under the International project ISTC # K-1704 “Development of methods to construct recombinant prophylactic means for sheep pox with use of transgenic plants” and under the Grant Project RK MES G.2015/0115RK01983 "Recombinant vaccine for sheep pox prophylaxis".

Keywords: prophylactic preparation, recombinant protein, sheep pox virus, subunit vaccine

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727 Approaching a Tat-Rev Independent HIV-1 Clone towards a Model for Research

Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

Abstract:

Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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726 Therapeutic Potential of mAb KP52 in Human and Feline Cancers

Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

Abstract:

Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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725 Mutation Profiling of Paediatric Solid Tumours in a Cohort of South African Patients

Authors: L. Lamola, E. Manolas, A. Krause

Abstract:

Background: The incidence of childhood cancer incidence is increasing gradually in low-middle income countries, such as South Africa. Globally, there is an extensive range of familial- and hereditary-cancer syndromes, where underlying germline variants increase the likelihood of developing cancer in childhood. Next-Generation Sequencing (NGS) technologies have been key in determining the occurrence and genetic contribution of germline variants to paediatric cancer development. We aimed to design and evaluate a candidate gene panel specific to inherited cancer-predisposing genes to provide a comprehensive insight into the contribution of germline variants to childhood cancer. Methods: 32 paediatric patients (aged 0-18 years) diagnosed with a malignant tumour were recruited, and biological samples were obtained. After quality control, DNA was sequenced using an ion Ampliseq 50 candidate gene panel design and Ion Torrent S5 technologies. Sequencing variants were called using Ion Torrent Suite software and were subsequently annotated using Ion Reporter and Ensembl's VEP. High priority variants were manually analysed using tools such as MutationTaster, SIFT-INDEL and VarSome. Putative identified candidates were validated via Sanger Sequencing. Results: The patients studied had a variety of cancers, the most common being nephroblastoma (13), followed by osteosarcoma (4) and astrocytoma (3). We identified 10 pathogenic / likely pathogenic variants in 10 patients, most of which were novel. Conclusions: According to the literature, we expected ~10% of our patient population to harbour pathogenic or likely pathogenic germline variants, however, we reported about 3 times (~30%) more than we expected. Majority of the identified variants are novel; this may be because this is the first study of its kind in an understudied South African population.

Keywords: Africa, genetics, germline-variants, paediatric-cancer

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724 To Smile or Not to Smile: How Engendered Facial Cues affect Hiring Decisions

Authors: Sabrina S. W. Chan, Emily Schwartzman, Nicholas O. Rule

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Past literature showed mixed findings on how smiling affects a person’s chance of getting hired. On one hand, smiling suggests enthusiasm, cooperativeness, and enthusiasm, which can elicit positive impressions. On the other hand, smiling can suggest weaker professionalism or a filler to hide nervousness, which can lower a candidate’s perceived competence. Emotion expressions can also be perceived differently depending on the person’s gender and can activate certain gender stereotypes. Women especially face a double bind with respect to hiring decisions and smiling. Because women are socially expected to smile more, those who do not smile will be considered stereotype incongruent. This becomes a noisy signal to employers and may lower their chance of being hired. However, women’s smiling as a formality may also be an obstacle. They are more likely to put on fake smiles; but if they do, they are also likely to be perceived as inauthentic and over-expressive. This paper sought to investigate how smiling affects hiring decisions, and whether this relationship is moderated by gender. In Study 1, participants were shown a series of smiling and emotionally neutral face images, incorporated into fabricated LinkedIn profiles. Participants were asked to rate how hireable they thought that candidate was. Results showed that participants rated smiling candidates as more hireable than nonsmiling candidates, and that there was no difference in gender. Moreover, individuals who did not study business were more biased in their perceptions than those who did. Since results showed a trending favoritism over female targets, in suspect of desirability bias, a second study was conducted to collect implicit measures behind the decision-making process. In Study 2, a mouse-tracking design was adopted to explore whether participants’ implicit attitudes were different from their explicit responses on hiring. Participants asked to respond whether they would offer an interview to a candidate. Findings from Study 1 was replicated in that smiling candidates received more offers than neutral-faced candidates. Results also showed that female candidates received significantly more offers than male candidates but was associated with higher attractiveness ratings. There were no significant findings in reaction time or change of decisions. However, stronger hesitation was detected for responses made towards neutral targets when participants perceived the given position as masculine, implying a conscious attempt of making situational judgments (e.g., considering candidate’s personality and job fit) to override automatic processing (evaluations based on attractiveness). Future studies would look at how these findings differ for positions which are stereotypically masculine (e.g., surgeons) and stereotypically feminine (e.g., kindergarten teachers). Current findings have strong implications for developing bias-free hiring policies in workplace, especially for organizations who maintain online/hybrid working arrangements in the post-pandemic era. This also bridges the literature gap between face perception and gender discrimination, highlighting how engendered facial cues can affect individual’s career development and organization’s success in diversity and inclusion.

Keywords: engendered facial cues, face perception, gender stereotypes, hiring decisions, smiling, workplace discrimination

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723 Positive-Negative Asymmetry in the Evaluations of Political Candidates: The Mediating Role of Affect in the Relationship between Cognitive Evaluation and Voting Intention

Authors: Magdalena Jablonska, Andrzej Falkowski

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The negativity effect is one of the most intriguing and well-studied psychological phenomena that can be observed in many areas of human life. The aim of the following study is to investigate how valence framing and positive and negative information about political candidates affect judgments about similarity to an ideal and bad politician. Based on the theoretical framework of features of similarity, it is hypothesized that negative features have a stronger effect on similarity judgments than positive features of comparable value. Furthermore, the mediating role of affect is tested. Method: One hundred sixty-one people took part in an experimental study. Participants were divided into 6 research conditions that differed in the reference point (positive vs negative framing) and the number of favourable and unfavourable information items about political candidates (a positive, neutral and negative candidate profile). In positive framing condition, the concept of an ideal politician was primed; in the negative condition, participants were to think about a bad politician. The effect of independent variables on similarity judgments, affective evaluation, and voting intention was tested. Results: In the positive condition, the analysis showed that the negative effect of additional unfavourable features was greater than the positive effect of additional favourable features in judgements about similarity to the ideal candidate. In negative framing condition, ANOVA was insignificant, showing that neither the addition of positive features nor additional negative information had a significant impact on the similarity to a bad political candidate. To explain this asymmetry, two mediational analyses were conducted that tested the mediating role of affect in the relationship between similarity judgments and voting intention. In both situations the mediating effect was significant, but the comparison of two models showed that the mediation was stronger for a negative framing. Discussion: The research supports the negativity effect and attempts to explain the psychological mechanism behind the positive-negative asymmetry. The results of mediation analyses point to a stronger mediating role of affect in the relationship between cognitive evaluation and voting intention. Such a result suggests that negative comparisons, leading to the activation of negative features, give rise to stronger emotions than positive features of comparable strength. The findings are in line with positive-negative asymmetry, however, by adopting Tversky’s framework of features of similarity, the study integrates the cognitive mechanism of the negativity effect delineated in the contrast model of similarity with its emotional component resulting from the asymmetrical effect of positive and negative emotions on decision-making.

Keywords: affect, framing, negativity effect, positive-negative asymmetry, similarity judgements

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