Search results for: Multiple trauma
2409 Use of Zikani’s Ribosome Modulating Agents for Treating Recessive Dystrophic & Junctional Epidermolysis Bullosa with Nonsense Mutations
Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur
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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation
Procedia PDF Downloads 1032408 Genetic Variations of CYP2C9 in Thai Patients Taking Medical Cannabis
Authors: Naso Isaiah Thanavisuth
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Medical cannabis can be used for treatment including pain, multiple sclerosis, Parkinson's disease, and cancer. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 and CYP2C9*3 on exon 7 to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are apharmacogenetics marker for the prediction of THC-induced AEs in Thai patients. We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. We enrolled 39 Thai patients with medical cannabis treatment who were classified by clinical data. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay. All Thai patients who received the medical cannabis consist of twenty-four (61.54%) patients were female, and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty-nine (7.69%) and one of thirty-nine (2.56%), respectively. Although, our results indicate that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for the prevention of medical cannabis-induced AEs.Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450
Procedia PDF Downloads 1222407 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease
Authors: Huafeng Wei
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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis
Procedia PDF Downloads 2122406 Translating History in a Brazilian Graphic Novel: A Translation Project for Angola Janga by Marcelo D'Salete
Authors: Carolina Rezende, Julio Cesar Neves Monteiro
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Traditionally, History and fiction are considered to be opposing fields of study. While one is linked to the study of facts, things that have happened within the limits of ‘reality’, the other explores a made-up world, originated from imagination and fantasy. However, despite their apparent discrepancies, there is a fundamental trait that brings them closer. Historical narratives, similarly to fiction ones, are produced based on multiple interpretations of an event, which are transmitted in a rather subjective way by language. It is within this perspective of history and fiction intertwined that this paper aims to discuss the translation of historical facts in the graphic novel Angola Janga, by Marcelo D’Salete, as well as presenting it as a historical document. The novel, which is divided into 11 short stories, narrates the rebellions that took place in Serra da Barriga, between the 16th and 17th centuries, that resulted in the Guerra dos Palmares. The graphic novel in question is a result of the author’s 11-year historical and bibliographical research, which combines history and fiction in order to shed a light of the confrontation that history seems to overlook. Also, the book includes a foreword, glossary, chronological line of Guerra dos Palmares, as well as maps and references used by the author during his research. For that, a few segments from the book will be selected and translated in order to show such connection between history and fiction, and the discussion resulted from it will be based on the works of Southgate (2009), Pym (2001) and D’hulst (2001).Keywords: graphic novel, history, fiction, Palmares
Procedia PDF Downloads 1812405 Components of Effective Learning Environments: Global Perspectives on Student Perceptions
Authors: Victoria Appatova
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internal and external, that are largely shaped by the student’s perceptions. Since 2006, the ELE concept has been studied by an international group of scholars through the creation of an ELE survey which was administered in nine countries and translated into five languages. The survey compares students’ perceptions of their learning environments and self-efficacy across A student’s effective learning environment (ELE) is comprised of multiple factors, both cultures as well as distinguishes similarities and differences in the students’ needs related to their learning. The main objectives of this international project include the following: Determine a system of components constituting ELE from the perspective of students and other academic populations Analyze students’ expectations, and their chances to succeed in college based on their expectations Conceptualize a comprehensive approach for assessing the effectiveness of a learning environment Compare the actualization of the ELE concept in American schools versus other national educational systems Compare student perceptions of ELE with those of faculty, administrators, and professional staff Four major factors influencing student learning across cultures and various national educational systems were determined: students’ initiative in using support services; learning skills; external comfort; and curriculum. Recent changes in the students’ perceptions, resulting from technology advances and a rapid shift to online learning, are being explored. The findings call for administrative and pedagogical actions which would cultivate more equitable education systems.Keywords: learning environment, student perception, global perspectives, self-efficacy
Procedia PDF Downloads 942404 The Role of Inflammasomes for aβ Microglia Phagocytosis in Alzheimer Disease
Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka
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Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3
Procedia PDF Downloads 4582403 A Verification Intellectual Property for Multi-Flow Rate Control on Any Single Flow Bus Functional Model
Authors: Pawamana Ramachandra, Jitesh Gupta, Saranga P. Pogula
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In verification of high volume and complex packet processing IPs, finer control of flow management aspects (for example, rate, bits/sec etc.) per flow class (or a virtual channel or a software thread) is needed. When any Software/Universal Verification Methodology (UVM) thread arbitration is left to the simulator (e.g., Verilog Compiler Simulator (VCS) or Incisive Enterprise Simulator core simulation engine (NCSIM)), it is hard to predict its pattern of resulting distribution of bandwidth by the simulator thread arbitration. In many cases, the patterns desired in a test scenario may not be accomplished as the simulator might give a different distribution than what was required. This can lead to missing multiple traffic scenarios, specifically deadlock and starvation related. We invented a component (namely Flow Manager Verification IP) to be intervening between the application (test case) and the protocol VIP (with UVM sequencer) to control the bandwidth per thread/virtual channel/flow. The Flow Manager has knobs visible to the UVM sequence/test to configure the required distribution of rate per thread/virtual channel/flow. This works seamlessly and produces rate stimuli to further harness the Design Under Test (DUT) with asymmetric inputs compared to the programmed bandwidth/Quality of Service (QoS) distributions in the Design Under Test.Keywords: flow manager, UVM sequencer, rated traffic generation, quality of service
Procedia PDF Downloads 1022402 Towards a Broader Understanding of Journal Impact: Measuring Relationships between Journal Characteristics and Scholarly Impact
Authors: X. Gu, K. L. Blackmore
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The impact factor was introduced to measure the quality of journals. Various impact measures exist from multiple bibliographic databases. In this research, we aim to provide a broader understanding of the relationship between scholarly impact and other characteristics of academic journals. Data used for this research were collected from Ulrich’s Periodicals Directory (Ulrichs), Cabell’s (Cabells), and SCImago Journal & Country Rank (SJR) from 1999 to 2015. A master journal dataset was consolidated via Journal Title and ISSN. We adopted a two-step analysis process to study the quantitative relationships between scholarly impact and other journal characteristics. Firstly, we conducted a correlation analysis over the data attributes, with results indicating that there are no correlations between any of the identified journal characteristics. Secondly, we examined the quantitative relationship between scholarly impact and other characteristics using quartile analysis. The results show interesting patterns, including some expected and others less anticipated. Results show that higher quartile journals publish more in both frequency and quantity, and charge more for subscription cost. Top quartile journals also have the lowest acceptance rates. Non-English journals are more likely to be categorized in lower quartiles, which are more likely to stop publishing than higher quartiles. Future work is suggested, which includes analysis of the relationship between scholars and their publications, based on the quartile ranking of journals in which they publish.Keywords: academic journal, acceptance rate, impact factor, journal characteristics
Procedia PDF Downloads 3062401 Lower Extremity Injuries and Landing Kinematics and Kinetics in University-Level Netball Players
Authors: Henriette Hammill
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Background: Safe landing in netball is fundamental. Research on the biomechanics of multidirectional landings is lacking, especially among netball players. Furthermore, few studies reporting the associations between lower extremity injuries and landing kinematics and kinetics in university-level netball players have been undertaken. Objectives: The aim is to determine the relationships between lower extremity injuries and landing kinematics and kinetics in university-level netball players that have been undertaken during a single season. Methods: This cross-sectional repeated measure study consisted of ten university-level female netball players. The injury prevalence data was collected during the 2022 netball season. The kinematic and kinetic data were collected during multidirectional single-leg landing trials and was collected. Results: Generally, the ankle strength of netball players was below average. There was evidence of negative correlations between the ankle range of motion (ROM), and muscle activity amplitudes. A lack of evidence precluded the conclusion that lower extremity dominance was a predisposing factor for injury and that any specific body part was most likely to be injured among netball players. Conclusion: Landing forces and muscle activity are direction-dependent, especially for the dominant extremity. Lower extremity strength and neuromuscular control (NMC) across multiple jump-landing directions should be an area of focus for female netball players.Keywords: netball players, landing kinetics, landing kinematics, lower extremity
Procedia PDF Downloads 502400 Vehicular Speed Detection Camera System Using Video Stream
Authors: C. A. Anser Pasha
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In this paper, a new Vehicular Speed Detection Camera System that is applicable as an alternative to traditional radars with the same accuracy or even better is presented. The real-time measurement and analysis of various traffic parameters such as speed and number of vehicles are increasingly required in traffic control and management. Image processing techniques are now considered as an attractive and flexible method for automatic analysis and data collections in traffic engineering. Various algorithms based on image processing techniques have been applied to detect multiple vehicles and track them. The SDCS processes can be divided into three successive phases; the first phase is Objects detection phase, which uses a hybrid algorithm based on combining an adaptive background subtraction technique with a three-frame differencing algorithm which ratifies the major drawback of using only adaptive background subtraction. The second phase is Objects tracking, which consists of three successive operations - object segmentation, object labeling, and object center extraction. Objects tracking operation takes into consideration the different possible scenarios of the moving object like simple tracking, the object has left the scene, the object has entered the scene, object crossed by another object, and object leaves and another one enters the scene. The third phase is speed calculation phase, which is calculated from the number of frames consumed by the object to pass by the scene.Keywords: radar, image processing, detection, tracking, segmentation
Procedia PDF Downloads 4692399 Clinical Application of Mesenchymal Stem Cells for Cancer Therapy: A Review of Registered Clinical Trials
Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc
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Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials
Procedia PDF Downloads 962398 Corn Production in the Visayas: An Industry Study from 2002-2019
Authors: Julie Ann L. Gadin, Andrearose C. Igano, Carl Joseph S. Ignacio, Christopher C. Bacungan
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Corn production has become an important and pervasive industry in the Visayas for many years. Its role as a substitute commodity to rice heightens demand for health-particular consumers. Unfortunately, the corn industry is confronted with several challenges, such as weak institutions. Considering these issues, the paper examined the factors that influence corn production in the three administrative regions in the Visayas, namely, Western Visayas, Central Visayas, and Eastern Visayas. The data used was retrieved from a variety of publicly available data sources such as the Philippine Statistics Authority, the Department of Agriculture, the Philippine Crop Insurance Corporation, and the International Disaster Database. Utilizing a dataset from 2002 to 2019, the indicators were tested using three multiple linear regression (MLR) models. Results showed that the land area harvested (p=0.02), and the value of corn production (p=0.00) are statistically significant variables that influence corn production in the Visayas. Given these findings, it is suggested that the policy of forest conversion and sustainable land management should be effective in enabling farmworkers to obtain land to grow corn crops, especially in rural regions. Furthermore, the Biofuels Act of 2006, the Livestock Industry Restructuring and Rationalization Act, and supported policy, Senate Bill No. 225, or an Act Establishing the Philippine Corn Research Institute and Appropriating Funds, should be enforced inclusively in order to improve the demand for the corn-allied industries which may lead to an increase in the value and volume of corn production in the Visayas.Keywords: corn, industry, production, MLR, Visayas
Procedia PDF Downloads 2202397 Temperature-Stable High-Speed Vertical-Cavity Surface-Emitting Lasers with Strong Carrier Confinement
Authors: Yun Sun, Meng Xun, Jingtao Zhou, Ming Li, Qiang Kan, Zhi Jin, Xinyu Liu, Dexin Wu
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Higher speed short-wavelength vertical-cavity surface-emitting lasers (VCSELs) working at high temperature are required for future optical interconnects. In this work, the high-speed 850 nm VCSELs are designed, fabricated and characterized. The temperature dependent static and dynamic performance of devices are investigated by using current-power-voltage and small signal modulation measurements. Temperature-stable high-speed properties are obtained by employing highly strained multiple quantum wells and short cavity length of half wavelength. The temperature dependent photon lifetimes and carrier radiative times are determined from damping factor and resonance frequency obtained by fitting the intrinsic optical bandwidth with the two-pole transfer function. In addition, an analytical theoretical model including the strain effect is development based on model-solid theory. The calculation results indicate that the better high temperature performance of VCSELs can be attributed to the strong confinement of holes in the quantum wells leading to enhancement of the carrier transit time.Keywords: vertical cavity surface emitting lasers, high speed modulation, optical interconnects, semiconductor lasers
Procedia PDF Downloads 1292396 An Experimental Study of the Influence of Particle Breakage on the Interface Friction Angle and Shear Strength of Carbonate Sands
Authors: Ruben Dario Tovar-Valencia, Eshan Ganju, Fei Han, Monica Prezzi, Rodrigo Salgado
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Particle breakage occurs even in strong silica sand particles. There is compelling evidence that suggests that particle breakage causes changes in several properties such as permeability, peak strength, dilatancy and critical state friction angle. Current pile design methods that are based on soil properties do not account for particle breakage that occurs during driving or jacking of displacement piles. This may lead to significant overestimation of pile capacity in sands dominated by particles susceptible to breakage, such as carbonate sands. The objective of this paper is to study the influence of shear displacement on particle breakage and friction angle of carbonate sands, and to furthermore quantify the change in friction angle observed with different levels of particle breakage. To study the phenomenon of particle breakage, multiple ring shear tests have been performed at different levels of vertical confinement on a thoroughly characterized carbonate sand to find i) the shear displacement necessary to reach stable friction angles and ii) the effect of particle breakage on the mobilized friction angle of the tested sand. The findings of this study can potentially be used to update the current pile design methods by developing a friction angle which is a function of shear displacement and breakage characteristics of the sand instead of being a constant value.Keywords: breakage, carbonate sand, friction angle, pile design, ring shear test
Procedia PDF Downloads 3062395 Fill Rate Window as a Criterion for Spares Allocation
Authors: Michael Dreyfuss, Yahel Giat
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Limited battery range and long recharging times are the greatest obstacles to the successful adoption of electric cars. One of the suggestions to overcome these problems is that carmakers retain ownership of batteries and provide battery swapping service so that customers exchange their depleted batteries for recharged batteries. Motivated by this example, we consider the problem of optimal spares allocation in an exchangeable-item, multi-location repair system. We generalize the standard service measures of fill rate and average waiting time to reflect the fact that customers penalize the service provider only if they have to wait more than a ‘tolerable’ time window. These measures are denoted as the window fill rate and the truncated waiting time, respectively. We find that the truncated waiting time is convex and therefore a greedy algorithm solves the spares allocation problem efficiently. We show that the window fill rate is generally S-shaped and describe an efficient algorithm to find a near-optimal solution and detail a priori and a posteriori upper bounds to the distance from optimum. The theory is complemented with a large scale numerical example demonstrating the spare battery allocation in battery swapping stations.Keywords: convex-concave optimization, exchangeable item, M/G/infinity, multiple location, repair system, spares allocation, window fill rate
Procedia PDF Downloads 4952394 Two Cases of VACTERL Association in Pregnancy with Lymphocyte Therapy
Authors: Seyed Mazyar Mortazavi, Masod Memari, Hasan Ali Ahmadi, Zhaleh Abed
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Introduction: VACTERL association is a rare disorder with various congenital malformations. The aetiology remains unknown. Combination of at least three congenital anomalies of the following criteria is required for diagnosis: vertebral defects, anal atresia, cardiac anomalies, tracheo-esophageal fistula, renal anomalies, and limb defects. Case presentation: The first case was 1-day old male neonate with multiple congenital anomalies was bore from 28 years old mother. The mother had history of pregnancy with lymphocyte therapy. His anomalies included: defects in thoracic and lumbar vertebral, anal atresia, bilateral hydronephrosis, atrial septal defect, and lower limb abnormality. Other anomalies were cryptorchidism and nasal canal narrowing. The second case was born with 32 weeks gestational age from mother with history of pregnancy with lymphocyte therapy. He had thoracic vertebral defect, cardiac anomalies and renal defect. Conclusion: diagnosis based on clinical finding is VACTERL association. Early diagnosis is very important to investigation and treatment of other coexistence anomalies. VACTERL association in mothers with history of pregnancy with lymphocyte therapy has suggested possibly of relationship between VACTERL association and this method of pregnancy.Keywords: anal atresia, tracheo-esophageal fistula, atrial septal defect, lymphocyte therapy
Procedia PDF Downloads 4562393 Identification of Functional T Cell Receptors Reactive to Tumor Antigens from the T Cell Repertoire of Healthy Donors
Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui
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Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.Keywords: cancer, TCR, tumor antigens, immunotherapy
Procedia PDF Downloads 712392 A Study of the Trap of Multi-Homing in Customers: A Comparative Case Study of Digital Payments
Authors: Shari S. C. Shang, Lynn S. L. Chiu
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In the digital payment market, some consumers use only one payment wallet while many others play multi-homing with a variety of payment services. With the diffusion of new payment systems, we examined the determinants of the adoption of multi-homing behavior. This study aims to understand how a digital payment provider dynamically expands business touch points with cross-business strategies to enrich the digital ecosystem and avoid the trap of multi-homing in customers. By synthesizing platform ecosystem literature, we constructed a two-dimensional research framework with one determinant of user digital behavior from offline to online intentions and the other determinant of digital payment touch points from convenient accessibility to cross-business platforms. To explore on a broader scale, we selected 12 digital payments from 5 countries of UK, US, Japan, Korea, and Taiwan. With the interplays of user digital behaviors and payment touch points, we group the study cases into four types: (1) Channel Initiated: users originated from retailers with high access to in-store shopping with face-to-face guidance for payment adoption. Providers offer rewards for customer loyalty and secure the retailer’s efficient cash flow management. (2) Social Media Dependent: users usually are digital natives with high access to social media or the internet who shop and pay digitally. Providers might not own physical or online shops but are licensed to aggregate money flows through virtual ecosystems. (3) Early Life Engagement: digital banks race to capture the next generation from popularity to profitability. This type of payment aimed to give children a taste of financial freedom while letting parents track their spending. Providers are to capitalize on the digital payment and e-commerce boom and hold on to new customers into adulthood. (4) Traditional Banking: plastic credit cards are purposely designed as a control group to track the evolvement of business strategies in digital payments. Traditional credit card users may follow the bank’s digital strategy to land on different types of digital wallets or mostly keep using plastic credit cards. This research analyzed business growth models and inter-firms’ coopetition strategies of the selected cases. Results of the multiple case analysis reveal that channel initiated payments bundled rewards with retailer’s business discount for recurring purchases. They also extended other financial services, such as insurance, to fulfill customers’ new demands. Contrastively, social media dependent payments developed new usages and new value creation, such as P2P money transfer through network effects among the virtual social ties, while early life engagements offer virtual banking products to children who are digital natives but overlooked by incumbents. It has disrupted the banking business domains in preparation for the metaverse economy. Lastly, the control group of traditional plastic credit cards has gradually converted to a BaaS (banking as a service) model depending on customers’ preferences. The multi-homing behavior is not avoidable in digital payment competitions. Payment providers may encounter multiple waves of a multi-homing threat after a short period of success. A dynamic cross-business collaboration strategy should be explored to continuously evolve the digital ecosystems and allow users for a broader shopping experience and continual usage.Keywords: digital payment, digital ecosystems, multihoming users, cross business strategy, user digital behavior intentions
Procedia PDF Downloads 1662391 Correlation of Depression and Anxiety with Glycemic Control in Children with Type I Diabetes Mellitus
Authors: Sujata Sethi, Pawan Kumar, Sameer Aggarwal
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Depression and anxiety are of significant concern in youth with type 1 diabetes mellitus (T1DM) and these are correlated with glycemic control in multiple ways. The extent of depression and anxiety in children with T1DM remains poorly studied in India. The index study aimed to find the prevalence of depression and anxiety and their correlation with HbA1c (glycated hemoglobin) levels in children with T1DM. Material and methods: This study was a cross-sectional study carried out on a purposive sample of 45 children with T1DM. Depressive symptoms were assessed using Children’s Depression Rating Scale-Revised (CDRS-R) and anxiety symptoms were assessed using Spence Children’s Anxiety Scale (SCAS). Glycated hemoglobin (HbA1c) levels of all the participants were recorded. Results: 43 out of 45 children were analyzed as HbA1c status for two was not known. 48.8% were females. Mean age was 12.95+2.04. The average duration of diabetes was 3.63+1.82. Mean CDRS-R score was 41.6+12.25 and mean SCAS score was 33.07+12.29. Mean recording of HbA1c level was 7.90+1.51. 27 (62.8%) out of 43 participants had abnormal scores on CDRS-R and 24 (55.8%) out of 43 had abnormal scores on SCAS. The correlation coefficient between HbA1c levels and the CDRS-R score came out to be 0.57 and between HbA1c and SCAS, it was 0.53. Both correlations were significant with the p-value of < 0.02. Conclusion: Children with T1DM have high co-morbidity of depression and anxiety which is significantly correlated with the HbA1c levels. Thus, it becomes important to screen the patients for depression and anxiety for better outcomes.Keywords: anxiety, depression, HbA1c, T1DM
Procedia PDF Downloads 2292390 Vegan Low Glycemic Index Diet in Appetite Reduction Among Polycystic Ovarian Syndrome (PCOS) Patients Carrying Melanocortin 4 Receptor (MC4R) Variants of (rs12970134), and (rs17782313): A Mini Review
Authors: Jumanah S. Alawfi
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Polycystic ovary syndrome (PCOS) is a common endocrinopathy among females in their reproductive years. The incidence cases are nearly 1.55 million among females across the globe, with 0.43 million associated disability-adjusted life-years (DALYs). This syndrome is associated with intricate mechanisms typically characterized by insulin resistance (IR), infertility, overweight and/or obesity. Lifestyle interventions are often prescribed as an adjective treatment. Nonetheless, obesity is a complex disease that encompasses multiple dimensions, such as excessive energy intake and genetics. The melanocortin 4 receptor mutation (MC4R) is an important mediator in appetite. There is emerging evidence that suggests its role in the Body Mass Index (BMI) among PCOS subjects, which poses the question of obesity and/or overweight among the PCOS patients who carry the MC4R variants may be caused by overconsumption. Thereby, using other satiety techniques may be beneficial as a part of personalized nutrition. Therefore, the aim of the current mini-review is to discuss the effect of the vegan low glycemic diet on reducing appetite among PCOS patients. The review shows that there is a gap in the knowledge of the effect of the vegan diet on PCOS patients who carry MC4R variants which need further research.Keywords: polycystic ovarian syndrome (PCOS), Appetite, Melanocortin 4 Receptor Mutation (MC4R)., Obesity
Procedia PDF Downloads 1322389 Computational Approach for Grp78–Nf-ΚB Binding Interactions in the Context of Neuroprotective Pathway in Brain Injuries
Authors: Janneth Gonzalez, Marco Avila, George Barreto
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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics
Procedia PDF Downloads 3452388 Food Irradiation in the Third Sector Development and Validation of Questionnaire to Standard Measuring Instrument for Evaluation of Acceptance and Sensory Analysis of Irradiated Foods
Authors: Juliana Sagretti, Susy Sabato
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Despite the poverty in the world, a third of all food produced in the world is wasted. FAO, the United Nations Organization of Agriculture and Food, points out the need to combine actions and new technologies to combat hunger and waste in contrast to the high production of food in the world. The energy of ionizing radiation in food brought many positive results, such as increased validity and insect infestation control. The food banks are organizations that act at various points of food chain to collect and distribute food to the needy. So, the aim of this study was to initiate a partnership between irradiation and the food bank through the development of a questionnaire to evaluate and disseminate the knowledge and acceptance of individuals in the food bank in Brazil. In addition, this study aimed to standardize a basis questionnaire for future research assessment of irradiated foods. For the construction of the questionnaire as a measuring instrument, a comprehensive and rigorous literature review was made. Its covered qualitative research, questionnaires, sensory evaluation and food irradiated. Three stages of pre - tests were necessary and related fields of experts were consulted. As a result, the questionnaire has three parts, personal issues, assertive issues and questions of multiple choices and finally an informative question. The questionnaire was applied in Ceagesp food bank in the biggest center of food in Brazil (data not shown).Keywords: food bank, food irradiation, food waste, sustainability
Procedia PDF Downloads 3292387 Quantifying Impairments in Whiplash-Associated Disorders and Association with Patient-Reported Outcomes
Authors: Harpa Ragnarsdóttir, Magnús Kjartan Gíslason, Kristín Briem, Guðný Lilja Oddsdóttir
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Introduction: Whiplash-Associated Disorder (WAD) is a health problem characterized by motor, neurological and psychosocial symptoms, stressing the need for a multimodal treatment approach. To achieve individualized multimodal approach, prognostic factors need to be identified early using validated patient-reported and objective outcome measures. The aim of this study is to demonstrate the degree of association between patient-reported and clinical outcome measures of WAD patients in the subacute phase. Methods: Individuals (n=41) with subacute (≥1, ≤3 months) WAD (I-II), medium to high-risk symptoms, or neck pain rating ≥ 4/10 on the Visual Analog Scale (VAS) were examined. Outcome measures included measurements for movement control (Butterfly test) and cervical active range of motion (cAROM) using the NeckSmart system, a computer system using an inertial measurement unit (IMU) that connects to a computer. The IMU sensor is placed on the participant’s head, who receives visual feedback about the movement of the head. Patient-reported neck disability, pain intensity, general health, self-perceived handicap, central sensitization, and difficulties due to dizziness were measured using questionnaires. Excel and R statistical software were used for statistical analyses. Results: Forty-one participants, 15 males (37%), 26 females (63%), mean (SD) age 36.8 (±12.7), underwent data collection. Mean amplitude accuracy (AA) (SD) in the Butterfly test for easy, medium, and difficult paths were 2.4mm (0.9), 4.4mm (1.8), and 6.8mm (2.7), respectively. Mean cAROM (SD) for flexion, extension, left-, and right rotation were 46.3° (18.5), 48.8° (17.8), 58.2° (14.3), and 58.9° (15.0), respectively. Mean scores on the Neck Disability Index (NDI), VAS, Dizziness Handicap Inventory (DHI), Central Sensitization Inventory (CSI), and 36-Item Short Form Survey RAND version (RAND) were 43% (17.4), 7 (1.7), 37 (25.4), 51 (17.5), and 39.2 (17.7) respectively. Females showed significantly greater deviation for AA compared to males for easy and medium Butterfly paths (p<0.05). Statistically significant moderate to strong positive correlation was found between the DHI and easy (r=0.6, p=0.05), medium (r=0.5, p=0.05)) and difficult (r=0.5, p<0.05) Butterfly paths, between the total RAND score and all cAROMs (r between 0.4-0.7, p≤0.05) except flexion (r=0.4, p=0.7), and between the NDI score and CSI (r=0.7, p<0.01), VAS (r=0.5, p<0.01), and DHI (r=0.7, p<0.01) scores respectively. Discussion: All patient-reported and objective measures were found to be outside the reference range. Results suggest females have worse movement control in the neck in the subacute WAD phase. However, no statistical difference based on gender was found in patient-reported measures. Suggesting females might have worse movement control than males in general in this phase. The correlation found between DHI and the Butterfly test can be explained because the DHI measures proprioceptive symptoms like dizziness and eye movement disorders that can affect the outcome of movement control tests. A correlation was found between the total RAND score and cAROM, suggesting that a reduced range of motion affects the quality of life. Significance: The NeckSmart system can detect abnormalities in cAROM, fine movement control, and kinesthesia of the neck. Results suggest females have worse movement control than males. Results show a moderate to a high correlation between several patient-reported and objective measurements.Keywords: whiplash associated disorders, car-collision, neck, trauma, subacute
Procedia PDF Downloads 722386 Breaking the Silence and Rewriting the Script
Authors: Carlette Groome
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This paper examined the role of drama in the lives of four women. The researcher concluded that drama can be an avenue of healing and could be an effective means of social work intervention in the communities as well as female empowerment. The participants in the study were able to, through the dramatic process; re-write their life’s scripts by resolving paradoxes and conflicts related to the themes unearthed. The research conducted examined the role of drama in the lives of four women living in volatile communities in Jamaica, who were each exposed to violence in one, or multiple, forms. The women were trained by Sistren Theatre Collective in the use of drama for education (edutainment), and were actresses in Sistren's street theatre drama group. Using their own personal and collective experiences, they used drama to raise social consciousness at the community level, about violence and other issues affecting women. The study employed a narrative case study approach and was grounded in a constructivist paradigm. This paradigm was coupled with a basic interpretive qualitative method and the concept of the reflective practitioner provided the foundation for the analysis. Through individual conversations with the women, themes of abuse, resilience, self- esteem, and empowerment arose sharply. The women explored drama and understood it to be instrumental in healing different aspects of their lives. Also, through the dramatic process; they were able to re-write their life’s scripts by resolving paradoxes and conflicts related to the themes unearthed.Keywords: women, drama, healing, community
Procedia PDF Downloads 3412385 A Study on Learning Styles and Academic Performance in Relation with Kinesthetic, Verbal and Visual Intelligences
Authors: Salina Budin, Nor Liawati Abu Othman, Shaira Ismail
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This study attempts to determine kinesthetic, verbal and visual intelligences among mechanical engineering undergraduate students and explores any probable relation with students’ learning styles and academic performance. The questionnaire used in this study is based on Howard Gardner’s multiple intelligences theory comprising of five elements of learning style; environmental, sociological, emotional, physiological and psychological. Questionnaires are distributed amongst undergraduates in the Faculty of Mechanical Engineering. Additional questions on students’ perception of learning styles and their academic performance are included in the questionnaire. The results show that one third of the students are strongly dominant in the kinesthetic intelligent (33%), followed by a combination of kinesthetic and visual intelligences (29%) and 21% are strongly dominant in all three types of intelligences. There is a statistically significant correlation between kinesthetic, verbal and visual intelligences and students learning styles and academic performances. The ANOVA analysis supports that there is a significant relationship between academic performances and level of kinesthetic, verbal and visual intelligences. In addition, it has also proven a remarkable relationship between academic performances and kinesthetic, verbal and visual learning styles amongst the male and female students. Thus, it can be concluded that, academic achievements can be enhanced by understanding as well as capitalizing the students’ types of intelligences and learning styles.Keywords: kinesthetic intelligent, verbal intelligent, visual intelligent, learning style, academic performances
Procedia PDF Downloads 3042384 Relations between Psychological Adjustment and Perceived Parental, Teacher and Best Friend Acceptance among Bangladeshi Adolescents
Authors: Tariqul Islam, Shaheen Mollah
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The study's main objective is to assess the relationship between psychological adjustment and parental acceptance-rejection, teacher acceptance-rejection, and best friend acceptance-rejection among secondary school students. This study was conducted on a sample of 300 (6th through 10th-grade students) recruited from over ten schools in Dhaka. While the schools were selected purposively, the respondents within each school were selected conveniently. The collected data were analyzed using Pearson product-moment correlation, hierarchical regression, and simultaneous regression analysis. The results showed that psychological adjustment is positively correlated with paternal, maternal, teacher, and best friend acceptance. The paternal acceptance was significantly connected with maternal acceptance. The teacher and best friend acceptance are correlated substantially with paternal and maternal acceptance. The hierarchical multiple regressions indicated that maternal, paternal, teacher, and best friend acceptance-rejection contributed significantly to students' psychological adjustment. The results revealed substantial independent contributions of maternal, paternal, teacher, and best friend acceptance on the students' psychological adjustment. The simultaneous regression analysis indicates that the maternal and best friend acceptances (but not paternal acceptance) were significant predictors of psychological adjustments. It showed that 41.7% variability in psychological adjustment could be explained by paternal, maternal, and best friend acceptance. The findings of the present study are exciting. They may contribute to developing insight in parents and best friends for behaving properly with their offspring and friend, respectively, for better psychological adjustment.Keywords: adjustment, parenting, rejection, acceptance
Procedia PDF Downloads 1492383 The Effect of Contextual Factors on Degree of Trust in Kuwaiti Business Organization
Authors: Ali Muhammad
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The study investigates the effect of a number of contextual on the degree of trust within Kuwaiti business organizations. The model used in this study suggests that degree of trust within the organization is determined by four contextual variables, namely, centralization, formalization, role ambiguity, and procedural justice. Organizational trust refers to employee’ positive assumptions in regard to the goal and behaviors of other members in the organization according to organizational duties, relationships, experiences, and interrelatedness. According to the norm of reciprocity, individuals with high perceived organizational justice will be compelled to react positively to the organization in the form of higher degree of trust. The duty to exchange kindness for kindness. Based on the exchange theory, this research proposes that procedural justice, role clarity, and voice in the organization will lead to the perception of an organization’s discretionary positive treatment of employees and, in return enhances their trust in the organization. Survey data were collected from a sample of 206 employees working in Kuwaiti business organizations. Results of multiple regression analysis revealed that both organizational justice and formalization have positive effects on organizational trust. Furthermore, results indicate that lower degree of role ambiguity leads to higher degree of organizational trust. On the other hand, centralization was not found to have a significant effect on organizational trust. Implications of the findings and directions for future research are discussed.Keywords: centralization, formalization, organizational justice, organizational trust, role ambiguity
Procedia PDF Downloads 1922382 Phage Therapy of Staphylococcal Pyoderma in Dogs
Authors: Jiri Nepereny, Vladimir Vrzal
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Staphylococcus intermedius/pseudintermedius bacteria are commonly found on the skin of healthy dogs and can cause pruritic skin diseases under certain circumstances (trauma, allergy, immunodeficiency, ectoparasitosis, endocrinological diseases, glucocorticoid therapy, etc.). These can develop into complicated superficial or deep pyoderma, which represent a large group of problematic skin diseases in dogs. These are predominantly inflammations of a secondary nature, associated with the occurrence of coagulase-positive Staphylococcus spp. A major problem is increased itching, which greatly complicates the healing process. The aim of this work is to verify the efficacy of the developed preparation Bacteriophage SI (Staphylococcus intermedius). The tested preparation contains a lysate of bacterial cells of S. intermedius host culture including culture medium and live virions of specific phage. Sodium Merthiolate is added as a preservative in a safe concentration. Validation of the efficacy of the product was demonstrated by monitoring the therapeutic effect after application to indicated cases from clinical practice. The indication for inclusion of the patient into the trial was an adequate history and clinical examination accompanied by sample collection for bacteriological examination and isolation of the specific causative agent. Isolate identification was performed by API BioMérieux identification system (API ID 32 STAPH) and rep-PCR typing. The suitability of therapy for a specific case was confirmed by in vitro testing of the lytic ability of the bacteriophage to lyse the specific isolate = formation of specific plaques on the culture isolate on the surface of the solid culture medium. So far, a total of 32 dogs of different sexes, ages and breed affiliations with different symptoms of staphylococcal dermatitis have been included in the testing. Their previous therapy consisted of more or less successful systemic or local application of broad-spectrum antibiotics. The presence of S. intermedius/pseudintermedius has been demonstrated in 26 cases. The isolates were identified as a S. pseudintermedius, in all cases. Contaminant bacterial microflora was always present in the examined samples. The test product was applied subcutaneously in gradually increasing doses over a period of 1 month. After improvement in health status, maintenance therapy was followed by application of the product once a week for 3 months. Adverse effects associated with the administration of the product (swelling at the site of application) occurred in only 2 cases. In all cases, there was a significant reduction in clinical signs (healing of skin lesions and reduction of inflammation) after therapy and an improvement in the well-being of the treated animals. A major problem in the treatment of pyoderma is the frequent resistance of the causative agents to antibiotics, especially the increasing frequency of multidrug-resistant and methicillin-resistant S. pseudintermedius (MRSP) strains. Specific phagolysate using for the therapy of these diseases could solve this problem and to some extent replace or reduce the use of antibiotics, whose frequent and widespread application often leads to the emergence of resistance. The advantage of the therapeutic use of bacteriophages is their bactericidal effect, high specificity and safety. This work was supported by Project FV40213 from Ministry of Industry and Trade, Czech Republic.Keywords: bacteriophage, pyoderma, staphylococcus spp, therapy
Procedia PDF Downloads 1742381 Nuclear Characteristics of a Heterogeneous Thorium-Based Fuel Design Aimed at Increasing Fuel Cycle Length of a Typical PWR
Authors: Hendrik Bernard Van Der Walt, Frik Van Niekerk
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Heterogeneous thorium-based fuels have been proposed as an alternative for conventional reactor fuels and many studies have shown promising results. Fuel cycle characteristics still have to be explored in detail. This study investigates the use of a novel thorium-based fuel design aimed at increasing fuel cycle length of a typical PWR with an explicit focus on thorium- uranium content, neutron spectrum, flux considerations and neutron economy.As nuclear reactions are highly dependent on reactor flux and material matrix, analytical and numerical calculations have been completed to predict the behaviour of the proposed nuclear fuel. The proposed design utilizes various ratios of thorium oxide and uranium oxide pellets within fuel pins, divided into heterogeneous sections of specified length. This design renders multiple regions with unique characteristics. The goal of this study is to determine and optimally utilize these characteristics. Proliferation considerations result in the need for denaturing of heterogeneous regions, which renders more unique characteristics, these aspects were examined in this study. Finally, the use of fertile thorium to emulate a burnable poison for managing excess BOL reactivity has been investigated, as well as an option for flux shaping in a typical PWR.Keywords: nuclear fuel, nuclear characteristics, nuclear fuel cycle, thorium-based fuel, heterogeneous design
Procedia PDF Downloads 1402380 Molecular Interactions Driving RNA Binding to hnRNPA1 Implicated in Neurodegeneration
Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan
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Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins
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