Search results for: Petrus Joubert

Authors: Aran Abd Al Rahman

Abstract:

Joubert syndrome regards as a congenital cerebellar ataxia caused by autosomal recessive carried on X chromosome. The disease diagnosed by brain imaging—the so-called molar tooth sign. Neurological signs were present from the neonatal period and include hypotonia progressing to ataxia, global developmental delay, ocular motor apraxia, and breathing dysregulation. These signs are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton, and liver. 30 causative genes have been identified so far, all of which encode for proteins of the primary cilium or its apparatus, The purpose of our project was to detect the mutant gene (INPP5E gene) which cause Joubert syndrome. There were many methods used for diagnosis such as MRI and CT- scan and molecular diagnosis by doing ARMS PCR for detection of mutant gene that we were used in this research project. In this research for individual family which reported, the two children with parents, the two children were affected and were carrier.

Keywords: Joubert syndrome, genetic disease, Kurdistan region, Sulaimani

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Authors: Bajraktarevic Adnan, Djukic Branka, Sporisevic Lutvo, Krdzalic Zecevic Belma, Uzicanin Sajra, Hadzimuratovic Admir, Hadzimuratovic Hadzipasic Emina, Abduzaimovic Alisa, Kustric Amer, Suljevic Ismet, Serafi Ismail, Tahmiscija Indira, Khatib Hakam, Semic Jusufagic Aida, Haas Helmut, Vladicic Aleksandra, Aplenc Richard, Kadic Deovic Aida

Abstract:

Introduction: Joubert syndrome has an autosomal recessive pattern of inheritance. It is referred as the brain malfunctioning and caused due to the underdevelopment of the cerebellar vermis. Associated conditions involving the eye, the kidney, and ocular disease are well described. Aims: Research helps us better understand this diseases, Joubert syndrome and can lead to advances in diagnosis and treatment. Methods: Different several conditions have been described in which the molar tooth sign and characteristics of Joubert syndrome in ten different places in the world. Carrier testing and diagnosis are available if one of these gene mutations has been identified in an affected family member. Results: Authors have described eleven cases during twenty years of Joubert syndrome. It is a clinically and genetically heterogeneous group of disorders characterized by hypoplasia of the cerebellar vermis with the characteristic neuroradiologic molar tooth sign, and accompanying neurologic symptoms, including dysregulation of breathing pattern and developmental delay. We made confirmation of diagnosis in twin sisters with Joubert syndrome with renal anomalies. Ocular symptoms have existed in seven cases (63.64%) from total eleven. Eleven cases were different sex, five boys (45.45%) and six girls (54.44%). Conclusions: Joubert syndrome is inherited as an autosomal recessive genetic disorder with several features of the disease.

Keywords: Joubert syndrome, cerebellooculorenal syndrome, autosomal recessive genetic disorder (ARGD), children

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Authors: Ali Al Orf, Khawaja Bilal Waheed

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Background and objective: Joubert syndrome (JS) is a rare, autosomal-recessive condition. Early recognition is important for management and counseling. Magnetic resonance imaging (MRI) can help in diagnosis. Therefore, we sought to evaluate clinical presentation and MRI findings in Joubert syndrome and related disorders. Method: A retrospective review of genetically proven cases of Joubert syndromes and related disorders was reviewed for their clinical presentation, demographic information, and magnetic resonance imaging findings in a period of the last 10 years. Two radiologists documented magnetic resonance imaging (MRI) findings. The presence of hypoplasia of the cerebellar vermis with hypoplasia of the superior cerebellar peduncle resembling the “Molar Tooth Sign” in the mid-brain was documented. Genetic testing results were collected to label genes linked to the diagnoses. Results: Out of 12 genetically proven JS cases, most were females (9/12), and nearly all presented with hypotonia, ataxia, developmental delay, intellectual impairment, and speech disorders. 5/12 children presented at age of 1 or below. The molar tooth sign was seen in 10/12 cases. Two cases were associated with other brain findings. Most of the cases were found associated with consanguineous marriage Conclusion and discussion: The molar tooth sign is a frequent and reliable sign of JS and related disorders. Genes related to defective cilia result in malfunctioning in the retina, renal tubule, and neural cell migration, thus producing heterogeneous syndrome complexes known as “ciliopathies.” Other ciliopathies like Senior-Loken syndrome, Bardet Biedl syndrome, and isolated nephronophthisis must be considered as the differential diagnosis of JS. The main imaging findings are the partial or complete absence of the cerebellar vermis, hypoplastic cerebellar peduncles (giving MTS), and (bat-wing appearance) fourth ventricular deformity. LimitationsSingle-center, small sample size, and retrospective nature of the study were a few of the study limitations.

Keywords: Joubart syndrome, magnetic resonance imaging, molar tooth sign, hypotonia

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Authors: Hanli Joubert

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In South Africa, teaching large classes is a reality that lecturers face in most higher institutions. When teaching a large group, literature normally refers to groups of about 50 to 500 students. At the University of the Free State, the first-year accounting group comprises around 1300 students. Apart from extremely large classes, the problem is exacerbated by the diversity of students’ previous schooling in accounting as well as their socio-economic backgrounds. The university scenario is further complicated by a lack of venues, compressed timetables, as well as lack of resources. This study aims to investigate the challenges and effectiveness of teaching a large and diverse group of first-year accounting students by drawing from personal experience, a literature study, interviews with other lecturers as well as students registered for first year accounting. The results reveal that teaching first-year accounting students in a large group is not the ideal situation but that it can be effective if it is managed correctly.

Keywords: diverse backgrounds, large groups, limited resources, first-year accounting students

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Authors: Franky Michael Hamonangan Siagian, Affan Maulana, Himawan Tri Bayu Murti Petrus, Widi Astuti

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In this study, the feasibility of the direct electrowinning method was used to produce zero-valent iron from red mud. The bauxite residue sample came from the Tayan mine, Indonesia, which contains high hematite (Fe₂O₃). Before electrolysis, the samples were characterized by various analytical techniques (ICP-AES, SEM, XRD) to determine their chemical composition and mineralogy. The direct electrowinning method of red mud suspended in NaOH was introduced at low temperatures ranging from 30 - 110 °C. Variations of current density, red mud: NaOH ratio and temperature were carried out to determine the optimum operation of the direct electrowinning process. Cathode deposits and residues in electrochemical cells were analyzed using XRD, XRF, and SEM to determine the chemical composition and current recovery. The low-temperature electrolysis current efficiency on Redmud can reach 20% recovery at a current density of 920,945 A/m². The moderate performance of the process was investigated with red mud, which was attributed to the troublesome adsorption of red mud particles on the cathode, making the reduction far less efficient than that with hematite.

Keywords: red mud, electrochemical reduction, Iron production, hematite

Procedia PDF Downloads 41

Authors: Franky Michael Hamonangan Siagian, Affan Maulana, Himawan Tri Bayu Murti Petrus, Panut Mulyono, Widi Astuti

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In this study, the feasibility of the direct electrowinning method was used to produce zero-valent iron from red mud. The bauxite residue sample came from the Tayan mine, Indonesia, which contains high hematite (Fe₂O₃). Before electrolysis, the samples were characterized by various analytical techniques (ICP-AES, SEM, XRD) to determine their chemical composition and mineralogy. The direct electrowinning method of red mud suspended in NaOH was introduced at low temperatures ranging from 30 - 110 °C. Variations of current density, red mud: NaOH ratio and temperature were carried out to determine the optimum operation of the direct electrowinning process. Cathode deposits and residues in electrochemical cells were analyzed using XRD, XRF, and SEM to determine the chemical composition and current recovery. The low-temperature electrolysis current efficiency on Redmud can reach 20% recovery at a current density of 920,945 A/m². The moderate performance of the process was investigated with red mud, which was attributed to the troublesome adsorption of red mud particles on the cathode, making the reduction far less efficient than that with hematite.

Keywords: alumina, red mud, electrochemical reduction, iron production

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Authors: Awatef Hicheur Cairns, Billel Gueni, Hind Hafdi, Christian Joubert, Nasser Khelifa

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Given the ever changing needs of the job markets, education and training centers are increasingly held accountable for student success. Therefore, education and training centers have to focus on ways to streamline their offers and educational processes in order to achieve the highest level of quality in curriculum contents and managerial decisions. Educational process mining is an emerging field in the educational data mining (EDM) discipline, concerned with developing methods to discover, analyze and provide a visual representation of complete educational processes. In this paper, we present our distributed computation platform which allows different education centers and institutions to load their data and access to advanced data mining and process mining services. To achieve this, we present also a comparative study of the different clustering techniques developed in the context of process mining to partition efficiently educational traces. Our goal is to find the best strategy for distributing heavy analysis computations on many processing nodes of our platform.

Keywords: educational process mining, distributed process mining, clustering, distributed platform, educational data mining, ProM

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Authors: Getachew T. Sedebo, Stephan V. Joubert, Michael Y. Shatalov

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Conventional configuration of the vibratory disc gyroscope is based on in-plane non-axisymmetric vibrations of the disc with a prescribed circumferential wave number. Due to the Bryan's effect, the vibrating pattern of the disc becomes sensitive to the axial component of inertial rotation of the disc. Rotation of the vibrating pattern relative to the disc is proportional to the inertial angular rate and is measured by sensors. In the present paper, the authors investigate a possibility of making a 3D sensor on the basis of both in-plane and bending vibrations of the disc resonator. We derive equations of motion for the disc vibratory gyroscope, where both in-plane and bending vibrations are considered. Hamiltonian variational principle is used in setting up equations of motion and the corresponding boundary conditions. The theory of thin shells with the linear elasticity principles is used in formulating the problem and also the disc is assumed to be isotropic and obeys Hooke's Law. The governing equation for a specific mode is converted to an ODE to determine the eigenfunction. The resulting ODE has exact solution as a linear combination of Bessel and Neumann functions. We demonstrate how to obtain an explicit solution and hence the eigenvalues and corresponding eigenfunctions for annular disc with fixed inner boundary and free outer boundary. Finally, the characteristics equations are obtained and the corresponding eigenvalues are calculated. The eigenvalues are used for the calculation of tuning conditions of the 3D disc vibratory gyroscope.

Keywords: Bryan’s effect, bending vibrations, disc gyroscope, eigenfunctions, eigenvalues, tuning conditions

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Authors: A. Bruce Janati, Muhammad Umair Khan, Naif Alghassab, Ibrahim Alzeir, Assem Mahmoud, M. Sammour

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Rationale: Lennox-Gastaut syndrome(LGS) is an electro-clinical syndrome composed of the triad of mental retardation, multiple seizure types, and the characteristic generalized slow spike-wave complexes in the EEG. In this article, we report on two patients with LGS whose brain MRI showed dysgenesis of corpus callosum(CC). We review the literature and stress the role of CC in the genesis of secondary bilateral synchrony(SBS). Method: This was a clinical study conducted at King Khalid Hospital. Results: The EEG was consistent with LGS in patient 1 and unilateral slow spike-wave complexes in patient 2. The MRI showed hypoplasia of the splenium of CC in patient 1, and global hypoplasia of CC combined with Joubert syndrome in patient 2. Conclusion: Based on the data, we proffer the following hypotheses: 1-Hypoplasia of CC interferes with functional integrity of this structure. 2-The genu of CC plays a pivotal role in the genesis of secondary bilateral synchrony. 3-Electrodecremental seizures in LGS emanate from pacemakers generated in the brain stem, in particular the mesencephalon projecting abnormal signals to the cortex via thalamic nuclei. 4-Unilateral slow spike-wave complexes in the context of mental retardation and multiple seizure types may represent a variant of LGS, justifying neuroimaging studies.

Keywords: EEG, Lennox-Gastaut syndrome, corpus callosum , MRI

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Authors: Cheng-Yang Lee, Petrus Tang, Tzu-Hao Chang

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Copy number variations (CNVs) have played an important role in many kinds of human diseases, such as Autism, Schizophrenia and a number of cancers. Many diseases are found in genome coding regions and whole exome sequencing (WES) is a cost-effective and powerful technology in detecting variants that are enriched in exons and have potential applications in clinical setting. Although several algorithms have been developed to detect CNVs using WES and compared with other algorithms for finding the most suitable methods using their own samples, there were not consistent datasets across most of algorithms to evaluate the ability of CNV detection. On the other hand, most of algorithms is using command line interface that may greatly limit the analysis capability of many laboratories. We create a series of simulated WES datasets from UCSC hg19 chromosome 22, and then evaluate the CNV detective ability of 19 algorithms from OMICtools database using our simulated WES datasets. We compute the sensitivity, specificity and accuracy in each algorithm for validation of the exome-derived CNVs. After comparison of 19 algorithms from OMICtools database, we construct a platform to install all of the algorithms in a virtual machine like VirtualBox which can be established conveniently in local computers, and then create a simple script that can be easily to use for detecting CNVs using algorithms selected by users. We also build a table to elaborate on many kinds of events, such as input requirement, CNV detective ability, for all of the algorithms that can provide users a specification to choose optimum algorithms.

Keywords: whole exome sequencing, copy number variations, omictools, pipeline

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Authors: Rueyhung Weng, Chia-En Huang, Jung-Chi-Liao

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The transition zone (TZ) serves as a diffusion barrier to regulate the ins and outs of the proteins recruited to the primary cilia. TCTN2 is one of the TZ proteins and its mutation causes Joubert syndrome, a serious multi-organ disease. Despite its important medical relevance, the functions of TCTN2 remain elusive. Here we created a TCTN2 gene deleted retinal pigment epithelial cells (RPE1) using CRISPR/Cas9-based genome editing technique and used this knockout line to reveal roles of TCTN2. TCTN2 knockout RPE1 cells displayed a significantly reduced ciliogenesis or a shortened primary cilium length in the cilium-remaining population. Intraflagellar transport protein IFT88 aberrantly accumulated at the tip of TCTN2 deficient cells. Guanine nucleotide exchange factor Arl13B was mostly absent from the ciliary compartment, with a small population localizing at the ciliary tip. The deficient TZ was corroborated with the mislocalization of two other TZ proteins TMEM67 and MKS1. In addition, TCTN2 deficiency induced TZ impairment led to the suppression of Sonic hedgehog signaling in response to Smoothened (Smo) agonist. Together, depletion of TCTN2 destabilizes other TZ proteins and considerably alters the localization of key transport and signaling-associated proteins, including IFT88, Arl13B, and Smo.

Keywords: CRISPR/Cas9, primary cilia, Sonic hedgehog signaling, transition zone

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Authors: Po-Jung Huang, Chi-Ching Lee, Bertrand Chin-Ming Tan, Yuan-Ming Yeh, Julie Lichieh Chu, Tin-Wen Chen, Cheng-Yang Lee, Ruei-Chi Gan, Hsuan Liu, Petrus Tang

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Whole-exome sequencing focuses on the protein coding regions of disease/cancer associated genes based on a priori knowledge is the most cost-effective method to study the association between genetic alterations and disease. Recent advances in high throughput sequencing technologies and proteomic techniques has provided an opportunity to integrate genomics and proteomics, allowing readily detectable mutated peptides corresponding to mutated genes. Since sequence database search is the most widely used method for protein identification using Mass spectrometry (MS)-based proteomics technology, a mutant proteome database is required to better approximate the real protein pool to improve disease-associated mutated protein identification. Large-scale whole exome/genome sequencing studies were launched by National Cancer Institute (NCI), Broad Institute, and The Cancer Genome Atlas (TCGA), which provide not only a comprehensive report on the analysis of coding variants in diverse samples cell lines but a invaluable resource for extensive research community. No existing database is available for the collection of mutant protein sequences related to the identified variants in these studies. CMPD is designed to address this issue, serving as a bridge between genomic data and proteomic studies and focusing on protein sequence-altering variations originated from both germline and cancer-associated somatic variations.

Keywords: TCGA, cancer, mutant, proteome

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Authors: Chi-Ching Lee, Po-Jung Huang, Kuo-Yang Huang, Petrus Tang

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Background: Recent advances in high-throughput research technologies such as new-generation sequencing and multi-dimensional liquid chromatography makes it possible to dissect the complete transcriptome and proteome in a single run for the first time. However, it is almost impossible for many laboratories to handle and analysis these “BIG” data without the support from a bioinformatics team. We aimed to provide a web-based analysis platform for users with only limited knowledge on bio-computing to study the functional genomics and proteomics. Method: We use NCI-60 as an example dataset to demonstrate the power of the web-based analysis platform and data delivering system: C-eXpress takes a simple text file that contain the standard NCBI gene or protein ID and expression levels (rpkm or fold) as input file to generate a distribution map of gene/protein expression levels in a heatmap diagram organized by color gradients. The diagram is hyper-linked to a dynamic html table that allows the users to filter the datasets based on various gene features. A dynamic summary chart is generated automatically after each filtering process. Results: We implemented an integrated database that contain pre-defined annotations such as gene/protein properties (ID, name, length, MW, pI); pathways based on KEGG and GO biological process; subcellular localization based on GO cellular component; functional classification based on GO molecular function, kinase, peptidase and transporter. Multiple ways of sorting of column and rows is also provided for comparative analysis and visualization of multiple samples.

Keywords: cancer, visualization, database, functional annotation

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Authors: Tshipeng Mwenze, Charles Okujeni, Abdi Siad, Russel Bailie, Dirk Frei, Marcelene Voigt, Petrus Le Roux

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The Platreef is a platinum group element (PGE) deposit in the northern limb of the Bushveld Igneous Complex (BIC) which was emplaced as a series of mafic and ultramafic sills between the Main Zone (MZ) and the country rocks. The PGE mineralisation in the Platreef is hosted in different rock types, and its distribution and style vary with depth and along strike. This study contributes towards understanding the processes involved in the genesis of the Platreef. Twenty-four Platreef (2 harzburgites, 4 olivine pyroxenites, 17 feldspathic pyroxenites and 1 gabbronorite) and few MZ (1 gabbronorite and 1 leucogabbronorite) quarter core samples were collected from four drill cores (e.g., TN754, TN200, SS339, and OY482) and analysed for whole-rock Sr-Nd isotope data. The results show positive ɛNd values (+3.53 to +7.51) for harzburgites suggesting their parental magmas derived from the depleted Mantle. The remaining Platreef rocks have negative ɛNd values (-2.91 to -22.88) and show significant variations in Sr-Nd isotopic compositions. The first group of Platreef samples has relatively high isotopic compositions (ɛNd= -2.91 to -5.68; ⁸⁷Sr/⁸⁶Sri= 0.709177 - 0.711998). The second group of Platreef samples has Sr ratios (⁸⁷Sr/⁸⁶Sri= 0.709816-0.712106) overlapping with samples of the first group but slightly lower ɛNd values (-7.44 to -8.39). Lastly, the third group of Platreef samples has low ɛNd values (-10.82 to -14.32) and low Sr ratios (⁸⁷Sr/⁸⁶Sri= 0.707545-0.710042) than those from samples of the two Platreef groups mentioned above. There is, however, a Platreef sample with ɛNd value (-5.26) in range with the Platreef samples of the first group, but its Sr ratio (0.707281) is the lowest even when compared to samples of the third Platreef group. There are also five other Platreef samples which have either anomalous ɛNd or Sr ratios which make it difficult to assess their isotopic compositions relative to other samples. These isotopic variations for the Platreef samples indicate both multiple sources and multiple magma chambers where varying crustal contamination styles have operated during the evolution of these magmas prior their emplacements into the Platreef setting as sills. Furthermore, the MZ rocks have different Sr-Nd isotopic compositions (For OY482 gabbronorite [ɛNd= +0.65; ⁸⁷Sr/⁸⁶Sri= 0.711746]; for TN754 leucogabbronorite [ɛNd= -7.44; ⁸⁷Sr/⁸⁶Sri= 0.709322]) which do not only indicate different MZ magma chambers, but also different magmas from those of the Platreef. Although the Platreef is still considered a single stratigraphic unit in the northern limb of the BIC, its genesis involved multiple magmatic processes which evolved independently from each other.

Keywords: crustal contamination styles, magma chambers, magma sources, multiple sills emplacement

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Authors: Ciara Pienaar, J. W. Odendaal, J. Joubert, J. C. Smit

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Radar cross section (RCS) of dielectric objects play an important role in many applications, such as low observability technology development, drone detection, and monitoring as well as coastal surveillance. Various materials are used to construct the targets of interest such as metal, wood, composite materials, radar absorbent materials, and other dielectrics. Since simulated datasets are increasingly being used to supplement infield measurements, as it is more cost effective and a larger variety of targets can be simulated, it is important to have a high level of confidence in the predicted results. Confidence can be attained through validation. Various computational electromagnetic (CEM) methods are capable of predicting the RCS of dielectric targets. This study will extend previous studies by validating full-wave and asymptotic RCS simulations of dielectric targets with measured data. The paper will provide measured RCS data of a number of canonical dielectric targets exhibiting different material properties. As stated previously, these measurements are used to validate numerous CEM methods. The dielectric properties are accurately characterized to reduce the uncertainties in the simulations. Finally, an analysis of the sensitivity of oblique and normal incidence scattering predictions to material characteristics is also presented. In this paper, the ability of several CEM methods, including method of moments (MoM), and physical optics (PO), to calculate the RCS of dielectrics were validated with measured data. A few dielectrics, exhibiting different material properties, were selected and several canonical targets, such as flat plates and cylinders, were manufactured. The RCS of these dielectric targets were measured in a compact range at the University of Pretoria, South Africa, over a frequency range of 2 to 18 GHz and a 360° azimuth angle sweep. This study also investigated the effect of slight variations in the material properties on the calculated RCS results, by varying the material properties within a realistic tolerance range and comparing the calculated RCS results. Interesting measured and simulated results have been obtained. Large discrepancies were observed between the different methods as well as the measured data. It was also observed that the accuracy of the RCS data of the dielectrics can be frequency and angle dependent. The simulated RCS for some of these materials also exhibit high sensitivity to variations in the material properties. Comparison graphs between the measured and simulation RCS datasets will be presented and the validation thereof will be discussed. Finally, the effect that small tolerances in the material properties have on the calculated RCS results will be shown. Thus the importance of accurate dielectric material properties for validation purposes will be discussed.

Keywords: asymptotic, CEM, dielectric scattering, full-wave, measurements, radar cross section, validation

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Authors: Petrus Louis Nolte

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University sport in South Africa is not isolated from the complexity of globalization and professionalization of sport, as it forms an integral part of the sport development environment in South Africa. In order to align their sport programmes with global and professional requirements, several universities opted to develop elite sport programmes; recruit specialized personnel such as coaches, administrators and athletes; provide expert coaching; scientific and medical services; sports testing; fitness, technical and tactical expertise; sport psychological and rehabilitation support; academic guidance and career assistance; and student-athlete accommodation. In addition, universities provide administrative support and high-quality physical resources (training facilities) for the benefit of the overall South African sport system. Although it is not compulsory for universities to develop elite sport programmes to prepare their teams for competitions, elite competitions such as the annual Varsity Sport, University Sport South Africa (USSA) and local club competitions and leagues within university international competitions where universities not only compete but also deliver players for representative national netball teams. The aim of this study is therefore to describe the perceptions of players of the university elite netball programmes they were participating in. This study adopted a descriptive design with a quantitative approach, utilizing a self-structured questionnaire as research technique. As this research formed part of a national research project for NSA with a population of 172 national and provincial netball players, a sample of 92 university netball players from the population was selected. Content validity of the self-structured questionnaire was secured through a test-retest process, with construct validity through a member of the Statistical Consultation Services (STATCON) of the University of Johannesburg that provided feedback on the structural format of the questionnaire. Reliability was measured utilising Cronbach Alpha on p<0.005 level of significance. A reliability score of 0.87 was measured. The research was approved by the Board of Netball South Africa and ethical conduct implemented according to the processes and procedures approved by the Ethics Committees of the Faculty of Health Sciences, University of Johannesburg with clearance number REC-01-30-2019. From the results it is evident that university elite netball programmes are professional, especially with regards to the employment of knowledgeable and competent coaches and technical officials such as team managers and sport sciences staff. These professionals have access to elite training facilities, support staff, and relatively large groups of elite players, all elements of an elite programme that could enhance the national federation’s (Netball South Africa) system. Universities could serve the dual purpose of serving as university netball clubs, as well as providing elite training services and facilities as performance hubs for national players.

Keywords: elite sport programmes, university netball, player experiences, Varsity Sport netball

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Authors: Wim Hollander, Petrus Louis Nolte

Abstract:

University sport in South Africa is not isolated from the complexity of globalization and professionalization of sport, as it forms an integral part of the sports development environment in South Africa. In order to align their sports programs with global and professional requirements, several universities opted to develop elite sports programs; recruit specialized personnel such as coaches, administrators, and athletes; provide expert coaching; scientific and medical services; sports testing; fitness, technical and tactical expertise; sport psychological and rehabilitation support; academic guidance and career assistance; and student-athlete accommodation. In addition, universities provide administrative support and high-quality physical resources (training facilities) for the benefit of the overall South African sport system. Although it is not compulsory for universities to develop elite sports programs to prepare their teams for competitions, elite competitions such as the annual Varsity Sport, University Sport South Africa (USSA) and local club competitions and leagues within international university competitions where universities not only compete but also deliver players for representative national netball teams. The aim of this study is, therefore, to describe the perceptions of players of the university elite netball programs they were participating in. This study adopted a descriptive design with a quantitative approach, utilizing a self-structured questionnaire as a research technique. As this research formed part of a national research project for NSA with a population of 172 national and provincial netball players, a sample of 92 university netball players from the population was selected. Content validity of the self-structured questionnaire was secured through a test-retest process, with construct validity through a member of the Statistical Consultation Services (STATCON) of the University of Johannesburg that provided feedback on the structural format of the questionnaire. Reliability was measured utilizing Cronbach Alpha on p < 0.005 level of significance. A reliability score of 0.87 was measured. The research was approved by the Board of Netball South Africa and ethical conduct implemented according to the processes and procedures approved by the Ethics Committees of the Faculty of Health Sciences, the University of Johannesburg with clearance number REC-01-30-2019. From the results, it is evident that university elite netball programs are professional, especially with regards to the employment of knowledgeable and competent coaches and technical officials such as team managers and sport sciences staff. These professionals have access to elite training facilities, support staff, and relatively large groups of elite players, all elements of an elite program that could enhance the national federation’s (Netball South Africa) system. Universities could serve the dual purpose of serving as university netball clubs, as well as providing elite training services and facilities as performance hubs for national players.

Keywords: elite sport programmes, university netball, player experiences, varsity sport netball

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Authors: M. Pienaar, J. W. Odendaal, J. C. Smit, J. Joubert

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Simulations are commonly used to predict the bistatic radar cross section (RCS) of military targets since characterization measurements can be expensive and time consuming. It is thus important to accurately predict the bistatic RCS of targets. Computational electromagnetic (CEM) methods can be used for bistatic RCS prediction. CEM methods are divided into full-wave and asymptotic methods. Full-wave methods are numerical approximations to the exact solution of Maxwell’s equations. These methods are very accurate but are computationally very intensive and time consuming. Asymptotic techniques make simplifying assumptions in solving Maxwell's equations and are thus less accurate but require less computational resources and time. Asymptotic techniques can thus be very valuable for the prediction of bistatic RCS of electrically large targets, due to the decreased computational requirements. This study extends previous work by validating the accuracy of asymptotic techniques to predict bistatic RCS through comparison with full-wave simulations as well as measurements. Validation is done with canonical structures as well as complex realistic aircraft models instead of only looking at a complex slicy structure. The slicy structure is a combination of canonical structures, including cylinders, corner reflectors and cubes. Validation is done over large bistatic angles and at different polarizations. Bistatic RCS measurements were conducted in a compact range, at the University of Pretoria, South Africa. The measurements were performed at different polarizations from 2 GHz to 6 GHz. Fixed bistatic angles of β = 30.8°, 45° and 90° were used. The measurements were calibrated with an active calibration target. The EM simulation tool FEKO was used to generate simulated results. The full-wave multi-level fast multipole method (MLFMM) simulated results together with the measured data were used as reference for validation. The accuracy of physical optics (PO) and geometrical optics (GO) was investigated. Differences relating to amplitude, lobing structure and null positions were observed between the asymptotic, full-wave and measured data. PO and GO were more accurate at angles close to the specular scattering directions and the accuracy seemed to decrease as the bistatic angle increased. At large bistatic angles PO did not perform well due to the shadow regions not being treated appropriately. PO also did not perform well for canonical structures where multi-bounce was the main scattering mechanism. PO and GO do not account for diffraction but these inaccuracies tended to decrease as the electrical size of objects increased. It was evident that both asymptotic techniques do not properly account for bistatic structural shadowing. Specular scattering was calculated accurately even if targets did not meet the electrically large criteria. It was evident that the bistatic RCS prediction performance of PO and GO depends on incident angle, frequency, target shape and observation angle. The improved computational efficiency of the asymptotic solvers yields a major advantage over full-wave solvers and measurements; however, there is still much room for improvement of the accuracy of these asymptotic techniques.

Keywords: asymptotic techniques, bistatic RCS, geometrical optics, physical optics

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Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

Abstract:

A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

Procedia PDF Downloads 219

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

Abstract:

Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

Procedia PDF Downloads 174

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

Abstract:

Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

Procedia PDF Downloads 128