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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Imagerie multispectrale, vers une conception adaptée à la détection de cibles

Minet, Jean 01 December 2011 (has links) (PDF)
L'imagerie hyperspectrale, qui consiste à acquérir l'image d'une scène dans un grand nombre de bandes spectrales, permet de détecter des cibles là où l'imagerie couleur classique ne permettrait pas de conclure. Les imageurs hyperspectraux à acquisition séquentielle sont inadaptés aux applications de détection en temps réel. Dans cette thèse, nous proposons d'utiliser un imageur multispectral snapshot, capable d'acquérir simultanément un nombre réduit de bandes spectrales sur un unique détecteur matriciel. Le capteur offrant un nombre de pixels limité, il est nécessaire de réaliser un compromis en choisissant soigneusement le nombre et les profils spectraux des filtres de l'imageur afin d'optimiser la performance de détection. Dans cet objectif, nous avons développé une méthode de sélection de bandes qui peut être utilisée dans la conception d'imageurs multispectraux basés sur une matrice de filtres fixes ou accordables. Nous montrons, à partir d'images hyperspectrales issues de différentes campagnes de mesure, que la sélection des bandes spectrales à acquérir peut conduire à des imageurs multispectraux capables de détecter des cibles ou des anomalies avec une efficacité de détection proche de celle obtenue avec une résolution hyperspectrale. Nous développons conjointement un démonstrateur constitué d'une matrice de 4 filtres de Fabry-Perot accordables électroniquement en vue de son implantation sur un imageur multispectral snapshot agile. Ces filtres sont développés en technologie MOEMS (microsystèmes opto-électro-mécaniques) en partenariat avec l'Institut d'Electronique Fondamentale. Nous présentons le dimensionnement optique du dispositif ainsi qu'une étude de tolérancement qui a permis de valider sa faisabilité.
42

Fernand Braun, photographe et éditeur à Royan (1895-1920) / Fernand Braun, photographer and publisher in Royan (1895-1920)

Caillaud, Benjamin 13 December 2012 (has links)
Le photographe français Fernand Braun (1852-1948) quitte les ateliers alsaciens de son oncle Adolphe Braun (1812-1877) en 1878 pour s’’installer à Angoulême, en Charente. Profitant du marché porteur du portrait, le jeune entrepreneur prend une part active aux recherches sur le gélatino-bromure d’’argent, une technique qui ouvre l’ère de l’instantané en photographie. Rejoignant les élites républicaines au sein de la société de gymnastique de la ville, le jeune homme exprime son sentiment de revanche face à la Prusse victorieuse de 1870. Gymnaste accompli et influent, les sentiments patriotiques du personnage le conduisent alors à rejoindre la Ligue des patriotes en 1884. Fréquentant Royan dès 1893, Fernand Braun s’installe en Charente-Inférieure en 1895 pour relancer ses activités. Inséré au réseau des élites conduisant le projet balnéaire de la cité et l’œuvre républicaine d’’instruction de la jeunesse, il entame une carrière d’éditeur de cartes postales. Le photographe crée à partir de 1900, un catalogue de milliers de clichés baptisé la Grande Série et valorisant les paysages et la vie des Charentais. Connaissant un succès phénoménal, la carte postale s’impose comme le medium de prédilection du début du XXe siècle. Les publications de l’éditeur témoignent alors des mutations des paysages régionaux ainsi que des évolutions sociales sur lesquelles le photographe porte un regard d’homme concerné et engagé. Cependant, le dynamisme de la Grande Série ralentit au début des années 1910 et l’auteur cherche de nouveaux débouchés pour son imagerie de cartes postales.L’année 1913 marque une rupture dans sa politique éditoriale et davantage influencé par l’industrie touristique, le personnage renouvelle sa manière de mettre en image les territoires. La Grande Guerre remobilise l’éditeur dès 1914 et ce dernier s’attache alors à exposer les conséquences du conflit à ses contemporains. Néanmoins, ne produisant guère plus que des vues touristiques après 1918, la Grande Série s’arrête en 1920. / The French photographer Fernand Braun (1852-1948) leaves his uncle’s factories, Adolphe Braun’s, in Alsace, for Angouleme in Charente where he settles in 1878. Taking advantage of the successful vogue for portraits, the young business man takes an active part in the researches into gelatine silver process, a revolutionary technique witch was to open a new era for modern photography : the snapshot. When he joined the gymnastic circle, and with it,the republican elite of the place, it was highly significant of his desire for revenge on the victorious Prussia of 1870.He’s not only a brilliant and influent gymnast but also a passionate patriot, when in 1884, he joins the Patriot’s league. From 1893 he often stays in Royan, and in 1895 he definitively settles there, in Inferior-Charente, to give a new start to his activities. Closely connected to the network of the local elite interested in the two main projects for the town : the development of Royan into a great seaside resort and the republican achievement of education of the youth, he starts, then, a career as a postcard publisher. From the year 1900, Fernand Braun produces his Great Collection, a catalogue containing thousands of pictures that shows the landscapes of the Charentes and the dailylife of its inhabitants. Being a prodigious success, the postcard reveals to be the first rank medium at the beginning of 20th century. The publisher’s productions bear witness of the environmental and social changes of the region on which Fernand Braun has a very attentive look. However, in the early 1910’s, the dynamism of the Great Collection slows down and its author looks for new openings in the issue of his pictures. By the year 1913, there is a break in his editorial policy and being more influenced by the tourism industry, the man imagines a new way of picturing the surrounding territories. As soon as the Great War breaks out, in 1914, the publisher finds a new motivation,eager to show his contemporaries its consequences. Nevertheless, by 1918, scarcely producing anything else but touristic views, the Great Collection comes to an end in 1920.
43

Využití metody reálného potenciálu zlepšení pro zvýšení efektů investic do informačních technologií / VYUŽITÍ METODY REÁLNÉHO POTENCIÁLU ZLEPŠENÍ PRO ZVÝŠENÍ EFEKTŮ INVESTIC DO INFORMAČNÍCH TECHNOLOGIÍ

Blahanravau, Yauheni January 2009 (has links)
This thesis is dealing with the problematic of relationship between information technology and business, IT and business alignment and the role of CIO in these processes. The further topic I describe in my thesis is the evaluating of the investing projects into information technologies. In connection with this I analyze various financial methods for evaluating of investments in information technologies. The mail goals of this work are: analyze and create a detailed description of modern trends in information technology management and in business and IT alignment, another goal is make comparison of the financial methods and frameworks that help to measure the efficiency of investments in IT and show how these methods can be applied. The further goal is analyze in details the real potential of improvement method and create new set of tools (spreadsheets) for the complex support of this method and show how it can be applied in practice. In the theoretical part of my thesis I focused on the analysis of the role of information technology and CIO in modern organizations and on ways of effective communication of added value to top management of the organization. Analysis is based on the literature review and aimed on searching of skills and knowledge that the modern and successful CIO must have. In this relation were made the analysis of popular financial methods, their comparison and examples how to apply it. Practical part of this work was aimed on the detailed analysis of the real potential of improvement method and how to use it in practice. In this chapter I described the basic principles of this method and created a set of MS Excel tools for better efficiency while using the method of the real potential of improvement. After creation of the tools the practical application of it was shown as an example of improvement of one business process in organization.
44

Studie efektivnosti využití pracovišť ve vybraném provozu / The Study Efficiency of Utilization of Workplacess in Selected Operation

Milota, Tomáš January 2017 (has links)
This thesis deals with the analysis of data obtained by observing and measuring workplaces of assembly lines with a focus on the efficiency of their utilization, through selected elements of industrial engineering, which the reader can get acquainted with in the theoretical part of the thesis. In this thesis the line productivity during the shifts is analyzed, an ideal line balancing condition is defined and suggestion for changing the time of line consumption norm according to the measured line cycle time is made. According to the complex analyzes of the workplaces, suggestions are concluded and an economic appreciation of these proposals is also elaborated. The author of this thesis finds the main benefit of this work in increasing of the productivity of the analyzed line in the case of implementation of solution designs.
45

Le maintien de la cohérence dans les systèmes de stockage partiellement repliqués / Ensuring consistency in partially replicated data stores

Saeida Ardekani, Masoud 16 September 2014 (has links)
Dans une première partie, nous étudions la cohérence dans les systèmes transactionnels, en nous concentrant sur le problème de réconcilier la scalabilité avec des garanties transactionnelles fortes. Nous identifions quatre propriétés critiques pour la scalabilité. Nous montrons qu’aucun des critères de cohérence forte existants n’assurent l’ensemble de ces propriétés. Nous définissons un nouveau critère, appelé Non-Monotonic Snapshot Isolation ou NMSI, qui est le premier à être compatible avec les quatre propriétés à la fois. Nous présentons aussi une mise en œuvre de NMSI, appelée Jessy, que nous comparons expérimentalement à plusieurs critères connus. Une autre contribution est un canevas permettant de comparer de façon non biaisée différents protocoles. Elle se base sur la constatation qu’une large classe de protocoles transactionnels distribués est basée sur une même structure, Deferred Update Replication(DUR). Les protocoles de cette classe ne diffèrent que par les comportements spécifiques d’un petit nombre de fonctions génériques. Nous présentons donc un canevas générique pour les protocoles DUR.La seconde partie de la thèse a pour sujet la cohérence dans les systèmes de stockage non transactionnels. C’est ainsi que nous décrivons Tuba, un stockage clef-valeur qui choisit dynamiquement ses répliques selon un objectif de niveau de cohérence fixé par l’application. Ce système reconfigure automatiquement son ensemble de répliques, tout en respectant les objectifs de cohérence fixés par l’application, afin de s’adapter aux changements dans la localisation des clients ou dans le débit des requête. / In the first part, we study consistency in a transactional systems, and focus on reconciling scalability with strong transactional guarantees. We identify four scalability properties, and show that none of the strong consistency criteria ensure all four. We define a new scalable consistency criterion called Non-Monotonic Snapshot Isolation (NMSI), while is the first that is compatible with all four properties. We also present a practical implementation of NMSI, called Jessy, which we compare experimentally against a number of well-known criteria. We also introduce a framework for performing fair comparison among different transactional protocols. Our insight is that a large family of distributed transactional protocols have a common structure, called Deferred Update Replication (DUR). Protocols of the DUR family differ only in behaviors of few generic functions. We present a generic DUR framework, called G-DUR. We implement and compare several transactional protocols using the G-DUR framework.In the second part, we focus on ensuring consistency in non-transactional data stores. We introduce Tuba, a replicated key-value store that dynamically selects replicas in order to maximize the utility delivered to read operations according to a desired consistency defined by the application. In addition, unlike current systems, it automatically reconfigures its set of replicas while respecting application-defined constraints so that it adapts to changes in clients’ locations or request rates. Compared with a system that is statically configured, our evaluation shows that Tuba increases the reads that return strongly consistent data by 63%.
46

Podpora snapshotu a rollbacku pro konfigurační soubory v distribuci Fedora / Snapshot and Rollback Support for Configuration Files in Fedora

Ježek, Michal January 2008 (has links)
The purpose of this thesis is to design and implement tools for support of a snapshot and a rollback for configuration files on the GNU/Linux distribution. The set of the tools enables an automatic/periodical saving of the configuration files into the selected placement. The creation of backups reacts to file events by watching the changes with kernel subsystem inotify. Tools are enabling to return to the selected backup. The way of the backup actualization is configurable. This tool permits the data comparison from selected backups, to show the differences in configurations and eventually to manage a merge among actual and selected backup. Tools also allows a comparison of a configurations of one client or configurations among clients, and to display the mutual differences, eventually to manage their merge.
47

Viability of Scrum Elements in Mechatronic System Testing : An Exploratory Case Study at Husqvarna AB

Axelsson, Arvid, Ossiansson, Viktor January 2023 (has links)
Mechatronics is an interdisciplinary field of engineering involving components from software engineering, as well as physical components from mechanics and electronics. Development of a mechatronic system requires special interdisciplinary knowledge from multiple fields of engineering. This becomes especially relevant when a mechatronic system is integrated for full system testing, where all the components are combined, and the client-specified use-case requirements are tested. Agile project methods, originally only intended for software engineering, are spreading in the field of mechatronics with positive effect, though there are concerns that such methods cannot be broadly applied to all sub-disciplines of the field or stages of development. A major Swedish mechatronic development firm has begun experimenting with Scrum elements for the system testing department of their products. The purpose of this thesis was to investigate the viability of Scrum elements for system testing of mechatronic products, through an exploratory, qualitative case study. Specifically, we wanted to understand how the use of Scrum elements can benefit mechatronic system testing, and what challenges can emerge. Data collection for our study consisted of semi-structured interviews with members of the chosen system test department, as well as with system test representatives from other mechatronic development firms. The data was transcribed and then analysed using inductive thematic content analysis. The results consisted of four distinct themes, describing the benefits and challenges of using Scrum elements in mechatronic system testing: 1: The Importance and Challenges of Planning, 2: How to Handle Task Prioritisation and Estimation, 3: The Benefits and Challenges of Inter-Departmental Collaboration, and 4: Adjustment of the Scrum Framework. The most significant benefits were found with adopting the incremental Sprint cycle structure, with corresponding Sprint Planning meetings, as well as Sprint Retrospectives. The Daily Scrum meeting was also identified as a useful impediment bulldozer, letting the team refocus efforts on the tasks requiring the most attention. An important challenge identified was learning how to effectively collaborate with other departments in the company who may not be using an Agile framework. A comparison was made between different approaches to adapting the Scrum framework to best fit the needs of your team, concluding that simply picking individual Scrum elements to include in your work structure may yield underwhelming results compared to the combined effect of a complete Scrum framework.
48

Exploring Techniques for Providing Privacy in Location-Based Services Nearest Neighbor Query

Asanya, John-Charles 01 January 2015 (has links)
Increasing numbers of people are subscribing to location-based services, but as the popularity grows so are the privacy concerns. Varieties of research exist to address these privacy concerns. Each technique tries to address different models with which location-based services respond to subscribers. In this work, we present ideas to address privacy concerns for the two main models namely: the snapshot nearest neighbor query model and the continuous nearest neighbor query model. First, we address snapshot nearest neighbor query model where location-based services response represents a snapshot of point in time. In this model, we introduce a novel idea based on the concept of an open set in a topological space where points belongs to a subset called neighborhood of a point. We extend this concept to provide anonymity to real objects where each object belongs to a disjointed neighborhood such that each neighborhood contains a single object. To help identify the objects, we implement a database which dynamically scales in direct proportion with the size of the neighborhood. To retrieve information secretly and allow the database to expose only requested information, private information retrieval protocols are executed twice on the data. Our study of the implementation shows that the concept of a single object neighborhood is able to efficiently scale the database with the objects in the area. The size of the database grows with the size of the grid and the objects covered by the location-based services. Typically, creating neighborhoods, computing distances between objects in the area, and running private information retrieval protocols causes the CPU to respond slowly with this increase in database size. In order to handle a large number of objects, we explore the concept of kernel and parallel computing in GPU. We develop GPU parallel implementation of the snapshot query to handle large number of objects. In our experiment, we exploit parameter tuning. The results show that with parameter tuning and parallel computing power of GPU we are able to significantly reduce the response time as the number of objects increases. To determine response time of an application without knowledge of the intricacies of GPU architecture, we extend our analysis to predict GPU execution time. We develop the run time equation for an operation and extrapolate the run time for a problem set based on the equation, and then we provide a model to predict GPU response time. As an alternative, the snapshot nearest neighbor query privacy problem can be addressed using secure hardware computing which can eliminate the need for protecting the rest of the sub-system, minimize resource usage and network transmission time. In this approach, a secure coprocessor is used to provide privacy. We process all information inside the coprocessor to deny adversaries access to any private information. To obfuscate access pattern to external memory location, we use oblivious random access memory methodology to access the server. Experimental evaluation shows that using a secure coprocessor reduces resource usage and query response time as the size of the coverage area and objects increases. Second, we address privacy concerns in the continuous nearest neighbor query model where location-based services automatically respond to a change in object*s location. In this model, we present solutions for two different types known as moving query static object and moving query moving object. For the solutions, we propose plane partition using a Voronoi diagram, and a continuous fractal space filling curve using a Hilbert curve order to create a continuous nearest neighbor relationship between the points of interest in a path. Specifically, space filling curve results in multi-dimensional to 1-dimensional object mapping where values are assigned to the objects based on proximity. To prevent subscribers from issuing a query each time there is a change in location and to reduce the response time, we introduce the concept of transition and update time to indicate where and when the nearest neighbor changes. We also introduce a database that dynamically scales with the size of the objects in a path to help obscure and relate objects. By executing the private information retrieval protocol twice on the data, the user secretly retrieves requested information from the database. The results of our experiment show that using plane partitioning and a fractal space filling curve to create nearest neighbor relationships with transition time between objects reduces the total response time.
49

Underwater Use of a Hyperspectral Camera to Estimate Optically Active Substances in theWater Column of Freshwater Lakes

Seidel, Michael, Hutengs, Christopher, Oertel, Felix, Schwefel, Daniel, Jung, András, Vohland, Michael 21 April 2023 (has links)
Freshwater lakes provide many important ecosystem functions and services to support biodiversity and human well-being. Proximal and remote sensing methods represent an efficient approach to derive water quality indicators such as optically active substances (OAS). Measurements of above-ground remote and in situ proximal sensors, however, are limited to observations of the uppermost water layer. We tested a hyperspectral imaging system, customized for underwater applications, with the aim to assess concentrations of chlorophyll a (CHLa) and colored dissolved organic matter (CDOM) in the water columns of four freshwater lakes with different trophic conditions in Central Germany. We established a measurement protocol that allowed consistent reflectance retrievals at multiple depths within the water column independent of ambient illumination conditions. Imaging information from the camera proved beneficial for an optimized extraction of spectral information since low signal areas in the sensor’s field of view, e.g., due to non-uniform illumination, and other interfering elements, could be removed from the measured reflectance signal for each layer. Predictive hyperspectral models, based on the 470 nm–850 nm reflectance signal, yielded estimates of both water quality parameters (R² = 0.94, RMSE = 8.9 µg L−1 for CHLa; R² = 0.75, RMSE = 0.22 m−1 for CDOM) that were more accurate than commonly applied waveband indices (R² = 0.83, RMSE = 13.2 µg L−1 for CHLa; R² = 0.66, RMSE = 0.25 m−1 for CDOM). Underwater hyperspectral imaging could thus facilitate future water monitoring efforts through the acquisition of consistent spectral reflectance measurements or derived water quality parameters along the water column, which has the potential to improve the link between above-surface proximal and remote sensing observations and in situ point-based water probe measurements for ground truthing or to resolve the vertical distribution of OAS.
50

Investigation of the genetic aetiology of aminoglycoside-induced hearing loss in South African populations

Human, Hannique 12 1900 (has links)
Thesis (MScMedSc (Biomedical Sciences. Molecular Biology and Human Genetics))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: South Africa is currently facing a major multidrug-resistant tuberculosis (MDR-TB) epidemic and has one of the highest incidences in the world. Aminoglycoside antibiotics are commonly used in this country as a treatment against MDR-TB. A well known side-effect of aminoglycosides is permanent hearing loss and this is thought to have a significant genetic component. To date, at least six mutations in the mitochondrial genome are known to confer susceptibility to aminoglycosideinduced hearing loss. It is imperative that we investigate the frequency of these mutations in our populations and determine whether certain sub-groups are at increased risk. The aim of the present study was therefore to investigate the genetic aetiology of aminoglycoside-induced hearing loss in the South African population. A multiplex method using the ABI Prism® SNaPshotTM Multiplex system was optimised to screen for six mutations in the MT-RNR1: A1555G, C1494T, T1095C, 961delT+C(n), A827G and T1291C. A total of 115 MDR-TB patients from the Brooklyn Chest Hospital in Cape Town who were receiving high doses of either streptomycin, kanamycin or capreomycin were recruited for this study. Furthermore, 439 control samples, comprising of 93 Afrikaner, 104 Caucasian, 112 Black and 130 Mixed Ancestry individuals were recruited and screened for the presence of the six mutations. Identification of novel variants in the MT-RNR1 and the entire mitochondrial genome was performed using High Resolution Melt analysis (HRM) and whole mitochondrial DNA sequencing, respectively. A total of 97 family members from a South African family known to harbour the A1555G mutation were recruited and genotyped using SNaPshot analysis. In addition, mitochondrial functioning in the presence of different streptomycin drug concentrations, in transformed lymphoblasts of an individual harbouring the A1555G, was assessed by means of the MTT colorimetric assay. Detection of heteroplasmic mutations was performed using PCRRestriction Fragment Length Polymorphism (RFLP) analysis and UN-SCAN-IT software. We successfully developed a robust and cost-effective method that detects the presence of all six mutations simultaneously. The method worked equally well on both blood (from adults) and buccal swabs (from children). The C1494T, T1095C and T1291C mutations were not detected in any of the MDR-TB or control groups. Alarmingly, the A1555G mutation was detected in 0.9% of the Black control samples and in 1.1% of the Afrikaner controls (in one sample in the heteroplasmic state 25%). The A827G mutation was present at a frequency of 0.9% in the MDR-TB patients and in 1.1% of the Afrikaner controls. The 961delT + insC(n) mutation was found in relatively high frequencies in both the MDR-TB patients (3.5%) and control groups (1.1% of the Afrikaner, 1.5% of the Mixed Ancestry and 7.1% of the Black samples). Similarly, the T961G mutation was III detected at high frequencies in the Caucasian (2.9%) and Afrikaner (3.2%) controls. Screening for novel variants in MT-RNR1 in MDR-TB patients experiencing ototoxicity revealed two novel variants (G719A and T1040C). However, G719A and T1040C are not likely to be pathogenic since they were detected in ethnic-matched controls: Mixed Ancestry (20.7%) and Black (1.8%) controls. Furthermore, a total of 50 novel variants were identified within the mitochondrial genome of eight MDR-TB patients with ototoxicity. Only five of the 50 variants (one in the MT-TH, ND3, COX3 and two in the CYTB gene) were shown to reside at positions that are evolutionarily conserved across five species from human to frog, and the four variants in the protein coding genes resulted in missense changes. A total of 76 of the 97 family members recruited were found to be A1555Gpositive (on mitochondrial haplogroup L0d) and are therefore at risk of developing irreversible hearing loss. Genes and variants known to act as genetic modifiers: tRNASer(UCN), homozygous A10S in TRMU and 35delG in GJB2 were not present in this family. For the MTT assay, decreased mitochondrial functioning of cells harbouring the A1555G mutation in the presence of streptomycin were (compared to wild type) observed but this was not statistically significant (p-value: 0.615- 0.999). The high frequency of the A1555G mutation (0.9%) in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. However, future studies with larger numbers of samples are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. Our data suggests that the 961delT + insC(n) and T961G variants are common non-pathogenic polymorphisms due to the high frequencies observed in controls (>1%). The identification of the first novel variants within protein coding genes that could possibly be associated with aminoglycoside-induced hearing loss holds great possibilities with regards to the identification of a second gene involved in drug induced hearing loss. Future studies where the possible effect of these variants on the normal functioning of these genes could be assessed would contribute greatly to this field of research. All 76 A1555Gpositive members of the family were given genetic reports and counseled about their risk and that of their children for developing hearing loss due to aminoglycoside use. The development of a rapid and cost-effective genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is of critical important in a low-resource country like South Africa where, despite their adverse sideeffects, aminoglycosides will be continue to be used routinely and are accompanied with very limited or no audiological monitoring. Future studies and greater public awareness is therefore needed to address this serious problem. / AFRIKAANSE OPSOMMING: Suid Afrika beleef tans „n grootskaalse tuberculose epidemie (veral weerstandige vorme van tuberculose) (MDR-TB), met een van die hoogste voorkomssyfers in die wêreld. Aminoglikosied antibiotikums word baie algemeen gebruik in Suid Afrika vir die behandeling van MDR-TB. ‟n Bekende newe effek van die middels is permanente gehoor verlies en dit is van mening dat dit gekoppel is aan „n genetiese component. Daar is tans ses mutasies in die mitochondriale genoom wat vatbaarheid tot aminoglikosied-geinduseerde gehoor verlies veroorsaak. Daarom is dit van uiterse belang dat die frekwensie van die mutasies in ons populasies bepaal word sodat daar vasgestel kan word watter groepe „n hoë risiko het om gehoor verlies te kan ontwikkel. Die ABI Prism® SNaPshotTM Multipleks sisteem is gebruik en geoptimiseer om te toets vir die ses mutasies in die MT-RNR1: C1494T, T1095C, 961delT+C(n), A827G and T1291C. „n Totaal van 115 MDR-TB pasiente van die Brooklyn Chest Hospital in Kaap Stad is gewerf vir die studie. Hierdie pasiente ontvang daaglikse hoë dosese van een van die volgende aminoglikosiede: streptomycin, kanamycin of capreomycin. Verder is „n totaal van 439 kontrole DNA monsters gewerf vanuit die volgende etniese groepe: 93 Afrikaner, 104 Blank, 112 Swart and 130 Kleurling. Hierdie monsters is ook getoets vir die ses mutatsies. Hoë Resolusie Smelt analise (HRS) is gebruik om nuwe DNS volgorde veranderinge in die MT-RNR geen te identifiseer. Die hele mitochondriale genoom is blootgestel aan DNA volgorde bepaling in „n poging om nuwe DNS volgorde verandering in die genoom te identifiseer wat moontlik betrokke kan wees by aminoglikosied-geinduseerde gehoor verlies. „n Total van 97 lede van „n Suid Afrikaanse familie waar die A1555G mutasie teenwoordig is, is deur middle van die SNaPshot metode gegenotipeer. Verder is die normale funcitoneering van die mitochondrion in getransformeerde witbloed selle, getoets in die teenwoordigheid van verskillende konsentrasies streptomycin met behulp van die MTT kleurmetrie toets. Deteksie van heteroplasmiese mutasies is gedoen deur middle van die PCR-RFLP tegniek en alle analises is gedoen op die UN-SCAN-IT program. Ons was suksesvol in die ontwikkeling van „n vinnige, koste effektiewe en kragtige tegniek wat al ses die mutasies in MT-RNR1 in een reaksie kan optel. Hierdie tegniek het goed gewerk met DNA monsters van bloed en van selle verkry vanuit die wangholte (geneem van kinders jonger as 12 jaar). Die C1494T, T1095C en T1291C mutasies is glad nie waargeneem in enige van ons MDR-TB patiente of kontroles nie. Skrikwekkend is die hoë frekwensie (0.9%) waarby die A1555G mutasie in die Swart kontrole groep waargeneem is. Hierdie mutasie is ook in 1.1% van die Afrikaner kontrole groep opgemerk in heteroplasmie van 25%. Die A827G mutasie was teenwoordig in 0.9% en 1.1% van die MDR-TB patiente en Afrikaner kontrole monsters, onerskeidelik. Die 961delT + insC(n) mutasie is opgemerk in baie hoë frekwensies in beide die MDR-TB (3.5%) en kontrole groepe (1.1% van die Afrikaner, 1.5% van die Kleurling en 7.1% van die Swart monsters). Die T961G mutasie is ook in hoë frekwensies in slegs die Blanke (2.9%) en die Afrikaner (3.2%) kontrole groepe waargeneem. Nuwe DNS volgorde veranderinge in MT-RNR1 is gesoek in „n groep MDR-TB patiente wat gehoor verlies ondervind. Slegs twee nuwe verandering is ontdek (G719A en T1040C). Dit is onwaarskynlik dat hierdie veranderinge patogenies is siende dat hulle teen frekwensies van 20.7% en 1.8% waargeneem is in die Kleurling en Swart kontrole groepe onderskeidelik. Tydens die soeke na nuwe DNS volgorde veranderinge wat moontlik geassosieer is met aminoglikosied-geinduseerde gehoor verlies in die mitochondriale genoom is 50 onbekende veranderinge ontdek (een in die MT-TH, ND3, COX3 en twee in die CYTB gene). Die veranderinge is verder ondersoek vir evolusionêre konservasie op beide die nukliotied en amino suur vlak van mens to padda. Dit is bevind dat 76 uit die 97 familie lede positief is vir die A1555G mutasie en het dus „n hoë risiko om aminoglikosied-geinduseerde gehoor verlies te ontwikkel as hul bloot gestel word aan hierdie antibiotikums. Verder is gevind dat hierdie familie op die L0d mitochondriale haplogroep lê. Geen van die sogenaamde genetiese modifiseerde gene of DNS volgorde veranderinge in hierdie gene (tRNASer(UCN), A10S in TRMU in homosigotiese vorm en die 35delG in GJB2) is gevind in die familie nie. Die MTT toets het „n afname in die mitochondriale funksioneering van selle waar die A1555G mutasie teenwoordig was getoon, alhoewel die verskil tussen selle wat nie die A1555G mutasie het nie, nie statisties betekenisvol was nie (p-waarde: 0.615-0.999). Die hoë frekwensie van die A1555G mutasie (0.9%) in die Swart populasie van Suid Afrika is skrikwekkend siende dat die voorkomssyfer van MDR-TB in hierdie groep baie hoog is. Toekomstige studies met grooter getalle is nodig om die ware frekwensie van die mutasies geassosieer met aminoglikosied-geinduseerde gehoor verlies in die algemende Suid Afrikaanse populasie te bepaal. Ons data dui aan dat die 961delT + insC(n) en die T961G mutasies slegs algemene nie-patogeniese polimorphismis is siende dat dit in sulke hoë frekwensies (>1%) in kontroles opgemerk is. Die identifiseering van die eerste DNS volgorde veranderinge in proteïen kodeerende gene wat moontlik geassosieer is met aminoglikosied-geinduseerde gehoor verlies hou groot en belowende moontlikehede in, interme van die identifiseering van „n tweede geen. Toekomstige studies waarin die effek van hierdie veranderinge op die normale funktioneering van hierdie gene ondersoek word sal „n besondere groot bydrae lewer tot hierdie veld van navorsing. Al 76 van die A1555G positiewe familie lede is voorsien van genetiese verslae en het berading ontvang in verband met hul risiko en die risiko van hul kinders om aminoglikosied-geinduseerde gehoor verlies te ontwikkel. Die ontwikkeling van „n kragtige, vinnige en koste-effektiewe genetiese metode vergemaklik die vinnige identifiseering van hoë risiko individue vir die ontwikkeling van gehoor verlies voordat hulle met hul aminoglikosiede behandeling begin. Dit is veral noodsaaklik in „n derde wêreld land soos Suid Afrika waar, ten spyte van hul gevaarlike newe effekte, aminoglikosied antibiotikums steeds gebruik sal word. Daarom is grooter publieke bewusmaking nodig om hierdie problem te probeer oplos en te verhoed.

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