Tesis sobre el tema "BCOM"

These studies have focused on identifying the mathematical requirements of first-year BCom students at Nelson Mandela Metropolitan University. The research methodology used in this quantitative study was to make use of interviewing, questionnaire investigation, and document analysis in the form of textbook, test and examination analysis. These methods provided data that fitted into a grounded theory approach. The study concluded by identifying the list of mathematical topics required for the first year of the core subjects in the BCom degree programme. In addition, the study found that learners who study Mathematics in the National Senior Certificate should be able to cope with the mathematical content included in their BCom degree programme, while learners studying Mathematical Literacy would probably need support in some of the areas of mathematics, especially algebra, in order to cope with the mathematical content included in their BCom degree programme. It makes a valuable contribution towards elucidating the mathematical requirements needed to improve the chances of successful BCom degree programme studies at South African universities. It also draws the contours for starting to design an efficient support course for future “at-risk” students who enter higher education studies.

Hierdie studie fokus op positief sielkundige konstrukte soos veerkragtigheid as positiewe krag en die sterk invloed daarvan op alle vlakke van uitbranding. Die studie neem die standpunt in dat dit belangrik is om ondersoek in te stel na die invloed van positiewe konstrukte en die invloed daarvan op die lewens van mense. Verder bied die studie meer spesifieke insig rakende die faktore wat studente in staat stel om bo algemene akademiese en persoonlike uitdagings uit te styg en te floreer. Die doel van die studie was om die verband tussen veerkragtigheid en uitbranding te bepaal, en verder om ondersoek in te stel rakende die vraag of daar verskille bestaan met betrekking tot ras, geslag, jaar van studie, beskouing van akademiese prestasie, persepsies rakende werkslading en tevredenheid met prestasie. Data is ingesamel deur elektroniese opnames per e-pos uit te stuur aan voorgraadse studente aan die Universiteit van Pretoria (UP) deur gebruik te maak van die Universiteit se Qualtrics-sisteem. ? Totaal van (n=361) studente het deelgeneem aan die studie. Die studie het gebruik gemaak van bevestigende faktorontleding om die teoretiese strukture van konstrukte te evalueer. Strukturele vergelykingsmodellering (SVM) is gebruik om beide meervoudige regressie ("multiple regression"), en bevestigende faktorontleding te kombineer. Die aard van verhoudinge tussen veranderlikes is met behulp van SVM verduidelik. Die resultate toon dat die passing van beide modelle aanvaarbaar is nadat sekere items verwyder is. Verder toon resultate dat daar nie ? betekenisvolle verband bestaan tussen veerkragtigheid en uitbranding nie en dat slegs die dimensie van vasberadenheid ? statisties betekenisvolle negatiewe verwantskap met uitbranding toon (b4=?0.614, p<0.01 en ?=0.01). Resultate toon betekenisvolle verskille met betrekking tot geslag, beskouing van akademiese prestasie, persepsies rakende werkslading, asook tevredenheid met akademiese prestasie. Met betrekking tot etnisiteit en jaar van studie was daar geen betekenisvolle verskille in veerkragtigheid of uitbranding nie.
Mini Dissertation (MCom)--University of Pretoria, 2015.
Human Resource Management
MCom
Unrestricted

This thesis deals with possible interconnections between two concepts playing a big role in contemporary business and IT world. These concepts are Business Continuity Management and Cloud Computing. In the scope of this thesis there are certain areas identified where both concepts are complement, where Cloud Computing brings new opportunities for Business Continuity Management and where could possible problems arise during particular implementation. From the BCM perspective the impact lies on IT services, from the Cloud Computing perspective the thesis deals especially with security aspects. The thesis is also aimed at the characteristics of higher education and basic differences from commercial sphere. Based on defined differences and identified interconnections between BCM and Cloud Computing, the thesis argues for usage of suitable Cloud Computing solution for higher education regarding Business Continuity improvement. The multi-criterion comparison of several Infrastructure-as-a-Service solutions stems from this analysis focusing on technical, financial, and Business Continuity aspects. The result from this comparison together with conclusions from previous chapters serve as an input for subsequent practical proposal of Cloud Computing solution and its verification against Business Continuity improvement in specific conditions on University of Economics in Prague. The proposal is also represented by strategic map.

In ambito di ricerca (clinica e sportiva), la necessità di sviluppare un approccio ‘multilaterale’ (qualitativo e quantitativo) che caratterizzi matematicamente la traiettoria tri-dimensionale di una variabile fisica assolutamente importante ma spesso dimenticata, quale il centro di massa corporeo (CMC) (ovvero, il punto immaginario assimilabile al corpo umano in cui si suppone che tutte le masse corporee stiano concentrate), diviene oggi sempre più impellente e quanto mai urgente. Pertanto l’obiettivo di questo dottorato, perseguito tramite un differente utilizzo delle classiche metodologie biomeccaniche, è rappresentare le grandezze cinematiche che descrivono il movimento dei segmenti corporei e del suddetto CMC nel tempo e nello spazio. Per conseguire questo traguardo si sono pensati e realizzati due diversi progetti. Con il primo progetto si sono previsti: a) lo sviluppo di un metodo matematico quantitativo (Serie di Fourier) per descrivere e rappresentare graficamente la traiettoria tri-dimensionale del CMC durante la locomozione su treadmill (la cosiddetta Impronta Digitale Locomotoria, specifica per soggetto/popolazione); b) la caratterizzazione della simmetria nella traiettoria del CMC (il cosiddetto Indice di Simmetria); infine, c) la costituzione di un database di valori normali (coefficienti di equazioni) in un insieme piuttosto esteso di condizioni, al variare di sesso (maschi versus femmine), età (dai 6 ai 65 anni), tipologia di locomozione (marcia versus corsa), velocità e pendenza (piano, salita e discesa). Questo database iniziale rappresenta il parametro principale di riferimento per la locomozione sana. Attraverso questo studio è stato ampiamente dimostrato che la locomozione umana risulta genericamente asimmetrica. Nello specifico: 1) tra maschi e femmine non si sono riscontrate differenze significative; 2) indipendentemente da età e pendenza, le velocità più basse, meno naturali e comuni, sono caratterizzate da pattern di Impronte Digitali Locomotorie più variabili. Viceversa, un aumento di velocità è accoppiato con un progressivo e continuo innalzamento del CMC; 3) l’asimmetria destra e sinistra del passo è molto probabilmente correlata sia con l’anatomia (lunghezza della gamba) che con la predominanza dell’arto; in linea con l’ipotesi iniziale, 4) mediamente, la corsa è più asimmetrica della marcia; infine, 5) i bambini e gli anziani presentano maggiori asimmetrie (marcia e corsa): questo è dovuto alla progressiva maturazione del ciclo del cammino (nei bambini) ed alle caratteristiche muscolari e scheletriche dell’apparato locomotore (negli anziani). Pertanto, attraverso una caratterizzazione matematica della traiettoria tri-dimensionale del CMC, si è potuto: a) quantificare il suo spostamento nel tempo e nello spazio; b) individuare l’Impronta Digitale Locomotoria specifica di sesso, età, tipologia di locomozione, velocità e pendenza. Questo importante traguardo permetterà, in un immediato futuro, la comparazione con la situazione di normalità di condizioni di locomozione compromessa o impedita (ad esempio, bambini con paralisi cerebrale infantile, obesi e amputati). Infine, la stima della principali variabili biomeccaniche è risultata fondamentale sia nel descrivere la meccanica di marcia e corsa che nel caratterizzarne la corrispondente impronta locomotoria. Le nostre misure di tali variabili (semplici e complesse), ottenute con metodo discreto (ciclo per ciclo), con l’impiego di una funzione matematica continua (Serie di Fourier) e con l’applicazione di un’equazione predittiva (misura indiretta), soddisfano completamente ed addirittura ampliano la letteratura già esistente. Nel secondo progetto, partendo da uno studio sulla performance dei cavalli, si è cercato di verificare se esiste una correlazione tra simmetrie corporee (statiche e dinamiche) ed economia nella corsa anche in corridori umani variamente allenati (classificati in tre gruppi sulla base del loro miglior tempo nella maratona). Inoltre: a) si sono sviluppati metodi di analisi bi- e tri-dimensionale delle Risonanze Magnetiche per Immagini (regione pelvica ed arti inferiori), impiegate come riferimento per le simmetrie statiche; b) attraverso sia l’Impronta Digitale Locomotoria che l’Indice di Simmetria si sono caratterizzate le simmetrie dinamiche; infine c) l’economia della corsa è stata espressa attraverso il suo reciproco, ovvero il costo metabolico. L’analisi sia bi- che tri-dimensionale delle immagini ha evidenziato differenze davvero esigue in base al livello di allenamento. Positivamente ed indipendentemente dai corridori, si è dimostrato che ad una maggiore simmetria nella regione del ginocchio corrisponde una maggiore simmetria nella regione della caviglia. Inoltre l’analisi delle simmetrie dinamiche ha permesso di osservare che: 1) il CMC si solleva leggermente in funzione della velocità; 2) le asimmetrie destre e sinistre del passo sono principalmente marcate lungo la direzione di movimento e, contemporaneamente, ridotte lungo la direzione verticale. Esse sono strettamente dipendenti dall’anatomia e dall’arto dominante; 3) diversamente da quanto ci si aspettava, sono state comunque evidenziate solamente poche differenze tra i corridori. Negativamente, l’economia della corsa non mostra differenze significative tra i gruppi testati. Perciò, diversamente dall’ipotesi iniziale, non è stata evidenziata l’esistenza di alcuna relazione tra le simmetrie corporee e l’economia della corsa, quanto piuttosto solo la presenza di una discreta variabilità in simmetria statica e dinamica. Infine, l’analisi di bioenergetica (treadmill versus pista) e biomeccanica (variabili semplici/complesse e variabilità spazio/temporale del CMC) della corsa ha evidenziato la presenza solamente di poche differenze dovute al livello di allenamento dei soggetti studiati.
In both research laboratory and sport/clinical settings, it becomes very important to develop a ‘multilateral approach’ (qualitative and quantitative) to fully describe the individual behaviour of the centre of mass of the human body (BCOM) (i.e. the imaginary specific point at which the body behaves as if its masses were concentrated) over time and space. Consequently, the aim of this doctorate is to describe kinematic variables of the BCOM in varying locomotion conditions. This purpose, focusing on the BCOM as the investigation object fulfilling such a need, has been achieved through a different use of classic biomechanical procedures. In effect, two different studies were carried out. The first project sought: a) to develop a mathematical method (Fourier Series) which could describe and graphically represent each individual (subject or population) gait signature (i.e. Digital Locomotory Signature, a global index of the BCOM dynamics) during locomotion on a treadmill; b) to assess the symmetry (i.e. Symmetry Index) in each movement direction, along the BCOM trajectory, between the two stride phases; finally, c) to build up an initial comprehensive database of ‘healthy values’ (equation coefficients) in a set of different conditions considering gender (males versus females), age (from 6 to 65 years), gait (walking versus running), speed and gradient (level, uphill and downhill). Although only slight gender differences were found, human ‘healthy’ gait is rather asymmetrical. To be precise: 1) the lowest speeds have the most peculiar signature independently of age and gradient: indeed, these speeds are not so completely natural and common. However, if speed increases, the BCOM raises in such a way that its corresponding 3D contour becomes more regular; 2) right and left sides of the stride are quite asymmetrical (i.e. in the forward direction). Globally, this asymmetry is probably related both to anatomy (i.e. leg length) and which hand you use (i.e. right-handedness); 3) on average, the symmetry pattern is slightly lower in running gaits; and as expected, 4) young children and elderly adults are the most asymmetrical subjects, independently of testing conditions: while, during the early stages of life, this global asymmetry could be ascribed to the process of gait development, old age asymmetries are probably due to structural wearing down of the musculoskeletal system. Importantly, the mathematical methodology used here, by analysing even subtle changes in the 3D BCOM trajectory: a) characterizes its displacements over both time and space; b) quantitatively describes the individual gait signature; and c) represents the basis for the evaluation of gait anomaly/pathology (e.g. children with cerebral palsy, obese people and amputees). Finally, knowing the main biomechanical variables becomes fundamental both to fully describe the mechanics of walking and running and to extract and characterize the individual gait signature. In effect, our measurements (discrete method versus continuous mathematical function, and direct versus indirect measurement) of both simple and complex variables wholly confirm, complete and amplify previous literature data. Similarly to what previously demonstrated in horse performances, the second project tried: a) to verify both static anatomical and kinematic functional symmetries as important and relevant indicators of running economy (i.e. the reciprocal of metabolic cost) in humans featuring different running levels (i.e. occasional, skilled and top runners categorized primarily upon their best marathon time); b) to develop imaging based bi- and three-dimensional methods to analyse static symmetries recorded by Magnetic Resonance Imaging (lower limbs and pelvic area); c) to describe the kinematic symmetries defining both the Digital Locomotory Signature and the Symmetry Index; finally, d) to investigate running economy as a performance determinant. In effect, both the 2D/3D analysis of static symmetries highlight very few differences among runners; however, a strong relationship between ankle and knee areas has been underlined in all runners. Furthermore, independently of training ability: as expected, 1) the BCOM raises and lifts slightly as a function of running speed; 2) right and left steps are mostly asymmetrical in the forward direction and symmetrical in the vertical direction (i.e. combined action of gravity and ground reaction force); 3) differently to what was expected, slight differences have been found among runners. On the whole, the asymmetry is probably related both to anatomy and handedness. Other than that, no running economy differences were found. In conclusion, while a relationship between symmetries and running economy has not been found, significant results have however been underlined in each trial (static and dynamic symmetries). Finally, the deep investigation of both bioenergetics (treadmill versus over-ground) and biomechanics (simple/complex variables and spatial/temporal variability of the BCOM) of running has highlights only little (significant) differences among groups.

The transition period post-apartheid in South Africa since 1994 brought a number of changes in policy making process and the initiated programs by the government in all level with the aim of addressing inequality and poverty reduction strategies. In South Africa prior 1994 division in terms of location access to resources and information was meant for the certain group and participation in the Community development matters. The aim of this research study is to seek and find out the impact of the government policy projects, programme (strategies) in the community to poverty reduction and try to identify the reasons for the failure of other project and to what extend is the capacity building in community members in terms of skill development before the implementation of projects for sustainability and viability of those projects. Also is to explore the community participation or involvement in policy making process such as the formulation of Integrated Development Plan .The study attempts to answer community involvement into their own development, their role and impact to fight poverty and other socio-economic challenges that are faced by the community. The research design for the study could be classified as the mixed design which will include qualitative and quantitative approaches. A sample of 30 participants will be drawn from the community unemployed respondents, project employees, those searching for employment, 5 municipality officials from Blue Crane Route, Ward Councillor and projects leaders. On my findings community participation on community development issues must be strengthen for the sake of development .The issue of centralisation of offices for availability of resources to same of the communities makes it difficult to access resources. Lack of skills and training acquired in the job market for artisans, technical and management skills.

Enterprises during their operation are impacted many threats and risks that could dramatically affect their business. Business Continuity Management has evolved to provide resistance against the eternal operational risks. BCM aims to ensure business continuity in case of its danger. The goal of this thesis is to apply the selected methods of the BCM into emergency planning, which is regulated by legislatively for businesses in the Czech Republic.

The RBF strategy has successfully produced fungal mycelial biomass and EPS in a very strictly regulated manner at high productivity rates compared to batch fermentation. The problematic lag phase and seed culture preparation were reduced in length; harvesting volume doubled, yield of product increased, and medium consumption was reduced in an RBF relative to batch. 80% broth replacement volume and transition phase were optimised. Dispersed mycelial filaments with ovoid-shaped pellets are the typical morphological characteristics associated with EPS production. N-limiting medium in an unbaffled 2.5-L bioreactor stimulated EPS formation during RBF compared to in baffled condition. The current study has managed to alter the molecule's hydrophobicity thus making it water-soluble as proved by compositional analysis and spectroscopy. The sulphated derivative of native glucan was identified as (1, 3)-(Sb(B-D-glucan. Sulphation was an effective approach to improve antibacterial, antifungal, antiproliferative and immunomodulatory (NO stimulation) activity of the sulphated (1,3)-(Sb(B-D-glucan or GS. GS maybe safe in in vitro trials due to its demonstrated lack of toxicity towards a normal human prostate cell line (PN2TA). GS also showed antimicrobial-antifungal-immunomodulatory activities derived from a single compound. Fungal cells tended to grow well in the porous structure of PUF cubes and the RBF using immobilised fungal cells was an efficient method for production of (Sb(B-glucan with a high yield. This study could be beneficial for other medicinal mushroom fermentation.

In questa tesi viene illustrato il modello BCM, formulato nel 1982 con l'intento di spiegare il fenomeno di apprendimento neuronale, definito come "plasticita sinaptica". Si passa successivamente ad una descrizione dettagliata del comportamento di un singolo neurone, per poi estendere la trattazione alle reti neuronali. L'esposizione degli argomenti viene effettuata considerando cellule esposte a distribuzioni di input linearmente indipendenti. Viene proposto infine un metodo per adattare il modello al caso linearmente dipendente.

Coronavírus bovino (BCoV) é o agente causador de doença, tanto entérica como respiratória em bovinos, mas até agora existem controvérsias sobre a relação genealógica entre as amostras de BCoV em diferentes tecidos. Neste estudo, amostras de fezes e secreções nasais de 14 vacas de um mesmo rebanho apresentando simultaneamente disenteria epizoótica e doença respiratória foram estudados quanto a presença de BCoV. As amostras virais detectadas tiveram tanto o gene de espícula (S) como o gene hemaglutinina-esterase (HE) parcialmente sequenciados. Para o gene HE, foram obtidas 12 sequências de secreções nasais e 12 de amostras de fezes e para o gene S, foram obtidas 14 sequências de secreções nasais e 12 de amostras de fezes, com 100% de identidade nucleotídica para cada gene para as amostras deste estudo. Estes resultados apresentam algumas divergências com estudos anteriores os quais relatam que linhagens diferentes de BCoV podem ser esperados em casos de disenteria e doença respiratória em vacas, pois linhagens com sequências idênticas dos genes S e HE podem não mostrar diferenças em relação tropismo pelos diferentes tecidos. Sequências completas de duas amostras brasileiras de BCoV mostram que o já descrito padrão filogeográfico baseado no sequenciamento do gene S parcial foi mantido, foram encontradas substituições de aminoácidos específicos.
Bovine coronavirus (BCoV) is the causative agent of both enteric and respiratory disease in cattle, but hitherto there were some controversy on the genealogic relationship amongst strains from these different tissues. In this study, samples of feces and nasal secretions of 14 cows from a same herd simultaneously presenting epizootic dysentery and respiratory disease were screened for BCoV and the strains detected had both the spike (S) and hemagglutinin-esterase (HE) genes partially sequenced. For HE gene, 12 sequences from nasal secretions and 12 from fecal samples were obtained and for S gene, 14 sequences from nasal secretions and 12 from fecal samples were obtained, with 100% nucleotide identities for each gene for the strains of this study. These results have some disagreements with previous reports which try to put forward that divergent BCoV strain should be expected in cases of dysentery and respiratory disease in cows, showing that strain with identical S and HE sequences might show no differences in tropisms. Complete S gene sequences of two Brazilian BCoV strains show that the already described phylogeographic pattern based on partial S gene is sustained, though specific amino acids subtitutions are found.

Les phénomènes d'adhérence entre les globules rouges (GR) drépanocytaires et la paroi vasculaire interviennent dans la physiopathologie des accidents d'ischémie-reperfusion caractéristiques de la maladie. Parmi les molécules d'adhérence, Lu/BCAM est le seul ligand érythrocytaire de la laminine. Cependant aucune étude n'a montré son implication dans les manifestations cliniques de la drépanocytose. Enfin, l'effet de l'hydroxycarbamide (HC) sur la fonction de Lu/BCAM n'a pas été étudié. Nous avons montré que l'adhérence des GR drépanocytaires à la laminine est augmentée au cours des crises vaso-occlusives sévères et chez les patients ayant des atteintes viscérales sévères à l'état basai. Les patients traités par l'HC ont une adhérence diminuée. Il existe une augmentation paradoxale de Lu/BCAM sous HC. Cependant l'HC diminue la phosphorylation de Lu/BCAM dans les GR de façon parallèle à la diminution d'adhérence. Cette diminution de phosphorylation est liée à l'inhibition d'une voie d'activation PKA/AMPc dépendante. Nous avons confirmé cette diminution d'adhérence et de phosphorylation sous HC dans un modèle cellulaire érythroleucémique (K562). Enfin nous avons montré que la voie d'activation de Lu/BCAM par phosphorylation était presque exclusivement présente dans les réticulocytes. Ce travail montre pour la première fois que la fonction d'adhérence de Lu/BCAM à la laminine est corrélée à la gravité clinique. D'autre part il démontre l'action de l'HC sur l'inhibition de la fonction d'adhérence de Lu/BCAM, par un mécanisme distinct de l'expression de l'hémoglobine fœtale, ouvrant ainsi de nouvelles perspectives thérapeutiques
Sickle cell disease is characterized by painful vaso-occlusive crises during which abnormal interactions between erythroid adhesion molecules and vesselwall proteins are thought to play a critical role. Hydroxyurea, the only drug with proven benefit in sickle cell disease, diminishes these interactions, but its mechanism of action is not fully understood. We report that, under hydroxyurea, expression of the unique erythroid laminin receptor Lu/BCAM was increased, but red blood cell adhesion to laminin decreased. Because Lu/BCAM phosphorylation is known to activate cell adhesion to laminin, it was evaluated and found to be dramatically lower in hydroxyureatreated patients. Analysis of the protein kinase A pathway showed decreased intracellular levels of the upstream effector cyclic adenosine monophosphate during hydroxyurea treatment. Using a cellular model expressing recombinant Lu/BCAM, we showed that hydroxyurea led to decreased intracellular cyclic adenosine monophosphate levels and diminished Lu/BCAM phosphorylation and cell adhesion. We provide evidence that hydroxyurea could reduce abnormal sickle red blood cell adhesion to the vascular wall by regulating the activation state of adhesion molecules independently of their expression level

The U.K. financial sector, being the largest contributor to the national economy, needs to have robust contingency arrangements to counter any major operational disruption. As such, this doctoral research identified the premise of the need to raise the status of BCM in financial organisations.

The thesis gives an overview of the issue of control of full-color RGB LED panels with a large number of rows and columns. It deals with communication protocols for image transfer and information exchange. It focuses on implementing the FPGA into the RGB LED control structure. In the first half, the thesis focuses on deepening the theoretical knowledge about LED technologies, their control and color display. It further solves communication with superior elements. The last part of the theory is dedicated to FPGA circuits. The second part of the thesis describes the practical design of the FPGA circuit from UART and SPI communication through data storage from the communication to the panel control itself.

Les coronavirus sont caracterises par un potentiel evolutif important par l’intermediaire de recombinaisons genetiques et de mutations ponctuelles. Ces evenements peuvent avoir pour consequences l’emergence reussie d’un nouveau variant dans une nouvelle population hote, apres un franchissement de barriere d’espece. L’un de ces franchissement inter-especes a eu lieu a la fin du xixeme siecle avec l’emergence du hcov-oc43 a partir du bcov. Le genotypage du hcov-oc43 a permis de mettre en evidence une diversification intraspecifique en de nombreux genotypes incluant des genotypes recombinants. Parallelement, le genotypage du bcov n’a pas permis d’observer d’evenements de recombinaisons. Cependant, nous avons observe une organisation des bcov selon une distribution geographique avec un cluster amerique/asie et un cluster europe. L’emergence d’un coronavirus dans la population humaine a partir d’un reservoir animal doit faire l’objet d’une surveillance, comme le montre l’emergence du sars-cov et le mers-cov, a l’origine d’epidemies associees a des mortalites globales d’environ 10% et 40% respectivement
Coronaviruses are characterized by an important evolutionary potential by genetic recombination and single nucleotide polymorphisms. These events could lead to the successful emergence of a new variant in a new host population, following a species barrier crossing. One such event occurred at the end of the 19th century, with the emergence of hcov-oc43 from bcov. Genotyping of hcov-oc43 has made it possible to show an intraspecific diversification into numerous genotypes, including recombinant variants. In parallel, genotyping of bcov did not reveal recombinant events. However, we observed an organization of bcov with a geographical distribution, with a european cluster and an american/asian cluster. There is a need for monitoring the emergence of coronaviruses in the human population from an animal reservoir, such as has been seen in the emergence of sars-cov and mers-cov at the origin of epidemics associated with global mortality rates of around 10% and 40%, respectively

The Buffalo City Metropolitan Municipality (BCMM), situated in the second largest province in South Africa, the Eastern Cape, is an unfortunate victim of low economic development and high unemployment. The South African Government, through the Department of Trade and Industry, identified the need for SMMEs to address these issues with the inception of the White Paper on National Strategy for the Development and Promotion of Small Business in South Africa over 20 years ago. SMMEs in South Africa are noted to have a failure rate of around 70% which does not bode well for the efforts to improve economic development and reduce unemployment through SMMEs. This research sets out to determine the significance of variables such as human resources, financial resources, information systems, government assistance and competitive intelligence on the sustainability of SMMEs. The researcher examined the literature relating to the challenges and issues faced by SMMEs with particular emphasis on the use of competitive intelligence as a tool to assist in sustainability. The literature review was followed by an analysis and interpretation of a qualitative study of SMMEs within the BCMM. Through an analysis of the results it was possible to determine the nature of the relationships between the independent variables and sustainability. Finally, the researcher was able to make recommendations based on the research.

Neuropsychology as a discipline has not taken root in low- and middle-income countries. Most neurocognitive tests used in these countries were developed and normed in high-income, mostly western countries. The psychometric robustness of these tests is often weak when they are used on low to middle-income clinical populations. The objectives of this study were to select, adapt and generate normative data for a suitable neurocognitive screen for use in Zimbabwe. To achieve these objectives, we divided the study into 4 phases. In Phase 1 of the study, we did a systematic review that identified 83 neurocognitive assessment instruments commonly used in low- and middle-income countries on patients who have suffered a stroke. From these instruments, we selected, adapted and normed the Birmingham Cognitive Screen (BCoS; Humphreys al., 2012) through phases 2 to 4 of this study. The screen offers a robust and sufficiently broad but shallow assessment tool for cognitive deficits across key cognitive domains commonly impaired following a stroke. In particular, in Phase 2 of the study, we evaluated the cross-cultural sensitivity of BCoS on healthy participants (N=105). We then performed surveys using the Delphi method on a panel of experts to culturally adapt BCoS for use in Zimbabwe (Zim-BCoS). We evaluated the inter-rater and test-retest reliability of the translated and validated Zim-BCoS and also compared its agreement with the original BCoS version to determine its robustness. In Phase 3, we evaluated the effects of demographic variables on performance on the cognitive domains assessed by Zim-BCoS. To do this, we performed multiple linear regression analyses to calculate regression-based norms using scores from a sample of healthy participants (N=412). From these analyses, participants' age, level of education and sex had significant effects, mainly on subtests in the language cognitive domain (Picture Naming, Sentence/Word Reading/Writing and Instruction Comprehension). In Phase 4 of the study, we performed neurocognitive assessments using Zim-BCoS (and other tests) to assess and determine the frequency of specific neurocognitive deficits in patients who had suffered a stroke and were attending two major hospitals in Harare, Zimbabwe's capital city (N=103). We also compared the performance of these patients to a matched control sample (N=103). To determine the psychometric stability of Zim-BCoS we determined its validity and reliability by comparing scores on its subtests to parallel neurocognitive tests that assess similar cognitive domains. We also assessed the predictive value of Zim-BCoS on patients' neuropsychiatric and functional outcomes. We evaluated the convergence and predictive validity as well as the inclusivity of Zim-BCoS to assess patients with aphasia. We used the Zim-BCoS test scores to establish prevalence rates of cognitive deficits and other post-stroke sequelae in the sample of patients with stroke. We also assessed the predictive value of ZimBCoS subtests on patients' neuropsychiatric and functional outcomes. All comparisons of ZimBCoS against standard cognitive tests and post-stroke sequelae measures had statistically significant convergence, predictive validity and inclusivity. In this study, we demonstrated the utility of Zim-BCoS for assessing cognitive impairment in patients who have suffered a stroke, particularly in resource poor contexts typical of low-income countries. We concluded that ZimBCoS is a robust neuropsychological screen suitable for research and clinical use in Zimbabwe. The screen has the potential to offer a cost effective and easy to use neurocognitive screen for patients with acquired neurological changes in low-income countries in Southern Africa.

Le domaine des neurosciences computationnelles s'intéresse à la modélisation des fonctions cognitives à travers des modèles numériques bio-inspirés. Dans cette thèse, nous nous intéressons en particulier à l'apprentissage dans un contexte multimodal, c'est à dire à la formation de représentations cohérentes à partir de plusieurs modalités sensorielles et/ou motrices. Notre modèle s'inspire du cortex cérébral, lieu supposé de la fusion multimodale dans le cerveau, et le représente à une échelle mésoscopique par des colonnes corticales regroupées en cartes et des projections axoniques entre ces cartes. Pour effectuer nos simulations, nous proposons une bibliothèque simplifiant la construction et l'évaluation de modèles mésoscopiques. Notre modèle d'apprentissage se base sur le modèle BCM (Bienenstock-Cooper-Munro), qui propose un algorithme d'apprentissage non-supervisé local (une unité apprend à partir de ses entrées de manière autonome) et biologiquement plausible. Nous adaptons BCM en introduisant la notion d'apprentissage guidé, un moyen de biaiser la convergence de l'apprentissage BCM en faveur d'un stimulus choisi. Puis, nous mettons ce mécanisme à profit pour effectuer un co-apprentissage entre plusieurs modalités. Grâce au co-apprentissage, les sélectivités développées sur chaque modalité tendent à représenter le même phénomène, perçu à travers différentes modalités, élaborant ainsi une représentation multimodale cohérente dudit phénomène.

A major challenge in the post-genomic era is to understand how genome sequence variants (genotype) give rise to the enormous diversity observed in terms of morphology, physiology and behavior (phenotype) among living organisms. Domestic animals—with their tremendous phenotypic variation—are excellent model organisms for determining the relationships between genotype and phenotype. In this thesis, I describe the utilization of the chicken, in combination with modern genetic and genomic approaches, in developing our understanding of the genetic mechanisms underlying phenotypic variation. These studies provide novel information on the genetics behind variation in carotenoid- and melanin-based pigmentation—observed in many organisms—and also cast light on the genetic basis of chicken domestication. In paper I, we report that the yellow skin phenotype—observed in most commercial chickens—is caused by one or several tissue-specific mutations altering the expression of beta-carotene oxygenase 2 (BCO2 or BCDO2) in skin. In addition, we present the first conclusive evidence of a hybrid origin of the domestic chicken, since the allele causing yellow skin most likely originates from the grey jungle fowl (Gallus sonneratii) and not from the previously described sole ancestor, the red jungle fowl (Gallus gallus). In paper II, we detect a number of loci that were likely important during the domestication process of chicken and the later specialization into meat (broiler) and egg (layer) producing lines. One of the major findings was that worldwide, almost all domestic chickens carry a missense mutation in TSHR (thyroid stimulating hormone receptor) in a position that is completely conserved amongst vertebrates. We speculate that this “domestication-mutation” has played an important role in the transformation of the wild red jungle fowl ancestor into the modern domestic chicken. In paper III, we demonstrate that the dilution of red (pheomelanin) pigmentation—observed in the plumage of the Inhibitor of Gold chicken—is caused by a frame-shift mutation in the catechol-O-methyltransferase domain containing 1 (COMTD1) gene. The production and regulation of pheomelanin is poorly understood and this discovery advances our current knowledge of this pathway.

Questa tesi si propone di studiare l’invecchiamento dei sensori che compongono il Beam Condition Monitor System (BCM), il sistema di protezione di ALICE da eventuali problematiche legate al fascio di particelle, come i beam failures o beam losses. ALICE (A Large Ion Collider Experiment) è uno dei grandi esperimenti presenti ad LHC (Large Hadron Collider) presso il CERN di Ginevra, dedicato allo studio delle proprietà dello stato della materia chiamato Quark Gluon Plasma (QGP). Per riuscire in questo studio, ALICE si serve di una grande quantità di dati raccolti durante collisioni tra ioni pesanti di piombo (Pb) e protoni. ALICE è composto da numerosi e sofisticati rivelatori, alcuni dei quali posti in prossimità del fascio di particelle. Ogni rivelatore che compone l’esperimento è dedicato alla misura di un particolare segnale fisico o di una caratteristica della collisione analizzata. Il danneggiamento di anche solo uno di tali rivelatori potrebbe quindi limitare le performance di tutto l’esperimento, o addirittura arrestare la presa dati. I detector sono progettati per essere estremamente sensibili alle particelle che vengono generate nelle collisioni studiate: risultano così vulnerabili alle imperfezioni che si possono presentare nel fascio o nella sua iniezione nell’anello di LHC dopo essere stato accelerato dai precedenti acceleratori. Il sistema di protezione dal fascio presso ALICE è dato da una combinazione di "hardware interlocks" che compongono il Beam Interlock System (BIS) di LHC e del Beam Condition Monitor System. Le analisi effettuate in questa tesi, che hanno come oggetto di studio la risposta degli 8 sensori al diamante pCVD che compongono la Stazione 0 del BCM in funzione della luminosità dell’esperimento, hanno permesso di evidenziare come la risposta dei sensori sia variata negli anni, indicando quindi un loro invecchiamento.

This study determined the potential feasibility of surface catalyzed Fenton treatment to remediate soil and groundwater contaminated with bis(2-chloroethyl ether (BCEE), bis(2-chloroethoxy) methane (BCEM), and 1,2-dichloroethane (1,2-DCA) among other contaminants. Parameters that affect the contaminant loss rate such as pH, hydrogen peroxide concentration and solid/water ratio were systematically evaluated. Batch reactors were set-up utilizing either contaminated or uncontaminated soil that was mixed with synthetic groundwater containing the contaminants of interest. The results show an increase in contaminant reduction with a decrease in pH, an increase in hydrogen peroxide concentration, or an increase in the solid/water ratio. For the same set of conditions, contaminant reduction was greater for systems utilizing contaminated soil as compared to the systems containing uncontaminated soil. In addition, specific oxygen uptake rates were measured for an activated sludge exposed to different dilutions of untreated and surface catalyzed Fenton treated water to evaluate whether the residual BCEE, BCEM, and 1,2 DCA as well as their oxidation by products were potentially inhibitory or can potentially serve as a substrate for the activated sludge. The measured specific oxygen uptake rates show that the surface catalyzed Fenton treatment enhanced the biodegradability of the contaminated groundwater and served as a substrate for the activated sludge.
Master of Science

Ewing-like sarcomas (ELS) are a heterogenous group of neoplasms that typically occur in the bone and soft tissue of pediatric and young adult patients. ELS share various degrees of morphological, immunohistochemical, molecular, and clinical similarity with Ewing sarcomas. However, these tumors lack the pathognomonic molecular hallmark of Ewing sarcoma, which is defined as translocation between a gene of the RNA-binding TET family (EWSR1 or FUS) with a gene of the ETS-transcription family (FLI1, ERG, ETV1, ETV4, or FEV). Accurate classification and distinction from classical Ewing sarcomas is important for patient management. A subset of ELS harboring the BCOR-CCNB3 fusion has been described recently – the majority of which that have been reported to date are bone-based tumors, though there have been cases of discrete soft tissue-based tumors. We herein present a case of ELS harboring the BCOR-CCNB3 translocation occurring in a pediatric patient presenting with a large abdominal mass discovered on chest CT after failed outpatient treatment for pneumonia with effusion. This patient was a 14-year-old Caucasian boy with a past medical history significant for obesity and three episodes of pneumonia since 6-years-old. Imaging showed a large heterogeneous mass at the posterior left upper quadrant of the abdomen protruding through the posterior aspect of the left hemidiaphragm causing atelectasis. The mass abuts the inferior leftward aspect of the descending thoracic aorta and also protrudes between the 11th and 12th posterior lateral left rib. Pathology revealed this mass to be an Ewing-like sarcoma with a BCOR-CCNB3 fusion. Patient was treated with chemotherapy and radiation. This case demonstrates the importance of determining an accurate diagnosis to provide specific management.

This thesis presents the concept of a neural network starting from its corresponding biological model, paying particular attention to the learning algorithms proposed by Oja and Bienenstock Cooper & Munro. A brief introduction to Data Analysis is then performed, with particular reference to the Principal Components Analysis and Singular Value Decomposition. The two previously introduced algorithms are then dealt with more thoroughly, going to study in particular their connections with data analysis. Finally, it is proposed to use the Singular Value Decomposition as a method for obtaining stationary points in the BCM algorithm, in the case of linearly dependent inputs.

Nel 1982 Elie Bienestock, Leon Cooper e Paul Munro scrissero ”Theory for the development of neuron selectivity” proponendo uno schema di evoluzione sinaptica nel quale competono i modelli in arrivo piuttosto che la convergenza degli afferenti. Brevemente divenne nota come teoria BCM e fu il trampolino di lancio per ulteriori lavori sulla modificazione delle sinapsi corticali. Durante le ultime due decadi sono state fatte nuove formulazioni, come la IBCM di Nathan Intrator e Leon Cooper del 1992, e nuovi metodi sono stati introdotti permettendo la creazione di reti neurali più complicate ed efficienti. Lo studio di questi modelli evidenzia la capacità di adattamento a diverse situazioni in un modo semplice. Sono stati fatti studi allevando animali in un periodo critico per lo sviluppo sella selettività corticale e l’accordo tra i dati e la teoria è stato provato. Tutta la teoria, valida per i neuroni corticali, potrebbe essere migliorata con una maggiore capacità di calcolo che permetterebbe di sbarazzarsi di alcune approssimazioni.

La glycoprotéine Lu/BCAM, a initialement été découverte comme un antigène de groupe sanguin. Etant fortement exprimée dans l’endothélium rénal, on suggère qu'elle a un rôle majeur dans l'adhérence leucocytaire ainsi que dans le contrôle de permsélectivité glomérulaire. C'est un récepteur avec deux types moléculaire. D'une part la laminine α5 qui compose en particulier les laminines 10 et 11 de la matrice sous-endothéliale, d'autre part l'intégrine α4ß1 (VLA-4) présente à la surface leucocytaire. Les souris Lu/BCAM1' présentent de légères anomalies au niveau de la morphologie glomérulaire, telles qu'un épaississement local de la membrane basale glomérulaire (MBG) et parfois un élargissement des pieds des podocytes. Nous avons donc émis deux hypothèses : Premièrement, l'expression endothéliale de Lu/BCAM pourrait favoriser l'adhérence leucocytaire à l’endothélium via l'intégrine α4ß1 (VLA-4) ; deuxièmement, Lu/BCAM pourrait limiter la permsélectivité glomérulaire en favorisant l'ancrage des cellules endothéliales à la MBG contenant la laminine. Afin de tester notre première hypothèse, un modèle de glomérulonéphrite rapidement progressive (GNRP) a été induit par injection de sérum néphrotoxique (NTS) contenant un anticorps anti-MBG. Les souris Lu/BCAM~ NTS-traitées montrent une protection dans le contexte de protéinurfe, de la fonction rénale, de l'histologie rénale, de la formation des glomérulaires à croissant, du dépôt de fibrine, du nombre de podocyte et de l'infiltration leucocytaires (CD3, F4/80, MAC-1, MAC-3, CD68). Le test d'adhérence leucocytaire humain a confirmé que les leucocytes adhèrent sur Lu-Fc via α4ß1. Pour répondre à notre deuxième hypothèse, les souris ont été soumises au modèle d'HTA par perfusion d'angiotensine II pendant 28 jours ou par administration d'un inhibiteur de NO synthase (L-NAME) pendant 90 jours. Les deux traitements induisent une augmentation similaire de la pression artérielle chez les deux groupes de souris. Pourtant, les souris Lu/BCAM ~ présentent une augmentation plus importante de l'albuminurie avec un traitement à l'AngII et au L-NAME comparées aux souris contrôles. Une précipitation massive de l'albumine a été fréquemment observée dans la chambre urinaire chez les souris Lu/BCAM1' traitées à l'AngII. De plus, nous avons testé la permsélectivité vasculaire au niveau des carotides. La diffusion sous endothéliale de dextran (70KDa) couplé au FITC était augmentée en absence de Lu/BCAM. Enfin, les souris Lu/BCAM ~ présentent une augmentation de perméabilité au BE au niveau des reins. Cette hyperperméabilité n'est pas différente dans le cerveau, la rate ou le foie. En conclusion, nos résultats suggèrent que : 1, Lu/BCAM entraine une accumulation des leucocytes (notamment monocytes et polynucléaires neutrophiles) dans le glomérule inflammatoire. Les effets de cette Glycoprotéine sur le recrutement leucocytaire sont possibles via la liaison Lu/BCAM/VLA-4. 2, Lu/BCAM n'a pas d'effet sur la pression artérielle systolique induite par l'AnglI mais elle joue un rôle essentiel dans la perméabilité glomérulaire au cours de l'HTA et dans la perméabilité endothéliale extra-rénale
Lu/BCAM blood group glycoprotein, due to its important expression in renal endothelium, is suggested involved in facilitating accumulation of leukocyte and maintained the glomerular permselectivity. Lu/BCAM has been recognized as a receptor for two types of molecules. On one hand, it is a receptor for laminin α5 chain which constitute in particular lamininlO and 11 in the sub-endothelial matrix; on the other hand, it is a receptor for integrin α4ß1 (VLA-4) which present on the surface of leukocyte. Lu/BCAM-/-mice exposes abnormalities characterized by an irregular thickening of the glomerular basement membrane and sometimes an abnormal enlargement of foot process of podocyte. We have made two hypotheses: firstly, Lu/BCAM could promote leukocyte adhesion on endothelium via integrin α4ß1; secondly, Lu/BCAM could limit glomerular permselectivity by maintaining EC to GBM containing laminin α5 chain. To respond our first hypothesis, a passive RPGN model has been used. In this model, Lu/BCAM-/-mice attenuated glomerular accumulation of T cells and macrophages, crescent formation, and proteinuria, correlating with reduced fibrin and platelet déposition in glomeruli. Furthermore, we found pro-adhesive interaction between human monocyte α4ß1 integrin and Lu/BCAM proteins. For proving our second hypothesis, hypertension and glomerulosclerosis were induced by high salt diet (5% NaCl) and chronic infusion of Angiotensin II (l μ g/kg/min) or PBS in an osmotic mini-pump for 28 days or by administration of a NO syntheses inhibitor L-NAME in Lu-/-mice for 90 day in Lu/BCAM-/- mice and their wild-type littermates. Despite of a similar arterial tension, Lu/BCAM-/- hypertensive mice exhibited higher albuminuria. During Dextran-FITC (70K Da) diffusion test, a vascular hyper-permeability was observed in Lu/BCAM-/- carotid compared with their WT group. Furthermore, Lu/BCAM-/- mice displayed also a renal hyper-permeability during evans bleu permeability test, but this hyperpermeability was not found in the other organs such as brain, spleen and liver. In conclusion, the results indicated that: 1, Lu/BCAM-/- mice could possess a nephroprotective function in the early stage of GNRP when the leukocyte (monocyte and macrophage in particular) attached to into inflammatory glomerulus. It's function of leukocyte recruitment was possibly accomplished via VLA-4 ; 2,Lu/BCAM has no effect on systolic blood pressure but it plays a major role in glomerular permselectivity during hypertension and it has a extra reral endotherial permeability

The proposed energy harvesting system intends to harvest vibrational energy via an electromagnetic generator (EMG). The proposed circuit intends to extract maximum power from the EMG by utilizing the maximum power transfer theorem which states that maximum power is transferred to the load when the source resistance equals the load resistance. The proposed circuit is a synchronous split-capacitor boost converter operating in boundary conduction mode (BCM) to achieve impedance matching and therefore maximum power transferred to the load. The circuit topology combines the rectifier and power stage to reduce power loss of the power management integrated circuit (PMIC). The proposed circuit is designed and fabricated in 130 nm BiCMOS technology. The circuit is validated through schematic level simulations and post-layout simulations. The results conclude the proposed circuit and control operates in a manner to achieve BCM.
Master of Science

Coronavirus bovino (BCoV), um membro da família i>Coronaviridae, causa severa diarréia em bezerros neonatos e tem sido associado a diarréias de inverno em vacas leiteiras em vários paises, incluindo o Brasil. A morbidade da disenteria de inverno e alta chegando ate 100% , sendo um fator importante para economia já que causa queda da produção leiteira, levando a grandes perdas as criações de vacas leiteiras. O objetivo deste trabalho foi pesquisar a ocorrência de BCoV em vacas, diagnosticando amostras positivas por RT-PCR gene Rp Rd e isolando estas amostras positivas em células da linhagem HRT-18G. As amostras de fecais foram obtidas de 43 vacas leiteiras com disenteria de 8 propriedades dos Estados de São Paulo e Minas Gerais, Brasil. Das dez (10/43=23%) amostras positivas para esta técnica, 7 foram inoculadas em células da linhagem HRT-18G, sendo que o isolamento foi comprovado pela mesma técnica após seis passagens seriadas em 4 inoculações. Com isso, mostra-se que o BCoV também esta envolvido em disenterias de inverno em vacas leiteiras no Brasil. E através de isolamentos deste vírus, podemos contribuir para estudos continuados ajudar no esclarecimento de sua epidemiologia e possibilitar com um banco de vírus a prevenção de ordem também especifica da enfermidade.
Bovine coronavirus (BCoV), a member of Coronaviridae family, causes severe diarrhea in newborn calves and has been associated with outbreaks of winter dysentery (WD) in adult cattle in several countries, including Brazil. The morbidity rate of WD is very high (50-100%) and the disease causes severe economic losses once it decreases milk production. The aim of the present study was to survey for the occurrence of BCoV in cows using a RT-PCR targeted to the replicase gene and to isolate positive samples in HRT-18G cells. The fecal samples were obtained from 43 adult dairy cows with dysentery from São Paulo and Minas Gerais States, Brazil. Ten (23%) of the 43 fecal samples were positive for BCoV and 7 of these were inoculated in HRT-18G cells, when the isolation of 4 samples was proved by RT-PCR after sex passages. These findings indicate that BCoV is also involved in outbreaks of dysentery in adult cattle in Brazil. This shows the importance of more comprehensive studies on coronavirus in dairy cattle in the surveyed area and, with the isolation of the virus strains studied herein, one may contribute to other studies to enlighten the epidemiology and prevention of the disease.

Negli ultimi anni la tecnologia blockchain si è distinta sia per i risultati portati nel campo dello scambio di valore digitale, tramite le criptovalute, sia per la possibilità di utilizzarla come alternativa ai tradizionali strumenti di memorizzazione delle informazioni. Una peculiarità della tecnologia blockchain infatti è quella di conservare le informazioni in “blocchi”, collegati gli uni agli altri tramite tecniche crittografiche; il risultato di questa particolare struttura dati è la possibilità di tracciare tutta la storia di un dato e i suoi scambi, arrivando al punto in cui è stato inserito all’interno del sistema. Contemporaneamente allo sviluppo della tecnologia blockchain l’IoT ha trovato campo di applicazione in una quantità enorme di applicazioni industriali, al fine di effettuare il monitoraggio e il controllo da remoto o automatico di sistemi elettronici. I dispositivi IoT sono fondamentali per lo sviluppo delle cosiddette smart cities, poiché abilitano l’automazione di tipologie di azioni e controlli che normalmente dovevano essere realizzati in maniera manuale. La commistione delle due tecnologie sopracitate ha preso il nome di Blockchain of Things (BCoT), e rappresenta l’ultima evoluzione dello scambio informativo tra dispositivi IoT, che sono quindi in grado, oltre che di effettuare operazioni sull’ambiente, anche di certificare i dati raccolti in maniera automatica tramite la blockchain e fornirli all’utente finale all’interno di un ledger decentralizzato (letteralmente “libro mastro”, termine inglese usato per indicare la struttura dati che sostiene una generica blockchain). Lo scopo di questo elaborato é quindi quello di proporre una soluzione general-purpose che faccia uso della tecnologia BCoT per rispondere ad un insieme di criticità trasversali e riscontrate in vari campi applicativi.

The proposed circuit intends to harvest kinetic energy from ElectroMagnetic Generators (EMGs). In order to extract maximum power from an EMG, an AC-DC boost rectifier is designed to match the impedance of the EMG. Rather than operate a buck-boost converter in Discontinuous Conduction Mode (DCM) in other impedance matching cases, the proposed method is running the boost topology in Boundary Conduction Mode (BCM). So it would perform resistive input matching, while reducing the converter power loss. The boost rectifier also merges a rectifier and a boost converter to reduce power loss for rectification. It also utilizes the internal inductance of the EMG to eliminate the impedance matching error and reduce the off-chip inductor size. An optional buck converter regulates the output voltage to 5 V to power devices through USB ports. The proposed circuit is designed and fabricated in BiCMOS 0.18 μm technology. Its functionality is shown through simulation results. The measurement of the IC is also performed. However, since the IC only work partially, test result is gathered using some discrete components as substitutes. It indicates the circuit can realize the proposed control method.
Master of Science

O coronavírus bovino (BCoV) é classificado no Grupo 2 do gênero Coronavirus da ordem Nidovirales, família Coronaviridae, causando disenteria (disenteria de inverno) em bovinos adultos, diarréia em bezerros neonatos e processos respiratórios em bovinos adultos e jovens. No presente estudo, 21 amostras fecais de vacas leiteiras colhidas durante um surto de disenteria em uma propriedade de Paranapanema no Estado de São Paulo positivas para BCoV foram submetidas a reações de PCR para amplificação parcial dos genes codificadores das proteínas S (448pb) e HE (441pb) do BCoV. Destas amostras, 14 foram positivas para cada PCR (não simultaneamente), sendo os fragmentos amplificados submetidos a seqüenciamento de DNA para reconstrução genealógica por máxima parcimônia através de algoritmo heurístico em conjunto com seqüências homólogas recuperadas do GenBank. Considerando-se o gene S, a identidade de nucleotídeos entre as 14 amostras aqui estudadas foi de 100%, tendo as mesmas segregado em um grupo exclusivo; além disso, demais amostras brasileiras incluídas no estudo segregam em outros dois grupos. Em relação ao gene HE, as 14 amostras estudadas apresentaram identidade de nucleotídeos de 100%, mas a árvore genealógica apresentou topologia pouco resolvida, tendo estas amostras, segregado em grupo politômico com as seqüências homólogas incluídas. Comparações entre os diversos grupos nas árvores do gene S em termos de aminoácidos revelaram marcadores grupo-específicos, com substituições exclusivas para as amostras de BCoV aqui estudadas. Com base nestes resultados, conclui-se que, durante o transcorrer do surto de disenteria de inverno, uma única linhagem de BCoV estava presente, baseado no seqüenciamento parcial dos genes S e HE e que há pelo menos três genótipos de BCoV presentes no Brasil em relação ao gene S e ao menos um em relação ao gene HE, considerando-se as regiões gênicas e as seqüências incluídas no presente estudo.
Bovine coronavirus (BCoV) is classified in group 2 of the genus Coronavirus, family Coronaviridae, order Nidovirales, and causes winter dysentery in adult bovine, neonatal calf diarrhea, and respiratory disorders in both adult and young bovine. In this investigation, 21 fecal samples from dairy cows collected during an outbreak of dysentery in a farm located at Paranapanema, São Paulo State, all positive to BCoV, were submitted to PCRs to partial amplification of genes S (448bp) and HE (441bp ) of BCoV. Fourteen out of these samples were positive for each PCR (not simultaneously) and the amplicons were submitted to DNA sequencing for genealogic reconstruction with maximum parsimony and heuristic algorithm with homologous sequences retrieved from the GenBank. Regarding S gene, the nucleotide identity among the 14 strains was 100% and these segregated in an exclusive cluster; furthermore, the other Brazilian strains included in the analysis segregated in other two clusters. Taking into account the HE gene, the 14 strains analyzed presented a nucleotide identity of 100%, but the genealogic tree showed a low-resolved topology, having these samples segregated in a polytomic cluster with the homologous sequences included. Amino acid comparisons among the different clusters in the trees of gene S revealed cluster-specific markers, with exclusive substitutions for the BCoV strains studied herein. Based on these results, one can conclude that, during the winter dysentery outbreak, a single BCoV lineage was involved based on partial S and HE genes sequences and that there are at least three genotypes of BCoV in Brazil regarding S gene and at least one regarding HE gene, taking into account the gene regions and the sequences included in this investigation.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
As propriedades diferenciadas de materiais nanoestruturados, provenientes do efeito de escala, tem chamado muita atenção nos últimos anos. Tais características, fazem desses materiais propícios para o emprego em nanoeletrônica, nanofiltração, engenharia tecidual e outros. Isso, aliado a miniaturização dos dispositivos, tem gerado uma grande demanda por materiais com características aprimoradas, desenvolvimento de novas técnicas de produção e aprimoramento das já existentes, tudo isso associado a um menor custo de produção e uma maior produtividade. Neste trabalho é apresentado um estudo sobre o emprego da técnica de “Solution Blow-spinning” (SBS) na produção de nano e microfios supercondutores dos sistemas cerâmicos (TR)BCO e BSCCO. Esta recente técnica tem se destacado por apresentar maior taxa de produção, baixo custo e fácil implementação quando comparado com técnicas já consolidadas. Primeiramente foram produzidas fibras de PVP puro onde foi possível extrair informações referentes às variáveis de produção tais como: taxa de injeção, pressão do ar, distância de trabalho e escolha do diâmetro da agulha interna. Em seguida, a produção dos nano/microfios de YBa2Cu3O7- δ (YBCO) obtidos por SBS revelaram detalhes referente à produtividade, reprodutibilidade e das características morfológicas dos fios cerâmicos obtidos com o emprego da referida técnica. Posteriormente, as melhores condições de síntese observadas na produção do YBCO foram utilizadas na obtenção dos nano/microfios supercondutores de GdBa2Cu3O7- δ (GdBCO)e Bi2Sr2CaCu2O8+x (BSCCO). Por fim, as análises de MEV confirmaram a obtenção de nano/microfios de YBCO com diâmetro médio de 359 nm e, para GdBCO e BSCCO, de 531 nm e 635 nm respectivamente. A obtenção das fases cerâmicas supercondutoras é mostrada nas análises de DRX. Medidas magnéticas AC e DC mostraram a transição de fase normal/supercondutora com Tc ~ 92 K para o YBCO, Tc ~ 93 K para o GdBCO e de Tc ~ 80 K para o BSCCO.
The single properties presented by nanostructured materials is due to a scale effect and have been attracted much attention in recent years. Such characteristics make these materials suitable for applications in nanoelectronics, nanofiltration, tissue engineering and so on. These issues coupled with the miniaturization of the devices, have generated a great demand for materials with improved characteristics, development of new production techniques and improvement of the existing ones. All such things are associated with lower production costs and higher productivity. In this work is presented a study focused on the use of the "Solution Blow-spinning" technique (SBS) in the production of superconducting nano and microwires of the ceramic systems (TR)BCO and BSCCO. This new technique has payed attention due to its higher production rate, low cost and easy implementation when compared to other consolidated techniques. First, pure PVP fibers were produced to obtain information related to the production variables such as: injection rate, air pressure, working distance and choice of the internal needle diameter. Then, the production of nano/microwires of YBa2Cu3O7- δ (YBCO), obtained by SBS, revealed details regarding the productivity, reproducibility and morphological characteristics of the ceramic wires. Consequently, the best synthesis conditions were used to obtain the GdBa2Cu3O7- δ (GdBCO) and Bi2Sr2CaCu2O8+x (BSCCO) superconducting nanowires. Finally, SEM analysis confirmed the production of nanoscale YBCO with average diameter of 359 nm and, for GdBCO and BSCCO, of 531 nm and 635 nm, respectively. The formation of the desired phases of the superconducting ceramic was confirmed by XRD analyzes. AC and DC magnetic measurements showed the normal/superconducting phase transition with Tc ~ 92 K for YBCO, Tc ~ 93 K for GdBCO and Tc ~ 80 K for BSCCO.
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The main aim of this study is to determine genetic diversity of milk protein genes associated with milk traits, namely beta-casein, kappa-casein and betalactoglobulin, in native Turkish cattle breeds (Turkish Grey, Eastern Anatolian Red, Anatolian Black, and Southern Anatolian Red) and Turkish Holstein. Only 11% deviation from the Hardy-Weinberg equilibrium and insignificant Fis values for the populations were observed, indicating that samples are free of inbreeding. B alleles of these genes, which are positively related with cheese yield and quality, seem to be relatively high in native Turkish breeds. Therefore, the results suggest that milk of Turkish native breeds is advantageous for producing high-quality and -yield cheese. A1 allele of beta-casein, which releases a bioactive peptide called BCM-7 after successive gastrointestinal proteolytic digestions, has been claimed to have adverse health effects on humans. Another aim of this study is to develop a protocol and assess the potential detrimental effects of BCM-7 on human peripheral blood cells. Despite the fact that the results are inconclusive, the optimized experimental protocol will guide further researchers while judging the effect of BCM-7 on human health. Even though A1 beta-casein, which has a low frequency in native Turkish breeds, and hence BCM-7 have no adverse health effects on humans, this probability should be enough to keep its frequency low in native cattle breeds. Bulls must be screened for A1 allele of beta-casein as well as E allele of kappa-casein, which is absent in native breeds and known to have detrimental effects on cheese quality.

Lu/BCAM est une molécule d'adhérence, récepteur de la laminine 511/521 dans les cellules érythroïdes, endothéliales ainsi que dans les tissus épithéliaux. Elle lie la spectrine dans les globules rouges. La lysine 585 présente dans son domaine cytoplasmique, interagit avec l'enzyme Ubc9 dans les cellules épithéliales rénales. Ubc9 forme un complexe avec Lu/BCAM endogène ou recombinant dans les cellules épithéliales A498 et MDCK respectivement. Les cellules MDCK transfectées avec un mutant de Lu/BCAM incapable de lier Ubc9, montrent une localisation membranaire basolatérale, une demi-vie membranaire augmentée et une adhérence et un étalement à la laminine renforcée. La spectrine-all forme un complexe avec Lu/BCAM endogène ou recombinant dans les cellules épithéliales A498 et MDCK, respectivement. Le mutants mt-Lu indique que l'absence d'interaction avec la spectrine conduit à un affaiblissement de l'interaction avec le squelette dépendant de la spectrine, comme le montre l'augmentation de son extractabilité au Triton X-100. Les cellules MDCK transfectées avec mt-Lu, incapable de lier la spectrine, montrent une localisation membranaire basolatérale, une demi-vie à la membrane augmentée et une, adhérence "et un étalement significativement renforcée à la laminine qui n'est pas corrélée à l'état de phosphorylation de Lu/BCAM. Nous montrons pour la première fois, que cette interaction est impliquée dans une signalisation allant de la laminine à Tactine conduisant à la formation de fibres de stress dans les cellules cultivées sur laminine. Ce signal est associé à l'activation de la petite GTPase RhoA qui est dépendante de l'intégrité du motif d'interaction de Lu/BCAM la laminine
Lu/BCAM is an adhésion molecule, receptor of laminin 511/521 in erythroïd cells as well as in epithelial tissues and endothelial cells. Lu/BCAM binds also directly to al spectrin in red blood cells. The lysine 585 present in its cytoplasmic domain interacts directly with the enzyme Ubc9 in renal epithelial MDCK cells. Ubc9 forms a complex with endogenous or recombinant Lu/BCAM in epithelial MDCK and A498 cells respectively. MDCK cells transfected with a mutant of Lu/BCAM, unable to bind Ubc9, showed a basolateral membrane localization, greater extended half-life at the membrane and enhanced adhesion and spreading on laminin. The all-spectrin forms a complex with endogenous or recombinant Lu/BCAM in epithelial MDCK and A498 cells respectively. The mutant mt-Lu indicates that the lack of interaction with all-spectrin leads to a weakening of the interaction with the cell membrane cytoskeleton of non-erythroïd cells, as shown by the increase in its extractability with Triton X-100. MDCK cells transfected with a Lu/BCAM mutant unable to bind spectrin (mt-Lu) exhibited a normal basolateral expression but enhanced half-life at the membrane. In addition, adhesion and spreading of epithelial MDCK cells on laminin were significantly reinforced in the mt-Lu and this is not related to the phosphorylation status of Lu/BCAM. We show for the first time that this interaction is involved in signaling from laminin to actin leading to the formation of stress fîbers in cells growning on laminin. This rearrangement of the actin skeleton is associated with an activation of the small GTP specifîcally -binding protein RhoA that is dependant to the laminin binding site integrity of the Lu/BCAM

Magister Educationis - MEd
Ideology reveals itself in the commonly shared ideas and ideals which act as the driving force responsible for group formation underlying nationalist aspirations in society. It reveals itself in various ways with politics as the most visible and education as the most powerful, yet unobtrusive, manifestation. In South Africa Afrikaner Nationalism and Black Nationalism have been involved in a titanic battle for the last fifty years. The ideology of Afrikaner Nationalism developed as a striving for political, cultural and educational freedom from British imperialist domination. An important part of this struggle was waged in the field of education, leading to the development of the sub-ideology of Christian National Education. The tenacity with which the Afrikaner pursued his nationalist aspirations was rewarded with the recognition of Afrikaans as official language in 1925, the National Party gaining political power in 1948 and the establishment of the Afrikaner educational ideology, Christian National Education, as state education policy in 1967. The Afrikaner Broederbond, under the cover of an Afrikaner cultural society, exercised a tremendously strong influence in the political, economic and social spheres. With the support of the extremely influential Dutch Reformed Church hegemonic rule was further consolidated. In order to attain its ideals and maintain its position of power, Afrikanerdom engaged in suppressing the Black sector of the population. This manifested in the denial of political and human rights to Blacks, and was reinforced by an education system which offered Blacks inferior education to that of Whites to ensure that they would not become a threat to Afrikaner power. The Afrikaner Broederbond, under the cover of an Afrikaner cultural society, exercised a tremendously strong influence in the political, economic and social spheres. With the support of the extremely influential Dutch Reformed Church hegemonic rule was further consolidated. In order to attain its ideals and maintain its position of power, Afrikanerdom engaged in suppressing the Black sector of the population. This manifested in the denial of political and human rights to Blacks, and was reinforced by an education system which offered Blacks inferior education to that of Whites to ensure that they would not become a threat to Afrikaner power tendency towards communalism in Black society resulted in Black Nationalism adopting the ideology of Black Liberation Socialism, under whose banner many former colonies had attained independence from their European mother countries. The educational sub ideology of People's Education served the Black Nationalist ideal by adopting in its curricula, syllabi and organisational structure an approach which supported Black liberation from the apartheid regime. The South African state (government, the police, the legal system, etc.) acted in a repressive manner under the influence of the Afrikaner ideology. The oppression Afrikaners suffered at the hand of British imperialism was repeated when Afrikaner Nationalism assumed power under the Nationalist government. It subjected Blacks to oppression and totally negated Black nationalist aspirations. Education always serves the dominant ideology - a concept clearly manifested in Christian National Education as it served the Afrikaner Nationalist ideology. In the same manner People's Education proved to be an extension of the Black Liberation Struggle. Ideology is thus in the service of power. Ample evidence exists that Afrikaner Nationalism and Christian National Education served to entrench Afrikanerdom in a position of seemingly unassailable power for an extended period of time after it had discarded the British imperialist yoke. This dominant position was maintained despite being a minority group. Should the same pattern prevail one would expect the African National Congress to abuse its present position of power to oppress the White minority and take revenge for the suffering that the latter had inflicted on Blacks for so many years. Both the Oppressed and the Oppressor are dehumanised in the process of oppression. Although the Afrikaner was in a dominant, powerful position and seemingly free, he became enslaved to his own ideology. He was deprived of independent opinion and thought by the prescriptive ideology of Afrikaner Nationalism and its educational ideology of Christian National Education. Non-compliance was frowned upon and deviants ostracised. It is ironic that, by ousting the Afrikaner nationalist regime, the African National Congress actually became the agent which liberated the Afrikaner from his self inflicted ideological oppression. Oppression thus seems to follow a vicious circle with both the Oppressor and the Oppressed suffering dehumanisation. Unless the Oppressed is rehumanised the oppressive role model presented by the Oppressor is emulated and the former Oppressed become the new Oppressor. The necessity for the process of rehumanisation to occur in the postapartheid South African society can not be over-emphasised and thus various steps that can be taken to effect rehumanisation are suggested.

This diploma project is showen possibilities in classification of genomic sequences with CGR and FCGR methods in pictures. From this picture is computed classificator with BCM. Next here is written about the programme and its opportunities for classification. In the end is compared many of sequences computed in different options of programme.

Frank Rosenblatt, padre del percettrone, nel 1962 sottolineò che l’ obiettivo ultimo della ricerca nel campo delle reti neurali artificiali doveva essere “indagare le strutture fisiche ed i principi neurodinamici che stanno alla base dell’intelligenza naturale”. A differenza di quel che desiderava Rosenblatt, i metodi maggiormente utilizzati e di conseguenza studiati sono quelli supervisionati, non biologicamente plausibili, ritenuti maggiormente efficaci rispetto alle reti che sfruttano metodi di apprendimento ispirati dalla biofisica dei neuroni. L’ obiettivo della tesi è quello di analizzare due metodi di apprendimento non supervisionati basati su sistemi neuronali biologici: il modello di L.Bienenstock, N.Cooper e W. Mundro del 1982 (BCM) ed il modello di D.Krotov e J.Hopfield del 2019, e comprenderne le reali capacità. La prima parte della tesi rappresenta un’ introduzione al concetto di rete neurale artificiale, al significato di rete multistrato e all’ algoritmo di apprendimento della retro propagazione dell’ errore, tipico delle reti supervisionate. La seconda parte della tesi illustra il funzionamento della BCM e della rete di Hopfield e Krotov. Nei risultati riguardanti la rete del 2019, viene riportato un confronto tra questo modello ed un modello addestrato tramite retro propagazione dell’ errore, con cui riesce a competere nel riconoscimento delle immagini appartenenti a due data set: il MNIST ed il CIFAR-10. Per quanto riguarda la BCM, vengono riportati e discussi i risultati di alcune simulazioni effettuate con la rete modello BCM della libreria Plasticity. Lo scopo delle simulazioni era quello di portare i pesi della rete a memorizzare il maggior numero di pattern differenti possibili, appartenenti al data set MNIST.

O coronavírus bovino (BCoV) é classificado no grupo 2 do gênero Coronavirus da ordem Nidovirales, família Coronaviridae, causando diarréia em bezerros neonatos, processos respiratórios em bezerros não neonatos e disenteria em vacas adultas. No presente estudo, 203 amostras fecais de bezerros de 19 propriedades leiteiras nos Estados de São Paulo e Minas Gerais foram submetidas à prova de hemaglutinação/ inibição da hemaglutinação (HA/HI) para a detecção de coronavírus e a uma reação de PCR dirigida ao gene codificador da RNA-polimerase RNA-dependente dos coronavírus (PCR pol), sendo feita a comparação entre as duas técnicas através dos testes Kappa e J de Youden. Amostras positivas à PCR pol foram submetidas a uma reação de PCR para amplificação de um segmento de 488 pares de bases correspondentes à região hipervariável do gene codificador da subunidade S1 da proteína S, sendo os fragmentos submetidos a seqüenciamento de DNA para a reconstrução genealógica das amostras estudadas. Ainda, a presença de rotavírus foi pesquisada pela técnica de PAGE. Segundo a técnica de HA/ HI, 35,47% das amostras e 73,68% das propriedades rurais forma positivas para BCoV, enquanto que pela PCR pol 25,12% das amostras e 52,63% das propriedades rurais foram positivas para este vírus. A comparação entre as duas técnicas resultou valores de kappa de -0,048 para os resultados individuais e -0,08 em relação às propriedades rurais e J de Youden de -0,045 para os resultados individuais e -0,1 em relação às propriedades rurais, demonstrando baixa concordância entre as duas provas. A genealogia obtida por máxima parcimônia através de algoritmo heurístico e baseada em seqüências da região hipervariável do gene codificador da subunidade S1 da proteína S de 15 amostras de campo aqui estudadas, da amostra Kakegawa de coronavírus bovino utilizada como controle positivo e de 10 seqüências recuperadas dos GenBank revelou a existência de dois genotipos dentro desta espécie viral, sendo os dois genotipos encontrados entre amostras brasileiras. A identidade média de nucleotídeos entre as 15 amostras brasileiras foi de 98,34%, com similaridade média de aminoácidos de 98%. Amostras pertencentes ao genotipo 2 apresentaram uma deleção de 18 nucleotídeos/ 6 aminoácidos dentro da região correspondente ao domínio II da proteína S. A árvore de máxima parcimônia enraizada tendo bredavírus como grupo externo revelou que esta deleção ocorreu em um único momento na genealogia dos coronavírus bovinos. Rotavírus foi encontrado em 12,6% das amostras fecais individuais e 28, 57% das propriedades rurais pesquisadas. Estes resultados são os primeiros baseados em amostras brasileiras de coronavírus bovino e contribuem para a caracterização molecular do BCoV, para a predição da eficiência de imunógenos e para o encontro de marcadores moleculares úteis para estudos epidemiológicos continuados em relação às diarréias neonatais em bovinos.
Bovine coronavirus (BCoV) belongs to group 2 of the genus Coronavirus from the order Nidovirales, family Coronaviridae and causes diarrhea in newborn calves, respiratory diseases in non-newborn calves and dysentery in cows. In the present study, 203 stool samples of calves from 19 dairy farms from São Paulo and Minas Gerais States were submitted to hemagglutination/ hemagglutination inhibition test (HA/HI) to bovine coronavirus detection and a PCR assay targeted to the RNA-polymerase RNA-dependent gene of coronaviruses (PCR pol), the comparison between the two tests carried out with Kappa and Youden´s J tests. Samples positive to PCR pol were submitted to a PCR assay that amplifies a 488 base-pair fragment which corresponds to the hypervariable region of the gene coding for the S1 subunit of the S protein; the amplified fragments were submitted to DNA sequencing aiming the genealogic reconstruction of the studied samples. Rotavirus was surveyed with the PAGE test. The HA/ HI test resulted 35.47% of samples and 73.68% of farms positive to BCoV, while, according to PCR pol, 25.12% of the samples and 52.63% of the farms were positive to this virus. The comparison between the two tests produced a kappa value of -0.048 to individual results and -0.08 to the farms and Youden´s J value of -0.045 to individual results and -0.1 to the farms, showing low agreement between the two tests. Maximum parsimony genealogy with an heuristic algorithm based on sequences of the hypervariable region of the gene coding for the S1 subunit of the S protein from 15 field samples here studied, from the Kakegawa bovine coronavirus strain used as positive control and from 10 sequences retrieved from GenBank showed the existence of two genotypes in this viral species. Mean nucleotide identity between the 15 Brazilian samples was 98.34%, with mean amino acid similarity of 98%. Samples from genotype 2 showed a deletion of 18 nucleotides/ 6 amino acids inside the domain II region of the S protein. Rooted maximum parsimony tree with bredavirus as an outgroup revealed that this deletion has happened only once in bovine coronavirus genealogy. Rotavirus was found in 12.6 % of stool samples and 28.57% of the surveyed farms. These are the first results based on Brazilian strains of bovine coronavirus and contribute to molecular characterization of BCoV, to the prediction of the efficiency of immunogens and to the finding of molecular markers useful to continued epidemiologic surveys on newborn bovine diarrhea.

Le globule rouge est une cellule simple avec l’une des fonctions les plus importantes de l’organisme : participer aux échanges gazeux et fournir l’oxygène aux tissus. C'est un disque biconcave hautement élastique grâce à un réseau de protéines du cytosquelette et de protéines membranaires spécifiques. La fonction, ainsi que la structure des globules rouges sont altérées dans plusieurs pathologies humaines telles que les hémoglobinopathies et les anomalies de membrane. La drépanocytose est une maladie héréditaire génétique caractérisée par une hémoglobine anormale qui polymérise en conditions hypoxiques provoquant la déformation des globules rouges circulants. La drépanocytose se caractérise également par une anémie hémolytique chronique et des crises vaso-occlusives douloureuses dues à l'obstruction des capillaires.Dans le but de mieux comprendre les mécanismes responsables des manifestations cliniques, nous avons étudié les propriétés mécaniques et adhésives des globules rouges de patients atteints de drépanocytose en évaluant 1) l'impact de contraintes mécaniques répétées sur la survie des globules rouges à l'aide d'un appareil microfluidique qui mime la microcirculation et 2) le rôle du stress oxydant dans l'activation des protéines d'adhérence érythroïde.Nous avons conçu une puce microfluidique et montré que le stress mécanique est un paramètre critique sous-jacent à l'hémolyse intravasculaire dans la drépanocytose et que des taux intracellulaires élevés d'hémoglobine fœtale préviennent cette lyse. Outre ces résultats, nous avons constaté que le traitement à l'hydroxyurée protège les globules rouges de la lyse lors d'un stress mécanique, même en l'absence d'expression de l'hémoglobine fœtale. D'autre part, nous avons étudié la structure et la fonction de la protéine d'adhérence érythroïde Lu/BCAM dans des conditions oxydantes en utilisant des approches biochimiques et d'imagerie. Nous avons observé que le stress oxydant active la fonction adhésive de Lu/BCAM par des modifications post-traductionnelles qui modifient sa distribution membranaire. Nous décrivons un nouveau mécanisme qui affecte les interactions en cis de Lu/BCAM à la surface cellulaire et qui pourraient expliquer l'adhérence anormale des globules rouges à la laminine en l'absence d'événements de phosphorylation.En conclusion, nous avons développé un modèle microfluidique reproduisant les dimensions physiologiques des microvaisseaux humains, permettant d’évaluer les caractéristiques cellulaires jusque-là inexplorées dans la drépanocytose. Nous montrons que le stress mécanique répété est en partie responsable de l'hémolyse chez les patients atteints d'anémie falciforme, ce qui pourrait contribuer aux niveaux élevés de stress oxydant en raison de l'hème libre dans la circulation. Nos travaux démontrent l'importance de la dimension mécanique dans l’obstruction des capillaires et la contribution critique du stress oxydant dans l'adhérence anormale des globules rouges dans cette maladie. Améliorer la déformabilité des globules rouges et cibler le stress oxydant pour inhiber l'adhérence des globules rouges serait une stratégie prometteuse pour cibler les principales caractéristiques de cette pathologie et alléger le fardeau de la maladie
The red blood cell is a simple cell with one of the most important functions in the organism, that is fulfilling the gas exchange function and delivering oxygen to the tissues. It is a highly elastic biconcave disk thanks to a network of specific skeletal and membrane proteins. The function and structure of the red cell are altered in several human pathologies like hemoglobinopathies and membrane disorders. Sickle cell disease is a genetic hereditary disorder characterized by abnormal hemoglobin that polymerizes under hypoxic conditions leading to the sickling and alteration of circulating red cells. The hallmarks of sickle cell disease are hemolytic anemia and painful vaso-occlusive crises due to the obstruction of fine capillaries.With the aim of better understanding the mechanisms behind these clinical manifestations we investigated the mechanical and adhesive properties of red blood cells from patients with sickle cell disease by assessing 1) the impact of repeated mechanical stress on red cell survival using a microfluidic device that mimic human microcirculation, and 2) the role of oxidative stress in the activation of erythroid adhesion proteins.We designed a microfluidic device that allowed us to show that mechanical stress is a critical parameter underlying intravascular hemolysis in sickle cell disease and that high intracellular levels of fetal hemoglobin protect against lysis. Furthermore, we found that treatment with hydroxyurea protects red blood cells from lysis upon mechanical stress even in the absence of fetal hemoglobin expression. On the other hand, we investigated the structure and function of the erythroid adhesion protein Lu/BCAM under oxidative conditions using biochemical and imaging approaches. We observed that oxidative stress activates the adhesive function of Lu/BCAM through post-translational modifications that alter its membrane distribution. We describe a novel mechanism that affects Lu/BCAM cis-interactions at the cell surface that might account for the abnormal adhesion of sickle red cells to laminin in the absence of phosphorylation events.In conclusion, we developed a microfluidic device replicating the physiological dimensions of human microvessels that allows assessing previously unexplored cellular characteristics in sickle cell disease. We show that repeated mechanical stress is partly responsible for hemolysis in patients with sickle cell disease, which might contribute to the high levels of oxidative stress because of free heme in the circulation. Our work demonstrates the importance of the mechanical dimension in the blockade of small capillaries and the critical contribution of oxidative stress in the abnormal adhesion of red cells in this disease. Improving red cell deformability and targeting oxidative stress to inhibit red cell adhesion would be promising strategies to target the main hallmarks of this pathology and alleviate the disease burden

International Telemetering Conference Proceedings / October 27-30, 1997 / Riviera Hotel and Convention Center, Las Vegas, Nevada
This paper describes a Smart Sensor Network System for applications requiring sensors connected in a multidrop configuration in order to minimize interconnecting cables. The communication protocol was optimized for high speed data collection. The Smart Sensor Network System was developed with the following goals in mind: cost reduction, reliability and performance increase.