The primary outcome of this thesis is found in three contributions. First, we developed an automatic converter from the cube representation of incompletely specified multiple-output Boolean function, given in Espresso format, to VHDL. The converter is designed specifically for updating functions of Feedback Shift Register (FSRs) in the Galois configuration, namely it reads in the description of a combinatorial function and adds register stages to the appropriate positions. The converter can handle both, Linear and Non-Linear feedback Shift Registers. The second contribution is modifying the automatic converter to design a tool which gives the user the opportunity to see the hardware characteristics of its circuit quickly from the espresso format of its design. The third contribution is applying the resulting converter to evaluate the results of the CRC generation algorithm presented in [6]. We computed the hardware characteristics such as area, timing and power dissipation on most popular CRCs in ASIC and FPGA technologies. Furthermore, we introduced a simple interface used to provide the user a good estimation of the power diagram during the executing time which is similar to probing the current of the circuit.

The purpose of this study is to investigate how South African and Swedish legislation as wellas case law regarding domestic violence and punishment against children is presented in both legal systems. Two methods are used as help to answer the two core questions in this thesis.The result of the study showed that the definitions of physical, psychological and sexual abusein both countries are listed as the same assaults and each country has an obligation to relocate children that have been exposed to those forms of violence. Many children in both countries have experienced some type of domestic violence during their childhood which makes the institutions whom work and have qualifications in questions regarding abused children to protect them from all forms of violence and have to strive more in order to make a better living for the next generations forward. When it comes to decision making courts and authorities in both countries have an obligation to always act in the child’s best interest which clearly appears in both constitutions.

Det blir vanligare att barn och ungdomar slutar spela fotboll när dem blir äldre vilket bland annat beror på avsaknad av tillhörighet, brist på autonomi och en känsla av otillräcklig kompetens, delar som är centrala i barnkonventionens grundprinciper. I Sverige blev barnkonventionen lag den första januari 2020 efter att Sverige kritiserats av FN:s barnrättskommitté, där brister upptäckts. För fotbollstränare innebär lagändringen ett ökat ansvar att arbeta i linje med barnkonventionen. Syftet med studien var att beskriva fotbollstränares uppfattningar av hur de, utifrån barnkonventionen, arbetar med att skapa goda förutsättningar att främja en hälsosam och pedagogisk miljö för barn i fotbollsföreningar. Det empiriska materialet har inhämtats från nio fotbollstränare genom intervjuer och bearbetats genom en kvalitativ innehållsanalys. Den teoretiska referensramen utgår från frigörande pedagogik och känsla av sammanhang. Den insamlande empirin analyserades och skapade följande kategorier i resultatet: genom arbete med jämlikhet, genom att se till varje individ och genom att skapa delaktighet. Resultatet visade att fotbollstränares arbetssätt i förhållande till barnen gick emot barnkonventionen men att det även fanns arbetssätt hos tränarna som gick i linje med barnkonventionen. Tränarna ansåg att dem arbetade med jämlikhet och lika villkor för barnen. Samtidigt förekom vissa skillnader mellan könen samt selektering där barn kunde exkluderas. Det ansågs viktigt att se till barnens bästa men att fokus ibland hamnade på prestation istället. Tränarna arbetade med delaktighet men brister förekom även här. Vid de situationer som tränarna arbetar i linje med barnkonventionen kan vi se att de främjar en hälsosam och pedagogisk miljö. / It’s becoming more common for children and young people to stop playing football when they grow older due to lack of belonging, lack of autonomy and a sense of inadequate competence, parts central to the Convention on the Rights of the Child (CRC). In Sweden, the CRC became law on the first of January 2020 after Sweden was criticized by the UN Committee on the Rights of the Child, where shortcomings were discovered. The amendment increases responsibility on football coaches to work along the law. The purpose of the study was to describe football coaches perceptions of how, based on CRC, they work to create good conditions for promoting a healthy and pedagogic environment for children in football clubs. Empirical material has been obtained from nine football coaches through interviews and processed through a qualitative content analysis. The theoretical frame of reference is based on critical pedagogy and sense of coherence. The empirics were analyzed and created these categories in the result: through work with equality, by seeing each individual and by creating participation. Results showed that the coaches worked both against and along CRC. Selections occured where children could get excluded and there were inequalities between genders, even though the coaches established that they worked with equality. To look after the children's best interests was considered important but the focus sometimes ended up on performance instead. The coaches worked with participation but shortcomings also occurred here. When the coaches worked along with CRC it promoted a healthy and pedagogic environment.

Field Programmable Gate Arrays (FPGAs) are being used more frequently in space applications because of their reconfigurability and intensive processing capabilities. FPGAs in environments like space are susceptible to ionizing radiation which can cause Single Event Upsets (SEUs) in the FPGA's configuration memory. These upsets may cause the programmed user design on the FPGA to deviate from its normal behavior. Space missions cannot afford to allow important data processing applications to become corrupted due to these radiation upsets.Configuration scrubbing is an upset mitigation technique that detects and corrects upsets in an FPGA's configuration memory. Configuration scrubbing periodically monitors an FPGA's configuration memory utilizing mechanisms such as Error Correction Codes (ECCs), Cyclic Redundancy Checks (CRCs), a protected golden file, and partial reconfiguration to detect and correct upset memory bits. This work presents improved Xilinx 7-Series configuration scrubbing architectures that achieve minimal hardware footprints, competitive performance metrics, and robust detection and correction capabilities. The two principal scrubbing architectures presented in this work are the readback and hybrid scrubbers which detect and correct Single Bit Upsets (SBUs) and Multi-Bit Upsets (MBUs). Harnessing the performance advantages granted by the 7-Series internal Readback CRC scan, a hybrid scrubber built in software for the Zynq XZC07020 FPGA has been measured to correct SBUs in 8.024 ms, even-numbered MBUs in 13.38 ms, and odd-numbered MBUs in 21.40 ms. It can also perform a full readback scrub of the entire device in under two seconds. These scrubbing architectures were validated in radiation beam tests, where one of the architectures corrected MBUs as large as sixteen bits in a single frame.

Yes / Abstract Objective Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. / NIHR/EME Yorkshire Cancer Research (YCR)

Recent knowledge suggests that the onset of cancer is modulated by the interplay of internal and external environmental factors along with numerous gene variants. Structural chromsomal aberrations in peripheral blood lymphocytes are considered as biomarkers of effect of genotoxic carcinogens and reflect elevated risk of cancer. Incomplete or deficient repair of double-strand breaks in DNA underlie chromosomal aberrations and the measurement of cytogenetic alterations may reflect interindividual differences in the response towards the mutagen. In this study the expected deficiences in the DNA repair capacity have been determined in incident oncological patients with breast, colorectal and urogenital cancers. The determination of chromosomal aberrations have been supplemented by the measurement of variants in genes involved in double-strand breaks repair (XRCC3, rs861539; RAD54L, rs1048771). Methodologically, we employed conventional cytogenetic analysis, cytogenetic analysis following the induction of chromocomal damage by bleomycin ("Challenge assay"), TaqMan discrimination analysis for the detection of allelic variants and statistical analyses. By using these methods we did not observe statistically signifiant differences either in chromosomal breaks (p=0,354) or in a percentage of cells with...

L’objectif principal de ce projet de recherche doctorale est la mise au point d’approches méthodologiques fiables et reproductibles permettant la caractérisation génétique de cellules rares circulantes isolées par la méthode de filtration ISET® (Rarecells®, France). La première application développée consiste en la détection des mutations du gène suppresseur de tumeur VHL (Von Hippel Lindau) dans les cellules rares circulantes (CRC) uniques isolées du sang de 30 patients atteints de carcinome rénal à cellules claires (CRCC), et réalisée comparativement à l’analyse cytopathologique. L’étude génétique a également été conduite en parallèle dans les 30 tissus tumoraux correspondants. Les résultats ont mis en lumière une potentielle complémentarité de l’approche de génétique moléculaire sur cellules uniques avec l’analyse cytomorphologique de référence et suggèrent que combiner ces approches permettrait d’obtenir une plus grande sensibilité de détection des cellules cancéreuses circulantes chez les patients atteints de CRCC. Une deuxième application a consisté en le développement d’une approche innovante pour le diagnostic prénatal non-invasif des maladies génétiques récessives par analyse de cellules trophoblastiques rares collectées au niveau du col de l’utérus. Enfin, des développements supplémentaires ont permis d’optimiser les analyses de séquençage à haut débit et de les appliquer à des CRC individuelles isolées par ISET®. Cette nouvelle approche, associée à l’isolement de CRC non fixées, est en mesure de fournir des données génétiques élargies à l’exome entier pour des applications à la fois en oncologie prédictive et en diagnostic prénatal non invasif. / The aim of this doctoral research project is the development of reliable and reproducible methodological approaches enabling the genetic characterization of circulating rare cells (CRC) isolated by ISET® filtration (Rarecells®, France). The first application developed consists in detecting mutations of the VHL (Von Hippel Lindau) tumor suppressor gene in single CRC isolated from the blood of 30 patients patients with clear cell renal cell carcinoma (ccRCC), assessed according to the results obtained by cytopathological analysis. In parallel, genetic analysis of VHL mutations was conducted in the corresponding tumor tissues. Results revealed a potential complementarity of the molecular genetic approach targeted to single cells with the reference method of cytopathological analysis and suggested that combining both strategies could improve the sensitivity of circulating cancer cells’ detection in patients with ccRCC. A second application consisted in the development of an innovative approach for non-invasive prenatal diagnosis of recessive genetic diseases by analysis of rare trophoblastic cells collected from the cervix. Finally, further developments allowed to optimize high-throughput sequencing analyses and to apply them to single CRC isolated by ISET®. This approach, combined with the isolation of living CRC, enabled us to obtain broader genetic data from the whole exome and should foster innovative applications to both predictive oncology and non-invasive prenatal diagnosis.

Die Wnt/ β-Catenin-Signaltransduktion nimmt eine exponierte Stellung in der kolorektalen Karzinogenere ein. Niclosamid ist ein Derivat der Salicylsäure, das bei Bandwurm- infektionen eingesetzt wird. Es konnte gezeigt werden, dass Niclosamid den Wnt/ β-Catenin-Signalweg moduliert. Ziel der vorliegenden Arbeit war es, den therapeutischen Einsatz des Niclosamids beim kolorektalen Karzinom zu evaluieren. Die Zellproliferation von kolorektalen Karzinomzelllinien (humane SW480 und SW620 Zellen sowie CC531 Zellen einer Ratte) und von Rattenfibroblasten wurde nach 12 und 24 Stunden Inkubation mit Niclosamid durch lichtmikroskopische Zellzahlbestimmungen beurteilt. Die Apoptoseraten wurden mit einem Zelltod-Assay ermittelt. Eine Immunfluoreszenzfärbung gab Aufschluss über das Expressionsmuster von aktivem β-Catenin. Die Promotoraktivität des LEF/ TCF-Transkriptionsfaktors wurde nach Transfektion mit TOPflash mithilfe eines Luciferase Assays analysiert. Die Genexpression von Wnt-modulierenden Faktoren (Bcl-9 und Wif1), von Komponenten des ß-Catenin- Degradationskomplexes (Axin2 und GSK 3β), von kanonischen Zielgenen (Met, MMP7 und Cyclin D1) und von c-jun als Schlüsselprotein des nicht-kanonischen Wnt/ JNK-Signalweges wurde in der RT-PCR untersucht. Auf Proteinebene wurden zur Bestätigung zusätzlich Western Blots mit Antikörpern gegen aktives β-Catenin und c-jun durchgeführt. Die Zellproliferation kolorektaler Karzinomzelllinien wurde dosisabhängig inhibiert, und Niclosamid führte zu Apoptose. Nach Inkubation mit Niclosamid kam es nicht zur Umverteilung von aktivem β-Catenin von der nukleären in die zytosolische Fraktion. Die Wnt-Promotor-Aktivität von LEF/ TCF wurde nach 12 Stunden Inkubation mit 10 und 50 μM Niclosamid jedoch signifikant gesenkt. Kanonische Wnt-Zielgene (Met, MMP7 und Cyclin D1) sowie der Koaktivator Bcl-9 wurden auf Transkriptionsebene gehemmt, während das nicht-kanonische Schlüsselprotein c-jun aktiviert wurde. Fasst man zusammen, so führt die Inkubation mit Niclosamid zu inhibitorischen Effekten auf kolorektale Karzinomzelllinien und zu einer reduzierten kanonischen Wnt-Aktivität. Diese Effekte können durch eine gestörte Formation des Triple-Komplexes aus Bcl-9, β- Catenin und LEF/ TCF und einer Aktivierung von c-jun und damit des nicht-kanonischen Wnt/ JNK-Signalweges bedingt sein. In in vivo-Untersuchungen beabsichtigen wir, in einem Tiermodell die Daten zu verifizieren und so den Einsatz des Niclosamids als Option für Patienten mit metastasiertem kolorektalem Karzinom weiterführend zu beurteilen.

Hur samverkar de nationella folkhälsomålen med fysisk planering, och på vilket sätt kan folkhälsomålen beaktas för att förbättra förutsättningarna för ökad fysisk aktivitet hos barn? Denna studie är en fallstudie i Hjo kommun. Studien tar utgångspunkt i kommunens folkhälsoproblematik som visar att det finns en hög förekomst av övervikt hos barn. Intentionen är att undersöka vilka organisatoriska processer som kan underbygga det kommunala arbetet med folkhälsomålen, liksom att ta reda på vilka faktorer i den fysiska miljön som skapar förutsättningar för barns fysiska aktivitet. Avsikten med studien har varit att skapa ett underlag för Hjo kommuns översiktliga planering. Resultatet av studien tydliggör vilka strukturella processer som påverkar arbetet med folkhälsa, men även hur utformningen av folkhälsomålen kan påverka den fysiska planeringens beaktande av folkhälsan. Resultatet åskådliggör även faktorer i den fysiska miljön som påverkar barns förutsättningar till fysisk aktivitet, liksom vikten av beaktandet av barnkonventionen. ABSTRACT How does national public health objectives cooperate with spatial planning, and in which way can public health objectives be considered in order to improve the conditions for increasing physical activity in children? This study is a case study in the municipality of Hjo. The starting point of the study is the municipal public health problem which indicates that there is a high prevalence of obesity in children. The intention is to examine the organizational processes that can underpin the municipal work of public health objectives, as well as to find out which factors in the built environment that can establish the conditions for children's physical activity. The purpose of this study was to provide a basis for the conceptual planning for the municipality of Hjo. Results of the study illustrates the structural processes that affect the work of public health, but also how the design of public health objectives may influence on the physical planning considerations of public health. The result also illustrates factors in the built environment that affect children's opportunities for physical activity, but also the importance of taking into account of the Convention on the Rights of the Child (CRC).

Error-control codes provide a mechanism to increase the reliability of digital data being processed, transmitted, or stored under noisy conditions. Cyclic codes constitute an important class of error-control code, offering powerful error detection and correction capabilities. They can easily be generated and verified in hardware, which makes them particularly well suited to the practical use as error detecting codes.A cyclic code is based on a generator polynomial which determines its properties including the specific error detection strength. The optimal choice of polynomial depends on many factors that may be influenced by the underlying application. It is therefore advantageous to employ programmable cyclic code hardware that allows a flexible choice of polynomial to be applied to different requirements. A novel method is presented in this thesis to realise programmable cyclic code circuits that are fast, energy-efficient and minimise implementation resources.It can be shown that the correction of a single-bit error on the basis of a cyclic code is equivalent to the solution of an instance of the discrete logarithm problem. A new approach is proposed for computing discrete logarithms; this leads to a generic deterministic algorithm for analysed group orders that equal Mersenne numbers with an exponent of a power of two. The algorithm exhibits a worst-case runtime in the order of the square root of the group order and constant space requirements.This thesis establishes new relationships for finite fields that are represented as the polynomial ring over the binary field modulo a primitive polynomial. With a subset of these properties, a novel approach is developed for the solution of the discrete logarithm in the multiplicative groups of these fields. This leads to a deterministic algorithm for small group orders that has linear space and linearithmic time requirements in the degree of defining polynomial, enabling an efficient correction of single-bit errors based on the corresponding cyclic codes.