The cancer stem cell (CSC) concept is still very controversial; therefore identification and isolation of this specific population remain challenging. A variety of putative markers have been described and measurement of high aldehyde dehydrogenase (ALDH) activity has been defined as a characteristic of stem cells (SCs). In this study, a library of novel small molecules (1,4-di-substituted acetalanthraquinones, AAQs), containing an acetal group as protected aldehyde functionality, was designed with the aim of probing affinity for ALDH metabolism and demonstrating their potential as molecular fluorescent probes to identify CSCs. The AAQs were shown to be subjective to acidic hydrolysis using 2M HCl at 37ºC; however compounds containing secondary or tertiary amine functionalities in their sidechain were only partly hydrolysed at 70 ºC. Metabolism studies were conducted using cytosolic fractions from rat liver enriched in ALDHs, yeast ALDH and human recombinant ALDH1A1. Some evidence was demonstrated which linked ALDH metabolism with aldehyde functionalities of hydrolysed AAQs (HAAQs). The AAQs were shown to emit far-red fluorescence (600-750 nm). A close relationship between structure modifications and alteration of cellular localisation, with gained specificity for selected sub-cellular compartments were achieved when assessed in A549 and U-2 OS cell lines. Thermal DNA denaturation and chemosensitivity assays were used to obtain information about DNA binding properties and cytotoxicity of AAQs and HAAQ congeners. All compounds were shown to be weak*to*moderately binding to DNA, and symmetrical 1,4-di-substituted compounds were shown to be non*toxic (IC50 = 100 :/! with non-symmetrical analogues generating IC50 values in the 1-100 :/ range. No fundamental variation in the biological activity was observed when comparing AAQs with HAAQs in the A549 (+ALDH) and MCF7 (-ALDH) cell lines. A pilot investigation revealed that aberrant gene methylation was cell-type dependent for three ALDH isoforms (1A1, 2, 3A1). Decitabine treatment led to enhanced protein expression for ALDH1A1 (A549), ALDH2 (MCF7) and ALDH3A1 (A549). In contrast, the protein level was reduced for ALDH1A1 in HT29 cells after decitabine treatment. ALDH1A1, ALDH2 and ALDH3A1 were highly expressed in prostate cell lines, with expression linked to promoter methylation. In contrast, low levels of DNA methylation were found in primary prostate cancer cells and benign prostatic hyperplasia. Interestingly, ALDH1A1, considered a SC marker, was found to be expressed at low levels in CD133+/ α2β1hi stem cell fraction and upregulated in CD133-= α2β1lo differentiated prostate cancer cells. In summary, the results in this thesis demonstrate the complexity and tumour type specificity of ALDH expression. This creates challenges for the development of selective probes for CSC isolation, such as the AAQs discussed in this thesis. Although inconclusive results were obtained in regard to AAQs and their potential in targeting ALDHs, selected AAQs were shown to reveal interesting biological features highlighting them as potential non-invasive cytometric probes for tracking molecular interactions in live cells. / EPSRC, Biostatus / The full text was made available at the end of the re-embargo period, 1st September 2017.

The main aim of this thesis was to evaluate the performance of the contrast sensitivity clock (CSC), a new screening device for measuring contrast sensitivity (CS) and glare. This device allows CS without glare, with glare and disability glare scores to be recorded. After initial data collection the design of the CSC was slightly amended improving the performance of the device. The amended design of the CSC was shown to be a valid, discriminative and repeatable measure for purpose. The CSC is also a quick test to perform and is relatively cheap to produce. If all these factors are considered it shows potential to become the test of choice for the assessment of visual glare. A head-mounted display system was also evaluated in terms of the glare effects it may cause. The monocular display screen of the device significantly reduced the CS of the eye directly exposed but also had an effect on binocular performance, reducing amounts of binocular summation. Electronic devices, including head-mounted displays and satellite navigation systems can seriously affect CS at low luminance levels, similar to those found when driving at night.

Made available in DSpace on 2016-04-25T18:39:36Z (GMT). No. of bitstreams: 1 Francisco Clairton Araujo.pdf: 525978 bytes, checksum: 3101f9a1e0593821687d983cfc750405 (MD5) Previous issue date: 2010-11-19 / In a dynamic and highly competitive business environment, the pressure for results is growing within organizations. On the market only organizations that best work up their competitive edges through a good management and creativity will remain. In this sense, shared services centers have contributed to organizations because they provide a consolidation of the company common activities optimizing resources, integrating technologies, processes and people, and above all generation of value for shareholders. When shared services centers are related internally to other business units of the organization it becomes necessary the valorization of intercompany transactions; hence the importance of transfer pricing because the lack of pricing methods for transfer price may jeopardize the measurement of results between business units and consequently the overall result of the organization. The objective of this work is to evaluate the various methods of transfer pricing between business units aiming at identifying the most suitable for evaluation and measurement of performance of a shared services center. To achieve this purpose, one has chosen to adopt as a research methodology, in addition to the literature a case study with action research in a German multinational company that has a shared services center. To achieve this purpose, in addition to a bibliographical survey one has chosen to adopt as research methodology a case study with research-action in a German multinational company having a shared services center. The research results have confirmed the expectation of cost reduction provided by the centralization of services through the SSC, and also in the light of the results obtained by the application of several methods of pricing for transfer pricing the most appropriate one to value intercompany transactions is the method based on market value / Num ambiente empresarial dinâmico e altamente competitivo, a pressão por resultados torna-se cada vez maior dentro das organizações. Permanecerão no mercado somente as organizações que melhor trabalharem seus diferenciais por meio de uma boa gestão e criatividade. Nesse sentido, é que os centros de serviços compartilhados têm contribuído com as organizações, pois propiciam uma consolidação das atividades comuns da empresa otimizando recursos, integrando tecnologias, processos, pessoas e, sobretudo, geração de valor aos acionistas. Quando os centros de serviços compartilhados se relacionam internamente com outras unidades de negócios da organização, torna-se necessária a valorização das transações intercompanhias; daí a importância do preço de transferência, pois a ausência de métodos de apreçamento do preço de transferência poderá comprometer a aferição dos resultados entre as unidades de negócio, e por consequência, o resultado global da organização. O objetivo da presente obra é o de avaliar os diversos métodos de preço de transferência entre as unidades de negócio, visando à identificação dos mais apropriados para avaliação e mensuração de desempenho de um centro de serviços compartilhados. Para atingir o objetivo proposto, optou-se por adotar como metodologia de pesquisa, além do levantamento bibliográfico, um estudo de caso conjugado com pesquisa-ação, em uma empresa multinacional alemã, que possui um centro de serviços compartilhados. Os resultados da pesquisa confirmaram a expectativa de redução de custos proporcionados pela centralização dos serviços por intermédio do CSC, e também, que à luz dos resultados apurados pela aplicação dos diversos métodos de apreçamento do preço de transferência, o método mais adequado para valorização das transações intercompanhias é o método com base no valor de mercado

La corrosion sous contrainte (CSC) est un phénomène synergique d'endommagement qui résulte d'un processus de corrosion (dissolution, adsorption) et d'une rupture mécanique (fissuration). Les mécanismes de couplage mécano-électrochimique en pointe de fissure nécessaires à la compréhension du phénomène sont encore mal connus puisqu'ils dépendent du système d'étude (métal/milieu agressif) et font intervenir de nombreux facteurs mécaniques et électrochimiques. Dans cette thèse, nous nous proposons d'étudier les interactions réciproques entre la dissolution et l'état de contrainte mécanique en pointe de fissure (facteurs d'intensité des contraintes) pour le cas du Zircaloy-4 en milieu aqueux halogéné. Les éprouvettes sont d'abord pré-fissurées par fatigue à l'air avec la technique du Load-Shedding, ce qui permet alors de maîtriser le facteur d'intensité des contraintes résiduel de pré-fissuration par fatigue. Ensuite, une pré-oxydation thermique est réalisée pour produire une couche de film passif sur les surfaces de l'éprouvette. Les réactions électrochimiques sont alors concentrées en pointe de fissure qui induit également une concentration des effets mécaniques. Des techniques de corrélation d'images sont développées dans le but d'identifier les facteurs d'intensité des contraintes et d'estimer la longueur de fissure en temps réel. Ainsi des essais originaux de CSC, permettant d'imposer les facteurs d'intensité en pointe de fissure, sont conduits et les résultats montrent alors clairement les effets synergiques entre l'évolution des mesures mécaniques et des courants de dissolution. D'autre part, l'existence d'un facteur d'intensité des contraintes seuil de propagation en CSC, présentant une forte dépendance à l'histoire de chargement et à la variation de l'état de contrainte locale en pointe de fissure (variation des facteurs d'intensité des contraintes), est mise en évidence. Ceci montre alors que la plasticité doit évoluer pour que la dissolution se produise. Ainsi, le temps caractéristique d'arriver de nouvelles dislocations en pointe de fissure ne doit pas dépasser la durée caractéristique des réactions de passivation. Enfin sur la base des résultats expérimentaux, un modèle de loi de propagation phénoménologique de fissure en CSC est proposé et ses paramètres sont identifiés et validés à partir de différents essais de CSC.

La crise financière de 2008 et la recherche de ses causes profondes a donné un nouvel élan au paradigme marxiste. Cette recherche offre une analyse marxiste des trajectoires des organisations syndicales en Belgique, ainsi qu'une analyse organisationnelle inspirée de Mintzberg. Les apports principaux de l'analyse marxiste sont la prise en compte de l'historicité des organisations, de l'importance de l'idéologie et particulièrement des luttes idéologiques qui se déroulent au sein et en dehors des organisations.Les deux organisations étudiées sont les organisations syndicales chrétienne (ACV-CSC) et socialiste (ABVV-FGTB). L'origine de ces organisations repose sur un conflit d'intéret radical entre le capital et le travail. De plus, elles disposent d'une profondeur historique de plus d'un siècle, se développent dans une démocratie consociative qui privilégie le consensus au conflit, et construisent une architecture de concertation sociale dont l'évolution permet d'interroger le rôle de l’État.Les résultats de cette recherche prennent la forme d'hypothèses théoriques, vérifiées dans les cas étudiés, illustrant les apports d'une analyse marxiste, davantage dialectique et orientée sur l'analyse de classe, qui permet d'accorder davantage d'importance au rôle et à l'influence de l'idéologie au sein et en dehors des organisations.Ces hypothèses dessinent trois types de trajectoires futures pour les organisations syndicales en Belgique. La trajectoire qui sera suivie ces prochaines années dépend fortement de la façon dont les organisations syndicales – aux différents niveaux de l'organisation, opéreront un travail idéologique de recentrage sur le clivage de classe. / Doctorat en Sciences économiques et de gestion / info:eu-repo/semantics/nonPublished

Dans un contexte normatif toujours plus sévère concernant les rejets automobiles polluants, la substitution des aciers par des alliages d’aluminium dans les structures des véhicules est en plein essor. Ce projet de thèse, qui s’inscrit dans un programme de développement de la société Constellium, cible plus précisément les alliages d’aluminium de la série 7xxx (Al-Zn-Mg) qui, malgré leurs propriétés mécaniques élevées, peuvent présenter une sensibilité à la corrosion sous contrainte (CSC) liée au phénomène de fragilisation par l’hydrogène (FPH). La compréhension des mécanismes mis en jeu dans ce type d’endommagement constitue donc une première étape vers une optimisation métallurgique en vue d’une industrialisation future de ces alliages dans le secteur automobile. La première partie de ces travaux est consacrée à l’étude de l’influence de l’état métallurgique de l’alliage 7046 sur son comportement en CSC et à l’identification des mécanismes de dégradation. Un lien direct a pu être mis en évidence entre l’abattement des propriétés mécaniques et les modes de rupture actifs et la quantité d’hydrogène dans l’alliage. Les deux modes d’endommagement observés, intergranulaire-fragile et transgranulaire-fragile, ont respectivement été attribués à un enrichissement en hydrogène aux joints de grains et au piégeage de l’hydrogène au niveau des précipités intragranulaires. Les interactions entre l’hydrogène et les précipités fins d’une part et les dislocations d’autre part, identifiés comme deux hétérogénéités microstructurales critiques vis-à-vis de la FPH, ont été étudiées à une échelle plus locale dans la seconde partie du travail de thèse. Les essais ont été réalisés sur des échantillons modèles, chargés en hydrogène en milieu H2SO4 sous polarisation cathodique et la profondeur de pénétration de l’hydrogène a été évaluée par SKPFM (Scanning Kelvin Probe Force Microscopy). L’ensemble des résultats obtenus met en évidence : 1/ un effet « barrière » des précipités fins et des dislocations sur la diffusion de l’hydrogène en relation avec un abattement des propriétés mécaniques moins important, 2/ un transport possible de l’hydrogène par les dislocations et 3/ l’efficacité du SKPFM pour déterminer précisément des coefficients de diffusion apparents de l’hydrogène. Ces résultats ouvrent ainsi de nouvelles pistes vers la compréhension des mécanismes de CSC dans les alliages Al-Zn-Mg.

There is an increasing acknowledgement in Eco-municipalities – cities using the Framework for Strategic Sustainable Development (FSSD) as a tool for their planning process – of the need for Cross-Sector Collaboration, but the necessary expertise is often lacking. The purpose of this study is to better understand effective CSC in Eco-municipalities through indicating potential leverage points and inform the use of the FSSD in this specific context. An 'effective CSC' lens is constructed from general CSC literature and documents from Eco-municipalities. 187 barriers and enablers to effective cross-sector collaboration are identified from interviews with experts and interviews from the In-depth Case Study in the city of Eindhoven. An 'Importance Index' defined by alignment with Lens Factors is developed to select key indicators. These key indicators are clustered into 45 potential leverage points for effective CSC in Eco-municipalities. The use of these potential leverage points is checked in an In-depth Case Study through a Causal Loop Diagram in which nine leverage points were identified. Interrelations between these leverage points, unexpected results and methodology are discussed, conclusions are drawn, and further research is suggested.

There has been a rapid increase interest in computational number theory ever since the invention of public-key cryptography. Various attempts to solve the underlying hard problems behind public-key cryptosystems has led to interesting problems in computational number theory. One such problem, called the cubic sieve congruence problem, arises in the context of the cubic sieve method for solving the discrete logarithm problem in prime fields. The cubic sieve method requires a nontrivial solution to the Cubic Sieve Congruence (CSC)x3 y2z (mod p), where p is a given prime. A nontrivial solution must satisfy x3 y2z (mod p), x3 ≠ y2z, 1≤ x, y, z < pα , where α is a given real number ⅓ < α ≤ ½. The CSC problem is to find an efficient algorithm to obtain a nontrivial solution to CSC. This thesis is concerned with the CSC problem. Recently, the parametrization x y2z (mod p) and y υ3z (mod p) of CSC was introduced. We give a deterministic polynomial-time (O(ln3p) bit-operations) algorithm to determine, for a given υ, a nontrivial solution to CSC, if one exists. Previously it took Õ(pα) time to do this. We relate the CSC problem to the gap problem of fractional part sequences. We also show in the α = ½ case that for a certain class of primes the CSC problem can be solved deterministically Õ(p⅓) time compared to the previous best of Õ(p½). It is empirically observed that about one out of three primes are covered by this class, up to 109

Energianvändningen idag är den största bidragande faktorn till de globala klimatförändringarna vilket ställer krav på mer hållbar och resurseffektiv energihantering. I Sverige står sektorn bostäder och service för ca 40 % av den slutgiltiga energianvändningen motsvarande 144 TWh. För att nå en mer hållbar byggnadssektor har EU i direktivet för Byggnaders Energiprestanda satt målet att byggnadssektorn ska vara fossilfri till 2050, samt beslutat att varje medlemsstat ska etablera en långsiktig renoveringsstrategi. Nationellt finns därmed målet att minska den totala energianvändningen per uppvärmd area med 50 % till 2050 jämfört med 1995. Detta innebär att omfattande energieffektiviseringsåtgärder (EEÅ) behöver implementeras i Sveriges byggnadsbestånd. I examensarbetet jämförs den nationella potentialen avseende energibesparing, kostnadseffektivitet samt utsläppsreduktion av koldioxidekvivalenter (CO2eq) för olika energieffektiviseringsåtgärder (EEÅ) kopplade till uppvärmning och tappvarmvattenanvändning i flerbostadshus. Vidare undersöks även hur väl anpassade befintliga styrmedel är för de studerade EEÅ. För att besvara frågeställningarna har sex olika typhus tagits fram vilka är representativa för Sveriges bestånd av flerbostadshus. Dessa byggnader har modellerats i programvaran IDA ICE och energisimuleringar har genomförts för att undersöka effekterna av samtliga EEÅ. Vidare, styrmedel kopplade till energieffektivisering av flerbostadshus har analyserats och dess innebörd för olika EEÅ granskats. Resultatet visar att inom det svenska flerbostadshusbeståndet har installation av spillvattenvärmeåtervinning och FTX störst tekniskt möjlig energibesparingspotential med en årlig nationell energibesparingspotential på 5,3 TWh respektive 4,7 TWh. Isolering av tak är den EEÅ med högst kostnadseffektivitet per sparad energienhet, 334–579 SEK/MWh beroende på klimatzon, följt av spillvattenvärmeåtervinning och FTX som har en kostnadseffektivitet på 1267–1503 SEK/MWh respektive 1882–3587 SEK/MWh. Takisolering är även den EEÅ som är mest kostnadseffektiv för utsläppsminskning av koldioxidekvivalenter följt av spillvattenvärmeåtervinning och FTX. För takisolering är kostnadseffektiviteten 5,9–10,3 tSEK/ton CO2eq, 28,2–33,5 tSEK/ton CO2eq för spillvattenvärmeåtervinning och 39,5–93 tSEK/ton CO2eq för installation av FTX. Utifrån de styrmedel som studerats konstateras det att befintliga styrmedel för energieffektivisering i flerbostadshus inkluderar konventionella EEÅ men att det finns bristfällig information och krav gällande återvinning av värme från spillvatten trots åtgärdens höga energibesparingspotential och kostnadseffektivitet. Bättre kunskap och information gällande kostnadseffektiviteten för olika EEÅ kan leda till mer resurseffektiva åtgärdsförslag från energiexperter och även öka renoveringstakten. / Today's energy use is the largest contributing factor to global climate change, which calls for a more sustainable and resource-efficient energy management. In Sweden, the residential and service sector accounts for about 40% of the final energy use, corresponding to 144 TWh. To achieve a more sustainable building sector, the European Commission has set a target in the Energy Efficiency Directive that the building sector should be fossil-free by 2050 and decided that every Member State should establish a long-term renovation strategy. Nationally, there is a target to reduce the total energy use per heated area by 50% by 2050. This requires a large-scale implementation of energy efficiency measures (EEMs) in Sweden's building stock. This master thesis compares the national potential regarding energy saving, cost-effectiveness and emission reduction of carbon dioxide equivalents (CO2eq) for various EEMs linked to heating and domestic hot water use in multi-family buildings. Furthermore, it is also examined how well-adjusted existing policy instruments are to the studied EEMs. To answer the research questions, six different reference buildings, which are representative of Sweden’s stock of multi-family buildings, have been developed. These buildings have been modeled using the software IDA ICE and energy simulations have been carried out to investigate the effects for all EEMs. Policy instruments regarding energy efficiency in multi-family buildings have been analyzed and their significance for various EEMs have been investigated. The results show that installation of wastewater heat recovery and exhaust air heat recovery has the highest technically possible energy saving potential with an annual national saving potential of 5.3 TWh and 4.7 TWh, respectively Roof insulation is the EEM with the highest cost-effectiveness per saved energy unit, 334–579 SEK/MWh depending on climate zone, followed by wastewater heat recovery with a cost-effectiveness of 1267–1503 SEK/MWh and exhaust air heat recovery with 1882–3587 SEK/MWh. Roof insulation is also the EEM that is most cost-effective regarding reduced CO2eq -emissions, followed by wastewater heat recovery and exhaust air heat recovery. For roof insulation, the cost-effectiveness is 5.9–10.3 kSEK/ton CO2eq, 28.2–33.5 kSEK/ton CO2eq for wastewater heat recovery and 39.5–93 kSEK/ton CO2eq for installation of exhaust air heat recovery. Based on the studied policy instruments, it is found that the existing policy instruments for EMMs in multi-family buildings include conventional EMMS. However, there is insufficient information and requirements regarding recovery of heat from wastewater despite the measure's high energy saving potential and cost-effectiveness. Better knowledge and information regarding the cost-effectiveness of various EEMs can lead to more resource-efficient suggestions from energy experts and increase the pace of renovation.

International Telemetering Conference Proceedings / October 25-28, 1999 / Riviera Hotel and Convention Center, Las Vegas, Nevada / Today’s telemetry systems can reduce spectrum demand and maintain secure voice by encoding analog voice into digital data using; Continuously Variable Slope Delta Modulation ( CVSD ) format and imbedding it into a telemetry stream. The model CSC-0390 DvD system is an excellent choice in decoding digital voice, designed with flexibility, efficiency, and simplicity in mind. Flexibility in design brings forth a capability of operating on a wide variety of telemetry systems and data formats without any specialized interfaces. The utilization of 74HC series circuit technology makes this DvD system efficient in design, low cost, and lower power consumption. In addition the front panel display and control function is also is an example of Simplicity in design and operation.