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EC State aid rules : An analysis of the selectivity criterionAldestam, Mona January 2005 (has links)
The application of Art. 87(1) EC to taxes above all is connected to the application of the derogation method, which appears to be part of the selectivity criterion. This dissertation examines the application of the derogation method and the assessment of the selectivity criterion applied to taxes, primarily de lege lata, but also de lege ferenda. It begins with an analysis of the relationship among the criteria of Article 87(1) EC and continues with an analysis of the relationship between the derogation method and the assessment of the selectivity criterion applied to taxes. Several scholars have criticised the application of the derogation method because of the difficulty of identifying a derogation and of establishing the benchmark against which the derogation should be assessed. In this dissertation both the benchmark and the establishment of a derogation is analysed, partly with reference to the tax expenditure debate that occurred in the subject area of international taxation during the 1970s and 1980s. The selectivity criterion applied to taxes contains an assessment of justification, whereby the selective nature of a measure can be justified on the basis of the nature or general scheme of the system: Therfore the meaning and implications of this assessment are also examined. After all these issues have been examined de lege lata, the extents to which the application of the derogation method and the assessment of the selectivity criterion follow a logical system are discussed and recommendations for eliminating the identified deficiences are put forward.
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Design and synthesis of small molecule inhibitors of zinc metalloenzymesPatil, Vishal 28 October 2011 (has links)
Histone deacetylases (HDACs) are a class of enzymes that play a crucial role in DNA expression by removing an acetyl group from the ɛ-N-acetyl lysine residue on histone proteins. Out of 18 isoforms of HDAC enzymes which are classified into 4 classes, only 11 of them are metalloenzymes that require zinc for its catalytic activity. HDACs are considered promising target for drug development in cancer and other parasitic diseases due to their role in gene expression. Histone deacetylase inhibitors (HDACi) can cause cell cycle arrest, and induce differentiation or apotosis. While HDACi shows promising antitumor effects, their mechanism of action and selectivity against cancer cells have not been adequately defined yet. In addition, low oral bioavailability, short half-life time, bone marrow toxicity, and cardiotoxicity limit their use in clinic. Therefore, there is considerable interest in developing compounds with selectivity and specificity towards individual family members of HDACs. The prototypical pharmacophore for HDAC inhibitors consist of a metal-binding moiety that coordinates to the catalytic metal ion within the HDAC active site, a capping group that interacts with the residues at the entrance of the active site and a linker that appropriately positions the metal-binding moiety and capping group for interactions in the active site. It has been shown that modification of cap, cap linking moiety, linker or zinc binding group (ZBG) shows promises of superior potency and isoform selectivity. My thesis research involves manipulating different aspects of the pharmacophoric model to yield not only more potent, selective, and effective drugs but also to help understand the biology of HDAC isoforms. In addition, I was successful in extending studies on HDAC isoforms to other zinc metalloenzymes such as leishmanolysin (gp63) and spliceosome associated zinc-metalloenzymes to understand biology of these zinc metalloenzymes by developing potent and selective small molecule inhibitors. This will aid in improvement of existing therapeutics for treatment of cancer, leishmania, malaria and other genetic disorders.
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A critical appraisal of the criminalisation and prosecution of sexual violence under international criminal lawAkia, Brenda January 2011 (has links)
<p>Sexual violence leaves the victims psychologically traumatised and stigmatised in the eyes of its community. Used on a large scale, sexual violence can destabilise a society as a whole and when used during armed conflicts, it serves as a powerful weapon against members of a community. During armed conflicts, sexual violence is widespread and systematically used as a tool of war and this makes sexual violence amount to crimes against humanity, genocide and war crimes. This research paper critically analyses and evaluates sexual violence as an international crime, as well as its prosecution under international criminal law mainly by the International Criminal Court (hereafter ICC), International Criminal Tribunal for the Former Yugoslavia (hereafter ICTY) and International Criminal Tribunal for Rwanda (hereafter ICTR). It discusses the problem of selectivity that can be observed in prosecuting sexual violence that has in fact, left many victims of sexual violence dissatisfied. By doing so, it analyses the law as it is to determine whether the law applied during sexual violence prosecutions is sufficient. The paper also states recommendations that can contribute to the effective prosecution of sexual crimes under international criminal law.</p>
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Heterocyclic Cations as Potential Anticancer Agents: An Approach that Targets G-quadruplex with Different Binding ModesMusetti, Caterina Livia 16 April 2010 (has links)
G-quadruplex structures are found in important regions of the eukaryotic genome, such as telomeres and regulatory sequences of genes, and are likely to play important roles in regulation of biological events. The significant structural differences with duplex DNA make quadruplex DNA a very attractive target for anticancer drug design. The purpose of this study is to explore conformational space in a series of heterocyclic cations to discover novel structural motifs that can selectively bind and stabilize specific G-quadruplex arrangements. A variety of biophysical techniques such as thermal melting experiments, biosensor surface plasmon resonance, circular dichroism, fluorescence displacement assay and mass spectrometry were employed to evaluate the affinity of the compounds and their recognition properties. The screening of the molecules allowed the identification of not only selective G-quadruplex ligands but also potential quadruplex groove binders. These results can be useful for the development of new efficient telomerase inhibitors which are endowed with pharmacological activity.
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Structure and Function in Plant Ä12 Fatty Acid Desaturases and AcetylenasesGagne, Steve Joseph 22 December 2008
This study provides insight into the structure/function relationship between desaturases and acetylenases, and indicates amino acid residues within acetylenases which influence
reaction outcome. <i>Oleate desaturases</i> belong to a family of enzymes capable of introducing cis
double bonds between C12 - C13 in oleate esters. Acetylenases are a subset of oleate desaturase
enzymes which introduce a triple bond in the C12 - C13 position of linoleate. To better
understand which amino acids could be responsible for differentiating the activity of
acetylenases from typical desaturases, a total of 50 protein sequences were used to compare the
two classes of enzymes resulting in the identification of 11 amino acid residues which are
conserved within either separate family but differ between the two groups of enzymes. These
identified amino acid residues were then singularly altered by site-directed mutagenesis to test their role in fatty acid modification. Specifically, the wild type acetylenase, Crep1 from <i>Crepis alpina</i>, and a number of point mutants have been expressed in <i>Saccharomyces cerevisiae</i>,
followed by fatty acid analysis of the resulting cultures. Results indicate the importance of 4
amino acid residues within Crep1 (Y150, F259, H266, and V304) with regards to desaturase
and acetylenase chemoselectivity, stereoselectivity, and/or substrate recognition. The F259L mutation affected the acetylenase by converting it to an atypical FAD2 capable of producing both cis and trans isomers. The V304I mutation resulted in the conversion of Crep1 into a stereoselective FAD2, where only the cis isomers of 16:2 and 18:2 were produced. The Y150F
mutation led to a loss of acetylenase activity without affecting the inherent desaturase activity
of Crep1. The H266Q mutation appears to affect substrate selection causing an inability to bind
substrate (16:1-9c and/or 18:1-9c) in a cisoid conformation, resulting in an increased
accumulation of trans product. The changes in enzyme activity detected in cultures expressing
Crep1 mutants demonstrate the profound effect that exchanging as little as one amino acid can
have on an enzyme properties. Enzymes retain some conservation of amino acids necessary for
activity, such as those involved in metal ion binding, whereas subtle changes can affect overall
enzyme function and catalysis.
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The effect of client affiliation on the performance attributions of fund managers in South AfricaEnaw, Enih Ebot January 2011 (has links)
<p>This study seeks to evaluate the performance of unit trust managers based on their client affiliation classification. Worldwide, the number of investors investing in unit trusts is on the rise and increasingly they want to be able to evaluate the performance of the managers managing their funds so as to make better investment decisions. This increase in the asset size and number of unit trusts funds could be attributed but not limited to the low capital required for investment by small investors who before could not afford to invest in portfolios requiring large capital (Prather, Bertin, and Henker, 2004). In addition, the fund managers of these units are believed to have special skills such as market timing and stock selectivity which contribute to the performances they achieve. The evaluation of the performance of unit trust fund managers is a largely unexplored area in South Africa. As a result, the study focuses on South Africa fund managers and has as aim to evaluate the performance of two groups of fund managers (independent and dependent) who were classified based on their client affiliation structure. The client affiliation classification is as a result of the fund managerâs clientele base. The dependent group are those who formed part of a group structure and offer other wealth management services for which their clients or investors in the unit trust services originate from within the group while the independent group are those whose clients are pulled together from diverse individuals or institutions and does not form part of a group or render other services other than fund management. Two fund types were selected namely / general equity funds and balanced funds. It has also examined the underlying skills the different groups of fund managers possess. The performance of unit trust has an effect on many parties who are related in one way or the other to the unit trust funds. The results of this study will inform individual investors, trustees and asset consultants in their decision making process of selecting a fund manager. The results of the study will be of value to the asset management industry in terms of assessing their structures and restructuring the investment service business to meet the expectations of their clients / the investors. It could also be used as a marketing tool. Publicly available historical data on the returns generated by fund managers for a five year period from  / 2005 to 2009 was obtained. Analyses were done using the independent sampled t-test and the Treynor Mazel model respectively for the different research questions posed. The results obtained indicated that there were no statistically significant differences between the performances of independent fund managers with those of dependent fund managers. However, dependent fund managers of equity funds performed better than their counterparts the independent fund managers. In the case of balanced funds, the independent fund managers performed better than their dependent counterparts. On average, both fund  / manager types possessed selectivity skills for equity funds and none for balanced funds. However for both fund types, the dependent fund manager demonstrated more selectivity skills than their independent counterparts. The results for market timing skills demonstrated that on average, both fund managers did not possess market timing skills for balanced funds while possessing these skills for equity funds. The dependent  / fund managers demonstrated more market timing skills for balanced funds though negative when compared to that of their counterparts. On the other hand, the equity fund independent fund  / managers demonstrated more market timing skills than the dependent fund managers.</p>
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Sno2 based oxide systems: synthesis, material science and sensing properties as a function of surface hydroxylsPavelko, Roman G. 22 March 2010 (has links)
The thesis is dedicated to the synthesis, comprehensive material science and some sensing properties of SnO2-MetOx oxide systems (where MetOx are IVB and IIIB metal oxides). The study was performed in comparison with blank SnO2, and SnO2 doped with noble metals (Pd, Pt, Rh and their binary mixtures). Results of 8 ex-situ (TEM, HRTEM, XRD, FTIR, UV-Vis, BET, XPS and element analysis), 5 in-situ (TGA, MS-analysis, DRIFT, TXRD, TPR) techniques and sensing properties characterization (DC measurements as a function of temperature and gas composition) are discussed regarding surface chemistry of SnO2 sensing phenomenon. The special attention is paid to the role of surface hydroxyls in the processes related with conductivity change of semiconductor adsorbents upon hydrogen chemisorption and oxidation in dry and humid air. / Los principales objetivos de la presente investigación fueron la síntesis de las sistemas oxídicos SnO2-MetOx (donde MetOx corresponde a los óxidos de grupos IVB y IIIB), el estudio extensivo de sus propiedades fisicoquímicas y sus propiedades como sensores de gases. La investigación se ha basado en la comparación de estos materiales con el SnO2 puro y el SnO2 dopado con metales nobles (Pd, Pt, Rh y sus combinaciones binarias). Resultados de 8 estudios ex-situ (TEM, HRTEM, XRD, FTIR, UV-Vis, BET, XPS y MS-análisis de elementos), 5 estudios in-situ (TGA, MS-analysis, DRIFT, TXRD, TPR) y la caracterización de los sensores de gases (conductividad de los materiales semiconductores en función de la temperatura y los componentes de los gases compuestos) se analizan considerando las reacciones químicas superficiales del SnO2. Se ha prestado una especial atención en la participación de los grupos hidroxilo superficiales en el mecanismo de cambio de conductividad del adsorbente semiconductor durante la quimisorción u oxidación del hidrógeno en el aire seco o húmedo.
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Structure and Function in Plant Ä12 Fatty Acid Desaturases and AcetylenasesGagne, Steve Joseph 22 December 2008 (has links)
This study provides insight into the structure/function relationship between desaturases and acetylenases, and indicates amino acid residues within acetylenases which influence
reaction outcome. <i>Oleate desaturases</i> belong to a family of enzymes capable of introducing cis
double bonds between C12 - C13 in oleate esters. Acetylenases are a subset of oleate desaturase
enzymes which introduce a triple bond in the C12 - C13 position of linoleate. To better
understand which amino acids could be responsible for differentiating the activity of
acetylenases from typical desaturases, a total of 50 protein sequences were used to compare the
two classes of enzymes resulting in the identification of 11 amino acid residues which are
conserved within either separate family but differ between the two groups of enzymes. These
identified amino acid residues were then singularly altered by site-directed mutagenesis to test their role in fatty acid modification. Specifically, the wild type acetylenase, Crep1 from <i>Crepis alpina</i>, and a number of point mutants have been expressed in <i>Saccharomyces cerevisiae</i>,
followed by fatty acid analysis of the resulting cultures. Results indicate the importance of 4
amino acid residues within Crep1 (Y150, F259, H266, and V304) with regards to desaturase
and acetylenase chemoselectivity, stereoselectivity, and/or substrate recognition. The F259L mutation affected the acetylenase by converting it to an atypical FAD2 capable of producing both cis and trans isomers. The V304I mutation resulted in the conversion of Crep1 into a stereoselective FAD2, where only the cis isomers of 16:2 and 18:2 were produced. The Y150F
mutation led to a loss of acetylenase activity without affecting the inherent desaturase activity
of Crep1. The H266Q mutation appears to affect substrate selection causing an inability to bind
substrate (16:1-9c and/or 18:1-9c) in a cisoid conformation, resulting in an increased
accumulation of trans product. The changes in enzyme activity detected in cultures expressing
Crep1 mutants demonstrate the profound effect that exchanging as little as one amino acid can
have on an enzyme properties. Enzymes retain some conservation of amino acids necessary for
activity, such as those involved in metal ion binding, whereas subtle changes can affect overall
enzyme function and catalysis.
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Design and Application of Left-Handed Metamaterial-Based Negative Group Delay Circuits and Filters with High Selectivity Based on Composite Right/Left-Handed StructureLin, Chia-Chi 26 July 2011 (has links)
In a communication system, the group delay variation (GDV) causes the distortion of signal and the degradation of symbol error rate. Usually, the compensation of group delay (GD) utilizing positive group delay (PGD) results in further propagation delay. Therefore, this research studies the negative group delay (NGD) behavior of metamaterial. Through analyzing the effects on GD caused by poles and zeros of circuit, the group delay circuit capable of switching between NGD and PGD is presented. Further, adjustable negative group delay circuits (NGDCs) are designed based on the concept of poles and zero. The NGD generated by NGDC is used to achieve the equalization of GD and recover the distorted signal in time domain.
Additionally, owing to the limited frequency band of communication, a filter with high selectivity is required to utilize the available bandwidth. The character of left-handed metamaterial is applied to the design of filter for reducing the size and cost of traditional microstrip line filters with high selectivity. Under the balanced condition, composite right/left-handed (CRLH) transmission line behaves right- and left- handed characteristics in different frequency bands. Thus, a coplanar waveguide (CPW) filter with high selectivity, size reduction and low cost is presented utilizing such a CRLH structure.
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Age, working memory, and the strategic control of attention at encodingHayes, Melissa Gail 28 February 2011 (has links)
The current study investigated the effects of aging on the strategic control of attention at encoding and the extent to which this relationship was mediated by working memory capacity. The value-directed remembering task used by Castel et al. (2009) was modified to include an inhibitory task demand (i.e., value-directed forgetting), and age differences were predicted due to declines in the efficiency of inhibitory mechanisms. Results confirmed this prediction, as older adults were less efficient in maximizing their selectivity scores upon the inclusion of task interference, and working memory was found to be supportive of performance. Results additionally support an age-related decline in the directed forgetting effect, such that older adults recalled and recognized fewer TBR items and more TBF items, relative to younger adults. Taken together, results suggest an age-related decline in the ability to inhibit goal-irrelevant information, thereby limiting working memory resources available for greater processing of goal-relevant information.
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