This work refers to the area of bio-nanotechnology and concerns the selective immobilization of DNA or other bio-template on microstructured gold contacts and which then permit a coordinated cooperation of several of these nanotemplate, e.g., within a microreactor. The immobilization of such nano-objects should be realized through functional thin polymer films which provide binding groups. Thus, the main aim of this work was the development of polymeric materials for thin functional films which permit to deposit on different substrates a wide variation of functional elements or metal structures and to achieve a pattern formation using optical grid methods. In order to realize this concept it was necessary to design and develop a polymer system based on suitable photolabile units and in addition having anchoring groups which attach on specific substrates like gold. In this terpolymer concept was aimed for which consists of three components with particular functions in suitable molar ratios, which allow the tune the properties of the materials, and provide: amino photolabile protected groups for the photolithographic creation of patterned areas with free amino groups, which are available for further modifications like attachment of colloids, metallization or attachment of DNA strands; disulfide derivative anchor groups providing anchoring capacity for gold surface and spacer groups for adjusting the film quality. These multifunctional terpolymers should be synthesised by free radical polymerisation of suitable monomers. Although these techniques are successful, they are limited by their complexity, rigorous synthetic demands, as well as incompatibility with many functional termolabile and highly reactive functionalities. To overcome these difficulties a polymerisation technique based on “living” free radical polymerisation has been used in this work. A highly efficient polymer-analogous modification allows to introduce the functionalities after the polymer construction reaction. The production of suitable prepolymers [poly(styrene-r-4-propargyl-oxystyrene)] was carried out with the help of a controlled synthesis methodology “nitroxide mediate radical polymerization" followed by polymer analogous reaction using one of the most efficient click reactions, the Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition between terminal acetylenes and azides to attach further functionalities through the formation of a stable 1,4-disubstituted 1,2,3-triazol ring . The combination of nitroxide mediated radical polymerization (NMRP) and click chemistry was used to produce well-defined random copolymer. It could already be shown that also block copolymers can be prepared which give the chance to combine nanostructure formation in block copolymers with special functionality. Thus, the special properties of these functional polymers like the capability for photopatterning and anchoring onto gold substrates make them very interesting for nanotechnology applications. / Diese Arbeit bezieht sich auf das Gebiet der Bionanotechnologie und betrifft ein neuartiges Verfahren zur selektiven Immobilisierung der DNA oder anderer Biomoleküle auf mikrostrukturierten Goldkontakten, welche dann ein koordiniertes Zusammenwirken von einzelnen Nanomolekülen ermöglichen, z.B. in einem Mikroreaktor. Die Immobilisierung solcher Nanoobjekte soll durch dünne Funktionsschichten realisiert werden, die die Anbindungsgruppen liefern. Folglich war das Hauptziel dieser Arbeit die Entwicklung von Polymermaterialien für dünne Funktionsschichten, die die Aufbringung einer großen Vielzahl von Funktionselementen oder metallischen Strukturen auf verschiedenen Substraten gestatten und die Strukturierung durch den Einsatz von lithographischen Methoden ermöglichen. Um dieses Konzept zu realisieren, war es notwendig, ein Polymersystem zu gestalten und zu entwickeln, welches auf geeignete photolabile Einheiten basiert und zusätzlich Ankergruppen hat, die mit spezifischen Substraten wie Gold verbunden ist. Dieses Terpolymerkonzept wurde gezielt aus drei Komponenten mit speziellen Funktionen in entsprechenden molaren Verhältnissen gebildet, die eine Abstimmung der Materialeigenschaften ermöglicht und folgendes bereitstellt: photolabile geschützte Aminogruppen für die photolitographische Strukturerzeugung mit freien Aminogruppen, welche für weitere Modifikationen verfügbar sind wie das Anhängen von Kolloiden, die Metallisierung oder Anfügung von DNA-Strängen; disulfide Derivate für die kovalente Anbindung auf der Goldoberfläche und Spacer-Gruppe für Verbesserung der Schichtenbildung. Diese multifunktionalen Terpolymere sollen durch eine freie radikalische Polymerisation von entsprechenden Monomeren synthetisiert werden. Obwohl diese Techniken erfolgreich sind, sind sie eingeschränkt durch ihre Komplexität, den strengen synthetischen Anforderungen, sowie der Inkompatibilität mit vielen funktionalen thermolabilen und hochreaktiven Funktionalitäten. Um diese Schwierigkeiten zu überwinden wurde eine Polymerisationstechnik für diese Arbeit genutzt, die auf der „lebenden“ freien radikalischen Polymerisation basiert. Eine hoch effiziente polymeranaloge Modifizierung erlaubt die Einführung von Funktionalitäten nach der Polymeraufbaureaktion. Die Herstellung von entsprechenden Präpolymeren Poly(Styrol-r-4-Propargyl-oxystyrol) wurde mittels einer kontrollierten Synthesemethodik „Nitroxid-mediated controled radical polymerisation“ (NMRP) durchgeführt, gefolgt von der Polymeranalogreaktion, die eine der effizientesten Click-Reaktion - die Cu(I) katalysierte 1,3-dipolar Cycloaddition von terminalen Alkinen an Aziden nach Huisgen nutzt, um weiter Funktionalitäten durch die Bildung eines stabilen 1,4-disubstituierten-[1,2,3]-Triazolringes anzufügen. Die Kombination von NMRP und Click-Chemie wurde zur Herstellung eines exakt definierten Random Copolymers genutzt. Es konnte bereits gezeigt werden, dass auch Blockcopolymere geschaffen werden können, die eine Möglichkeit zur Kombination von Nanostrukturformationen in Blockcopolymeren mit speziellen Funktionaltäten bieten. Folglich sind die speziellen Eigenschaften dieser Funktionalpolymere wie die Fähigkeit zur Photostrukturierung und Verankerung auf Goldsubstraten für nanotechnologische Anwendungen sehr interessant.

DAISY has published a Specification for DAISY Protected Digital Talking Book. This paper discusses why such a specification is useful, not only for rightsholders but also for readers with print disabilities. An implementation of PDTB2 is proposed, called dtbprotect. It makes possible to simply produce an encrypted book from a book in DAISY format. It is currently experimented on the Helene Digital Library for the blind. It will be made available open source as to facilitate its implementation by other digital libraries.

本稿は、会社の倒産局面で株主が会社に対して有する債権について、他の一般債権と異なる取扱いを認めることの根拠およびそのような取扱いを認める必要性を考察するものである。 / 博士(法学) / Doctor of Laws / 同志社大学 / Doshisha University

Silyl ether protecting groups are important tools in organic synthesis, ensuring selective reactions of hydroxyl functional groups. Enantiospecific formation or cleavage could simultaneously enable the resolution of racemic mixtures and thus significantly increase the efficiency of complex synthetic pathways. Based on reports that lipases, which today are already particularly important tools in chemical synthesis, can catalyze the enantiospecific turnover of trimethylsilanol (TMS)-protected alcohols, the goal of this study was to determine the conditions under which such a catalysis occurs. Through detailed experimental and mechanistic investigation, we demonstrated that although lipases mediate the turnover of TMS-protected alcohols, this occurs independently of the known catalytic triad, as this is unable to stabilize a tetrahedral intermediate. The reaction is essentially non-specific and therefore most likely completely independent of the active site. This rules out lipases as catalysts for the resolution of racemic mixtures of alcohols through protection or deprotection with silyl groups.

To study the functions of glycoconjugates in biological systems reliable and efficient protocols for glycoconjugate synthesis are needed. To reach this goal we have developed methods for solid-phase synthesis of glycoconjugates that can be monitored with gel-phase 19F spectroscopy using fluorinated linkers, building blocks, and protecting groups. We have developed a new fluorine containing linker suitable for solid-phase synthesis of glycoconjugates. The linker was more acid-labile than similar linkers in order to enable cleavage under mild conditions of the target compound from the linker resin.  A carbamate-based strategy has been applied to attach a spacer carrying an amino group to a fluorinated Wang linker for synthesis of amino-functionalized glycoconjugates using thioglycoside donors with fluorinated protective groups. Cleavage from the solid support was performed with trifluoroacetic acid and subsequent protecting group removal gave the target compound. The terminal amine was conjugated with didecyl squarate and this derivative can be attached to various proteins and solid surfaces carrying primary or secondary amines. To evaluate this methodology we have immobilized glycoconjugates in amino-functionalized microtiter plates and successfully probed them with lectin. In addition, a novel fluorine containing protecting group has been designed, synthesized and evaluated. The protecting group was used for protection of the unreactive 4-OH in a galactose building block that was applied in the synthesis of 6-aminohexyl galabioside and was removed with TBAF in THF. Adenovirus serotype 8 (Ad8), Ad19, and Ad37 cause the severe ocular infection, epidemic keratoconjunctivities (EKC). During infection, the adenoviruses interact with sialic acid containing glycoconjugates on the epithelial cells via fiber structures extending from the viral particles. The virus particle most likely binds to the host cell in a multivalent way by simultaneously using multiple fiber proteins and binding sites. Multivalent sialic acid containing conjugates could efficiently inhibit Ad37 cell attachment and subsequent infection of human corneal epithelial (HCE) cells. Three compact tri- and tetravalent sialic acid conjugates were prepared and evaluated as inhibitors of adenoviral host cell attachment and subsequent infection and all conjugates were potent as anti-adenoviral agents. The conjugates can readily be synthesized from accessible starting materials. A crystal structure of the Ad37 fiber knob protein and the trivalent sialic acid conjugate showed that the three binding sites were all occupied by one sialic acid residue each.

近來各國政府對於公共服務的提供，越來越傾向公私協力的方式，以滿足人民的多元需求，但是有時因為政府的監督效率不彰甚至是政府與財團勾結，以至於企業組織的不法行為嚴重影響了公共利益。而外部的監督機制效果失靈，弊端揭發(whistle blowing)就成為了最後一道防線。但是，不論在公私部門，只要是在組織內揭露不法情事，勢必牽涉許多複雜的因素，以及可能對揭發者造成風險，再加上我國法制的不健全難以對揭弊者提供完善的保護，這些都將影響成員揭發的意願。 因此，為探討上述問題，本研究採取質性研究的方式，運用文獻回顧與深度訪談作為研究方法。本研究的研究架構是從弊端揭發者的心理進程發展依序探討，首先，以公務倫理或企業倫理、揭弊前因素以及預期揭弊後因素之三類現有因素做出初步判斷，再者，以前述判斷結果作為依據，將揭弊管道、對象以及手段納入綜合考量，最後做出揭發弊端與否的決定。本研究之研究發現認為，第一，企業倫理與公務倫理難以促使揭弊行為產生。第二、有利組織弊端揭發的情境與結構包括溝通管道暢通、扁平化的組織以及創新傾向的組織文化並且權力在其中居於主導地位。第三、現行保護機制無法保障私部門成員之工作與公務人員之安全。 另外，建議後續研究者可以選擇公私協力之個案，或是可以就組織中的「有權者」的角度來探討。最後，本研究根據研究發現提出幾點實務建議： 一、 制定公益揭發專法 二、 增加組織成員職涯規劃的多元性 三、 加重行賄者責任 四、 改善政風單位處理程序 關鍵詞：弊端揭發過程、公務倫理、企業倫理、弊端揭發者保護機制 / Nowadays, to satisfy the diverse demands from people, governments tend to work with business organizations to provide better public service. However, due to the possibilities of poor supervision from governments and collusion between both parties, public interest is often under great threat or even severely violated. Therefore, whistle-blowing will be the last defense once the external control systems fail. No matter in public or private organizations, it may put the whistleblower at risk while disclosing wrongdoings which involves many complex factors. And it could also affect people’s willingness of being a whistleblower due to the lack of protecting system in our existing legal regime. To investigate above topic, this study is conducted with qualitative research analysis, and is to use documentary analysis and depth interview as the research methods. The conceptual framework is to investigate by the whistleblower’s psychological process in sequence. First of all, the whistleblower will make the initial judgments with three existing factors: administrative ethics or business ethics, the factors prior to whistle-blowing, and the expected factors after whistle-blowing. Therefore, based on the initial judgments mentioned above, the whistleblower will decide whether to blow the whistle or not after taking channels, objects, and means into account. The findings of this research indicate three following points: (1) Administrative ethics or business ethics lead to little possibility that brings out whistle-blowing. (2) The situations or structures which are conducive to whistle-blowing include unimpeded communication channel, horizontal organization, and innovation-tended organizational culture. And the power holds a dominant position. (3) Existing protecting system cannot ensure the right to work of people working in private sector, nor the safety of public servant. In addition, the author suggests that succeeding investigators choose the case related to public private partnership, or probe from the perspective of the powers. At last, the practical suggestions based on the findings of this study are as following: 1. To legislate for public interest disclosure 2. To enrich the diversity of members’ career development 3. To aggravate the consequences of giving bribes 4. To improve the working procedures of the department of civil service ethics Keywords: the Process of Whistle-blowing, Administrative Ethics, Business Ethics, Whistleblower Protecting System

Submitted by Nara Lays Domingues Viana Oliveira (naradv) on 2015-06-11T18:49:45Z No. of bitstreams: 1 000000B7.pdf: 849834 bytes, checksum: e36fdbff75b31763153fcaca5244644a (MD5) / Made available in DSpace on 2015-06-11T18:49:45Z (GMT). No. of bitstreams: 1 000000B7.pdf: 849834 bytes, checksum: e36fdbff75b31763153fcaca5244644a (MD5) Previous issue date: 2012-06-26 / Nenhuma / O direito à saúde é um direito fundamental, formal e materialmente constitucional, mas que, apesar de sua previsão constitucional, conforme dicção do art. 196 da Constituição Federal, um “direito de todos e dever do Estado, garantido mediante políticas sociais e econômicas que visem à redução do risco de doença e de outros agravos e ao acesso universal e igualitário às ações e serviços para sua promoção, proteção e recuperação”, na prática, ele não é concretizado. Essa dissertação traça um histórico dos direitos humanos e fundamentais, conceitos e história da saúde e suas formas interventivas, demonstra a inefetividade da proteção ao direito fundamental à saúde pelos atuais modelos de intervenção, aponta as principais causas da crise na saúde, demonstra o papel dos princípios na concretização do direito fundamental à saúde, especialmente o princípio da prevenção, destaca o direito fundamental à boa administração pública para concretização desse direito fundamental, apresenta novas reflexões sobre a saúde, pela implantação de medidas preventivas e os desafios a serem superados para sua implantação, para, ao final, construir pressupostos para uma atuação preventiva na saúde para concretização do direito fundamental à saúde. / The right to health is a fundamental right, formal and materially constitutional, but, despite its constitutional provision, as the diction of Federal Constitution art. 196 a “right of all and duty of the State, warranted by social and economic politics that aimed at reducing the risk of disease and other hazards and at universal and equal access to actions and services for its promotion, protection and recovery”, in practice it is not achieved. This thesis outlines a history of human rights and fundamental concepts and health history forms and interventional demonstrates the ineffectiveness of protecting the fundamental right to health by current models of intervention, indicates that the main causes of the crisis in health, demonstrates the role of principals in the implementation of the fundamental right to health, especially the principle of prevention, highlights the fundamental right, presents new perspectives on health, the implementation of preventive measures and the challenges to be overcome for their installation, to , ultimately to build assumptions a preventive action in health for achieving the fundamental right to healt.

Made available in DSpace on 2016-04-26T20:19:34Z (GMT). No. of bitstreams: 1 Thereza Christina Vieira Marcondes.pdf: 2532269 bytes, checksum: 2ae6fdff0ccc6ceb50d9df6a1e34a948 (MD5) Previous issue date: 2010-06-30 / The issues related to domestic violence and gender inequality require interest for several reasons. The promulgation of Law 11,340, of 07 August 2006, appointed by the President of "Maria da Penha Maia" prompted many debates, both in the legal world and in society. With three years of duration, the mood is not quieted. Persist sometimes heated discussions. This justifies studies and reflections on the law that expanded the concepts of domestic violence against women, proposed a system of protection and the concentrated focus of attention on the victim. The woman, as victim of this violence is considered from the perspective of a complete individual: that is, deserves the protection of the law in the physical, psychological, sexual, property, moral. The Law of Domestic and Family Violence against Women proposed the creation of mechanisms to deter and prevent abuse within families and establish guidelines to combat discrimination, affirming the Human Rights of women, while recognizing the vulnerability of women under domestic relations or family. The constitutional principles of equality and dignity require the guarantee of Human Rights of Women, derived from the process of specialization and individualization of Human Rights. Law 11.340/06 was edited to meet the recommendations, in order to achieve an effective response to domestic violence and conceived from the perspective of gender, seek multidisciplinary solutions to the issue of violence against women, including measures awareness and training of professionals in various areas to give concreteness to a legal system out for Human Rights, in accordance with the democratic State of Law / Os temas relacionados à violência doméstica e à desigualdade de gênero demandam interesse por diversas razões. A promulgação da Lei 11.340, de 07 de agosto de 2006, nomeada pelo Presidente da República de Lei Maria da Penha Maia incitou diversos debates, tanto no mundo jurídico quanto na sociedade civil. Com de três anos de vigência, os ânimos não se aquietaram. Persistem discussões por vezes acaloradas. Isso justifica reflexões e estudos sobre a lei que ampliou os conceitos de violência intrafamiliar contra a mulher, propôs um sistema de proteção e centrou o foco de atenções na vítima. A mulher, vítima dessa modalidade de violência é considerada sob o prisma de um indivíduo completo: vale dizer, merece a proteção da lei sob o aspecto físico, psicológico, sexual, patrimonial, moral. A lei de Violência Doméstica e Familiar contra a Mulher propôs-se a criar mecanismos para coibir e prevenir os abusos intrafamiliares e estabelecer diretrizes para o combate da discriminação, reafirmando os Direitos Humanos das mulheres, sem deixar de reconhecer a condição de vulnerabilidade feminina no âmbito das relações domésticas ou familiares. Os princípios constitucionais da igualdade e da dignidade pressupõem a garantia dos Direitos Humanos das Mulheres, derivados do processo de especialização e individualização dos Direitos Humanos. A Lei 11.340/06 foi editada para atender a recomendações internacionais, com o objetivo de alcançar uma resposta efetiva contra a violência doméstica e concebeu, sob a perspectiva de gênero, buscar soluções multidisciplinares para a questão da violência contra a mulher, inclusive com medidas de sensibilização e capacitação de profissionais de diversas áreas, para dar concretude a um sistema jurídico atento aos Direitos Humanos, em conformidade com o Estado Democrático de Direito

Submitted by Elesbão Santiago Neto (neto10uepb@cche.uepb.edu.br) on 2016-09-06T20:02:14Z No. of bitstreams: 1 PDF - Marília Cordeiro Serra.pdf: 24917357 bytes, checksum: 517aeb31269b5fc1a744fb037dc0995c (MD5) / Made available in DSpace on 2016-09-06T20:02:14Z (GMT). No. of bitstreams: 1 PDF - Marília Cordeiro Serra.pdf: 24917357 bytes, checksum: 517aeb31269b5fc1a744fb037dc0995c (MD5) Previous issue date: 2015-07-24 / CAPES / This work aims to verify if the Responsibility to Protect (RWP) is innovation in the position of Brazil in UN forums, as well as its compatibility with the foreign policy strategies of the country, detailing it's innovative aspects and explaining in which previous occasions such proposals and positions emerged while argument of the country or third parties. The work presents a study regarding the development of rules of conduct existing in the international system for cases of intervention, emphasizing the normative evolution of UN peacekeeping operations and the concept of Responsibility to Protect (R2P). It details the Brazilian proposal, with its many points of contact with the aforementioned concept and its reception in the international system through the analysis of statements issued by the United Nations, representatives of NGOs, IOs and civil society organizations. It also discusses about the major foreign policy biases adopted by the Brazilian government from 1990 to 2014, through the analysis of the speeches of the national delegation to the General Assembly and the UN Security Council. Therefore, it is able to verify that the RWP presents no major outbreaks of incongruity with the R2P—dating back to the standard ratified by the United Nations for the construction of most of its normative basis—and is extremely consistent with the lines of foreign policy adopted by Brazil over the past 24 years. / Este trabalho visa verificar se a Responsabilidade ao Proteger (RwP) representa inovação no posicionamento do Brasil nos foros onusianos, bem como sua compatibilidade com as estratégias de política externa do país, detalhando seus aspectos inovadores e explicitando em quais ocasiões anteriores tais propostas e posições surgiram enquanto argumento do próprio país ou de terceiros. Para tanto, realiza um estudo sobre o desenvolvimento das normas de conduta vigentes no sistema internacional para os casos de intervenção, com ênfase na evolução normativa das operações de paz da ONU e no conceito da Responsabilidade de Proteger (R2P). Detalha a proposta brasileira, apresentando seus—muitos—pontos de contato com o supracitado conceito e sua recepção no sistema internacional, através da análise de declarações emitidas por membros das Nações Unidas, representantes de ONGs, OIs e organizações de sociedade civil. Versa, ainda, sobre os principais vieses de política externa adotados pelos governos brasileiros no período de 1990 a 2014, por meio a análise dos discursos da delegação nacional na Assembleia Geral e no Conselho de Segurança das Nações Unidas. Sendo assim, é possível verificar que a RwP não apresenta grandes focos de incongruência com a R2P—remontando à norma ratificada pelas Nações Unidas para a construção da maior parte de seu embasamento normativo—e é extremamente coerente com as linhas de política externa adotadas pelo Brasil ao longo dos últimos 24 anos.

<p>The first part of the work describes a procedure of oligonucleotide purification using a reversed-phase cartridge. The developed method employs a very efficient yet mild oligonucleotide detritylation on the cartridge support allowing fast purification of oligonucleotides regardless of their 5´-modification. Thiol- and amino-modified oligonuc-leotides were detritylated and purified with the same high efficiency as non-modified oligonucleotides. The method enables fast, parallel and automated purification of many oligonucleotide probes that was not possible before. In combination with the method of removal of tritylated failure fragments oligonucleotides were produced with purity superior to that of oligonucleotides purified using RP HPLC.</p><p>In the second part of the present study a method of solid-phase RNA synthesis using 2´-tert-butyldithiomethyl (2´-O-DTM) is discussed. The stability of the DTM group during oligonucleotide assembly and deprotection in ammonia, together with its ability for rapid deprotection under mild conditions, allowed the synthesis of RNA with the quality similar to that of synthetic DNA oligonucleotides. The advantage of the 2´-O-DTM group is that it is completely orthogonal to all protecting groups used for the traditional solid-phase DNA synthesis. Therefore, the synthesis can be performed using a standard DNA synthesis procedure – no changes are needed for the product assembly. RNA oligonucleotides synthesized with retained 5´-terminal trityl group can be subjected to a cartridge-based purification using the procedure described in the first part of the study. The phosphoramidite synthesis was optimized for a large scale preparation and gives versatility for introduction of other alkyldithiomethyl groups according to the preference to their certain properties.</p><p>The third part of the thesis describes the synthesis of a dithiomethyl linker and its utility for reversible conjugation of oligonucleotides. A dithiomethyl group, cleavable under mild conditions, was introduced onto 3´-OH of tritylated nucleosides via 3´-O-methylthiomethyl derivatives. The influence of different alkyl substituents on the disulfide bond stability was investigated, and stable analogues were employed in oligosyntheses. Two applications were developed using the present linker: 1) purification of oligonucleotides linked to the solid support; and 2) cartridge-based purification of tritylated oligonucleotides having an additional hydrophobic group on their 3´- terminus.</p>