[ES] El espectro de la luz solar está compuesto por una amplia gama de radiaciones electromagnéticas las cuales tienen diferentes impactos sobre la vida en la tierra. Entre ellas, las pertenecientes a la región ultravioleta toman un papel principal cuando nos referimos a la fotobiología, ya que pueden interactuar con las biomoléculas por medio de procesos tanto directos como fotosensibilizados. Como resultado, estas biomoléculas pueden sufrir modificaciones que no siempre tienen efectos beneficiosos. En este contexto, los daños fotoinducidos al ADN son de gran relevancia ya que están estrechamente relacionados con la creciente incidencia de cáncer de piel. Por ello, es necesario investigar tanto los mecanismos involucrados en dichos procesos como el desarrollo de nuevas estrategias para combatirlos. En la presente tesis se da respuesta a estas necesidades mediante el desarrollo y empleo de grupos protectores fotolábiles (PPG). En una primera parte se avanza en el desarrollo de nuevos PPG basados en filtros solares. Estos ofrecen la ventaja de actuar, una vez liberados, como un escudo protector frente a la radiación ultravioleta. En este contexto, en el Capítulo 3 se profundiza en las propiedades fotofísicas y fotoquímicas de los sistemas formados por la avobenzona como PPG de ácidos carboxílicos, más concretamente del ketoprofeno (KP) y del naproxeno (NPX). En este estudio se analiza por medio de modelado molecular y técnicas espectroscópicas la influencia que tiene la energía relativa del triplete de la avobenzona en su forma dicetónica, 3AB(K)*, respecto a la de los compuestos protegidos en el proceso de liberación. Siguiendo en esta misma línea de trabajo, en el Capítulo 4 se ha desarrollado un nuevo PPG capaz de liberar el filtro solar oxibenzona (OB) junto con compuestos carbonílicos. En una segunda parte, el foco de atención se ha puesto en el concepto de "Caballo de Troya", el cual establece que ciertas lesiones del ADN pueden actuar a su vez como fotosensibilizadores endógenos generando así nuevas lesiones en su entorno. En este contexto, en el Capítulo 5 se han estudiado, mediante métodos tanto experimentales como teóricos, las propiedades fotosensibilizantes de dos de los daños oxidativos del ADN, el 5-formiluracilo (ForU) y la 5-formilcitosina (ForC), poniendo especial énfasis en la capacidad de estos para poblar sus estados tripletes, así como de inducir la formación fotosensibilizada de dímeros ciclobutánicos de pirimidina (CPD). Por último, en el Capítulo 6 se ha desarrollado una nueva alternativa sintética para la incorporación del ForU en oligonucleótidos. Debido a la inestabilidad del grupo aldehído, esta síntesis se lleva a cabo generalmente mediante la incorporación de un precursor el cual es posteriormente convertido en el ForU mediante la acción de un agente oxidante. Por el contrario, en la nueva alternativa planteada el aldehído es protegido con un PPG, de manera que una vez insertado en el ODN, el aldehído es liberado de forma selectiva mediante el empleo de luz. Este trabajo supone un avance en el estudio de las propiedades fotosensibilizantes del ForU ofreciendo una nueva herramienta para la evaluación de las mismas en un entorno más cercano al del ADN. / [CA] L'espectre de la llum solar està compost per una àmplia gamma de radiacions electromagnètiques les quals tenen diferents impactes sobre la vida en la terra. Entre elles, les pertanyents a la regió ultraviolada prenen un paper principal quan ens referim a la fotobiologia, ja que poden interactuar amb les biomolècules per mitjà de processos tant directes com fotosensibilitzats. Com a resultat, aquestes biomolècules poden patir modificacions que no sempre tenen efectes beneficiosos. En este context, els danys fotoinduits a l'ADN són de gran rellevància ja que estan estretament relacionats amb la creixent incidència de càncer de pell. Per això, és necessari tant d'investigar els mecanismes involucrats en els processos com el desenvolupament de noves estratègies per a combatre'ls. En la present tesi es dóna resposta a aquestes necessitats per mitjà del desenvolupament i ús de grups protectors fotolàbils (PPG). En una primera part s'avança en el desenvolupament de nous PPG basats en filtres solars. Estos ofereixen l'avantatge d'actuar, una vegada alliberats, com un escut protector enfront de la radiació ultraviolada. En este context, en el capítol 3 s'aprofundeix en les propietats fotofísiques i fotoquímiques dels sistemes formats per l'avobenzona com PPG d'àcids carboxílics, més concretament del ketoprofé (KP) i del naproxé (NPX). En este estudi s'analitza per mitjà de modelatge molecular i tècniques espectroscòpiques la influència que té en el procés d'alliberament l'energia relativa del triplet de l'avobenzona en la seua forma dicetònica, 3AB(K)*, respecte a la dels compostos protegits. En esta mateixa línia de treball, en el capítol 4 s'ha desenvolupat un nou PPG capaç d'alliberar el filtre solar oxibenzona (OB) junt amb compostos carbonílics. En una segona part, el focus d'atenció s'ha posat en el concepte de "Cavall de Troia", el qual estableix que certes lesions de l'ADN poden actuar al seu torn com fotosensibilitzadors endògens generant així noves lesions en el seu entorn. En este context, en el capítol 5 s'han estudiat, per mitjà de mètodes tant experimentals com teòrics, les propietats fotosensibilitzants de dos dels danys oxidatius de l'ADN, el 5-formiluracil (ForU) i la 5-formilcitosina (ForC), posant especial èmfasi tant en la capacitat d'estos per a poblar els seus estats triplet, com d'induir la formació fotosensibilitzada de dímers ciclobutànics de pirimidina (CPD). Finalment, en el capítol 6 s'ha desenvolupat una nova alternativa sintètica per a la incorporació del ForU en oligonucleòtids. A causa de la inestabilitat del grup aldehid, esta síntesi es duu a terme generalment per mitjà de la incorporació d'un precursor el qual és posteriorment convertit en el ForU per mitjà de l'acció d'un agent oxidant. Al contrari, en la nova alternativa plantejada l'aldehid és protegit amb un PPG, de manera que una vegada inserit en l'oligonucleòtid, l'aldehid és alliberat de forma selectiva per mitjà de l'ús de llum. Este treball suposa un avanç en l'estudi de les propietats fotosensibilitzants del ForU i ofereix una nova ferramenta per a l'avaluació de les mateixes en un entorn més pròxim al de l'ADN. / [EN] The solar spectrum is composed of a wide range of electromagnetic radiations which have different impacts on life on earth. Among them, those belonging to the ultraviolet region are of utmost importance when we refer to photobiology, since they can interact with biomolecules through both direct and photosensitized processes. As a result, these biomolecules can undergo modifications that do not always have beneficial effects. In this context, photoinduced DNA damage is of great relevance as it is closely related to the increasing incidence of skin cancer. Therefore, it is necessary both to investigate the mechanisms involved in these processes and to develop new strategies to avoid them. In this Thesis these issues have been addressed through the development and use of photolabile protecting groups (PPG). The first part of this Thesis involves the development of new PPG based on solar filters. Once released, these PPG offer the advantage of acting as ultraviolet shields. In this context, Chapter 3 looks into the photophysical and photochemical properties of those systems formed by avobenzone as PPG of carboxylic acids, more specifically ketoprofen (KP) and naproxen (NPX). In this study, the influence on the photorelease process of the relative energetic location of the avobenzone triplet manifold in its diketo form, 3AB(K)*, with respect to that of its caged compound, is duly analyzed by means of molecular modeling and spectroscopic techniques. Following this same line of work, a new PPG capable of releasing oxybenzone (OB) solar filter along with carbonyl compounds has been developed in Chapter 4. The second part of this Thesis focuses on the "Trojan Horse" concept, which establishes that certain DNA lesions can act as endogenous photosensitizers, thus generating new lesions in their neighborhood. In this context, in Chapter 5 the photosensitizing properties of two oxidatively generated DNA damages, namely 5-formyluracil (ForU) and 5-formylcytosine (ForC), have been studied by means of experimental and theoretical approaches. Here, special emphasis has been placed on unraveling their capacity to photoinduce the formation of cyclobutane pyrimidine dimers (CPD). Finally, in Chapter 6 a new synthetic alternative for the incorporation of ForU into oligodeoxynucleotides (ODN) has been developed. Due to the instability of the aldehyde group, this synthesis is generally carried out by incorporating a precursor which is subsequently converted into ForU by the action of an oxidative agent. On the contrary, in the new approach, the aldehyde is protected with a PPG, so that once inserted into the ODN, the aldehyde is selectively released through the use of light. This work entails a step forward in the study of the photosensitizing properties of ForU, offering a new tool for their evaluation within the DNA environment. / Lineros Rosa, M. (2021). Photoremovable protecting groups for carbonyl compounds of biological interest [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/167764

Le dommage causé à soi-même a très longtemps constitué un sujet hors du droit, synonyme de stigmatisation morale ou de fatalité. Depuis la fin du XXème siècle, c’est un enjeu essentiel des politiques publiques qui fait encore aujourd’hui l’objet d’un débat éthique et juridique. D’une part, la volonté de se causer un dommage exprime les aspirations de l’homme contemporain à obtenir la maîtrise de son corps, qu’il s’agisse de choisir le temps et les conditions de sa mort, de revendiquer des pratiques masochistes ou bien de faire don de ses organes. D’autre part, cette prise de risque dommageable pour soi révèle très souvent une opposition de l’État et de la société en général, en raison de l’atteinte susceptible d’être portée aux valeurs sociales et aux équilibres budgétaires. En tant que sources croissantes de préoccupation, les manifestations et les limites du dommage causé à soi-même méritent d’être soumises à l’étude de leur contexte historique, social et juridique. / The damage caused to oneself was for a very long time a topic outside the law, as a synonym for moral stigmatization or for fate. Since the end of the XXth century, it is an essential public policy issue that is the object even today of an ethical and legal debate. On the one hand, the will to harm oneself reflects the aspiration of the contemporary man to have the control of its body, that it is a question of choosing the time and the conditions of its death or claiming masochistic practices or donating organs. On the other hand, this harmful risk-taking for oneself reveals frequently an opposition of the State and more generally of the society, because of the potential violation of the social values and the budget balances. As increasing sources of concerns, the manifestations and the limits of the damage caused to oneself deserve to be subjected to the study of their historic, social and legal context.

Obwohl die methodische Entwicklung der Peptidsynthese gewöhnlich eine automatisierte Herstellung erlaubt, sind für die Herstellung einer Reihe von Peptiden auch gegenwärtig Grenzen gesetzt. Einerseits kann eine im Verlauf der Kettenverlängerung auftretende Bildung intra- und /oder intermolekularer Wasserstoffbrücken zu einer begrenzten Solvatation und damit Zugänglichkeit der zu acylierenden Aminokomponente am Syntheseharz führen, andererseits kommt es beim Einbau sterisch anspruchsvoller Aminosäuren zu ungenügenden Acylierungsausbeuten. Urethangeschützte Aminosäurefluoride haben sich für den Einbau von alpha, alpha-Dialkylaminosäuren als geeignet erwiesen. Die reaktiveren urethangeschützten Aminosäurechloride sind zwar herstellbar, besitzen aber in Gegenwart einer Hilfsbase, die zum Abfangen der während ihrer Reaktion gebildeten HCl notwendig ist, eine zu geringe Stabilität (Oxazolonbildung, Abspaltung der Schutzgruppen). Erst die Verwendung von N(alpha)-Schutzgruppen, die keinen reaktionsfähigen Carbonylkohlenstoff enthalten, wie Arensulfonyl- Schutzgruppen, ermöglichen die volle Ausschöpfung der hohen Reaktivität der Aminosäurechloride. Mit Hilfe dieser Schutzgruppen gelang ein erster Vergleich der Reaktivität der Aminosäurechloride und -fluoride. Bei den durchgeführten Reaktionen wurde keine Stereomutation beobachtet. Unter Verwendung von Arensulfonylschutzgruppen war es erstmals möglich, zwei aufeinanderfolgende N-Alkyl-alpha, alpha-dialkylaminosäuren in Peptide einzubauen. Weiterhin konnten wir zeigen, daß derart geschützte Aminosäuren sich für in situ Aktivierungen mit Thionylchlorid eignen. Als Fänger für überschüssiges Aktivierungsreagenz wurden tertiäre Alkohole bzw. Amine eingesetzt. Arensulfonyl-geschützte Aminosäurechloride haben wir darüber hinaus erfolgreich in der Festphasenpeptidsynthese verwendet. In Kombination von Arensylfonyl-Schutz mit der Standard-Fmoc-Strategie gelang die Synthese eines biologisch aktiven Analogen des CRF, eines 41-mer Peptides mit einer eingefügten Tetrapeptidsequenz -Ala-MeAib-MeAib-Aib-. / Despite its wide field of application automatic peptide synthesis is still limited in certain cases. One of the limiting factors is the possibility of intra- or intermolecular hydrogen bond formation during the elongation of the peptide chain. This causes decreased solvation and thus reduced accessibility to the resin-bound amino component. Another limitation is the incorporation of sterically hindered amino acids that usually give rise to insufficient yields of acylation. Urethane protected amino acid fluorides have been shown suitable for the incorporation of alpha,alpha-dialkyl amino acids. Though the more reactive urethane protected amino acid chlorides can be readily synthesized, they do not possess the necessary stability in the presence of an auxiliary base that must be used for trapping of the hydrochloric acid formed during the reaction. Formation of oxazolons and deprotection of formerly protected functional groups would occur. Only the advent of protecting groups for the amino acid N-alpha that do not have a reactive carbonyl function - like arene sulfonyl groups - allowed to take full advantage of the high reactivity of the amino acid chlorides. These protecting groups enabled us to compare the reactivities of amino acid chlorides and fluorides for the first time. We didn't observe any stereo mutation in our experiments. The use of arene sulfonyl protecting groups permitted the consecutive incorporation of two N-alkyl-alpha,alpha-dialkyl amino acids into a peptide for the first time. Furthermore we could show, that amino acids protected in this way, are suitable for in situ activation with thionyl chloride. Tertiary alcohols and amines were used as scavenger for excessive activating reagent. Arene sulfonyl protected amino acids were also successfully used in solid phase peptide synthesis. By combining this protecting concept with the standard Fmoc approach we were able to synthesize a biologically active analogue of CRF, a peptide containing 41 residues into which we inserted the tetrapeptide Ala-MeAib-MeAib-Aib.

The analysis of the rules evolution, in particular internationally, demonstrates normative and principles conflicts that serve as power play instrument and the colonizer-colonized dichotomy, even when its essence is directed to the maintenance of peace. The the Responsibility While protecting (RWP) presented by Brazil in 2011, within the context of the development of global standards, permeated by non-linear conflictual interactions, where the interventions based on a Responsibility to Protect(R2P) civilians, have challenged the existing structures in the global order and therefore has sparked great debate regarding the prevalence of decisions emanating from the United Nations Security Council - UNSC against the sovereignty and self-determination of peoples, since there is no control of legality and legitimacy of that discretion which the United Nations - UN holds. In this sense, the present work aims to analyze if the Responsibility to Protect can be considered as an attempt to influence from the Global South countries in the production of global standards and this can work as a capable principle of safeguarding the coercive nature of measures by of the UNSC, a way of accountability that implies a large extent by the level of responsibility of emanating acts from the UN Security Council that determ interventions, and what tools are needed for the Responsibility to Protect is an effective tool of prior control of legality and legitimacy. In order to meet this goal, we adopted a dialectical approach, drawing on the monographic method, through bibliographical and documentary research and interdisciplinary literature, among others that apply to the subject under study. / A análise da evolução das normas, em específico no âmbito internacional, demonstra conflitos normativos e principiológicos que servem de instrumento de reprodução de poder e da dicotomia colonizador-colonizado, mesmo quando sua essência está voltada para a manutenção da paz. O Princípio da Responsabilidade ao Proteger (RWP, sigla em inglês), apresentado pelo Brasil em 2011, surge no contexto da evolução das normas globais, permeadas por interações não lineares conflituosas, onde a implementação cada vez maior de intervenções baseadas em uma Responsabilidade de Proteger (R2P, sigla em inglês) civis, tem desafiado as estruturas existentes na ordem global e por isso tem suscitado grande debate no que toca a prevalência de decisões emanadas do Conselho de Segurança das Nações Unidas - CSNU face à soberania e a autodeterminação dos povos, uma vez que não há um controle de legalidade e legitimidade desse poder discricionário do qual a Organização das Nações Unidas - ONU é detentora. Nesse sentido, a presente dissertação visa analisar se a Responsabilidade ao Proteger pode ser considerada como uma tentativa de influência a partir dos países do Sul Global na produção de normas globais e se esta pode funcionar como um princípio capaz de acautelar as medidas de natureza coercitiva por parte do CSNU, isto é, uma forma de accountability que implique em um maior nível de responsabilidade por parte dos atos emanados do Conselho de Segurança da ONU que determinem intervenções, bem como quais são os instrumentos necessários para que a Responsabilidade ao Proteger seja uma ferramenta eficaz de controle prévio de legalidade e legitimidade. De forma a cumprir esse objetivo, adotou-se uma abordagem dialética, valendo-se do método monográfico, por meio de pesquisa bibliográfica e documental e literatura especializada interdisciplinar, dentre outras que aplicáveis ao tema em estudo.

In the introduction of the diploma thesis there is discussed the question which every social worker knows: Could I have done something different? This is the question which is asked by almost everyone, especially a social worker. Further there is a brief outline of topics which are delineated in the diploma thesis. First chapter describes the institution Children´s Center JK Strakonice. Father there is a list of necessary knowledge which a social work should have for his or her occupation. Also the liabilities of the social worker to the clients are not left out. In this part there can be found also work with specific types of clients. For better understanding of the demands of social work in Children ´s Center JK Strakonice the thesis contains selected life stories of the women clients. These life stories should help to the reader to see the problems from different point of view and help to understand how much is important so that the clients decides himself or herself to solve his or her problems. In the second chapter there are described psychological and ethical dimensions of the profession, burnt out syndrome which is threat for everyone of us, especially for a social worker. In this chapter there are depicted causes of formation and manifestations of burnt out syndrome. The third chapter is also connected with the burnt out syndrome. The focus in this chapter is on prevention and protection. The attention is also paid to the personality of a social worker, his or her abilities to perceive the problem, but also experiences in moral decision-making and hierarchical position of values. The compliance of the principles of psycho hygiene and presence of supervision plays a very significant role. In the conclusion of the diploma thesis there is the summary of performance of a social worker in Children´s Center JK Strakonice. Every social worker should realise his or her responsibility not only to his or her clients, employer and colleagues but especially to himself or herself and his or her conscience. The interdependence of profession and conscience merges with the diploma thesis.

Bibliography: leaves 441-459 / The shepherd metaphor is a prominent and significant one in the Old Testament. However, it has shifted from an agrarian context, of shepherd and sheep in the literal sense, to a socio-political context, of rulers and people in the political sense: a king is a shepherd to the people. A careful review of the given metaphor raises the question whether the metaphor should be the basis of the pastoral and leadership models that are derived from the image of the shepherd, and whether such models can be enriched by the analysis of the said metaphor as applied to the implementation of the shepherding responsibility described in the Old Testament. This research aims to examine various pastoral and leadership models and their use of the shepherd metaphor in the light of the significance of the said metaphor in the Old Testament. It utilises rhetorical criticism in consultation with metaphorical theory to examine the given metaphor used in the models of pastoral and leadership roles and their relationship with the shepherd metaphor in the New Testament. The objective is threefold: (1) exploring the use of the shepherd metaphor in the Old Testament; (2) examining the use of the shepherd metaphor in pastoral and leadership models, which could include pointing out that some of these models rely heavily on their understanding of New Testament uses of this metaphor; and (3) comparing the Old Testament and pastoral/leadership models’ uses of the shepherd metaphor and drawing conclusions based on this comparison. To achieve that end, the discussion also includes the ancient Near Eastern literature and deuterocanonical texts. The thesis shows that a careful analysis of the uses of the shepherd metaphor in the Old Testament could enrich the literature on Christian leadership as well as pastoral models that use this metaphor as their point of departure. / Old Testament and Ancient Near Eastern Studies / D. Phil. (Old Testament)

Masters thesis is engaged of chosen parts of technological-buildig project of administrativ and housing complex of Sochorova in Brno, Žabovřesky. Contains technological-buildig study of first phase with brief description of advancement of construction with grafical scripts of particular steps, timetable and pecuniarytable of objects AB3, AB4, diagrams with various possibilities of using operatives. Thesis continous with calculation of entire first phase and item budged of object AB3(draft construction), statement of masurement, technical report of construction-technological AB3, plan of situaction of the building, technological manual of reiforced concrete ceiling of AB3 including plan of planking parts PERI, timetable, design of construction site equipment with technical report, proposal of machineries and crane, plane of inspections for chosen items, ecology and report about safety and health protecting on construction site.