No description available.

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2017-08-15T18:08:30Z No. of bitstreams: 1 Mariangela mendes Lomba Pinho.pdf: 3323000 bytes, checksum: cf5e189449ea8dd8e383ede49e2b7d05 (MD5) / Made available in DSpace on 2017-08-15T18:08:30Z (GMT). No. of bitstreams: 1 Mariangela mendes Lomba Pinho.pdf: 3323000 bytes, checksum: cf5e189449ea8dd8e383ede49e2b7d05 (MD5) Previous issue date: 2017-04-12 / Universidade Católica de Santos - Católica de Santos / Although the International Climate Change Regime has been growing to higher proportions day after day, problems related to global warming seem to have been causing successive losses to mankind; Several initiatives, however, have been implemented towards the mitigation of climate hazards. There is need to go beyond that, though, and take adapting actions to current and future conditions to ensure sustainable development. The State has evidenced its lack of conditions to act efficiently in that segment and that said space is being slowly occupied by subnational players, who become important agents in the international relations. In that context, and considering the capitalist economies in a globalized environment, this thesis analyzes the environmental and economic paradiplomacy as a governance tool to contribute with more effective results, using soft law tools and acting in transnational climate networks, which by means of environmental economic instruments enable project financing. If the adapt is a new path taken in climate-related discussions, an innovative initiative, called Regions Adapt, still in the structuring phase, presents a bold proposal for subnational players. To achieve the outlined goals, this research was initially composed of the bibliographic and documentary method, with a review of the scholarly literature on the topic in general, since specific scientific works have not been found, complemented by technical visits and open interviews. Afterwards, the works was developed on a single case study to test the research compilations. Under such standpoint, São Paulo State was selected, once it holds the economic leadership in the country and because it is the region where this doctoral program is inserted, in addition to the vast experience in several actions already implemented in the international agenda of sustainability. Results indicate that the environmental paradiplomacy and economic paradiplomacy are indispensable tools to help face climate change and foment the new concept of economy, with an array of environmental economic instruments being offered in the market, although, in practical terms, access to the resources is still complex. Researches evidenced that due to the recent installation of the Regions Adapt initiative, economic aspects are not yet outlined. As to the State of São Paulo, object of the single case study, nowadays, despite the difficulties, it presents itself as a pioneer in environmental and paradiplomacy matters. / El Régimen Internacional del Cambio Climático asume proporciones cada vez significativas, pero los problemas relacionados con el calentamiento global siguen causando pérdidas sucesivas en la humanidad. Sin embargo, numerosas iniciativas han sido implementadas para mitigar los riesgos climáticos, pero hay que ir más allá y realizar acciones de adaptación a las condiciones actuales y futuras que pueden asegurar un escenario de desarrollo sostenible. El Estado ha demostrado que no puede actuar con eficacia en este segmento de manera aislada y este espacio ha sido ocupado gradualmente por los actores subnacionales que se convierten en actores importantes en las relaciones internacionales. En este contexto, y teniendo en cuenta las economías capitalistas en un mundo globalizado, esta tesis analiza la paradiplomacia ambiental y económica como herramienta de gobernanza global para contribuir con resultados más eficaces, con el uso de herramientas de soft law y actuando en redes climáticas transnacionales que, a través de instrumentos económicos ambientales, permiten la financiación de proyectos. Si la adaptación es una nueva dimensión en las discusiones de los problemas climáticos, una iniciativa innovadora, llamada Regions Adapt, que aún se está estructurando, se presenta como una propuesta audaz para los actores subnacionales. Para alcanzar los objetivos indicados, el presente tesis consistió en inicialmente adoptar el método bibliográfico y documental, con una revisión de la literatura académica sobre el tema en general, ya que no se encontraron artículos científicos específicos sobre paradiplomacia ambiental y economica, complementados con visitas técnicas y entrevistas abiertas. En la secuencia, se realizó un estudio de caso único para probar la investigación. Bajo este prisma, el Estado de Sao Paulo ha sido elegido, por su liderazgo económico en el país y por ser la región donde se inserta este programa de doctorado y también por su amplia experiencia en diversas acciones ya implementadas en el agenda internacional de la sostenibilidad. Los resultados indican que la paradiplomacia ambiental y económica son herramientas esenciales para ayudar en la lucha contra el cambio climático y promover un nuevo concepto de la economía, ya que se ofrecen en el mercado una amplia gama de instrumentos económicos ambientales, aunque en la práctica el acceso a esos recursos sigue siendo complejo. La investigación demostró que, debido a la reciente instalación de la iniciativa Regions Adapt, todavía sus instrumentos económicos no están bien delineados. En cuanto al Estado de Sao Paulo, estudio de caso único de esta investigación, en nuestros días, a pesar de las dificultades, sigue como pionero en temas ambientales y paradiplomáticos. / O Regime Internacional de Mudanças Climáticas vem tomando proporções cada vez maiores, porém os problemas relacionados ao aquecimento global vêm ocasionando sucessivas perdas à humanidade. Entretanto, inúmeras iniciativas têm sido implementadas no sentido de mitigar os riscos climáticos, mas é preciso ir além e efetuar ações de adaptação para que as condições atuais e futuras possam garantir o desenvolvimento sustentável. O Estado já demonstrou que não apresenta condições de atuar eficientemente neste segmento e este espaço vem sendo ocupado paulatinamente por atores subnacionais, que se tornam importantes agentes nas relações internacionais. Neste contexto, e considerando as economias capitalistas em um ambiente globalizado, a presente tese analisa a paradiplomacia ambiental e econômica como instrumento de governança global para contribuir com resultados mais efetivos, utilizando ferramentas de soft law e atuando em redes climáticas transnacionais que, por meio de instrumentos econômicos ambientais, possibilitam financiamento aos projetos. Se a adaptação é uma nova vertente nas discussões das questões climáticas, uma iniciativa inovadora, denominada Regions Adapt, que ainda está em estruturação, apresenta uma proposta arrojada para os atores subnacionais. Para atingir os objetivos traçados, esta pesquisa compôs-se inicialmente do método bibliográfico e documental, com uma revisão da literatura acadêmica sobre o tema em geral, visto que não foram encontrados trabalhos científicos específicos, complementados por visitas técnicas e entrevistas abertas. Na sequência, efetuou-se um estudo de caso único para testar as compilações da pesquisa. Sob tal prisma, foi selecionado o Estado de São Paulo, por ser a liderança econômica no pais e por ser a região onde este programa de doutorado está inserido, além de possuir vasta experiência em diversas ações já implementadas na agenda internacional da sustentabilidade. Os resultados indicam que a paradiplomacia ambiental e econômica são ferramentas imprescindíveis para auxiliar no enfrentamento das mudanças climáticas e no fomento a um novo conceito de economia, sendo oferecido no mercado uma gama de instrumentos econômicos ambientais, embora na prática o acesso aos recursos ainda seja complexo. As pesquisas evidenciaram que em função da recente instalação da iniciativa Regions Adapt, os aspectos econômicos ainda não estão delineados. Quanto ao Estado de São Paulo, objeto do estudo de caso único, hodiernamente, apesar das dificuldades, apresenta pioneirismo nas questões ambientais e paradiplomáticas.

abstract: There are federal mandates attached to funding for behavioral health programs that require the use of evidence-based treatments (EBTs) to treat mental health disorders in order to improve clinical outcomes. However, these EBTs have not been constructed with American Indian/Alaskan Native (AI/AN) populations. There are over 340 EBTs, and only two outcome controlled studies have demonstrated effectiveness with AI/AN populations to treat mental health disorders. AI/AN communities often have to select an EBT that is not reflective of their culture, language, and traditions. Although EBTs are frequently used in AI/AN communities, little is known about the adaptation process of these interventions with the AI/AN population. For this study, a qualitative design was used to explore how American Indian behavioral health (AIBH) organizations in the Southwest adapted EBTs for cultural relevancy and cultural appropriateness. One urban and two tribal AIBH programs were recruited for the study. Over a six-week period, 24 respondents (practitioners and cultural experts) participated in a semi-structured interview. Transcripts were analyzed using the constant comparative analysis approach. As a result, four themes emerged: 1) attitudes towards EBTs, 2) how to build culturally competent clinical skills, 3) steps to adapt EBTs, and 4) internal and external organizational factors required to adopt EBTs. The four themes identify how to build a culturally responsive behavioral health program in Indian country and are the purview of this dissertation. / Dissertation/Thesis / Doctoral Dissertation Social Work 2020

Normal-hearing listeners can locate sound sources, using binaural cues for azimuth angle. These binaural differences in the timing and intensity of sound arriving at the two ears, interaural time differences (ITDs) and interaural intensity differences (IIDs), also support selective listening in multi-talker environments. Auditory-brainstem neurons of the medial superior olive (MSO) and lateral superior olive (LSO) encode ITD in the envelope of sound (ITDENV) and in the temporal fine structure of low-frequency sound (ITDTFS); LSO neurons encode IID. Bilateral-cochlear-implant (bCI) listeners generally receive only IID and ITDENV. Experimental bCI pulse-bursts overcome adaptation, and convey electrical ITDTFS. Improving the understanding of mechanisms for ITD sensitivity can help bCI developers convey acoustic ITDTFS. In this dissertation, models for auditory-brainstem neurons are developed that explain human ability to detect small differences in ITD, as neuronal and MSO population mechanisms. Promoting binaural-coincidence detection and limiting backpropagation, model MSO ion-channels set resting potentials that reproduce dendritic and somatic KLT activation, somatic Na+ inactivation, and a lower amount of axonal Na+ inactivation. Sensitivity to ITDTFS in moderately fast and very fast model MSO neurons collectively match physiological data from 150 to 2000 Hz. The best-ITD (the ITD of highest spike rate) can be made contralateral-leading, by contralateral inhibition of moderate speed, or by asymmetric axon location, leveraging dendritic filtering. Leveraging standard binaural-display models, neuronal populations based on these model MSO neurons match normal-hearing human discrimination thresholds for ITDTFS in sine tones from 39 to 1500 Hz. Adaptation before binaural interaction helps model MSO neurons glimpse the ITDTFS of sound direct from a source, before reflected sound arrives from different directions. With inputs from adapting model spherical bushy cells, a moderately fast model MSO neuron reproduces in vivo responses to amplitude-modulated binaural beats, with a frequency-dependent emphasis of rising vs. peak sound-pressure for ITDTFS encoding, which reflects human ITD detection and reverberation times in outdoor environments. Distinct populations of model LSO neurons, spanning the range of electrical membrane impedance as a function of frequency in LSO neurons, collectively reflect discrimination thresholds for ITDENV in transposed tones across carrier frequency (4-10 kHz) and modulation rate (32-800 Hz). / 2022-09-28T00:00:00Z

Small stable protein domains are attractive scaffolds for engineering affinity proteins due to their high tolerance to mutagenesis without loosing structural integrity. The albuminbinding domain is a 5 kDa three-helix bundle derived from the bacterial receptor Protein G with low-nanomolar affinity to albumin. In this thesis, the albumin-binding domain is explored as a scaffold for engineering novel affinity proteins with the possible benefit of combining a prolonged serum half-life with specific targeting in a single small scaffold protein. Previously, a library was created by randomizing surface-exposed residues in order to engineer affinity to a new target antigen in addition to the inherent albumin affinity. Here, phage display selections were separately performed against the tumor antigens ERBB2 and ERBB3. The ERBB3 selection resulted in a panel of candidates that were found to have varying affinities to ERBB3 in the nanomolar range, while still retaining a high affinity to albumin. Further characterization concluded that the clones also competed for binding to ERBB3 with the natural activating ligand Heregulin. The selections against ERBB2 resulted in sub-nanomolar affinities to ERBB2 where the binding site was found to overlap with the antibody Trastuzumab. The binding sites on ABD to albumin and either target were found in both selections to be mutually exclusive, as increased concentrations of albumin reduced the level of binding to ERBB2 or ERBB3. An affinity-matured ERBB2 binder, denoted ADAPT6, which lacked affinity to albumin was evaluated as a radionuclide-labeled imaging tracer for diagnosing ERBB2-positive tumors. Biodistribution studies in mice showed a high renal uptake consistent with affinity proteins in the same size range and the injected ADAPT quickly localized to the implanted tumor. High contrast images could be generated and ERBB2-expressing tissue could be distinguished from normal tissue with high contrast, demonstrating the feasibility of the scaffold for use as diagnostic tool. In a fourth study, affinity maturation strategies using staphylococcal cell-surface display were evaluated by comparing two replicate selections and varying the stringency. A sub-nanomolar target concentration was concluded to be inappropriate for equilibrium selection as the resulting output was highly variable between replicates. In contrast, equilibrium sorting at higher concentrations followed by kinetic-focused off-rate selection resulted in high output overlap between attempts and a clear correlation between affinity and enrichment. / <p>QC 20160510</p>

Demokratizuojant Lietuvos Respublikos švietimo sistemą, Lietuvoje nuo 1991 metų įteisintas specialiųjų poreikių vaikų integruotas ugdymas. Vykstant pokyčiams Lietuvoje prasidėjo permainos, teikiant pedagoginę, socialinę, medicininę, teisinę pagalbą neįgaliems vaikams ir suaugusiems optimaliai integruojant juos į visuomenę. Akcentuotina tai, jog SUP mokinių adaptacijos bendrojo lavinimo mokykloje problemos nėra išsamiai tyrinėtos. Be to, daugelyje tyrimų orientuojamasi ne į pačių neįgaliųjų savijautą mokykloje, pasitenkinimą savo bendraklasiais bei mokymosi procesu, o į pedagogų, tėvų ar bendraklasių nuomonę. Kitaip tariant, iš tyrimo konteksto dažnai „iškrinta“ patys SUP mokiniai, nors kaip tik jų jausenos ir būsenos mokykloje yra pačios svarbiausios. Tyrimo objektas: specialiųjų poreikių mokinių adaptacija bendrojo lavinimo mokykloje. Hipotezė: SUP poreikių mokiniai bendrojo lavinimo mokykloje adaptuojasi sunkiau nei mokiniai neturintys mokymosi sunkumų. Darbo tikslas: išanalizuoti integruotai besimokančių 3-4 klasėse specialiųjų poreikių mokinių adaptacijos bendrojo lavinimo mokykloje ypatumus. Tyrimo imtis: 25 SUP mokiniai ir 25 kontrolinės grupės mokiniai, besimokantys 3-4 klasėse. Atlikus integruotai besimokančių specialiųjų ugdymosi poreikių mokinių adaptacijos bendrojo lavinimo mokykloje tyrimą, kurio pirmame etape savo mintis bei išgyvenimus ir problemas išreiškė patys SUP mokiniai rašinėliuose „Aš ir mano mokykla“, o antrame etape pravedus sociometrinį tyrimą, norint... [toliau žr. visą tekstą] / Since 1990, democratizing the education system of the Republic of Lithuania, the integrated education of children with special needs has been validated. Lithuania began to change the course of change in the provision of educational, social, medical and legal assistance to disabled children and adults to optimize their integration into society. It should be emphasized that SEN pupils’ adaptation problems in comprehensive school have not been thoroughly investigated. In addition, most researches focus not on the disabled pupil's feelings at school, satisfaction with their classmates and learning process. Mostly they focus on the opinion of teachers, parents or classmates. In other words, SEN pupils often ‚fall out‘ from the context of research, though exactly their feelings and conditions at school are the most important. The object of the research: Learners‘with special needs adaptation in a comprehensive school. Hypothesis: SEN pupils adapt in a comprehensive school more difficult than students without learning difficulties. The aim: to analyse the adaptation features of 3 - 4 formers with special needs studying in a comprehensive school integrally. The sample of the research: 25 SEN pupils and 25 control group pupils, studying in classes 3 - 4. At the first stage of the adaptation research of pupils with special needs studying at a comprehensive school integrally, SEN pupils expressed their thoughts, experiences and problems in their essays ‘Me and My School‘ . At the... [to full text]

Lat est clé dans le développement des cellules T. En l'absence de Lat, le développement des cellules T au niveau du thymus est complètement bloqué au stade DN3. Le développement des lymphocytes T est très diminué dans des souris knockin LatY136F dans lesquelles la tyrosine présente en position 136 de la protéine Lat est remplacée par une phénylalanine. De manière paradoxale, le petit nombre de cellules T qui émergent dans la périphérie des souris LatY136F donnent naissance à un syndrome lymphoprolifératif Th2 sévère. Ce projet vise à identifier les facteurs génétiques qui contribuent au développement d'un tel syndrome lymphoprolifératif. A la suite d'un crible génétique basée sur une mutagenèse à l'ENU (N-éthyl-N-nitrosurea), des lignées de souris mutantes LatY136F présentant une pathologie atténuée ou exacerbée ont été fixées et les mutations induites chimiquement ont été cartographiées et identifiées. En particulier, nous avons obtenu une lignée mutante appelée Basilic dépourvue du syndrome lymphoprolifératif. Le clonage positionnel assisté par les techniques de séquençage à haut-débit de l'ADN ont permis l'identification d'un gène appelé, Rltpr ou Lrrc16c, et ne possédant aucune fonction immunologique connue. Nous avons montré que Rltpr constitue un élément clé de la voie de signalisation opérée par la molécule de costimulation CD28. Les résultats principaux obtenus au cours de la thèse sont présentés sous forme d'un article publié. Un chapitre de perspective est consacré ensuite aux améliorations que nous pourrions apporter au type d'approche que nous avons réalisé. Enfin une dernière rubrique traite des outils permettant la manipulation du génome de la souris. / Lat is essential for proper T cell development. In the absence of Lat, intra thymic T cell development is completely blocked at an early stage known as the DN3 stage. LatY136F mice in which the tyrosine found at position 136 of Lat was replaced by a phenylalanine, also showed an impaired sequence of intrathymic T cell development. Paradoxically, the small number of improperly selected T cells that reach the periphery of LatY136F mice expand in an uncontrolled manner and trigger a severe Th2 lymphoproliferative disorder. The present thesis project aimed at identifying genetic factors contributing to the development of such a lymphoproliferative disorder. Using a sensitized ENU mutagenesis screen, we identified and characterized mutations that dampened or exacerbated the LatY136F pathology. A mutation that is called Basilic and that acts in a T cell intrinsic manner and completely prevented the LatY136F lymphoproliferative disorder was characterized in a comprehensive manner. Positional cloning assisted by next generation DNA sequencing demonstrated that Basilic corresponds to a mutation in a gene called Rltpr or Lrrc16c, the function of which was previously completely unknown in the frame of the immune system. Further functional studies performed during this project showed that Rltpr corresponded to a “missing link” involved in the signaling cascade that mediates the function of the co-stimulatory molecule CD28. Consistent with that view, nullozygous Cd28 mutant mice were found to be a phenocopy of the Basilic mice and as such prevented lymphoproliferative disorder in LatY136F mice. The Basilic mutation also resulted in a defect in regulatory T cell development.

No description available.

<p>This master’s thesis presents experiences from an evaluation of AdApt, a multi- modal, conversational dialogue system, using PARADISE, PARAdigm for Dialogue System Evaluation, a general framework for evaluation. The purpose of this master’s thesis was to assess PARADISE as an evaluation tool for such a system. An experimental study with 26 subjects was performed. The subjects were asked to interact with one of three different system versions of AdApt. Data was collected through questionnaires, hand tagging of the dialogues and automatic logging of the interaction. Analysis of the results suggests that further research is needed to develop a general framework for evaluation which is easy to apply and can be used for varying kinds of spoken dialogue systems. The data collected in this study can be used as starting point for further research.</p>

No description available.