Differential segregation in a cell-cell contact interface: the dynamics of the immunological synapse

Receptor-ligand couples in the cell-cell contact interface between a T cell and an antigen-presenting cell form distinct geometric patterns and undergo spatial rearrangement within the contact interface. Spatial segregation of the antigen and adhesion receptors occurs within seconds of contact, central aggregation of the antigen receptor then occurring over 1-5 min. This structure, called the immunological synapse, is becoming a paradigm for localized signaling. However, the mechanisms driving its formation, in particular spatial segregation, are currently not understood. With a reaction diffusion model incorporating thermodynamics, elasticity, and reaction kinetics, we examine the hypothesis that differing bond lengths (extracellular domain size) is the driving force behind molecular segregation. We derive two key conditions necessary for segregation: a thermodynamic criterion on the effective bond elasticity and a requirement for the seeding/nucleation of domains. Domains have a minimum length scale and will only spontaneously coalesce/aggregate if the contact area is small or the membrane relaxation distance large. Otherwise, differential attachment of receptors to the cytoskeleton is required for central aggregation. Our analysis indicates that differential bond lengths have a significant effect on synapse dynamics, i.e., there is a significant contribution to the free energy of the interaction, suggesting that segregation by differential bond length is important in cell-cell contact interfaces and the immunological synapse

Zytogenetik niedrigmaligner Lymphome der B-Zell-Reihe: Relevanz der Stimulation mit dem CpG-Oligonukleotid DSP30 in Kombination mit Interleukin-2

Zytogenetik niedrigmaligner Lymphome der B-Zell-Reihe: Relevanz der Stimulation mit dem CpG-Oligonukleotid DSP30 in Kombination mit Interleukin-

Henkilökohtaisen valmennuksen tuottama palvelukokemus ja koettu asiakasarvo : case Nettitreeni.com

Hyvinvointibuumi on luonut kasvavat markkinat erilaisille henkilökohtaisille valmennuspalveluille. Valmennuspalveluiden henkilökohtaisuuden vuoksi, palvelun tarjoajille on olennaista ymmärtää, millaista asiakasarvoa palvelun saajille syntyy palvelukokemuksen kautta. Asiakkaan näkökulman ymmärtäminen palvelukeskeisessä liiketoiminnassa tarkoittaa asiakkailta oppimista ja mukautumista asiakkaiden yksilöllisiin ja muuttuviin tarpeisiin. Tämän tutkimuksen tarkoituksena on kuvata ja analysoida henkilökohtaisen valmennuksen tuottamaa palvelukokemusta sekä koettua asiakasarvoa. Tämä tapahtuu tarkastelemalla palvelukokemuksen elementtejä, asiakasarvon käsitettä sekä sen ulottuvuuksia ja sitä, miten ainoastaan palvelun saajat voivat arvioida palvelukokemuksen ja koetun asiakasarvon. Tutkimuksen teoreettinen viitekehys muodostuu kolmesta kokonaisuudesta. Ensimmäinen osa käsittelee arvolupausta sekä palvelukokemusta ja sen rakentumista asiakasarvoa edeltävänä tekijänä. Toisessa osassa käsitellään asiakasarvon käsitettä sekä asiakasarvon ulottuvuuksia. Viimeisessä osassa tarkastellaan asiakasarvon kautta mahdollisesti syntyviä asiakasuskollisuuden ulottuvuuksia. Kvalitatiivinen tutkimusaineisto luotiin puolistrukturoitujen haastattelujen avulla, jotka toteutettiin syksyllä 2017. Tutkimuksen toteutukseen valittiin yhdeksän 22–48-vuotiasta naista. Syntynyttä aineistoa analysoitiin sisällönanalyysin keinoin teoriasidonnaisesti ja osittain aineistolähtöisesti. Sisällönanalyysi mahdollisti kuluttajien kokemusten kuvailun kadottamatta tärkeää informaatiota. Tutkimuksen tuloksena havaittiin palvelukokemuksen muodostuvan arvolupauksen, yksilöllisten ja tilannekohtaisten tekijöiden sekä lopputulosten kokonaisuutena ja siitä mahdollisesti syntyvän asiakasarvoa toiminnallisessa, kokemuksellisessa, symbolisessa sekä kustannuksiin ja uhrauksiin lukeutuvissa ulottuvuuksissa. Koetun asiakasarvon seurauksena palvelun saaja voi kokea asiakasuskollisuutta behavioraalisella tai asenteellisella ulottuvuudella. Johtopäätöksenä palvelukokemuksen positiivisuuteen vaikuttaa arvolupauksen pitäminen ja palvelun saajan subjektiivinen kokemus ja saavutetut lopputulokset suhteessa tavoitteisiin. Palvelun saaja voi kokea asiakasarvoa usealla eri ulottuvuudella, mikäli palvelukokemus on ollut kokonaisuudessaan onnistunut. Uskollisuus ei aina seuraa koettua asiakasarvoa, mutta sitä voi syntyä useamman arvoulottuvuuden seurauksena

Teletrabalho: proposta de regra jurídica fundamentada no princípio de proteção do empregado para o Brasil

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Jurídicas, Programa de Pós-Graduação em Direito, Florianópolis, 2014.O tema da tese é o teletrabalho, sendo que este foi delimitado no sentido de buscar uma proposta de regra jurídica fundamentada no princípio de proteção do empregado, para o teletrabalho no Brasil. O teletrabalho é um assunto relativamente novo, já que seus primórdios datam do ano de 1970. Referida modalidade de trabalho apresenta peculiaridades muito específicas, por permitir o cumprimento, total ou parcialmente, das atividades profissionais distante do estabelecimento empresarial e, o exercício e a transmissão das tarefas laborais, assim como, o controle, o comando e a supervisão do teletrabalhador se efetuarem a partir do uso meios telemáticos e informatizados. A legislação brasileira definiu o teletrabalho e equipara-o ao trabalhador tradicional, sem prever regras especiais e intrínsecas à atividade, o que deixa esta Relação de Emprego desprotegida em diversos aspectos. Assim, o problema a ser enfrentado pela tese consiste em verificar se é possível elaborar uma regra jurídica fundamentada no princípio de proteção do empregado para o teletrabalho no Brasil. Desta maneira, buscou-se estudar o princípio de proteção do empregado uma vez que é o critério que baliza e orienta a essência do Direito do Trabalho. Para tanto, averiguou-se o Direito e os princípios jurídicos trabalhistas, os princípios do trabalho e do Direito do Trabalho, o Direito do Trabalho e sua natureza protetora, o princípio de proteção do empregado, em si, e a proteção jurídica trabalhista. Também fez-se digressões sobre o teletrabalho e suas perspectivas sociais e laborais para a partir da verificação das tecnologias como motor de desenvolvimento da sociedade; do estudo da sociedade contemporânea frente aos efeitos da Revolução da Tecnologia da Informação, do teletrabalho e das suas perspectivas de emprego e das vantagens e das desvantagens do mesmo. Ainda, pretendeu-se pesquisar a proteção jurídica existente sobre o tema, passando, então, pela apreciação da Convenção nº. 184, da Recomendação nº. 177, ambas da Organização Internacional do Trabalho  OIT, pelo Acordo Marco Europeu, pela legislação que trata do teletrabalho na iniciativa privada na Europa e na América Latina. Por fim, pretendeu-se contribuir a partir da elaboração de uma regra jurídica para o teletrabalho no Brasil que se fundamente no princípio de proteção do empregado, compreendendo que para que isso ocorra deve haver a inclusão dos artigos 231-A a 231-F, na Consolidação das Leis do Trabalho  CLT, sendo que estes artigos devem tratar do objetivo da lei; do conceito; do Contrato de Teletrabalho; do registro do teletrabalhador; da jornada de trabalho; do caráter voluntário e da reversibilidade da atividade; dos postos de trabalho e dos equipamentos; dos custos; da proteção dos dados; da igualdade; da formação e da capacitação; da privacidade; da confidencialidade; da concorrência; do Direito de Propriedade Industrial; saúde, da segurança e da higiene; dos Direitos Coletivos e da liberdade sindical; da implementação; da responsabilidade social; das políticas públicas de fomento ao teletrabalho e das situações excepcionais, sempre levando em conta que a fundamentação dos mesmos deve estar embasada no princípio de proteção do empregado, que é o que garantirá a proteção jurídica específica para esta modalidade de trabalho e o resguardo do mínimo civilizatório e a dignidade dos teletrabalhadores.Abstract : The theme of the thesis is teleworking, and this was defined in order to seek a proposal legal rule based on the principle of protecting the employee to telework in Brazil. Telework is a relatively new subject, since its beginnings date from 1970 Referred working mode presents very specific peculiarities, for permit compliance, wholly or partly, apart from professional activities and the business establishment, exercise and transmission labor tasks, as well as control, command and supervision of teleworkers are effected from the use of computerized and telematic means. Brazilian law only defines telework and equate it to the traditional worker without providing special, intrinsic activity, which leaves this Employment Relationship unprotected rules in several respects. Thus, the problem being faced by the thesis is whether it is possible to draw up a legal rule based on the principle of protecting the employee to telework in Brazil. Thus, we sought to study the principle of protection of the employee since it is the criterion that guides and directs the essence of labor law. To do so, we ascertained the law and labor law principles, the principles of labor and Employment Law, Labor Law and its protective nature, the principle of protection of the employee itself and the legal labor protection. Also became digressions on teleworking and its social and labor perspectives from the technology verification as motor development of society; the study of contemporary society against the effects of the Revolution of Information Technology, teleworking and their employment prospects and the advantages and disadvantages of it. Still, it was intended to investigate the existing legal protection on the subject, then passing by the appreciation of the Agreement number. 184, Recommendation no. 177, both of the International Labour Organization - ILO, the European Framework Agreement on Telework laws that deal with the private sector in Europe and Latin America. Finally, we sought to contribute from the development of a legal rule to telework in Brazil that is based on the principle of protection of the employee, realizing that for this to occur there must be the inclusion of Articles 231-A to 231-F, the Consolidation of Labor Laws - CLT, and these articles should discuss the purpose of the law; the concept; the Telework Agreement; of the telecommuter record; working hours; the voluntary and reversibility of the activity; of workplaces and equipment; costs; data protection; equality; training and capacity building; privacy; confidentiality; competition; Law of Industrial Property; health, safety and hygiene; of Collective Rights and Freedom; implementation; social responsibility; public policies to encourage telecommuting and exceptional situations, taking into account that the reasons thereof should be grounded on the principle of protection of the employee, which is the guarantee of specific legal protection for this type of work and the guard of the minimum civilizing and the dignity of teleworkers

Índice de progresso social para as unidades da federação brasileira

Nos últimos trinta anos surgiram métodos buscando medir o bem-estar e o progresso social que adotam critérios que vão além da produção de bens e serviços, como a expansão das liberdades humanas, a preservação do meio ambiente e a felicidade. O processo de definição do que e como mensurar evidencia um problema ético da qual não há uma solução em definitivo. Através de uma adaptação da metodologia do Índice de Progresso Social para as 27 unidades federativas do Brasil, com dados primordialmente de 2019, este trabalho espera contribuir com a literatura empírica sobre desenvolvimento regional e com o uso de novas metodologias de mensuração do desenvolvimento. Para isso, foi utilizado diversos indicadores agrupados através do método de Análise dos Componentes Principais. Após os testes e tratamentos estatísticos, foi identificado que todos os estados brasileiros possuem possibilidade de melhoria em pelo menos uma dimensão.In Thé last 30 years, methods have emerged that seeking to measure well-being and social progress beyond the production of goods and services, such as the expansion of human freedoms, the preservation of the environment, and happiness. The process of defining what and how to measure these dimensions highlights an ethical problem for which there is not definitive solution. Through an adaptation of the Social Progress Index methodology for the 27 federative units of Brazil, with data primarily from 2019, this work hopes to contribute to the empirical literature on regional development and the use of new methodologies for measuring development. For this, several indicators grouped using the Principal Component Analysis method were used. After statistical tests and treatments, it was identified that all Brazilian states have the possibility of improvement in at least one dimension

O indivíduo hobbesiano versus o indivíduo contemporâneo: o problema da dignidade

O objetivo desse estudo é fazer uma relação entre o indivíduos hobbesiano (descrito por Thomas Hobbes, filósofo inglês, no livro “O Leviatã) e o indivíduo contemporâneo, buscando desenvolver a problemática da garantia da dignidade por meio do uso da metodologia indutiva bibliográfica/documental. A vida em Hobbes, é um bem inviolável, e deve ser defendida mesmo sobre o protesto do maior dos poderes, o Estado Leviatã. E, é em busca da dignidade, que em Hobbes é verbalizada com maior clareza nas palavras “paz” e “sobrevivência”, que os indivíduos se sujeitarão a viver em sociedade, formando uma “ponte dogmática”, ligando os indivíduos entre si, que na contemporaneidade se concretiza no respeito aos Direitos Humanos. Assim, a conquista da dignidade em Hobbes ou na contemporaneidade traduz-se em uma luta constante pelo direito de ter uma vida tranqüila, em segurança, de respeito entre um e outro, da garantia da alteridade pois é “preciso procurar a paz quando se tem a esperança de obtê-la”

The Induction and Regulation of Epidermal Flavonoid Accumulation at Low Temperature in Arabidopsis thaliana

The central subject of this work was to find answers to the question of how flavonoid accumulation might be induced at low temperature in Arabidopsis thaliana (A. thaliana). Specifically, the question was addressed how low temperature is sensed. Several hypotheses were investigated. A reduction of the plastoquinone pool in the photosynthetic electron transport chain by low temperature, which would also involve differential gene expression (Huner et al. 1998, Wilson & Huner 2000) was considered as a potential sensor for the induction of flavonoid biosynthesis as well as a low temperature derived signal of oxidative stress through the accumulation of reactive oxygen species (ROS) (Foyer & Noctor 2003). Two further hypotheses included a low temperature-linked calcium signal (Monroy et al. 1993, Örvar et al. 2000) and the involvement of one or more light receptors in the low temperature-induced flavonoid accumulation. In order to solve this question, comparative analysis of flavonoid accumulation at high light and supplemental UV-B radiation were also performed. The kinetics of flavonoid accumulation as well as their composition in rosette leaves of A.thaliana were comprehensively analysed. A role of ROS, the reduction state of the plastoquinone pool and the photoreceptors phototropin and cryptochrome in the induction of flavonoid accumulation at low temperature was investigated by several different experiments. In addition, the induction of flavonoid biosynthesis at low temperature, high light or UV-B radiation on the transcriptional level was analysed by microarray analysis and northern blotting. A comparative analysis of gene expression of one third of the Arabidopsis genome at the three conditions via microarray analysis was also performed in order to discover relevant signal transduction components. In experiments with A. thaliana an accumulation of six flavonols, three kaempferol- and three quercetin glycosides, could be demonstrated after treatment with low temperature, high light or UV-B radiation. Distinct differences in the pattern of accumulation after UV-B treatment were detected which involved a strong accumulation of quercetin glycosides and a rapid induction of several flavonoid biosynthetic genes. Experiments with mutants defective in photoreceptors could prove a light- and low temperature-dependent accumulation of quercetin glycosides which was regulated mainly by the blue light sensor cryptochrom 1. In contrast, most of the kaempferol accumulation at low temperature was blue light independent. This result implies that low temperature might change signal transduction processes following cryptochrome 1 perception. ROS and the reduction state of the photosynthetic electron transport chain (psETC) could be excluded as signal carriers. Results show that at least two low temperature sensing systems in A. thaliana might exist: One, that seems to interact with cryptochrome and seems to control the enzyme flavonol-3’-hydroxylase, and an independent second, which apparently controls kaempferol biosynthesis.Die Beantwortung der Frage, wie unter Kühle die Flavonoidbiosynthese in Arabidopsis thaliana induziert wird, war zentrale Aufgabe dieser Arbeit. Insbesondere wurde die Frage adressiert, wie Kühle wahrgenommen wird. Verschiedene Hypothesen wurden bearbeitet. Eine Reduktion des Plastochinon-Pools in der photosynthetischen Elektronentransportkette durch geringe Temperaturen und eine damit verbundene differentielle Genexpression (Huner et al. 1998, Wilson und Huner 2000) wurde als möglicher Sensor für eine Induktion der Flavonoidbiosynthese ebenso betrachtet, wie ein durch Kühle hervorgerufenes Signal von oxidativem Stress durch die Akkumulation von reaktiven Sauerstoffspezies (ROS) (Foyer und Noctor 2003). Zwei weitere Hypothesen umfassten ein Kühle-gekoppeltes Calciumsignal (Monroy et al. 1993, Örvar et al. 2000) und die Beteiligung eines oder mehrerer Lichtrezeptoren an der kühleinduzierten Flavonoid-akkumulation. Zur Klärung dieser Frage wurde vergleichend auch die Flavonoidakkumulation unter hohen Lichtstärken und durch UV-B untersucht. Sowohl die Kinetik der Flavonoid-akkumulaion als auch ihre Zusammensetzung in Rosettenblättern von A. thaliana wurde dabei umfassend analysiert. Die Rolle von ROS, vom Reduktionsgrad des Plastochinon-Pools und von den Lichtrezeptoren Phototropin und Cryptochrom in der Induktion der Flavonoidakkumulation wurde mit verschiedenen Experimenten untersucht. Zusätzlich wurde die Induktion der Flavonoidbiosynthese durch Kühle, hohe Lichtstärken und UV-B Strahlung auf Genexpressionsebene mittels Microarrays und Northernblots analysiert. Eine vergleichende Analyse der Genexpression von einem Drittel des Arabidopsis-Genoms unter den drei Bedingungen mittels Microarrays wurde durchgeführt um relevante Komponenten der entsprechenden Signaltransduktionswege zu entdecken. In Versuchen mit A. thaliana konnte eine Akkumulation von sechs Flavonolen (je drei Kämpferol- und Quercetinglykosiden) bei Kühle, unter hohen Lichtbedingungen und nach UV-B –Bestrahlung nachgewiesen werden. Dabei waren deutliche Unterschiede in der Akkumulation nach UV-B Behandlung zu den beiden anderen Behandlungen zu beobachten, die in einer starken Quercetinakkumulation und einer schnellen Induktion verschiedener Biosynthesegene bestanden. In Experimenten mit Photorezeptor-Mutanten konnte nachgewiesen werden, dass eine licht- und kühlebedingte Akkumu-lation von Quercetinglykosiden vor allem durch den Blaulichtsensor Cryptochrom 1 vermittelt wird. Dagegen war ein großer Teil der Akkumulation von Kämpferol-glykosiden Blaulicht-unabhängig. Das bedeutet, dass offenbar Kühle eine Cryptochrom-vermittelte Signaltransduktion verändern kann. ROS und der Reduktionsgrad der photosynthetischen Elektronentransportkette konnten als Signalgeber ausgeschlossen werden. Die Ergebnisse zeigen, dass mindestens zwei Kühle rezeptierende Systeme in A. thaliana existieren: Eines, das mit Cryptochrom interagiert und die Flavonol-3’-Hydroxylase kontrolliert sowie ein davon unabhängiges System, das die Kämpferolbiosynthese kontrolliert