The bird GPS - long-range navigation in migrants

Nowadays few people consider finding their way in unfamiliar areas a problem as a GPS (Global Positioning System) combined with some simple map software can easily tell you how to get from A to B. Although this opportunity has only become available during the last decade, recent experiments show that long-distance migrating animals had already solved this problem. Even after displacement over thousands of kilometres to previously unknown areas, experienced but not first time migrant birds quickly adjust their course toward their destination, proving the existence of an experience-based GPS in these birds. Determining latitude is a relatively simple task, even for humans, whereas longitude poses much larger problems. Birds and other animals however have found a way to achieve this, although we do not yet know how. Possible ways of determining longitude includes using celestial cues in combination with an internal clock, geomagnetic cues such as magnetic intensity or perhaps even olfactory cues. Presently, there is not enough evidence to rule out any of these, and years of studying birds in a laboratory setting have yielded partly contradictory results. We suggest that a concerted effort, where the study of animals in a natural setting goes hand-in-hand with lab-based study, may be necessary to fully understand the mechanism underlying the long-distance navigation system of birds. As such, researchers must remain receptive to alternative interpretations and bear in mind that animal navigation may not necessarily be similar to the human system, and that we know from many years of investigation of long-distance navigation in birds that at least some birds do have a GPS-but we are uncertain how it works.

Análise crítica ao processo de auditoria da qualidade

Dissertação apresentada ao Instituto Superior de Contabilidade para a obtenção do Grau deMestre em Auditoria Orientada por Alcina Augusta de Sena Portugal Dias

NCRF 9 – locações: implicações fiscais e de auditoria

Dissertação apresentada ao Instituto Superior de Contabilidade e Administração do Porto para a obtenção do Grau de Mestre em Auditoria ORIENTAÇÃO: DR. JOÃO COSTA

HARNESSING iNKT CELLS WITH RECOMBINANT CD1d FUSION PROTEINS TO REDIRECT INNATE AND ADAPTIVE IMMUNITY TO THE TUMOR

Les thérapies du cancer, comme la radiothérapie et la chimiothérapie, sont couramment utilisées mais ont de nombreux effets secondaires. Ces thérapies invasives pour le patient nécessitent d'être améliorées et de nombreuses avancées ont été faites afin d'adapter et de personnaliser le traitement du cancer. L'immunothérapie a pour but de renforcer le système immunitaire du patient et de le rediriger de manière spécifique contre la tumeur. Dans notre projet, nous activons les lymphocytes Invariant Natural Killer T (iNKT) afin de mettre en place une immunothérapie innovatrice contre le cancer. Les cellules iNKT sont une unique sous-population de lymphocytes T qui ont la particularité de réunir les propriétés de l'immunité innée ainsi qu'adaptative. En effet, les cellules iNKT expriment à leur surface des molécules présentes aussi sur les cellules tueuses NK, caractéristique de l'immunité innée, ainsi qu'un récepteur de cellules T (TCR) qui représente l'immunité adaptative. Les cellules iNKT reconnaissent avec leur TCR des antigènes présentés par la molécule CD1d. Les antigènes sont des protéines, des polysaccharides ou des lipides reconnus par les cellules du système immunitaire ou les anticorps pour engendrer une réponse immunitaire. Dans le cas des cellules iNKT, l'alpha-galactosylceramide (αGC) est un antigène lipidique fréquemment utilisé dans les études cliniques comme puissant activateur. Après l'activation des cellules iNKT avec l'αGC, celles-ci produisent abondamment et rapidement des cytokines. Ces cytokines sont des molécules agissant comme des signaux activateurs d'autres cellules du système immunitaire telles que les cellules NK et les lymphocytes T. Cependant, les cellules iNKT deviennent anergiques après un seul traitement avec l'αGC c'est à dire qu'elles ne peuvent plus être réactivées, ce qui limite leur utilisation dans l'immunothérapie du cancer. Dans notre groupe, Stirnemann et al ont publié une molécule recombinante innovante, composée de la molécule CD1d soluble et chargée avec le ligand αGC (αGC/sCD1d). Cette protéine est capable d'activer les cellules iNKT tout en évitant l'anergie. Dans le système immunitaire, les anticorps sont indispensables pour combattre une infection bactérienne ou virale. En effet, les anticorps ont la capacité de reconnaître et lier spécifiquement un antigène et permettent l'élimination de la cellule qui exprime cet antigène. Dans le domaine de l'immunothérapie, les anticorps sont utilisés afin de cibler des antigènes présentés seulement par la tumeur. Ce procédé permet de réduire efficacement les effets secondaires lors du traitement du cancer. Nous avons donc fusionné la protéine recombinante αGC/CD1d à un fragment d'anticorps qui reconnaît un antigène spécifique des cellules tumorales. Dans une étude préclinique, nous avons démontré que la protéine αGC/sCD1d avec un fragment d'anticorps dirigé contre la tumeur engendre une meilleure activation des cellules iNKT et entraîne un effet anti-tumeur prolongé. Cet effet anti-tumeur est augmenté comparé à une protéine αGC/CD1d qui ne cible pas la tumeur. Nous avons aussi montré que l'activation des cellules iNKT avec la protéine αGC/sCD1d-anti-tumeur améliore l'effet anti- tumoral d'un vaccin pour le cancer. Lors d'expériences in vitro, la protéine αGC/sCD1d-anti- tumeur permet aussi d'activer les cellules humaines iNKT et ainsi tuer spécifiquement les cellules tumorales humaines. La protéine αGC/sCD1d-anti-tumeur représente une alternative thérapeutique prometteuse dans l'immunothérapie du cancer. - Les cellules Invariant Natural Killer T (iNKT), dont les effets anti-tumoraux ont été démontrés, sont de puissants activateurs des cellules Natural Killer (NK), des cellules dendritiques (DC) et des lymphocytes T. Cependant, une seule injection du ligand de haute affinité alpha-galactosylceramide (αGC) n'induit une forte activation des cellules iNKT que durant une courte période. Celle-ci est alors suivie d'une longue phase d'anergie, limitant ainsi leur utilisation pour la thérapie. Comme alternative prometteuse, nous avons montré que des injections répétées d'αGC chargé sur une protéine recombinante de CD1d soluble (αGC/sCD1d) chez la souris entraînent une activation prolongée des cellules iNKT, associée à une production continue de cytokine. De plus, le maintien de la réactivité des cellules iNKT permet de prolonger l'activité anti-tumorale lorsque la protéine αGC/sCD1d est fusionnée à un fragment d'anticorps (scFv) dirigé contre la tumeur. L'inhibition de la croissance tumorale n'est optimale que lorsque les souris sont traitées avec la protéine αGC/sCD1d-scFv ciblant la tumeur, la protéine αGC/sCD1d-scFv non-appropriée étant moins efficace. Dans le système humain, les protéines recombinantes αGC/sCD1d-anti-HER2 et anti-CEA sont capables d'activer et de faire proliférer des cellules iNKT à partir de PBMCs issues de donneurs sains. De plus, la protéine αGC/sCD1d-scFv a la capacité d'activer directement des clones iNKT humains en l'absence de cellules présentatrices d'antigènes (CPA), contrairement au ligand αGC libre. Mais surtout, la lyse des cellules tumorales par les iNKT humaines n'est obtenue que lorsqu'elles sont incubées avec la protéine αGC/sCD1d-scFv anti- tumeur. En outre, la redirection de la cytotoxicité des cellules iNKT vers la tumeur est supérieure à celle obtenue avec une stimulation par des CPA chargées avec l'αGC. Afin d'augmenter les effets anti-tumoraux, nous avons exploité la capacité des cellules iNKT à activer l'immunité adaptive. Pour ce faire, nous avons combiné l'immunothérapie NKT/CD1d avec un vaccin anti-tumoral composé d'un peptide OVA. Des effets synergiques ont été obtenus lorsque les traitements avec la protéine αGC/sCD1d-anti-HER2 étaient associés avec le CpG ODN comme adjuvant pour la vaccination avec le peptide OVA. Ces effets ont été observés à travers l'activation de nombreux lymphocytes T CD8+ spécifique de la tumeur, ainsi que par la forte expansion des cellules NK. Les réponses, innée et adaptive, élevées après le traitement avec la protéine αGC/sCD1d-anti-HER2 combinée au vaccin OVA/CpG ODN étaient associées à un fort ralentissement de la croissance des tumeurs B16- OVA-HER2. Cet effet anti-tumoral corrèle avec l'enrichissement des lymphocytes T CD8+ spécifiques observé à la tumeur. Afin d'étendre l'application des protéines αGC/sCD1d et d'améliorer leur efficacité, nous avons développé des fusions CD1d alternatives. Premièrement, une protéine αGC/sCD1d dimérique, qui permet d'augmenter l'avidité de la molécule CD1d pour les cellules iNKT. Dans un deuxième temps, nous avons fusionné la protéine αGC/sCD1d avec un scFv dirigé contre le récepteur 3 du facteur de croissance pour l'endothélium vasculaire (VEGFR-3), afin de cibler l'environnement de la tumeur. Dans l'ensemble, ces résultats démontrent que la thérapie médiée par la protéine recombinante αGC/sCD1d-scFv est une approche prometteuse pour rediriger l'immunité innée et adaptive vers le site tumoral. - Invariant Natural Killer T cells (iNKT) are potent activators of Natural Killer (NK), dendritic cells (DC) and T lymphocytes, and their anti-tumor activities have been well demonstrated. However, a single injection of the high affinity CD1d ligand alpha-galactosylceramide (αGC) leads to a strong but short-lived iNKT cell activation followed by a phase of long-term anergy, limiting the therapeutic use of this ligand. As a promising alternative, we have demonstrated that when αGC is loaded on recombinant soluble CD1d molecules (αGC/sCD1d), repeated injections in mice led to the sustained iNKT cell activation associated with continued cytokine secretion. Importantly, the retained reactivity of iNKT cell led to prolonged antitumor activity when the αGC/sCD1d was fused to an anti-tumor scFv fragments. Optimal inhibition of tumor growth was obtained only when mice were treated with the tumor-targeted αGC/CD1d-scFv fusion, whereas the irrelevant αGC/CD1d-scFv fusion was less efficient. When tested in a human system, the recombinant αGC/sCD1d-anti-HER2 and -anti-CEA fusion proteins were able to expand iNKT cells from PBMCs of healthy donors. Furthermore, the αGC/sCD1d-scFv fusion had the capacity to directly activate human iNKT cells clones without the presence of antigen-presenting cells (APCs), in contrast to the free αGC ligand. Most importantly, tumor cell killing by human iNKT cells was obtained only when co- incubated with the tumor targeted sCD1d-antitumor scFv, and their direct tumor cytotoxicity was superior to the bystander killing obtained with αGC-loaded APCs stimulation. To further enhance the anti-tumor effects, we exploited the ability of iNKT cells to transactivate the adaptive immunity, by combining the NKT/CD1d immunotherapy with a peptide cancer vaccine. Interestingly, synergistic effects were obtained when the αGC/sCD1d- anti-HER2 fusion treatment was combined with CpG ODN as adjuvant for the OVA peptide vaccine, as seen by higher numbers of activated antigen-specific CD8 T cells and NK cells, as compared to each regimen alone. The increased innate and adaptive immune responses upon combined tumor targeted sCD1d-scFv treatment and OVA/CpG vaccine were associated with a strong delay in B16-OVA-HER2 melanoma tumor growth, which correlated with an enrichment of antigen-specific CD8 cells at the tumor site. In order to extend the application of the CD1d fusion, we designed alternative CD1d fusion proteins. First, a dimeric αGC/sCD1d-Fc fusion, which permits to augment the avidity of the CD1d for iNKT cells and second, an αGC/sCD1d fused to an anti vascular endothelial growth factor receptor-3 (VEGFR-3) scFv, in order to target tumor stroma environment. Altogether, these results demonstrate that the iNKT-mediated immunotherapy via recombinant αGC/sCD1d-scFv fusion is a promising approach to redirect the innate and adaptive antitumor immune response to the tumor site.

Analysis of Some Stochastic Inventory Models with Pooling/ Retrial of Customers

In this thesis we have presented several inventory models of utility. Of these inventory with retrial of unsatisfied demands and inventory with postponed work are quite recently introduced concepts, the latt~~ being introduced for the first time. Inventory with service time is relatively new with a handful of research work reported. The di lficuity encoLlntered in inventory with service, unlike the queueing process, is that even the simplest case needs a 2-dimensional process for its description. Only in certain specific cases we can introduce generating function • to solve for the system state distribution. However numerical procedures can be developed for solving these problem.

Untersuchungen zur Eliminierung und Resorption von Zink aus Säugerspermatozoen während der Nebenhodenpassage

Während der Spermatogenese wird das Element Zink an die Sulfhydrylreste der Cysteine in den Mantelfaserproteinen der Spermienflagellen gebunden. So kann in den noch unreifen Mantelfasern die ungerichtete Ausbildung von Disulfidbrücken verhindert werden. Im Zuge der Spermatozoenreifung während der Nebenhodenpassage wird dieses Zink androgenabhängig zu einem hohen Prozentsatz wieder eliminiert. Die nun gerichtete Ausbildung von Disulfidbrücken ermöglicht die Versteifung der Mantelfasern. Diese Rigidität stellt die Voraussetzung zur progressiven Motilität dar, ohne die eine Fertilisierung der Eizelle im weiblichen Genitaltrakt nicht möglich ist. Da eine negative Korrelation zwischen dem Zinkgehalt von Flagellen und ihrer Motilität besteht (Henkel et al., 1999), hat die Zinkeliminierung während der Nebenhodenpassage eine entscheidende Bedeutung in der Entwicklung der Spermatozoen. Die vorliegende Arbeit untersucht die Mechanismen der epididymalen Zinkeliminierung sowie die an diesem Prozess beteiligten Komponenten und den Verbleib des eliminierten Zinks am System des Bullen, der Ratte und des Menschen. Mittels proteinchemischer Verfahren kann im bovinen System ein zinkbindendes 60 kDa-Protein als Albumin identifiziert werden. Ein 80 kDa-Protein mit zinkbindenden Eigenschaften bleibt unidentifiziert. Die Zinkbindungskapazität der fraktionierten Proteine ist dabei im Caput epididymidis am stärksten ausgeprägt. Atomabsorptionsspektralphotometrische Untersuchungen zeigen die höchsten flagellären Zinkwerte in den Spermien des Rete testis und eine Abnahme des Zinkgehalts zwischen Nebenhodenkopf und -körper. Durch Autometallographie kann eine epitheliale Zinkresorption im Nebenhodenschwanz nachgewiesen werden. Dort erfolgt auch die basale Anreicherung des Zinks. Am Zinkstoffwechsel scheint auch der Macrophage Migration Inhibitory Factor (MIF) beteiligt zu sein. Dieser ist ein Zytokin mit Oxidoreduktasecharakter und kommt unter anderem im Nebenhodenepithel sowie in den Vesikeln des Nebenhoden-Fluids der Ratte vor. MIF zeigt in den hier durchgeführten Untersuchungen sowohl in systemhomologer, als auch in rekombinanter Form in vitro eine Zink-eliminierende Wirkung auf Rattenspermatozoen des Caputs und der Cauda epididymidis und hat somit möglicherweise Einfluss auf den Reifungsprozess der Spermien im Nebenhoden. Lit.: Henkel R, Bittner J, Weber R, Hüther F, Miska W (1999). Relevance of zinc in human sperm flagella and its relation to motility. Fertil Steril 71: 1138-1143

Mejoramiento Productivo "Apparel Basic Ltda"

Para el presente trabajo realizado en la Universidad del Rosario, buscamos hacer un mejoramiento productivo de la empresa Apparel Basic Ltda. Teniendo en cuenta todas las herramientas aprehendidas durante la academia y aplicando esto a una empresa del sector real de confecciones. Se centrara el análisis principalmente en las tres áreas donde se observan los mayores problemas organizacionales: Producción, manejo de inventarios y entrega de producto. En el primer análisis se realizara todo el estudio del proceso de producción, teniendo en cuenta la distribución en planta, las rutas críticas de proceso, los diagramas de flujo de producto, el análisis de las principales referencias, entre otros. Todo esto con el fin de identificar los principales errores y poder proponer herramientas y procesos de mejora que sean de ayuda para esta organización. El siguiente análisis se desarrollara en el manejo de inventarios; dentro de este aspecto se analizaran la distribución de las bodegas de producto, la identificación de los productos de mayor rotación, el planteamiento de indicadores de gestión, entre otros procesos, con el fin de identificar procesos benéficos para la empresa que aceleren y mejoren el flujo de producto al interior de la organización. Luego de esto, se analiza todo el proceso de alistamiento y entrega de producto ya que es uno de los principales problemas dentro de la organización porque se esta incumpliendo con los pedidos de los clientes lo que genera un problema de insatisfacción por parte de los clientes.

A motivação empreendedora e a satisfação com o desempenho organizacional em empresas de pequeno e médio porte de Blumenau: uma análise da indústria local

The current study arose from previous studies made by McClelland (1972), Namam; Slevin (1993), Kuratko; Hornsby; Naffziger (1997), Hoeltgebaum; Kato (2002); Hoeltgebaum;Debastini (2003), Hoeltgebaum; Santos; Loesch (2003) and Hoeltgebaum; Santos (2003). Its objective is to understand the reasons that that lead an entrepreneur to open his ownbusiness, his degree of satisfaction and to perceive if there is a relation between entrepreneurial motivation and the performance of companies. In order to concretize the objective, a descriptive qualitative/quantitative research was realized, amounting to 88 questions of a closed type, statistically ordered. Data collection was achieved by means of a questionnaire divided into 4 parts. Once responses to the questionnaires were obtained, analysis was performed on them, using LHSTAT software. Among the principal results, it was evident in the analysis of the questionnaires that there were a variety of motivations for opening a new business present among the interviewed, with a small, distinct difference in the frequency of the responses. When the satisfaction of the respondents regarding the performance of the company was analyzed, it was perceived that the greatest satisfaction derived from gross and net profit margin and return on investment. Several interdependencies between motivation and satisfactionand performance were evident in the research, with three in particular being the strongest. It was decided to include a category regarding behavioral characteristics of entrepreneurs tothe objectives of the project in which, according to the interviewees, these have a strong entrepreneurial profile; results showed that all the characteristics are well developed. It wasconcluded that the intrinsic motivations are more evident in the entrepreneurs interviewed and that the greatest satisfaction among them lies in the area of gross and net profit margin andin return over investment. It was perceived that there are clear relationships between the motivation of entrepreneurs and satisfaction with the performance of companies.

Attention and selection behavior on ‘universal search’ result pages

The ISO norm line 9241 states some criteria for ergonomics of human system interaction. In markets with a huge variety of offers and little possibility of differentiation, providers can gain a decisive competitive advantage by user oriented interfaces. A precondition for this is that relevant information can be obtained for entrepreneurial decisions in this regard. To test how users of universal search result pages use those pages and pay attention to different elements, an eye tracking experiment with a mixed design has been developed. Twenty subjects were confronted with search engine result pages (SERPs) and were instructed to make a decision while conditions “national vs. international city” and “with vs. without miniaturized Google map” were used. Different parameters like fixation count, duration and time to first fixation were computed from the eye tracking raw data and supplemented by click rate data as well as data from questionnaires. Results of this pilot study revealed some remarkable facts like a vampire effect on miniaturized Google maps. Furthermore, Google maps did not shorten the process of decision making, Google ads were not fixated, visual attention on SERPs was influenced by position of the elements on the SERP and by the users’ familiarity with the search target. These results support the theory of Amount of Invested Mental Effort (AIME) and give providers empirical evidence to take users’ expectations into account. Furthermore, the results indicated that the task oriented goal mode of participants was a moderator for the attention spent on ads. Most important, SERPs with images attracted the viewers’ attention much longer than those without images. This unique selling proposition may lead to a distortion of competition on markets.

Eye tracking data representation and visualization : on information and communication studies at CETAC.MEDIA

Eye tracking has become a preponderant technique in the evaluation of user interaction and behaviour with study objects in defined contexts. Common eye tracking related data representation techniques offer valuable input regarding user interaction and eye gaze behaviour, namely through fixations and saccades measurement. However, these and other techniques may be insufficient for the representation of acquired data in specific studies, namely because of the complexity of the study object being analysed. This paper intends to contribute with a summary of data representation and information visualization techniques used in data analysis within different contexts (advertising, websites, television news and video games). Additionally, several methodological approaches are presented in this paper, which resulted from several studies developed and under development at CETAC.MEDIA - Communication Sciences and Technologies Research Centre. In the studies described, traditional data representation techniques were insufficient. As a result, new approaches were necessary and therefore, new forms of representing data, based on common techniques were developed with the objective of improving communication and information strategies. In each of these studies, a brief summary of the contribution to their respective area will be presented, as well as the data representation techniques used and some of the acquired results.

Crowding no varejo: diferenças na satisfação e percepção de valor hedônico de consumidores de alta e baixa renda no Brasil

Esta investigação visa o melhor entendimento do fenômeno do crowding em lojas, dentro do contexto do mercado brasileiro, procurando identificar como as respostas dos consumidores variam entre os de renda baixa e renda alta, e buscando fatores que possam melhor explicar essas diferenças. Para atender esses objetivos, adotou-se uma metodologia experimental para testar como o aumento da densidade humana afeta diferentemente as respostas dos consumidores de alta e baixa renda. Como moderadoras da relação entre densidade humana e as respostas de consumidores, utilizaram-se as variáveis renda (alta e baixa) e familiaridade (alta e baixa). Três experimentos de desenhos fatoriais permitiram o teste das hipóteses propostas, por meio de análises multivariadas: ANOVAs, ANCOVAs e regressões lineares. Os estudos demonstraram que renda efetivamente modera as respostas dos consumidores, pois existe substancial diferença entre os consumidores de alta e baixa renda para situações de alta densidade humana em lojas. Foram verificadas as seguintes respostas dos consumidores com menor renda em situações de alta densidade humana: atitude mais positiva e maior nível de satisfação do que os de alta renda; percepção de maior valor hedônico em lojas mais cheias de gente versus os de maior renda. Os resultados contrariam a maioria dos achados de estudos realizados nos Estados Unidos nas últimas décadas. Enquanto a maioria desses estudos indica uma resposta negativa à densidade humana, os resultados desta pesquisa evidenciaram que existem respostas mais positivas para o segmento econômico de consumidores de baixa renda. Constatou-se também o efeito moderador do controle informacional (familiaridade) na relação entre densidade humana e as respostas dos consumidores, e o efeito mediador da percepção de valor hedônico na relação entre densidade e satisfação. Os achados oferecem uma contribuição teórica para enriquecer o entendimento do fenômeno de crowding e ressaltam a importância de se considerar a diversidade do contexto socioeconômico para se garantir o desenvolvimento de generalizações que corretamente reflitam as várias realidades do mercado. Do ponto de vista gerencial, o estudo reforça a necessidade de o varejo desenvolver uma maior distinção em ambientes de loja para melhor satisfazer as diferentes preferências dos diversos segmentos de mercado.

Gestão de satisfação e fidelidade do cliente: um estudo dos fatores que afetam a satisfação e fidelidade dos compradores de automóveis

This Master s thesis presents a discussion on customer satisfaction models investigating the relations of antecedent variables service quality, price index, complaint handling, image, affective and calculative commitment, with satisfaction and loyalty. The scope of the research is the influence of service dimensions in the car buyer s satisfaction and loyalty. A sample of 91 customers was surveyed among new cars buyers of one brand in Natal city, Brazil, and the data was analyzed using multiple regression analysis. The literature review covers subjects such as customer satisfaction, management system, customer satisfaction measurement index models. The main findings suggest that satisfaction with the car brand is mainly influenced by customization of the service, time for accomplishing servicing, and the way the dealer handle complains. Regarding the dealer itself the main variable related to satisfaction is also time for accomplishing servicing. Considering customer loyalty, the customer satisfaction with the dealer explain strongly the loyalty with the brand/manufacturer. Also, the satisfaction, affective commitment and complains handling were found related to loyalty, as the stronger variables explaining the loyalty variance. One main conclusion is that service provided by dealers is one key factor influencing the customer satisfaction and loyalty in auto industry

Bone spreading technique a case report

Bone spreading technique (BST) is a horizontal augmentation with minimal trauma for simultaneous implant placement and an alternative to Summer's osteotome technique both for its clinical use and for the armamentarium. The foremost advantage of the crest dilation technique is a substantially less invasive method; the buccal wall expands after the medullary bone is compressed against the cortical bone. The lateral dilation and compaction of medullary bone improved primary stability. The vital difference is that the BST used in this case report avoided discomfort of the patient, thus eliminating the need for malleting.

Sistema de coleta, análise e detecção de código malicioso baseado no sistema imunológico humano

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)