Bardet-Biedl syndrome (BBS) is a rare genetic disease that causes retinal degradation, obesity, kidney dysfunction, polydactyly, and other cilium-related disorders. To date, more than 20 BBS genes, whose mutants cause BBS phenotypes, have been identified, and eight of those (BBS1-2, 4-5, 7-9, and 18) are known to form the BBSome complex. Recent studies have revealed that the BBSome is closely involved in the trafficking of signaling proteins in the primary cilium. Mutations in BBS genes are highly pathogenic because trafficking in the primary cilium is not fully functional when BBS mutations impair assembly of the BBSome. However, the functional links between onset of BBS and BBSome assembly are not well understood. To address this gap in knowledge, we examined the structure of a BBSome assembly intermediate, the BBSome core complex (BBS2, 7, and 9). We employed a combination of chemical crosslinking coupled with mass spectrometry (XL-MS) and electron microscopy (EM) to determine the structure. We applied this structural information to BBS mutations in the core complex to understand how these mutations might cause the disease. These results provide the first structural model of the BBSome core complex and give insight into the molecular basis of Bardet-Biedl syndrome. We have also investigated the mechanism of assembly of the two mTOR kinase complexes (mTORC1 and 2). mTOR is a master regulator of cell metabolism, growth and proliferation. As such, mTOR is a high-value drug target. We investigated the mechanism of assembly of these mTOR complexes and found that the cytosolic chaperonin CCT contributes to mTOR signaling by assisting in the folding of mLST8 and Raptor, components of mTORC1 and mTORC2. To understand the function of CCT in mTOR complex assembly at the molecular level, we have isolated the mLST8-CCT complex and performed a structural analysis using chemical cross-linking couple with mass spectrometry (XL-MS) and cryogenic EM. We found that mLST8 binds CCT deep in its folding cavity, making specific contacts with the CCTα and γ subunits and forming a near-native β-propeller conformation. This information can be used to develop new therapeutics that regulate mTOR activity by controlling mTOR complex assembly.

<p>Adjustment to a new culture is a slow and step-wise process, which can be facilitated by cross-cultural training. First, a comprehensive review of current theories about cross-cultural adjustment and different training techniques is presented. Then, the study looks at the preparation and training of expatriates at Ericsson in relation to these theories. In-depth interviews with two Area Managers at Ericsson have been carried out in order to establish how the company’s training program is structured. We found that Ericsson follows a sequential model with both pre-departure and post-arrival training, mainly didactic in nature. The pre-departure training is very culturegeneral, whereas the post-arrival training is more specific for the host culture. The post-arrival training is, however, not offered in all host countries. Language training is also offered, and expatriates are encouraged to visit the host country prior to the departure. Many components in Ericsson’s training program are supported by theory,but several other techniques described in the theory are not in use. A suggestion is made to further formalize the post-arrival training and make the overall training more culture-specific.</p>

Adjustment to a new culture is a slow and step-wise process, which can be facilitated by cross-cultural training. First, a comprehensive review of current theories about cross-cultural adjustment and different training techniques is presented. Then, the study looks at the preparation and training of expatriates at Ericsson in relation to these theories. In-depth interviews with two Area Managers at Ericsson have been carried out in order to establish how the company’s training program is structured. We found that Ericsson follows a sequential model with both pre-departure and post-arrival training, mainly didactic in nature. The pre-departure training is very culturegeneral, whereas the post-arrival training is more specific for the host culture. The post-arrival training is, however, not offered in all host countries. Language training is also offered, and expatriates are encouraged to visit the host country prior to the departure. Many components in Ericsson’s training program are supported by theory,but several other techniques described in the theory are not in use. A suggestion is made to further formalize the post-arrival training and make the overall training more culture-specific.

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Taiwan society had evolved in the past 15 years, and the citizens had more opportunities to participate in puclic policy decisions.However, the formation of the policy about Mainland China in Taiwan is a very diffcult thing. A lot of different opinions and ideology we can not control. Coping with Mainland China affairs is invitable to Taiwan. No matter economic, politics or society, Taiwan always faces the menace of the Mainland China. Therefore, making a good Mainland China policy is important. Cohering a common comsensus is also essential.And Social Judgment Theory is a descriptive and normative approach to judgment and decision making developed by Kenneth Hammond (1965,1975,1996) on the basis of Lens Model. Social Judgment Theory has been applied to the analysis of multiple cue probability learning, interpersonal conflict, interpersonal learning, and social policy decisions. It has also produced the policy decision aid. Moreover, Social Judgment Theory emphasizes that the¡§Judgment¡¨is generally more effective (reaches a higher achievement level), and more efficient(reaches a given achievement level more quickly) by utilizing of cognitive feedback while making decision. In this study, a serious of simulated decision maing tast about importing Mainland China talent and the Social Jugdement Theory and Cognition Conflict Paradigm have been employed and tested by way of a laboratory quasi-experiment. The research prove : 1.Cognitive feedback is more effective than outcome feedback in regard to the improvement of individual decision quality. 2. Dual cognitive feedback is more effective than outcome feedback in regard to the improvement of individual decision quality. 3.Dual cognitive feedback is more effective than outcome feedback in regard to the elimination of cognitive conflict. Comparing Taiwan with Mainland China MPA students, we can find the students in Taiwan and Mainland China are all concerning about the cues variable of polotics. They all think the politics is the most important variable about the strait affairs.

Cilia are evolutionarily conserved microtubule-based organelles projecting from nearly all vertebrate cells, and ciliary defects result in a variety of human disorders known as ciliopathies. Recent studies have shown that several planar cell polarity (PCP) proteins are essential for cilia functions. Here, we focused on Fritz, known as a novel PCP effector protein in Drosophila, in multi-ciliated cells in the epidermis of Xenopus laevis embryos. To investigate the role of Fritz, using confocal and scanning electron microscopy, we discovered that Fritz localizes along the ciliary axonemes and that knockdown of Fritz causes severe reductions in both axoneme length and number. Then, using pull-downs and mass-spectrometry, we identified Chaperonin Containing T-complex polypeptide 1 (CCT) and septin as interacting partners of Fritz. CCT is the key chaperonin interacting with septins, and both have been implicated in ciliogenesis. Using tagged CCT subunit constructs, we found that the tagged CCTα and CCTε co-localize with Fritz along the ciliary axonemes of multi-ciliated cells. Knockdown of Fritz resulted in the accumulation of CCT at the apical cytoplasm of multi-ciliated cells; however, it was confirmed that Fritz does not affect the CCT holoenzyme assembly. Septins, another interacting partner of Fritz, are novel cytoskeletal elements. Using septin antibodies, we found that endogenous septins also localize along the ciliary axonemes and accumulate in the apical cytoplasm of multi-ciliated cells in Fritz morphants. Similar ciliary defects were observed in septin morphants. Our results reveal that Fritz is essential for ciliogenesis, and that CCT and septin interact with Fritz to control ciliogenesis in Xenopus multi-ciliated cells. Additionally, tubulin acetylation is markedly reduced by Fritz knockdown, suggesting that Fritz affects tubulin acetylation.

Bacterial toxins have co-opted host cell machinery in order to enter cells and exert their deleterious effects. Anthrax toxin is composed of the receptor binding protein protective antigen (PA), and the enzymatic subunits lethal factor (LF) and edema factor (EF), which form the binary toxin complexes lethal toxin, LeTx (PA + LF), and edema toxin, EdTx (PA + EF). PA binds to receptors on the surface of host cells and shuttles LF and EF into cells through the endocytic pathway. Upon endosome acidification, PA oligomers insert into the endosomal membrane and form functional pores that deliver LF and EF into the cytoplasm. Translocation of the N-terminal domain of LF, \(LF_N\), through PA pores formed in lipid bilayers in vitro does not require host machinery. However, translocation of the related fusion protein \(LF_N\)-DTA across the membrane of toxin-loaded endosomes in vitro requires the addition of cytosolic translocation factors that include the COPI coatamer complex. We performed high-throughput small molecule and RNAi screens to identify host factors required for LF translocation, using LeTx-induced cell death as a phenotype. We describe the characterization of small molecule inhibitors of LeTx-induced cell death that inhibit toxin entry. Further, we describe the role of the endosomal chaperone GRP78 and the cytoplasmic CCT chaperonin in toxin translocation. RNAi knockdown of GRP78 and CCT subunits inhibited LeTx and EdTx delivered through the endocytic pathway. CCT knockdown additionally inhibited translocation of LF through PA pores formed directly in the plasma membrane, while GRP78 had no effect. Furthermore, we show that the role of GRP78 in toxin translocation is specific to translocation from the early endosome. Together with biochemical data, we propose that GRP78 facilitates translocation by unfolding LF and EF at near-neutral pH. In addition, we show that in CCT-knockdown cells, lethal levels of toxin reach the endosome, suggesting that CCT has a role in translocation and/or refolding of LF and EF. These studies highlight previously unidentified strategies used by anthrax toxin to hijack host cellular machinery in order to gain access to the cytosol.

The aim of the thesis is to contribute to the CCT research field on social identity, by placing a focus on power from a customer perspective and studying how power can be accentuated within social identity. Theory from CCT with a focus on social identity has been used in combination with extensive literature on power and authority from a sociological perspective and literature from Fashion-Studies focusing on power-dressing, conspicuous consumption and luxury. The research question is: How is power-dressing and consumption of high-end luxury fashion brands used by female executives/senior managers in an attempt to accentuate power as a part of their social identity? In-depth semi-structured interviews where used as the main data collection method interviewing five female senior managers/female executives working in Stockholm; using the fashion consumption of female senior managers as its empirical sample. The main conclusion on this thesis is the creation of the concept of power-coded-dressing.This thesis implications are that it develops the CCT field slightly by adding a consumer-power perspective into the theoretical discourse. Its practical and social implications help women accentuate their power through, power-coded-dressing.

Foram coletadas amostras de uma chapa grossa temperada, de aço microligado ao boro com 8 mm de espessura. O aço foi produzido em aciaria do tipo LD, laminado na forma de chapa grossa em laminador de cadeira única reversível e finalmente recebeu tratamento de têmpera em forno de tubos radiantes e máquina de têmpera com fluxo de água. Todas as etapas de produção tiveram os parâmetros de processo controlados para obtenção das melhores propriedades possíveis. As amostras foram retiradas da região situada a um quarto da largura da chapa e submetidas a diversos ciclos térmicos em aparelho de dilatometria. Com auxílio de técnicas de microscopia ótica, microscopia eletrônica de varredura e medidas de dureza, o aço pôde ser caracterizado e foi possível levantar as curvas de resfriamento contínuo (TRC). As microestruturas revelaram a presença de múltiplos microconstituintes, principalmente em resfriamentos a partir de resfriamentos 25°C/s, quando surgem elementos aciculares como ferrita acicular e bainita misturados com ferrita poligonal e perlita. Acima desta taxa de resfriamento o campo perlítico é suprimido e a partir de 45°C/s surge a martensita. A 100°C/s a microestrutura é dominada predominantemente por martensita. As amostras resfriadas nas 3 taxas mais severas também revelaram a presença de austenita retida e constituinte MA, detectados por meio de difração de raios-x e ataque com reagente de Klemm. / Samples were taken from a quenched plate with 8mm thickness and chemical composition consisting of carbon, manganese, silicon, aluminum, niobium, titanium and boron. The steel was produced in LD converter, rolled in a reversible single chair rolling mill and quenched in a radiating tube furnace and quenching machine with water flow. All production stages had the process parameters controlled to obtain the best possible properties. The samples were extracted from a position situated at one quarter of the plate´s width and submitted to various thermal cycles in dilatometry device. With the aid of optical microscopy, scanning electron microscopy and hardness measurements, the steel could be characterized and the continuous cooling transformation curves could (CCT) be plotted. The microstructures revealed the presence of multiple components, especially when cooling rates reach 25°C/s, where acicular elements, like acicular ferrite and bainite, are found along with polygonal ferrite and pearlite. Above this cooling rate the pearlite field is suppressed and starting at 45°C/s martensite was found. At 100°C/s the microstructure is mainly martensitic. The samples cooled at the 3 most severe rates also revealed the presence of retained austenite and MA constituent, which were detected by x-ray diffraction and attack using Klemm reagent.

A partir d'un cadre théorique pragmatique, cette recherche étudie le rôle des concours professionnels de café dans la formation d'un nouveau régime de goût (1) et dans l'émergence depuis le début des années 2010 du marché des coffee shops en France (2). Plus particulièrement, il s'agit de comprendre comment les concours influencent les pratiques de préparation et de service des baristas, d'abord lors de la compétition puis au quotidien dans leurs établissements. En d'autres termes, l'enjeu et de saisir comment une situation non-marchande performe une situation marchande. Une enquête ethnographique de deux ans et demi a été réalisée. Elle s'appuie sur des observations participantes et non­participantes réalisées lors des concours et dans les coffee shops, sur des entretiens avec baristas, juges et organisateurs de concours ainsi que sur une analyse de données secondaires. Les résultats de l'enquête montrent que les juges de concours produisent un discours normatif qui orchestre de manière douce la manière dont les candidats baristas préparent et servent le café. Ce discours normatif se diffuse hors de la situation non-marchande et influence les pratiques quotidiennes des baristas, qu'ils aient ou non participé aux concours. Non seulement le discours normatif des experts modèle le marché naissant des coffee shops, mais il modèle aussi trois marchés connexes : le marché des équipements, le marché des formations et le marché du travail des baristas. Cette thèse contribue à la littérature B2B sur la performation des marchés, à la littérature marketing d'inspiration pragmatique sur le goût et à la littérature sur l'expertise. / Building on a pragmatic theoretical framework, this research investigates the role of professional contests in a new taste regime elaboration ( 1) and in the French coffee shops market emergence since 2010 (2). More specifically, the goal is to understand how contests influence baristas' coffee preparation and service practices during championships first, and then baristas' mundane practices in coffee shops. In other words, I aim at understanding how a non-market situation shapes a market situation. A two and half years ethnography has been done. The inquiry is based on participant and non-participant observations in both coffee contests and coffee shops, on interviews with baristas, judges and contests organizers, and on a secondary data analysis. Results show judges produce a normative discourse that softly orchestrates the way baristas prepare and serve coffee. Such a normative discourse spreads outside the non-market situation and shapes baristas' mundane practice whether they participate to the championship or not. Experts' normative discourse shapes the emerging coffee shop market but also three related markets: the equipment market, the training market and the barista job market. This dissertation contributes to the B2B literature about market performation, to the pragmatic literature about taste and finally to the literature about expertise.