Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Este trabalho tem como propÃsito explicitar a continuidade do pensamento de Heidegger a respeito da relaÃÃo entre o Dasein e a linguagem, especificamente a partir da abordagem de trÃs textos: Ser e tempo (1927); Sobre o humanismo (1946) e O caminho para a linguagem (1959). O objetivo principal à examinar esta relaÃÃo antes e depois do que foi considerado uma âviradaâ (Kehre) na filosofia de Heidegger, destacando uma nova concepÃÃo de linguagem e ser humano que resulta desse movimento. Parte-se de uma abordagem hermenÃutica de Heidegger e de uma ampliaÃÃo do contexto da analÃtica existencial nÃo no sentido de uma âantropologia filosÃficaâ, em que se poderia firmar a essÃncia do homem, de seu pensar e agir, mas no sentido de uma âfilosofia antropolÃgicaâ, se assim for possÃvel propor, que pressupÃe a contingÃncia e a faticidade. A centralidade da reviravolta lingÃÃstica na filosofia contemporÃnea, como uma forma de radicalizaÃÃo da relaÃÃo de âpertenÃaâ entre linguagem e âhumanoâ, à atrelada a este contexto em funÃÃo de sua importÃncia no pensamento filosÃfico que pÃe em xeque o pensar metafÃsico. Neste movimento, busca-se saber atà que ponto o pensamento de Heidegger efetivamente se transforma, ou simplesmente se desdobra a partir de pressupostos que jà estavam dados desde Ser e tempo. Por um lado, o abandono da analÃtica existencial do Dasein como âmediaÃÃoâ em favor de uma ampliaÃÃo do sentido da linguagem do ser distancia Heidegger da âantropologiaâ, por outro, se consideramos a centralidade da poesia no pensamento da âhistÃria do serâ e da âverdade do serâ, vemos que o Dasein permanece uma referÃncia central reconfigurada, e que nos remete a uma nova possibilidade de âantropologiaâ. Opondo-se à determinaÃÃo lÃgica do conhecimento em favor do aspecto hermenÃutico da compreensÃo, o pensamento de Heidegger aponta a âlogiaâ como determinante para que o anthropos tenha se tornado a referÃncia central da filosofia. Abandonando-se a âlogiaâ do logos enquanto lÃgica, e este parece ser o caminho de Heidegger desde o inÃcio, remanesce a centralidade do Dasein como abertura ao ser e como pÃlo da diferenÃa ontolÃgica; vigora o homem no lugar do sujeito do conhecimento; permanece o logos enquanto linguagem. / This work intends to explain the continuity of Heideggerâs thought on the relation between Dasein and language, specifically through the approach of three texts: Sein und Zeit (1927), Ãber humanismus (1946) and Der Weg zur Sprache (1959). The main objective is approaching this relation before and after the so called turn (Kehre) in Heideggerâs philosophy, emphasizing a new conception of language and human being which results of this movement. Our starting point is an hermeneutical approach of Heidegger and an enlargement of the existential analyses not towards a âphilosophic anthropologyâ, in which we could set up the essence of the human being, of his thinking and acting, but in the sense of an âanthropological philosophyâ, if it is possible, which presupposes contingency and facticity. The preponderance of the linguistic turn in the contemporary philosophy, as a way of increasing the âbelongingâ relation between language and the dimension of âhumanâ, is linked to this context, according to its importance in the philosophical thought that keeps in check the metaphysical thinking. This approach aims to know how far Heideggerâs thought effectively moves towards a transformation or barely unrolls itself starting to presumptions which were already in Being and time. On one hand, when Heidegger leaves the existential analyses of the Dasein as âmediationâ on behalf of an ampliation of the sense on seinâs language, he stays apart from the anthropology. On the other hand, if we consider the preponderance of poetry in the thinking of the âhistory of beingâ and âtruth of beingâ, we see that Dasein remains as an important reference in other terms, which send us to a possibility of a new anthropology. Criticizing the logical determination of knowledge in the name of hermeneutical feature of comprehension, Heideggerâs thought indicates that âlogyâ has determine the anthropos to become the central reference of philosophy. Abandoning the âlogyâ of logos, and this seems to be Heideggerâs orientation since his beginning, the preponderance of the Dasein stays as openness of being and as pole of the ontological difference; the man is in verve instead of the epistemic subject; the logos remains as language.

Since its publication in 1898, The Turn of the Screw has been the focus of diverse critical interpretation. It has reflected shifts in critical theory that include the Freudian, psychoanalytic, mythological, structuralist, reader-response, linguistic, and new-historical schools. The majority of critical interpretations have focused on the governess's narrative and have excluded the prologue, or frame narrative, that begins the novella. The critics who did examine the prologue overlooked James's departure from the traditional use of frame narration and the importance of the structure of the frame in creating a text of insoluble ambiguity. James departed from traditional frame narration in four ways. By using only an opening frame, the reader is forced to rely on the prologue in order to determine narrative reliability. By creating a condition of reciprocal authority between the unnamed narrator and Douglas, the opening frame denies the possibility of using either character to substantiate the reliability of the other. The condition of reciprocal authority is constructed through a dialogue pattern in which the narrator and Douglas interpret each other's gestures and comments and finish each other's sentences. It is the use of the pattern in the prologue that prepares the reader to accept it in the governess's narrative. The governess repeats the dialogue pattern with Mrs. Grose and Miles. Their discussions appear to validate the governess as a reliable narrator when in fact her reliability is as impossible to determine as the reliability of Douglas or the frame narrator. The result of these departures from traditional frame narration is the construction of a text of insoluble ambiguity.

Most safety analysis is conducted using crash data. Surrogate safety measures, such as various time-based measures of time-to-collision can be related to crash potential and used to gain insight into the frequency and severity of crashes at a specific location. One of the most common and acknowledged measures is post-encroachment time (PET) which defines the time between vehicles occupying a conflicting space. While commonly used in studies of motor vehicle interactions, studies of PET for bicycle-vehicle interactions are few. In this research, the PET of bicycle-vehicle interactions measured in the field, a driving simulator, and in a micro-simulation are compared. A total of 52 right-hook conflicts were identified in 135 hours of video footage over 14 days at a signalized intersection in Portland, OR (SW Taylor and SW Naito Pkwy). The results showed that 4 of 17 high-risk conflicts could not be identified by the conventional definition of PET and PET values of some conflicts did not reflect true risk of collision. Therefore, right-hook conflicts were categorized into two types and a modified measure of PET was proposed so that their frequency and severity were properly measured. PETs from the field were then compared to those measures in the Oregon State University driving simulator during research conducted by Dr. Hurwitz et al. (2015) studying the right-hook conflicts. Statistical and graphical methods were used to compare field PETs to those in the simulator. The results suggest that the relative validity of the OSU driving simulator was good but not conclusive due to differences in traffic conditions and intersections. To further explore the field-observed PET values, traffic simulation models of the field intersection were developed and calibrated. Right-hook conflicts were extracted from the simulation files and conflicts observed in PM-peak hours over 6 days in the field were compared to those obtained from 24 traffic simulation runs. The field-observed PET values did not match the values from the simulation values very well. However, the approach does show promise. Further calibration of driving and bicycling behaviors would likely improve the result.

Ce travail théorique et empirique est centré sur la validité de construit des comportements de civisme organisationnel (CCO). Nous proposons une définition « théorique » (caractéristiques observables) qui synthétise les principaux éléments des définitions précédentes. La caractéristique essentielle des CCO est qu'ils sont discrétionnaires (non-imposables, leur omission n'est pas punissable). Cette définition « théorique » est articulée à une définition du « contenu » du domaine, fondée sur le modèle de Borman, Penner et al. (2001). Le questionnaire en français développé sur ce modèle s'ajuste plutôt au modèle de Williams et Anderson (1991, CCO qui bénéficient à l'organisation vs. CCO qui bénéficient aux individus). La validité divergente est étudiée au regard du modèle des cinq facteurs de personnalité. Il est argumenté qu'une meilleure compréhension des relations personnalité-CCO peut être obtenue en considérant les relations au niveau des facettes.<br /><br />Dans une seconde version du questionnaire, les CCO correspondent à un construit latent général, qui peut être distingué en plusieurs facettes plus spécifiques, comme le suggèrent Tepper et al. (2004) et la méta-analyse de LePine et al. (2002). Une analyse théorique et empirique tend à confirmer l'hypothèse d'antécédents communs aux CCO et au turn-over volontaire. La relation entre la motivation à s'engager des marins et les CCO est également étudiée. Globalement, la motivation semble être un antécédent majeur des CCO (Borman et Penner, 2001 ; Organ, 1990). Nous proposons un réseau nomologique des relations entre les CCO et divers construits de la psychologie industrielle et des organisations, incluant la dimension motivationnelle.

<p>The major aim of the studies that this thesis is based on has been to better define the topological determinants of the formation of so-called helical hairpins during membrane protein assembly in the ER membrane.</p><p>The helical hairpin is a basic folding unit in membrane proteins. It is composed of two closely spaced transmembrane helices with a short connecting loop and it is believed to be inserted into the membrane as one compact unit. It is becoming increasingly clear that the helical hairpin is a very common structural element in membrane proteins and a detailed understanding of its properties is of central importance.</p><p>We demonstrate that the efficiency of formation of helical hairpins depends both on the overall length of the hydrophobic segment, on the amino acids flanking the transmembrane segment, and on the identity of the central, potentially turn-forming residues. We also show that interhelical hydrogen bonds between pairs of Asn or Asp residues can induce helical hairpin formation.</p><p>A detailed topology mapping is also reported for the <i>Escherichia coli </i>inner membrane chloride channel YadQ, a protein for which the X-ray structure is known. Our results provide a critical test of the reporter fusion approach and offer new insights into the YadQ folding pathway.</p><p>In summary, the results present in this thesis have increased our understanding of the determinants of membrane protein topology and structure. Furthermore, the information obtained can be used to improve current models for predictions of membrane protein topology.</p>

<p>During the early 1990´s, the Swedish commercial air traffic was de-regulated and the new market-condition made it possible for low-budget airlines to enter the Swedish market. The former monopolistic airline company, Scandinavian Airline Systems (SAS), was facing a new type of competition which had the advantage of offering much cheaper air trips than SAS. Adding the decrease of profitability that struck SAS as well as other airline companies after the terrorist attacks on the 11th of September, forced them to carry out a mayor reorganization programme. The programme, called “Turn Around 2005”, was a direct economical measure that begun in 2002 and lasted until 2005 and resulted in a cost saving of 14,5 billion SEK as well as a notice or a transfer of 6000 employees.</p><p>The purpose of this essay is to investigate if the opinion of the consumer, the image, corresponds with the profile that SAS wishes to mediate today. Our intentions are also to see if the changes during the reorganization have reached the consumers. This essay is a case study based on both a quantitative and a qualitative method. The quantitative study included questionnaires handed out to 143 persons and a former costumer satisfaction study made by “Svenskt Kvalitetsindex”. The qualitative study included deep interviews with employees on SAS. The results of the questionnaires, interviews and theories about image, profile, identity and GAP-analysis, clearly shows that SAS’s profile of being a low- cost airline and being the most price worthy alternative doesn’t correspond with the opinion of the consumers. The result also shows that the consumers have not detected any of the changes, apart from the price reduction, that was made during the reorganization. However SAS have succeeded to be known by the business-passengers as a bit better regarding the ground services and departures, and that part of their image are therefore close to their profile. Our conclusion states that there is an indistinctness regarding SAS profile since the costumers cannot decide if SAS is a low-cost or a traditional airline company.</p>

<p>Antisense RNAs regulate gene expression in many bacterial systems. The best characterized examples are from prokaryotic accessory elements such as phages, plasmids and transposons. Many of these antisense RNAs have been identified as plasmid copy number regulators where they regulate the replication frequency of the plasmid by negative feedback. Instability and fast binding kinetics is crucial for the regulatory efficiency of these antisense RNAs. </p><p>In this thesis, the interaction of the cis-encoded antisense RNA CopA with its target CopT was studied in detail using <i>in vivo</i> reporter gene fusion expression and different <i>in vitro </i>methods, such as surface plasmon resonance, fluorescence resonance energy transfer, and gel-shift assays.</p><p>Formation of inhibitory complexes differs from simple hybridization reactions between complementary strands. E.g., the binding pathway of CopA and CopT proceeds through a hierarchical order of steps. It initiates by reversible loop-loop contacts, resulting in a helix nucleus of two or three base pairs. This is followed by rapid unidirectional helix progression into the upper stems, resulting in a four-way helical junction structure. It had been suggested that the loop of CopT carries a putative U-turn, a structure first found in tRNA anticodon loops. We showed that this putative U-turn is one of the structural elements of CopA/CopT required to achieve fast binding kinetics. Furthermore, the hypothetical U-turn structure determines the direction of helix progression when the kissing complex progresses to a four-way helical junction structure. Another structural element in CopT is the helical stem adjacent to the recognition loop. This stem is important to present the recognition loop appropriately to provide a scaffold for the U-turn.</p><p>Furthermore, the role of protein Hfq in the interaction of antisense/target RNA was investigated, since several trans-encoded antisense RNAs had been shown to need this protein to exert their function. In contrast, studies of two cis-encoded antisense RNA systems showed that these antisense RNAs do not rely on Hfq for activity. In this study it was also shown that MicF, a trans-encoded antisense RNA which is dependent on Hfq, is greatly stabilized by this protein.</p>

Antisense RNAs regulate gene expression in many bacterial systems. The best characterized examples are from prokaryotic accessory elements such as phages, plasmids and transposons. Many of these antisense RNAs have been identified as plasmid copy number regulators where they regulate the replication frequency of the plasmid by negative feedback. Instability and fast binding kinetics is crucial for the regulatory efficiency of these antisense RNAs. In this thesis, the interaction of the cis-encoded antisense RNA CopA with its target CopT was studied in detail using in vivo reporter gene fusion expression and different in vitro methods, such as surface plasmon resonance, fluorescence resonance energy transfer, and gel-shift assays. Formation of inhibitory complexes differs from simple hybridization reactions between complementary strands. E.g., the binding pathway of CopA and CopT proceeds through a hierarchical order of steps. It initiates by reversible loop-loop contacts, resulting in a helix nucleus of two or three base pairs. This is followed by rapid unidirectional helix progression into the upper stems, resulting in a four-way helical junction structure. It had been suggested that the loop of CopT carries a putative U-turn, a structure first found in tRNA anticodon loops. We showed that this putative U-turn is one of the structural elements of CopA/CopT required to achieve fast binding kinetics. Furthermore, the hypothetical U-turn structure determines the direction of helix progression when the kissing complex progresses to a four-way helical junction structure. Another structural element in CopT is the helical stem adjacent to the recognition loop. This stem is important to present the recognition loop appropriately to provide a scaffold for the U-turn. Furthermore, the role of protein Hfq in the interaction of antisense/target RNA was investigated, since several trans-encoded antisense RNAs had been shown to need this protein to exert their function. In contrast, studies of two cis-encoded antisense RNA systems showed that these antisense RNAs do not rely on Hfq for activity. In this study it was also shown that MicF, a trans-encoded antisense RNA which is dependent on Hfq, is greatly stabilized by this protein.

The major aim of the studies that this thesis is based on has been to better define the topological determinants of the formation of so-called helical hairpins during membrane protein assembly in the ER membrane. The helical hairpin is a basic folding unit in membrane proteins. It is composed of two closely spaced transmembrane helices with a short connecting loop and it is believed to be inserted into the membrane as one compact unit. It is becoming increasingly clear that the helical hairpin is a very common structural element in membrane proteins and a detailed understanding of its properties is of central importance. We demonstrate that the efficiency of formation of helical hairpins depends both on the overall length of the hydrophobic segment, on the amino acids flanking the transmembrane segment, and on the identity of the central, potentially turn-forming residues. We also show that interhelical hydrogen bonds between pairs of Asn or Asp residues can induce helical hairpin formation. A detailed topology mapping is also reported for the Escherichia coli inner membrane chloride channel YadQ, a protein for which the X-ray structure is known. Our results provide a critical test of the reporter fusion approach and offer new insights into the YadQ folding pathway. In summary, the results present in this thesis have increased our understanding of the determinants of membrane protein topology and structure. Furthermore, the information obtained can be used to improve current models for predictions of membrane protein topology.

Peptidomimetics derived from the bioactive hexapeptide angiotensin IV (Ang IV, Val1-Tyr2-Ile3-His4-Pro5-Phe6) have been designed and synthesized. These peptidomimetics are aimed at inhibiting the insulin-regulated amino peptidase (IRAP), also known as the AT4 receptor. This membrane-bound zinc-metallopeptidase is currently under investigation regarding its potential as a target for cognitive enhancers. The work presented herein was based on stepwise replacement of the amino acid residues in Ang IV by natural and unnatural amino acids, non-peptidic building blocks, and also on the introduction of conformational constraints. Initially, we focused on the introduction of secondary structure mimetics and backbone mimetics. The C-terminal tripeptide His-Pro-Phe was successfully replaced by a γ-turn mimetic scaffold, 2-(aminomethyl)phenylacetic acid (AMPA), which was coupled via an amide bond to the carboxyl terminus of Val-Tyr-Ile. Substitution of Val-Tyr-Ile, Val-Tyr, Tyr-Ile and Tyr, respectively, by 4-hydroxydiphenylmethane scaffolds comprising a 1,3,5-substituted benzene ring as a central moiety unfortunately rendered peptidomimetics that were less potent than Ang IV. The subsequent approach involved the introduction of conformational constraints into Val-Tyr-Ile-AMPA by replacing Val and Ile by amino acid residues appropriate for disulfide cyclization or ring-closing metathesis. Chemically diverse structures encompassing an N-terminal 13- or 14-membered macrocyclic tripeptide and a C-terminal non-peptidic moiety were developed. Tyr2 and AMPA were modified to acquire further knowledge about the structure-activity relationships and, in addition, to improve the metabolic stability and reduce the polarity. Several of the compounds displayed a high capacity to inhibit IRAP and exhibited Ki values in the low nanomolar range. Hence, the new compounds were more than ten times more potent than the parent peptide Ang IV. Enhanced selectivity over the closely related aminopeptidase N (AP-N) was achieved, as well as improved stability against proteolysis by metallopeptidases present in the assays. However, additional investigations are required to elucidate the bioactive conformation(s) of the relatively flexible N-terminal macrocycles. The compounds presented in this thesis have provided important information on structure-activity relationships regarding the interaction of Ang IV-related pseudopeptides and peptidomimetics with IRAP. The best compounds in the series constitute important starting points for further discovery of Ang IV peptidomimetics suitable as tools in the investigation of IRAP and other potential targets for Ang IV. The literature presents strong support for the hypothesis that drug-like IRAP inhibitors would serve as a new type of future cognitive enhancers with potential use in the treatment of cognitive disorders, e.g. Alzheimer’s disease.