Les venins animaux sont largement distribués à travers le monde, en particulier dans les régions tropicales et subtropicales. Les venins d'animaux sont utilisés comme un mécanisme de défense, d'immobilisation, et de digestion des proies dans la nature. Les venins sont des mélanges complexes des protéines enzymatiques et non enzymatiques avec de spécifiques fonctions physiopathologiques et les peptides des toxines isolés à partir de venins ciblent principalement les canaux ioniques, les récepteurs de la membrane et les composants du système hémostatique avec une affinité élevée. Les venins de serpents ont également été utilisés comme outils médicaux pour des milliers d'années en particulier dans la médecine traditionnelle chinoise. Par conséquent, les venins peuvent être considérés comme des bibliothèques de mini-drogues dans lesquelles chaque médicament est actif sur un plan pharmacologique. Toutefois, moins de 0,01% de ces toxines ont été identifiés et caractérisés. La nouvelle identification de la toxine se déroule généralement à partir d'un test de dépistage, soit in vivo ou sur une cible pharmacologique à intérêt industriel. Dans ce travail, nous criblons pour des composés bioactifs à partir du venin du serpent égyptien noir Walterinnesia aegyptia, qui est capable d'activer la motilité des spermatozoïdes in vitro chez des souris mâles OF1. / Venomous animals are widely distributed throughout the world especially in tropical and subtropical regions. Animal venoms are used as a defense mechanism or to immobilize and digest prey in nature. In fact, venoms are complex mixtures of enzymatic and non- enzymatic proteins components with specific pathophysiological functions. Toxin peptides isolated from animal venoms target mainly the ion channels, membrane receptors and components of the hemostatic system with high affinity. Snake venoms have also been used as medical tools for thousands of years especially in Chinese traditional medicine. Consequently, venoms can be considered as mini-drug libraries in which each drug is pharmacologically active. However, less than 0.01% of these toxins have been identified and characterized. New toxin identification generally proceeds from a screening test, either in vivo or on a pharmacological target of interest to the industry. Herein, we screened for bioactive compounds from the venom of the Egyptian black snake Walterinnesia aegyptia capable to activate sperm motility in vitro from male mice OF1.

<p>Criminological studies have shown that economical and/or occupational crimes are committed within all examined trades and occupations. This is also a fact in the gendered occupational context the Norwegian and Swedish long-distance trucking trade constitutes. This dissertation sets out to determine, by qualitative in-depth interviews with 24 interviewees and field observations, what certain gaining occupational and economical crimes mean to trade actors and how to interpret the meaning criminologically. A hermeneutical orientation constitutes the methodological and epistemological basis of the interpretation.</p><p>Analysis of the material shows two central consistent patterns in the interpretations made by interviewees and other trade actors:</p><p>1) T<u>he actors´ explanations of why law violations are committed</u>. These are influenced by the actors´ view of how wide the specific violations are spread and influence the violation’s acceptability.</p><p>2) <u>The actors´ normative evaluation of the law violations</u>. The actors construct normative distinctions between normal, acceptable and unacceptable actions. The distinction is influenced by how the law violations are explained and how widespread they are considered to be.</p><p>The first pattern; actors interpretation of why law violations are committed, corresponds with explanations in established criminological theories. The actors’ explanations are discussed as techniques of neutralisation. However, explanations of cause of actions are established also in the discourse of trade-actors who do not violate laws, and a deeper interpretation is called for. A discussion about law violations, based on interviewees discourse, as caused by criminogenic structures are developed. The actors identify the structures as criminogenic and this discourse of coersive structures implies conservation of law violations as part of normality. An interpretation of why several but not all individuals violate laws even if the law violations considers to be normal and acceptable, is developed in terms of differential association.</p><p>However, solely use of established theoretical perspectives is not a sufficient interpretation of the law violations; the perspective of interpretation indicated by the second pattern will then be lost. Why is law violations considered both normal and deviant? This dissertation applies a gender-theoretical perspective and argues that actors constitute masculinity through acceptable law violations and that masculinity and normality are correlated. A cultural discourse of borders between normality and deviance is conserved and processed, and the actors discourses of law violations as without victims and as a necessity to continue as truckers, are central in the normalization of normative borders.</p>

Criminological studies have shown that economical and/or occupational crimes are committed within all examined trades and occupations. This is also a fact in the gendered occupational context the Norwegian and Swedish long-distance trucking trade constitutes. This dissertation sets out to determine, by qualitative in-depth interviews with 24 interviewees and field observations, what certain gaining occupational and economical crimes mean to trade actors and how to interpret the meaning criminologically. A hermeneutical orientation constitutes the methodological and epistemological basis of the interpretation. Analysis of the material shows two central consistent patterns in the interpretations made by interviewees and other trade actors: 1) T<u>he actors´ explanations of why law violations are committed</u>. These are influenced by the actors´ view of how wide the specific violations are spread and influence the violation’s acceptability. 2) <u>The actors´ normative evaluation of the law violations</u>. The actors construct normative distinctions between normal, acceptable and unacceptable actions. The distinction is influenced by how the law violations are explained and how widespread they are considered to be. The first pattern; actors interpretation of why law violations are committed, corresponds with explanations in established criminological theories. The actors’ explanations are discussed as techniques of neutralisation. However, explanations of cause of actions are established also in the discourse of trade-actors who do not violate laws, and a deeper interpretation is called for. A discussion about law violations, based on interviewees discourse, as caused by criminogenic structures are developed. The actors identify the structures as criminogenic and this discourse of coersive structures implies conservation of law violations as part of normality. An interpretation of why several but not all individuals violate laws even if the law violations considers to be normal and acceptable, is developed in terms of differential association. However, solely use of established theoretical perspectives is not a sufficient interpretation of the law violations; the perspective of interpretation indicated by the second pattern will then be lost. Why is law violations considered both normal and deviant? This dissertation applies a gender-theoretical perspective and argues that actors constitute masculinity through acceptable law violations and that masculinity and normality are correlated. A cultural discourse of borders between normality and deviance is conserved and processed, and the actors discourses of law violations as without victims and as a necessity to continue as truckers, are central in the normalization of normative borders.

This dissertation investigates the role of grammatical versus methodological influences in the production and perception of final devoicing in experimentally-elicited speech from Russian. It addresses the question of how the partial preservation of the phonological voicing contrast in word-final obstruents is affected by (i) task-independent factors that reflect phonological and lexical properties of stimuli words (underlying voicing, word length, lexical competition) and (ii) task-dependent biases that arise due to the nature of the experimental task performed by the speaker (availability of orthographic inputs, presence of minimal pairs among the stimuli). Results of a series of acoustic production and perceptual identification tasks reveal that task-dependent factors account for the presence of robust and perceptually salient differences in the parameter of phonetic voicing. Several types of stimuli items also show limited but statistically significant differences in closure/frication duration and release duration that are independent of the presence of orthography or inclusion of full minimal pairs among test items. Taken together, these findings indicate that non-grammatical factors can play a prominent biasing role in both production and perception of the voicing contrast in experimentally-elicited speech, such that certain voicing-dependent cues are maintained only in the presence of task-dependent pressures. However, not all incompletely neutralized differences between phonologically voiced versus voiceless final obstruents can be attributed to the effects of orthography or inclusion of minimal pairs among the stimuli. In the theoretical domain, these results are argued to favour a less restrictive definition of neutralization and a model of phonology that views devoicing as a loss of the primary acoustic cue to the underlying voicing contrast rather than complete identity of the [voiced] feature.

Unauthorized computer access by employees is the most common hacking behavior in every company. Hence, it is necessary to first understand why an employee engages to commit it and then find effective methods of prevention to reduce the crime rate. Many studies on computer hacking has discussed the reasons for the behavior, for example: neutralization theory, differential association theory and containment theory. However, those theories and perspectives were adopted independently in past research. In this study, we combine those perspectives and create an integrated model to explain the employee¡¦s intention to commit unauthorized computer access. Data collected from 351employees in Taiwan confirmed our hypotheses and were tested against the research model. The results support the theoretical model in explaining how neutralization theory and containment theory may affect an employee¡¦s intention to commit unauthorized computer access. Finally, we found that neutralization is the most important factor to take into account when organizations develop and implement security policies or education which can decrease employees¡¦ intentions to commit unauthorized computer access.

Thesis (Ph. D.)--Institute of Paper Chemistry, 1966. / Includes bibliographical references (p. 114-117).

Recent studies have shown that even highly-proficient Spanish-English bilinguals, who acquired their second language (L2) in childhood and have little or no foreign accent in English, may require more acoustic information than monolinguals in order to identify English vowels and may have more difficulty than monolinguals in understanding speech in noise or reverberation (Mayo, Florentine, and Buus, 1997; Febo, 2003). One explanation that may account for this difference is that bilingual listeners use acoustic cues for vowel identification differently from monolinguals (Flege, 1995).In this study, we investigated this hypothesis by comparing bilingual listeners use of acoustic cues to vowel identification to that of monolinguals for six American English vowels presented under listening conditions created to manipulate the acoustic cues of vowel formant dynamics and duration. Three listener groups were tested: monolinguals, highly proficient bilinguals, and less proficient bilinguals. Stimulus creation included recording of six target vowels (/i, I, eI, E, ae, A/) in /bVd/ context, spoken in a carrier phrase by four American monolinguals (two females, two males). Six listening conditions were created: 1) whole word, 2) isolated vowel, 3) resynthesized with no change, 4) resynthesized with neutralized duration, 5) resynthesized with flattened formants, and 6) resynthesized with flattened formats and neutralized duration. The resynthesized stimuli were created using high-fidelity synthesis procedures (Straight; Kawahara, Masuda-Katsuse, and Cheveigne 1998) and digital manipulation. A six-alternative forced choice listening task was used. The main experiment was composed of 240 isolated vowel trials and 48 whole word trials.

Macrophages are target cells for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection that serve as viral reservoirs in brain, lung, gut, and other tissues, and play important roles in disease pathogenesis, particularly HIV/SIV-associated neurological disease. Macrophages express low levels of the HIV/SIV receptor CD4, but mechanisms by which macrophage-tropic viruses use low CD4 to mediate spreading infections are poorly understood. One mechanism involves enhanced envelope glycoprotein (Env) interaction with CD4 or CCR5, but this phenotype is frequently associated with increased neutralization sensitivity to antibodies targeting CD4/CCR5 binding sites. Moreover, this mechanism does not explain how these neutralization-sensitive viruses evade immune responses while establishing spreading infections. In this dissertation, we sought to identify SIV Env determinants for macrophage tropism and characterize mechanisms by which they enhance virus replication in macrophages. To identify viral variants capable of inducing macrophage-associated pathogenesis, we cloned Env sequences from SIV-infected macaques at early and late stage infection, and identified an early variant in blood that shares >98% sequence identity with the consensus sequence of late variants in brain from macaques with neurological disease. SIV clones encoding this Env variant mediated high levels of fusion, replicated efficiently in rhesus PBMC and macrophages, and induced multinucleated giant cell formation upon infection of macrophage cultures. We identified an N-linked glycosylation site, N173 in the V2 region, as a determinant of macrophage tropism. Loss of N173 enhanced SIVmac239 macrophage tropism, while restoration of N173 in SIVmac251 reduced macrophage tropism, but enhanced neutralization resistance to CD4/CCR5 binding site antibodies. SIVmac239 N173Q, which lacks the N173 glycosylation site, mediated CD4-independent fusion and cell-to-cell transmission with CCR5-expressing cells, but could not infect CD4-negative cells in single-round infections. Thus, CD4-independent phenotypes were detected only in the context of cell-cell contact. The N173Q mutation had no effect on SIVmac239 gp120 binding to CD4 in BIACORE and co-immunoprecipitation assays. These findings suggest that loss of the N173 glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell transmission through CCR5-mediated fusion. This mechanism may facilitate escape of macrophage-tropic viruses from neutralizing antibodies, while promoting spreading infections by these viruses in vivo.

The influenza virus hemagglutinin (HA) surface protein is a primary antigenic target for neutralization of viral infection. HA also mediates membrane fusion between the virus and a cell, which is the first critical step during infection. Traditional techniques to study infection neutralization by antibodies or the membrane fusion process rely on ensemble measurements, confounding the precise mechanism of infection neutralization and obscuring transient conformational intermediates. This dissertation describes advances made in a fluorescence microscopy-based single-particle fusion assay to overcome the limitations of ensemble measurements in these types of studies. Virus particles are labeled to visualize lipid mixing between a virus and a target membrane formed upon a glass or polymer support. Optionally, the viral lumen can be labeled to visualize the subsequent release of viral contents.

A major goal of this research was to evaluate a variety of cell lines for theirpermissiveness to equine arteritis virus (EAV) infection and then identify the mechanismthat restricts EAV infection in certain cell lines. The cell lines BHK-21, RK-13, andC2C12 were found to support productive infection with EAV strain VBS53, whereasHela, Hep-2, and L-M cell lines exhibited limited susceptibility to infection with thisvirus. In the course of the study, it was found that the Hela cell line became moresusceptible to infection with EAV strain VBS53 after extended serial passage. Therespective cell lines were referred to as Hela High (passage 170-221) and Hela Low(passage 95-115) lines. While the Hela High cell line was more susceptible than the HelaLow cell line, it was still considerably less susceptible than the BHK-21 cell line to EAVinfection. Subsequent studies demonstrated that infection with EAV strain VBS53 wasrestricted at the entry step in Hela, Hep-2, and L-M cell lines.The second major goal of this research was to establish an in vitro model ofpersistent EAV infection using cell culture and then use the persistently infected culturesas a tool to study virus-host cell interactions, and to investigate virus and host cellevolution. Persistent infection was successfully established in the Hela High cell line withthe VBS53 strain of EAV. Properties of the persistently infected Hela High cell line werecharacterized. Virus evolution with respect to virus growth characteristics, ability of thevirus to initiate secondary persistent infection, and genetic changes during persistentEAV infection in Hela cells was investigated. Neutralization phenotypic changes of viruses were observed during the course of persistent EAV infection in Hela cells. Reverse genetics studies identified that amino acid 98 of the GP5 protein is a new neutralization determinant of EAV. Using an in vitro assay, it was found that EAV probably became progressively less virulent during the course of persistent infection in Hela cells. The potential changes in pathogenicity of EAV during persistent infection of Hela cells need to be verified by inoculation of horses.