<p>The small GTPases <italic>HRAS, <italic>NRAS and <italic>KRAS are mutated in approximately one-third of all human cancers, rendering the proteins constitutively active and oncogenic. Lung cancer is the leading cause of cancer deaths worldwide, and more than 20% of human lung cancers harbor mutations in <italic>RAS, with 98% of those occurring in the <italic>KRAS isoform. While there have been many advances in the understanding of <italic>KRAS&ndash;driven lung tumorigenesis, it remains a therapeutic challenge. To further this understanding and assess novel approaches for treatment, I have investigated two aspects of <italic>Kras&ndash;driven tumorigenesis in the lung:</p><p>(<italic>I) Despite nearly identical protein sequences, the three <italic>RAS proto-oncogenes exhibit divergent codon usage. Of the three isoforms, <italic>KRAS contains the most rare codons resulting in lower levels of KRAS protein expression relative to <italic>HRAS and <italic>NRAS. To determine the consequences of rare codon bias during <italic>de <italic>novo tumorigenesis, we created a knock-in <italic>Kras<super>ex3op mouse in which synonymous mutations in exon 3 converted codons from rare to common. These mice had reduced tumor burden and fewer oncogenic mutations in the <italic>Kras<super>ex3op allele following carcinogen exposure. The reduction in tumorigenesis appeared to be a product of rare codons affecting both the oncogenic and non&ndash;oncogenic alleles. Converting rare codons to common codons yielded a more potent oncogenic allele that promoted growth arrest and enhanced tumor suppression by the non-oncogenic allele. Thus, rare codons play an integral role in <italic>Kras tumorigenesis.</p><p>(<italic>II) Lung cancer patients exhale higher levels of NO and <italic>iNOS<super>-/- mice are resistant to chemically induced lung tumorigenesis. I hypothesize that NO promotes <italic>Kras&ndash;driven lung adenocarcinoma, and NOS inhibition may decrease <italic>Kras&ndash;driven lung tumorigenesis. To test this hypothesis, I assessed efficacy of the NOS inhibitor L&ndash;NAME in a genetically engineered mouse model of <italic>Kras-driven lung adenocarcinoma. Adenoviral Cre recombinase was delivered into the lungs intranasally, resulting in expression of oncogenic <italic>Kras<super>G12D and dominant-negative <italic>Trp53<super>R172H in lung epithelial cells. L&ndash;NAME treatment was provided in the water and continued until survival endpoints. In this model, L&ndash;NAME treatment decreased tumor growth and prolonged survival. These data establish a potential clinical role for NOS inhibition in lung cancer treatment.</p> / Dissertation

Most academic disciplines have a gender bias that exists in the recognition of research publications: women’s publications are cited at lower rates than men’s publications. In this paper, we examined whether a similar gender bias existed for publications by dendrochronologists. Tree-ring research is a fairly small field where males outnumber females, and therefore the sample size was limited to 20 female dendrochronologists and 20 male dendrochronologists. It was determined that native language (English or non-native English speaker), current employment (government or academic), and gender of the first-author do not significantly influence a paper’s probability of being cited. However, years since dissertation completion was a good predictor of a paper’s citation rate. We suggest that the high productivity of female dendrochronologists and a pattern of co-authoring with male colleagues bring the work of females to the attention of their male colleagues and thus eliminate the gender bias in citation of women’s work common to other disciplines.

<p>An abundance of research in the social sciences has demonstrated a persistent bias against nonnative English speakers (Giles & Billings, 2004; Gluszek & Dovidio, 2010). Yet, organizational scholars have only begun to investigate the underlying mechanisms that drive the bias against nonnative speakers and subsequently design interventions to mitigate these biases. In this dissertation, I offer an integrative model to organize past explanations for accent-based bias into a coherent framework, and posit that nonnative accents elicit social perceptions that have implications at the personal, relational, and group level. I also seek to complement the existing emphasis on main effects of accents, which focuses on the general tendency to discriminate against those with accents, by examining moderators that shed light on the conditions under which accent-based bias is most likely to occur. Specifically, I explore the idea that people’s beliefs about the controllability of accents can moderate their evaluations toward nonnative speakers, such that those who believe that accents can be controlled are more likely to demonstrate a bias against nonnative speakers. I empirically test my theoretical model in three studies in the context of entrepreneurial funding decisions. Results generally supported the proposed model. By examining the micro foundations of accent-based bias, the ideas explored in this dissertation set the stage for future research in an increasingly multilingual world.</p> / Dissertation

Preclinical research using animals often precedes and informs clinical trials; however, most attempts to translate findings from “bench-to-bedside” fail. There is growing concern that an important cause of failed translations is that much of preclinical research is not reproducible, with poor experimental methodology believed to be a major contributor. Four studies were conducted: (1) an assessment of reported study designs of preclinical experiments published in leading cardiovascular journals; (2) an examination of sex bias in preclinical cardiovascular research; (3) a comparison of experimental practices between male and female preclinical cardiovascular researchers; and (4) an analysis of the influence of journal initiatives on preclinical research quality. These studies suggest that (1) methodological shortcomings are prevalent and persistent in preclinical cardiovascular research; (2) women’s involvement in preclinical cardiovascular research is positively associated with considering sex as a biological variable; and (3) journals can exert considerable influence on the quality of published data.

In an effort to make documented and fair decisions on work‐related opportunities and career progressions, job performance has emerged as a pivotal Human Resource tool due to its link to quasi‐every career‐related decision in the organization. Indeed, differences in performance evaluations can influence a number of career advancement variables. Performance measurement differences can impart both pay and promotions (Roth, Purvis & Bobko, 2012), lead to lower levels of job satisfaction (Colquitt, Conlon, Wesson, Porter & Ng, 2001; King et al. 2010) and lower levels of perceived organizational justice (Colquitt et al. 2001; Motowidlo, 2003), which in turn break efforts to create a fair and balanced workplace. If within an organization allocation of bonuses, wages, responsibilities and promotions are partially or entirely determined by job performance evaluations, then job performance is likely to mediate the relationship between gender and career advancement, particularly for women in male dominated organizations.The centrality of job performance calls for scrutiny; as job performance has a potential to constitute a powerful mechanism in terms of its potential to marginalize and/or exclude women. Despite legislative and organizational efforts to alleviate gender inequality and shatter the glass ceiling, women are still disadvantaged in the labor market.In fact, women who have managed to enter male‐dominated organizations and occupations are still under‐represented and face numerous hurdles. Empirical evidence is plentiful on gender discrimination even when women are successful at their job (e.g. Parks‐Stamm et al. 2008, Heilman & Okimoto, 2007) and have secured positions in upper management (Heilman et al. 2004). However, little evidence is available on women’s experience of discrimination within the performance appraisal context and how existing job performance prototypes are affecting the perception of their work, including bias by other women.This dissertation is interested in filling that research gap and contributing to the body of knowledge on women’s experience in male‐dominated organizations. The potential of job performance having a marginalizing effect on women, in the sense of limiting women’s career opportunities, is examined with regard to women’s work experience and how women themselves can perpetuate their marginal position in the workplace. The intent is to reveal the mechanisms upholding and reinforcing the glass ceiling and gender inequity in the workplace.Based on the literature review and identified knowledge gaps two lines of enquiry have emerged and will be investigated in this dissertation:-  How job performance functions as a mean of (re)producing gender inequality in male dominated organizations and occupations by its gendered character-  How women in male‐dominated organizations can be participants in maintaining inequality by relying on gender stereotype expectations to evaluate their job performance and that of other female colleagues.In order to grasp and address the complexity of the potentially gendered character of job performance the dissertation takes on a multidisciplinary approach.The dissertation is divided into two main parts. The first part comprising chapters 1 to 3 reviews the current literature on women’s experience in male‐dominated organizations. These chapters provide the theoretical framework for the research contributions, presented as essays in part two of the dissertation. Chapter 1 presents a literature review depicting the situation of women in the European labor market and the persistent horizontal and vertical segregation. The specificities of token women (less than 15% representation; Kanter, 1977a) in male dominated organizations and the impact of tokenism on women’s job performance are discussed.Chapter 2 details gender stereotypes and explicates their direct impact on the assessment of women’s work and job performance. This chapter argues the case for genders stereotypes as the leading social psychological mechanisms impeding the perception of women’s work as being equivalent to that of men. Perceived incongruity between gender stereotype attributes gives rise to expectations on women’s performance, generally, that they will perform poorly in male‐typed occupations (Heilman, 1983, 1995, 2001). This can therefore penalize women in their career paths and become significant barriers to their social and economic opportunities. In fact, stereotype beliefs about attitudes, characteristics and roles of women and men influence the evaluation process and constitute the backbone of the analysis of this dissertation.Chapter 3 explores the existing literature on women’s participation in biased evaluation of themselves and other women. Women’s roles as evaluators as well as their self‐ perception as performers is outlined in relation to the way they can maintain and reinforce gendered performance norms. Building on system justification theory, this chapter highlights the complexity of gender inequality in organizations and seeks to acknowledge internalized and often unconscious gender biases at work.Subsequent to the literature review of part one, part two (chapters 4 to 8) presents the research contributions of the dissertation, namely the mechanisms, which maintain and reinforce gender inequality in male dominated organizations. Chapters 4 to 5 outline the investigations into the research enquiries posited. Each chapter of part two constitutes an independent essay highlighting through various analytical lenses the complexity of marginalization through job performance. In line with a multidisciplinary approach, the essays presented in chapters 4 and 5 are of a theoretical nature whereas chapters 6, 7 and 8 comprise empirical studies.Chapter 4 sets out to investigate the potential gendered character of job performance and the legitimating effects of meritocracy as the ideological framework, which informs each stage of job performance; from setting the criteria to using performance evaluation information to distribute organizational goods. The major contribution of this chapter is to bring forth the way in which performance and merit intertwine to perpetuate mechanisms of inequality and invalidate contestation at each stage of job performance. Gender‐blind and merit‐based HR (Human Resources) processes such as performance are rarely put to question and revealed as inherently biased themselves. The findings call for a critique of meritocracy on a systemic level as well as the implementation of an outcome‐oriented approach to job performance evaluations and reward allocation.Chapter 5 applies and extends social identity theory to explain the underrepresentation and marginalized position of women in European academia. The chapter illustrates the extent to which the Leading Academic Performer (LAP) is based on male characteristics and therefore contributes to the marginalization of female academics. This chapter endeavors to further the theoretical underpinnings by proposing an applicable taxonomy of social identity theory performance (Klein, Spears & Reicher, 2007). The chapter illustrates how social identities can be strategically performed to enhance the perception of female academics as leading academic performers.Chapter 6 and chapter 7 are contributions based on an empirical study using a social psychological experiment methodology, involving 163 Master students (Business major) from a Belgian university. The objective of the study was two fold. Chapter 6 investigated the standards and criteria used to evaluate male versus female job performance. Chapter 7 looked at how female and male evaluators differed in their evaluations and how they perceived the value of their evaluative work when evaluating a woman versus a man.More specifically, in chapter 6 participants were asked to evaluate the job performance of a randomly assigned female or male IT manager and to decide on whether they should retain their position. Major findings of this study show that not only did evaluators (regardless of their gender) automatically assign female IT managers higher interpersonal skills, thereupon confirming the use of stereotype beliefs, but they also used double standards to decide the retention of the female employee. When it came to female employees, their retention decision was directly linked to their performance evaluation. This was not the case for male employees. Other standards outside of job performance were used to retain the male employee. In addition, results reveal that female evaluators systematically gave lower ratings than their male counterparts. The results in this study show that both men and women evaluators not only use similar norms to evaluate but are also harsher when evaluating female performance.Chapter 7 explores the evaluators’ perceived entitlement in regards to the task of evaluating the job performance of a man versus that of a woman. Contrary to previous research on the depressed entitlement effect (i.e. phenomenon where by women underpay themselves relative to men but are just as satisfied with their employment situation as men) in this study, all evaluators, men and women expressed an elevated sense of entitlement when appraising the performance of a female worker. Evaluators assessing a woman’s job performance felt that they deserved 19,64% more (monetary reward) compared to those evaluating a man’s job performance. Interestingly, evaluators who gave high interpersonal skill ratings exhibited a depressed entitlement effect. It would seem that focusing on female associated skills gives evaluators the perception that this work is less worthy. Both chapters 6 and 7 highlight the gendered character of evaluating performance and point to the difficulty evaluators might have in evaluating female job performance. Equally, the findings support the claim that women themselves participate in system‐maintaining mechanisms that stress communality injunctions on female workers.Chapter 8 presents a study, using qualitative methodology, conducted in a Belgian subsidiary of a multinational IT corporation. The study is based on semi‐structured interviews with 32 managers and employees across organizational departments. The aim is to highlight job performance expectations and to render visible criteria thought to be best predictive of good employee performance. To bring forth existing yet hidden gendered elements in the discourse on job performance, gender subtext was chosen as the analytical tool. Gender subtext analysis allows for an understanding of how seemingly gender‐blind language is in fact embedded with gendered meanings. Results of this fieldwork support the analysis in previous chapters: Job performance expectations perpetuates a prototype of the exemplary performer as masculine, thereby forcing the few token women to position themselves in masculine terms or risk increased marginalization from deviating the dominant management style. Finally, a section of the chapter is dedicated to analyze how women do work in their predominately male dominated organization and how this could lead to perpetuating masculine norms of performance.A general discussion concludes the dissertation and analyses the findings (i.e. the four mechanisms that have been identified, which reinforce the glass ceiling and maintain gender inequality through job performance). Overall, the investigations into the research enquiries have revealed the gendered and thus biased character of job performance. If within an organization, androcentric job performance criteria and evaluations are partially or entirely used to determine the allocation of bonuses, wages, responsibilities and promotions, then job performance constitutes a powerful gendered mechanism legitimating and maintaining gender inequalities. Each essay in part two has examined and brought to light the (re)production of gender inequality in male dominated organizations and occupations through job performance. By using a multidisciplinary approach, the theoretical analyses presented, is consolidated the laboratory experiments and fieldwork. Equally, the role of women in maintaining gendered performance norms by relying on gender stereotypes, albeit unconsciously, is uncovered. The participation of women themselves in maintaining and reproducing the status quo limits the possibilities for contestation and hinders attempts at transformation towards more gender equity. To conclude, the chapter proposes practical recommendations alleviate contributing mechanisms behind the glass ceiling. / Doctorat en Sciences économiques et de gestion / info:eu-repo/semantics/nonPublished

Palliativa vårdens ändamål är att öka livskvalitén och stödja både patienten och dennes familj genom ett obotligt sjukdomsförlopp. Palliativa vårdens målgrupp är inte enbart de med en cancerdiagnos utan alla med en obotlig sjukdom. Förförståelsen kring begreppet palliativ är stor och kan innebära en risk för sämre vård för patienten. Studiens syfte har varit att beskriva förförståelsen i palliativ vård utifrån sjuksköterskans perspektiv. Metoden i studien är en litteraturöversikt som utgår från Fribergs litteraturöversiktsmetod (2017, ss. 141–148). En kvantitativ och nio kvalitativa artiklar analyserades. Resultatet av litteraturöversikten lyfter fram tre huvudteman följt av tre underteman. Huvudtemat kunskapsproblem tar upp riskerna när sjuksköterskans påverkas av sin förförståelse i kommunikation, utbildning och strategier. Huvudtemat vårdkonsekvenser belyser hur fördomar och förförståelse utifrån definitioner, möten och hinder i vården kan skapas. Huvudtemat lidande tar upp det lidande som förförståelsen kan leda till utifrån sjuksköterskans självbild, sjuksköterskans/patientens delaktighet och skapandet av patientrelationer. Förförståelse leder till att patientrelationen påverkas och innebär ett ökat lidande för patienten. Sjuksköterskans förförståelse kan skapa vård som inte tillför något till patientens egentliga behov. Den palliativa vården innebär utmaningar för sjuksköterskan. I den palliativa vården har författarna identifierat brister i förförståelsen hos sjuksköterskor i framför allt hur kommunikation och information framförs till patienten. En kontinuerlig vård med självreflektioner utifrån evidensbaserade utbildningar är en grundförutsättning för en mer fördomsfri palliativ vård.

Since bias threatens the validity of a study, it should be avoided where possible. Across all phases of a research project, bias could be introduced, and in most situations the researcher has reasonable control over processes that may be the source of bias. However, within a quantitative research context in social sciences, where the opinions, attitudes and intentions of people are often sought, response styles patterns due to cultural background, for example, are not within the control of the researcher. Typical response style patterns include acquiescence bias, a tendency to be agreeable to statements, which could be more prevalent in certain cultural groups than other. Another response style pattern is extremity ratings, where respondents tend to avoid the middle categories and mark the scale extremes. When practitioners sample respondents from different cultural groups, it is difficult, and depending on the research design, sometimes impossible to know whether significant differences are an artefact of substantive differences, or of differences in response styles. Adjusting scores for bias has a significant effect on the interpretation of research findings. To correct for bias, the method most commonly used to adjust scores within each cultural group is standardisation. In this research, SIMNORM, a target distribution estimation approach was used for the simultaneous estimation of a class of non-linear transformation functions that transform the composite scores within each cultural group to a standard normal distribution. SIMNORM was found to perform better than standardisation to obtain equivalence across cultural groups when composite scores are used. In addition, SIMITNORM, an item normalisation approach was developed, which is a simultaneous non-linear transformation of item scores to a standard normal target distribution. The results of seven nested SIMITNORM models were compared to raw item scores and standardised scores, using a multi-group confirmatory factor analysis approach, a method that is suitable to test for construct equivalence, metric equivalence and scalar equivalence. SIMITNORM had significant advantages over standardisation as an approach to obtain equivalence over items in a set of data where bias is present.

The study explores language bias in the NEO-PI-R both quantitatively and qualitatively. A sample of 28 postgraduate psychology student volunteers completed a questionnaire containing the NEO-PI-R and two open-ended questions about the instrument. These responses were then analysed across English first language and second language speakers to explore issues of bias. Reliability of the NEO-PI-R appeared to be robust at a domain level. The reliability of the facets, while appropriate for the most part, still yielded low alpha coefficients for the Excitement-seeking, Actions, Values and Straightforwardness facets. ANOVA’s at the domain and facet scale levels indicated no significant differences across home language. However ANOVA’s at the item level yielded 33 in total that were problematic, comprising of 12 items that were significant at the 5% level of significance and 21 items at the 10% level of significance. These items were primarily from the N and E domains. Thematic analysis of the open-ended questions of the questionnaire indicated 26 items were difficult to understand and/or inappropriate for the South African context. These items were primarily from the E and A domains. From the original sample of 28 volunteers, two focus groups were formed, comprising of volunteers from the initial sample. The focus groups explored several qualitative issues, including concepts of personality, language and culture and the applicability of the NEO-PI-R for South African user groups. It was perceived that there is a presence of American socio-cultural references within the use of language, grammar and socio-cultural context in the instrument. Thus the results show evidence of language bias in the NEO-PI-R, and subsequently identify particular aspects and items of the instrument that are especially problematic for a South African user group. The present study suggests that the NEO-PI-R would need to be revised to suit the South African context by changing the problematic items.

Cette thèse s'inscrit dans la thématique des TA-MRAM, nouvelles mémoires non volatiles qui utilisent des impulsions de courant pour chauffer et ainsi permettre le renversement de l'aimantation d'une couche ferromagnétique. Un premier but de ce travail a été de comprendre les mécanismes d'écriture (chauffage) des cellules TA-MRAM. Mesures électriques et simulations thermiques sont alors comparées. De manière générale les TA-MRAM associent deux couches ferromagnétiques dont les directions relatives des aimantations sont stabilisées par des couches antiferromagnétiques. Une action développement matériaux a été menée dans la conception de jonctions tunnel magnétiques utilisant l'alliage FeMn dans la couche de stockage. Nous avons alors cherché à optimiser les couches ferromagnétiques et antiferromagnétique de la couche de stockage afin de minimiser le champ magnétique nécessaire au renversement de l'aimantation de ces couches et donc de diminuer la consommation d'énergie. Enfin ce manuscrit présente une partie gravure par faisceau d'ion (IBE) de points mémoires magnétiques qui donnent les clefs de fabrication des mémoires MRAM. / This thesis addresses a current topic of TA-MRAM, new non volatile memories using pulses to heat and thus allows the reversal of the magnetization of a ferromagnetic layer. A first goal was to learn the writing mechanism (heating) of TA-MRAM cells. Therefore, we compared electrical measurements and thermal simulations. Generally speaking, TA-MRAM combines two ferromagnetic layers where the relative direction of the magnetization is pinned by antiferromagnetic layers. Moreover, we developed new magnetic tunnel junctions using FeMn in the storage layer. We thus optimized the ferromagnetic and antiferromagnetic layers of the storage layer in order to minimize the magnetic field needed to reverse the magnetization of these layers and thus to decrease the power consumption. To finish, the etching of magnetic memory dots is explored, giving the pattern key of magnetic devices.

No description available.