<p>Every living cell faces a multitude of DNA threats in its lifetime because damage to DNA is intrinsic to life itself. A double-strand break (DSB) is the most cytotoxic type of DNA damage and is a potent inducer of chromosomal aberrations. Defects in DSB repair are a major driver of tumorigenesis and are associated with numerous developmental, neurological and immunological disorders. To counteract the deleterious effects of DSBs, organisms have evolved a homologous repair (HR) mechanism that is highly precise. The key to its error-free nature lies in its use of a homologous template in restoring the DSB and its preferential occurrence during late S and G2 phase of the cell cycle when identical sister chromatids are available as templates for repair. However, HR can also engage homologous chromosomes and ectopic substrates that share homology, resulting in mitotic loss-of-heterozygosity (LOH) and unwanted chromosomal aberrations. In this case, understanding of the underlying mechanisms and molecular factors that influence accurate sequence transfer and exchange between two homologous substrates becomes crucial. </p><p>The focus of this dissertation is examination of the genetic factors and molecular processes occurring at early intermediate steps (DNA end resection and DNA synthesis) of mitotic recombination in Saccharomyces cerevisiae. To model DSB repair, we established a unique plasmid-based assay with a small 8-base pair (bp) gap in the middle of an 800-bp plasmid substrate. To delineate the molecular structures of strand exchange intermediates during HR, we used a 2% diverged plasmid substrate relative to a chromosomal repair template to generate mismatch-containing heteroduplex DNA (hetDNA) intermediates. The assay was performed in a mismatch repair (MMR)-defective background allowing hetDNA to persist and to segregate into daughter cells at the next round of replication. Unexpectedly, even when MMR was inactivated, sequence analysis of the recombinants revealed patches of gene conversion and restoration reflecting mismatch correction within hetDNA tracts. We showed that, in this system, MMR and nucleotide excision repair (NER) correct mismatches via two different mechanisms. While mispairing of nucleotides triggers MMR, NER is recruited by the subtle 6-methyladenine mark on the plasmid substrate, leading to coincident correction of mismatches. The methylation marks on the plasmid were acquired from the bacterial host’s native restriction-modification system during plasmid propagation. </p><p>Formation of hetDNA occurs when a plasmid substrate engages the chromosomal template for repair, forming a D-loop intermediate. D-loop extension requires DNA synthesis by DNA polymerase/s. Translesion synthesis (TLS) polymerases have been implicated in HR in both chicken DT40 cells and fruit fly, but not in yeast. This class of polymerases is known for its low fidelity due to a lack of exonuclease domain and is commonly used for lesion bypass and in extending ends with mismatches. We reported for the first time a requirement of Polζ-Rev1 and Polη (TLS polymerases in S. cerevisiae) for completing gap repair. Moreover, gap-repair efficiency suggested that these two polymerases function independently. We concluded that TLS polymerases are involved in either extending the invading 3’ end and/or in the gap-filling process that completes recombination. </p><p>DNA resection of a DSB serves as a primary step to generate a 3’ single-stranded DNA (ssDNA) for subsequent homologous template invasion, but this process has mostly been studied in the absence of a repair template or when downstream HR steps are disabled. To analyze the individual contributions of identified nucleases to DSB resection in the context of repair, we established a chromosomal assay; the substrate size was increased to 4 kilobases (kb) and 85 SNPs were present at ~50 bp intervals. In this chromosomal assay, resection and DNA synthesis influence the length of hetDNA tracts in the final recombinants, allowing these two steps to be analyzed. We specifically focused on synthesis-dependent strand annealing (SDSA) events, where hetDNA reflects DNA synthesis and extent of resection. Our main conclusions are as follows. DNA end resection on the annealing end of NCO products generated by SDSA is not as extensive as one might expect from resection measured in single-strand annealing (SSA) assays. In addition, although the two long-range resection pathways (Sgs1-Dna2 and Exo1) can support recombination in a redundant manner, hetDNA was significantly reduced upon loss of either. End processing of DSBs is predominantly 5’ to 3’, but we also observed loss of sequences (greater than 8 nt but less than 40 nt) at the 3’ termini. We have tested and ruled out the involvement of Mre11 and Polε proofreading activity. Lastly, Pol32 functions as a subunit of Polδ to promote extensive repair synthesis during SDSA. hetDNA tract lengths were significantly shorter in the absence of the Pol32 subunit of Polδ, providing direct evidence that Polδ extends the invading end during HR. Together, this work advances our understanding of how resection nucleases and DNA polymerase/s function to regulate mitotic recombination outcome and influence the molecular patterns of NCOs.</p> / Dissertation

Syftet med denna studie var att kvalitativt undersöka vilka förväntningar som finns på HR-funktionen utifrån chefernas perspektiv på en mindre kommun i Sverige. Studien baserades på elva intervjuer och analyserades genom induktiv tematisk analys. Resultatet visade att respondenterna saknade stöd från HR-funktionen samt en tydlig ansvarsfördelning i arbetsuppgifter. Respondenterna upplevde dessutom en otydlighet i vad de kunde förvänta sig av HR-funktionen. Resultatet visade även att respondenterna saknade en grundlig arbetsplatsintroduktion för att klara av sitt arbete som chef inom organisationen. Dessutom upplevde respondenterna att HR-funktionen var underbemannad då de inte upplevde att de fick det stöd de behövde. Förslag till förbättringsområden är att förtydliga vilket stöd som erbjuds från HR-funktionen, förtydliga ansvarsfördelningen mellan HR-funktion och chef samt skapa en välfungerande arbetsplatsintroduktion. Dessutom behöver HR-funktionen förtydliga riktlinjer och policys samt utforma dokument om vad HR-funktionen faktiskt erbjuder inom organisationen.

Syftet med studien var att förstå arbetsgivarsidans syn på förhållandet till fackliga organisationer och undersöka huruvida detta förhållande förklarar varför den svenska modellen fungerar så bra som den gör. För att uppnå målet med studiens ställdes följande frågeställningar: Hur ser arbetsgivarrepresentanter på förhållandet till fackförbund? Hur bidrar arbetsgivarrepresentanternas syn på fackförbunden till den svenska modellens framgång och fortlevnad? För att besvara dessa frågeställningar genomfördes sju semistrukturerade intervjuer med arbetsgivarrepresentanter i Stockholms största företag. Dessa resultat analyserades mot ett teoretiskt ramverk från tre tongivande sociologers gemensamma beröringspunkter kring kollektiva idéer. Tidigare studier inom området har dominerats av kvantitativ forskning om hur arbetsgivare sett på fackförbund i förhandlingssammanhang. Denna uppsats avser därmed att fylla en kunskapslucka av en djupare förståelse för arbetsgivarrepresentanters syn på fackförbund. Resultaten från studien visar på att arbetsgivarrepresentanterna främst har en positiv syn på förhållandet till fackförbunden, men att det även finnas aspekter där de ser problem.  Den positiva synen tenderar också att bidra till den svenska modellens framgång och fortlevnad. Det förekommer däremot resultat som visar på motsatsen. Det finns därmed ett behov av vidare studier inom området för att reda ut det tvetydliga resultaten.

The current volume of research in the field of High Performance Work Systems (HPWS) is focused on identifying the factors, which influence their effectiveness. The realisation that there is a need to move forwards from the structural aspects of HPWS towards understanding their implementation has led to two new sectors of research. The first sector is investigating the role of actors in implementation using aspects such as cross functionality, shared responsibility and interaction. Another sector is investigating the impact of contextual factors on the implementation of HPWS. This research has combined the two sectors and looks at the implementation of HPWS from the perspectives of both the actors and the environment. This research investigates how the interaction between actors affects the implementation of HPWS. Also how internal and external institutional factors affect this interaction as well as the implementation. This research is qualitatively based on an interpretivist paradigm. Case study research design was used to conduct the research. Two Saudi Arabian banks were selected as case studies. Data was collected using 54 semi-structured interviews and 61 focus group interviews. Data about implementation and the impact of institutional factors was obtained through semi-structured interviews with human resource managers, line managers and senior managers. Data about employee outcomes was obtained using focus group interviews with the employees. This research finds evidence of conflict between the intended and actual outcomes of HPWS in the Saudi banking sector due to institutional pressures. This research contributes and extends the growing body of research on HPWS implementation by including the interaction of actors and accounting for institutional pressures. The finding highlights that the combination of these two factors are contextual institutional conductors and contribute to diversity in the implementation of HPWS practices. The managerial benefit of this research is that its model can help practitioners to improve their social interaction conditions for better performance.

Osteoporosis is an age-related skeletal disease characterised by an increased incidence of fragility fractures. In this thesis I develop a new technique capable of measuring the thickness of the previously unmeasured endocortical region, and providing an improved measure of the cortical bone mineral density (cBMD) from in-vivo clinical CT scans. These features are of interest as both have been linked to fracture risk. \\ The new technique is developed within the cortical bone mapping (CBM) framework so that it provides localised architectural measurements over a bone's surface. Its performance is assessed using simulated QCT data from three simulated phantoms with differing bone architecture, and two paired datasets of ex-vivo QCT and HR-pQCT scans across the proximal femur and the lumbar spine. The simulated data allows for inaccuracies in CBM measurements caused by beam hardening effects to be considered for the first time: I show that beam hardening leads to an underestimation in cortical thickness and an overestimation in trabecular BMD and that these inaccuracies can be reduced through adjustments to the CBM optimisation process. \\ A new technique of analysing HR-pQCT scans is also developed, for the validation of the new CBM method. It was used in place of other established HR-pQCT techniques for its ability to provide localised measurements of the endocortical region. A comparison with the well known full-width half-maximum (FWHM) method shows that it is less susceptible to errors caused by beam hardening. It also measures the mean cBMD, which has a greater clinical relevance than the peak cBMD measured by the FWHM method as it includes the impact of porosity. I demonstrate that the endocortical thickness can be measured to an accuracy of \(-0.15\pm0.71\thinspace\mathrm{mm}\), and that local cBMD measurements are possible down to \(300\thinspace\mathrm{mg/cm}^3\) from QCT scans over the proximal femur. I also validate CBM methods over the vertebrae for the first time and demonstrate that the cortical thickness and endocortical thickness can be measured with accuracies of \(0.10\pm0.30\thinspace\mathrm{mm}\) and \(-0.20\pm0.53\thinspace\mathrm{mm}\). \\ Two clinical trials involving Teriparatide are used to demonstrate that the new CBM method is able to detect significant regional changes in the dense cortical and endocortical bone over the proximal femur and lumbar spine, which can be attributed to changes in intracortical remodelling and endosteal apposition. The analysis of a cross-sectional fracture discrimination trial shows that fracture incidence is associated with significant decreases in endocortical thickness over specific regions.

The study has been conducted to examine the direct and indirect relationship between the determinants of electronic recruitment and firm performance through the mediating role of human resources management capabilities based on the resource based view theory. Therefore, this study examines the relationship between the internal determinants of e-recruitment (technology quality, service quality, and security assurance) and the external determinants (e.g. empowered manager and member team, content of an implementation plan for e-recruitment, HR and IT collaboration in e-recruitment, job seeker trust in e-recruitment, organizational reputation, decentralization of selection decision, and government objectives) on e-recruitment, and the effect of e-recruitment on HR capability and firm performance. This study adopted a positivist philosophy. A deduction approach and quantitative method were also suitable for this study. A questionnaire was delivered to some companies in Saudi Arabia. A total of 500 questionnaires were sent, but only 418 were received; for 84.0 percent response rates. This study used PLS to test the research hypotheses. The measurement model has confirmed that the measure indicates accepted reliability and validity. Based on the research results, most hypotheses are accepted. This means that the e-recruitment play a crucial role in improving firm performance. The findings of this study support the argument that e-recruitment plays an important role in improving firm performance. Therefore, firms that use e-recruitment to attract new job seekers will improve their performance. These findings extend prior literature by showing, for the first time, how e-recruitment and HR capability influence firm performance. This study has confirmed that e-recruitment has a positive and significant effect on firm performance. These variables account for 43% and 78% of the variety in HR capability and firm performance, respectively, whereas 57% and 22% are related to other variables. This finding is consistent with the argument that if firm use e-recruitment, they are more likely to improve firm performance. Moreover, high HR capability enhances firm performance. Our study moves beyond previous studies that focus on e-recruitment by correlating e recruitment with HR capability and firm performance. This study contributes by arguing that e-recruitment and HR capability has a positive relation towards firm performance, which conforms to previous studies in similar areas. Apart from the re-examination of resource-based theory in the online recruitment context, our study attempts to make some other fundamental contributions in understanding e-recruitment in the Saudi Arabia context. However, given that this is the first known test of resource-based theory in the Internet recruiting domain, we recommend that future research be done to conduct additional tests of this theory. These findings have both theoretical and practical implications in that the results have provided empirical evidence on the indirect impact of e-recruitment on firm performance and can serve as an indication in practice for firms in understanding e-recruitment and its effects on firm performance. The current study would help professionals in the field of HR to enhance their awareness of the critical role that recruiting highly skilled applicants may play in terms of sustainable competitive advantage and firm performance.

Schizophrenia is often a debilitating psychiatric disorder, characterised by both positive and negative symptoms, and cognitive and psychosocial impairments. The established disorder has been associated with a number of brain abnormalities, however it is at present unknown whether these brain changes occur prior to onset of schizophrenia, or in unaffected relatives with a familial vulnerability to develop the disorder, or only in those at high risk that go on to develop the disorder. Furthermore, most studies have been conducted cross-sectionally, which may have obscured subtle longitudinal changes in familial high risk individuals, and these studies tend to have focused on localized cortical gray matter , and thus it is unclear whether they affect different cortical parameters differentially. Prospective familial high risk studies utilizing surface based MRI programmes provide a good method to investigate this. In the Edinburgh High Risk Study, structural magnetic resonance imaging (MRI) scans of 150 young individuals at familial high risk of schizophrenia, 34 patients with first-episode schizophrenia and 36 matched controls were obtained. Of the high risk participants with scans suitable for analysis, 17 developed schizophrenia after the scans were taken, whilst 57 experienced isolated or sub-clinical psychotic symptoms, and 70 remained well. We used Freesurfer to extract volumetric and surface-based measurements of several cortical and localized sub-cortical regions with the aim of assessing whether any alterations found were present in all those at high risk, or selectively in the high risk cohort based on future clinical outcome, or only in those experiencing their first-episode of psychosis. It was found that those experiencing their first episode of schizophrenia exhibited significantly more widespread brain alterations compared to those at high risk or controls, both on a more global cortical level and in more localized regions of the cortex, with cortical thickness being generally thinner than in the other groups, and cortical surface area and gyrification increased compared to the other groups. An increased global surface area was also shared with the HR[ill] group, suggesting that this could be a marker that is predictive of future transition to psychosis. Within the high risk cohort, some brain alterations seemed to present as general vulnerability markers, specifically in the temporal lobe at baseline, whilst longitudinally both localized and global cortical alterations distinguished the high risk cohort from the control group, and a different developmental trajectory of the hippocampus was also found. These findings show that some brain alterations may be more accurately characterized as general vulnerability markers of the disorder, whilst some are specifically present in patients who have experienced their first episode of schizophrenia, whilst some also occur before disorder onset in those at high risk that go on to develop schizophrenia. The findings have some clinical implications, as they suggest that it is possible to assess who at high risk will go on to develop schizophrenia based on brain structural alterations. This may provide clinicians with an early window of opportunity for intervention, as it has been found that early intervention may improve patient's prognosis. The findings also have important implications for the understanding of the underlying eitology of schizophrenia, as they suggest that some of these alterations are present before illness onset, and not associated with medication effects, thus potentially lying on the causal path of developing schizophrenia.

The theme of this thesis is "The system of personnel management in an organization." People are the most important source of businesses because it is human resource management as an important activity for the competitiveness of the organization. The aim of thesis was to analyze the system of personnel work in the selected company and suggest changes to improve. Company selected for this thesis comes from the engineering industry and is manufacturer and after-sales servicer of brakes for railway vehicles. The analysis was made on personnel department, labor costs and human resources practices. To the company were recommended proposals for changes, from the findings of the investigation, that would lead to the improvement of personnel management.

Este estudo trata das relações entre práticas de recursos humanos, comprometimento e desempenho organizacional. Seu objetivo central é o desenvolvimento de um modelo teórico descritivo para explicar como a percepção de práticas de recursos humanos influencia o comprometimento e o desempenho organizacional. Pesquisas anteriores indicaram a existência de relacionamentos entre práticas de recursos humanos e performance empresarial, bem como relacionamentos entre práticas de recursos humanos e comprometimento organizacional sem, no entanto, estabelecer relações causais consistentes. O objetivo do estudo foi atingido através de combinação de procedimentos metodológicos qualitativos e quantitativos. Uma primeira etapa, exploratória, foi baseada em entrevistas em profundidade com executivos de empresas gaúchas de ponta em seus segmentos produtivos, e serviu para a elaboração da escala do construto ‘práticas de RH’. A segunda etapa, quantitativa, foi baseada em um estudo de caso num grupo industrial paulista com múltiplas instalações. Investigou-se, junto aos empregados, através de uma survey, a sua percepção a respeito das práticas de RH, além de mensurar o seu grau de comprometimento organizacional com a utilização da escala de Meyer e Allen (1991). As medidas de desempenho utilizadas foram objetivas, ou seja, indicadores de desempenho real foram fornecidos pela empresa objeto do estudo de caso. Para testar as relações entre os construtos da pesquisa, foi utilizada a Modelagem de Equações Estruturais. Os resultados encontrados indicam forte relacionamento entre os três construtos empregados, cujas escalas de mensuração apresentaram evidências de validade. Os parâmetros do modelo sugerem que a percepção das práticas de RH induzem a um aumento do comprometimento, contribuindo para melhor desempenho organizacional (relação entre práticas de RH e comprometimento organizacional – γ= 0,89; relação entre comprometimento e desempenho organizacional – β= 0,70). A seleção interna explica 60% da variabilidade do construto de práticas de RH, enquanto que treinamento, coaching, desenvolvimento de líderes, responsabilidade social e segurança explicam 55% dessa variabilidade. A análise das inter-relações das diversas variáveis que compõem os construtos do modelo fornece informações importantes e relevantes para a gestão de recursos humanos, contribuindo para uma linha de pesquisa que, internacionalmente, investiga o relacionamento da gestão de recursos humanos e o desempenho organizacional. / This study approaches the relations between human resource practices, commitment and organizational performance. It primarily aims at the development of a technical descriptive model to explain how the perception of human resource practices influence both the commitment and organizational performance. Previous research has indicated the existence of relation between human resources practices and enterprise performance, as well as human resources practices and organizational commitment, without, however, establishing consistent causal relations. The objective of this study was achieved through a combination of qualitative and quantitative methodological procedures. A first step, called exploratory, was based on in-depth interviews with executives of major companies in their productive segments from the State of Rio Grande do Sul, The interviews were used to elaborate the scale of the construct ‘HR Practices’. The second stage – qualitative - was based on a case study in an industrial group with multiple facilities located in the State of São Paulo. The perception of employees about HR practices was investigated through a survey. The degree of organizational commitment was measured using the Meyer and Allen (1991) scale. The performance measures were objective, meaning that real performance indicators were supplied by the company. The Structural Equation Modeling was used in order to test the relations between research constructs. The results indicate a strong association between the three constructs employed, and the measurement scales seem to be valid. The model parameters suggest that the perception of the HR practices induces an increase in commitment, contributing to a better organizational performance (relation between HR practices and organizational commitment – γ= 0.89; and between organizational commitment and performance – β = 0.70). The internal labor market explains 60% of the variability of the HR practice construct, while training, coaching, leader development, social responsibility and security explain 55% of such variability. The interrelation analysis of the variables that compose the model constructs offer relevant information to human resource management, contributing to a research line that, internationally, investigates the relation between human resource management and organizational performance.

Studien syftar till att utforska hur HR-medarbetare upplever sin yrkesrolls status och det strategiska värde som de bidrar med. Genom att se över den utveckling HR som yrkesgrupp har genomgått under 1900-talet, samt den transformation som ägt rum, utforskar studien de förändringar som lett fram till det HR vi ser idag. Vidare lägger detta grunden till den statusproblematik som studien behandlar. Den diskussion som förs i studien tar avstamp i en sociologisk infallsvinkel tillsammans med begreppsverktyg som härstammar från sociologen Pierre Bourdieu. Genom dessa verktyg ämnar vi att analysera den verklighet som HR-medarbetarna befinner sig i. Studien är av kvalitativ karaktär där vi genom att intervjua HR-medarbetare utforskar den status de upplever sig inneha, alternativt saknar. Med HR-medarbetare innefattas enbart HR-generalister och HR-specialister då tidigare studier tenderat att främst studera HR-chefer och deras upplevda status. Resultatet visar på att de HR-medarbetare som deltagit i studien upplever sig inneha en viss grad av status och att denna status främst tillskrivs dem genom den stödfunktion de besitter. Genom att studera den transformation som HR genomgått, tillsammans med den empiri som samlats in genom denna studie, visar det sig däremot att HR som yrkesgrupp och dess tillvägagångsätt för att erhålla status skiljer sig från HR-medarbetarnas sätt att erhålla status. / The aim of this study is to explore how HR employees experience their own profession, their status, and the strategic value that they contribute to the organization. Through a historical view of the HR profession, and the transformation that took place during the late 1900s, we examine the changes that helped to create the HR profession we see today. This process gives us the foundation of what this study seeks to explore. The discussion that takes place later on is inspired by a sociological perspective, as well as the tools originated by sociologist Pierre Bourdieu, which are used to analyze the reality of our interviewees. We conduct the study using a qualitative approach where HR generalists and HR specialists are interviewed about their perceived status (or lack thereof). HR employees with a title such as HR manager or HR supervisor have been excluded, since most of the previous studies already covered their experience regarding status and strategic value. The result shows that the HR employees participating in the study experience status and strategic value mainly through the assistant role that they have been appointed, acting as the right hand of the managers they are helping. However, by studying the transformation of HR, along with the data collected through the interviews, we find that there is a difference between how HR as a professional group acquire status, and how HR employees - the generalists and specialists - acquire status.