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Chromosome Instability (CIN) is defined as an increase in the rate at which whole chromosomes or large parts are gained or lost. CIN is not only associated with virtually all tumor types, but it is associated with aggressive tumors, tumor recurrence, acquisition of multidrug resistance and poor patient prognosis. However, the genes and molecular defects that contribute to CIN are poorly understood. I hypothesize that KIF11 is an essential gene for chromosomes integrity during mitosis and therefore any defect in KIF11 expression or function will induce CIN and contribute to tumorigenesis. Accordingly, KIF11 was either silenced using siRNA or inhibited using monastrol within two distinct human cell lines and was investigated for CIN associated phenotypes. Here, I have identified and validated KIF11 as a novel CIN gene. This study represents the first steps necessary to identify and develop novel treatments design to target origins of CIN in CIN associated cancers. / February 2017

The thesis deals with the automation of the production process of the workplace for forging of metal parts for a specific customer in a specific environment. In the introduction, there is an analysis of the industrial revolution. In the next part, the thesis is devoted to the virtual commissioning in Process Simulate. It then deals with the technical part of the design and detailed specifications of the individual components. Finally, the success of the project after the implementation is evaluated.

<p>Wilson's disease (WD), bepatolenticular degeneration, is an autosomal recessive disorder caused by mutations in the ATP7B gene, and is characterised by abnormal metabolism and deposition of copper in the liver, brain and other organs. The main aim of this thesis was to investigate the occurrence of psychopathology, as well as personality traits and neuropsychological function in Swedish patients with treated WD. The research subjects were 29 patients with confirmed WD, investigated at the Department of Internal Medicine at Uppsala University Hospital between 1996 and 2000. </p><p>The treated WD patients showed prominent psychopathology as determined by the Comprehensive Psychopathological Rating Scale. The spectrum of psychopathological symptoms is not typical of classic psychiatric syndromes, and includes symptoms from Anxiety, Depression and Obsessive-Compulsive disorders as well as Negative Symptoms. In self-assessment, the WD patients tended to underestimate the presence of psychopathological symptoms. The treated WD patients differed in their sleep pattern from the control group, as measured with the Uppsala Sleep Inventory. The spectrum of self-reported symptoms suggests an altered REM sleep function. </p><p>The treated WD patients had significant deviations in personality traits, especially in aggressivity-hostility related scales and Psychic anxiety, compared to healthy controls, as measured with the Karolinska Scales of Personality. The deviations were not related to age, age at onset or duration of WD. The treated WD patients displayed a specific profile of moderate neuropsychological impairment, as determined by the Automated Psychological Test battery. Finally, an attempt was made to search for, possible genotype-phenotype relationships in some ATP7B mutations. </p>

<p>The subjects were 130 male prisoners in Swedish jails were examined by SCID and the diagnoses given in terms of DSM-IV. The most common mental disorder was drug abuse. On Axis II several personality disorders were diagnosed. Personality assessments were made by KSP. High scores were mainly found for e.g. impulsiveness, sensation seeking, aggression and low scores in socialisation.</p><p>MAO assays were performed in 99 male criminal offenders and in 60 non-criminal volunteers. Offenders had lower MAO activity than controls also with the confounding factor smoking under control. It is proposed that platelet MAO is linked to personality traits, which can predispose for criminality. </p><p>For testing the existence of combinations of vulnerability factors, a configuration frequency analysis (CFA) was used. The criteria which formed the basis for the subgrouping were; MAO activity below or above –0.5 SD of the mean (L and H), the presence or absence of an Axis I disorder (= drug abuse) (Y/N), the presence or absence of an Axis II disorder (Y/N), or the presence or absence of an Axis I and II disorder (Y/N). In this way eight subgroups were formed. Two significant "types" were found among the criminals: One was characterised by low platelet MAO activity, Cluster B personality diagnosis as well as Drug Abuse Disorder diagnosis (LYY); and the other by a pattern of normal platelet MAO activity, no Cluster B personality disorder, and no Drug Disorder diagnosis (HNN). Also two "antitypes", occurring less frequent than expected, were identified; LYN and LNY. Thus, the aggregation of certain risk factors in the same individual has been shown to contribute to the development of criminal behaviour.</p><p>The subgroups HNN, LYN, LNY and LYY were then analysed for a variety of criminological factors. There was a difference in mean age between the subgroups, the HNN being lowest. Economical crimes were more common at an early criminal debut and crimes involving violence at an adult debut. The HNN subgroup had a lower number of crimes and times spent in jail than the other subgroups. More than 50% of the clients in all groups had previously been sentenced to Reformatory.</p>

<p>The sick building syndrome (SBS) comprises eye, nose, skin, and throat symptoms, headache and fatigue. Gender, personality aspects, and psychosocial factors at work have lately been at focus in health research. The main aim of this thesis was to investigate the relationships between SBS and personal factors, personality traits, and psychosocial work stress. Two different populations were studied: a cohort of 195 subjects working in suspected “sick buildings” followed 1988-1999, and a random sample of 695 subjects from the Swedish population, 20-65 y. Two personality scales were used; the Karolinska Scales of Personality (KSP) and the Sense of Coherence (SOC). Two stress questionnaires were used: the 3-dimensional demands-control-support model (DCS) and the Assessment of Perceived Psychosocial Work Environment (PPWE). SBS and personal factors were assessed by a postal symptoms questionnaire and a symptom score (SC) was calculated. Personality was assessed by means of two verbal personality scales, the KSP and the SOC. Females in problem buildings had more SBS than men, and females had a lower SOC and more anxiety and aggressivity in the KSP. Females and males in the general working population reported differences in psychosocial work environment. Moreover, the associations between personality traits and SBS, and between DCS and SBS, differed between males and females. Over all, the investigated occupants of suspected sick-buildings were within the normal range for both KSP and SOC norms. However, those with symptoms showed prominent personality vulnerability, especially in anxiety, aggressivity, and lower SOC, compared to those that were not reporting symptoms. Female gender, low age, asthma, and a history of atopy were related to SBS in the general working population. A combination of low social support and either passive, strained, or active work situation, as well as a combination of high social support and active work situation, were associated with SBS. In conclusion, measurements of personality and psychosocial work environment could be of value in future studies on environmental syndromes. Moreover, the demans-control-support model can predict SBS, but in a more complex way than indicated by earlier research. </p>

Wilson's disease (WD), bepatolenticular degeneration, is an autosomal recessive disorder caused by mutations in the ATP7B gene, and is characterised by abnormal metabolism and deposition of copper in the liver, brain and other organs. The main aim of this thesis was to investigate the occurrence of psychopathology, as well as personality traits and neuropsychological function in Swedish patients with treated WD. The research subjects were 29 patients with confirmed WD, investigated at the Department of Internal Medicine at Uppsala University Hospital between 1996 and 2000. The treated WD patients showed prominent psychopathology as determined by the Comprehensive Psychopathological Rating Scale. The spectrum of psychopathological symptoms is not typical of classic psychiatric syndromes, and includes symptoms from Anxiety, Depression and Obsessive-Compulsive disorders as well as Negative Symptoms. In self-assessment, the WD patients tended to underestimate the presence of psychopathological symptoms. The treated WD patients differed in their sleep pattern from the control group, as measured with the Uppsala Sleep Inventory. The spectrum of self-reported symptoms suggests an altered REM sleep function. The treated WD patients had significant deviations in personality traits, especially in aggressivity-hostility related scales and Psychic anxiety, compared to healthy controls, as measured with the Karolinska Scales of Personality. The deviations were not related to age, age at onset or duration of WD. The treated WD patients displayed a specific profile of moderate neuropsychological impairment, as determined by the Automated Psychological Test battery. Finally, an attempt was made to search for, possible genotype-phenotype relationships in some ATP7B mutations.

The subjects were 130 male prisoners in Swedish jails were examined by SCID and the diagnoses given in terms of DSM-IV. The most common mental disorder was drug abuse. On Axis II several personality disorders were diagnosed. Personality assessments were made by KSP. High scores were mainly found for e.g. impulsiveness, sensation seeking, aggression and low scores in socialisation. MAO assays were performed in 99 male criminal offenders and in 60 non-criminal volunteers. Offenders had lower MAO activity than controls also with the confounding factor smoking under control. It is proposed that platelet MAO is linked to personality traits, which can predispose for criminality. For testing the existence of combinations of vulnerability factors, a configuration frequency analysis (CFA) was used. The criteria which formed the basis for the subgrouping were; MAO activity below or above –0.5 SD of the mean (L and H), the presence or absence of an Axis I disorder (= drug abuse) (Y/N), the presence or absence of an Axis II disorder (Y/N), or the presence or absence of an Axis I and II disorder (Y/N). In this way eight subgroups were formed. Two significant "types" were found among the criminals: One was characterised by low platelet MAO activity, Cluster B personality diagnosis as well as Drug Abuse Disorder diagnosis (LYY); and the other by a pattern of normal platelet MAO activity, no Cluster B personality disorder, and no Drug Disorder diagnosis (HNN). Also two "antitypes", occurring less frequent than expected, were identified; LYN and LNY. Thus, the aggregation of certain risk factors in the same individual has been shown to contribute to the development of criminal behaviour. The subgroups HNN, LYN, LNY and LYY were then analysed for a variety of criminological factors. There was a difference in mean age between the subgroups, the HNN being lowest. Economical crimes were more common at an early criminal debut and crimes involving violence at an adult debut. The HNN subgroup had a lower number of crimes and times spent in jail than the other subgroups. More than 50% of the clients in all groups had previously been sentenced to Reformatory.

The sick building syndrome (SBS) comprises eye, nose, skin, and throat symptoms, headache and fatigue. Gender, personality aspects, and psychosocial factors at work have lately been at focus in health research. The main aim of this thesis was to investigate the relationships between SBS and personal factors, personality traits, and psychosocial work stress. Two different populations were studied: a cohort of 195 subjects working in suspected “sick buildings” followed 1988-1999, and a random sample of 695 subjects from the Swedish population, 20-65 y. Two personality scales were used; the Karolinska Scales of Personality (KSP) and the Sense of Coherence (SOC). Two stress questionnaires were used: the 3-dimensional demands-control-support model (DCS) and the Assessment of Perceived Psychosocial Work Environment (PPWE). SBS and personal factors were assessed by a postal symptoms questionnaire and a symptom score (SC) was calculated. Personality was assessed by means of two verbal personality scales, the KSP and the SOC. Females in problem buildings had more SBS than men, and females had a lower SOC and more anxiety and aggressivity in the KSP. Females and males in the general working population reported differences in psychosocial work environment. Moreover, the associations between personality traits and SBS, and between DCS and SBS, differed between males and females. Over all, the investigated occupants of suspected sick-buildings were within the normal range for both KSP and SOC norms. However, those with symptoms showed prominent personality vulnerability, especially in anxiety, aggressivity, and lower SOC, compared to those that were not reporting symptoms. Female gender, low age, asthma, and a history of atopy were related to SBS in the general working population. A combination of low social support and either passive, strained, or active work situation, as well as a combination of high social support and active work situation, were associated with SBS. In conclusion, measurements of personality and psychosocial work environment could be of value in future studies on environmental syndromes. Moreover, the demans-control-support model can predict SBS, but in a more complex way than indicated by earlier research.

In view of the problem of uneven load distribution and energy consumption among nodes in a multi-hop wireless sensor network, this research constructs the routing schedule problem as a MOP (Multi-objective Optimization Problem), and proposed an energy-aware routing optimization scheme RDSEGA based on multi-objective optimization. In this scheme, in order to avoid the searching space explosion problem caused by the increase of nodes, KSP Yen's algorithm was applied to prune the searching space, and the candidate paths selected after pruning are recoded based on priority. Then adopted the improved strengthen elitist genetic algorithm to get the entire network routing optimization scheme with the best energy efficiency. At the same time, in view of the problem of routing discontinuity in the process of path crossover and mutation, new crossover and mutation method was proposed that based on the gene fragments connected by the adjacent node or the same node to maximize the effectiveness of the evolution result. The experimental results prove that the scheme reduced the energy consumption of nodes in the network, the load between nodes becomes more balanced, and the working time of the network has been prolonged nearly 40% after the optimization. This brings convenience to practical applications, especially for those that are inconvenient to replace nodes.