Structural analysis of the major lightharvesting complex II by electron paramagnetic resonance (EPR) : comparison between monomers and trimers

Der Haupt-Lichtsammenkomplex II (LHCII) höherer Pflanzen ist das häufigsternMembranprotein der Welt und in die chloroplastidäre Thylakoidmembran integriert. DerrnLHCII kann als Modellsystem genutzt werden, um die Funktionsweise vonrnMembranproteinen besser zu verstehen, da 96 % seiner Struktur kristallografisch aufgelöstrnist und er in rekombinanter Form in vitro rückgefaltet werden kann. Hierbei entsteht einrnvoll funktionaler Protein-Pigment.Komplex, der nahezu identisch mit der in vivo Varianternist.rnElektronenparamagnetischen Resonanz (EPR) Spektroskopie ist eine hoch sensitive undrnideal geeignete Methode, um die Strukturdynamik von Proteinen zu untersuchen. Hierzurnist eine ortsspezifische Markierung mit Spinsonden notwendig, die kovalent an Cysteinernbinden. Möglich wird dies, indem sorgfältig ausgewählte Aminosäuren gegen Cysteinerngetauscht werden, ohne dass die Funktionsweise des LHCII beeinträchtigt wird.rnIm Rahmen dieser Arbeit wurden die Stabilität des verwendeten Spinmarkers und diernProbenqualität verbessert, indem alle Schritte der Probenpräparation untersucht wurden.rnMithilfe dieser Erkenntnisse konnte sowohl die Gefahr einer Proteinaggregation als auchrnein Verlust des EPR Signals deutlich vermindert werden. In Kombination mit derrngleichzeitigen Etablierung des Q-Band EPR können nun deutlich geringer konzentrierternProben zuverlässig vermessen werden. Darüber hinaus wurde eine reproduzierbarernMethode entwickelt, um heterogene Trimere herzustellen. Diese bestehen aus einemrndoppelt markierten Monomer und zwei unmarkierten Monomeren und erlauben es, diernkristallografisch unvollständig aufgelöste N-terminale Domäne im monomeren undrntrimeren Assemblierungsgrad zu untersuchen. Die Ergebnisse konnten einerseits diernVermutung bestätigen, dass diese Domäne im Vergleich zum starren Proteinkern sehrrnflexibel ist und andererseits, dass sie in Monomeren noch mobiler ist als in Trimeren.rnZudem wurde die lumenale Schleifenregion bei unterschiedlichen pH Werten undrnvariierender Pigmentzusammensetzung untersucht, da dieser Bereich sehr kontroversrndiskutiert wird. Die Messergebnisse offenbarten, dass diese Region starre und flexiblerernSektionen aufweist. Während der pH Wert keinen Einfluss auf die Konformation hatte,rnzeigte sich, dass die Abwesenheit von Neoxanthin zu einer Änderung der Konformationrnführt. Weiterführende Analysen der strukturellen Dynamik des LHCII in einerrnLipidmembran konnten hingegen nicht durchgeführt werden, da dies eine gerichteternInsertion des rückgefalteten Proteins in Liposomen erfordert, was trotz intensiverrnVersuche nicht zum Erfolg führte.

Software tools and efficient algorithms for the feature detection, feature tracking, event localization, and visualization of large sets of atmospheric data

Data sets describing the state of the earth's atmosphere are of great importance in the atmospheric sciences. Over the last decades, the quality and sheer amount of the available data increased significantly, resulting in a rising demand for new tools capable of handling and analysing these large, multidimensional sets of atmospheric data. The interdisciplinary work presented in this thesis covers the development and the application of practical software tools and efficient algorithms from the field of computer science, aiming at the goal of enabling atmospheric scientists to analyse and to gain new insights from these large data sets. For this purpose, our tools combine novel techniques with well-established methods from different areas such as scientific visualization and data segmentation. In this thesis, three practical tools are presented. Two of these tools are software systems (Insight and IWAL) for different types of processing and interactive visualization of data, the third tool is an efficient algorithm for data segmentation implemented as part of Insight.Insight is a toolkit for the interactive, three-dimensional visualization and processing of large sets of atmospheric data, originally developed as a testing environment for the novel segmentation algorithm. It provides a dynamic system for combining at runtime data from different sources, a variety of different data processing algorithms, and several visualization techniques. Its modular architecture and flexible scripting support led to additional applications of the software, from which two examples are presented: the usage of Insight as a WMS (web map service) server, and the automatic production of a sequence of images for the visualization of cyclone simulations. The core application of Insight is the provision of the novel segmentation algorithm for the efficient detection and tracking of 3D features in large sets of atmospheric data, as well as for the precise localization of the occurring genesis, lysis, merging and splitting events. Data segmentation usually leads to a significant reduction of the size of the considered data. This enables a practical visualization of the data, statistical analyses of the features and their events, and the manual or automatic detection of interesting situations for subsequent detailed investigation. The concepts of the novel algorithm, its technical realization, and several extensions for avoiding under- and over-segmentation are discussed. As example applications, this thesis covers the setup and the results of the segmentation of upper-tropospheric jet streams and cyclones as full 3D objects. Finally, IWAL is presented, which is a web application for providing an easy interactive access to meteorological data visualizations, primarily aimed at students. As a web application, the needs to retrieve all input data sets and to install and handle complex visualization tools on a local machine are avoided. The main challenge in the provision of customizable visualizations to large numbers of simultaneous users was to find an acceptable trade-off between the available visualization options and the performance of the application. Besides the implementational details, benchmarks and the results of a user survey are presented.

Work-related behavior and experience patterns and predictors of mental health in German physicians in medical practice

Background and Objectives: Work-related stress and burnout among physicians are of increasing relevance. The aim of this study was to investigate work-related behavior and experience patterns and predictors of mental health of physicians working in medical practice in Germany. Methods: We surveyed a stratified, random sample of 900 physicians from different specialties. The questionnaire included the standardized instruments Work-related Behavior and Experience Pattern (AVEM) and the Short Form-12 Health Survey (SF-12). Results: Only one third of physicians reported high or very high general satisfaction with their job, but 64% would choose to study medicine again. Only 18% of physicians presented a healthy behavior and experience pattern. Almost 40% presented a pattern of reduced motivation to work, 21% were at risk of overexertion, and 22% at risk for burnout. Willingness to study medicine again, fulfilled job expectations, professional years, marital status, and behavior patterns were significant predictors of mental health and accounted for 35.6% of the variance in mental health scores. Job-related perceptions also had a significant effect on burnout. Conclusions: The strong influence of work-related perceptions suggests a need for realistic expectation management in medical education, as well as support in stress management and coping strategies during medical training.

The Body of Margaret Atwood: Sex Work and Prostitution within Margaret Atwood's The Handmaid's Tale, Oryx and Crake, and The Year of the Flood

In this paper, I will argue that Canadian author Margaret Atwood uses fiscal and socially conservative dystopias to show how sex work and prostitution are choices that women would never have to make in a world with true gender equality. In these radically different worlds, women have no agency beyond their sexuality and no ability to express themselves as equals within either society. And while the structures of both societies, the society of The Handmaid’s Tale and that of both Oryx and Crake and The Year of the Flood, are inherently different, they both stem from modern conservative philosophies: for example, the country of Gilead in The Handmaid’s Tale holds Christian conservative beliefs on the role of religion in the state and the culturally designated roles of women. I define social conservatism as the idea that government organizations are used to pursue an agenda promoting traditional religious values such as “public morality” and opposing “immoralities” such as abortion, prostitution, and homosexuality. I define fiscal conservatism as an agenda promoting privatization of the market, deregulation and lower taxes. In this paper I argue that because these philosophies are incompatible with gender equality, they drive women to occupations such as sex work. Women find that they have no choices and sex work provides something to “trade.” For Offred, this “trading” is more limited, because she is a sex slave. For Oryx, this trading allows her to travel to the West, yet not before her childhood is marked by prostitution and pornography. Sex work allows for Ren to reclaim some agency over her life, yet she only chooses sex work because she is presented with few other options. All of these issues stem from the philosophies that define these dystopias.

Functional neuroimaging of emotional learning and autonomic reactions

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.

Effects of fixed night shift work on 24 hour blood pressure regulation, state anxiety levels and total sleep time

Nearly 22 million Americans operate as shift workers, and shift work has been linked to the development of cardiovascular disease (CVD). This study is aimed at identifying pivotal risk factors of CVD by assessing 24 hour ambulatory blood pressure, state anxiety levels and sleep patterns in 12 hour fixed shift workers. We hypothesized that night shift work would negatively affect blood pressure regulation, anxiety levels and sleep patterns. A total of 28 subjects (ages 22-60) were divided into two groups: 12 hour fixed night shift workers (n=15) and 12 hour fixed day shift workers (n=13). 24 hour ambulatory blood pressure measurements (Space Labs 90207) were taken twice: once during a regular work day and once on a non-work day. State anxiety levels were assessed on both test days using the Speilberger’s State Trait Anxiety Inventory. Total sleep time (TST) was determined using self recorded sleep diary. Night shift workers demonstrated increases in 24 hour systolic (122 ± 2 to 126 ± 2 mmHg, P=0.012); diastolic (75 ± 1 to 79 ± 2 mmHg, P=0.001); and mean arterial pressures (90 ± 2 to 94 ± 2mmHg, P<0.001) during work days compared to off days. In contrast, 24 hour blood pressures were similar during work and off days in day shift workers. Night shift workers reported less TST on work days versus off days (345 ± 16 vs. 552 ± 30 min; P<0.001), whereas day shift workers reported similar TST during work and off days (475 ± 16 minutes to 437 ± 20 minutes; P=0.231). State anxiety scores did not differ between the groups or testing days (time*group interaction P=0.248), suggesting increased 24 hour blood pressure during night shift work is related to decreased TST, not short term anxiety. Our findings suggest that fixed night shift work causes disruption of the normal sleep-wake cycle negatively affecting acute blood pressure regulation, which may increase the long-term risk for CVD.

The association between beliefs about low back pain and work presenteeism

OBJECTIVE: To examine the influence of beliefs about low back pain (LBP) on reduced productivity at work ("presenteeism") caused by LBP. METHODS: Two thousand five hundred seven individuals completed the Back Beliefs Questionnaire, the Fear Avoidance Beliefs questionnaire (FABQ), and questions about LBP-related work-absence, reduced work-productivity, pain, comorbidity, and demographics. RESULTS: Six hundred seventy (25%) individuals were of working age, employed and reported current LBP. Univariate models showed beliefs were more "negative" in individuals with work-absence and reduced productivity (P = 0.0001). In multivariable analysis, controlling for confounders, "FABQwork" was a unique predictor of both absenteeism and presenteeism (each, P = 0.0001), though with small effect sizes. CONCLUSIONS: Negative beliefs about LBP are associated with both work absence and reduced work-productivity. Further investigations should examine their potential as a target for educational interventions when considering initiatives to reduce the socioeconomic costs of LBP.

Seasonal variation of VO 2 max and the VO2-work rate relationship in elite Alpine skiers

PURPOSE: Alpine ski performance relates closely to both anaerobic and aerobic capacities. During their competitive season, skiers greatly reduce endurance and weight training, and on-snow training becomes predominant. To typify this shift, we compared exhaustive ramp cycling and squat (SJ) and countermovement jumping (CMJ) performance in elite males before and after their competitive season. RESULTS: In postseason compared with preseason: 1) maximal oxygen uptake (VO 2 max) normalized to bodyweight was higher (55.2 +/- 5.2 vs 52.7 +/- 3.6 mL x kg(-1) x min(-1), P < 0.01), but corresponding work rate (W) was unchanged; 2) at ventilatory thresholds (VT), absolute and relative work rates were similar but heart rates were lower; 3) VO2/W slope was greater (9.59 +/- 0.6 vs 9.19 +/- 0.4 mL O2 x min(-1) x W(-1), P = 0.02), with similar flattening (P < 0.01) above V T1 at both time points; and 4) jump height was greater in SJ (47.4 +/- 4.4 vs 44.7 +/- 4.3 cm, P < 0.01) and CMJ (52.7 +/- 4.6 vs 50.4 +/- 5.0 cm, P < 0.01). DISCUSSION: We believe that aerobic capacity and leg power were constrained in preseason and that improvements primarily reflected an in-season recovery from a fatigued state, which was caused by incongruous preseason training. Residual adaptations to high-altitude exposure in preseason could have also affected the results. Nonetheless, modern alpine skiing seemingly provides an ample cardiovascular training stimulus for skiers to maintain their aerobic capacities during the racing season. CONCLUSIONS: We conclude that aerobic fitness and leg explosiveness can be maintained in-season but may be compromised by heavy or excessive preseason training. In addition, ramp test V O2/W slope analysis could be useful for monitoring both positive and negative responses to training.

Youth Work and Schools in ‘Full-day’ education systems: International Comparison of Links between Formal and Non-formal Education

In this article I will outline the methodological approach of a non-empirical comparative research project which I began in 2003. The project is situated in the context of the research training group “Youth Welfare in Transition” at the universities of Bielefeld and Dortmund, funded by the German Research Council (Deutsche Forschungsgemeinschaft). In that context I have organised an international conference about the modes of cooperation between school and youth work agencies with colleagues from Canada, France, Finland, Italy, Japan, the Netherlands, Russia, Switzerland, the United Kingdom, the United States, Israel, and Germany. Meeting in Bielefeld from the 9th to the 11th of October 2003, we compared the respective national arrangements of formal and non-formal education (www.uni-bielefeld.de/paedagogik/agn/ag8/Ganztagsbildung.html). This note is based on the scheme of comparison which was given to the contributors in order to help them preparing their presentations. At the moment the scheme is nearing completed with significant data prepared by the contributors/authors (see Otto/Coelen 2004), supplemented with data from research works published in German and English. The next step will be to set up an empirical project about the relationships between schools and youth work agencies in three European countries (probably France, Finland and the Netherlands).

Homelessness, Social Work, Social Policy and the Print Media in Australian Cities

Homelessness is a significant social problem worldwide. This paper describes an Australian study that examined print media representations of homelessness and social work, social policy and social work responses to homelessness in three Australian cities. The research included a content analysis of seven Australian newspapers and semi-structured interviews with 39 social workers employed in the field of homelessness in Adelaide, Melbourne and Sydney. The detailed results of these studies have been published separately elsewhere. This paper reports on how discourses in the print media, social policy and social work practice co-exist in constructing homelessness as a particular social problem, influencing social work responses to homelessness. The research found that individualism is central to many dominant discourses evident in the print media, social policy and social work practice, and that social work is practiced within unequal power relations embedded in organisational contexts.

High self-esteem prospectively predicts better work conditions and outcomes

We examined the reciprocal prospective relations between self-esteem and work conditions and outcomes, including justice at work, support at work, work stressors, job satisfaction, job success, and counterproductive work behavior. Data came from two independent longitudinal studies, including five assessments over an 8-month period (N = 663, age 16–62 years) and three assessments over a 2-year period (N = 600, age 22–51 years), respectively. Across both studies, high self-esteem prospectively predicted better work conditions and outcomes, whereas nearly all of the reverse effects (i.e., work conditions and outcomes predicting self-esteem) were nonsignificant. The results held for both male and female participants. If future research supports the causality of the self-esteem effects, interventions aimed at improving self-esteem might be useful in increasing an individual’s well-being and success at work, which consequently might be beneficial for employers.

A BAYESIAN APPROACH TO DOSE-RESPONSE ASSESSMENT AND DRUG-DRUG INTERACTION ANALYSIS: APPLICATION TO IN VITRO STUDIES

The considerable search for synergistic agents in cancer research is motivated by the therapeutic benefits achieved by combining anti-cancer agents. Synergistic agents make it possible to reduce dosage while maintaining or enhancing a desired effect. Other favorable outcomes of synergistic agents include reduction in toxicity and minimizing or delaying drug resistance. Dose-response assessment and drug-drug interaction analysis play an important part in the drug discovery process, however analysis are often poorly done. This dissertation is an effort to notably improve dose-response assessment and drug-drug interaction analysis. The most commonly used method in published analysis is the Median-Effect Principle/Combination Index method (Chou and Talalay, 1984). The Median-Effect Principle/Combination Index method leads to inefficiency by ignoring important sources of variation inherent in dose-response data and discarding data points that do not fit the Median-Effect Principle. Previous work has shown that the conventional method yields a high rate of false positives (Boik, Boik, Newman, 2008; Hennessey, Rosner, Bast, Chen, 2010) and, in some cases, low power to detect synergy. There is a great need for improving the current methodology. We developed a Bayesian framework for dose-response modeling and drug-drug interaction analysis. First, we developed a hierarchical meta-regression dose-response model that accounts for various sources of variation and uncertainty and allows one to incorporate knowledge from prior studies into the current analysis, thus offering a more efficient and reliable inference. Second, in the case that parametric dose-response models do not fit the data, we developed a practical and flexible nonparametric regression method for meta-analysis of independently repeated dose-response experiments. Third, and lastly, we developed a method, based on Loewe additivity that allows one to quantitatively assess interaction between two agents combined at a fixed dose ratio. The proposed method makes a comprehensive and honest account of uncertainty within drug interaction assessment. Extensive simulation studies show that the novel methodology improves the screening process of effective/synergistic agents and reduces the incidence of type I error. We consider an ovarian cancer cell line study that investigates the combined effect of DNA methylation inhibitors and histone deacetylation inhibitors in human ovarian cancer cell lines. The hypothesis is that the combination of DNA methylation inhibitors and histone deacetylation inhibitors will enhance antiproliferative activity in human ovarian cancer cell lines compared to treatment with each inhibitor alone. By applying the proposed Bayesian methodology, in vitro synergy was declared for DNA methylation inhibitor, 5-AZA-2'-deoxycytidine combined with one histone deacetylation inhibitor, suberoylanilide hydroxamic acid or trichostatin A in the cell lines HEY and SKOV3. This suggests potential new epigenetic therapies in cell growth inhibition of ovarian cancer cells.

Return to Work after Traumatic Hand Injuries: Medical, Personal and Work-related Factors

PURPOSE This study aimed to examine the work-related impact of open hand injuries, specifically, the amount of lost work days subsequent to the injury and factors associated with work-related rehabilitation. PATIENTS AND METHODS We retrospectivley included consecutive patients with acute hand injuries who were operated between 2008 and 2009 in the Division of Hand Surgery (n=435) at the Department of Orthopaedic, Plastic and Hand Surgery. Information was obtained from the medical records and via a self-reported questionnaire sent out in 2011. Patients younger than 18 or older than 65 years, as well as the unemployed were excluded from the study. Descriptive group analysis was used to establish statistical relationships between time off work (TOW) and possible influencing variables. Multiple linear regression was applied to analyse the impact of injury, personal and/or work-related factors on TOW. RESULTS The sample included 290 patients with a mean age of 38.9 (SD 13.2) years of whom 98.6% returned to work after a median absence of 45.5 days. Univariate analysis demonstrated an association of length of absence from work with socio-demographic, clinical and work-related factors. Multiple regression analysis indicated that the location of injury, the number of injured regions, the need for secondary surgery, age, and the type of occupation were independently associated with TOW. CONCLUSION Most factors associated with TOW after traumatic hand injuries could not be influenced. Possible interventions should probably target improved injury prevention, optimal clinical treatment and rehabilitation starting early after injury. Whether improvements in communication and enhancement of cooperation between the treatment teams, the workplace and the insurance carrier may support a staged and earlier return to work remains to be investigated.

Personality complexes in adolescence: Traits, interests, work values, and self-evaluations

Following the recent trend in psychology towards a more integrative view of personality, the study attempted to establish the connections and underlying complexes of fundamental personality dispositions within two cohorts of Swiss adolescents in eighth and eleventh grade (N = 492, ages 13 to 19): Big-Five basic traits, big six vocational interests, work values, and generalized self-efficacy and externality of control beliefs. Five factors were identified which accounted for 60% of variance among the relations of the variables: (1) enterprisingconventional interests, (2) favorable personality dispositions, (3) social-artistic personality characteristics, (4) investigative-realistic interests, and (5) work value endorsement. Crosssectional findings indicate that particularly agreeableness and conscientiousness become closer related to interests and work values with increasing grade-level.

The Evolution of Routines under flexible Information Technology

Many technological developments of the past two decades come with the promise of greater IT flexi-bility, i.e. greater capacity to adapt IT. These technologies are increasingly used to improve organiza-tional routines that are not affected by large, hard-to-change IT such as ERP. Yet, most findings on the interaction of routines and IT stem from contexts where IT is hard to change. Our research ex-plores how routines and IT co-evolve when IT is flexible. We review the literatures on routines to sug-gest that IT may act as a boundary object that mediates the learning process unfolding between the ostensive and the performative aspect of the routine. Although prior work has concluded from such conceptualizations that IT stabilizes routines, we qualify that flexible IT can also stimulate change because it enables learning in short feedback cycles. We suggest that, however, such change might not always materialize because it is contingent on governance choices and technical knowledge. We de-scribe the case-study method to explore how routines and flexible IT co-evolve and how governance and technical knowledge influence this process. We expect to contribute towards stronger theory of routines and to develop recommendations for the effective implementation of flexible IT in loosely coupled routines.