Test beam studies of pixel detector prototypes for the ATLAS-Experiment at the High Luminosity Large Hadron Collider

The upgrade of the Large Hadron Collider (LHC) in the mid-2020’s to the High Luminosity Large Hadron Collider will provide large amounts of data, enabling precision measurements of Standard Model processes and searches for new physics. This will also maximise the physics potential of the experiments located at the LHC. In order to record the desired inte- grated luminosity, the ATLAS detector will face challenges regarding the radiation damage, pile-up and amount of data. To cope with those challenges, the entire tracking detector is replaced by the new Inner Tracker, ITk. In order to develop novel detector modules, test beam measurements are a crucial tool to study and understand new read-out chips, novel sensor technologies, as well as the effect of radiation on the sensor and read-out chip. Not only in the R&D-phase but also in the phase of module production, test beams need to play a necessary role in the continuous quality assurance procedure. This thesis is focused on the test beam measurements of pixel modules for the ITk upgrade. Several aspects of test beams are covered and have been improved. Modifications to one of the used DAQ systems at test beams (USBpix) have been made. A new measurement technique using the USBpix system to make so-called in-time measurements at test beams has been developed. The measurement method as well as results from such a measurement are discussed in this thesis. Furthermore, many parts of the reconstruction framework have been modernised and improved. The track fit based on the General-Broken-Line algorithm now allows track reconstruction together with ATLAS pixel modules. Also, test cases were implemented to ensure long-term stability, and guarantee a consistent reconstruction, even in future versions. Additionally, a Monte Carlo framework was expanded to enable validation of the reconstruction algorithms

Clinical and Mechanistic Insights into Novel Probiotic Functions and Formulations

Using a combination of hypothesis and discovery based approaches, the goal of this thesis was to better describe novel probiotic functions and their mechanisms while striving to better understand the effect of formulation on Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei and L. rhamnosus. Using RNA-Seq, a bacterial metatranscriptome analysis of a commonly consumed probiotic yogurt showed that the organisms adapted to storage time and flavor additions. This led to the discovery that in addition to the probiotic health benefits, members of the L. casei group (L. rhamnosus and L. paracasei) produce volatile sulfur compounds mediated by a novel sulfur/taurine metabolism gene cluster that affect taste and texture. The benefits of selected probiotic strains were tested in a further series of human studies. A systems biology approach was developed and a double-blind, placebo-controlled clinical trial of post-menopausal women showed that vaginally administered probiotics could influence the microbiota and host responses. Changes in the vaginal microbiota were noted in late pregnancy in a rural Tanzanian population, and maternal intake of Moringa supplemented L. rhamnosus GR-1 yogurt appeared to improve the gut microbiota profile of the newborn babies. Having discovered that L. rhamnosus GR-1, and selected other lactobacilli, could sequester heavy metals in vitro, a randomized open-label pilot study was performed and showed a reduction in toxic metal uptake in Tanzanian pregnant women and school children. The latter series of findings led to the discovery, development and characterization of a new strain, L. rhamnosus Lr60, with high potential to reduce toxic metal accumulation in the host. Using a mouse model, strains of L. rhamnosus were tested to better understand mechanisms of protection against mercury as well as to examine potential modulation of host xenobiotic metabolism by probiotics. Data suggest it is possible to sequester mercury and prevent it from entering the bloodstream. Collectively, these studies have increased our knowledge of probiotic mechanisms as well as lead to the development of novel applications of relevance to human health

A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols.

Catechol dehydroxylation is a central chemical transformation in the gut microbial metabolism of plant- and host-derived small molecules. However, the molecular basis for this transformation and its distribution among gut microorganisms are poorly understood. Here, we characterize a molybdenum-dependent enzyme from the human gut bacterium Eggerthella lenta that dehydroxylates catecholamine neurotransmitters. Our findings suggest that this activity enables E. lenta to use dopamine as an electron acceptor. We also identify candidate dehydroxylases that metabolize additional host- and plant-derived catechols. These dehydroxylases belong to a distinct group of largely uncharacterized molybdenum-dependent enzymes that likely mediate primary and secondary metabolism in multiple environments. Finally, we observe catechol dehydroxylation in the gut microbiotas of diverse mammals, confirming the presence of this chemistry in habitats beyond the human gut. These results suggest that the chemical strategies that mediate metabolism and interactions in the human gut are relevant to a broad range of species and habitats

Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt

The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world\u27s population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother\u27s microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study

"Die zwei gehören zusammen, aber das geht nicht."

Die vorliegende Diplomarbeit zum Thema „,Die zwei gehören zusammen, aber das geht nicht.„ Eine psychoanalytisch-pädagogische Einzelfallstudie über das Erleben von Zweisamkeit im Pflegeheim mit Blick auf die Ausbildung von Pflegepersonen“ wurde im Kontext des universitären Forschungsprojekts „Lebensqualität im Pflegeheim“ verfasst, an welchem das Institut für Bildungswissenschaft, Pflegewissenschaft und Soziologie beteiligt waren. Für die Arbeit wurde dazu mit Hilfe der Methode der psychodynamischen Einzelbeobachtung nach dem Tavistock-Konzept Frau Gürtler über einen Zeitraum von drei Monaten einmal wöchentlich für eine Stunde beobachtet. Frau Gürtler ist an Demenz erkrankt und wohnt im Pflegeheim. Anhand der Analyse von Beobachtungsprotokollen wurde deutlich, dass vor allem das Thema der Zweisamkeit für Frau Gürtler von Bedeutung war. Ausgehend davon wurde der Frage nachgegangen, inwiefern das Erleben von Zweisamkeit einen emotional bedeutsamen Aspekt im Alltag von Frau Gürtler darstellt. Vor dem Hintergrund des Ergebnisses, dass Frau Gürtler den Wunsch hatte, Zweisamkeit zu erleben, da dies mit angenehmen Gefühlen verbunden war, die sonst im Pflegeheimalltag nicht aufkamen, wurde der Blick auf die Pflegepersonen gerichtet. Betrachtet wurde dabei, ob es ihnen gelingt, Frau Gürtlers Wunsch nach Zweisamkeit wahrzunehmen. In diesem Zusammenhang wurde das Container-Contained-Modell von Wilfred Bion betrachtet. Dabei zeigte sich, dass Pflegepersonen kaum Fähigkeiten im Sinne des Container-Contained-Modells besitzen, um Gefühle, Wünsche und Bedürfnisse von PflegeheimbewohnerInnen wahrzunehmen und sie in Interaktionen mit BewohnerInnen zu berücksichtigen. Vor diesem Hintergrund wurde schließlich diskutiert, was dafür spricht, dass Pflegepersonen solche Fähigkeiten in ihrer Ausbildung vermittelt bekommen sollten und es wurden die Methoden der Einzelbeobachtung sowie der Work Discussion vorgeschlagen, um angehende Pflegepersonen für die Belange von PflegeheimbewohnerInnen zu sensibilisieren.Underlying thesis discussing “‟The two belong together, but it doesn‟t work out.‟, A psychoanalytical-pedagogical single case study about experiencing togetherness in nursing homes focusing on the education of nursing staff” was composed in context within the academic research project “life quality in the nursing home” by the faculties of pedagogy, nursing and sociology. Composing this paper Mrs. Gürtler, a nursing home resident, was observed using a method of psychodynamic single-observation after the Tavistock-Concept. This observation was carried out over three months, once a week for an hour. Analyzing the observing-protocols it is a stated fact that the topic togetherness is of high importance to Mrs. Gürtler. Due to this fact the question to what extent the experience of togetherness has an emotional meaningful aspect in the everyday life of Mrs. Gürtler, a nursing home resident, who came down with dementia was followed up. Based on the fact that Mrs. Gürtler desired to experience togetherness, hence it is related to pleasurable feelings that do not arise in everyday nursing home life, focus was put on nursing staff to look if they are able to notice Mrs. Gürtlers desire for togetherness. Beholding the Container-Contained-Model by Wilfred Bion in this context, it turned out that in terms of the Container-Contained-Model nursing staff is hardly able to notice feelings, wishes and needs of nursing home residents and to take these into account when interacting with residents. Thereafter it was discussed if such abilities of nursing staff should be trained during their education and methods of single-observation as well as the work discussion were recommended to sensibilize prospective nursing staff on interests of nursing home residents

Schreiben über Stalinismus und Kommunismus

In ihren autobiografischen Texten, die heute der RenegatInnenliteratur zugeordnet werden, berichten Margarete Buber-Neumann („Als Gefangene bei Stalin und Hitler“ 1949, „Von Potsdam nach Moskau“ 1957, „Freiheit, du bist wieder mein…“ 1978) und Susanne Leonhard („Gestohlenes Leben“ 1956) von ihrer Zuwendung und späteren Abwendung von der kommunistischen Partei, von der Emigration in die Sowjetunion sowie der Gefangenschaft in den Lagern unter Stalin und – in Buber-Neumanns Fall – unter Hitler. Die Textanalyse der Zeuginnenberichte widmet sich zuerst der Frage, ob Autobiografien authentisch sein können und wie Authentizität erzeugt wird. Im Zentrum der Untersuchung steht schließlich die Form der literarischen Verarbeitung traumatischer Erfahrungen und der politisch heiklen Vergangenheit. Der Zeitpunkt des Schreibens und die unterschiedlichen politischen Ausgangspunkte der Autorinnen in Bezug auf den Kommunismus spielen dabei eine entscheidende Rolle und wirken sich deutlich auf die Beschreibung des Wegs zum Kommunismus und zur Partei, den Blick auf Stalin und die Sowjetunion sowie die Wiedergabe der Erfahrungen in der Gefangenschaft aus. Ein Abriss über die Rezeption der Texte vertieft die Frage nach deren politischen Dimension und veranschaulicht das Problem des „Entweder – oder“ der kommunistischen beziehungsweise antikommunistischen Ideologie, zwischen welcher sich die Texte bewegen. Weiters sind in der Untersuchung der Texte genderspezifische Fragen relevant: die Position einer dominierenden männlichen Figur im Text, das Frauenbild der Autorinnen, die Darstellung des (weiblichen) Körpers in der Gefangenschaft sowie die Rolle von Zwischenmenschlichkeit und Sexualität

Set1/COMPASS repels heterochromatin invasion at euchromatic sites by disrupting Suv39/Clr4 activity and nucleosome stability.

Protection of euchromatin from invasion by gene-repressive heterochromatin is critical for cellular health and viability. In addition to constitutive loci such as pericentromeres and subtelomeres, heterochromatin can be found interspersed in gene-rich euchromatin, where it regulates gene expression pertinent to cell fate. While heterochromatin and euchromatin are globally poised for mutual antagonism, the mechanisms underlying precise spatial encoding of heterochromatin containment within euchromatic sites remain opaque. We investigated ectopic heterochromatin invasion by manipulating the fission yeast mating type locus boundary using a single-cell spreading reporter system. We found that heterochromatin repulsion is locally encoded by Set1/COMPASS on certain actively transcribed genes and that this protective role is most prominent at heterochromatin islands, small domains interspersed in euchromatin that regulate cell fate specifiers. Sensitivity to invasion by heterochromatin, surprisingly, is not dependent on Set1 altering overall gene expression levels. Rather, the gene-protective effect is strictly dependent on Set1's catalytic activity. H3K4 methylation, the Set1 product, antagonizes spreading in two ways: directly inhibiting catalysis by Suv39/Clr4 and locally disrupting nucleosome stability. Taken together, these results describe a mechanism for spatial encoding of euchromatic signals that repel heterochromatin invasion

Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium

© 2018, © 2018 The Author(s). Published by Taylor & Francis. Heavy metals are highly toxic elements that contaminate the global food supply and affect human and wildlife health. Purification technologies are often too expensive or not practically applicable for large-scale implementation, especially in impoverished nations where heavy metal contamination is widespread. Lactobacillus rhamnosus GR-1 (LGR-1) was shown in previous work to reduce heavy metal bioaccumulation in a Tanzanian cohort of women and children through indeterminant mechanisms. Here, it was hypothesized that LGR-1 could sequester the heavy metals lead (Pb) and cadmium (Cd), thereby reducing their absorption across intestinal epithelium. LGR-1 and other lactobacilli significantly reduced the amount of Pb and Cd in solution at all concentrations tested (0.5 mg/L–50 mg/L) and exhibited sustained binding profiles over a 48-hour period. Relative binding efficiency of LGR-1 decreased as Pb concentration increased, with an absolute minimum binding threshold apparent at concentrations of 2 mg/L and above. Electron microscopy revealed that Pb formed irregular cell-surface clusters on LGR-1, while Cd appeared to form intracellular polymeric clusters. Additionally, LGR-1 was able to significantly reduce apical-to-basolateral translocation of Pb and Cd in a Caco-2 model of the intestinal epithelium. These findings demonstrate the absorbent properties of LGR-1 can immobilize Pb and Cd, effectively reducing their translocation across the intestinal epithelium in vitro. Oral administration of heavy metal-binding Lactobacillus spp. (many of which are known human symbionts and strains of established probiotics) may offer a simple and effective means to reduce the amount of heavy metals absorbed from foods in contaminated regions of the world

A Multi-Platform Metabolomics Approach Identifies Highly Specific Biomarkers of Bacterial Diversity in the Vagina of Pregnant and Non-Pregnant Women

Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour, and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women, and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV include 2-hydroxyisovalerate and γ-hydroxybutyrate (GHB), but not succinate, which is produced by both Lactobacillus crispatus and BV-associated anaerobes in vitro. Biomarkers associated with high diversity and clinical BV are independent of pregnancy status, and were validated in a blinded replication cohort from Tanzania (n = 45), where we predicted clinical BV with 91% accuracy. Correlations between the metabolome and microbiota identified Gardnerella vaginalis as a putative producer of GHB, and we demonstrate production by this species in vitro. This work illustrates how changes in community structure alter the chemical composition of the vagina, and identifies highly specific biomarkers for a common condition