Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Reading matters

The present book is a special gift for a special colleague and friend. Defined as an “Unfestschrift,” it gives colleagues, students, and friends of Regina Bendix an opportunity to express their esteem for Regina’s inspiration, cooperation, leader¬ship, and friendship in an adequate and lasting manner. The title of the present book, Reading Matters, is as close as possible to an English equivalent of the beautiful German double entendre Erlesenes (meaning both “something read/a reading” and “something exquisite”). Presenting “matters for reading,” the Unfestschrift unites short contributions about “readings” that “mattered” in some way or another for the contributors, readings that had an impact on their understanding of whatever they were at some time or presently are interested in. The term “readings” is understood widely. Since most of the invited contributors are academics, the term implies, in the first place, readings of an academic or scholarly nature. In a wider notion, however, “readings” also refer to any other piece of literature, the perception of a piece of art (a painting, a sculpture, a performance), listening to music, appreciating a “folkloric” performance or a fieldwork experience, or just anything else whose “reading” or individual perception has been meaningful for the contributors in different ways. Contrary to a strictly scholarly treatment of a given topic in which the author often disappears behind the subject, the presentations unveil and highlight the contributor’s personal involve¬ment, and thus a dimension of crucial importance for ethnographers such as the dedicatee

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI less than;25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.Version of Recor

IgE-mediated food allergy in childhood

IgE-vermittelte Nahrungsmittelallergien nehmen weltweit insbesondere bei Kindern zu. Grund-legend für die Betreuung der chronisch kranken Patienten ist das sichere und eindeutige Di-agnostizieren der Erkrankung bzw. auch das Erkennen einer möglichen Toleranzentwicklung. Dafür sind Kenntnisse über die Charakteristika der relevanten Allergene wichtig. Für den individuellen Patienten ist die Prädiktion seiner allergischen Reaktionen, seines individuel-len Verlaufs und seiner Atopikerkarriere essentiell. In dieser Habilitationsschrift geht es da-rum, Vorhersageparameter im Rahmen der IgE- vermittelten Nahrungsmittelallergie bei Kin-dern zu identifizieren, um klinische Reaktionen im Rahmen der Doppel-blind Placebo-kontrollierten Nahrungsmittelprovokation (DBPCFC), dem Goldstandard in der Diagnostik, besser einschätzen zu können und um individuelle Biomarker im Serum der Kinder zu identi-fizieren, die sich als Prädiktoren für die (Entstehung einer) Nahrungsmittelallergie bzw. einer Toleranz eignen und sich dadurch sogar die aufwendige Provokation erübrigt. Wir konnten herausarbeiten, dass auch bei Säuglingen und Kleinkindern, insbesondere mit einer Anamnese der atopischen Dermatitis, eine Verblindung der oralen Nahrungsmittelprovo-kation und eine Placebo Kontrolle hilfreich ist, da falsch positive Placebo-Reaktionen insbe- sondere bei dieser Patientengruppe gehäuft vorkommen. In Anerkennung spezieller Charakteristika von gewissen Allergenen auf die Schwere der Re- aktionen konnten wir ein bestimmtes Verteilungsmuster von klinischen Reaktionen nach ora-len Nahrungsmittelprovokationen feststellen. Die Entwicklung von gastrointestinalen Sympto-men geschah häufiger nach Provokationen mit Hühnerei verglichen mit Kuhmilch, Soja und Weizen, wohingegen die schwerwiegenderen, respiratorischen Symptome häufiger nach Pro- vokationen mit Erdnuss auftraten. Ebenfalls konnten wir die starke Allergenität der Erdnuss in einem experimentellen Modell be-stätigen. In diesem in vivo Modell gelang es uns darüber hinaus den Einfluss einer Nah- rungsmittelprozessierung (gekochtes versus rohes Nahrungsmittel) auf immunologische Pa-rameter widerzuspiegeln. Neben einer Einschätzung einer Reaktion auf ein bestimmtes Allergen aufgrund der jeweiligen Eigenschaften des Allergens per se, sind Biomarker zum Beispiel im Serum der Patienten wünschenswert, die prädiktive Funktionen erfüllen und nicht zuletzt helfen können orale Nah-rungsmittelprovokationen zu ersetzen. Die Messung von Hühnerei- und Kuhmilch-spezifischem IgG oder IgG4 und auch die Einzelkomponentenanalyse war in unseren Studien jedoch weder hinsichtlich Diagnostik noch Prognose einer Hühnerei- bzw. einer Kuhmilchal-lergie weiterführend. Dahingegen konnten wir eine klare Assoziation von CCL25, dessen korrespondierender Re-zeptor CCR9 primär gastrointestinal lokalisiert ist, bei einer Nahrungsmittel-Sensibilisierung nachweisen. Obwohl wir zum jetzigen Zeitpunkt noch nichts über das prädiktive Potential er-höhter CCL25-Spiegel im Rahmen einer sich entwickelnden Nahrungsmittelallergie (Primäre Prädiktion) oder einer anstehenden (schweren) klinischen Reaktion sagen können, sind die Ergebnisse zu einer Relevanz der CCL25-CCR9 Achse im Rahmen der Nahrungsmittel-induzierten Entzündungsprozesse vielversprechend, bedürfen aber noch weiterer Untersu-chungen. Die Verknüpfung der Eigenschaften einzelner Allergene in Kombination mit der Identifikation gewisser Prädiktoren sind die Basis für die Generierung neuer Präventionsstrategien und spiegeln sich sowohl in der aktuellen Literatur als auch in den eigenen laufenden Forschungs- projekten wieder. Wir hoffen, dass wir mit unseren Daten einen Beitrag leisten, um das Wissen der durch Nah-rungsmittelallergene ausgelösten Immunreaktionen besser zu verstehen und den betroffenen Patienten im Rahmen von Diagnostik, Prädiktion und langfristig auch der Prävention von Nah- rungsmittelallergien zu helfen.IgE-mediated food allergies appear to have increased worldwide and especially children are affected. Diagnosing food allergy is a challenging and often time-consuming procedure. Fortunately, in hen’s egg, cow’s milk, wheat or soy allergy natural tolerance develops frequently. However, peanut and tree nut allergy often persists. For the individual patient, prediction of clinical signs and severity of allergic symptoms, as well as the likelihood of getting tolerant, is of main interest. Aim of this work (Habilitationsschrift) is the identification of predictors for clinical reactions in course of double-blind placebo-controlled food-challenges (DBPCFC), not least in combination to preference of allergen related organ-specific symptoms but also in consideration of individual patient’s characteristics. Moreover, biomarkers in sera of children were analyzed, in order to identify children at risk for development of food allergies respectively to predict tolerance development in food allergic children. We were able to show, that especially in infants with atopic dermatitis, a blinded and placebo-controlled food-challenge is beneficial. These young children (age <= 1.5 yrs) seem to be affected more often from positive placebo challenges. Therefore - contrary to current recommendations – DBPCFC tests should be considered. With regard to special characteristics of allergens on clinical symptoms, our data indicates that certain foods show a preference for organ-specific symptoms during oral food challenge (OFC). As an example, the development of gastrointestinal symptoms is more likely after challenges with hen’s egg and peanut compared to challenges with cow’s milk, soy, and wheat. In addition, the development of respiratory symptoms is more likely after peanut challenges. Further on, we were able to confirm the allergenicity of different allergens in an experimental model of food allergy. Allergens with high allergenic potential (like peanut, OVA, soy) caused a stronger immunological response than allergens with low allergenic potential such as RuBisCO and apple. Moreover, the immunological responses were reduced when using boiled instead of raw soy and pea proteins. Next to the estimation of allergic reactions on certain allergens due to its underlying characteristics per se, predictive biomarkers are needed. These may help for instance to replace elaborate food challenge procedures. The analysis of hen’s egg- or cow’s milk-specific IgG or IgG4 or even the analysis of single allergen components, was not helpful with regard to diagnosis nor prediction of hen’s egg, respectively cow’s milk allergy in our studies. Interestingly we observed in food-sensitized infants significantly higher serum levels of CCL25, ligand of CCR9, localized primarily in the gastrointestinal tract. Although so far, we have no data showing a predictive potential for sensitization against food allergens for an individual (primary prediction). Nevertheless, these data indicate an impact on CCL25, with its ligand CCR9, in the context of food allergen-induced inflammation. Therefore, the role of CCL25-CCR9 axis and its predictive potential for food allergies is of interest in future studies. In summary, the combination of characteristics of an allergen per se together with the identification of promising predictors are the basis for the generation of novel prevention strategies. We hope, that our data supports the increase of knowledge on food allergies, to enable a better understanding on allergen- specific immunological reactions and to help affected patients in course of diagnostic procedures, in prediction of (persistent) food allergy, as well as the development of novel prevention strategies

Die Ästhetik des weiblichen Widerstands : zur Thematisierung deutscher Geschichte in Irmtraud Morgners Salman-Trilogie /

Diss. doct. lettere