Videospielturniere in öffentlichen Schweizer Bibliotheken

Diese Arbeit behandelt das Thema Videospielturniere in öffentlichen Schweizer Bibliotheken. Den praktischen Teil dieser Arbeit bildet das Pilotprojekt in Form eines Videospielturniers in der Stadtbibliothek Katharinen in St. Gallen. Als Grundlage für die Auswertungen dienen sowohl Beobachtungen wie auch Befragungen der Teilnehmerinnen des Turniers. Ziel war einerseits, die Wirkung des Videospielturniers auf die Stadtbibliothek und Teilnehmerinnen zu dokumentieren, und andererseits, allfällige Mängel und Verbesserungsoptionen für die Organisation künftiger Veranstaltungen zusammenzufassen

The Role of p38a in stress erythropoiesis

Während der Erythropoiese von Säugetieren entwickeln sich hämatopoetische Stammzellen zu Erythroblasten, welche zusammen mit Makrophagen Blutinseln bilden und in der terminalen Differenzierung zu Erythrozyten schließlich den Nukleus ausstoßen. In der Stresserythropoiese, wie zum Beispiel während fötaler Entwicklung oder Anämie, nimmt die Produktion von Erythrozyten dramatisch zu. Es gibt ein stetig wachsendes Wissen über hormonelle Regulierung von Basal- und Stresserythropoiese und neue Einblicke in molekulare Netzwerke, welche essentiell für die Erythroblastendifferenzierung sind. Die molekularen Netzwerke der Erythroblastendifferenzierung, besonders in Stresssituationen, sind jedoch noch immer größtenteils unbekannt. Zuvor wurde gezeigt, dass Mäuse denen p38a im embryonalen Gewebe oder in hämatopoetischen Zellen fehlt, eine erhöhte Anzahl an nuklerierten Erythrozyten in der fötalen Leber und im peripheren Blut von Neugeborenen aufweisen. Darüberhinaus wird die Anzahl von nukleierten Erythrozyten in der Milz und dem peripheren Blut von Mäusen mit spezifischer Deletion von p38a in hämatopoetischen Zellen durch Phenylhydrazin induzierte Anämie erhöht. Zusätzlich wurde gezeigt, dass p38a-defiziente Erythroblasten während der in vitro Differenzierung fast komplett versagen zu enukleieren. Dies legt nahe, dass die Funktion von p38a in der Enukleierung zellautonom ist. In der hier vorliegenden Arbeit beschreibe ich meine Versuche Substrate von p38a zu bestimmen, welche essentiell für die Enukleirung von Erythroblasten sind. Weiteres zeige ich, daß die Funktion von p38a in der Enukleierung von Erthroblasten zellautonom ist und daß p38a eine Schlüsselfunktion in der erythroiden Differenzierung in Stresssituationen hat. Der Phänotyp der gestörten Enukleierung wird in Mäusen, denen p38a speziell in der erythroiden Linie fehlt, aber nicht in Mäusen mit spezifischer Deletion von p38a in Makrophagen rekapituliert. Zusätzlich haben p38a-defiziente Erythroblasten abweichende Expression von Genen, welche mit der erythroiden Differenzierung in Zusammenhang stehen, wie zum Beispiel Gata1 und diverse Hämoglobinisoformen. Der Phänotyp der gestörten Enukleierung ähnelt dem von Rb-defizienten Erythroblasten. Wichtig ist, daß p38a-defiziente Erythroblasten ein reduziertes Maß an negativen Regulatoren von Rb, und zwar p53, p21 und p27, und ein erhöhtes Maß an hyperphosphorylierten Rb aufweisen. Ebenso hat eine Analyse des Genexpressionsprofils ergeben, dass Zielgene von E2F-1, welcher von Rb repremiert wird, hochreguliert sind; zum Beispiel Cyclin E, Cdk2 und Pcna. Diese Daten zeigen, daß die Rolle von p38a in der Enuklerierung von Erythroblasten während der Stresserythropoiese zellautonom ist und p38a essentiell ist für die Regulierung von differenzierungsbezogener Genexpression. Darüberhinaus vermute ich, daß p38a seine Funktionen durch die Aktivierung des Rb Singalweges ausübt.During mammalian erythropoiesis, hematopoietic stem cells develop into erythroblasts, which form blood islands with macrophages and further extrude the nucleus during terminal differentiation into erythrocytes. The production of erythrocytes dramatically increases in stress erythropoiesis, such as during fetal development or anemia. There is increasing knowledge about hormonal signaling regulating steady state and stress erythropoiesis and new insights into molecular pathways essential for erythroblast differentiation. However, the molecular pathways involved in erythroblast differentiation, especially under stress conditions are still largely unknown. It was shown previously that mice lacking p38α in embryonic tissues or specifically in hematopoietic cells show increased numbers of nucleated erythrocytes in the fetal liver and newborn peripheral blood. Moreover, phenylhydrazine (PHZ)-induced anemia increases the number of nucleated erythrocytes in the spleen and peripheral blood of mice with hematopoietic deletion of p38α. Additionally, erythroblasts lacking p38a almost completely fail to enucleate during in vitro differentiation, suggesting that the function of p38a in enucleation is cell-autonomous. Here I will describe my attempts to identify substrates of p38a, which are essential for erythroblast enucleation. Furthermore, I will demonstrate that the function of p38a in enucleation of erythroblasts is cell-autonomous and that p38a is a key mediator of erythroid differentiation under stress conditions. The impaired enucleation phenotype is recapitulated in mice lacking p38a specifically in the erythroid lineage, but not in mice with macrophage-specific deletion of p38a. Moreover, p38α-deficient erythroblasts show aberrant expression of genes related to erythroid differentiation, such as Gata1 and different hemoglobin isoforms. The impaired enucleation phenotype of p38α-deficient erythroblasts is similar to that of erythroblasts lacking Rb. Importantly, negative regulators of Rb, such as p53, p21 and p27 were down-regulated and the level of hyperphosphorylated Rb is increased in p38a-deficient erythroblasts. Gene expression profiling analysis also reveals that target genes of E2F-1, which is repressed by Rb, are up-regulated, such as Cyclin E, Cdk2 and Pcna. These data indicate that p38a is essential for enucleation of erythroblasts in a cell-autonomous manner and for the regulation of differentiation-related gene expression under stress erythropoiesis, likely through activating the Rb pathway

PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis

New therapeutic approaches to counter the increasing prevalence of obesity and type 2 diabetes mellitus are in high demand. Deregulation of the phosphoinositide-3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT), mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) pathways, which are essential for glucose homeostasis, often results in obesity and diabetes. Thus, these pathways should be attractive therapeutic targets. However, with the exception of metformin, which is considered to function mainly by activating AMPK, no treatment for the metabolic syndrome based on targeting protein kinases has yet been developed. By contrast, therapies based on the inhibition of the PI3K/AKT and MAPK pathways are already successful in the treatment of diverse cancer types and inflammatory diseases. This contradiction prompted us to review the signal transduction mechanisms of PI3K/AKT, MAPK and AMPK and their roles in glucose homeostasis, and we also discuss current clinical implication

Going back to basics in design science: from the information technology artifact to the information systems artifact

The concept of the “IT artifact” plays a central role in the information systems research community’s discourse on design science. We pose the alternative concept of the “IS artifact,” unpacking what has been called the IT artifact into a separate “information artifact,” “technology artifact,” and “social artifact.” Technology artifacts (such as hardware and software), information artifacts (such as a message), and social artifacts (such as a charitable act) are different kinds of artifacts that together interact in order to form the IS artifact. We illustrate the knowledge value of the IS artifact concept with material from three cases. The result is to restore the idea that the study of design in information systems needs to attend to the design of the entire IS artifact, not just the IT artifact. This result encourages an expansion in the use of design science research methodology to study broader kinds of artifacts

Twelve-month psychosis-predictive value of the ultra-high risk criteria in children and adolescents

Objective The validity of current ultra-high risk (UHR) criteria is under-examined in help-seeking minors, particularly, in children below the age of 12 years. Thus, the present study investigated predictors of one-year outcome in children and adolescents (CAD) with UHR status. Method Thirty-five children and adolescents (age 9–17 years) meeting UHR criteria according to the Structured Interview for Psychosis-Risk Syndromes were followed-up for 12 months. Regression analyses were employed to detect baseline predictors of conversion to psychosis and of outcome of non-converters (remission and persistence of UHR versus conversion). Results At one-year follow-up, 20% of patients had developed schizophrenia, 25.7% had remitted from their UHR status that, consequently, had persisted in 54.3%. No patient had fully remitted from mental disorders, even if UHR status was not maintained. Conversion was best predicted by any transient psychotic symptom and a disorganized communication score. No prediction model for outcome beyond conversion was identified. Conclusions Our findings provide the first evidence for the predictive utility of UHR criteria in CAD in terms of brief intermittent psychotic symptoms (BIPS) when accompanied by signs of cognitive impairment, i.e. disorganized communication. However, because attenuated psychotic symptoms (APS) related to thought content and perception were indicative of non-conversion at 1-year follow-up, their use in early detection of psychosis in CAD needs further study. Overall, the need for more in-depth studies into developmental peculiarities in the early detection and treatment of psychoses with an onset of illness in childhood and early adolescence was further highlighted

A Multi-Institutional Analysis of Prostate Cancer Patients With or Without 68Ga-PSMA PET/CT Prior to Salvage Radiotherapy of the Prostatic Fossa

Introduction: 68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only. Material and Methods: This retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters. Results: Median follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= <0.001), Gleason score (GS ≤ 7 vs. GS8-10; p=0.003), pre-sRT PSA (<0.5 vs. ≥0.5ng/ml; p<0.001) and sRT dose (<70 vs. ≥70Gy; p<0.001) were the only factors significantly associated with improved BRFS. This was not seen for the use of 68Ga-PSMA PET/CT prior to sRT (p=0.789). Matched-pair analysis consisted of 95 pairs of PCa patients with or without PET/CT and no significant difference in BRFS based on the use of PET/CT was evident (p=0.884). Conclusion: This analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best “diagnostic window” for 68Ga-PSMA PET/CT

Outcome of individuals “not at risk of psychosis” and prognostic accuracy of the Basler Screening Instrument for Psychosis (BSIP)

We aimed to determine the prognostic accuracy of the Basel Screening Instrument for Psychosis (BSIP) in terms of specificity, sensitivity, positive and negative predictive value by following up individuals that were initially not considered to be at increased risk of psychosis based on the BSIP. Moreover, clinical characteristics of these individuals were examined given the relative lack of such information in the literature.; As part of the "Früherkennung von Psychosen" (FePsy) study, 87 individuals were screened with the BSIP. Of these, 64 were classified at baseline as being in an at-risk mental state (ARMS+) for psychosis using the BSIP and followed up at regular time intervals for at least 2 years to determine a putative transition to psychosis. Twenty-three individuals were classified at baseline as not being in an at-risk mental state (ARMS-) using the BSIP and re-assessed after 4 years. Sensitivity, specificity, positive and negative predictive value of the BSIP were computed. Clinical characteristics of the ARMS- group were analysed descriptively.; During the follow-up period, none of the ARMS- individuals, but 21 of ARMS+ had developed psychosis. Sensitivity of the BSIP was 1.0, specificity was 0.35. The majority of ARMS- individuals showed depressive disorders or anxiety disorders and varying levels of functioning.; The BSIP has good prognostic accuracy for detecting the prodromal phase of psychosis with an excellent sensitivity and a specificity similar to other risk instruments and the advantage of a relatively short duration. Depressive and anxiety symptoms commonly develop in ARMS- individuals

Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8+ Dendritic Cells

Apoptotic cell death of Dendritic cells (DCs) is critical for immune homeostasis. Although intrinsic mechanisms controlling DC death have not been fully characterized up to now, experimentally enforced inhibition of DC-death causes various autoimmune diseases in model systems. We have generated mice deficient for Protein Phosphatase with EF-Hands 2 (Ppef2), which is selectively expressed in CD8+ DCs, but not in other related DC subtypes such as tissue CD103+ DCs. Ppef2 is down-regulated rapidly upon maturation of DCs by toll-like receptor stimuli, but not upon triggering of CD40. Ppef2-deficient CD8+ DCs accumulate the pro-apoptotic Bcl-2-like protein 11 (Bim) and show increased apoptosis and reduced competitve repopulation capacities. Furthermore, Ppef2−/− CD8+ DCs have strongly diminished antigen presentation capacities in vivo, as CD8+ T cells primed by Ppef2−/− CD8+ DCs undergo reduced expansion. In conclusion, our data suggests that Ppef2 is crucial to support survival of immature CD8+ DCs, while Ppef2 down-regulation during DC-maturation limits T cell responses

Attosecond state-resolved carrier motion in quantum materials probed by soft x-ray XANES

Recent developments in attosecond technology led to table-top x-ray spectroscopy in the soft x-ray range, thus uniting the element- and state-specificity of core-level x-ray absorption spectroscopy with the time resolution to follow electronic dynamics in real-time. We describe recent work in attosecond technology and investigations into materials such as Si, SiO2, GaN, Al2O3, Ti, and TiO2, enabled by the convergence of these two capabilities. We showcase the state-of-the-art on isolated attosecond soft x-ray pulses for x-ray absorption near-edge spectroscopy to observe the 3d-state dynamics of the semi-metal TiS2 with attosecond resolution at the Ti L-edge (460 eV). We describe how the element- and state-specificity at the transition metal L-edge of the quantum material allows us to unambiguously identify how and where the optical field influences charge carriers. This precision elucidates that the Ti:3d conduction band states are efficiently photo-doped to a density of 1.9 x 1021 cm 3. The light-field induces coherent motion of intra-band carriers across 38% of the first Brillouin zone. Lastly, we describe the prospects with such unambiguous real-time observation of carrier dynamics in specific bonding or anti-bonding states and speculate that such capability will bring unprecedented opportunities toward an engineered approach for designer materials with pre-defined properties and efficiency. Examples are composites of semiconductors and insulators like Si, Ge, SiO2, GaN, BN, and quantum materials like graphene, transition metal dichalcogens, or high-Tc superconductors like NbN or LaBaCuO. Exiting are prospects to scrutinize canonical questions in multi-body physics, such as whether the electrons or lattice trigger phase transitions