Moduli spaces of irregular singular connections

In the geometric version of the Langlands correspondence, irregular singular point connections play the role of Galois representations with wild ramification. In this paper, we develop a geometric theory of fundamental strata to study irregular singular connections on the projective line. Fundamental strata were originally used to classify cuspidal representations of the general linear group over a local field. In the geometric setting, fundamental strata play the role of the leading term of a connection. We introduce the concept of a regular stratum, which allows us to generalize the condition that a connection has regular semisimple leading term to connections with non-integer slope. Finally, we construct a symplectic moduli space of meromorphic connections on the projective line that contain a regular stratum at each singular point.Comment: 53 pages. A new section (Section 4.4) has been added making precise the relationship between formal types and isomorphism classes of formal connections. Significant revisions and additions have also been made to Sections 3.1 and 4.3 and the introduction to Section

Generalized serre conditions and perverse coherent sheaves

In algebraic geometry, one often encounters the following problem: given a scheme X, find a proper birational morphism Y → X where the geometry of Y is nicer than that of X. One version of this problem, first studied by Faltings, requires Y to be Cohen-Macaulay; in this case Y → X is called a Macaulayfication of X. In another variant, one requires Y to satisfy the Serre condition S r. In this paper, the authors introduce generalized Serre conditions-these are local cohomology conditions which include S r and the Cohen-Macaulay condition as special cases. To any generalized Serre condition Sρ, there exists an associated perverse t-structure on the derived category of coherent sheaves on a suitable scheme X. Under appropriate hypotheses, the authors characterize those schemes for which a canonical finite Sρ-ification exists in terms of the intermediate extension functor for the associated perversity. Similar results, including a universal property, are obtained for a more general morphism extension problem called Sρ-extension. © 2013 Elsevier Inc

A theory of minimal K-types for flat G-bundles

The theory of minimal K-types for p-adic reductive groups was developed in part to classify irreducible admissible representations with wild ramification. An important observation was that minimal K-types associated to such representations correspond to fundamental strata. These latter objects are triples (x, r, β), where x is a point in the Bruhat-Tits building of the reductive group G, r is a nonnegative real number, and β is a semistable functional on the degree r associated graded piece of the Moy-Prasad filtration corresponding to x. Recent work on the wild ramification case of the geometric Langlands conjectures suggests that fundamental strata also play a role in the geometric setting. In this paper, we develop a theory of minimal K-types for formal flat G-bundles. We show that any formal flat G-bundle contains a fundamental stratum; moreover, all such strata have the same rational depth. We thus obtain a new invariant of a flat G-bundle called the slope, generalizing the classical definition for flat vector bundles. The slope can also be realized as the minimum depth of a stratum contained in the flat Gbundle, and in the case of positive slope, all such minimal depth strata are fundamental. Finally, we show that a flat G-bundle is irregular singular if and only if it has positive slope

Entwicklung neuer Bildgebungsverfahren zur Diagnose von chronisch entzündlichen Erkrankungen im Tiermodell

Die Verhinderung von Pathogenesen und Entwicklung gezielter therapeutischer Behandlungsstrategien sind die Hauptziele der modernen Biomedizin. Daher ist es unabdingbar Zell- und Gewebefunktionen im naturgetreuen Kontext, den lebenden Organismus, beobachten zu können. Zu diesem Zweck werden Tiermodelle eingesetzt, die unter anderem verschiedene Aspekte chronisch entzündlicher Erkrankungen des Zentralnervensystems (ZNS) simulieren. Dabei ist der Zugang zum Cortex, Hirnstamm oder Rückenmark meist nur durch invasive und oft terminale Eingriffe möglich, wodurch wiederholte Aufnahmen in einem Individuum in verschiedenen Stadien der Erkrankung nicht möglich sind. Die Retina hingegen ist der einzige Bestandteil des ZNS, welcher durch optische Methoden nichtinvasiv abgebildet werden kann. Dabei können Veränderungen in der Retina auch Prozesse in anderen Regionen des ZNS widerspiegeln und somit indirekt charakterisiert werden. In diesem Sinne ist in dieser Arbeit eine neuartige Methode entwickelt worden, mit dessen Hilfe die Retina von lebenden Mäusen longitudinal untersucht werden kann. Sie basiert auf der Zwei-Photonen-Mikroskopie, wodurch zelluläre Infiltration und Interaktion in vivo beobachtet werden können. Erprobt wurde die neue Methode am Mausmodell der experimentellen autoimmunen Uveoretinitis (EAU), bei der autoreaktive T-Zellen die Blut-Retina-Schranke überwinden und eine Gewebeschädigung durch Rekrutierung von weiteren peripheren Leukozyten einleiten. Dabei stellte sich in der vorliegenden Arbeit heraus, dass der Prozess der Retinainfiltration von CD4 + T-Zellen und LysM + Phagozyten vom Sehnervkopf aus beginnt und sich radial zum äußeren Rand hin ausbreitet. Zudem konnte eine morphologische Veränderung und Ansammlung der CX3CR1 + Mikrogliazellen vor allem an beschädigten Blutgefäßen festgestellt werden. Des Weiteren konnten aktivierte und hochmotile CX3CR1 + Zellen im perivaskulären Raum beobachtet werden. Interessanterweise bewegt sich die Mehrheit dieser Zellen in Mäusen mit EAU in Richtung des Sehnervkopfs, im Gegensatz zu den Zellen in den gesunden Kontrollen. Funktionelle Calciummessungen in der Retina während der EAU zeigen, dass bis zu 28 Tage nach Immunisierung keine signifikant schädigende Erhöhung des intrazellulären Calciums in den Ganglienzellen eintritt. Dank der neu entwickelten Methode können nun immunrelevante Prozesse mit zellulärer Auflösung über den gesamten Krankheitsverlauf chronisch entzündlicher Erkrankungen evaluiert werden.Preventing pathogenesis and developing selective therapeutic strategies are the main goals in modern biomedicine. Therefore, it is absolutely necessary to probe cellular and tissue functions in the living organism. Animal models can be used to study different aspects of chronic inflammatory diseases taking place in the central nervous system (CNS). Imaging the brain stem, spinal cord or cortex needs invasive and often terminal surgery. Thus, longitudinal measurements in one and the same animal at several time points during the whole time course of disease are not possible. The retina is the only part of the CNS that can be imaged non-invasively by optical methods. Changes in the retina may reflect pathogenesis from other parts of the CNS as earlier studies have shown e.g. in patients with multiple sclerosis in which thinning of the retinal nerve fiber layer is one of the first symptoms. In the here presented work a new method has been developed to observe the retina from living mice longitudinally. The method is based on the two-photon-absorption, thereby near infrared radiation is used to excite fluorescent proteins or dyes. This allows imaging of cellular infiltration, migration and function of fluorescently labelled leukocytes in vivo. The new approach was tested in the animal model for experimental autoimmune uveoretinitis (EAU) where T cells overcome the blood-retinal-barrier to inflict retinal inflammation followed by recruitment of peripheral leukocytes that induce tissue damage. The process of CD4 + T cell infiltration starts from the optic nerve head towards the retinal periphery followed by LysM + phagocyte infiltration in a radial manner. The CX3CR1 + microglia show a change from a more probing state towards an activated phenotype and accumulate mainly around disrupted blood vessels. A small population of activated and highly motile CX3CR1 + cells could only be observed in the perivasculature. Interestingly, most of this motile cells are moving towards the optic nerve head in mice affected by EAU compared to healthy controls. Unexpectedly, functional calcium measurements during the course of EAU up to 28 days after immunisation showed no significant increase in intracellular calcium levels as an indicator for cellular apoptosis in the ganglion cell layer. The newly developed approach allows longitudinal retinal imaging of cellular infiltration, migration and function over time repeatedly over the whole course of chronic inflammatory diseases. This method is not only limited to ocular diseases but also can be used to observe indirectly pathogenic processes of the CNS

Cost-savings and potential cost-savings through the distribution of generic antiretroviral drugs within the statutory health insurance market of Germany between January 2017 and June 2019

Background: Recent patent losses for antiretroviral drugs (ARV) have led to the debate of cost-saving through the replacement of patented drugs with generic drugs. The split of recommended single-tablet regimens (STR) into their single substance partners is one of the considerations mentioned in said debate. Particularly, generic tenofovir disoproxil/emtricitabine (TDF/FTC) is expected to hold untapped cost-saving potential, which may curb increasing overall expenditures for combined antiretroviral therapy (cART) within the statutory health insurance (SHI) of Germany. Methods: Data of ARV reimbursed by the SHI were used to describe the trends of defined daily doses (DDD) as well as the revenue within the German ARV market. They were also used to determine the cost-savings of moving to generic drugs. The time period observed was between January 2017 and June 2019. The potential cost-savings were determined with following assumption in mind: the maximum possible use of generic ARV, including 1) the split of STR and replacing all substance partners with generic ones, and 2) replacing patented tenofovir alafenamide/emtricit- abine (TAF/FTC) with generic TDF/FTC. Results: Throughout the observation period, the DDD of generic ARV increased nearly five-fold while their revenue increased more than four-fold. Total cost-saving showed a sharp increase over the same period, with generic TDF/FTC accounting for a share of around 70%. The largest potential cost-saving could have been achieved through replacing patented TAF/FTC with generic TDF/FTC, peaking at nearly 10% of total revenue, but showing decreasing trends in general. Conclusion: The progressive distribution of generic ARV ensured increasing cost-savings, but consequently curbed the potential cost-savings. Unique price reductions of generic TDF/FTC have played a pivotal role for these effects. In any case, substituting with generic ARV should not fail to adhere to the treatment guidelines and continue to con- sider the medical requirements for the treatment.Peer Reviewe

Sport und Gesellschaft: ZIBALDONE. Zeitschrift für italienische Kultur der Gegenwart

apropos weist gern darauf hin: In ZIBALDONE Zeitschrift für italienische Kultur der Gegenwart erscheint im Juli 2019 ein ebenfalls interessantes und thematisch verwandtes Dossier (Sport und Gesellschaft). Das PDF bietet mit dem Inhaltsverzeichnis sowie dem Vorwort der Herausgeber (Thomas Bremer und Daniel Winkler) ein Vorgeschmack auf diese Nummer. ZIBALDONE ist ein Forum für kritische Debatten mit Streifzügen ins Kulinarische, Historische und Künstlerische. Eine Zeitschrift, die Heft für Heft überraschende Perspektiven wagt. Geschrieben von Schriftstellern, Journalisten, Wissenschaftlern, fotografiert, gezeichnet und illustriert für alle, die nie genug haben können von ITALIEN. Hier geht es zur Internetseite der Zeitschrift