Untersuchung von Folatrezeptor alpha und Thymidylatsynthase im mesenchymalen Gewebe von Weichteilsarkomen

Im Mittelpunkt dieser Arbeit stand die Frage, ob mesenchymale Tumorzellen die Proteine FRα und TS exprimieren. Hierfür wurden Weichteilsarkombiopsien durch immunhistochemische Färbemethoden gescreent. Beide Proteine sind in essenzielle zelluläre Stoffwechselwege eingebunden und stellen bereits wichtige Biomarker in der Diagnostik und Behandlung epithelialer Tumoren dar. Bislang wurden sie jedoch nicht im mesenchymalen Gewebe von Weichteilsarkomen erforscht. Die Experimente zeigten keine Expression von FRα in der untersuchten Studienpopulation. Dagegen konnte eine Expression von TS bestätigt werden. Die Mehrzahl der Proben zeigte eine geringe TS-Expression in der semiquantitativen Analyse, was im Hinblick auf aktuelle Forschungsarbeiten mit einem besseren Ansprechen auf gegen TS gerichtete Medikamente verbunden sein könnte und einen möglichen Therapieansatz darstellt. Das Liposarkom wies im Vergleich den größten Anteil niedriggradiger Proben auf. In der statistischen Auswertung wurden keine signifikanten Zusammenhänge zwischen den demographischen und klinischen Charakteristika der Patienten und der Ausprägung der TS-Expression festgestellt. Dies könnte in der geringen Fallzahl begründet liegen. Darüberhinaus gelang es in der retrospektiven Analyse von mit Pemetrexed behandelten Studienteilnehmern nicht, die Wirkung des Medikamentes in der Auswertung isoliert zu betrachten. Eine Liposarkomprobe fiel durch eine auffallend lange Krankheitsstabilisierung unter der Behandlung mit dem Multi-Enzym-Inhibitor auf. Dabei wies das Gewebe eine ausgeprägte Nekrose auf. Eine allgemeine Aussage lässt sich daraus nicht ableiten. Im Rahmen der vorliegenden Dissertation gelang der Ausschluss einer FRα-Expression und der qualitative Nachweis von TS in mesenchymalen Tumorzellen. Mögliche Korrelationen zwischen Tumorsubtyp, klinischen und demographischen Charakteristika und dem Ansprechen auf eine gegen TS-gerichtete Therapie sind zum Zeitpunkt des Verfassens dieser Arbeit als Hypothesen zu betrachten, die für eine signifikante Bewertung in größer angelegten Studien validiert werden müssten

Wrapped Branes and Supersymmetry

Configurations of two or more branes wrapping different homology cycles of space-time are considered and the amount of supersymmetry preserved is analysed, generalising the analysis of multiple branes in flat space. For K3 compactifications, these give the Type II or M theory origin of certain supersymmetric four-dimensional heterotic string solutions that fit into spin-3/2 multiplets and which become massless at certain points in moduli space. The interpretation of these BPS states and the possibility of supersymmetry enhancement are discussed.Comment: 18 pages, Latex with Revtex, minor corrections and references added, version to appear in Nuclear Physics

Classification of Supersymmetric Flux Vacua in M Theory

We present a comprehensive classification of supersymmetric vacua of M-theory compactification on seven-dimensional manifolds with general four-form fluxes. We analyze the cases where the resulting four-dimensional vacua have N = 1,2,3,4 supersymmetry and the internal space allows for SU(2), SU(3) or G_2 structures. In particular, we find for N = 2 supersymmetry, that the external space-time is Minkowski and the base manifold of the internal space is conformally K\"ahler for SU(2) structures, while for SU(3) structures the internal space has to be Einstein-Sasaki and no internal fluxes are allowed. Moreover, we provide a new vacuum with N = 1 supersymmetry and SU(3) structure, where all fluxes are non-zero and the first order differential equations are solved.Comment: 50 pages, clarification of the spinor ansatz added, references added, typos correcte

Development and validation of a reference data set for assigning Staphylococcus species based on next-generation sequencing of the 16S-23S rRNA region

Many members of the Staphylococcus genus are clinically relevant opportunistic pathogens that warrant accurate and rapid identification for targeted therapy. The aim of this study was to develop a careful assignment scheme for staphylococcal species based on next-generation sequencing (NGS) of the 16S-23S rRNA region. All reference staphylococcal strains were identified at the species level using Sanger sequencing of the 16S rRNA, sodA, tuf, and rpoB genes and NGS of the 16S-23S rRNA region. To broaden the database, an additional 100 staphylococcal strains, including 29 species, were identified by routine diagnostic methods, 16S rRNA Sanger sequencing and NGS of the 16S-23S rRNA region. The results enabled development of reference sequences encompassing the 16S-23S rRNA region for 50 species (including one newly proposed species) and 6 subspecies of the Staphylococcus genus. This study showed sodA and rpoB targets were the most discriminative but NGS of the 16S-23S rRNA region was more discriminative than tuf gene sequencing and much more discriminative than 16S rRNA gene sequencing. Almost all Staphylococcus species could be distinguished when the max score was 99.0% or higher and the sequence similarity between the best and second best species was equal to or >0.2% (min. 9 nucleotides). This study allowed development of reference sequences for 21 staphylococcal species and enrichment for 29 species for which sequences were publicly available. We confirmed the usefulness of NGS of the 16S-23S rRNA region by identifying the whole species content in 45 clinical samples and comparing the results to those obtained using routine diagnostic methods. Based on the developed reference database, all staphylococcal species can be reliably detected based on the 16S-23S rRNA sequences in samples composed of both single species and more complex polymicrobial communities. This study will be useful for introduction of a novel diagnostic tool, which undoubtedly is an improvement for reliable species identification in polymicrobial samples. The introduction of this new method is hindered by a lack of reference sequences for the 16S-23S rRNA region for many bacterial species. The results will allow identification of all Staphylococcus species, which are clinically relevant pathogens

Conformal Symmetry for General Black Holes

We show that the warp factor of a generic asymptotically flat black hole in five dimensions can be adjusted such that a conformal symmetry emerges. The construction preserves all near horizon properties of the black holes, such as the thermodynamic potentials and the entropy. We interpret the geometry with modified asymptotic behavior as the "bare" black hole, with the ambient flat space removed. Our warp factor subtraction generalizes hidden conformal symmetry and applies whether or not rotation is significant. We also find a relation to standard AdS/CFT correspondence by embedding the black holes in six dimensions. The asymptotic conformal symmetry guarantees a dual CFT description of the general rotating black holes.Comment: 26 page

General N = 1 Supersymmetric Fluxes in Massive Type IIA String Theory

We study conditions on general fluxes of massive Type IIA supergravity that lead to four-dimensional backgrounds with N = 1 supersymmetry. We derive these conditions in the case of SU(3)- as well as SU(2)-structures. SU(3)-structures imply that the internal space is constrained to be a nearly K\"ahler manifold with all the turned on fluxes, and the negative cosmological constant proportional to the mass parameter, and the dilaton fixed by the quantized ratio of the three-form and four-form fluxes. We further discuss the implications of such flux vacua with added intersecting D6-branes, leading to the chiral non-Abelian gauge sectors (without orientifold projections). Examples that break SU(3)-structures to SU(2)-ones allow for the internal space conformally flat (up to orbifold and orientifold projections), for which we give an explicit example. These results provide a starting point for further study of the four-dimensional (chiral) N = 1 supersymmetric solutions of massive Type IIA supergravity with D-branes and fluxes, compactified on orientifolds.Comment: 37 pages; changed the resulting gauge group on intersecting 6-branes, corrected the explicit example (with conformal flat internal space) as well as minor modifications and add a re

Concurrent validity and reliability of the Community Balance and Mobility scale in young-older adults

Background: With the growing number of young-older adults (baby-boomers), there is an increasing demand for assessment tools specific for this population, which are able to detect subtle balance and mobility deficits. Various balance and mobility tests already exist, but suffer from ceiling effects in higher functioning older adults. A reliable and valid challenging balance and mobility test is critical to determine a young-older adult’s balance and mobility performance and to timely initiate preventive interventions. The aim was to evaluate the concurrent validity, inter- and intrarater reliability, internal consistency, and ceiling effects of a challenging balance and mobility scale, the Community Balance and Mobility Scale (CBM), in young-older adults aged 60 to 70 years. Methods: Fifty-one participants aged 66.4 ± 2.7 years (range, 60–70 years) were assessed with the CBM. The Fullerton Advanced Balance scale (FAB), 3-Meter Tandem Walk (3MTW), 8-level balance scale, Timed-Up-and-Go (TUG), and 7-m habitual gait speed were used to estimate concurrent validity, examined by Spearman correlation coefficient (ρ). Inter- and intrarater reliability were calculated as Intra-class-correlations (ICC), and internal consistency by Cronbach alpha and item-total correlations (ρ). Ceiling effects were determined by obtaining the percentage of participants reaching the highest possible score. Results: The CBM significantly correlated with the FAB (ρ = 0.75; p < .001), 3MTW errors (ρ = − 0.61; p < .001), 3MTW time (ρ = − 0.35; p = .05), the 8-level balance scale (ρ = 0.35; p < .05), the TUG (ρ = − 0.42; p < .01), and 7-m habitual gait speed (ρ = 0.46, p < .001). Inter- (ICC2,k = 0.97), intrarater reliability (ICC3,k = 1.00) were excellent, and internal consistency (α = 0.88; ρ = 0.28–0.81) was good to satisfactory. The CBM did not show ceiling effects in contrast to other scales. Conclusions: Concurrent validity of the CBM was good when compared to the FAB and moderate to good when compared to other measures of balance and mobility. Based on this study, the CBM can be recommended to measure balance and mobility performance in the specific population of young-older adults. Trial registration Trial number: ISRCTN37750605 . (Registered on 21/04/2016)

Spacetime Instanton Corrections in 4D String Vacua - The Seesaw Mechanism for D-Brane Models

We systematically investigate instanton corrections from wrapped Euclidean D-branes to the matter field superpotential of various classes of N=1 supersymmetric D-brane models in four dimensions. Both gauge invariance and the counting of fermionic zero modes provide strong constraints on the allowed non-perturbative superpotential couplings. We outline how the complete instanton computation boils down to the computation of open string disc diagrams for boundary changing operators multiplied by a one-loop vacuum diagram. For concreteness we focus on E2-instanton effects in Type IIA vacua with intersecting D6-branes, however the same structure emerges for Type IIB and heterotic vacua. The instantons wrapping rigid cycles can potentially destabilise the vacuum or generate perturbatively absent matter couplings such as proton decay operators, mu-parameter or right-handed neutrino Majorana mass terms. The latter allow the realization of the seesaw mechanism for MSSM-like intersecting D-brane models.Comment: 40 pages, 3 tables, 7 figures; v2: typos corrected, references added; v3: minor sign adjustments, some comments added; v4: published versio