Preparations for the Spin-Filtering Experiments at COSY/Jülich

Polarized antiprotons allow unique access to a number of fundamental physics observables. One example is the transversity distribution which is the last missing piece to complete the knowledge of the nucleon partonic structure at leading twist in the QCD-based parton model. The transversity is directly measurable via Drell-Yan production in double polarized antiproton-proton collisions. This and a multitude of other findings, which are accessible via ppbar scattering experiments, led the Polarized Antiproton eXperiments (PAX) collaboration to propose such investigations at the High Energy Storage Ring (HESR) of the Facility for Antiproton and Ion Research (FAIR). Already the production of intense polarized antiproton beams is still an unsolved problem. The PAX anticipated time plan to experiments at HESR mainly consists of three phases. PAX@COSY, as first step, is aiming for an optimization of the polarization build-up in proton beams at the Cooler Synchrotron COSY Jülich. The spin-filtering method, where the originally unpolarized beam becomes polarized due to the spin-dependent part of the hadronic interaction with a Polarized Internal Target (PIT), will be applied. The feasibility of this method was shown to work for protons by the Filter Experiment (FILTEX) at the Test Storage Ring (TSR) in Heidelberg. PAX@CERN will determine the spin-dependent cross sections in ppbar scattering at beam energies of 50 - 450 MeV using the antiproton beam of the Antiproton Decelerator (AD) at CERN. PAX@FAIR constitutes the third phase where the antiproton beam will be polarized in a dedicated Antiproton Polarizer Ring (APR) at the HESR, converted into a double-polarized proton-antiproton collider, in order to study the transverse spin structure of nucleons. The present thesis discusses the preparations for the spin-filtering experiments at COSY. This includes the successful installation and commissioning of the experimental equipment such as a low-β section, a dedicated pumping system, an Atomic Beam Source (ABS), a Breit- Rabi Polarimeter (BRP), and a target chamber with an openable storage cell. In addition, the accomplished investigations of the beam lifetime dependencies, resulting in significantly improved beam lifetimes, and relevant machine parameters, e.g., the machine acceptance, are described. The results are utilized to calculate the expected polarization build-up in a cooled and stored proton beam with a kinetic energy of 49.3MeV using a target with an areal density of 5*10¹³ atoms/cm². Simulations of the determination of the beam polarization using elastic proton-deuteron scattering and a polarimeter, that consists of silicon micro-strip detectors, allows one to estimate the achievable precision of the measurement of the spin-dependent total hadronic cross section. The presented results constitute the basis of a beam time request for transverse spin-filtering to the COSY Program Advisory Committee (PAC), which was approved in spring 2011

Polarization of a stored beam by spin filtering

In 2011 the PAX Collaboration has performed a successful spin-filtering test using protons at Tp = 49.3 MeV at the COSY ring, which confirms that spin filtering is a viable method to polarize a stored beam and that the present interpretation of the mechanism in terms of the proton-proton interaction is correct. The equipment and the procedures to produce stored polarized beams was successfully commissioned and are established. The outcome of the experiment is of utmost importance in view of the possible application of the method to polarize a beam of stored antiprotons

Lymphknotenmetastasierung und Therapieresultate des muskelinvasiven Urothelkarzinoms der Harnblase

Im Rahmen der Dissertation wurde eine retrospektive Analyse von 196 Patienten mit einem Urothelkarzinom der Harnblase nach radikaler Zystektomie und pelviner Lymphadenektomie durchgeführt, um Prognosefaktoren für das Überleben zu identifizieren. Die Ergebnisse wurden bei einer mittleren Nachbeobachtungszeit von 53,5 Monaten evaluiert. Bei 53 Patienten wurden Lymphknotenmetastasen histologisch gesichert, das mittlere Alter dieser Gruppe betrug 66,1 Jahre. Im Mittel wurden beim Gesamtkollektiv 16,5 (1 bis 52) Lymphknoten entfernt, wobei insgesamt 35 Patienten eine ausgedehnte Lymphadenektomie erhielten. Die Daten der lymphknotenpositiven Fälle wurden weitergehend untersucht, für einzelne bekannte sowie neue Faktoren erfolgte eine statistische Analyse hinsichtlich der Überlebensfunktion. Ein signifikanter Einfluss auf das Überleben wurde für die Faktoren „Grösse der befallenen Lymphknoten“ (p=0,026), „pT-Klassifikation“ (p=0,002) sowie „Größe des Blasentumors“ (p=0,005), ein hochsignifikanter Einfluss für „Lymphknotenkapselperforation“ (p=0,0002) und „Lymphangiosis carcinomatosa“ (p=0,0028) nachgewiesen. In der multivariaten Analyse wurden die Parameter „Lymphknotenkapselperforation“ (p=0,010) und „Größe des Blasentumors“ (p=0,061) als signifikant identifiziert. Patienten mit extendierter Lymphadenektomie und Lymphknotenbefall überlebten im Mittel 66 Monate, ohne Ausdehnung des Dissektionsgebietes 41 Monate, ein signifikanter Einfluss wurde jedoch statistisch nicht nachgewiesen (p=0,246). Eine adjuvante Chemotherapie ergab keine signifikante Verbesserung des Überlebenszeitraums (p=0,215), wobei die Patienten aus der Gruppe mit Lymphknotenbefall und Chemotherapie im Mittel mit 54 Monaten länger überlebten, als diejenigen ohne adjuvante Behandlung mit 28 Monaten. Neben bekannten histopathologischen Parametern wurde für die extranodale Tumorausbreitung ein hochsignifikanter Einfluss auf das Überleben ermittelt. Mit diesem neuen prognostischen Faktor konnte ein Marker von immenser klinischer Bedeutung identifiziert werden. Dieser Parameter, sowie möglicherweise hinsichtlich Chemoresistenz auch molekulare Marker, könnte in Zukunft die Patientenselektion bezüglich Radikalität der Operation und Wahl der adjuvanten Therapie beeinflussen. Die radikale Zystektomie sollte mit einer beidseitigen pelvinen Lymphadenektomie erfolgen. Patienten mit organbegrenztem Tumor und Lymphknotenmikrometastasen können von einer extendierten Lymphadenektomie profitieren. Es resultiert eine Verbesserung des progressionsfreien Überlebens, jedoch nicht des Gesamtüberlebens. Begonnene prospektive Studien müssen den potenziell kurativen therapeutischen Stellenwert einer extendierten Lymphadenektomie klären und einen Standard für die Ausdehnung der pelvinen Lymphknotenentfernung definieren

О повышении мотивации подготовки иностранных граждан на кафедре факультетской терапии

ОБУЧЕНИЕ ИНОСТРАННЫХ ГРАЖДА

Classification of Chemical Compounds to Support Complex Queries in a Pathway Database

Data quality in biological databases has become a topic of great discussion. To provide high quality data and to deal with the vast amount of biochemical data, annotators and curators need to be supported by software that carries out part of their work in an (semi-) automatic manner. The detection of errors and inconsistencies is a part that requires the knowledge of domain experts, thus in most cases it is done manually, making it very expensive and time-consuming. This paper presents two tools to partially support the curation of data on biochemical pathways. The tool enables the automatic classification of chemical compounds based on their respective SMILES strings. Such classification allows the querying and visualization of biochemical reactions at different levels of abstraction, according to the level of detail at which the reaction participants are described. Chemical compounds can be classified in a flexible manner based on different criteria. The support of the process of data curation is provided by facilitating the detection of compounds that are identified as different but that are actually the same. This is also used to identify similar reactions and, in turn, pathways

Model Driven Machine Improvement of COSY Based on ORM Data

The COoler SYnchrotron in Jülich accelerates and stores unpolarized and polarized proton or deuteron beams in the momentum range between 0.3 GeV/c and 3.65 GeV/c [*,**]. This, in combination with its diverse capabilities of phase space cooling and the flexibility of the lattice with respect to ion-optical settings makes COSY an ideal test facility for accelerator technology development. High demands on beam control and beam based measurements have to be fulfilled for future experiments such as the proposed precursor experiment for a direct measurement of the electric dipole moment of the deuteron (see [***] and references within). The analysis of measured orbit response matrices (ORM), which com- prise the focussing structure of the ring, allows for a better understand- ing of machine imperfections such as gradient errors and misalignments of quadrupole magnets. This contribution presents the development of a MAD-X based LOCO (Linear Optics from Closed Orbits) algorithm [****] in a C++ program aiming to calibrate and correct linear optics as well as improving beam control at COSY

Interobserver agreement in interpretation of chest radiographs for pediatric community acquired pneumonia: Findings of the pedCAPNETZ-cohort.

Although chest radiograph (CXR) is commonly used in diagnosing pediatric community acquired pneumonia (pCAP), limited data on interobserver agreement among radiologists exist. PedCAPNETZ is a prospective, observational, and multicenter study on pCAP. N = 233 CXR from patients with clinical diagnosis of pCAP were retrieved and n = 12 CXR without pathological findings were added. All CXR were interpreted by a radiologist at the site of recruitment and by two external, blinded pediatric radiologists. To evaluate interobserver agreement, the reporting of presence or absence of pCAP in CXR was analyzed, and prevalence and bias-adjusted kappa (PABAK) statistical testing was applied. Overall, n = 190 (82%) of CXR were confirmed as pCAP by two external pediatric radiologists. Compared with patients with pCAP negative CXR, patients with CXR-confirmed pCAP displayed higher C-reactive protein levels and a longer duration of symptoms before enrollment (p < .007). Further parameters, that is, age, respiratory rate, and oxygen saturation showed no significant difference. The interobserver agreement between the onsite radiologists and each of the two independent pediatric radiologists for the presence of pCAP was poor to fair (69%; PABAK = 0.39% and 76%; PABAK = 0.53, respectively). The concordance between the external radiologists was fair (81%; PABAK = 0.62). With regard to typical CXR findings for pCAP, chance corrected interrater agreement was highest for pleural effusions, infiltrates, and consolidations and lowest for interstitial patterns and peribronchial thickening. Our data show a poor interobserver agreement in the CXR-based diagnosis of pCAP and emphasized the need for harmonized interpretation standards

Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis.

Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types. Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A. Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected. However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression