Investigation of heavy petroleum-derived material with thermogravimetry coupled to high resolution Fourier transform ion cyclotron resonance mass spectrometry

Fourier transform ion cyclotron resonance mass spectrometry enables the attribution of sum for-mulae on the basis of the measured m/z ratio to single compounds in a complex mixture due to its high mass accuracy and mass resolution. The aim of this PhD thesis was the characterisation of high complex, petroleum-derived materials by combining high-resolution mass spectrometry and ther-mal analysis.Fourier Transformation Ionenzyklotronresonanz Massenspektrometrie ermöglicht durch ihre sehr hohe Massenauflösung und Massengenauigkeit das Zuweisen auf der Basis des gemessenen m/z-Verhältnisses von Summenformeln zu einzelnen Verbindungen in komplexen Mischungen. Das Ziel dieser Arbeit war es, durch die Kombination von hochauflösender Massenspektrometrie und thermischer Analyse, hoch komplexe erdölbasierte Probenmaterialien zu charakterisieren

C-reactive protein (CRP) recognizes uric acid crystals and recruits proteases C1 and MASP1

Gout is caused by crystallization of uric acid in the form of monosodium urate (MSU) crystals, which induce a sterile inflammatory response that is hardly distinguishable from microbe-induced inflammatory responses. It is unclear, if MSU crystals (like microbes) are recognized by specific pattern recognition receptors. To identify possible soluble pattern recognition molecules for MSU crystals, we purified MSU-binding proteins from human body fluids. We identified C-reactive protein (CRP) as a major MSU-binding protein. Binding of CRP was strong enough to specifically deplete CRP from human serum. We found that CRP was required for fixation of complement components C1q, C1r, C1s and MASP1. Thus, we have identified a pattern recognition molecule for MSU crystals that links to the activation of complement. Notably, CRP does not show an even binding to the complete surface of the crystals. It rather binds to edges or distinct faces of the crystals

Decreased demand for olfactory periglomerular cells impacts on neural precursor cell viability in the rostral migratory stream

The subventricular zone (SVZ) provides a constant supply of new neurons to the olfactory bulb (OB). Different studies have investigated the role of olfactory sensory input to neural precursor cell (NPC) turnover in the SVZ but it was not addressed if a reduced demand specifically for periglomerular neurons impacts on NPC-traits in the rostral migratory stream (RMS). We here report that membrane type-1 matrix metalloproteinase (MT1-MMP) deficient mice have reduced complexity of the nasal turbinates, decreased sensory innervation of the OB, reduced numbers of olfactory glomeruli and reduced OB-size without alterations in SVZ neurogenesis. Large parts of the RMS were fully preserved in MT1-MMP-deficient mice, but we detected an increase in cell death-levels and a decrease in SVZ-derived neuroblasts in the distal RMS, as compared to controls. BrdU-tracking experiments showed that homing of NPCs specifically to the glomerular layer was reduced in MT1-MMP-deficient mice in contrast to controls while numbers of tracked cells remained equal in other OB-layers throughout all experimental groups. Altogether, our data show the demand for olfactory interneurons in the glomerular layer modulates cell turnover in the RMS, but has no impact on subventricular neurogenesis

Targeting a cancer-specific LYPD3 glycoform for tumor therapy

Introduction: One of the most drastic changes in cancer is the altered glycosylation of proteins and lipids, giving rise to truncated O-glycans like the Thomsen Friedenreich (TF) or Thomsen nouvelle (Tn) antigen, which are almost absent on normal cells. Combined protein-carbohydrate epitopes comprising these specific glycans are ideal candidates for potent targeted therapies given their excellent tumor specificity and broad cancer expression.Methods and results: We have generated GT-002, a monoclonal antibody specifically targeting the epithelial glycoprotein LYPD3 only in the presence of a TF glycosylation. It does not cross-react with non-glycosylated LYPD3 or TF on other glycoproteins in ELISA and flow cytometry. GT-002 binds to various tumor cell lines and stains tumor tissues of different cancer indications including squamous cell carcinoma of the head and neck. The remarkable tumor specificity was confirmed in an immunohistochemistry study on a normal human tissue panel including several LYPD3-positive organs, where GT-002 elicited almost completely abolished normal tissue binding. Consequently, we observed markedly reduced binding of GT-002 to normal human tissues compared to Lupartumab, a conventional anti-LYPD3 antibody previously in clinical development as antibody-drug conjugate (BAY1129980). Neuraminidase treatment of healthy tissues, resulting in cleavage of sialic acid residues, re-established binding of GT-002 comparable to Lupartumab, showing that the GT-002 epitope is masked by sialic acid in normal cells.Discussion: We believe that GT-002 is a promising candidate for development of antibody-drug- and radio-conjugates as well as bispecific molecules and chimeric antigen receptor therapeutics and highlights the powerful potential of antibodies against combined protein-carbohydrate epitopes to reduce on-target/off-tumor cytotoxicity

Finanzmärkte, Unternehmungen, Informationen: Ergebnisse des Projektes im Wintersemester 2015/2016

Der vorliegende Beitrag der Wirtschaftswissenschaftlichen Schriften ist ein Sammelband, der die Beiträge der Studierenden des 2. Fachsemesters im Masterstudiengang General Management aus dem Wintersemester 2015/2016 umfasst. Die Einzelbeiträge wurden in einer zwei Monate dauernden Projektarbeit im Herbst 2015 erarbeitet und im Januar 2016 präsentiert. Der diesjährige Themenschwerpunkt lag auf dem Bereich "Banken", jedoch fanden auch andere Bereiche Eingang in das Spektrum der Arbeiten. Das Besondere dieser Ausarbeitungen liegt darin, dass sie in Form eines journalistischen Artikels aufgebaut sind und die Autoren die Aufgabe hatten, eine auch für Nichtfachleute geeignete Form der Darstellung zu finden. Besonderer Wert wurde auch auf einen gut lesbaren Schreibstil und die Vielfalt der Gestaltungsformen gelegt. Die Arbeiten liegen hier in der Originalversion vor und wurden nicht redigiert. Die Fakten wurden nach bestem Wissen ermittelt, jedoch besteht kein Anspruch auf Vollständigkeit

Nous:

Im Rahmen eines Seminars der Fakultät für Philosophie I an der Ruhr-Universität Bochum setzten sich Studierende im Sommersemester 2017 mit populärwissenschaftlichen Einführungen in die Philosophie auseinander - ein Jahr später nahmen sie selbst die Feder in die Hand. In dem Seminar „Philosophisches Schreiben“ trafen sich im Sommersemester 2018 wöchentlich bis zu 45 Nachwuchsphilosoph:innen, die den Raum bekamen, ihre eigenen philosophischen Texte einander vorzustellen. Nach dem Vorbild der Gruppe 47 wurden die Beiträge kritisch reflektiert und diskutiert, um adressatengerechte und kreative Geschichten, Gedichte oder Essays zu entwickeln, die Lust auf mehr Philosophie machen. In dieser Anthologie mit dem Namen „Nous. Philosophische Texte zum Schmunzeln und Staunen“ finden sich ausgewählte Beiträge wieder, die in den verschiedensten literarischen Formen philosophische Phänomene und Theorien aufbereiten. Philosophie wird somit nicht nur unterhaltsam und lebensnah vermittelt, sondern ist auch ohne Vorwissen leicht zugänglich und verständlich. Das Ziel dieses Werks ist es, die Philosophie in ihren verschiedensten Facetten aus dem sprichwörtlichen „Elfenbeinturm“ der Universität heraus, in das alltägliche Leben von Jedermann zu bringen. So richten sich die Beiträge an Philosophieinteressierte und -begeisterte, die neugierig auf die bunte Welt der Philosophie sind. Die Herausgeber:innen Natalie Berg (geboren 1990 in Leipzig) studierte Philosophie und Religionswissenschaft im 2-Fach-Master an der Ruhr-Universität Bochum. Sie gehört zum Team der Arbeitsstelle „Kulturwissenschaftliche Grundlagen“ der Fakultät für Kultur- und Sozialwissenschaften an der FernUniversität in Hagen, wo sie Studierende bei ihren wissenschaftlichen Schreib- und Arbeitsprozessen begleitet. Ferner arbeitet sie an ihrer Promotion im Bereich Religionsphilosophie. Lisa Freund (geboren 1991 in Herne) studierte Philosophie und Geschichte auf Lehramt und ist nach Beendigung des Vorbereitungsdienstes als Lehrerin an einer Bochumer Schule tätig. Die Liebe zur Philosophie entwickelte sich vor gut 20 Jahren durch Jostein Gaarders Werk „Sofies Welt“. Eine solche Begeisterung möchte sie nicht nur bei ihren Schüler:innen, sondern auch bei den Lesenden des Buches wecken. Hans-Ulrich Lessing (geboren 1953 in Dortmund) promovierte 1981 in Bochum, wo er 1995 auch habilitierte. Er war seit 2001 apl. Professor für Philosophie an der Ruhr-Universität Bochum. Als Mitarbeiter der Dilthey-Forschungsstelle ist er unter anderem Mitherausgeber von Diltheys Gesammelten Schriften. Die Autor:innen Die Texte stammen von (ehemaligen) Bachelor- und Masterstudierenden der Philosophie an der Ruhr-Universität Bochum, die durch ihre Werke ihre Leidenschaft zum Fach ausdrücken

Federal Research, Additional Actions Needed to Improve Public Access to Research Results: Report to Congressional Requesters [with Responses from Federal Agencies]

Why GAO Did This Study Research and development helps catalyze breakthroughs that improve the overall health and wellbeing of our society. Federal research and development expenditures averaged about $135 billion annually for fiscal years 2015 to 2017. According to OSTP, providing free public access to federally funded research results can improve both the impact and accountability of this important federal investment. In February 2013, OSTP directed federal agencies with more than$100 million in annual research and development expenditures to develop a plan to support increased public access to the results of federally funded research. GAO was asked to examine public access to federally funded research results. This report examines the extent of agencies’ (1) progress implementing plans to increase public access to federally funded research results and (2) coordination on public access plan implementation. GAO administered a questionnaire to 19 federal agencies selected based on annual research and development expenditure amounts, among other criteria; reviewed agency documents; and interviewed officials from 11 agencies, OSTP, and 21 stakeholder organizations. What GAO Found The 19 agencies that GAO reviewed have made progress implementing their plans to increase public access to federally funded research results (publications and data), as called for in a 2013 Office of Science and Technology Policy (OSTP) memorandum. However, some agencies have not fully implemented some aspects of their plans, in particular those related to data access and mechanisms to ensure researchers comply with public access requirements. Agencies are coordinating with each other and with nonfederal stakeholders to implement public access plans, including through an interagency group led by OSTP and five other agencies. However, the group has not fully implemented selected leading practices identified by GAO that can enhance and sustain interagency collaboration, such as defining and articulating common outcomes. For example, according to OSTP staff, key outcomes have not yet been decided upon. Agency officials and stakeholders identified several challenges to implementing public access plans that interagency coordination might help them address, such as • Absence of common standards in several areas; • Measuring effectiveness of public access plan implementation; and • Balancing providing public access with safeguarding sensitive information. By taking steps to fully implement relevant leading collaboration practices, the interagency group could help agencies better marshal their collective efforts to address common challenges to public access plan implementation. What GAO Recommends GAO is making 37 recommendations to 16 agencies to promote full and effective implementation of agency public access plans. For example, GAO recommends that OSTP and 5 agencies leading a public access interagency group take steps to fully implement selected leading collaboration practices. Of the 16 agencies, 15 agreed with GAO’s recommendations while 1 (OSTP) disagreed. GAO continues to believe the recommendation to OSTP is warranted

Party rules, party resources, and the politics of parliamentary democracies: how parties organize in the 21st Century

This article introduces the first findings of the Political Party Database (PPDB) project, a major survey of party organizations in parliamentary and semi-presidential democracies. The project’s first round of data covers 122 parties in 19 countries. In this paper we describe the scope of the database, then investigate what it tells us about contemporary party organization in these countries, focussing on parties’ resources, structures and internal decision-making. We examine organizational patterns by country and party family, and where possible we make temporal comparisons with older datasets. Our analyses suggest a remarkable coexistence of uniformity and diversity. In terms of the major organizational resources on which parties can draw, such as members, staff and finance, the new evidence largely confirms the continuation of trends identified in previous research: i.e., declining membership, but enhanced financial resources and more paid staff. We also find remarkable uniformity regarding the core architecture of party organizations. At the same time, however, we find substantial variation between countries and party families in terms of their internal processes, with particular regard to how internally democratic they are, and in the forms that this democratization takes

The Worksite Health Promotion Capacity Instrument (WHPCI): development, validation and approaches for determining companies' levels of health promotion capacity

<p>Abstract</p> <p>Background</p> <p>The Worksite Health Promotion Capacity Instrument (WHPCI) was developed to assess two key factors for effective worksite health promotion: collective willingness and the systematic implementation of health promotion activities in companies. This study evaluates the diagnostic qualities of the WHPCI based on its subscales Health Promotion Willingness and Health Promotion Management, which can be used to place companies into four different categories based on their level of health promotion capacity.</p> <p>Methods</p> <p>Psychometric evaluation was conducted using exploratory factor and reliability analyses with data taken from a random sample of managers from n = 522 German information and communication technology (ICT) companies. Receiver operating characteristic (ROC) analyses were conducted to determine further diagnostic qualities of the instrument and to establish the cut-off scores used to determine each company's level of health promotion capacity.</p> <p>Results</p> <p>The instrument's subscales, Health Promotion Willingness and Health Promotion Management, are based on one-dimensional constructs, each with very good reliability (Cronbach's alpha = 0.83/0.91). ROC analyses demonstrated satisfactory diagnostic accuracy with an area under the curve (AUC) of 0.76 (SE = 0.021; 95% CI 0.72-0.80) for the Health Promotion Willingness scale and 0.81 (SE = 0.021; 95% CI 0.77-0.86) for the Health Promotion Management scale. A cut-off score with good sensitivity (71%/76%) and specificity (69%/75%) was determined for each scale. Both scales were found to have good predictive power and exhibited good efficiency.</p> <p>Conclusions</p> <p>Our findings indicate preliminary evidence for the validity and reliability of both subscales of the WHPCI. The goodness of each cut-off score suggests that the scales are appropriate for determining companies' levels of health promotion capacity. Support in implementing (systematic) worksite health promotion can then be tailored to each company's needs based on their current capacity level.</p

Emissions from a modern log wood masonry heater and wood pellet boiler : Composition and biological impact on air-liquid interface exposed human lung cancer cells

The consumption of wood fuel is markedly increasing in developing and industrialized countries. Known side effects of wood smoke inhalation manifest in proinflammatory signaling, oxidative stress, DNA damage and hence increased cancer risk. In this study, the composition and acute biological impact of emissions of state-of-the-art wood combustion compliances: masonry heater (MH) and pellet boiler (PB) were investigated. Therefore A549 cells were exposed to emission aerosols in an automated air-liquid interface exposure station followed by cytotoxicity, transcriptome and proteome analyses. In parallel, aerosols were subjected to a chemical and physical haracterization. Compared to PB, the MH combustion at the same dilution ratio resulted in a 3-fold higher particle mass concentration (PM2.5) and deposited dose (PB: 27 $\pm$ 2 ng/cm2, MH; 73 $\pm$ 12 ng/cm2). Additionally, the MH aerosol displayed a substantially larger concentration of aldehydes, polycyclic aromatic hydrocarbons (PAH) or oxidized PAH. Gene ontology analysis of transcriptome of A549 cells exposed to MH emissions revealed the activation of proinflammatory response and key signaling cascades MAP kinase and JAK-STAT. Furthermore, CYP1A1, an essential enzyme in PAH metabolism, was induced. PB combustion aerosol activated the proinflammatory marker IL6 and different transport processes. The proteomics data uncovered induction of DNA damage-associated proteins in response to PB and DNA doublestrand break processing proteins in response to MH emissions. Taking together, the MH produces emissions with a higher particle dose and more toxic compounds while causing only mild biological responses. This finding points to a significant mitigating effect of antioxidative compounds in MH wood smoke