The primary structure of a monoclonal λ-type immunoglobulin L-chain of subgroup II (Bence-Jones protein NEI): Evolutionary origin of antibody variability

ObjectiveThe objective of this study is to assess the gestational age at detection and prevalence of anencephaly in the North of The Netherlands over a 5-year period. MethodsA case list of all cases of anencephaly from two fetal medicine units was compiled. Cases were included if the estimated due date was between 1 August 2008 and 31 July 2013. ResultsOverall prevalence of anencephaly was 5.4 per 10.000 pregnancies (n=110). The majority of cases (69%) was detected before 18 weeks' gestation. Factors determining successful early diagnosis were competence level of the sonographers, with a significantly higher detection rate when scans were performed by a sonographer licensed by the Fetal Medicine Foundation (FMF) for nuchal translucency measurement (p=0.001), and gestational age at or beyond 11weeks of gestation (p=0.024). ConclusionImproving detection of anencephaly in the first trimester requires ultrasound screening at or after 11weeks of gestation, performed by experienced sonographers trained in recognizing fetal anomalies. Sonographers should be instructed that the goal of the first trimester scan is not only to measure nuchal translucency thickness but also to exclude major anomalies. (c) 2015 John Wiley & Sons, Ltd

The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

In healthy circumstances the immune system coordinates tissue repair responses in a tight balance that entails efficient inflammation for removal of potential threats, proper wound closure, and regeneration to regain tissue function. Pathological conditions, continuous exposure to noxious agents, and even ageing can dysregulate immune responses after injury. This dysregulation can lead to a chronic repair mechanism known as fibrosis. Alterations in wound healing can occur in many organs, but our focus lies with the lung as it requires highly regulated immune and repair responses with its continuous exposure to airborne threats. Dysregulated repair responses can lead to pulmonary fibrosis but the exact reason for its development is often not known. Here, we review the diversity of innate immune cells of myeloid origin that are involved in tissue repair and we illustrate how these cell types can contribute to the development of pulmonary fibrosis. Moreover, we briefly discuss the effect of age on innate immune responses and therefore on wound healing and we conclude with the implications of current knowledge on the avenues for future research

Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis-associated tumorigenesis in mice

Background and aims: Colitis-associated tumorigenesis is a balance between proliferation of tumour cells and tumour immunosurveillance. The role of T-helper-cell-derived cytokines in tumour growth is not fully understood. In this study the authors investigated the influence of interleukin (IL) 21 on intestinal tumorigenesis. Methods: Chronic colitis was induced in IL-21−/− and littermate control wild-type mice with three cycles of 1.5% dextran sulphate sodium (DSS) over 7 days followed by 7 days of drinking water. Mice received an azoxymethane injection on day 0 of DSS-colitis to induce tumorigenesis. Immunohistochemistry was performed on inflamed and tumour-bearing areas of colons. Cytokine expression of isolated colonic CD4 T cells was determined by ELISA. Cytotoxic capacity of isolated colonic CD8 T cells targeting tumour cells was evaluated by flow cytometry and quantitative cytotoxicity assay. Apoptosis of tumour cells was determined by TUNEL assay of colonic sections. Results: Increasing expression of IL-21 was observed in chronic colitis, which showed functional importance, since IL-21 deficiency prevented chronic DSS-colitis development. Further, in the absence of IL-21, significantly fewer tumour nodules were detected, despite a similar extent of intestinal inflammation. In wild-type mice, 8.6±1.9 tumour nodules were found compared with 1.0±1.2 in IL-21-deficient mice. In tumour-bearing IL-21-deficient mice, intestinal inflammation was restored and partly dependent on interferon (IFN)-γ, whereas the inflammation in wild-type mice showed high IL-17A concentrations. In these rare tumours in IL-21-deficient mice, tumour cell proliferation (Ki-67) was decreased, while cell apoptosis was increased, compared with wild-type mice. Increased IFNγ expression in tumour-bearing IL-21-deficient mice led to increased tumour immunosurveillance mediated by cytotoxic CD8CD103 T cells targeting E-cadherin+ colonic tumour cells and therefore limited tumour growth. Conclusion: These results indicate that IL-21 orchestrates colitis-associated tumorigenesis, leading to the hypothesis that high IFNγ and low IL-17A expression reduces tumour cell proliferation and increases tumour immunosurveillance

EpCAM an immunotherapeutic target for gastrointestinal malignancy: current experience and future challenges

Despite advances in surgery and adjuvant regimes, gastrointestinal malignancy remains a major cause of neoplastic mortality. Immunotherapy is an emerging and now successful treatment modality for numerous cancers that relies on the manipulation of the immune system and its effector functions to eradicate tumour cells. The discovery that the pan-epithelial homotypic cell adhesion molecule EpCAM is differentially expressed on gastrointestinal tumours has made this a viable target for immunotherapy. Clinical trials using naked anti EpCAM antibody, immunoconjugates, anti-idiotypic and dendritic cell vaccines have met variable success. The murine IgG2a Edrecolomab was shown to reduce mortality and morbidity at a level slightly lower than treatment with 5FU and Levamisole when administered to patients with advanced colorectal carcinoma in a large randomised controlled trial. Fully human and trifunctional antibodies that specifically recruit CD3-positive lymphocytes are now being tested clinically in the treatment of minimal residual disease and ascites. Although clinical trials are in their infancy, the future may bring forth an EpCAM mediated approach for the effective activation and harnessing of the immune system to destroy a pathological aberrance that has otherwise largely escaped its attention

A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators

Expression of the epithelial cell adhesion molecule EpCAM is upregulated in a variety of carcinomas. This antigen is therefore explored in tumour diagnosis, and clinical trials have been initiated to examine EpCAM-based therapies. Notably, the possible intracellular effects and signalling pathways triggered by EpCAM-specific antibodies are unknown. Here, we show treatment of the mouse lung carcinoma cell line A2C12, of the human lung carcinoma cell line A549 and the human colorectal cell line Caco-2 with the monoclonal EpCAM antibody G8.8 to cause dose dependently an increase in cell proliferation, as determined by the MTS and the 5′-bromo-2′-deoxyuridine (BrdU) labelling assay. Furthermore, a genome-wide approach identified networks of regulated genes, most notably cell cycle regulators, upon treatment with an EpCAM-specific antibody. Indeed, changes in the expression of cell cycle regulators agreed well with the BrdU labelling data, and an analysis of differentially expressed genes revealed the processes with the strongest over-representation of modulated genes, for example, cell cycle, cell death, cellular growth and proliferation, and cancer. These data suggest that EpCAM is involved in signal transduction triggering several intracellular signalling pathways. Knowing EpCAM signalling pathways might lead to a reassessment of EpCAM-based therapies

Participation in public places : Ermöglichungsflächen at Seestadt Aspern

In recent years, participation in the design of public spaces in Vienna has become increasingly important. Participation is a way to promote citizen involvement in planning process. Ermöglichungsflächen represent a new strategy to involve the people of Vienna to participate in co-creation; these areas are currently located in Seestadt Aspern. The residents of Seestadt Aspern should participate in public space around one to two years after first occupancy in the district (first occupancy 2014). Currently, this participation still has not taken place. The design of Ermöglichungsflächen is an interdisciplinary task and in order to truly meet all wishes and requirements, expertise is needed in various fields. This thesis aims to help collect, record and combine the relevant expertise of different disciplines to create awareness and promote participation in the co-creation of Ermöglichungsflächen. Furthermore, this thesis answers three research questions: Which preconditions need to be established to create and implement a sustainable socio-technical system in a public space?, How can people be made aware of and be motivated to use public space in a sustainable way?, \Which technological solutions can support these processes, and what functionalities should such a technological solution have?With the help of a literature search, a variety of topics were investigated to form the basis for answering the research questions and creating the prototype. Furthermore, expert interviews, observations, an online survey and interviews with residents of the City of Vienna were conducted to answer the research questions. The results of the thesis demonstrate that the app that was developed can make people aware of Ermöglichungsflächen and facilitate the co-design of these areas. The participation of residents in the design of the Ermöglichungsflächen is encouraged through the app, and the submission process is facilitated so that they are involved in the entire process and procedure.In den letzten Jahren hat die Beteiligung der Bürger an der Gestaltung des öffentlichen Raums in Wien zunehmend an Bedeutung gewonnen. Partizipation ist eine Möglichkeit, um die Bevölkerung in einschlägige Planungsprozesse zu integrieren. Ermöglichungsflächen stellen diesbezüglich eine neue Strategie dar; diese Flächen befinden sich derzeit in der Seestadt Aspern. Die BewohnerInnen der Seestadt Aspern sollen sich etwa ein bis zwei Jahre nach der Erstbelegung des Bezirks (Erstbezug 2014) für den öffentlichen Raum engagieren. Derzeit hat diese Beteiligung noch nicht stattgefunden. Die Gestaltung von Ermöglichungsflächen ist eine interdisziplinäre Aufgabe. Die vorliegende Arbeit sammelt und erfasst das relevante Fachwissen entsprechender Disziplinen zu, um Bewusstsein für die Ermöglichungsflächen zu schaffen und die Beteiligung an der Mitgestaltung zu fördern. Darüber hinaus werden in dieser Arbeit folgende Forschungsfragen beantwortet: Welche Voraussetzungen müssen geschaffen werden, um ein nachhaltiges sozio-technisches System im öffentlichen Raum zu schaffen und umzusetzen?, Wie können Menschen für eine nachhaltige Nutzung des öffentlichen Raums sensibilisiert und motiviert werden?, Welche technische Lösung kann diese Prozesse unterstützen und welche Funktionalitäten sollte sie haben? Mit Hilfe einer Literaturrecherche wurden Themen untersucht, die die Grundlage für die Beantwortung der Forschungsfragen und die Erstellung eines Prototyps bilden. Weiterhin wurden diesbezüglich Experteninterviews, Beobachtungen, Online-Befragungen und Interviews mit BewohnerInnen der Stadt Wien durchgeführt. Die Ergebnisse dieser Thesis zeigen, dass die entwickelte App Menschen auf Ermöglichungsflächen aufmerksam macht, deren Mitgestaltung erleichtern kann und die Beteiligung fördert. So wird der Einreichungsprozess erleichtert und die BürgerInnen werden in den gesamten Prozess und das Verfahren einbezogen.19

Wachstum ultradünner Fe-Schichten auf Cu-Einkristallen bei Laser Ablation

Zsfassung in engl. SpracheUltradünne Fe-Schichten auf Cu-Einkristallen haben schon seit längerem das Interesse der Wissenschaft auf sich gezogen. Insbesondere ihre strukturelle Vielfalt und ihr komplexes magnetisches Verhalten eignen sich hervorragend für die Untersuchung des noch nicht vollständig verstandenen Zusammenhanges zwischen Struktur und Magnetismus in dünnen Schichten. Außerdem können diese Schichten aufgrund ihrer unterschiedlichen Wachstumsmoden als Modellsystem für das heteroepitaktische Wachstum dünner Metallschichten auf Metallsubstraten herangezogen werden.Durch die Verwendung von Ablation mittels Laserpulsen (pulsed laser deposition, PLD) als Beschichtungsmethode (im Gegensatz zu der in der Forschung weit verbreiteten thermischen Deposition) können nicht nur wichtige Beschichtungs¬parameter, wie die momentane Depositionsrate und die Energie der deponierten Teilchen geändert werden, sondern auch Erkenntnisse über diese in Industrie und Forschung immer bedeutendere Methode erhalten werden. In dieser Arbeit wurden das Wachstum und die atomare Struktur von dünnen Fe-Schichten auf Cu(111) und Cu(100), die mittels PLD erzeugt wurden, untersucht und mit Ergebnissen von thermisch deponierten Schichten verglichen. Die verwendeten Methoden zur Oberflächenanalyse waren Rastertunnelmikroskopie (STM), Streuung niederenergetischer Ionen (LEIS) und Auger-Elektronen Spektroskopie (AES). Es konnte gezeigt werden, dass die bei Beschichtung mittels PLD beobachtete Änderung des Wachstumsmodus in Richtung Lagenwachstum nicht durch die im Vergleich zur thermischen Deposition um Größenordnungen höhere momentane Depositionsrate bedingt ist. Das Lagenwachstum im System Fe/Cu wird hauptsächlich durch Einlagerung von Fe-Atomen, oder Fe-Cluster in das Cu-Substrat verursacht. Diese entstehen mehrheitlich entweder durch einen Austauschprozess von Adatomen mit Substrat¬atomen [Fe auf Cu(100)], oder durch Implantation von energiereichen Teilchen aus dem Laserplasma ins Substrat [Fe auf Cu(111)]. Durch atomar aufgelöste STM-Bilder konnte weiters gezeigt werden, dass die Struktur der Schichten viele Übereinstimmungen mit der thermisch deponierter Filme aufweist, insbesondere bcc-artige Verzerrungen, die sowohl in Filmen auf Cu(100) als auch auf Cu(111) auftreten. Diese bcc-artigen Strukturen spielen eine wichtige Rolle bei der Erklärung der magnetischen Eigenschaften ultradünner Fe-Schichten.Ultrathin Fe-films on Cu single crystals have been in the focus of research for years. Especially their structural variety and their complex magnetic behavior are perfect prerequisites for the investigation of the correlation between structure and magnetism in thin films. Moreover these films, which show a wealth of different growth modes, can act as a model system for heteroepitaxial growth on metal substrates. Using pulsed laser deposition (PLD) for growing thin films allows us not only to change important deposition parameters like deposition rate or particle energy, but also to achieve scientific results concerning this method, which has an increasing importance in industry and research.In this work we investigate the growth and the atomic structure of thin Fe films grown by PLD on Cu(111) and Cu(100) and compare the results with thermally deposited films. The analytical methods used are scanning tunneling microscopy (STM), low-energy ion scattering (LEIS) and Auger-electron spectroscopy (AES). It could be shown that the growth mode change towards layer-by-layer growth observed in PLD-films is not triggered by the orders of magnitude higher instantaneous deposition rate of PLD. The reason for the improved layer-by-layer growth in the Fe/Cu system is the embedding of Fe-atoms or Fe-clusters into the Cu-substrate. This is primarily caused by an exchange process of adatoms and substrate atoms [Fe on Cu(100)], or by the implantation of highly energetic particles stemming from the laser plasma [Fe on Cu(111)].Atomically resolved STM images show that the structure of the PLD-grown films has many common features compared to films grown by thermal deposition, especially bcc-like distortions that occur on both types of substrates. These bcc-like structures play an important role in the explanation of the magnetism of ultrathin Fe-films.12

Einige chemische Aspekte der Osmiumtetroxidfixierung

Das Studium der Reaktionen des OsO4 mit den einzelnen biologischen Substanzen unter den üblichen Bedingungen der Fixierung ergibt, daß das OsO4 vorzüglich mit den Lipoiden reagiert. Die Proteine beteiligen sich in der Hauptsache mit ihren schwefelhaltigen Seitenketten an der Reaktion. Von beiden Substanzgruppen wird das OsO4 zu Os(VI) reduziert und gebunden. Die bevorzugten Bindungsorte des Osmiums in den verschiedenen Gewebestrukturen werden diskutiert. Polysaccharide und verwandte Verbindungen sowie Nucleinsäuren zeigen keine Osmiumaufnahme.</jats:p