Prognosis of Lung Cancer Mortality in West Germany: A Case Study in Bayesian Prediction. (REVISED, January 2000)

We apply a generalized Bayesian age-period-cohort (APC) model to a dataset on lung cancer mortality in West Germany, 1952-1996. Our goal is to predict future deaths rates until the year 2010, separately for males and females. Since age and period is not measured on the same grid, we propose a generalized APC-model where consecutive cohort parameters represent strongly overlapping birth cohorts. This approach results in a rather large number of parameters, where standard algorithms for statistical inference by Markov chain Monte Carlo (MCMC) methods turn out to be computationally intensive. We propose a more efficient implementation based on ideas of block sampling from the time series literature. We entertain two different formulations, penalizing either first or second differences of age, period and cohort parameters. To assess the predictive quality of both formulations, we first forecast the rates for the period 1987-1996 based on data until 1986. A comparison with the actual observed rates is made based on quantities related to the predictive deviance. Predictions of lung cancer mortality until 2010 both for males and females are finally reported

Localized Drug Delivery Systems in High‐Grade Glioma Therapy—From Construction to Application

High-grade gliomas are the most common and most malign primary brain tumors. Current therapy approaches only reach unsatisfactory results, still not providing a long-lasting time to relapse or a curative treatment. A novel approach to overcome the present challenges of medical attendance, as drug resistance, systemic side effects, and limited drug availability due to the blood-brain barrier, are localized drug delivery systems (DDSs), which are already used in clinical trials. Further development of this therapy regime may clearly improve patient's outcomes. In order to design compact, biocompatible, robust, and highly flexible systems which permit a prolonged drug release, a broad knowledge of the technical and medical field is required. Thus, this interdisciplinary article reviews different designs, testing, and validation models, and finally, clinical applications of localized DDSs, to utilize this available experience as a basis for the desperately needed reform of glioma treatment

Hetero-epitaxial EuO Interfaces Studied by Analytic Electron Microscopy

With nearly complete spin polarization, the ferromagnetic semiconductor europium monoxide could enable next-generation spintronic devices by providing efficient ohmic spin injection into silicon. Spin injection is greatly affected by the quality of the interface between the injector and silicon. Here, we use atomic-resolution scanning transmission electron microscopy in conjunction with electron energy loss spectroscopy to directly image and chemically characterize a series of EuO|Si and EuO|YAlO3 interfaces fabricated using different growth conditions. We identify the presence of europium silicides and regions of disorder at the EuO|Si interfaces, imperfections that could significantly reduce spin injection efficiencies via spin-flip scattering

Pulmonary vasculitis due to infection with Mycobacterium goodii : A case report

A 57-year-old Caucasian woman suffered from dyspnea on exertion. One year following a supposed pulmonary embolism event, a chronic thromboembolic vasculopathy was diagnosed and a pulmonary thromboendarterectomy was performed. However, a granulomatous pulmonary arterial vasculitis was identified upon examination. DNA of Mycobacterium goodii was detected as the most likely causative agent. Anti-inflammatory and anti-mycobacterial therapy was initiated for more than 12 months. Regular PET-CT scans revealed improvement under therapy. The last PET-CT did not show any tracer uptake following 10 months of therapy

High-quality EuO thin films the easy way via topotactic transformation

Epitaxy is widely employed to create highly oriented crystalline films. A less appreciated, butnonetheless powerful means of creating such films is via topotactic transformation, in which achemical reaction transforms a single crystal of one phase into a single crystal of a differentphase, which inherits its orientation from the original crystal. Topotactic reactions may beapplied to epitactic films to substitute, add or remove ions to yield epitactic films of differentphases. Here we exploit a topotactic reduction reaction to provide a non-ultra-high vacuum(UHV) means of growing highly oriented single crystalline thin films of the easily overoxidizedhalf-metallic semiconductor europium monoxide (EuO) with a perfection rivallingthat of the best films of the same material grown by molecular-beam epitaxy or UHV pulsedlaserdeposition. As the technique only requires high-vacuum deposition equipment, it hasthe potential to drastically improve the accessibility of high-quality single crystalline films ofEuO as well as other difficult-to-synthesize compounds

Shelf ice-associated cryo-benthos and environmental features

Incidences of cryo-benthic communities beneath ice shelves are rare and recent discoveries. Combined seal- and ROV-borne imagery and novel sampling technologies allowed for a re-assessment and augmentation of earlier findings on a cryo-benthic isopod community (Antarcturus cf. spinacoronatus), being attached head-down to the underside of floating shelf ice at depths of around 80-150m. The shelf ice-associated cryo-benthos was discovered at Drescher Inlet (-72.83667 -19.15300), Riiser-Larsen Ice Shelf (eastern Weddell Sea). The inlet constitutes a 25km long and between 2 and 4km wide crack in the surrounding shelf ice, which is associated with certain environmental features. Here we compile all available local physical, biological, and biogeochemical data and discuss their relevance in the wider regional context for this faunal hotspot. These include data on shelf, sea and platelet ice, seafloor topography, hydrography and water chemistry, as well as associated pelagic and benthic marine life, in particular affinities of the cryo-benthic isopod community to related fauna occurring in nearby seabed communities using molecular barcoding

Sequential Treatment with Temozolomide Plus Naturally Derived AT101 as an Alternative Therapeutic Strategy: Insights into Chemoresistance Mechanisms of Surviving Glioblastoma Cells

Glioblastoma (GBM) is a poorly treatable disease due to the fast development of tumor recurrences and high resistance to chemo- and radiotherapy. To overcome the highly adaptive behavior of GBMs, especially multimodal therapeutic approaches also including natural adjuvants have been investigated. However, despite increased efficiency, some GBM cells are still able to survive these advanced treatment regimens. Given this, the present study evaluates representative chemoresistance mechanisms of surviving human GBM primary cells in a complex in vitro co-culture model upon sequential application of temozolomide (TMZ) combined with AT101, the R(-) enantiomer of the naturally occurring cottonseed-derived gossypol. Treatment with TMZ+AT101/AT101, although highly efficient, yielded a predominance of phosphatidylserine-positive GBM cells over time. Analysis of the intracellular effects revealed phosphorylation of AKT, mTOR, and GSK3ß, resulting in the induction of various pro-tumorigenic genes in surviving GBM cells. A Torin2-mediated mTOR inhibition combined with TMZ+AT101/AT101 partly counteracted the observed TMZ+AT101/AT101-associated effects. Interestingly, treatment with TMZ+AT101/AT101 concomitantly changed the amount and composition of extracellular vesicles released from surviving GBM cells. Taken together, our analyses revealed that even when chemotherapeutic agents with different effector mechanisms are combined, a variety of chemoresistance mechanisms of surviving GBM cells must be taken into account

B‐cell receptors of EBV‐negative Burkitt lymphoma bind modified isoforms of autoantigens

Burkitt lymphoma (BL) represents the most aggressive B‐cell‐lymphoma. Beside the hallmark of IG‐MYC‐translocation, surface B‐cell receptor (BCR) is expressed, and mutations in the BCR pathway are frequent. Coincidental infections in endemic BL, and specific extra‐nodal sites suggest antigenic triggers. To explore this hypothesis, BCRs of BL cell lines and cases were screened for reactivities against a panel of bacterial lysates, lysates of Plasmodium falciparum, a custom‐made virome array and against self‐antigens, including post‐translationally modified antigens. An atypically modified, SUMOylated isoform of Bystin, that is, SUMO1‐BYSL was identified as the antigen of the BCR of cell line CA46. SUMO1‐BYSL was exclusively expressed in CA46 cells with K139 as site of the SUMOylation. Secondly, an atypically acetylated isoform of HSP40 was identified as the antigen of the BCR of cell line BL41. K104 and K179 were the sites of immunogenic acetylation, and the acetylated HSP40 isoform was solely present in BL41 cells. Functionally, addition of SUMO1‐BYSL and acetylated HSP40 induced BCR pathway activation in CA46 and BL41 cells, respectively. Accordingly, SUMO1‐BYSL‐ETA’ immunotoxin, produced by a two‐step intein‐based conjugation, led to the specific killing of CA46 cells. Autoantibodies directed against SUMO1‐BYSL were found in 3 of 14 (21.4%), and autoantibodies against acetylated HSP40 in 1/14(7.1%) patients with sporadic Burkitt‐lymphoma. No reactivities against antigens of the infectious agent spectrum could be observed. These results indicate a pathogenic role of autoreactivity evoked by immunogenic post‐translational modifications in a subgroup of sporadic BL including two EBV‐negative BL cell lines

B-cell receptor reactivity against Rothia mucilaginosa in nodular lymphocyte-predominant Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1*07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA’-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states