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Im Zeitalter von Internet und digitaler Wissensvermittlung hat auch die Geschichtswissenschaft die Photographie als Quellenmaterial zur Dokumentation historischer Lebensbedingungen und Ereignisse schätzen gelernt. Neben dem geisteswissenschaftlichen Aspekt solcher Photodokumente gibt es einen technisch-konservatorischen Aspekt.
Anomalous monism and mental causality : on the debate of Donald Davidson’s philosophy of the mental
(2004)
The English version of the first chapter of Erwin Rogler and Gerhard Preyer: Materialismus, anomaler Monismus und mentale Kausalität. Zur gegenwärtigen Philosophie des Mentalen bei Donald Davidson und David Lewis (2001) "Anomaler Monismus und Mentale Kausalität. Ein Beitrag zur Debatte über Donald Davidsons Philosophie des Mentalen" is a contribution to the current debates on the philosophy of the mental and mental causality initiated from Donald Davidson's philosophy with his article "Mental Events" (1970). It is the intent of the English version to give a response to the controversy among American, British and Australian philosophers in the context of a global exchange of ideas on problems understanding the mental. Contents 1. Preliminary Remarks 2. The Critique of Property-Epiphenomenalism and Counterarguments (a) The Enlargement of Nomological Reasoning (b) The Counterfactual Analysis (c) Supervenient Causality 3. Are Mental Properties real or unreal (fictive)? Abstract Things and events are fundamental entities in Davidson's ontology. Less distinct is the ontological status of properties, especially of mental types. Despite of some eliminative allusions there are weighty reasons to understand Davidson's philosophy of mind as including intentional realism. With it, the question of mental causality arises. There are two striking solutions to this problem: the epiphenomenalism of mental properties and the downward causation of mental events. Davidson cannot accept either. He claims to justify the mental as supervenient causality in order to thus integrate it into physicalism (his version of monism). But his argument at best proves the explanatory, not the causal relevance of mental properties. For this and for other reasons, Davidson fails the aspired synthesis of a sufficiently strong physicalism and the autonomy of the mental; a project whose realization is anyhow hard to achieve.
Background and Aim: In Germany, the discharge medication is usually reported to the general practitioner (GP) by an inital short report (SR) /notification (handed over to the patient) and later by a more detailed discharge letter (DL) of the hospital.
Material and Method: We asked N=536 GPs (from Frankfurt/Main and Luebeck) after the typical report format of their patients discharge medication by the local hospitals. The questionnaire asked for 26 items covering (1) the designation of the medication (brand name, generic name) in SR and DL, (2) further specifications e.g. possibilities of generic substitution or supervision of sensible medications, (3) reasons why GPs do not follow the hospitals recommendations and (4) possibilities for an improvement in the medication-related communication between GP and hospitals.
Results: 39% GPs responded sufficiently to the questionnaire. The majority of the GPs (82%) quoted that in the SR only brand names are given (often or ever) and neither the generic name or any further information on generic substitution is available (seldom or never). 65% of the responders quoted that even in the DL only brand names are given. Only 41% of the responders quoted that further treatment relevant specifications are given (often or ever). 95% responded that new medications or change of custom medication is seldom or never explained in the DL and GP were not explicitly informed about relevant medication changes. 58% of the responders quoted economic reasons for re-adjustment of the discharge medication e.g. by generic substitution. The majority of responders (83%) are favouring (useful or very useful) a pre-discharge information (e.g. via fax) about the medication and 54% a hot-line to some relevant person in the hospital when treatment problems emerge. 67% of the responders quoted in favour of regular meetings between GPs and hospital doctors regarding actual pharmacotherapy.
Conclusion: In conclusion, our survey pointed to marked deficiencies in reporting the discharge medication to GPs.
Conflict of interest: None
Background The detection of the new Coranavirus (CoV) causing agent of the severe acute respiratory syndrome (SARS) for diagnostic purposes is still a critical step in prevention of secondary hospital infections. In this respect the PCR for SARS diagnostic is the fastest and most sensitive method and was published very early after the description of the new pathogen by different groups. To evaluate the quality and sensitivity of the SARS PCR performed in diagnostic laboratories all over the world an external quality assurance (EQA) for SARS PCR was initiated by the WHO, the European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) and the Robert Koch-Institut. Methods Therefore 10 samples of inactivated SARS CoV strains isolated in Frankfurt and Hong Kong in different dilutions and negative controls were prepared. The freeze dried samples were send by mail to 62 different laboratories, in 37 countries in Europe and Israel (35), Asia (11), The Americas (11), Australia and New Zealand (4) and Africa (1). The results were returned by email or fax 1 week (13), 2 weeks (14), 3 weeks (6) and later (29) after receiving the material which does not mimic at all the possible speed of this fast method. But this was not considered in the evaluation of these first SARS EQA. Results 44 laboratories showed good or excellent results (26 = 100%, 18 = 90%) and even the 14 laboratories which archived only 80% (10) or 70% (4) correct results are mostly lacking sensitivity. The results of the other 4 laboratories show basic problems in regard to sensitivity, specificity and consistency of results and must be overcome as soon as possible. 4 laboratories seem to have problems with the specificity finding a positive signal in negative samples. The different methods used for preparation of the SARS CoV genome and diagnostic PCR test procedure used by the participating laboratories will be discussed in more detail in the presentation. Conclusion However, in contrast to previous EQAs for Ebola, Lassa and Orthopoxviruses the quality of PCR results was rather good which might be caused by the early publication and distribution of well developed PCR methods. An EQA for evaluation of SARS specific serology is still ongoing, first results will be available beginning of April 2004.
The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origin without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with retroviral vectors we have generated genetically modified NK-92 cells expressing chimeric antigen receptors specific either for the tumor-associated ErbB2 (HER2/neu) antigen or the human Epithelial Cell Adhesion Molecule (Ep-CAM). Both antigens are overexpressed by many tumors of epithelial origin. The chimeric antigen receptors consist of either the ErbB2 specific scFv(FRP5) antibody fragment or the Ep-CAM specific scFv(MOC31), a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 zeta chain. Transduced NK-92-scFv(FRP5)-zeta or NK-92-scFv(MOC31)-zeta cells express high levels of the fusion proteins on the cell surface as determined by FACS analysis. In europium release assays no difference in cytotoxic activity of NK-92 and transduced NK-92 cells towards ErbB2 or Ep-CAM negative targets was found. However, even at low effector to target ratios transduced NK-92 cells specifically and efficiently lysed established ErbB2 or Ep-CAM expressing tumor cells that were completely resistant to cytolytic activity of parental NK-92 cells. Similarly, ErbB2-positive primary breast cancer cells isolated from pleural effusions of patients with recurrent disease were selectively killed by NK-92-scFv(FRP5)-zeta. In an in vivo model in immunodeficient mice treatment with retargeted NK-92-scFv(FRP5)-zeta, but not parental NK-92 cells resulted in markedly delayed growth of ErbB2 transformed cancer cells. These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved, and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2 and Ep-CAM expressing malignancies. This therapeutic approach might be applicable for a large variety of different cancers where suitable cell surface antigens have been identified.
The receptor tyrosine kinase ErbB2 (HER2) is overexpressed in multiple human tumors of epithelial origin. High ErbB2 expression is functionally involved in tumorigenesis and correlates with poor clinical prognosis. For immunotherapy of ErbB2 expressing tumors, we developed a strategy to supply the tumor cells with costimulatory activity. A bispecific fusion protein was constructed (BIg5), containing the IgV-like domain of huCD86, the CH2/CH3 domain of huIgG1 and the ErbB2-specific single chain antibody fragment scFv(FRP5). A similar fusion protein lacking the CD86 domain (Ig5) was used as a control. Upon binding of BIg5 to ErbB2 on tumor cells, these cells display CD86 on their surface and thus can deliver costimulatory signals for T-cell activation. In addition, NK cells could be activated by CD86 binding to CD28. BIg5 is secreted by eukaryotic cells as a homodimer with increased stability compared to monomers and possibly enhanced costimulatory activity due to crosslinking of CD28 on effector cells. By FACS analysis, specific binding of the scFv(FRP5) domain to ErbB2 as well as CD86 IgV binding to CTLA-4 could be demonstrated. Together with anti-CD3 antibody, BIg5 stimulates proliferation of human CD2-purified lymphocytes in vitro. After binding to ErbB2 on murine Renca-lacZ/ErbB2 tumor cells, about 50% of initially bound BIg5 is still present on the cell surface after 4 hours. For delivery of chimeric fusion proteins in vivo, we used syngeneic, stably transfected HC11 mammary epithelial cells continuously secreting the proteins. Inoculation of these bystander cells close to subcutaneously growing Renca-lacZ/ErbB2 tumors should provide a long-lasting source to achieve high local concentrations of BIg5 at the tumor site. In vivo HC11-BIg5 cells proved to be non-tumorigenic and secreted BIg5 for several weeks, causing a strong anti-BIg5 antibody response. Treatment of established Renca-lacZ/ErbB2 or ErbB2-negative Renca-lacZ tumors by peritumoral inoculation of either HC11-BIg5 or HC11-Ig5 cells led to rejection of all Renca-lacZ/ErbB2, but none of the Renca-lacZ tumors. HC11neo control cells had no effect on tumor growth. Rejection of ErbB2+ tumors led to long-term protection also against subsequent challenge with intravenously injected ErbB2- tumor cells. Intraperitoneal injection of bystander cells secreting the fusion proteins did not lead to tumor regression suggesting that high local concentrations at the tumor site are necessary to target ErbB2 on tumor cells and to overcome elimination of BIg5 or Ig5 by neutralizing antibodies. The CD86 IgV domain of BIg5 did not play a major role in the observed antitumoral immune response suggesting NK-cell mediated ADCC as the initial effector mechanism followed by activation of tumor specific T cells. Targeting of ErbB2 on tumor cells with antibody fusion proteins that interact specifically with the host immune system could be an efficient and specific approach for therapy of solid ErbB2+ tumors.
Tumor-specific T lymphocytes can be regarded as a highly effective mechanism for tumor rejection. A substantial number of T-cell defined tumor antigens including mutated oncoproteins and differentiation antigens have been identified. However, while most spontaneous tumors appear to be antigenic, few are immunogenic. Activation of tumor-specific cytotoxic T cells (CTL) requires presentation of tumor antigens by professional antigen presenting cells (APCs) via MHC I molecules. Due to their crucial role in T-cell activation, APCs are being exploited for active cancer immunotherapy. Present experimental strategies include the incubation of dendritic cells with synthetic, tumor specific peptides to achieve uptake of tumor antigens and presentation in the context of MHC molecules. Alternatively, gene therapeutic approaches are aimed at the endogenous expression of tumor antigens in APCs upon transfer of suitable vector constructs. Our strategy for the presentation of tumor antigens by APCs is based on the intracellular delivery of tumor antigens as part of a fusion protein specifically targeted to APC cell surface receptors. We have constructed prototype molecules that contain a soluble fragment of CTLA-4 for cell binding via interaction with B7 molecules, genetically fused to a protein fragment derived from the tumor-associated antigen ErbB2. To improve uptake and direct the antigenic determinant preferentially to the MHC class I pathway, in one of these protein vaccines also the translocation domain of the bacterial Pseudomonas exotoxin A has been included. In the parental toxin this protein domain facilitates escape from the endosomal compartment to the cytosol upon receptor mediated endocytosis. Here we have investigated the in vitro cell binding activity of such reagents and their antitumoral activity in immunocompetent murine model systems. Specific binding to B7 molecules and uptake of bacterially expressed protein vaccines could be demonstrated. Ex vivo restimulation with an ErbB2-derived peptide of splenocytes from Balb/c mice injected with the fusion proteins resulted in enhanced IFN-gamma production by T cells. Protective and therapeutic effects of ErbB2 protein vaccines were also investigated. Vaccinated animals were protected against subsequent challenge with syngeneic ErbB2 expressing tumor cells. Likewise, s.c. injection of ErbB2 protein vaccines in the vicinity of established tumors resulted in tumor rejection and long lasting protection indicating that immunological memory was induced. Our results suggest that chimeric proteins combining a tumor antigen and specific recognition of APCs in a single molecule are suitable for targeted delivery of antigens to professional APCs and might become valuable tools for cancer immunotherapy.
Das E-Finance Lab publiziert jeweils quartalsweise einen digitalen sowie einen gedruckten Newsletter, die abwechselnd alle sechs Wochen erscheinen. Der digitale Newsletter gibt einen kurzen Überblick über ausgewählte Forschungsarbeiten und nutzt den Einsatz von Hyperlinks zu weiterführenden Informationen. s. http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:hebis:30:3-15886 . Der gedruckte Newsletter "EFL quarterly : an E-Finance Lab publication" hingegen beschreibt kompakt und ergebnisorientiert einzelne Forschungsprojekte.
We study the phase diagram of dense, locally neutral three-flavor quark matter as a function of the strange quark mass, the quark chemical potential, and the temperature, employing a general nine-parameter ansatz for the gap matrix. At zero temperature and small values of the strange quark mass, the ground state of matter corresponds to the color-flavor-locked (CFL) phase. At some critical value of the strange quark mass, this is replaced by the recently proposed gapless CFL (gCFL) phase. We also find several other phases, for instance, a metallic CFL (mCFL) phase, a so-called uSC phase where all colors of up quarks are paired, as well as the standard two-flavor color-superconducting (2SC) phase and the gapless 2SC (g2SC) phase.
We discuss gapless colour superconductivity for neutral quark matter in β equilibrium at zero as well as at nonzero temperature. Basic properties of gapless superconductors are reviewed. The current progress and the remaining problems in the understanding of the phase diagram of strange quark matter are discussed.