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Background: Allergen specific immunotherapy is the only disease modifying treatment of allergic diseases. It induces complex cellular and humoral changes leading to an inhibition of type-1 allergic reactions. Method: Twenty four young grass pollen allergic adults suffering from seasonal rhino-conjunctivitis were randomized to receive standard subcutaneous immunotherapy (n = 18) or to an open control group (n = 6). The number of FceRI receptors on basophils was measured by quantitative analysis of indirect immunofluorescence by flow cytometry. Grass binding to basophils was measured by staining with grass-conjugated fluorescent dye and analyzed by flow cytometry. Basophil sensitivity was determined by the EC50, the logarithm of the allergen concentration leading to half-maximum basophil activation. Results: The number of FceRI receptors decreased from a median 105196 (95% CI: 81283-132038) to 30903 (95% CI: 11482- 85114)/basophil in the treatment group (n = 0.016), while it remained constant in the control group (pre: 102424; post: 103753). We found only minor changes in maximal grass binding on the basophils. The allergen concentration leading to halfmaximum grass binding decreased slightly during SCIT, whereas the EC50 increased significantly by 2.48 (1.38-3.50, n = 16, P

Combining inhaled long‐acting β‐2 agonist (LABA) and inhaled corticosteroid (ICS) seems to offer asthma control at a lower dose of ICS than achieved by ICS alone. Fine mapping of T‐cell surface markers by flow cytometry offers a detailed status of the individual's inflammatory response. The frequency of MT2 (CD4+CD45RA–CD62L+CD11adim) and MT1 (CD4+CD45RA–CD62L–CD11abright) cells in peripheral blood, and their ratio, has been shown to differ predictably in atopics and patients with leprosy, where MT2 correlates with a Th2 phenotype and MT1 with a Th1 phenotype. Stable asthmatics, requiring fluticasone propionate (FP) 750–1000 µg daily or equivalent, were randomized to receive, double‐blinded, either Seretide®[salmeterol and fluticasone propionate (SFC, n = 16)] 50 µg/500 µg bd or FP 500 µg bd (n = 17). If asthma was controlled based on lung function and symptoms at clinic visits every 6 weeks, ICS dose was tapered until asthma exacerbated or 0 µg was reached. The frequency and ratio of MT2 and MT1 T cells of the patients was monitored at 6 week intervals. As treatment tapered, the frequency of MT2 cells decreased (P = 0038 from first to final visit), whereas that of MT1 cells increased. The ratio of MT2/MT1 decreased (P = 0049 from first to final visit). In patients receiving LABA + ICS, the fall in MT2/MT1 ratio appeared to be more pronounced than in patients receiving ICS alone. Thus, the MT2 phenotype may be associated with stable asthma, whereas an imminent exacerbation may associate with an increase in the MT1 phenotype. LABA may allow for a greater effect of FP on the MT ratio.

Diese Darstellung beschreibt das IKARUS-lnstrumentarium, das der Durchführung vonStrategieanalysen zur Reduktion von energiebedingten klimaschädlichen Emissionen inDeutschland dient, und stellt im Arbeitsbereich "Verifikation" die Verbindung zurKlimakonvention her. Sie basiert auf einer Zusammenfassung von sektorspezifischenEinzelberichten (Verzeichnis s. Anhang A), in denen die Details nachgelesen werdenkönnen. Zunächst wird ein Überblick über das Projekt und über die Bestandteile desInstrumentariums gegeben. Sodann wird die Datenbasis beschrieben, die in ihrerDetaillierung, Vollständigkeit und Zuverlässigkeit für die deutsche Energiediskussioneine wesentliche Rolle spielen dürfte. Es folgt die Beschreibung der Datenbank, diesowohl die Modelle versorgt, als auch ein eigenständiges, mit Auswertungssoftwareversehenes Informationssystem darstellt. Im Mittelpunkt des Instrumentariums steht dasgesamtenergiewirtschaftliche Optimierungsmodell mit etwa 2000 repräsentativenTechniken und ihren Verflechtungen im deutschen Energiesystem. Mit Hilfe diesesModells können Auswirkungen von Maßnahmen und Maßnahmenkombinationen zurEmissionsreduktion für ein gesamtwirtschaftlich kostenminimales Energiesystemabgeschätzt werden. Beispiele für solche Analysen werden angegeben. Detaillierteresektorspezifische Untersuchungen und ggf. Datenvorverarbeitung für dasOptimierungsmodell sind mit Simulationsmodellen möglich in den BereichenRaumwärme, Strom und Fernwärme, Industrie und Kleinverbraucher sowie Verkehr. Siehaben bisher einen unterschiedlichen Entwicklungsstand erreicht. Dievolkswirtschaftlichen Randbedingungen und Bezüge der Ein- und Ausgangsgrößen allerdieser technischen Modelle werden durch ein Wirtschaftsmodell hergestellt.Insbesondere der Energiebedarf wird hier abgeschätzt und als exogene Größe desOptimierungsmodells eingesetzt.

Subproject 9 of IKARUS investigates techniques and processes for verifying compliance by states party to the framework convention on climate change and its (future) protocols. They are obliged to limit their GHG emissions and take other climate protection measures and must make (regular) reports on the fulfilment of their obligations. In TP 9 verification is understood to be the independent monitoring of the completeness and correctness of these national reports (declarations) by a specially established organization, although only initial considerations are currently available concerning its form. With the inclusion of the international level, the consideration of all relevant anthropogenic emission sectors and the anticipation of future protocols (e. g. forest protection, agriculture), TP 9 goes beyond the national working field of IKARUS relative to GHG emissions from the energy sector, although it remains closely linked to the overall project since the greatest attention is paid in TP 9 to verifying the declarations via the energy-related GHG emissions. A verification of reports is also required within the framework of efforts by theIPCC and OECD to achieve a standardization of methods for the system of reporting on national GHG emissions (inventories) to be established worldwide. At least as yet the verification concepts of TP 9 and IPCC/DECD differ since they (implicitly) assume different state behaviour: IPCC/DECD concentrate on treaty violations by false or incomplete national declarations which express the states' capacity shortage. It is assumed that in spite of the states' willingness such deficiencies will hamper or delay proper balancing of their emissions. In this sense, verification intends to reveal weaknesses and assist willing but incompetent states to overcome these difficulties with help and advice. This approach is implementation-oriented and corrective. - Over and above this, TP 9 does not exclude the possibility that states or actors in the states deliberately (intentionally) falsify their emission data. Verification measures must therefore be more intensive and capabale of disclosing these intentional treaty violations. For this reason, the feasibility and usefulness of intrusive verification instruments are also examined in TP 9. Evaluation of the instruments, procedures and methods cover two large areas: firstly the (direct) determination of the quantities of GHG released by the respective states by means of measuring techniques and also with the aid of measuring networks and dispersion models; secondly the indirect estimate of the completeness, consistency and accuracy of the emission declarations or the [...]

T lymphocytes play a major role in many immune responses. In the last decade, special focus has been on the function of Th1 and Th2 effector cells. Now the importance of regulatory CD4+CD25+ T cells in maintenance of the immunological homeostasis emerges. Sarcoidosis is a multisystem granulomatous disorder often affecting the lungs. The typical sarcoid granulomas consists of epitheloid cells, macrophages and lymphocytes, mainly CD4+ T cells of Th1 phenotype. We have cultured T cells from bronchial biopsies of patients with sarcoidosis as well as from controls in high levels of interleukin 2 (IL‐2) and IL‐4 and demonstrate spontaneously arising CD4+ CD25+ populations and high concentrations of IL‐10 in these cultures. The main difference between cultures of sarcoid origin compared to controls is a very much higher concentration of the inflammatory cytokines IL‐6 and TNF‐α in cultures of sarcoid origin.

A methodology for a statistical trend analysis (STA) in failure rates is presented. It applies primarily to relatively rare events in changing technologies or components. The formulation is more general and the assumptions are less restrictive than in a previously published version. Relations of the statistical analysis and probabilistic assessment (PRA) are discussed in terms of categorization of decisions for action following particular failure events. The significance of tentatively identified trends is explored. In addition to statistical tests for trend significance, a combination of STA and PRA results quantifying the trend complement is proposed. The STA approach is compared with other concepts for trend characterization.

The historical development of steam boiler technology aboard steam- and later motor-ships is reviewed, setting the stage for statistical investigations of langer term trends in the frequency of boiler explosions. Two different measures of the safety performance have to beaddressed in such an analysis: The explosion rate per ship- or boiler-year in an entire fleet, and the failure ratio, i.e. the probability that a boiler of a certain vintage suffers an explosion during his useful life. The major obstacle for both analyses, the distortions due tostatistical fluctuations, have been dealt with by applying a special smoothing procedure. The failure ratio analysis requires further an estimation of failures to be statistically expected in the future; this is accomplished by means of a previously developed methodology. This paper is primarily concerned with the statistical analysis of boiler exolosion data. The methodology is published elsewhere.

Previous R&D work for the introduction of methanol as an alternative fuel for passenger cars, trucks, industrial burners and hause heating systems was based on the assumption of ever decreasing resources of fossil fuels. As a result of this work cars were developed with engines adapted to the different properties of methanol. Worldwide fleet test programs, and especially the Brazilian Alcohol Program, have clearly shown that alcohols are the best alternative to replace common fuels. Since that time, with the increasing demand for environmental protection and decreased energy supply difficulties, a second generation of methanol technologies has appeared. There are new prototype alcohol cars which are even superior to gasoline cars with modern catalytic converters. The use of a clean fuel further helps to avoid costly and complicated administrative controls. A similarly favourable situation exists for the introduction of methanol as a clean-burning fuel in heating and firingsystems. Methanol with its low carbon/hydrogen ratio represents a big step towards hydrogen technology with which lowest level pollution finally seems to be achievable.

Evaluating the safety of large dams by means of an average value of failures taken over a lang time-span of dam history leads to inadequate results, since it eliminates most of the declining trend. It appears that an analysis that evaluates the trend as such is required to obtain a proper assessment of the safety performance as a basis for failure prognosis and thereby for decision making an investments. Trends appear in dependencies an three different variables: yearof failure, year of construction,and age. Two different methods are presented to analyze these trends: one method for the trend analysis of the fatlure occurrence in time for a dam population, and a secend method for the combined analysis of trends in the construction year and age dependencies. The first method is applied to large dams in the U.S.A. and in Western Europe built after 1850, combined as well as for individual dam types, whereas the secend method is only applied to U.S. embankment dams because of its more extensive data requirements.

A methodology for statistically analysing rare failure events is proposed that may allow an improved evaluation of the longer term progress of the safety performance during the continuing evolution of a technology. The actuarial data base consists of the record of major failures, especially, construction year and age for the failed units, as well as construction rate and size of population. The state-of-the-art of safety is quantified by the failures up to the same age, that requires an augmentation of the actuarial information. A refined (average) age variation of the failure occurrence that is formally derived from the data is employed for the augmentation of the actual failure information. The application of this method is illustrated for the evaluation of the progress of the safety of large embankment dams in the U.S. for the period 1850 through 1980.