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Activation of the high-affinity receptor for IgE (FcepsilonRI) on allergic effector cells induces a multitude of positive signals via immunoreceptor tyrosine-based activation motifs, which leads to the rapid manifestation of allergic inflammatory reactions. As a counterbalance, the coaggregation of the IgG receptor FcgammaRIIB mediates inhibitory signals via immunoreceptor tyrosine-based inhibition motifs. Advances in the positive and negative regulation of Fc receptor expression and signaling have shed light on the role of Fc receptors in our immune system, indicating them to be bifunctional, inhibitory and activating structures. Based on these findings, exciting new therapeutic strategies have been developed, such as the use of chimeric fusion proteins, which concomitantly activate FcepsilonRI and FcgammaRIIB. These new approaches successfully take advantage of the bivalent character of Fc receptors and pave the way for innovative strategies to modulate allergic immune reactions.

Future missions that may be deployed in the European Space Agency's Cosmic Visions 2025 scientific programme may include high energy astrophysics observatories that require focusing optics with unprecedented collection area. We describe scientific drivers for such missions, and discuss various implementations of optics designs that could satisfy the requirements. Options for lightweight reflectors and a possible implementation scenario are described and trade-offs for various coatings are presented.

The next generation astronomical X-ray telescopes (such as the X-ray Evolving Universe Spectroscopy mission XEUS) require extremely large collecting areas (effective area of ~10 m2 at 1 keV) in combination with good angular resolution of ~5" or better. The existing technologies such as polished glass and nickel electroforming would lead to excessively heavy and expensive optics, and/or are not able to produce the required large area. We have developed an entirely novel technology for producing X-ray optics which results in very light, stiff and modular optics. These can be assembled into almost arbitrarily large apertures and are perfectly suited for future astrophysics missions such as XEUS. Indeed this crucial technology ensures that the ambitious mission profile is actually feasible. The technology makes use of commercially available silicon wafers from the semiconductor industry. The latest generation of 12 inch silicon wafers have a surface roughness that is sufficiently low (~0.3 nm) for X-ray reflection, almost perfect mechanical properties and are considerably cheaper than other high-quality optical materials. The wafers are bent into an accurate cone and assembled to form a stiff pore structure. The resulting light and stiff modules, which we term a High-performance Pore Optics (HPO), form a small segment of a Wolter-I optic, and are easily assembled into a modular optic with large collecting area. We have implemented an automated production process of HPOs on laboratory scale and describe facilities developed with ESA at the Cosine Research Centre. We present the status of the production and the results obtained with this highly innovative technology.

The Xeus mission is designed to explore the X-ray emission from objects in the Universe at high redshifts, and the success of the mission depends critically on the deployment of a 10 square metre class telescope system in a suitable orbit for science observations. The minimisation of the telescope mass and volume becomes of critical importance for such a large facility. We describe developments of novel light weight optics that enable a reduction in mass per unit area of more than an order of magnitude, compared with traditional replication optics technology. With such a large collection area, image confusion limits become a scientific driver as well, demanding arcsecond class resolution. We describe measurements that demonstrate the improvement in resolution that gives very high confidence that these requirements can be met. Some implementation details of the mission are briefly mentioned.

Producing the next generation of X-ray optics, both for large astrophysics missions and smaller missions such as planetary exploration, requires much lower mass and therefore much thinner mirrors. The use of pore structures allows very thin mirrors in a stiff structure. Over the last few years we have been developing ultra-low mass pore optics based on microchannel plate technology in glass, resulting in square, open-core glass fibres in a concentric geometry. The surface roughness inside the pores can be as low as 0.5 nm due to the extreme stretching of the surface during production. We show how improvements in the production process have led to an improved quality of the fibers and the quality of stacking the fibers in the required geometry. To achieve een higher imaging quality as required for XEUS we have developed in parallel a novel pore optics technology based on silicon wafers. The production process of silicon wafers is extremely optimised by the semiconductor industry, leading to optical qualities that are sufficient for high-resolution X-ray focussing. We have developed the technology to stack these wafers into accurate X-ray optics, set up automated assembly facilities for the production of these stacks and present very promising X-ray test results of 5.3 arcsec HEW from single reflection off such a stack, showing the great potential of this technology for XEUS and other high-resolution low mass X-ray optics.

Future planetary missions will require advanced, smart, low resource payloads and satellites to enable the exploration of our solar system in a more frequent, timely and multi-mission manner. A viable route towards low resource science instrumentation is the concept of Highly Integrated Payload Suites (HIPS), which was introduced during the re-assessment of the payload of the BepiColombo (BC) Mercury Planetary Orbiter (MPO). Considerable mass and power savings were demonstrated throughout the instrumentation by improved definition of the instrument design, a higher level of integration, and identification of resource drivers. The higher integration and associated synergy effects permitted optimisation of the payload performance at minimum investment while still meeting the demanding science requirements. For the specific example of the BepiColombo MPO, the mass reduction by designing the instruments towards a Highly Integrated Payload Suite was found to be about 60%. This has endorsed the acceptance of a number of additional instruments as core payload of the BC MPO thereby enhancing the scientific return. This promising strategic approach and concept is now applied to a set of planetary mission studies for future exploration of the solar system. Innovative technologies, miniaturised electronics and advanced remote sensing technologies are the baseline for a generic approach to payload integration, which is here investigated also in the context of largely differing mission requirements. A review of the approach and the implications to the generic concept as found from the applications to the mission studies are presented.

The success of the XEUS mission depends critically on the deployment of a 10 square metre class telescope system in a suitable orbit for science observations. The minimisation of the telescope mass and volume becomes of critical importance for such a large facility. We describe developments of novel light weight optics that enable a reduction in mass per unit area of more than an order of magnitude, compared with traditional replication optics technology. With such a large collection area, image confusion limits become a scientific driver as well, demanding arcsecond class resolution. We describe measurements that demonstrate the improvement in resolution that gives very high confidence that these requirements can be met.

The next generation astronomical X-ray telescopes (e.g. XEUS) require extremely large collecting area (10 m2) in combination with good angular resolution (5 arcsec). The existing technologies such as polished glass, nickel electroforming and foil optics would lead to excessively heavy and expensive optics, and/or are not able to produce the required large area or resolution. We have developed an entirely novel technology for producing X-ray optics which results in very light, stiff and modular optics which can be assembled into almost arbitrarily large apertures, and which are perfectly suited for XEUS. The technology makes use of commercially available silicon wafers from the semiconductor industry. The latest generation silicon wafers have a surface roughness that is sufficiently low for X-ray reflection, are planparallel to better than a micrometer, have almost perfect mechanical properties and are considerably cheaper than other high-quality optical materials. The wafers are bent into an accurate cone and assembled to form a light and stiff pore structure with pores of the order of a millimeter. The resulting modules form a small segment of a Wolter-I optic, and are easily assembled into an optic with large collecting area. We present the production principle of these silicon pore optics, the facilities that have been set up to produce these modules and experimental results showing the excellent performance of the first modules that have been produced. With further improvement we expect to be able to match the XEUS requirements for imaging resolution and mass.

The high affinity receptor for IgE, FcepsilonRI, is a multimeric surface receptor that is expressed exclusively as a tetramer on rodent cells, but exists as a tetramer or trimer on human cells. The tetrameric form is expressed on effector cells of allergic responses such as mast cells and basophils and is composed of an IgE-binding alpha-subunit, a beta-subunit and a gamma-subunit dimer. Complexes lacking the beta-subunit are found on human antigen-presenting cells. On mast cells and basophils, FcepsilonRI is essential for IgE-mediated acute allergic reactions. Crosslinking of FcepsilonRI by IgE and multivalent antigen induces a signaling cascade that culminates in the release of preformed mediators and the synthesis of lipid mediators and cytokines. The beta-subunit functions as an amplifier of FcepsilonRI expression and signaling. As a consequence, strongly enhanced mast cell effector functions and in vivo allergic reactions can be observed in the presence of FcepsilonRIbeta. In contrast, a truncated beta-isoform (betaT) that is produced by alternative splicing acts as an inhibitor of FcepsilonRI surface expression. Thus, by producing two proteins with antagonistic functions, the FcepsilonRIbeta gene could serve as a potent regulator of allergic responses. In addition, the genomic region encompassing the beta-chain has been linked to atopy and a number of polymorphisms within the FcepsilonRIbeta gene are associated with various atopic diseases. It remains to be elucidated how these polymorphisms might affect the allergic phenotype. These functions of the beta-chain together with the described genetic linkages to atopy make it a candidate for a role in the pathophysiology of allergic diseases.

A convenient synthesis of trisamido molybdenum(VI) alkylidyne complexes has been developed, in which the key step is the addition of a geminal dichloride to a trisamido molybdenum(III) complex in the presence of magnesium to continuously recycle unwanted side product 4, selectively generating the desired alkylidyne complexes in high yield.

In the Science Payload Technology Division of the European Space Agency X-ray optics are being developed for space based astrophysics observatories and planetary missions. Due to the gazing incidence geometries required in the x-ray regions of interest, and the high angular resolutions required, the mass of the optics becomes a major driver in mission design. New technologies have to be explored for future applications, simultaneously achieving good angular resolution and low mass while maintaining collecting aperture. The cosmology mission XEUS requires very large effective area, 30m2 at 1keV, x-ray optics with high angular resolution of below 5" with a goal of 2". This implies a large aperture for a single telescope system, which will necessarily require assembly or deployment in space, and which will be formed by basic mirror modules known as petals. The petals must remain compatible with compact ground handling and production tools and will require minimum modifications to existing calibration facilities. The technology for the implementation of this Wolter-I design is currently based on the European heritage of x-ray optics development and production, dating back to Exosat, launched in 1983, to the currently operating XMM-Newton observatory. Substantial further research and development is required, however, with the key aspects therefore being low mass design and industrialization of the production. New approaches are being considered in parallel to evolutions of the current state-of-the-art technologies. In addition to the XEUS mission optics options, extremely low mass Wolter-I optics are being developed for applications in very deep orbits or planetary remote sensing, having even stronger mass constraints, but having a more relaxed angular resolution requirement. Such optics systems feature dramatically reduced mirror thickness and therefore mass. The current state of development of the ultra-lightweight x-ray optics systems will be presented together with future development plans.

A decade ago, the discovery of the high-affinity receptor for IgE (FcϵRI) on epidermal Langerhans cells documented the end of the dogma that FcϵRI is only expressed on effector cells of anaphylaxis. Since then, the functional significance of this receptor on antigen-presenting cells (APCs) has been an area of intense research work. Scientists have focused on a better understanding of the molecular structure, regulation, and role of FcϵRI on APCs in the human immune system. Insights into the cellular events linked to the activation of APCs on ligation of FcϵRI by IgE and allergens might provide the basis for new aspects in the pathophysiology of allergic diseases and the design of future diagnostic and therapeutic strategies. This review is dedicated to the 10th anniversary of the discovery of FcϵRI on APCs and describes the numerous areas of research in this field. (J Allergy Clin Immunol 2003;111:38-44.)

The trimeric high-affinity IgE receptor (FcepsilonRI) on human epidermal Langerhans cells mediates IgE-dependent antigen uptake and subsequent antigen focusing. Its expression is upregulated on Langerhans cells (FcepsilonRIhigh Langerhans cells) and inflammatory dendritic epidermal cells (FcepsilonRIhigh inflammatory dendritic epidermal cells) in the skin of patients with atopic dermatitis. In the absence of the amplifying beta-chain in these cells, FcepsilonRI signaling (indicated by calcium mobilization and activation of the transcription factor nuclear factor-kappaB) is only detectable in FcepsilonRIhigh Langerhans cells from atopics, but not FcepsilonRIlow Langerhans cells from nonatopics. Therefore we investigated protein-tyrosine kinases putatively involved in FcepsilonRI signaling in Langerhans cells and asked whether differences in their expression and FcepsilonRI-induced activity could explain the dichotomic responses observed in atopic vs nonatopic individuals. First, we found the src protein-tyrosine kinases p53/56lyn, p59fyn, p56/59hck, p55c-fgr, and p60c-src to be expressed in Langerhans cells from all donors. In addition, whereas p56lck was lacking, p72syk and the negative regulatory p50csk were detected. Upon terminal maturation of Langerhans cells in vitro, no significant change of the protein- tyrosine kinase expression profile except downregulation of p56/59hck was observed. In contrast, significant upregulation of all protein-tyrosine kinase expressed except p50csk was detected in FcepsilonRIhigh Langerhans cells, but not in FcepsilonRIhigh inflammatory dendritic epidermal cells. Finally, the important protein-tyrosine kinases substrate phospholipase C-gamma1, which is also essential for downstream calcium mobilization, was only phosphorylated upon FcepsilonRI triggering in FcepsilonRIhigh Langerhans cells from atopics, but not in FcepsilonRIlow Langerhans cells from nonatopics. Therefore, upregulation of FcepsilonRI and protein-tyrosine kinase expression as well as subsequent protein-tyrosine kinase activity may explain, at least in part, that an efficient signaling pathway in terms of calcium mobilization is restricted to FcepsilonRIhigh Langerhans cells from atopic individuals. Key words

Langerhans cells (LC) are a unique population of dendritic cells (DC) found in the epidermis where they can be identified by the expression of CD1a, E-cadherin and cytoplasmic Birbeck granules (BG) as their hallmark. Over the past years many techniques have been described to generate LC in vitro from either monocytes or CD34(+) hematopoietic cell progenitors. Antibodies against Lag and Langerin (two epitopes associated with BG) and E-cadherin (a Ca(2+)-dependent homophilic adhesion molecule) have been used to detect in vitro-generated LC. In this study we investigated whether the expression of E-cadherin on in vitro-generated CD1a(+) from either CD34(+) cells or monocytes is able to discriminate LC from other DC. Our results demonstrate that E-cadherin alone is not a reliable marker to specifically identify in vitro-generated LC.

In contrast to mast cells and basophils, the high-affinity IgE receptor (Fc(epsilon)RI) on monocytes and dendritic cells (DC), including epidermal Langerhans cells, is not constitutively expressed and lacks the beta-chain. Fc(epsilon)RI is upregulated on Langerhans cells of atopic individuals, particularly in atopic dermatitis skin. Although Fc(epsilon)RI provides IgE-mediated antigen focusing on monocytes and DC/Langerhans cells, its relevance for cell activation remains elusive, and the transcription factors regulating Fc(epsilon)RI-induced genes are unknown. We show that NF-kappaB, known to regulate genes essential for inflammatory responses and DC differentiation and function, is activated upon Fc(epsilon)RI ligation in primary human monocytes and DC. In Langerhans cells isolated from epidermis, NF-kappaB activation is restricted to donors expressing high Fc(epsilon)RI amounts. Fc(epsilon)RI-induced NF-kappaB complexes in monocytes and DC contain p50 and p65, but no other NF-kappaB subunits despite increased RelB expression during differentiation. NF-kappaB activation is preceded by serine phosphorylation and degradation of its inhibitory protein IkappaB-alpha without involving other IkappaB proteins. Finally, we show that Fc(epsilon)RI ligation on monocytes and DC leads to synthesis and release of tumor necrosis factor-alpha and monocyte chemoattractant protein-1, which is decreased by two mechanistically distinct inhibitors of NF-kappaB activation. Thus NF-kappaB activation represents a novel mechanism by which Fc(epsilon)RI on monocytes and DC potentially controls inflammatory reactions.

Dimerization of the alkynylcarbene complex Cp(CO)(2)Re=C(Tol)C(triple bond)CCH(3) (8) occurs at 100 degrees C to give a 1.2:1 mixture of enediyne complexes [Cp(CO)(2)Re](2)[eta(2),eta(2)-TolC(triple bond)CC(CH(3))=C(CH(3))C(triple bond)CTol] (10-Eand 10-Z), showing no intrinsic bias toward trans-enediyne complexes. The cyclopropyl-substituted alkynylcarbene complex Cp(CO)(2)Re=C(Tol)C(triple bond)CC(3)H(5) (11) dimerizes at 120 degrees C to give a 5:1 ratio of enediyne complexes [Cp(CO)(2)Re](2)[eta(2),eta(2)-TolC(triple bond)C(C(3)H(5))C=C(C(3)H(5))C(triple bond)CTol] (12-E and 12-Z); no ring expansion product was observed. This suggests that if intermediate A formed by a [1,1.5] Re shift and having carbene character at the remote alkynyl carbon is involved, then interaction of the neighboring Re with the carbene center greatly diminishes the carbene character as compared with that of free cyclopropyl carbenes. The tethered bis-(alkynylcarbene) complex Cp(CO)(2)Re=C(Tol)C(triple bond)CCH(2)CH(2)CH(2)C(triple bond)CC(Tol)= Re(CO)(2)Cp (13) dimerizes rapidly at 12 degrees C to give the cyclic cis-enediyne complex [Cp(CO)(2)Re](2)[eta(2),eta(2)-TolC(triple bond)CC(CH(2)CH(2)CH(2))=CC(triple bond)CTol] (15). Attempted synthesis of the 1,8-disubstituted naphthalene derivative 1,8-[Cp(CO)(2)Re=C(Tol)C(triple bond)C](2)C(10)H(6) (16), in which the alkynylcarbene units are constrained to a parallel geometry, leads to dimerization to [Cp(CO)(2)Re](2)(eta(2),eta(2)-1,2-(tolylethynyl)acenaphthylene] (17). The very rapid dimerizations of both 13 and 16 provide compelling evidence against mechanisms involving cyclopropene intermediates. A mechanism is proposed which involves rate-determining addition of the carbene center of A to the remote alkynyl carbon of a second alkynylcarbene complex to generate vinyl carbene intermediate C, and rearrangement of C to the enediyne complex by a [1,1.5] Re shift.

The photoconductor detector arrays for the PACS instrument (Photoconductor Array Camera and Spectrometer) aboard the future ESA telescope Herschel have been developed during the engineering phase in 1999. In early 2000 the construction of the qualification models began for both, the highly and low stressed Ge:Ga arrays, which consist of 12 linear modules each. These two types of photoconductor arrays are dedicated for different wavelengths bands in the spectrometer section of the instrument. While the performance of a few engineering arrays has been studied and presented earlier, additional data are meanwhile available on the absolute responsivity and quantum efficiency of the detectors. Furthermore, experience has been obtained during manufacture of a larger series of arrays giving better statistics on performance aspects, such as uniformity of the cutoff wavelengths and of the responsivity or the maximum stress obtainable within such arrays. Considerable progress has also been made in the development and manufacture of the 4 Kelvin Cold Read-out Electronics (CRE), which will integrate and multiplex the signals generated in each linear array with its 16 detector pixels. Manufacture of the detector arrays for the qualification model is scheduled to be completed by this summer, and manufacture of the flight model has already started. The qualification model will be delivered to the test facilities, where absolute spectral performance of the 24 linear modules will be determined. In this paper we give a summary of the related activities and results as obtained during manufacturing and testing.

IgE receptors are implicated as important components of the immunological pathway in allergic and inflammatory diseases. Recent investigations have begun to unravel the structure, signal transduction and function of IgE receptors from different cell types in rodent and human systems. Studies of the mechanisms involved might provide opportunities for therapeutic intervention strategies in the treatment of allergic and hypersensitivity reactions.

Professional antigen-presenting cells (APC) such as monocytes and dendritic cells (DC) bearing high-affinity IgE receptors (FcΕRI) efficiently present IgE-bound antigens to T cells. FcΕRI expression is upregulated on APC from atopic donors, especially in inflamed tissues. These data suggest a pathophysiological concept of an IgE-mediated delayed-type hypersensitivity reaction in atopic diseases. However, FcΕRI ligation also leads to the synthesis of proinflammatory cytokines and other molecules involved in inflammatory reactions. The investigation of transcription factors mediating these effects has only recently commenced. In general, members of the NF-ĸB family are known to regulate APC function and differentiation, with the RelB subunit being especially important in DC generation. In addition, Ikaros and PU.1 have also been shown to be essential factors for DC differentiation, whereas Oct-2 is upregulated by differentiation towards macrophages. Recently, FcΕRI has been demonstrated to induce NF-ĸB activation via IĸB-α serine phosphorylation and degradation in monocytes and DC. Inhibitors of NF-ĸB activation such as N-acetylcysteine or N-tosyl-L-phenylalanine chloromethyl ketone can suppress FcΕRI-induced TNF-α and MCP-1 release. Interestingly, in human epidermal Langerhans’ cells (LC), NF-ĸB activation can only be observed when large amounts of FcΕRI are present. In addition, the composition of NF-ĸB complexes differs between monocytes, monocyte-derived DC and LC, suggesting a cell type-specific regulation. Moreover, the transcription factor NFAT is induced upon FcΕRI ligation in human APC. The elucidation of further transcription factors involved in FcΕRI signaling in APC should contribute to the employment of new inhibition strategies for the treatment of atopic and other inflammatory diseases.

The High Energy Transmission Grating Spectrometer of the Chandra X-Ray Observatory is a high spectral resolution instrument utilizing gold X-ray transmission gratings. The gratings have been subjected to a rigorous program of calibration, including testing at synchrotron facilities for the purpose of refining and testing the grating model. Here we conclude our investigation of the optical constants of gold, extending it below 2 keV to complete the coverage over the Chandra energy range. We investigate the carbon, nitrogen, oxygen and chromium edge structures introduced by the grating support membrane. Finally, we summarize the state of the grating model, identifying those energy regions where the residuals are most significant and suggesting where the model might be improved.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

For the instrument PACS (Photoconductor Array Camera and Spectrometer) aboard FIRST two photoconductor arrays dedicated for different wavelengths bands are foreseen in the spectrometer section. Each camera consists of 25 linear arrays of 16 stressed Ge:Ga crystals. The arrays with 2 X 400 pixels will be used for imaging line spectroscopy in the wavelengths ranges 60 micrometers to 110 micrometers and 110 micrometers to 210 micrometers . The detectors are read out by a new generation of integrating and multiplexing cryogenic read-out electronics, which is currently under redesign and further development. The development of the arrays has passed the engineering phase and entered the qualification status. We summarize the results obtained with the engineering arrays and the first 6 qualification models with respect to their performance such as uniformity of current sensitivity and cutoff wavelength. The impacts of the result of the first 6 linear arrays on the qualification model are described together with the final design which is supposed to fulfill the specifications and requirements of the instrument PACS.

The Photoconductor Array Camera and Spectrometer (PACS) will be equipped with two sensor arrays consisting of 16 X 25 pixels each. Arranged in linear arrays of 16 detectors the sensitivity of the sensors is tuned to the wavelength ranges 60 micrometers to 130 micrometers and 130 micrometers to 210 micrometers , by applying different levels of stress to the Ge:Ga crystal utilizing a special leaf spring which is part of each of the 25 modules. The electronics of the sensors are mounted on the same module but thermally isolated from the sensor level which is at a lower temperature of about 2 K. The sensors are read out by a specially developed integrating and multiplexing cryogenic read-out electronics. With a fore optics made of light cones in front of the detector cavities a 100% filling factor is achieved and a high quantum efficiency close to 0.5 is expected. In order to achieve extremely good stress uniformity in all detectors and therefore equal cutoff wavelengths, a high degree of the quality of the Ge:Ga detectors and of the assembling components used for this dedicated stress mechanism is required. The first 6 engineering modules have been successfully manufactured and tested afterwards. The relative responsivity of a set of pixels has been determined and a good performance has been demonstrated for the sensors, which are very close to fulfilling the requirements for PACS aboard the infrared spectra telescope FIRST.

We have performed a series of measurements with the Physikalisch-Technische Bundesanstalt beamline of the electron storage ring BESSY 1 which provide the basis for the absolute calibration of the Advanced CCD Imaging Spectrometer (ACIS). ACIS is a prime focal plane instrument aboard the recently-launched Chandra X-ray Observatory. We have achieved an absolute detection efficiency knowledge accurate to better than 5% over the 0.3 - 4 keV band. We describe our measurement and analysis techniques, including our detector response modeling and pileup corrections. We summarize a variety of external and internal consistency checks which provide the basis for our error estimates. We discuss the factors limiting the accuracy of our measurements.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Monocytes have a limited life span, and their homeostasis is regulated by apoptosis in vivo. When cultured in the absence of appropriate exogenous stimuli, they undergo apoptosis, but under the influence of survival signals, these cells differentiate into macrophages or dendritic cells. Here we show that ligation of the high-affinity IgE receptor (FcepsilonRI) on human monocytes from nonatopic individuals markedly reduces apoptosis induced by serum deprivation or by CD95/Fas ligation. Aggregation of FcepsilonRI reduces its own expression but fails to modulate CD95/Fas expression. In contrast, FcepsilonRI ligation enhances the expression of the antiapoptotic molecules Bcl-2 and Bcl-xL, but not Mcl-1, in monocytes. Incubation of unstimulated cells with culture supernatants of FcepsilonRI-activated monocytes prolongs their life span, whereas CD95/Fas expression remains unaffected. The incidence of apoptosis is restored considerably when the supernatant is depleted of TNF-alpha, whereas elimination of IL-1beta, GM-CSF, or IL-12 has no effect. These results indicate that FcepsilonRI mediates signals preventing monocyte apoptosis directly by increasing the levels of Bcl-2 and Bcl-xL, and indirectly by means of TNF-alpha in an autocrine and paracrine fashion. This process may contribute to the establishment of chronic allergic disorders such as atopic dermatitis.

For the Photoconductive Array Camera and Spectrometer (PACS) 2 sensor arrays consisting of each 16 X 25 pixels are foreseen. The sensors arranged in linear arrays with 16 detectors are tuned to the wavelength ranges 60 micrometer to 130 micrometer and 130 micrometer to 210 micrometer by applying different levels of stress to the Ge:Ga crystals utilizing a special leaf spring which is part of each of the 25 modules. The electronics of the sensors are mounted on the same module but thermally isolated from the sensor level which is linked to a 1.7 K stage. The sensors are read out by a new generation of the integrating and multiplexing cryogenic readout electronics (CRE). With the optical design a 100% filling factor is achieved and with a fore optics made of light cones in front of the detector cavities a high detection efficiency close to 1 is expected. In order to achieve extreme high stress uniformity among all detectors and therefore equal cutoff wavelengths, a high degree of the quality of the Ge:Ga detectors and of the assembling components used for this dedicated stress mechanism is required. The first two engineering modules have been successfully manufactured and tested afterwards. The relative responsivity of a set of pixels has been determined and a good performance demonstrated for the sensors which are very close to fulfill the requirements for PACS aboard the infrared telescope FIRST.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We have performed precise measurements of x-ray absorption constants for all the thin films comprising CCD gate structure, namely, phosphorous doped polysilicon, silicon dioxide, and silicon nitride. X-ray absorption of these films shows large oscillations around the corresponding absorption edges: nitrogen K, oxygen K, silicon L and K. As a result, quantum efficiency of a CCD in the soft x-ray range deviates significantly from the generally assumed simple model predictions. In order to cover the range of energies from 60 eV to 3000 eV transmission measurements were performed at several synchrotron beamlines at ALS, PTB BESSY, SRC. A model of the CCD response with near edge x-ray absorption structure taken into account predicts a very complicated shape of the energy dependence of the quantum efficiency around silicon and oxygen absorption edges. Experimental measurements of CCD quantum efficiency relative to a calibrated detector were performed at BESSY for both frontside illuminated and backside illuminated CCDs for energies around the oxygen absorption edge. Experimental results were found to be in a good agreement with our model.

Using a CdZnTe sample detector, a variety of diagnostic tools are applied, so as to assess the crystal characteristics and to compare these to the x-ray response measured with synchrotron radiation. Correlations are found, such that x-ray response degrading processes can be identified. In this respect the performance of the detector is found to be limited by both large scale defects such as some grain boundaries and also pipes and by crystal imperfections, together with impurities and other crystal defects, both at the surface and in the bulk crystal. The relatively soft CdZnTe crystals are very sensitive to improper handling, producing particularly surface damage, which in turn deteriorates the detector performance, as is rather clearly established by photoluminescence measurements.

The design, calibration, and performance of the high purity germanium (HPGe) solid state detectors (SSDs) used in the calibration of the Advanced X-ray Astrophysics Facility high resolution mirror assembly (HRMA) is discussed. The focal plane SSD was used with various apertures to measure the point response function, as well as the effective area of the mirror. The good energy resolution of the detector allowed the effective energy of the mirrors to be measured with a single exposure using a continuum source. The energy resolution was also exploited in measuring the molecular contamination on the mirror surfaces. The SSDs are the transfer detector standards for the HRMA calibration over the energy range from 700 eV to 10 keV. The calibration of the SSDs was performed mostly at the PTB radiometry laboratory using the electron storage ring BESSY. The spectral and spacial distribution of the undispersed synchrotron radiation can be calculated from first principles using the Schwinger Equation. With the electron storage ring being run in a reduced current mode of a few electrons, uncertainties in the calculated flux are below 1%. A comparison of the measured and calculated flux made it possible to determine the detector efficiency with an uncertainty of typically 1%. Electronic effects such as pile- up, count rate linearity and deadtime have been investigated.

The prelaunch calibration of AXAF encompasses many aspects of the telescope. In principle, all that is needed is the complete point response function. This is, however, a function of energy, off-axis angle of the source, and operating mode of the facility. No single measurement would yield the entire result. Also, any calibration made prior to launch will be affected by changes in conditions after launch, such as the change from one g to zero g. The reflectivity of the mirror and perhaps even the detectors can change as well, for example by addition or removal of small amounts of material deposited on their surfaces. In this paper, we give a broad view of the issues in performing such a calibration, and discuss how they are being addressed in prelaunch preparation of AXAF. As our title indicates, we concentrate here on the total throughput of the observatory. This can be thought of as the integral of the point response function, i.e. the encircled energy, out to the largest practical solid angle for an observation. Since there is no standard x-ray source in the sky whose flux is well known to the approximately 1% accuracy we are trying to achieve, we must do this calibration on the ground. We also must provide a means for monitoring any possible changes in this calibration from prelaunch until on-orbit operation can transfer the calibration to a celestial x-ray source whose emission is stable. In the paper, we analyze the elements of the absolute throughput calibration, which we call the effective area. We review the requirements for calibrations of components or subsystems of the AXAF facility, including the mirror, detectors, and gratings. We show how it is necessary to have an absolute calibrated detection system available during the prelaunch calibrations to measure the flux in the x-ray beam used for calibrating AXAF. We show how it is necessary to calibrate this ground-based detection system at standard man-made x-ray sources, such as electron storage rings. We present the status of all these calibrations, with indications of the measurements remaining to be done, even though the measurements on the AXAF flight optics and detectors will have been completed by the time this paper is presented. We evaluate progress toward the goal of making 1% measurements of the absolute x-ray flux from astrophysical sources, so that comparisons can be made with their emission at other wavelengths, in support of observations such as the Sunyaev-Zeldovitch effect, which can give absolute distance measurements independent of the traditional distance measuring techniques in astronomy.

IgE-bearing human epidermal Langerhans cells (LC) are suspected of playing a key role in the pathogenesis of atopic dermatitis (AD). We and others have shown that these cells bind IgE via the high affinity receptor Fc epsilon RI (FceRI) (1, 2). Recent findings have shown that the expression of this receptor on LC and related dendritic cells in the skin is highly upregulated in lesions skin of AD when compared with nonatopic individuals and this is correlated to a high IgE serum levels (3). Functionally, LC from normal skin differ from those of atopic skin in terms of calcium mobilization upon receptor ligation (4). Beside qualitative alterations in the activation cascade, unresponsiveness also may be related to inefficient triggering in normal LC displaying low amounts of receptors. Thus, the variations in receptor expression may be crucial for the outcome of the signal transduction initiated by FceRI-cross-linking on LC, implying the need of a better understanding of the mechanisms regulating the receptor display on LC. However, detailed functional, biochemical and molecular biological analysis of FceRI + LC is hampered by the limited number of LC routinely obtained from skin biopsies or surgical samples. Recently several cytokines, especially granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-α), have been identified that speed the development of dendritic cells from blood and bone marrow precursors in suspension cultures (5, 6, 7, 8, 9). We took advantage of this progress to establish a model for the study of the regulation of FceRI on LC and other dendritic cells.

Soft x-ray detectors for astronomical applications are often also sensitive to visible and UV photons. Filters of a new design have been developed, which could be used in future missions to suppress the flooding of x-ray detectors by low energy photons. Three series of filters are discussed: aluminum/silicon multilayers, Niobium and calcium/boron multilayers. The filters are typically 100 to 200 nm thick and reject the IR/visible/UV from 10-4 to 10-6. The transmission for soft x-rays is above 10% for wavelengths less than 30 nm, when combining the bandpasses of at least two filters. The optimum transmission band depends very much on the filter type. The IR/visible/UV has been measured using standard laboratory spectro- photometers while the x-ray transmission characteristics have been determined using synchrotron radiation.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

In order to characterize the instrumentation on AXAF, each of the science instrument teams carries out sub-assembly calibrations. For the high energy transmission grating (HETG) group, this means individual measurements of the diffraction efficiencies of each of the 336 grating elements that goes into the completed HETG assembly. Measurements are made at a number of energies (corresponding to x-ray emission lines) which fix the parameters of a model. This model is determined from first principles and verified by extensively testing sample grating elements at synchrotron radiation facilities. Here we present new synchrotron radiation (SR) data obtained at the national Synchrotron Light Source (NSLS) and at the radiometry laboratory of the Physikalisch-Technische Bundesanstalt (PTB) using the electron storage ring BESSY in Berlin. The gratings are from AXAF flight lots, and we apply an improved data reduction technique which builds on our experience from last year (Markert et al., SPIE Proceedings 2518, 424, 1995). Our analysis takes into account the effects of small extended wings in the diffraction of the various orders in the NSLS data. Our goal is to obtain efficiencies in the 0th and plus/minus 1st diffraction orders which are accurate in the 1% level, except near absorption edges, where accuracies in the 5% to 10% level are required. With a few exceptions (discussed here) our new data/improved model meets these goals.

A convenient synthesis of trisamido molybdenum(VI) alkylidyne complexes has been developed, in which the key step is the addition of a geminal dichloride to a trisamido molybdenum(III) complex in the presence of magnesium to continuously recycle unwanted side product 4, selectively generating the desired alkylidyne complexes in high yield.

The polymerization pathways of epoxidized and hydroxylated triglycerides with phosphoric acid (H3PO4) were investigated using model reactions. Involved epoxides and diols were derived from oleic acid methyl ester, which was easily monitored by one- and two-dimensional nuclear magnetic resonance (NMR) techniques as well as electrospray ionization mass spectroscopy (ESI-MS). Phosphoric acid played two key functions: (a) as a Bronsted acid catalyst that activated the epoxide toward nucleophilic attack by the diol, thus generating ether (C–O–C) cross-linkages; and (b) as a reaction partner establishing phosphate ester linkages [(RO)2(O)P–O–C, R = C or H]. In studies with 18O labeled diol, phosphate esters formed exclusively from H3PO4 and epoxide without incorporation of diol whereas diols acted as polymerization initiators in polyether formations.

We perform precise measurements of the x-ray transmission of the thin films comprising CCD gate structure, namely, phosphorus doped polysilicon, silicon dioxide, and silicon nitride. The x-ray transmission of these films shows large oscillations with small changes in energy in the vicinity of the following absorption edges: nitrogen K (400 eV), oxygen K (536 eV), silicon L and K (100 and 1840 eV, respectively). As a result, quantum efficiency of a CCD in the soft x-ray range deviates significantly from simple model predictions based on Henke et al. (1993) mass absorption coefficients. The measurements covered the range of energies from 60 to 3000 eV, using synchrotron beamlines at the Advanced Light Source (ALS; Berkeley), Physikalisch-Technische Bundesanstalt BESSY (Berlin), the Synchrotron Radiation Center (SRC; University of Wisconsin-Madison). Our model of the CCD response includes near edge x-ray absorption structure and predicts a very complicated shape of the energy dependence of the quantum efficiency around silicon and oxygen absorption edges. Experimental measurements of CCD quantum efficiency relative to a calibrated detector at the BESSY synchrotron confirmed our model predictions for both frontside and backside illuminated CCDs.

Inflammatory dendritic epidermal cells present in skin lesions of the atopic eczema/dermatitis syndrome display the highest expression of the high-affinity receptor for IgE (FcepsilonRI), ever detected on human antigen-presenting cells. Owing to the instability of the FcepsilonRI (alphagammagamma) complex and fast cleavage from the cell surface during the interleukin-4/granulocyte-macrophage colony-stimulating factor driven in vitro differentiation of monocytes, a method to generate inflammatory dendritic epidermal cells was not at our disposal in the past and the amount of ex vivo isolated inflammatory dendritic epidermal cells available for functional assays was limited. Therefore, information about the role of inflammatory dendritic epidermal cells and FcepsilonRI on this dendritic cell subtype in atopic and inflammatory skin diseases is completely missing. In this study, we were able to: (i) increase the expression of a functional FcepsilonRI complex on the cell surface of immature monocyte-derived dendritic cells from atopic donors by creating a reducing microenvironment; (ii) enhance significantly the intracellular pool of the FcepsilonRIgamma chains, which is the limiting parameter for the FcepsilonRI surface expression; and (iii) generate monocyte-derived dendritic cells displaying the phenotypical characteristics of inflammatory dendritic epidermal cells, producing high amounts of proinflammatory cytokines and chemokines similar to the cytokines found in lesional skin of the atopic eczema/dermatitis syndrome. Altogether the high expression of functional FcepsilonRI on these cells enables us for the first time to study inflammatory dendritic epidermal cells and FcepsilonRI-mediated mechanisms of inflammatory dendritic epidermal cells in vitro, in order to shed light on the putative role of this important cell type in the atopic eczema/dermatitis syndrome.

Patients with atopic dermatitis display substantial immunologic abnormalities, among which elevated total IgE is considered as a hallmark; however, a subgroup of atopic dermatitis patients exhibits normal IgE levels, but mechanisms contributing to the so-called "intrinsic" or "nonallergic" form of atopic dermatitis are obscure. In order to unravel similarities and differences of both atopic dermatitis subtypes, the phenotype of monocytes, total serum IgE levels, and serum levels of cytokines regulating the IgE production from nonatopic individuals and patients with allergic rhinitis, and extrinsic and intrinsic atopic dermatitis were measured. Concomitantly, genomic DNA probes of all subjects were analyzed for single nucleotide polymorphisms of candidate genes of structures involved in the regulation of the IgE synthesis, such as interleukin-4 and the interleukin-4R/interleukin-13R. Our data show that the surface expression of the high- and low-affinity receptor for IgE (FcepsilonRI and FcepsilonRII/CD23) and the interleukin-4Ralpha chain were significantly elevated in monocytes from patients with extrinsic atopic dermatitis. Furthermore, serum levels of interleukin-13 were significantly increased in patients with intrinsic atopic dermatitis. In addition, the frequency of the interleukin-4Ralpha polymorphism C3223T and the interleukin-4 polymorphism C590T tended to be higher in extrinsic atopic dermatitis than in intrinsic atopic dermatitis. Altogether our findings indicate that intrinsic atopic dermatitis patients exhibit phenotypic and immunologic features, which differ from those of patients with extrinsic atopic dermatitis or other atopic disorders.