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BACKGROUND Metastatic cutaneous squamous cell carcinoma (cSCC) carries a poor prognosis. Increased numbers of CD8+ cytotoxic T cells are associated with a favorable prognosis and programmed cell death receptor-1 is a suppressor of the CD8+ cytotoxic T cell response. We aim to define their expression in metastatic cutaneous squamous cell carcinoma. METHODS Cytotoxic T cell infiltrates and tumoral PD-L1 expression in lymph node metastases from patients with cSCC of the head and neck were analyzed. RESULTS High tumoral PD-L1 expression, intratumoral and peritumoral CD8+ cell density in metastases were significantly associated with poor primary tumor differentiation. Low PD-L1 expression, intratumoral and peritumoral CD8+ density were associated with lower grade primary tumor differentiation. Low PD-L1 expression correlated with disease progression. CONCLUSIONS Increased expression of PD-L1 correlates with increased CD8+ cell density. Increased expression of PD-L1 in poorly differentiated tumors may be more likely to benefit from anti PD-1/PD-L1 therapy.

Background Angiotropism is the histopathological correlate of pericytic mimicry and extravascular migratory metastasis (EVMM), a mechanism of melanoma spread by migration along the external surface of blood and lymphatic vessels. The frequency of angiotropism in primary cutaneous melanoma and the clinical utility of its detection remain unclear. Methods We investigated angiotropism in 179 primary cutaneous melanomas by hematoxylin and eosin (H&E), CD31, and S100/D240 stains. Results We detected angiotropism in 31 cases (17%) by H&E. CD31 immunohistochemistry increased detection to 59 cases (33%). When lymphatic vessels were included by using S100/D240 stains, 67 cases (37%) cases were positive. Angiotropism was associated with lymphatic invasion and mitotic rate with all detection methods. There was an association with increased tumor thickness when detected by H&E and CD31. No association with sentinel lymph node status was seen. By H&E and CD31 staining, angiotropism was associated with disease progression and distant metastases by univariate, but not multivariate analysis. Overall survival was not affected by the presence of angiotropism. Conclusions Angiotropism is relatively common in primary melanoma when immunohistochemical stains are used for detection and associated with mitotic rate and intravascular lymphatic invasion. The association with disease progression and distant metastasis suggests that it represents an alternative pathway of metastasis, that is, EVMM/pericytic mimicry vs intravascular spread.

Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer. We evaluated the efficacy of everolimus in aggressive, radioactive iodine–refractory (RAIR) thyroid cancer and correlated tumor mutational profiling with response. Exploratory medullary and anaplastic thyroid cancer cohorts were included. Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009 to 2013 in patients with incurable RAIR thyroid cancer who had radiographic progression six months prior to enrollment. The primary endpoint was progression-free survival (PFS) with a median follow-up of 31.8 months. The study is closed to enrollment but treatment and follow-up are ongoing. A targeted next-generation sequencing platform was used for mutational analysis. Results: Thirty-three patients with differentiated thyroid cancer (DTC), 10 with medullary thyroid cancer (MTC), and 7 with anaplastic thyroid cancer (ATC) enrolled. For the DTC cohort, median PFS was 12.9 months (95% CI, 7.3–18.5) with a 2-year PFS of 23.6% (95% CI, 10.5–39.5). Median OS was not reached; 2-year OS was 73.5% (95% CI, 53.8–85.8). Among ATC patients, 1 had a partial response and was progression-free until 17.9 months after study entry and one had disease stability for 26 months, respectively. The genomically profiled cohort enriched for PI3K/mTOR/Akt alterations. PI3K/mTOR/Akt–mutated ATC subgroups appeared to benefit from everolimus. Treatment-related adverse events were as anticipated. Conclusions: Everolimus has significant antitumor activity in thyroid cancer. While genomic profiling does not currently guide therapeutic selection in thyroid cancer patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine. Clin Cancer Res; 24(7); 1546–53. ©2018 AACR.

Access of melanoma cells to the cutaneous vasculature either via lymphatic invasion or angiotropism is a proposed mechanism for metastasis. Lymphatic invasion is believed to be a mechanism by which melanoma cells can disseminate to regional lymph nodes and to distant sites and may be predictive of adverse outcomes. Although it can be detected on hematoxylin- and eosin-stained sections, sensitivity is markedly improved by immunohistochemistry for lymphatic endothelial cells. Multiple studies have reported a significant association between the presence of lymphatic invasion and sentinel lymph node metastasis and survival. More recently, extravascular migratory metastasis has been suggested as another means by which melanoma cells can spread. Angiotropism, the histopathologic correlate of extravascular migratory metastasis, has also been associated with melanoma metastasis and disease recurrence. Although lymphatic invasion and angiotropism are not currently part of routine melanoma reporting, the detection of these attributes using ancillary immunohistochemical stains may be useful in therapeutic planning for patients with melanoma.

IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied—tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4–IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection.

Background The progression from a benign pigmented lesion on the skin to cutaneous melanoma is better understood, and it could be presumed that a similar progression occurs with mucosal lesions. However, to our knowledge, there has never been documentation of melanosis transforming into melanoma over time. Objective To describe a transformation of a mucosal melanosis into melanoma. Methods A 53-year-old man with diffuse melanosis of the nasal cavity underwent surgical resection. Results Pathology revealed melanocytic hyperplasia without evidence of melanoma. The patient was serially examined, with excisions for new areas of melanosis. The pathology progressed to severely atypical melanocytic proliferation and melanoma in situ over a 4-year period. Conclusion Nasal melanosis may be a precancerous lesion and may transform into melanoma. All melanosis should be biopsied with close endoscopic observation. Lesions with dysplasia or atypia should be excised due to potential transformation to melanoma.

Cutaneous squamous cell carcinomas mainly affect older, predominantly male patients. Most are due to chronic ultraviolet exposure, and associated with actinic keratoses. On the lower extremities, they occur more commonly in women. However, data on these tumors as a distinct group are scarce. We evaluated 61 squamous cell carcinomas of the lower extremities. Overall, 69% of patients were female. Mean age was 75 years. More than 90% of tumors were well differentiated, 3% showed perineural invasion, and none lymphovascular invasion. In all, 63.9% showed evidence of severe chronic sun damage. Associated actinic keratoses were identified in only 13% of cases. By contrast, 80% were associated with distinctive basal epidermal proliferations with a retiform growth pattern. These proliferations were evaluated immunohistochemically for keratinocyte stem cell markers, p53 and Notch1 in 15 cases. All cases were positive for cytokeratin 14, p53, and Notch1 (with variable intensity in the latter 2), and predominantly negative for cytokeratin 19. Interestingly, basal retiform proliferations were positive for cytokeratin 15 in 66% of cases. Fifteen head and neck squamous cell carcinomas were evaluated in comparison. Those lacked associated basal retiform proliferations except in 1 case. In contrast, 87% were associated with actinic keratoses and 100% with severe chronic sun damage. Actinic keratoses associated with head and neck tumors showed cytokeratin 15 staining only in 7% of cases ( P = .003 compared with cytokeratin 15 in basal retiform proliferations associated with leg carcinomas). These findings support the hypothesis that lower extremity squamous cell carcinomas are distinct and may exhibit a pathogenesis less reliant on actinic damage.

In support of future x-ray telescopes ESA is developing new optics for the x-ray regime. To date, mass and volume have made x-ray imaging technology prohibitive to planetary remote sensing imaging missions. And although highly successful, the mirror technology used on ESA’s XMM-Newton is not sufficient for future, large, x-ray observatories, since physical limits on the mirror packing density mean that aperture size becomes prohibitive. To reduce telescope mass and volume the packing density of mirror shells must be reduced, whilst maintaining alignment and rigidity. Structures can also benefit from a modular optic arrangement. Pore optics are shown to meet these requirements. This paper will discuss two pore optic technologies under development, with examples of results from measurement campaigns on samples. One activity has centred on the use of coated, silicon wafers, patterned with ribs, that are integrated onto a mandrel whose form has been polished to the required shape. The wafers follow the shape precisely, forming pore sizes in the sub-mm region. Individual stacks of mirrors can be manufactured without risk to, or dependency on, each other and aligned in a structure from which they can also be removed without hazard. A breadboard is currently being built to demonstrate this technology. A second activity centres on glass pore optics. However an adaptation of micro channel plate technology to form square pores has resulted in a monolithic material that can be slumped into an optic form. Alignment and coating of two such plates produces an x-ray focusing optic. A breadboard 20cm aperture optic is currently being built.

Due to the relatively large number of optical Earth Observation missions at ESA, this area is interesting for new space technology developments. In addition to their compactness, scalability and specific task customization, optical MEMS could generate new functions not available with current technologies and are thus candidates for the design of future space instruments. Most mature components for space applications are the digital mirror arrays, the micro-deformable mirrors, the programmable micro diffraction gratings and tiltable micromirrors. A first selection of market-pull and techno-push concepts is done. In addition, some concepts are coming from outside Earth Observation. Finally two concepts are more deeply analyzed. The first concept is a programmable slit for straylight control for space spectro-imagers. This instrument is a push-broom spectroimager for which some images cannot be exploited because of bright sources in the field-of-view. The proposed concept consists in replacing the current entrance spectrometer slit by an active row of micro-mirrors. The MEMS will permit to dynamically remove the bright sources and then to obtain a field-of-view with an optically enhanced signal-to-noise ratio. The second concept is a push-broom imager for which the acquired spectrum can be tuned by optical MEMS. This system is composed of two diffractive elements and a digital mirror array. The first diffractive element spreads the spectrum. A micromirror array is set at the location of the spectral focal plane. By putting the micro-mirrors ON or OFF, we can select parts of field-of-view or spectrum. The second diffractive element then recombines the light on a push-broom detector. Dichroics filters, strip filter, band-pass filter could be replaced by a unique instrument.

Summary The prognostic role of PDL1 expression, CD8+ and FoxP3+ lymphocytes in vulvar melanomas has not been studied. We correlated PDL1 expression and CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 75 vulvar melanomas. Tumoral PDL1 expression (>5%) was seen in 23% of cases. By Fisher exact test, PDL1 expression and peritumoral FoxP3+ lymphocytes significantly correlated with less disease-specific death. By linear regression analysis, correlations between tumoral PDL1 expression with the density of tumoral CD8+ and peritumoral CD8+ lymphocytes, tumoral FoxP3+ with tumoral CD8+ lymphocytes, and peritumoral FoxP3+ with peritumoral CD8+ lymphocytes were observed. By univariate analyses, tumor thickness >4 mm predicted poorer progression-free survival, melanoma-specific survival, and overall survival. PDL1 expression >5% and peritumoral CD8+, peritumoral FoxP3+, and tumoral FoxP3+ lymphocytes correlated with better overall survival. By multivariate analyses, high peritumoral FoxP3+ lymphocytes independently predicted better melanoma-specific survival ( P = .023), and tumor thickness independently predicted poorer progression-free survival ( P = .05) and overall survival ( P = .039). In conclusion, our study shows that, independent from tumor thickness, an increased density of peritumoral FoxP3+ lymphocytes may positively impact survival in a subset of vulvar melanomas. Tumoral PDL1 expression correlated with tumoral as well as peritumoral CD8+ and FoxP3+ lymphocytes, supportive of an adaptive immune response. Although the frequency of PDL1 expression is low in vulvar melanoma, its expression may identify a subset of vulvar melanoma that might respond to immunotherapy.

A 48-year-old man was evaluated for confusion that had developed while he was traveling in Mexico. He had purplish skin lesions, pancytopenia, and pleocytosis and an elevated protein level in the cerebrospinal fluid. Diagnostic tests were performed.

Background: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. Methods: We correlated PDL1, p53, and Ki-67 expression with CD8 1 and FoxP3 1 immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. Results: Tumoral PDL1 expression (>= 25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoral PDL1 expression correlated with thickness (P =.0041); p53 expression (P =.019); Ki-67 proliferation index (P =.0018); and tumoral CD8 (P =.0084), stromal CD8 (P

Objectives/Hypothesis To identify histopathologic features associated with poor correlation of frozen and permanent pathology margins following wide local excision for advanced cutaneous squamous cell carcinomas of the head and neck. Study Design Retrospective review. Methods A retrospective review of patients undergoing excision of advanced head and neck squamous cell carcinomas between the years 2010 AND 2013 was performed. Demographic, operative, and pathology data were collected. Overall correlation between frozen section margins and final margins on permanent section results was calculated. Positive and negative predictive values of several histopathologic features were determined. Results Forty-one cases were identified from the database. Perineural invasion, lymphovascular invasion, and a component of poorly differentiated carcinoma were identified in 61.3%, 34.5%, and 17.1% of cases, respectively. Discrepancy between frozen section margins and permanent margins was identified in eight cases (19.5%). The false-negative rate for poorly differentiated carcinoma, lymphovascular invasion, and perineural invasion was 14%, 36%, 26%, respectively. The positive and negative predictive value of poorly differentiated carcinoma, lymphovascular invasion, and perineural invasion in predicting discrepancy between frozen and permanent margins was 14% and 80%, 36% and 84%, and 26% and 92%, respectively. Conclusions This study demonstrated a moderate rate of discrepancy between frozen and permanent section analysis of operative margins from high-risk cutaneous squamous cell carcinomas of the head and neck. The presence or absence of certain histopathologic features appears to be associated with a higher rate of frozen section discrepancy. Evaluation of these features in a preoperative biopsy or staging excision may be useful in planning definitive excision and reconstruction. Level of Evidence 4 Laryngoscope, 125:636–639, 2015

Background Aleukemic cutaneous myeloid sarcoma (CMS) represents an important yet rare entity denoting the presence of a cutaneous myeloid leukemic infiltrate without concurrent peripheral blood or bone marrow disease. The clinicopathologic diagnosis remains elusive due to isolated skin findings and variable immunostaining. Cytogenetic and molecular findings have infrequently been reported. Methods Twenty-five patients with CMS were identified in the Massachusetts General Hospital pathology database between 2004 and 2012. Patients were excluded if concurrent blood or marrow acute myeloid leukemia (AML), myelodysplastic syndrome or lymphoproliferative disorder were diagnosed. Results Three patients were identified: a neonate with recurrent CMS and marrow disease that never met diagnostic criteria for AML and two patients relapsing as CMS without concurrent blood or marrow disease following chemotherapy-induced complete remission. Histology showed atypical mononuclear cell interstitial dermal infiltrates. All cases were CD68+, lysozyme+ and CD117−; one of two were CD34+; two of three were myeloperoxidase negative. 11q23 rearrangement, t(1;14), NPM1 (nucleophosmin I), FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication), and novel FLT3-D835 mutations were identified. Conclusion An isolated atypical cutaneous infiltrate may represent aleukemic CMS and should prompt a search for other extramedullary sites of involvement. Immunohistochemistry, molecular and cytogenetic studies can help differentiate aleukemic CMS from benign and malignant, monocytic and histiocytic mimickers, and may potentially indicate therapy and prognosis.

A 51-year-old woman presented with a history of recurrent epistaxis and oral ulcers that were transiently responsive to glucocorticoids. Examination revealed erosions of the mucous membranes of the tongue, soft palate, and buccal mucosa. A diagnostic procedure was performed.

Sentinel lymph node (SLN) metastasis is a powerful predictor of survival in primary cutaneous melanoma. Lymphatic invasion (LI) may correlate with increased risk of SLN metastasis. Intralymphatic metastases, often difficult to detect on hematoxylin and eosin (HE) stained sections, are readily identified with dual immunohistochemistry for melanocytic and lymphatic markers.We used dual S100/D240 immunohistochemistry to detect LI in 125 melanomas from patients who underwent SLN biopsy and correlated LI with melanoma staging parameters and disease status.Dual immunohistochemistry allowed for the identification of LI in 33 cases (26%), compared to only 2% on HE stained sections. Melanomas with LI showed greater thickness, higher mitotic rate and more frequent ulceration. Eleven of 33 cases with LI (33%) and 10 of 92 cases without LI (11%) were associated with a positive SLN (P = .006). More patients without LI were disease-free at last follow-up (80%) than patients with LI (50%; P = .002); LI was significantly associated with decreased progression-free survival.The detection of LI is improved by dual immunohistochemistry and predicts SLN metastasis. The presence of LI may impact therapeutic planning in melanoma, such as the decision to perform a SLN biopsy.

Background The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors. Patients and methods To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4–92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded. Results Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%). Conclusions Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.

Background Recent molecular advances suggest that Spitz nevi and other spitzoid neoplasms are biologically distinct from melanoma and conventional nevi. The ubiquitin ligase UBE2C and the homeobox transcription factor HOXA1 are candidate oncogenes in melanoma. Methods Using RNA expression analysis and immunohistochemistry, we evaluated these biomarkers in Spitz nevi (n = 20), melanoma (n = 20), and by immunohistochemistry in conventional nevi (n = 20). Results RNA analysis with branched DNA multiplex assay identified upregulation of UBE2C in melanomas vs Spitz nevi (P = .003), whereas HOXA1 was downregulated in melanoma (P < .0001). Immunohistochemical analysis confirmed increased nuclear expression of UBE2C in melanoma (mean = 18% of cells; range 3%-44%) when compared with Spitz nevi (mean = 9%; range 2%-28%; P = .001) and conventional nevi (mean = 1.5%; range 0-9%; P < .0001). Strong UBE2C staining was identified in cells undergoing mitosis. UBE2C RNA and protein detection correlated with mitotic rate (P < .0001). On the other hand, HOXA1 nuclear staining was low in melanoma (mean = 69%; range 5%-100%) when compared with Spitz nevi (mean = 94%; range 66%-100%; P = .0024) and conventional nevi (mean = 94%; range 83%-99%; P = .009). Conclusions UBE2C and HOXA1 RNA and protein are differentially expressed in conventional and Spitz nevi and melanoma.

Importance The abrupt appearance of melanocytic lesions is a unique phenomenon that can occur in the setting of eruptive nevi or epidermotropic melanoma metastases. Objective To examine the immunohistochemical and genetic mutative features of a novel case of an eczematous reaction followed by the abrupt appearance of melanocytic lesions. Design, Setting, and Participant Case report of a 48-year-old woman with no significant medical history who first presented with an eczematous dermatitis on her torso, extremities, and buttocks and who subsequently developed thousands of pinpoint, histologically atypical melanocytic tumors and invasive melanoma within the areas of inflammation. Main Outcomes and Measures Immunohistochemical and mutational analyses of the patient’s melanocytic tumors were conducted. Results Mutational analysis of the pigmented lesions did not identify any activating mutations in BRAF, PTEN, NRAS, KRAS, and HRAS . Immunohistochemical analyses of 9 biopsied pigmented lesions all showed normal expression of the tumor suppressors p16 and PTEN and no expression of mutated BRAF V600E protein. Conclusions and Relevance To our knowledge, this is a previously unreported eruption comprising 2 distinct components: an eczematous reaction and a wave of melanocytic proliferations within the inflammatory regions. Possible explanations for this patient’s condition, include immune stimulation leading to nevogenesis, benign “nevic” metastases, eruptive nevi, and epidermotropic metastatic melanoma.

Die Gansebachtalbrucke auf der Neubaustrecke zwischen Erfurt und Leipzig/Halle, Teil des Verkehrsprojektes Deutsche Einheit Nr. 8.2, ist eine integrale, also lagerlose, Eisenbahnbrucke aus Spannbeton. Sie ist fur den Hochgeschwindigkeitsverkehr mit Betriebsgeschwindigkeiten bis zu 300 km/h bestimmt. Die in der Realisierung befindliche Talbrucke basiert als alternativer Entwurf auf dem “Leitfaden: Gestalten von Eisenbahnbrucken” der DB AG. Die Gansebachtalbrucke ist eine Rahmenbrucke, ein Spannbetonplattenbalken monolithisch auf kreisrunden Pfeilern. Am Beispiel der Gansebachtalbrucke konnte gezeigt werden, dass die alternativen Entwurfe aus dem Leitfaden der DB AG hinsichtlich Tragfahigkeit, Gebrauchstauglichkeit und Verkehrssicherheit sowie Kosten mindestens gleichwertig und damit fur den Hochgeschwindigkeitsverkehr geeignet sind. Das Abweichen von der Rahmenplanung und die integrale Bauweise erforderten eine Zustimmung im Einzelfall und damit zahlreiche weiterfuhrende Untersuchungen, welche in diesem Aufsatz ausfuhrlich dargestellt werden, wie die Untersuchung zum dynamischen Verhalten bei Zuguberfahrten und moglicher Resonanzerscheinungen. Mit diesem alternativen Entwurf kommt eine Talbrucke zur Ausfuhrung, die robuster ist und sich besser in das flache Gansebachtal einfugt als der Ausschreibungsentwurf der Rahmenplanung. The Gansebach Valley Bridge, an Integral Valley Bridge owned by the DB AG on the New Railway Erfurt-Leipzig/Halle The new railway between Erfurt and Leipzig/Halle, part of the transportation project “Deutsche Einheit No. 8.2”, crosses the Gansebach valley via an intregal (i.e. no bearings) prestressed concrete bridge. The bridge is designed for high-speed traffic of up to 300 km/h. The bridge, currently under construction, is based on an alternative design in accordance with the guideline “Design of Railway Bridges” (“Leitfaden: Gestalten von Eisenbahnbrucken”) of the Deutsche Bahn AG. The Gansebach valley bridge is designed as a frame bridge, a monolithical prestressed concrete double T-beam on circular columns. The example of the Gansebach valley bridge proved that alternative designs following the DB AG guideline are to be regarded as at least equivalent with regard to load bearing capacity, serviceability and traffic safety as well as cost and therefore suitable for high-speed traffic. The deviation from the original plan and the integral design required a separate approval and consequently various further tests, such as examining the dynamic behavior under train crossings and possible resonance vibrations. These tests will be described in detail in this paper. This alternative design will result in a bridge which is more robust and will fit in more harmoniously with the shallow valley of the Gansebach than the original commissioned design would have.

9564Background: ICI has shown major benefit in cutaneous malignancies including melanoma and Merkel cell carcinoma. Efficacy data in cSCC is, however, limited. Here we report our institutional expe...

For future exploration of the solar system, the European Space Agency (ESA) is planning missions to Mercury (BepiColombo), the Sun (SolarOrbiter) and to the moons of Jupiter and Saturn. The expected intensity of radiation during such missions is hazardous for the scientific instruments and the satellite. To extend the lifetime of the satellite and its payload a multifunctional particle spectrometer (MPS) is being developed. The basic function of the MPS is to send an alarm signal to the satellite control system during periods of high radiation. In addition the MPS is a scientific instrument that will unfold the composition of the different contributing particles on-line by the dE/dx versus E method. The energy spectrum and angular distribution of the particles will be recorded as well. This article describes the main requirements and the base line design for the MPS. A readout scheme consisting of a 32 channel ASIC from IDEAS is proposed and the signal filtering algorithm will run on a digital signal processor based on FPGA technology. Results are shown from prototype calibration studies with a proton beam. (c) 2008 Elsevier B.V. All rights reserved.

Future planetary missions such as BepiColombo are resource limited in both mass and power. Due to the proximity of the spacecraft to the Sun, the instrumentation will encounter harsh environments as far as radiation levels and thermal loads are concerned. Only radiation hard detectors that need little or no cooling will be able to successfully operate after long cruise times and over the expected mission lifetimes. The next generation of lanthanum halide scintillators promises to provide sufficient resolution in the spectral range between I and 10 MeV where most of the elemental gamma-ray emission lines can be detected. In order to be suitable for planetary gamma-ray spectrometers with sufficient sensitivity it had to be proven that larger crystals of size 3" can be produced and that they maintain their resolution of similar to 3% at 662 keV. For that purpose we have produced and characterized several larger LaBr3 : Ce crystals and assessed their radiation hardness by exposing the crystals to radiation doses that are representative of the expected conditions in the space environment. Systematic measurements on several crystals allowed the determination of the activation potential and the performance verification from which the consequences for instrument flight performance can be derived. From these investigations we conclude that these scintillators are well suited for planetary missions, with excellent and stable performance.

Radiation effects caused by solar proton events will be a common problem for many types of sensors on missions to the inner solar system because of the long cruise phases coupled with the inverse square scaling of solar particle events. In support of the BepiColombo and Solar Orbiter missions we have undertaken a comprehensive series of tests to assess the effects on a wide range of sensors. Sensors based on scintillators have been proposed for both missions. In this paper, we report on a series of controlled irradiations on a set of five LaBr3:Ce scintillators. The crystals are 1 in. right circular cylinders of LaBr3, packaged in aluminium housings and viewed through BK7 optical windows. Four crystals were exposed to simulated solar proton events over the energy range 60-200 Mev having a spectral shape approximating that of the August 1972 solar particle event. Each crystal was exposed to a different total fluence. One crystal was exposed to an integral fluence of 10(9) protons cm(-2), a second to 10(10) protons cm(-2), the third to 10(11) protons cm(-2) and the fourth to 10(12) protons cm(-2). The latter corresponds to an absorbed dose in silicon of 1 Mrad or in SI units, 10 kGy. The fifth crystal served as a reference. The crystals were characterized both before and after the irradiations in terms of energy resolution, light output and background count rate. The key conclusions of the study are that LaBr3 is radiation tolerant showing no measurable degradation effects when exposed to experimentally simulated solar proton flare spectra with fluences up to 10(12) protons cm(-2) (similar to 1 Mrad or 10 kGy equivalent in silicon) and integrated above a 60 MeV energy threshold. LaBr3 behaves as a generic intermediate mass material showing similar activation yields as CsI(Tl) and Ge above 10(10) protons cm(-2) (similar to 10 krad (100 Gy) equivalent in silicon) and significantly less than Ge below this fluence. (c) 2007 Elsevier B.V. All rights reserved.

The uncertainties in the knowledge of the Instrument Spectral Response Function (ISRF), barycenter of the spectral channels and bandwidth / spectral sampling (spectral resolution) are important error sources in the processing of satellite imaging spectrometers within narrow atmospheric absorption bands. The exhaustive laboratory spectral characterization is a costly engineering process that differs from the instrument configuration in-flight given the harsh space environment and harmful launching phase. The retrieval schemes at Level-2 commonly assume a Gaussian ISRF, leading to uncorrected spectral stray-light effects and wrong characterization and correction of the spectral shift and smile. These effects produce inaccurate atmospherically corrected data and are propagated to the final Level-2 mission products. Within ESA's FLEX satellite mission activities, the impact of the ISRF knowledge error and spectral calibration at Level-1 products and its propagation to Level-2 retrieved chlorophyll fluorescence has been analyzed. A spectral recalibration scheme has been implemented at Level-2 reducing the errors in Level-1 products below the 10% error in retrieved fluorescence within the oxygen absorption bands enhancing the quality of the retrieved products. The work presented here shows how the minimization of the spectral calibration errors requires an effort both for the laboratory characterization and for the implementation of specific algorithms at Level-2.

BepiColombo is an interdisciplinary mission to the planet Mercury which will provide the detailed information necessary to understand Mercury and its magnetospheric environment. The mission is envisaged to consist of three spacecrafts, the Mercury Planetary Orbiter (MPO), the Mercury Magnetospheric Orbiter (MMO) and the Mercury Surface Element (MSE). The mission went through a re-assessment with the aim of optimizing resources and and advancing the scientific return. Various mission scenarios were investigated and new pay load concepts were adopted. The newly defined mission will be presented focusing on the launch scenario and the MPO reference payload.

The high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, plays a central role in the initiation and control of atopic allergic inflammation. On mast cells and basophils, the function of the receptor is well known and constitutes cellular degranulation and the release of various mediators. FcepsilonRI on antigen-presenting cells (APCs), however, does not lead to degranulation of preformed granula, but has different functions: signal transduction pathways like the activation of NF-kappaB are initiated to induce inflammatory cytokine gene expression. In addition, FcepsilonRI on APCs acts as an allergen-focusing structure and can efficiently amplify allergen presentation in an IgE-dependent manner. Recently, we and others have gained new insight into the regulation and function of FcepsilonRI on APCs, which has shed new light on the modulating effects of the immune system in atopic inflammation.

HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1–0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.

To date, no study has examined clinical, pathological, and surgical characteristics of D׳Amico low-risk patients according to active surveillance (AS) eligibility.We relied on patients with low-risk prostate cancer, who were classified based on the D׳Amico classification, treated with radical prostatectomy (RP) between 2008 and 2013 at the Martini-Clinic Prostate Cancer Center. We assessed differences in clinical, pathological, and surgical characteristics in D׳Amico low-risk patients according to AS eligibility (prostate-specific antigen [PSA]≤ 10 ng/ml, Gleason score ≤ 3 + 3, ≤ 2 positive cores,≤5 0% tumor content per core, and ≤ cT1-2a). Multivariable logistic regression analyses targeted 2 end points: (1) presence of either intermediate- or high-risk characteristics (Gleason score ≥ 3+4 or ≥ pT3 or pN1) or (2) exclusive presence of high-risk characteristics (Gleason score ≥ 4+4 or ≥ pT3 or pN1) at RP.Of 1,331 patients low-risk prostate cancer classified based on the D׳Amico classification, 825 (62%) men were eligible for AS. AS candidates were less frequently either upgraded (55% vs. 78%, P0.001) or upstaged (8% vs. 15%, P0.001). Similarly, at final pathology, AS candidates less frequently harbored either intermediate- or high-risk (56% vs. 78%, P0.001), or exclusive high-risk characteristics (9% vs. 16%, P0.001). Tumor involvement per core (50%) (most powerful), number of positive cores, PSA values, and age were independent predictors for either intermediate- or high-risk characteristics at RP. Tumor involvement per core and PSA values were independent predictors for exclusive high-risk characteristics at RP.D׳Amico low-risk patients did not have a homogeneous histology at RP. Especially, non-AS candidates were at a higher risk of either upgrading or upstaging at final pathology. Tumor involvement greater than 50% per core was the most powerful indicator of adverse pathology. Therefore, D'Amico low-risk criteria are not safe enough to identify AS candidates.

Sinonasal mucosal melanoma is a rare disease with poor survival. These tumors may have associated intraepithelial melanocytic proliferations, which are not extensively characterized. This retrospective analysis of 32 patients with sinonasal mucosal melanoma examined associated intraepithelial melanocytic proliferations in the context of diagnostic and prognostic features. Patient age ranged from 30 to 90 years (median 71) with a male to female ratio of approximately 3:2. Follow up for 31 patients ranged from 5 to 211 months (mean 42 months). Most patients died from melanoma-associated causes (18/31, 58 %), six (19 %) died from unknown causes, two (6 %) were alive with metastatic disease, and only five patients (16 %) remained alive without melanoma. The tumors were histopathologically heterogeneous, displaying epithelioid, spindled, and small cell cytomorphology. The presence of >2 mitoses/mm2 and necrosis correlated with tumor progression and overall survival, respectively (p = 0.04 for both). Melanoma in situ, defined as a confluent intraepithelial proliferation of cytologically atypical melanocytes, was identified in 20 of 30 evaluable cases (67 %) and confirmed with immunohistochemical staining for microphthalmia-associated transcription factor. Melanocytic hyperplasia, defined as intraepithelial melanocytic proliferation without confluent growth or marked atypia, was seen in five cases (16 %). This incidence of associated intraepithelial melanocytic proliferations (83 %) is higher than previously reported. Because of the locally aggressive nature of these tumors, an awareness of the high rate of associated intraepithelial melanocytic proliferations may inform future studies of therapeutic options.

Background: The efficacy of traditional Chinese medicine (TCM) as a treatment for atopic dermatitis has been evaluated in clinical trials. Until now, the underlying mechanism of this treatment has remained completely elusive; this is particularly true of its putative effects on dendritic cells (DCs), which might play a pivotal role in the disease. Objective: We investigated the influence of a standardized extract from 10 Chinese herbs that was successfully used in clinical trials on the generation of monocyte-derived DCs from atopic donors. Methods: Detailed phenotypic and functional exploration of DCs generated in the presence of IL-4 and GM-CSF and treated with different concentrations of TCM or a placebo control was performed. Results: TCM profoundly affected the morphology and phenotype of the developing DCs. They lost their typical dendritic morphology and decreased their expression of CD1a as well as the low-affinity IgE receptor CD23. Most importantly, TCM-exposed DCs exhibited a diminished stimulatory activity toward autologous antigen-specific and allogeneic T cells while secreting high amounts of IL-10. Conclusion: TCM induces immunopharmacologic alterations on DCs from atopic donors in vitro. These alterations might account, at least in part, for the therapeutic effect of this treatment in AD in vivo. (J Allergy Clin Immunol 2001;108:588-93.)

Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing incidence and socio-economical relevance. The diagnosis is made on clinical grounds and different diagnostic criteria sets have been established. The majority of all AD cases is associated with a sensitization to environmental allergens and increased serum IgE (so-called extrinsic AD), but about 10-30% of all cases suffer from the so-called intrinsic AD, which obviously lacks any link to the classical atopic diathesis. The genetic background of AD has been investigated by target gene approach by different groups with mostly contradictory results for each of the genes under study. An imbalance in the spectrum of Th1/Th2 responses, a disturbed prostaglandin metabolism, intrinsic defects in keratinocyte function, delayed eosinophil apoptosis, IgE-mediated facilitated antigen presentation by epidermal dendritic cells, a two phase model of the inflammatory response and staphylococcal superantigen effects are among the currently studied pathogenetical aspects of extrinsic AD, which are reviewed in this paper.

As part of the program to calibrate X-ray CCD detectors for the AXAF mission we have performed high-spectral resolution, absolute measurements of CCD quantum efficiency using the synchrotron radiation and grating monochromator facilities of the PTB radiometry laboratory at BESSY. We present here detailed measurements of the absolute quantum efficiency in the spectral region surrounding the oxygen K absorption edge for both front- and back-illuminated MIT Lincoln Laboratory CCDs. The absolute scale of the measurements is established by reference to an Electrical Substitution Radiometer. Near-edge absorption structure produces variations as large as 40% in the detection efficiency of the front-illuminated detectors. We find structure at energies immediately below the K absorption edge which we attribute to resonant absorption in the oxide layers of the CCD gate structure. The amplitude of edge structures in the back-illuminated devices is, as expected, much smaller. Finally, we demonstrate that edge structure can be reliably detected in CCD response using an electron impact source and a grating monochromator.

Background: Anaplastic thyroid carcinoma (ATC) is among the most aggressive solid tumors, with a uniformly fatal prognosis. No effective systemic therapies exist. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR or combined RAF/MEK inhibition, but experienced a dramatic response when both drug regimens were combined. Methods and Results: Nine biopsies of the tumor were obtained between diagnosis and autopsy. Multi-region whole-exome sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways respectively. We performed the largest meta-analysis of ATC to date and found a 7.4% co-occurrence of MAPK and PI3K pathway alterations in ATC. We analyzed 5,255 cancer exomes in the Cancer Genome Atlas (TCGA) to determine whether similar cancer genomes occurred outside of anaplastic thyroid carcinoma. We identified 11 tumors with BRAF V600E and non-silent PIK3CA mutations. These results indicate that this genotype occurs in other cancers and may predict response to combined therapy. Conclusions and future directions: We have identified a patient with ATC who had a dramatic response to combined inhibition of the MAPK and PI3K pathways, whereas neither MAPK inhibition nor PI3K inhibition alone was sufficient to produce tumor regression. These observations suggest that MAPK and PI3K/MTOR pathway blockade represents an effective dual therapy aimed at the founding oncogenic lesions in a subset of ATC. Citation Format: William J. Gibson, Daniel T. Ruan, Vera A. Paulson, Justine A. Barletta, Glenn J. Hanna, Stefan Kraft, Antonio Calles, Matthew Nehs, Francis Moore, Amaro Taylor-Weiner, Jeremiah Wala, Travis Zack, Thomas Lee, Fiona Fennessy, Erik Alexander, Tom Thomas, Pasi Jäne, Levi Garraway, Scott Carter, Rameen Beroukhim, Jochen Lorch, Eliezer Van Allen. Truncal activating MAPK and PI3K pathway alterations and exceptional response to dual pathway inhibition in anaplastic thyroid cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-227.

Recent studies have described an encapsulated and an infiltrative form of follicular variant of papillary thyroid carcinoma (FVPTC). While encapsulated tumors have been reported to have virtually no metastatic potential or recurrence risk if angioinvasion and capsular penetration are absent, infiltrative tumors have been found to have a significant metastatic potential and a risk of recurrence. In our experience, a substantial number of FVPTCs are neither fully encapsulated nor infiltrative, but instead are partially-encapsulated (PE) or well-circumscribed (WC). Thus, the aim of this study was to investigate the metastatic potential and recurrence risk of PE/WC FVPTCs in comparison with that of encapsulated and infiltrative tumors.We studied 77 FVPTCs resected between 2000 and 2002 and characterized the tumors as encapsulated, PE/WC, or infiltrative. Histologic assessment was then correlated with lymph node status and clinical outcome.In our cohort, 27 (35%) tumors were encapsulated, 35 (45%) were PE/WC, and 15 (19%) were infiltrative. Lymph node status was similar between PE/WC and encapsulated tumors, but was significantly different between encapsulated and infiltrative groups (p0.001), and PE/WC and infiltrative groups (p0.001). Lymph node metastases were absent in all 15 cases of encapsulated tumors and all 9 cases of PE/WC tumors with sampled lymph nodes, but were present in 7 of 9 (78%) cases of infiltrative tumors with sampled lymph nodes. For patients with available clinical follow-up (66 cases, 86%), the median follow-up time was 111 months. No patients with encapsulated tumors recurred, one (3%) patient with a PE/WC tumor had recurrent/residual disease, and two (15%) patients with infiltrative tumors had recurrent/residual disease. The one patient with a PE/WC tumor who had recurrent/residual disease had a tumor bed recurrence 7 years after initial resection. Significantly, this was the only patient in the PE/WC group that had a positive resection margin.Our results demonstrate that PE/WC FVPTCs have a very low metastatic potential/recurrence risk, indicating that they should be distinguished from more aggressive infiltrative FVPTCs.

In addition to their compactness, scalability and specific task customization, optical MEMS could generate new functions not available with current technologies and are thus candidates for the design of future space instruments. Most mature components for space applications are the Digital Mirror Device (DMD) from Texas Instruments (TI), the micro-deformable mirrors, the Programmable Micro Diffraction Grating and the tiltable micro-mirrors. Among 20-30 MEMS-based payloads concepts, two concepts are selected. The first concept is a programmable slit for straylight control for space spectro-imagers. This instrument is a push-broom spectro-imager for which some images cannot be exploited because of bright sources in the field-of-view. The proposed concept consists in replacing the current entrance spectrometer slit by an active row of micro-mirrors. The MEMS will permit to dynamically remove the bright sources and then to obtain a field-of-view with an optically enhanced signal-to-noise ratio. The second concept is a push-broom imager for which the acquired spectrum can be tuned by optical MEMS. This system is composed of two diffractive elements and a TI’s DMD component. The first diffractive element spreads the spectrum. A micro-mirror array is set at the location of the spectral focal plane. By putting the micro-mirrors ON or OFF, we can select parts of field-of-view or spectrum. The second diffractive element then recombines the light on a push-broom detector. Dichroics filters, strip filter, band-pass filter could be replaced by a unique instrument.

High-grade neuroendocrine carcinoma of the head and neck is an aggressive neoplasm which rarely arises in the oropharynx. Here we report a series of 8 oropharyngeal neuroendocrine carcinomas associated with both human papillomavirus (HPV) infection and tobacco exposure. The tumor occurred predominantly in male patients (6 of 8) at a mean age of 59 years. Histologically, these cases were all classified as poorly differentiated neuroendocrine carcinoma (small cell carcinoma) with high mitotic activity [mean 53.3 mitoses per 10 HPF], necrosis, high nuclear-to-cytoplasmic ratio, and nuclear molding. One case also exhibited a moderately differentiated component, and one other case had a component of squamous cell carcinoma with basaloid features. Neuroendocrine differentiation was confirmed by immunoreactivity for synaptophysin and/or chromogranin A in all cases. P63 staining was negative, except in 1 case. Seven of the 8 cases showed strong and diffuse p16 expression, a surrogate marker for high-risk HPV infection. HPV infection was confirmed in 6 of these 7 cases by HPV in situ hybridization and/or polymerase chain reaction analysis. HPV subtypes 16, 18, and 33 were identified in 1 case each by polymerase chain reaction testing. Six of the 7 patients for whom clinical history was available presented with advanced disease (4 with regional lymph node metastases, 1 with distant metastases, and 1 with distant and locoregional metastases). Disease recurred in 5 of the 6 patients with available clinical follow-up, with 3 developing distant metastases to brain, bones, lung, pleura, adrenal glands, and pancreas. These 3 cases were all from the HPV-positive group. In summary, neuroendocrine carcinoma of the oropharynx represents a rare novel HPV-associated entity with high-grade histologic features and aggressive clinical behavior.

Atypical or mitotically active dermal smooth muscle neoplasms are uncommon lesions, which are most often termed "cutaneous leiomyosarcoma," although preexisting-mostly small-series suggest a low risk of aggressive behavior. To further investigate these tumors, 84 cases from consultation and institutional files were analyzed for pathologic and clinical characteristics. There was a striking male-to-female preponderance (4.3:1), with a mean age of 56 years (range, 6 to 82y). Nine patients had a history of malignancies (6 of the skin). Tumors measured 1.3 cm on average and were predominantly located on the trunk (32) and lower extremities (30). Histologically, all tumors were confined to the dermis or showed only very superficial, focal subcutaneous extension. The majority showed an infiltrative growth pattern with fascicles of atypical eosinophilic spindle cells ramifying between dermal collagen fibers. Primary tumors showed a mean mitotic rate of 4.7/10 high-power fields. By the Fédération Nationale des Centres de Lutte Contre le Cancer grading system, 97% of primary tumors were grade I lesions, with only 3% showing necrosis. All tumors were immunopositive for smooth muscle actin; 98% expressed desmin, 90% caldesmon, and 45% pankeratin (usually focal). Follow-up in 52 cases (mean, 51 mo) showed no metastases or tumor-related deaths. Eighteen tumors showed local recurrence at a mean interval of 43 months; 12 of the recurrent lesions showed positive margins in the primary excision and 1 showed margins0.2 cm. Margin status was not available for the other 5 cases, which recurred locally. Recurrent tumors showed, on average, 13.7 mitoses/10 high-power fields. Of recurrences, 47% were grade I lesions, 35% were grade II, and 18% were grade III, and 28% showed necrosis. The primary excision of tumors, which later recurred, showed no difference in grade, presence of necrosis, or mitotic rate, compared with those that did not recur; there were no discernible clinical differences either. In summary, these tumors, when confined to the dermis or showing only minimal subcutaneous involvement, seem to carry no evident risk of metastasis; hence, the designation "sarcoma" is inappropriate. Margin status is the most important predictor of recurrence. On excision with clear margins, the risk of local recurrence is very low. Hence, we propose the term "atypical intradermal smooth muscle neoplasm" as being more appropriate.

A concept of a compact imaging spectrometer component based on an integrated waveguide array is elaborated and its design rules presented. The component, a focal plane array spectrometer (FPAS), is used in a similar way as a CMOS detector array or a CCD in a camera. The classical spectrometer, for instance an optical grating spectrometer, disappears from the optical system. The whole instrument is therefore reduced to the imaging optics and the FPAS in the focal plane which takes over the function of the spectrometer and detector array. Its potential for very high spectral resolution, minimal size, simple instrument integration, modularity and ruggedness makes it interesting for commercial and special applications like space. Two typical space optical instruments are reconceived using the FPAS with the result of a potential volume reduction of a factor five to eight while keeping the same performances. Also the specifications of simple and generic spectrometers based on the proposed component concept are very promising with respect to spectral resolution, volume and simplicity of instrument design and manufacturing.

The PANTER X-ray Test Facility was originally designed to support the development and construction of the ROSAT mirror system. A large instrument chamber (length 12 m, diameter 3.5m) accommodates the optics to be analysed. The X-ray sources covering an 0.2 - 50 keV energy range are located at a distance of 123m from the entrance to the chamber to provide an almost parallel X-ray beam. Both are connected by a vacuum tube of 1m diameter. In addition to ROSAT a large number of astronomical systems like telescopes for Exosat, BeppoSAX, JET-X, ABRIXAS, XMM-Newton and Swift - but also gratings (e.g., LETG on Chandra), filters, and focal plane detectors have been measured at the facility. As a "growing facility" we are currently planning to apply changes to the facility layout to support measurements of instrumentation for future missions like XEUS. Currently a parallel beam is set up using a spare CDS mirror ("Coronal Diagnostic Spectrometer", for the SOHO mission) as condensor. Moreover, extensions to vacuum tube and instrument chamber are under consideration, both to allow calibration of systems with focal lengths significantly longer than XMM-Newton. A new focal plane camera using a CCD developed for the eROSITA mission will improve spatial and spectral resolution. Finally, the energy coverage shall be extended to lower and to higher energies. Already with the present configuration important issues like performance under low temperatures could be investigated.

It has been demonstrated that silicon pore optics can serve as the new technology for building the next generation of X-ray telescopes for astronomical missions. In order to build up an optic in Wolter-I configuration, the high performance pore optics (HPO) have to be co-aligned and integrated into pairs, forming so-called X-ray optical units (XOU). The stringent co-alignment requirements for a 50 m focal length telescope like XEUS (e.g. 1 arcsecond between parabolic and hyperbolic HPO) demand holistic alignment concepts, which integrate the metrology, the fixation and the performance verification. The application in space and the resulting thermal requirements in combination with launch loads and other mechanical restrictions must also be considered. Finite element modelling of different fixation mechanisms and XOU configurations allow one both to assess difficulties at an early stage and to validate solution strategies. This paper reports on the concepts, which have been developed. The most promising candidate has been selected to build a form fit function model. The experimental set-up to align the HPOs, the required metrology and first results of the performance verification at test facilities will be shown and discussed.

The XEUS petals encompass the optical bench structure of the stand alone X-Ray Optical Units (XOU) based on the high performance and light weight Silicon Pore Optics technology. The performance aspects under consideration of the design drivers, the related trade offs (e.g. mechanical concepts, material selection, XOU butting efficiency etc.) and the current development activities wrt. the design, manufacturing, assembly and the functional and environmental test verification approach of the Form Fit Function Model are described in this paper. Special emphasis is given to the critical external optical and mechanical interfaces coherent to the mission design, e.g. the Mirror S/C frame work structure and the Detector S/C. The technology program is based on the heritage achieved within the context of the XMM/Newton telescope development. The investigations of the correlated programmatic aspects towards the FM production by application of effective robot system supported assembly procedures shall be illustrated.

New astronomical science missions demand X-ray telescopes with an angular resolution better than 5" and effective areas of up to 5 m2 at 1 keV. Traditional technologies like nickel electro-forming or polished glass surfaces lead to long and heavy structures, which require prohibitive mass resources to achieve the required large collecting area. To overcome this problem an entirely novel technology using silicon wafers has been developed resulting in pore X-ray optics, which form very light, stiff and modular structures. The suitability of silicon wafers to be used as high quality optical material has been demonstrated and semiconductor industry have developed methods to structure the wafers such, that they can be assembled into segments of Wolter-I optics. For the assembly of these, so called High Performance Pore Optics (HPO), we have developed an automated production robot. The assembly process and the required metrology is described in detail and experimental methods are shown, which allow to assess the quality of the HPOs during production and to predict their performance when measured in synchrotron radiation facilities.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

XEUS, the 'X-ray Early Universe Spectroscopy Mission', is a potential candidate for inclusion into the Cosmic Visions 1525 Science Programme of the European Space Agency ESA [1,2]. It is being studied jointly with the Japanese Aerospace Exploration Agency JAXA. The newly developed Silicon-based High resolution Pore Optics (HPO) combines low mass density with good angular resolution, and enables the development of novel mission design concepts for the implementation of a new generation of space based X-ray telescope [3, 4, 5]. This optics technology allows also for the application of complex reflective coatings [6], improving the effective area of the telescope and permitting an enhancement in the engineering of the desired response function. This paper gives an overview of the telescope optical design and optical bench architecture, including the deployment scheme. Further, the performance predictions based on ray tracing are discussed and the overall telescope design of XEUS is presented.

Silicon pore optics have been proposed earlier as modular optical X-ray units in large Wolter-I telescopes that would match effective area and resolution requirements imposed by missions such as XEUS. Since then the optics have been developed further and the feasibility of the production of high-performance pore optics has been demonstrated. Optimisation of the production and the assembly process allowed the generation of optics with larger areas with improved imaging performance; Silicon pore optics can now be manufactured with properties required for future X-ray telescopes. A suitable design that allows the implementation of pore optics into X-ray Optical Units in Wolter I configuration was derived and recently built including an appropriate telescope mounting structure with interfaces for the individual components. Based on the present experience the requirements for industrial mirror production, optics assembly, related metrology and performance verification are reviewed from a viewpoint of its implementation into a large scale production. Such production may lead to the provision of the large number of X-ray optical units that are required within reasonably short time scales and a feasible cost envelope. The present outcome of this investigation and the prospects to future production and test facilities will be presented.