Search

Full lists of authors: Thomas, N.; Hussmann, H.; Spohn, T.; Lara, L. M.; Christensen, U.; Affolter, M.; Bandy, T.; Beck, T.; Chakraborty, S.; Geissbuehler, U.; Gerber, M.; Ghose, K.; Gouman, J.; HosseiniArani, S.; Kuske, K.; Peteut, A.; Piazza, D.; Rieder, M.; Servonet, A.; Althaus, C. Behnke, T.; Gwinner, K.; Hüttig, C.; Kallenbach, R.; Lichopoj, A.; Lingenauber, K.; Lötzke, H. -G.; Lüdicke, F.; Michaelis, H.; Oberst, J.; Schrödter, R.; Stark, A.; Steinbrügge, G.; del Togno, S.; Wickhusen, K.; Castro, J. M.; Herranz, M.; Rodrigo, J.; Perplies, H.; Weigel, T.; Schulze-Walewski, S.; Blum, S.; Casciello, A.; Rugi-Grond, E.; Coppoolse, W.; Rech, M.; Weidlich, K.; Leikert, T.; Henkelmann, R.; Trefzger, B.; Metz, B.--This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/.Open Access funding provided by Universitat Bern., The BepiColombo Laser Altimeter (BELA) is the first European laser altimeter constructed for interplanetary flight. BELA uses a 50 mJ pulsed Nd:YAG laser operating at 10 Hz with a 20 cm aperture receiver to perform the ranging. The instrument also uses a digital approach for range detection and pulse analysis. The ranging accuracy is expected to be better than 2 metres and ∼20 cm in optimum conditions. With the given, only slightly elliptical, orbit, BELA should return a consistent data set for the most if not all of the planet. The instrument is required to function in an extreme environment with the thermal issues being particularly demanding. Novel solutions have been taken to resolve these issues. BELA is described in detail and its predicted performance outlined on the basis of pre-flight testing. © The Author(s) 2021, This work was supported by the Swiss State Secretariat for Education, Research and Innovation (SERI) under the PRODEX scheme (contract number C90191). The opinions expressed and arguments employed herein do not necessarily reflect the official views of the Swiss Government. DLR would like to thank all involved collaborators in the BELA transmitter team. Financial support was provided by the DLR Space Administration on behalf of the Federal Ministry of Economics and Technology of Germany. We acknowledge the financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award SEV-2017-0709, and from the research projects ESP 2014-54062-R, ESP 2016-76076-R and PGC 2018-099425-B-I00. Open Access funding provided by Universitat Bern.

We examined the potential of cricket farming as an innovative solution to improving household nutrition in Laos, where edible insects are already part of traditional diets. We conducted research with a total of 40 rural households in Central Laos, in which small-scale cricket farming was introduced to 20 intervention households. Nutritional situation and changes of all households and cricket production and consumption of the intervention households were assessed. Malnutrition was prevalent amongst the study population and we found indications for dietary inadequacies. Despite fluctuating harvest results and some production failures, most intervention households successfully produced and harvested crickets over five production cycles. Cricket farming was not only appreciated by the project participants, but also spread to non-project households. 70% of the total cricket harvest were used for own consumption and crickets were eaten by all family members, including small children and women, in amounts that improved nutritional adequacy during the brief period following harvest. To increase the nutritional impact, production has to be stabilised and adapted to provide a more continuous supply of crickets over the year.

Cricket farming can have a positive impact on rural development and rural economy in low- and middle-income countries. Moreover, crickets have the potential to address food and nutrition insecurity and promote food sovereignty through the promotion of local production and consumption. This paper presents and discusses five complementary studies conducted in Thailand, Cambodia, Lao People's Democratic Republic (Lao PDR), the Democratic Republic of the Congo (DRC) and Kenya. Cricket farming is being promoted in these countries under research projects, public-private partnerships, NGOs and international organisations. In the majority of the countries, cricket farming is still in its infancy and research into how to improve cricket farming systems is still on-going. Cricket farming in Cambodia, Lao PDR, DRC and Kenya remains relatively limited, and many farmers are still a part of pilot projects. In each of the five regions, different cricket species have been a part of traditional diets. As discussed in this paper, many of the potential benefits of the production and consumption of crickets have not yet been realised in many cases due to: (1) lack of adequate support and awareness from stakeholders (especially government agencies); (2) unknown trade volumes; (3) high costs of inputs; and (4) cultural taboos. The information presented in this paper will be especially useful to stakeholders from governmental institutions, non-governmental organisations, civil society organisations and research institutions.

Epidemiology Vulvar cancer can be classified into two groups according to predisposing factors: the first type correlates with a HPV infection and occurs mostly in younger patients. The second group is not HPV associated and occurs often in elderly women without neoplastic epithelial disorders. Histology Squamous cell carcinoma (SCC) is the most common malignant tumor of the vulva (95%). Clinical features Pruritus is the most common and long-lasting reported symptom of vulvar cancer, followed by vulvar bleeding, discharge, dysuria, and pain. Therapy The gold standard for even a small invasive carcinoma of the vulva was historically radical vulvectomy with removal of the tumor with a wide margin followed by an en bloc resection of the inguinal and often the pelvic lymph nodes. Currently, a more individualized and less radical treatment is suggested: a radical wide local excision is possible in the case of localized lesions (T1). A sentinel lymph node (SLN) biopsy may be performed to reduce wound complications and lymphedema. Prognosis The survival of patients with vulvar cancer is good when convenient therapy is arranged quickly after initial diagnosis. Inguinal and/or femoral node involvement is the most significant prognostic factor for survival.

The BepiColombo Spacecraft can’t tolerate to absorb a major fraction of the off-axis sunlight through larger payload apertures. Fortunately, there are solutions to design baffles such that they reflect the incoming radiation back through the front aperture rather than absorbing it. A Design Study, sponsored by ESA and performed by Contraves Space together with SAGEM Defense Securite, has analysed the potential of various solutions and assessed the options to manufacture them. The selected configuration has been analysed in detail for the optical, mechanical and thermal performance as well as the impact on mass and power dissipation. The size of the baffle was adapted to the needs of the BepiColombo Laser Altimeter (BELA) payload.

The rapid developments in optical technologies generate increasingly higher and sometimes completely new demands on the quality of materials, surfaces, components, and systems. Examples for such driving applications are the steadily shrinking feature sizes in semiconductor lithography, nanostructured functional surfaces for consumer optics, and advanced optical systems for astronomy and space applications. The reduction of surface defects as well as the minimization of roughness and other scatter-relevant irregularities are essential factors in all these areas of application. Quality-monitoring for analysing and improving those properties must ensure that even minimal defects and roughness values can be detected reliably. Light scattering methods have a high potential for a non-contact, rapid, efficient, and sensitive determination of roughness, surface structures, and defects.

The Colour and Stereo Surface Imaging System (CaSSIS) camera was launched on 14 March 2016 onboard the ExoMars Trace Gas Orbiter (TGO) and it is currently in cruise to Mars. The CaSSIS high resolution optical system is based on a TMA telescope (Three Mirrors Anastigmatic configuration) with a 4th powered folding mirror compacting the CFRP (Carbon Fiber Reinforced Polymer) structure. The camera EPD (Entrance Pupil Diameter) is 135 mm and the focal length is 880 mm, giving an F# 6.5 system; the wavelength range covered by the instrument is 400-1100 nm. The optical system is designed to have distortion of less than 2%, and a worst case Modulation Transfer Function (MTF) of 0.3 at the detector Nyquist spatial frequency (i.e. 50 lp/mm). The Focal Plane Assembly (FPA), including the detector, is a spare from the Simbio-Sys instrument of the Italian Space Agency (ASI). Simbio-Sys will fly on ESA’s BepiColombo mission to Mercury in 2018. The detector, developed by Raytheon Vision Systems, is a 2k×2k hybrid Si-PIN array with 10 μm-pixel pitch. The detector allows snap shot operation at a read-out rate of 5 Mpx/s with 14-bit resolution. CaSSIS will operate in a push-frame mode with a Filter Strip Assembly (FSA), placed directly above the detector sensitive area, selecting 4 colour bands. The scale at a slant angle of 4.6 m/px from the nominal orbit is foreseen to produce frames of 9.4 km × 6.3 km on the Martian surface, and covering a Field of View (FoV) of 1.33° cross track × 0.88° along track. The University of Bern was in charge of the full instrument integration as well as the characterisation of the focal plane of CaSSIS. The paper will present an overview of CaSSIS and the optical performance of the telescope and the FPA. The preliminary results of the on-ground calibration campaign and the first light obtained during the commissioning and pointing campaign (April 2016) will be described in detail. The instrument is acquiring images with an average Point Spread Function at Full-Width-Half-Maximum (PSF FWHM) of < 1.5 px, as expected.

On board of the ExoMars Trace Gas Orbiter (TGO), the Colour and Stereo Surface Imaging System (CaSSIS) developed under the lead of University of Bern, has the mission to provide stereo images of the planet's surface in colour at a resolution of better than 5 m (4.54m from a circular orbit of 400 km) for enhancing our knowledge of the surface of Mars [1].

Background: Imatinib is a tyrosine kinase inhibitor of BCR-ABL, ABL, PDGFR-α and -β, KIT, and DDR. In solid tumors, it inhibits proliferation and invasiveness and facilitates higher intratumoral cytotoxic drug concentrations. Vinorelbine has good tolerability and efficacy in metastatic breast cancer (MBC). This study evaluates the safety and efficacy of imatinib and vinorelbine in combination. Methods: In a prospective, open-label, phase I/II trial, 400 mg imatinib p.o. daily (corrected from 600 mg) was combined with an escalating dose of vinorelbine i.v. weekly in four dose levels of 10, 15, 20, and 25 mg/m2 (each n ≥ 5) to treat patients with MBC (expressing PDGFR-α and/or -β, and/or KIT). The last patient of each level was treated for >28 days, before enrolment for the next dose level started. Study endpoints were feasibility and tolerability, incidence of hematological and nonhematological toxicity, and clinical efficacy (data cutoff: November 18, 2011). A total of 33 patients have been enrolled, and all dose levels have been fully recruited. One patient is still on study medication. A translational subprotocol is ongoing. Results: All 33 included patients are evaluable for safety (32 within the ITT population). Eleven patients were excluded early from the study (progressive disease, toxicity, and withdrawal of consent). Twenty-two patients participated in the study for >28 days (‘ITT >28'). Within the ITT population, the response rate [complete response (CR) and partial response (PR)] was 9.4% (n = 3), the clinical benefit rate (CBR; CR+PR+stable disease) 50% (n = 16), and the median time to progression (TTP) 155 days. A total of 21.3% of the patients were on study medication for >6 months, and 15.2% for >12 months (mean 140 days, range 15-643). Within ‘ITT >28', the response rate was 13.6%, CBR 72.7%, and median TTP 176 days. The response was independent of the receptor status (PDGFR-α, -β, and KIT). Toxicities were as follows (safety population): 21.6% severe leukopenia, 9.1% severe neutropenia (with 1 febrile neutropenia), 1 case of bowel perforation, 36% diarrhea (3% severe), 84.8% nausea (severe 15.2%), 48.5% vomiting (severe 9.1%), 27.3% infections (severe 6.1%), 12.1% peripheral neuropathy (severe 9.1%), and 36.4% dyspnea (3% severe). Four patients on trial died (nondrug-related). Conclusion: The combination of imatinib and vinorelbine in MBC appeared to be feasible and tolerable. A CBR of 50% (ITT) in pretreated patients suggests that this combination may be active. Although toxicities were frequent, they appeared to be manageable.

The European Space Agency’s ExoMars Trace Gas Orbiter (TGO) seeks to investigate the biological or geological origin of trace gases found on Mars. The TGO carries a payload of four instruments in order to reach its scientific goals, including the Colour and Stereo Surface Imaging System (CaSSIS). CaSSIS is a colour and stereo telescopic camera that will be capable of taking high-resolution images of the martian surface. Before shipment of the instrument for integration onto the TGO, a detailed calibration campaign was performed, and a number of calibration products were gathered and utilised as part of the in-flight calibration campaign. This paper presents the results of on-ground calibration measurements carried out in order to assess the pre-flight performance of CaSSIS. All indications are that CaSSIS will perform very well on arrival at Mars and will be successful in reaching its scientific objectives.

The Colour and Stereo Surface Imaging System (CaSSIS) is the main imaging system onboard the European Space Agency’s ExoMars Trace Gas Orbiter (TGO) which was launched on 14 March 2016. CaSSIS is intended to acquire moderately high resolution (4.6 m/pixel) targeted images of Mars at a rate of 10–20 images per day from a roughly circular orbit 400 km above the surface. Each image can be acquired in up to four colours and stereo capability is foreseen by the use of a novel rotation mechanism. A typical product from one image acquisition will be a $9.5~\mbox{km} \times {\sim}45~\mbox{km}$ swath in full colour and stereo in one over-flight of the target thereby reducing atmospheric influences inherent in stereo and colour products from previous high resolution imagers. This paper describes the instrument including several novel technical solutions required to achieve the scientific requirements.

Aromatase inhibitors (AI) have improved the treatment of oestrogen receptor positive (ER+) breast cancer. Despite the efficacy of these agents over 40% of patients relapse with endocrine resistant disease. Here we describe an in vitro model of acquired resistance to long-term oestrogen deprivation (LTED). The LTED cells retain expression of the ER and appear hypersensitive to oestrogen as a result of altered kinase activity. Furthermore analysis of temporal changes in gene expression during the acquisition of resistance highlight growth factor receptor pathways as key mediators of this adaptive process.

Objective: Many patients with ovarian cancer disease relapse within 6 months after adjuvant chemotherapy, with a limited prognosis. Epigenetic modifications have been shown to play an important role in tumor development and formation. Therefore, global analysis of DNA methylation patterns might reveal specific CpG sites that correlate with progression-free interval (PFI) after therapy. Methods: Twenty samples of advanced ovarian cancer with a predominantly serous papillary histological subtype were subjected to DNA methylation profiling. Illumina HumanMethylation27 BeadChip technology was used for simultaneous analysis of 27,578 CpG sites in >14,000 genes. Results: Differential DNA methylation of various cytosines correlated with PFI. However, this becomes only significant by classification according to PFI with a cutoff of >28 months. Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). Gene ontology analysis revealed that differentially methylated genes were significantly overrepresented in the categories telomere organization, mesoderm development and immune regulation. Conclusion: Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value.

Breast cancer treatment has experienced several changes in the past decades due to the discovery of specific prognostic and predictive biomarkers that enable the application of more individualized therapies to different molecular subgroups. These subgroups show specific differences regarding biological clinical behavior. In addition to the classical clinical prognostic factors of breast cancer, established molecular biomarkers such as estrogen receptor and progesterone receptor have played a significant role in the selection of patients benefiting from endocrine therapy for many years. More recently, the human epidermal growth factor receptor 2 (HER2) has been validated to be not only a prognostic factor, but also a predictor of response to HER2 targeting therapy. The shift toward an earlier diagnosis of breast cancer due to improved imaging methods and screening programs highlights the need for new factors and combinations of biomarkers to quantify the residual risk of patients and to indicate the potential value of additional treatment strategies. The marker of proliferation Ki67 has recently emerged as an important marker due to several applications in neoadjuvant therapy in addition to its moderate prognostic value. With the introduction of high-throughput technologies, numerous multigene signatures have been identified that aim to outperform traditional markers: current prospective clinical trials are seeking evidence for their definitive role in breast cancer. There exist many more factors and approaches that have the potential to become relevant in the near future including the detection of single disseminating and circulating tumor cells in blood and bone marrow as well as of circulating cell-free DNA and microRNA. Careful randomized prospective testing and comparison with existing established factors will be required to select those emerging markers that offer substantial cost-effective benefit and thereby justify their routine use for breast cancer therapy decision-making.

Cyclo-oxygenase 2 (COX-2) is implicated in the regulation of aromatase transcription in malignant breast tissue and has been considered as a potential target for tissue specific aromatase suppression. We initiated a randomised controlled pre-surgical study of celecoxib versus no treatment in women with primary breast cancer to determine the effects of COX-2 inhibition on markers of biological response. Postmenopausal women (50-80 years of age) with stage I or II, primary breast cancer, were randomised 2:1 to receive 400 mg/day celecoxib or no treatment for 14 days prior to surgery. A core biopsy was obtained pre- and post-treatment. Paired baseline and endpoint biopsies were analysed for Ki67, apoptosis, COX-2, CD31, estrogen receptor (ER) and progesterone receptor (PgR). Comparisons between the treatment groups were conducted using the Mann-Whitney test with a two-sided 5% significance. Of the 25 patients treated, 23 had evaluable data and 19 (83%) were ER positive. Overall the geometric mean change in Ki67, the primary end point, relative to baseline in the celecoxib arm was -16.6% (P = 0.056). The change in the no-treatment group was -8.1% (P = 0.24). There was no statistically significant difference in the change between the two groups. Celecoxib did not significantly affect apoptosis, COX-2, ER or PgR expression. There is only modest evidence for a biological effect of celecoxib in primary breast cancer. However, the trend towards a reduction in Ki67 in ER-positive breast cancer warrants further investigations in a larger cohort of patients.

Introduction Imatinib mesylate is a tyrosine kinase receptor inhibitor targeted against PDGFR α and β, c-kit and bcr-abl. These receptors regulate cellular processes such as proliferation, differentiation, and survival. This study was performed to evaluate the effects of imatinib on breast cancer cell lines with respect to the activity of PDGFR β and Akt: a downstream modulator of cell growth and survival. Methods Expression of imatinib targets was analyzed with reverse transciptase PCR and immunoblotting assays in the breast cell lines MDA MB 231, MCF 7, ZR 75-1, and T 47-D. Changes on receptor expression and phosphorylation status under imatinib were evaluated using drug concentrations of 2 to 10 μM. The anti-proliferative and pro-apoptotic effects of imatinib alone and in combination with vinorelbine were investigated with an MTT and TUNEL assay. Results Imatinib inhibited growth and induced apoptosis of all cell lines examined. This effect was increased when combined with vinorelbine. A dose-dependent inhibitory effect on the phosphorylation of PDGFR β and Akt was detected. Conclusions The growth inhibitory effect of imatinib on breast cell lines may be caused by inhibiting the activity of the tyrosine kinases PDGFR β and Akt. Imatinib is a promising novel drug for targeted therapy of breast cancer patients.

The Colour and Stereo Surface Imaging System (CaSSIS) is the high-resolution scientific imager on board the European Space Agency’s (ESA) ExoMars Trace Gas Orbiter (TGO) which was launched on 14th March 2016 to Mars. CaSSIS will observe the Martian surface from an altitude of 400 km with an optical system based on a modified TMA telescope (Three Mirrors Anastigmatic configuration) with a 4th powered folding mirror. The camera EPD (Entrance Pupil Diameter) is 135 mm, and the expected focal length is 880 mm, giving an F# 6.5 in the wavelength range of 400- 1100 nm with a distortion designed to be less than 2%. CaSSIS will operate in a “push-frame” mode with a monolithic Filter Strip Assembly (FSA) produced by Optics Balzers Jena GmbH selecting 4 colour bands and integrated on the focal plane by Leonardo-Finmeccanica SpA (under TAS-I responsibility). The detector is a spare of the Simbio-Sys detector of the Italian Space Agency (ASI), developed by Raytheon Vision Systems. It is a 2kx2k hybrid Si-PIN array with a 10 μm pixel pitch. A scale of 4.6 m/px from the nominal orbit is foreseen to produce frames of 9.4 km × 47 km on the Martian surface. The University of Bern was in charge of the full instrument integration as well as the characterization of the focal plane and calibration of the entire instrument. The paper will present an overview of the CaSSIS telescope and FPA optical performance. The preliminary results of on-ground calibration and the first commissioning campaign (April 2016) will be described.

Purpose: Nilotinib is a selective tyrosine kinase inhibitor of c-Kit, Abl and platelet-derived growth factor receptor-α/β. To evaluate nilotinib's potential use as a treatment of human ovarian cancer, we tested nilotinib's preclinical activity in ovarian cancer cell lines with different tyrosine kinase expression patterns. Methods: The effects of nilotinib on ovarian cancer cell growth were studied alone and in combination with carboplatin and paclitaxel. Proapoptotic and antimigratory effects were examined using TUNEL and migration assays. Results: Nilotinib alone and in combination with carboplatin and paclitaxel significantly inhibited cell growth in PDGFR-α-positive ovarian cancer cell lines. The combination of nilotinib with carboplatin and paclitaxel showed synergistic effects on cell proliferation. Nilotinib treatment led to the inhibition of cell migration alone and in combination with carboplatin and paclitaxel. Apoptosis induction occurred in response to nilotinib that increased in combination with carboplatin. Conclusions: Nilotinib may be a feasible targeted therapy option for the treatment of ovarian cancer.

Zielgerichtete Medikamente fuhren zu einer Kostensteigerung der Brustkrebstherapie. Es gibt nur wenige Untersuchungen in Deutschland zur Kosteneffizienz dieser Substanzen. Die zitierten Studien aus verschiedenen Industrienationen, deren Gesundheitssysteme z. T. sehr unterschiedlich sind, konnen der Orientierung dienen, sind jedoch nicht direkt auf die deutsche Situation ubertragbar. Trastuzumab ist heute Teil der adjuvanten Standardtherapie bei einer HER-2/neu-Uberexpression. Eine Schweizer Analyse hat in dieser Indikation eine Kosteneffizienz gezeigt, besonders fur Follow-up-Perioden >10 Jahre. Fur HER-2/neu-positive metastasierte Mammakarzinome (MBC) unterstellte eine franzosische Untersuchung fur Trastuzumab ebenfalls kosteneffizient zu sein. In einer englischen Bewertung des National Institute for Health and Clinical Excellence wurde Lapatinib, das auch gegen HER-2/neu gerichtet ist, in Kombination mit Capecitabine bei MBC als nicht kosteneffizient eingeschatzt. Auch eine Schweizer Bewertung von Bevacizumab in Kombination mit Paclitaxel bei MBC ergab keine Kosteneffizienz. In Deutschland fehlt es an orientierenden Empfehlungen zur Kosteneffizienz neuer zielgerichteter Substanzen. Da auch hier die Ressourcen im Gesundheitswesen limitiert sind, ware eine intensive gesellschaftliche Diskussion daruber dringend notwendig.

Local treatment of breast cancer with tumor-free surgical margins is the standard procedure in the treatment of T1 and small T2 breast cancers. Surgery is followed by radiation therapy, and adjuvant systemic therapy is offered depending on primary tumor characteristics, such as tumor size, grade of differentiation, number of involved axillary lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and the expression of the human epidermal growth factor 2 (HER2) receptor. Although this approach implies a higher risk of ipsilateral breast tumor recurrence, the total risk of recurrence is low (1% per year), with rates of overall survival similar to that after radical procedures. The most peripheral part of epithelial tumors, the tumor margin, is the part which is most likely to remain in loco after surgical resection. Thus, understanding the biology of the invasion front is important as these tumor cells have been reported to lose epithelial properties, such as cohesiveness and keratin expression, and to acquire features of mesenchymal cells. The parallel appearance of tumor cells in different states of cell dedifferentiation implicates a dynamic equilibrium that is determined by the induction of epithelial-mesenchymal transition (EMT). EMT has been suggested to be of prime importance for tissue and vessel invasion. Furthermore, features of EMT are associated with the activity of tumor stem cells (TSC). TSC exist in breast cancer and their appearance varies depending on the used marker profile. Consequently, intratumoral heterogeneity is reflected by the grade of EMT activation. A specific function at the invasion front is hypothesized but has not yet been proven. Nevertheless, the molecular differentiation between the tumor center and the invasion front enhances the importance of tumor-free surgical margins.

RUAG Space developed, manufactured and demonstrated an afocal mirror telescope for space applications. The telescope is part of a Laser Communication Terminal (LCT) for GEO and LEO satellites. The design is off-axis and free of central obscuration. Optical interfaces are provided by pupils outside the telescope towards space (o=135 mm) and towards the payload (o=12.5 mm). The magnification is Γ=-10.8. The main characteristics are a WFE of ≤35nm, transmission

The BepiColombo Laser Altimeter (BELA) is selected to fly on board of the ESA's BepiColombo Mercury Planetary Orbiter (MPO). The instrument will be the first European planetary laser altimeter system. RUAG Space is the industrial prime for the Receiver part of the scientific instrument. The BELA Receiver is a joined effort of Swiss industries under the leading role of RUAG and University of Bern as co-Prime. A core element is the light weighted Receiver Telescope (RTL), to collect the laser pulse reflected from the planet’s surface. An innovative design was required to deal with the very challenging Mercury’s environmental conditions and with the very stringent instrument’s mass budget. The Optothermo- mechanical analyses lead to the design of a 1250mm focal length Cassegrain telescope made of Beryllium. It provides an aperture of 204 mm diameter and a 2 mm thick primary mirror for a total mass of less than 600gr. The manufacturing and the integration needed special developments. This paper presents the design analyses and the major challenges which had to be solved. Discussing some aspects of the telescope integration and test campaign, the finally achieved performances and lessons learnt will be presented.

We have found that the platelet-derived growth factor receptor (PDGFR)/Abl signaling pathway is up-regulated as a determinant of the acquisition of resistance to estrogen deprivation in vitro. We aimed to determine its clinical relevance in aromatase inhibitor (AI)-resistant breast cancer. We identified a cohort of 45 patients with estrogen receptor-positive breast cancer who had been treated with an AI, subsequently relapsed and had biopsy material available from both the presentation and post-AI recurrent lesion. PDGFR alpha, PDGFR beta and Abl expression was assessed in formalin-fixed paraffin-embedded sections. Tumor protein expression of PDGFR alpha (1.39-fold, P = 0.0065), PDGFR beta (4.32-fold, P = 0.006) and Abl (1.8-fold, P = 0.001) was increased at the point of relapse. Tumor and stromal expression of PDGFR alpha as well as PDGFR beta was significantly correlated in pre-treatment and relapse samples. High post-treatment tumor and stromal PDGFR beta levels were associated with a short time to treatment failure (TTF). Expression of PDGFR alpha in relapsing tumor specimens was correlated with Abl expression and Ki67 levels. Furthermore, changes in Abl correlated significantly with changes in ER expression. These clinical data support a role for enhanced PDGF/Abl signaling in AI-resistant disease and provide a rationale for targeting the pathway in endocrine-resistant breast cancer.

Introduction The majority of breast tumors at primary diagnosis are estrogen receptor positive (ER+). Estrogen (E) mediates its effects by binding to the ER. Therapies targeting the estrogenic stimulation of tumor growth reduce mortality from ER+ breast cancer. However, resistance remains a major clinical problem. Methods To identify molecular mechanisms associated with resistance to E-deprivation, we assessed the temporal changes in global gene expression during adaptation to long-term culture of MCF7 human breast cancer cells in the absence of estradiol (E2), long term estrogen deprived (LTED), that leads to recovery of proliferative status and models resistance to an aromatase inhibitor (AI). The expression levels of proteins were determined by western blotting. Proliferation assays were carried out using the dual platelet derived growth factor receptor (PDGFR)/Abelson tyrosine kinase (Abl) inhibitor nilotinib. Luciferase reporter assays were used to determine effects on ER-mediated transactivation. Changes in recruitment of cofactors to the gene regulated by estrogen in breast cancer 1 (GREB1) promoter were determined by chromatin immunoprecipitation (ChIP). Gene expression data were derived from 81 postmenopausal women with ER+ BC pre-treatment and at two-weeks post-treatment with single agent anastrozole in a neoadjuvant trial. Results The PDGF/Abl canonical pathway was significantly elevated as early as one week post E-deprivation (P = 1.94 E-04) and this became the top adaptive pathway at the point of proliferative recovery (P = 1.15 E-07). Both PDGFRβ and Abl protein levels were elevated in the LTED cells compared to wild type (wt)-MCF7 cells. The PDGF/Abl tyrosine kinase inhibitor nilotinib, suppressed proliferation in LTED cells in the presence or absence of E. Nilotinib also suppressed ER-mediated transcription by destabilizing the ER and reducing recruitment of amplified in breast cancer-1 (AIB1) and the CREB binding protein (CBP) to the promoter of the E-responsive gene GREB1. High PDGFRβ in primary ER+ breast cancer of 81 patients prior to neoadjuvant treatment with an AI was associated with poorer antiproliferative response. Additionally PDGFRβ expression increased after two weeks of AI therapy (1.25 fold, P = 0.003). Conclusions These preclinical and clinical data indicate that the PDGF/Abl signaling pathway merits clinical evaluation as a therapeutic target with endocrine therapy in ER+ breast cancer.

The new Cobas Core CMV IGM and IgG enzyme immunoassays (Roche Diagnostic Systems, Basle, Switzerland) were evaluated for their ability to detect cytomegalovirus (CMV)-specific IgM and IgG antibodies. Therefore, both were compared with some other commercially available and already established serological tests used in the laboratory diagnosis of CMV infection. These included the Abbott IMx CMV IgM and IgG assays, the Abbott CMV-M EIA, the Gull CMV IgM and IgG immunofluorescence tests, the medac CMV-IgM-ELA, and the Enzygnost anti-cytomegalovirus assay (Behringwerke). A total of 572 serum samples of various categories were examined and the results showed high concordances between all methods, ranging from 84.5% to 94.9%.. In a follow-up on renal transplant patients, the times of first detection of seroconversions were compared. Since a high overall agreement between the Cobas Core CMV IgM and IgG enzyme immunoassays and the other test systems were observed, these new assays represent useful and reliable tools for clinical CMV diagnosis.

Imatinib Mesylat ist ein Tyrosinkinase Inhibitor, der PDGF-R, den Stem Cell factor (SCF), c-Kit und abl blockiert. Neben der Hemmung wichtiger zellularer Vorgange kann besonders PDGF-β-Rezeptor vermittelt der Gewebsdruck in soliden Tumoren gesenkt werden. Eine Blockade ermoglicht so eine hohere Konzentration zytotoxischer Substanzen in der Tumorzelle. Diese Eigenschaften legen eine Kombination von Imatinib mit einer beim metastasierten Mammakarzinom etablierten Substanz, dem Vinorelbine, nahe. Patienten und Methoden Diese prospektive open-label, einarmige Phase I/II Studie kombiniert 400mg Imatinib Mesylat p.o. mit Vinorelbine i.v. wochentlich in einer Dosiseskalation bei Patientinnen mit fortgeschrittenem Mammakarzinom. Eingeschlossen warden Patientinnen, deren Tumoren PDGF-Rezeptor-α und/oder -β und/oder c-kit exprimieren und die eine vorherige Anthracyclin-haltige Polychemotherapie erhalten haben. Die Rekrutierung startet in Dosislevel 1 mit 10mg/m2 Vinorelbine und steigerte sich in den weiteren Dosisleveln auf 15, 20 und 25mg/m2. Die Patienten werden fur mindestens 28 Tage unter Therapie beobachtet, bevor der nachst hohere Dosislevel eroffnet wird. Ergebnisse: 33 Patientinnen wurden bislang in die Studie eingebracht. Zwei Patientinnen sind aktuell noch unter Therapie. Neben dem klinischen Ansprechen werden insbesondere die Gesamttoxizitat, sowie die Inzidenzen hamatologischer und nicht-hamatologischer Toxizitaten Grad 3 und 4 untersucht. Es schliest sich ein translationales Programm mit Tumoranalysen und einem Hautwunden-assay an. In der Prasentation wird die Rationale erlautert, die Rezeptorexpression dargestellt, der Studienplan diskutiert und ein Ausblick gegeben. Valide klinische Daten werden fruhestens Ende des Jahres zur Verfugung stehen.

Objectives Endometriosis is a common gynaecological disease with clinical symptoms such as chronic pain, infertility and intra-abdominal adhesions. Different theories on the pathogenesis of endometriosis and especially its aggressive subtype with infiltrative growth have been discussed. The objective of this study is to evaluate differences in proliferation and invasive properties of invasive colorectal endometriosis, superficial peritoneal endometriosis and endometrial carcinoma (G1 and G2). Study design Paraffin embedded tissues of peritoneal endometriosis, endometriosis of the intestine and endometrial carcinoma from 97 patients were stained immunohistochemically to assess differences in expression patterns of matrix metalloproteinases (MMP-2, MMP-9) as markers of invasion and the marker of proliferation PCNA. MMP expression was evaluated using the Immuno Reactive Score (IRS) (combining positive cell ratio and staining intensity) and PCNA expression was assessed as the percentage of positively stained cells in representative areas. Results MMP-2, MMP-9 and PCNA showed differential expression patterns in the different tissues examined. MMP-2 and PCNA expression was stronger in invasive colorectal endometriosis than in superficial peritoneal endometriosis ( p =0.0394). MMP-9, however, was more frequently expressed in peritoneal endometriosis (59.1%) than in colorectal endometriosis (44.4%). This result did not reach statistical significance. When colorectal endometriosis was compared to low grade endometrial carcinoma, proliferation detected by PCNA was significantly higher in endometriosis ( p =0.0008). MMP-2 and MMP-9 showed higher expression in endometrial carcinoma than in endometriosis. Conclusions There are obvious differences in expression patterns of MMP-2, MMP-9 and PCNA in different stages of endometriosis and in endometrial cancer. These markers can be helpful to evaluate aggressiveness and invasiveness of endometriosis in different localizations. The results obtained could be of relevance for a better understanding of the pathogenesis of endometriosis and the development of an individual therapy concept.

Treatment of ovarian cancer is still challenging especially in recurrent platinum refractory cases. Sunitinib is a multi tyrosine kinase inhibitor targeting receptors for vascular endothelial growth factor and platelet-derived growth factor which play a role in tumor angiogenesis. It has been approved for the treatment of recurrent gastro intestinal stroma tumors and metastatic renal cancer.In this study, sunitinib was tested for its effectiveness as a single agent in an ovarian cancer xenograft mouse model. Skov3 cells stably expressing firefly luciferase were injected into SCID beige mice. Mice received either 40 mg/kg bodyweight sunitinib or vehicle control. Tumor growth was monitored longitudinally by luciferase signal.Sunitinib significantly reduced tumor growth (p=0.0052) and peritoneal metastases, and was associated with a significantly reduced microvessel density count (p0.001).These results suggest that clinical trials are warranted for the evaluation of sunitinib for treatment of patients with recurrent or advanced ovarian cancer.

BMC cancer 10(412), (2010). doi:10.1186/1471-2407-10-412, Published by BioMed Central, London

Science return and high bandwidth communications are key issues to support the foreseen endeavors on spaceflights to the Moon and beyond. For a given mass, power consumption and volume, laser communications can offer an increase in telemetry bandwidth over classical RF technology allowing for a variety of new options, like more raw scientific data being sent back to Earth where data processing can be performed on ground. Recent European activities in the field of laser communications investigated mission scenarios for deep space and within the Earth's sphere of influence. Various link topologies have been investigated, involving Lissajous orbits at Libration points of the Earth-Sun and the Moon- Earth system, and also Martian orbiters. Different types of lasercom terminal concepts have been investigated, either operating fully autonomously or being attached to dedicated telecom orbiter spacecraft. Enhanced pulse position modulation formats were tested together with tailored FEC and interleaver technology in inter-island test campaigns using ESA's optical ground station on Tenerife. The paper summarizes the findings from all activities, highlights the potential and describes synergy aspects of involved technologies, all in view using lasercom as part of an integrated RF-optical TT&C subsystem to support enhanced science return.

In advanced ovarian cancers (OCs), p53 mutations are frequently observed. The objective of this study was to explore the value of the p53 mutational status, using four different techniques, in advanced OC patients as a predictive marker for responsiveness to platinum-based chemotherapy. One hundred and four, mostly serous papillary OC specimens were analyzed, of which all received a platinum containing chemotherapy after optimal cyto-reductive surgery. To verify the p53 mutational status, immunohistochemical staining with monoclonal antibodies, functional yeast assay (FASAY), single-strand conformation polymorphism analysis (SSCP) and genomic sequencing was performed in parallel. Out of ten OC patients [2 low malignant potential (LMP)/8 G1] only two had a mutant p53, whereas eight showed a wild-type p53. 40 out of 63 (G2/3) patients with G2/3 OC showed mutant p53 and 23 patients showed a wild-type pattern. p53 status was significantly different between these two groups (LMP/G1 vs. G2/3) (P = 0.015). A progressive disease after chemotherapy completion was noted in 35.6% of the patients (26 out of 73); in 69.2%, a mutated p53 and in 30.8%, a wild-type p53 was found. Nine (12.3%) patients showed a complete response at the end of the first-line chemotherapy. Out of these nine patients five had a mutated and four a wild-type p53. A partial response was observed in nine (12.3%) patients of whom four had a mutated p53. With respect to response to first-line chemotherapy (six cycles of platinum containing regimen), the p53 status was not predictive; no statistical significance regarding the p53 mutational status was observed when the two extreme groups PD versus PR/CR were compared (P > 0.05). In this study, the p53 mutational status was not predictive for responsiveness to platinum-based chemotherapy; but p53 was significantly more frequently mutated in poorly differentiated OCs.

Leiomyomatosis peritonealis disseminata (LPD) is a rare disease occurring as intraabdominal benign tumors. The underlying mechanism of LPD development in premenopausal females is still unknown, but high levels of estrogen and progesterone seem to play a major role. We present a case of a 29-year-old gravida 1, 22 6/7 weeks of gestation with symptoms of an acute abdomen. Abdominal ultrasound and MRI showed intraabdominal masses of uncertain origin most likely to be an extreme example of pseudomyxoma peritonei. Explorative laparotomy was performed, and histopathological analysis revealed benign tumors classified as leiomyomatosis. A cesarean section was performed due to increasing abdominal pain and excessive elevated inflammatory serum parameters. Postpartum, a spontaneous regression of the LPD was marked. LPD is a rare disease of young women. Excessive hormonal exposure seems to play a major role. Diagnosis is often difficult and a histopathological analysis is needed.

In this paper we prove that the (non-trivial) irreducible complex unipotent characters of a finite classical group G of type Bm or Cm in odd characteristic are reducible over any proper subgroup of G, apart from very few notable exceptions.

The BepiColombo Laser Altimeter (BELA) shall profile the surface of planet Mercury and operates on the day side as well as on the night side. Because of the high thermal loads, most interior surfaces of the front optics are highly reflective and specular, including the baffle. This puts a handicap on the straylight performance, which is needed to limit the solar background. We present the design measures used to reach an attenuation of about 10 -8 . We resume the method of backward straylight analysis which starts the rays at the detector and analyses the results in object space. The backward analysis can be quickly compiled and challenges computer resources rather than labor effort. This is very useful in a conceptual design phase when a design is iterated and trade-offs are to be performed. For one design, we compare the results with values obtained from a forward analysis.

Imatinib is a small molecule inhibiting the tyrosine kinases bcr-abl, c-kit, PDGFR-alpha and PDGFR-beta. Investigations were performed to screen ovarian cancer cell lines and tumor samples for target receptor expression. Effects of Imatinib on cell proliferation and apoptosis induction were measured with and without additional cytotoxic agents.Expression patterns of abl, c-kit, PDGFR-alpha and PDGFR-beta (Imatinib targets) were studied in 5 cell lines and 111 tissue arrays by PCR and immunohistochemistry. Proliferation assays were performed with single agent Imatinib or combined with Paclitaxel and Carboplatin. Apoptosis was measured by DNA fragmentation.All cell lines expressed abl and PDGFR-beta. C-kit was only expressed in 2/5 cell lines and PDGFR-alpha in 4/5. Imatinib reduced cell growth and lead to pro-apoptotic changes. Combination of Carboplatin, Paclitaxel and Imatinib showed synergistic activity.Our results suggest that Imatinib may be useful for the specific treatment of ovarian cancer as an add-on to conventional chemotherapy.

• Many different materials are available for augmentation mentoplasty. However, the optimal implant material for chin implantation has yet to be found. During the past several years, a number of experienced surgeons have turned to the use of Mersilene mesh. Mersilene mesh is a nonabsorbable Dacron polyester fiber that can be conformed easily into layers to achieve tailored dimensions and shape. At the McCollough Plastic Surgery Clinic PA, Birmingham, Ala, 277 patients over a 10-year period underwent chin augmentation with Mersilene mesh implants. The material provides excellent tensile strength, durability, and surgical adaptability. The overall complication rate was 3.2% (nine patients); infection rate, 2.5% (seven patients); and removal secondary to infection, 1.7% (five patients). Based on this 10-year experience, Mersilene mesh remains our material of choice for chin augmentation. (Arch Otolaryngol Head Neck Surg. 1990;116:1154-1158)

This work reports on an integrated RF-optical TT&C subsystem that can achieve increased TM link capacity but with almost the same mass and less power consumption than a conventional X-band or even upcoming Ka-band TT&C subsystem. Overall system design aspects are discussed, including considerations on atmospheric turbulence that significantly influence the achievable TM rate. The paper focuses on on-board terminal aspects and outlines the design approach to an optical deep space link (O-DSL) that is based on state-of-the-art technology.

The paper presents the general interplay of coarse and fine tracking sub systems for an optical intersatellite link terminal. It briefly describes the hardware items that were designed by the Contraves Space led team to realise the required pointing, acquisition and tracking (PAT) functionality, especially in view of a commercial use of the terminals. Additionally, the control concept is outlined and test results are presented that were obtained during PAT sub system tests, used to verify the acquisition algorithms and the closed loop tracking performance.