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Polarization entangled photon-pairs are generated and detected onboard a 3U CubeSat in low-Earth orbit that violate Bell’s inequality with a CHSH parameter of 2.60 ± 0.06. These results pave the way for space-based quantum networks.

Global quantum networks for secure communication can be realised using large fleets of satellites distributing entangled photon-pairs between ground-based nodes. Because the cost of a satellite depends on its size, the smallest satellites will be most cost-effective. This paper describes a miniaturised, polarization entangled, photon-pair source operating on board a nano-satellite. The source violates Bell's inequality with a CHSH parameter of 2.6 $\pm$ 0.06. This source can be combined with optical link technologies to enable future quantum communication nano-satellite missions., Comment: 15 pages, 6 figures

The Spectral Imaging of the Coronal Environment (SPICE) instrument is a high-resolution imaging spectrometer operating at extreme ultraviolet (EUV) wavelengths. In this paper, we present the concept, design, and pre-launch performance of this facility instrument on the ESA/NASA Solar Orbiter mission. The goal of this paper is to give prospective users a better understanding of the possible types of observations, the data acquisition, and the sources that contribute to the instrument's signal. The paper discusses the science objectives, with a focus on the SPICE-specific aspects, before presenting the instrument's design, including optical, mechanical, thermal, and electronics aspects. This is followed by a characterisation and calibration of the instrument's performance. The paper concludes with descriptions of the operations concept and data processing. The performance measurements of the various instrument parameters meet the requirements derived from the mission's science objectives. The SPICE instrument is ready to perform measurements that will provide vital contributions to the scientific success of the Solar Orbiter mission., Comment: A&A, accepted 19 August 2019; 26 pages, 25 figures

With the advent of standardised launch geometries and off-the-shelf payloads, space programs utilising nano-satellite platforms are growing worldwide. Thin-walled, flexible and self-deployable structures are commonly used for antennae, instrument booms or solar panels owing to their lightweight, ideal packaging characteristics and near zero energy consumption. However their behaviour in space, in particular in Low Earth Orbits with continually changing environmental conditions, raises many questions. Accurate numerical models, which are often not available due to the difficulty of experimental testing under 1g-conditions, are needed to answer these questions. In this study, we present on-earth experimental validations, as a starting point to study the response of a tape spring as a representative of thin-walled flexible structures under static and vibrational loading. Material parameters of tape springs in a singly (straight, open cylinder) and a doubly curved design, are compared to each other by combining finite element calculations, with experimental laser vibrometry within a single and multi-stage model updating approach. While the determination of the Young's modulus is unproblematic, the damping is found to be inversely proportional to deployment length. With updated material properties the buckling instability margin is calculated using different slenderness ratios. Results indicate a high sensitivity of thin-walled structures to miniscule perturbations, which makes proper experimental testing a key requirement for stability prediction on thin-elastic space structures. The doubly curved tape spring provides closer agreement with experimental results than a straight tape spring design.

This chapter describes the nature of the space environment that makes autonomous space systems a desirable application; describes the various types of space activities in near-Earth and deep space missions , and examples of autonomous systems deployed in space to date; outlines the current state-of-the-art of the intersection between trusted autonomous systems and autonomous space systems; and then presents a variety of possible future trusted autonomous space scenarios.

SPICE is an imaging spectrometer operating at vacuum ultraviolet (VUV) wavelengths, 70.4 – 79.0 nm and 97.3 - 104.9 nm. It is a facility instrument on the Solar Orbiter mission, which carries 10 science instruments in all, to make observations of the Sun’s atmosphere and heliosphere, at close proximity to the Sun, i.e to 0.28 A.U. at perihelion. SPICE’s role is to make VUV measurements of plasma in the solar atmosphere. SPICE is designed to achieve spectral imaging at spectral resolution >1500, spatial resolution of several arcsec, and two-dimensional FOV of 11 x16arcmins. The many strong constraints on the instrument design imposed by the mission requirements prevent the imaging performance from exceeding those of previous instruments, but by being closer to the sun there is a gain in spatial resolution. The price which is paid is the harsher environment, particularly thermal. This leads to some novel features in the design, which needed to be proven by ground test programs. These include a dichroic solar-transmitting primary mirror to dump the solar heat, a high in-flight temperature (60deg.C) and gradients in the optics box, and a bespoke variable-line-spacing grating to minimise the number of reflective components used. The tests culminate in the systemlevel test of VUV imaging performance and pointing stability. We will describe how our dedicated facility with heritage from previous solar instruments, is used to make these tests, and show the results, firstly on the Engineering Model of the optics unit, and more recently on the Flight Model. For the keywords, select up to 8 key terms for a search on your manuscript's subject.

This paper explores the concept of utilizing a long duration stratospheric airship as an astronomical observatory in the sub-millimetre wavelengths. In the first section of the paper, a conceptual description of the airship platform is presented along with the principles of operation of the platform. The results of a computer design code and trajectory simulation code are presented. These codes show that through the use of a modest power and propulsion system, the difficulty of constructing such a such a platform is greatly reduced. Finally, the results of a brief study into the accommodation and optical performance of a Ø3.5m class telescope and photometric and spectrographic instrument similar to the Herschel/SPIRE system within such an airship are presented. This study indicates that while the atmospheric absorption and emission characteristics impose some limitations on the spectrographic and photometric performance of the system in the 200μm to 1000μm band, the overall performance is more than adequate to render the concept viable and complementary to existing and planned ground, airborne and space based observatories.

Results of study optical performance of single pixel transition edge sensor (TES) bolometer presented at wavelength band 30-60 μm are presented. FIR radiation is coupled into a multimode horn with entrance aperture of 450 μm, length 4.5 mm and exit aperture of 45 μm , which feeds a metal integrating cavity containing the detector. The radiation band is defined by a pair of lowpass and highpass mesh filters in front of the horn. Here we present measurements of optical noise equivalent power (NEP), optical efficiency, dynamic range and time constant. The results show that measured TES detectors are close to meeting the requirement of the “Band S” of SAFARI FTS imaging instrument on the SPICA mission.

‘The definitive version is available at www3.interscience.wiley.com '. Copyright Wiley [Full text of this article is not available in the UHRA]

International audience; SPIRE, the Spectral and Photometric Imaging Receiver, is one of three instruments to fly on the European Space Agency's Herschel Space Observatory. It contains a three-band imaging photometer operating at 250, 350 and 500 μm, and an imaging Fourier transform spectrometer covering 194-672 μm. The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4 × 8', observed simultaneously in the three spectral bands. The spectrometer has an approximately circular field of view with a diameter of 2.6' The spectral resolution can be adjusted between 0.04 and 2 cm -1 (resolving power of 20-1000 at 250 μm). SPIRE will be used for many galactic and extragalactic science programmes, a number of which will be implemented as Herschel Key Projects. The SPIRE consortium's Guaranteed Time (GT) programme will devote more than 1000 h to Key Projects covering the high-redshift universe and local galaxies, which will be carried out in coordination with other GT programmes, especially that of the PACS consortium. It is also expected that substantial amounts of Herschel Open Time will be used for further extragalactic investigations. The high-redshift part of the SPIRE GT programme will focus on blank-field surveys with a range of depths and areas optimised to sample the luminosity-redshift plane and characterize the bolometric luminosity density of the universe at high-redshift. Fields will be selected that are well covered by Spitzer, SCUBA-2, PACS-GT and near-IR surveys, to facilitate source identifications and enable detailed studies of the redshifts, spectral energy distributions, and other properties of detected galaxies. The local galaxies programme will include a detailed spectral and photometric study of a sample of well resolved nearby galaxies, a survey of more than 300 local galaxies designed to provide a statistical survey of dust in the nearby universe, and a study of the ISM in low-metallicity environments, bridging the gap between the local universe and primordial galaxies.

As practitioners working with groups and organizations, we have reflected together on what we think is happening when we find ourselves acting into situations in which the intention motivating the action as its goal is itself emerging in the very action. Along with others, we have been excited by the ideas of self-organization in the natural sciences and also theories of practice, for example, tacit and explicit knowledge, in the social sciences. Together, these promise fresh insights into the potential of organizations. However, we find ourselves diverging significantly from writers who at first sight seem to be using similar ideas, but they do so with an exclusive focus on strategic choice and intention. To illustrate what we mean, we explore the work of Nonaka and Takeuchi and how they use Polanyi's idea of the participant observer. We do this to identify contradictions we see in their approach. We also discuss the implications of an alternative understanding of participation and what this indicates about what can and cannot be “managed” in the creation of new knowledge.

This paper describes a complexity perspective on organizational life by drawing on three distinctive sources. First, we describe the way different natural scientists talk of their work in simulating complex dynamical systems. Second, we listen to the contribution of social scientists in describing the dynamics of human interaction and third, we describe group analytic practice as it illuminates the emotional, prelinguistic processes at work in the group matrix. We argue that together these insights allow us to speak of the nature of self-organization in human systems in a way that emphasizes inter subjectivity, emergence and de-centred agency in contrast to the dominant voice in much management thinking which emphasizes objectivity, control and individual agency. We then relate how the complexity perspective we describe informs our approach to organizational consulting in which we participate in networks of self-organizing everyday conversation whereby the patterned structure of organizational activity is paradoxically both sustained and changed.

Introduction Section 1: Chaos Theory and Dissipative Structures 1. Chaos Theory and Strategy 2. Conditioned Emergence 3. Surfing the Edge of Chaos 5. The Science of Complexity 6. Leadership and the New Sciences Editors' Discussion of the Papers in Section 1 Section 2: Categorizing Complexity 7. Evolving Complexity in Social Science 8. Speaking of Complexity in Management Theory and Practice 9. Emergence Editors' Discussion of the Papers in Section 2 Section 3: Complexity in Social Settings 10. From Complexity Science to Complex Thinking 11. Learning as the Activity of Interdependent People 12. Complex Thinking Editors' Discussion of the Papers in Section 3. Concluding Remarks

SPICE is a high resolution imaging spectrometer operating at extreme ultraviolet wavelengths, 70.4 – 79.0 nm and 97.3 - 104.9 nm. It is a facility instrument on the Solar Orbiter mission. SPICE will address the key science goals of Solar Orbiter by providing the quantitative knowledge of the physical state and composition of the plasmas in the solar atmosphere, in particular investigating the source regions of outflows and ejection processes which link the solar surface and corona to the heliosphere. By observing the intensities of selected spectral lines and line profiles, SPICE will derive temperature, density, flow and composition information for the plasmas in the temperature range from 10,000 K to 10MK. The instrument optics consists of a single-mirror telescope (off-axis paraboloid operating at near-normal incidence), feeding an imaging spectrometer. The spectrometer is also using just one optical element, a Toroidal Variable Line Space grating, which images the entrance slit from the telescope focal plane onto a pair of detector arrays, with a magnification of approximately x5. Each detector consists of a photocathode coated microchannel plate image intensifier, coupled to active-pixel-sensor (APS). Particular features of the instrument needed due to proximity to the Sun include: use of dichroic coating on the mirror to transmit and reject the majority of the solar spectrum, particle-deflector to protect the optics from the solar wind, and use of data compression due to telemetry limitations.

The Far-Infrared Fourier transform spectrometer instrument SAFARI-SPICA which will operate with cooled optics in a low-background space environment requires ultra-sensitive detector arrays with high optical coupling efficiencies over extremely wide bandwidths. In earlier papers we described the design, fabrication and performance of ultra-low-noise Transition Edge Sensors (TESs) operated close to 100mk having dark Noise Equivalent Powers (NEPs) of order 4 × 10−19W/√Hz close to the phonon noise limit and an improvement of two orders of magnitude over TESs for ground-based applications. Here we describe the design, fabrication and testing of 388-element arrays of MoAu TESs integrated with far-infrared absorbers and optical coupling structures in a geometry appropriate for the SAFARI L-band (110 − 210 μm). The measured performance shows intrinsic response time τ ~ 11ms and saturation powers of order 10 fW, and a dark noise equivalent powers of order 7 × 10−19W/√Hz. The 100 × 100μm2 MoAu TESs have transition temperatures of order 110mK and are coupled to 320×320μm2 thin-film β-phase Ta absorbers to provide impedance matching to the incoming fields. We describe results of dark tests (i.e without optical power) to determine intrinsic pixel characteristics and their uniformity, and measurements of the optical performance of representative pixels operated with flat back-shorts coupled to pyramidal horn arrays. The measured and modeled optical efficiency is dominated by the 95Ω sheet resistance of the Ta absorbers, indicating a clear route to achieve the required performance in these ultra-sensitive detectors.

SPICA is an infra-red (IR) telescope with a cryogenically cooled mirror (~5K) with three instruments on board, one of which is SAFARI that is an imaging Fourier Transform Spectrometer (FTS) with three bands covering the wavelength of 34-210 μm. We develop transition edge sensors (TES) array for short wavelength band (34-60 μm) of SAFARI. These are based on superconducting Ti/Au bilayer as TES bolometers with a Tc of about 105 mK and thin Ta film as IR absorbers on suspended silicon nitride (SiN) membranes. These membranes are supported by long and narrow SiN legs that act as weak thermal links between the TES and the bath. Previously an electrical noise equivalent power (NEP) of 4×10-19 W/√Hz was achieved for a single pixel of such detectors. As an intermediate step toward a full-size SAFARI array (43×43), we fabricated several 8×9 detector arrays. Here we describe the design and the outcome of the dark and optical tests of several of these devices. We achieved high yield (

The next generation of space missions targeting far-infrared wavelengths will require large-format arrays of extremely sensitive detectors. The development of Transition Edge Sensor (TES) array technology is being developed for future Far-Infrared (FIR) space applications such as the SAFARI instrument for SPICA where low-noise and high sensitivity is required to achieve ambitious science goals. In this paper we describe a modal analysis of multi-moded horn antennas feeding integrating cavities housing TES detectors with superconducting film absorbers. In high sensitivity TES detector technology the ability to control the electromagnetic and thermo-mechanical environment of the detector is critical. Simulating and understanding optical behaviour of such detectors at far IR wavelengths is difficult and requires development of existing analysis tools. The proposed modal approach offers a computationally efficient technique to describe the partial coherent response of the full pixel in terms of optical efficiency and power leakage between pixels. Initial wok carried out as part of an ESA technical research project on optical analysis is described and a prototype SAFARI pixel design is analyzed where the optical coupling between the incoming field and the pixel containing horn, cavity with an air gap, and thin absorber layer are all included in the model to allow a comprehensive optical characterization. The modal approach described is based on the mode matching technique where the horn and cavity are described in the traditional way while a technique to include the absorber was developed. Radiation leakage between pixels is also included making this a powerful analysis tool.

The SAFARI instrument is a far-infrared imaging Fourier transform spectrometer for JAXA's SPICA mission. Taking advantage of the low emission of SPICA's 5 K telescope, SAFARI will provide sky background-limited, Nyquist-sampled spectroscopic imaging of a 2 ' × 2 ' field-of-view over 34-210 μm, creating significant new possibilities for far-infrared astronomy. SAFARI's aggressive science goals drive the development of a unique detector system combining large-format Transition Edge Sensor arrays and frequency division multiplexed SQUID readout with a high 160x multiplexing factor. The detectors and their cold readout electronics are packaged into 3 focal plane arrays that will be integrated into SAFARI's focal plane unit. Here we present the preliminary system design and current development status of the SAFARI detector system.

The magnetic field plays a pivotal role in many fields of Astrophysics. This is especially true for the physics of the solar atmosphere. Measuring the magnetic field in the upper solar atmosphere is crucial to understand the nature of the underlying physical processes that drive the violent dynamics of the solar corona -- that can also affect life on Earth. SolmeX, a fully equipped solar space observatory for remote-sensing observations, will provide the first comprehensive measurements of the strength and direction of the magnetic field in the upper solar atmosphere. The mission consists of two spacecraft, one carrying the instruments, and another one in formation flight at a distance of about 200m carrying the occulter to provide an artificial total solar eclipse. This will ensure high-quality coronagraphic observations above the solar limb. Solmex integrates two spectro-polarimetric coronagraphs for off-limb observations, one in the EUV and one in the IR, and three instruments for observations on the disk. The latter comprises one imaging polarimeter in the EUV for coronal studies, a spectro-polarimeter in the EUV to investigate the low corona, and an imaging spectro-polarimeter in the UV for chromospheric studies. SOHO and other existing missions have investigated the emission of the upper atmosphere in detail (not considering polarization), and as this will be the case also for missions planned for the near future. Therefore it is timely that SolmeX provides the final piece of the observational quest by measuring the magnetic field in the upper atmosphere through polarimetric observations.

Future Far-IR space telescopes, such as the SAFARI instrument of the proposed JAXA/ESA SPICA mission, will use horn antennas to couple to cavity bolometers to achieve high levels of sensitivity for Mid-IR astronomy. In the case of the SAFARI instrument the bolometric detectors susceptibility to currents coupling into the detector system and dissipating power within the bolometers is a particular concern of the class of detector technology considered.1 The simulation of such structures can prove challenging. At THz frequencies ray tracing no longer proves completely accurate for these partially coherent large electrical structures, which also present significant computational difficulties for the more generic EM approaches applied at longer microwave wavelengths. The Finite Difference Time Domain method and other similar commercially viable approaches result in excessive computational requirements, especially when a large number of modes propagate. Work being carried out at NUI-Maynooth is utilising a mode matching approach to the simulation of such devices. This approach is based on the already proven waveguide mode scattering code "Scatter"2 developed at NUI-Maynooth, which is a piece of mode matching code that operates by cascading a Smatrice while conserving power at each waveguide junction. This paper outlines various approaches to simulating such Antenna Horns and Cavities at THz frequencies, focusing primarily on the waveguide modal Scatter approach. Recently the code has been adapted to incorporate a rectangular waveguide basis mode set instead of the already established circular basis set.

The next generation of space missions targeting far-infrared bands will require large-format arrays of extremely lownoise detectors. The development of Transition Edge Sensors (TES) array technology seems to be a viable solution for future mm-wave to Far-Infrared (FIR) space applications where low noise and high sensitivity is required. In this paper we concentrate on a key element for a high sensitivity TES detector array, that of the optical coupling between the incoming electromagnetic field and the phonon system of the suspended membrane. An intermediate solution between free space coupling and a single moded horn is where over-moded light pipes are used to concentrate energy onto multimoded absorbers. We present a comparison of modeling techniques to analyze the optical efficiency of such light pipes and their interaction with the front end optics and detector cavity.

SPIRE, the Spectral and Photometric Imaging Receiver, is the Herschel Space Observatory's submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 {\mu}m, and an imaging Fourier transform spectrometer (FTS) covering 194-671 {\mu}m (447-1550 GHz). In this paper we describe the initial approach taken to the absolute calibration of the SPIRE instrument using a combination of the emission from the Herschel telescope itself and the modelled continuum emission from solar system objects and other astronomical targets. We present the photometric, spectroscopic and spatial accuracy that is obtainable in data processed through the "standard" pipelines. The overall photometric accuracy at this stage of the mission is estimated as 15% for the photometer and between 15 and 50% for the spectrometer. However, there remain issues with the photometric accuracy of the spectra of low flux sources in the longest wavelength part of the SPIRE spectrometer band. The spectrometer wavelength accuracy is determined to be better than 1/10th of the line FWHM. The astrometric accuracy in SPIRE maps is found to be 2 arcsec when the latest calibration data are used. The photometric calibration of the SPIRE instrument is currently determined by a combination of uncertainties in the model spectra of the astronomical standards and the data processing methods employed for map and spectrum calibration. Improvements in processing techniques and a better understanding of the instrument performance will lead to the final calibration accuracy of SPIRE being determined only by uncertainties in the models of astronomical standards., Comment: Accepted for publication in Astronomy&Astrophysics, Herschel First Results special issue

International audience; SPIRE, the Spectral and Photometric Imaging Receiver, is a submillimetre camera and spectrometer for Herschel. It comprises a three-band camera operating at 250, 350 and 500 Â\textmum, and an imaging Fourier Transform Spectrometer covering 194-672 \ensuremathμm. The photometer field of view is 4x8 arcmin., viewed simultaneously in the three bands. The FTS has an approximately circular field of view of 2.6 arcmin. diameter and spectral resolution adjustable between 0.04 and 2 cm^-1 ( \ensuremathλ/▵\ensuremathλ=20-1000 at 250 \ensuremathμm). Following successful testing in a dedicated facility designed to simulate the in-flight operational conditions, SPIRE has been integrated in the Herschel spacecraft and is now undergoing system-level testing prior to launch. The main design features of SPIRE are reviewed, the key results of instrument testing are outlined, and a summary of the predicted in-flight performance is given.

1. Introduction Ralph Stacey and Douglas Griffin 2. Finding Room for Values in Required Ways of Working: Values, Power, Conflict and Compromise in Aid Agencies Chris Mowles 3. Working at the Edge of Polarized Conflict in Organizations Arnie Grant 4. Compromising as Processes of Moving Forward in Organizations Iver Drabaek 5. Leadership and Self-Mastery Martin Daly 6. The Role of Propaganda in Managing Organizational Change: Ethics, Conflict and Compromise in Consulting Stephen Billing

1. Introduction 2. Ways of Thinking about Public Sector Governance 3. The Experience of Leading Public Sector Organizations in a Performance Management Regime 4. The Emotional Experience of Performance Management in the Health Sector: The Corridor 5. The Experience of Clinical Risk Assessment in the Health Sector 6. The Experience of Power, Blame and Responsibility in the Health Sector 7. The Experience of Strategic Planning and Performance Management in the Education Sector

The ESI instrument (European SPICA Instrument) is a proposed imaging spectrometer for the 30-210μm band for the JAXA SPICA mission. The instrument will have unprecedented spatial resolution and sensitivity due to the large 03.5m telescope aperture, cold fore-optics (~5K) and high sensitivity detectors (NEP~10-19W/√Hz). One of the key technical challenges of the design of the instrument is the thermal architecture due to the mass and cryogenic heat load constraints and the need for very low temperatures. Two candidate detector technologies have been pre-selected for inclusion in the instrument Phase-A study; Photoconductors and TES Bolometers. An overview of thermal architecture of the SPICA spacecraft is presented in order to explain the thermal interface constraints imposed on the instrument. Proposed thermal architectures for the instrument for both the TES and the Photoconductor options will be outlined including a novel design for a lightweight hybrid cooler for achieving sub 100-mK detector temperatures. This novel cooler architecture utilizes a combination of ADR and sorption coolers. Several design solutions for achieving high thermal isolation generic to both detector options are presented.

The design of the 300 mK system for Herschel-SPIRE is complex, with many difficult, sometimes conflicting, requirements and constraints placed upon it. Five detector arrays, mounted from a 2 K box, are linked to a single 3He sorption-cooler tip by a high-conductance copper strap network. This strap retains high thermal conductance, even though it incorporates an electrical break to comply with the SPIRE grounding scheme. It requires stiffness to withstand launch vibrations, but needs compliance to avoid transmission of loads to the detector arrays. The strap is stiffly supported by novel, compact cryogenic stand-offs which provide a high degree of thermal isolation from the 2 K stage. An additional complication is that the detectors reside in a 2 K environment, whilst the cooler tip is in a 4 K environment. Two of the cryogenic stand-offs also act as light-tight feed-throughs to pass the strap from the 4 K environment to the inside of the 2 K detector boxes. Active thermal control is provided on the 300 mK system to address the detector stability requirements. This paper describes the system, and gives results of the performance in SPIRE flight model ground tests.

The Spectral and Photometric Imaging REceiver (SPIRE) is one of the three scientific instruments to fly on the European Space Agency's Herschel Space Observatory, and contains a three-band imaging submillimetre photometer and an imaging Fourier transform spectrometer. The flight model of the SPIRE cold focal plane unit has been built up in stages with a cold test campaign associated with each stage. The first campaign focusing on the spectrometer took place in early 2005 and the second campaign focusing on the photometer was in Autumn 2005. SPIRE is currently undergoing its third cold test campaign following cryogenic vibration testing. Test results to date show that the instrument is performing very well and in general meets not only its requirements but also most of its performance goals. We present an overview of the instrument tests performed to date, and the preliminary results.

SPIRE, the Spectral and Photometric Imaging Receiver, is a submillimetre camera and spectrometer for the European Space Agency's Herschel Space Observatory. It comprises a three-band imaging photometer operating at 250, 360 and 520

The discovery of STI571, a drug targeting the tyrosine kinase activity of Bcr-Abl, c-Kit, and platelet-derived growth factor receptor (PDGFR), has demonstrated the feasibility of ATP-competitive small-molecule kinase inhibitors for the chronic treatment of molecularly defined cancers. The presence of an activated form of protein kinases targeted by STI571 in various malignancies appears to be mandatory for a clinical response to this drug. This also indicates that a certain subset of molecularly defined tumors depends upon the overactivation of one or more signaling pathways, which can be attacked by targeted therapy. The finding that STI571 resistance is often associated with mutations in the kinase domain unambiguously demonstrates that the targets of STI571 in these tumors are Bcr-Abl, c-Kit, and/or PDGFR. Generation of resistance to STI571 is most likely due to the binding mode of STI571 that stabilizes the inactive conformation of the target kinases. Recent mutational analysis combined with structural biology has provided the basis for the understanding of the binding mode of STI571, and the resistance mechanisms as well as activation mechanisms of Bcr-Abl, c-Kit, and PDGFR. Although this binding mode is key for the exquisite selectivity and tolerability of STI571, it is also its “weakness”, because it allows mutations to occur in the target kinase which appear not to affect the normal function of the kinase. Therefore, for an effective long-term cancer therapy with ATP-competitive small-molecule kinase inhibitors, it appears necessary to use more than one kinase inhibitor targeting different conformations of the same kinase, or each inhibitor needs to be aimed at a specific mutant and downstream signaling element.

The Spectral and Photometric Imaging REceiver (SPIRE) is one of the three scientific instruments on the European Space Agency's Herschel mission. At the start of 2004 the Cryogenic Qualification Model (CQM) of SPIRE was tested with the aim of verifying the instrument system design and evaluating key performance parameters. We present a description of the test facility, an overview of the instrument tests carried out on the CQM, and the first results from the analysis of the test data. Instrument optical efficiency and detector noise levels are close to the values expected from unit-level tests, and the SPIRE instrument system works well, with no degradation in performance from stray light, electromagnetic interference or microphonically induced noise. Some anomalies and imperfections in the instrument performance, test set-up, and test procedures have been identified and will be addressed in the next test campaign.