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Bone metastasis is a common, yet serious, complication of breast cancer. Breast cancer cells that extravasate from blood vessels to the bone devastate bone quality by interacting with bone cells and disrupting the bone remodeling balance. Although exercise is often suggested as a cancer intervention strategy and mechanical loading during exercise is known to regulate bone remodeling, its role in preventing bone metastasis remains unknown. We developed a novel in vitro microfluidic tissue model to investigate the role of osteocytes in the mechanical regulation of breast cancer bone metastasis. Metastatic MDA-MB-231 breast cancer cells were cultured inside a 3D microfluidic lumen lined with human umbilical vein endothelial cells (HUVECs), which is adjacent to a channel seeded with osteocyte-like MLO-Y4 cells. Physiologically relevant oscillatory fluid flow (OFF) (1 Pa, 1 Hz) was applied to mechanically stimulate the osteocytes. Hydrogel-filled side channels in-between the two channels allowed real-time, bi-directional cellular signaling and cancer cell extravasation over 3 days. The applied OFF was capable of inducing intracellular calcium responses in osteocytes (82.3% cells responding with a 3.71 fold increase average magnitude). Both extravasation distance and percentage of extravasated side-channels were significantly reduced with mechanically stimulated osteocytes (32.4% and 53.5% of control, respectively) compared to static osteocytes (102.1% and 107.3% of control, respectively). This is the first microfluidic device that has successfully integrated stimulatory bone fluid flow, and demonstrated that mechanically stimulated osteocytes reduced breast cancer extravasation. Future work with this platform will determine the specific mechanisms involved in osteocyte mechanoregulation of breast cancer bone metastasis, as well as other types of cancer metastasis and diseases.

International audience; We present an update on the overall integration progress of the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT), now scheduled for first light in early-2021, with almost all components now arrived at the observatory. We also present a summary of the current planning behind the 5-year initial phase of survey operations, and some detailed end-to-end science simulations that have been implemented to evaluate the final on-sky performance after data processing. WEAVE will provide optical ground-based follow up of ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 mini integral field units, or a single large IFU for each observation. The fibres are fed to a single (dual-beam) spectrograph, with total of 16k spectral pixels, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R~5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R~20000.

International audience; The WEAVE instrument nearing completion for the William Herschel Telescope is a fiber-fed spectrograph operating in three different modes. Two comprise deployable fibers at the prime focus for point-like objects and small integral field units (IFU), the third is a large IFU placed at the center of the field. Three distinct fiber systems support these modes and route the photons to the spectrograph located on the Nasmyth platform 33m away: the first features 960+940 fibers and is duplicated to allow configuring the fibers on one plate while observation is carried out on the other, the second has 20 hexagonal IFUs featuring 37 fibers each, the third is a large array of 609 fibers with twice the former's diameter. The large number of fibers and the diversity of their instantiation have made procurement of the parts and assembly of the custom cables a challenge. They involve project partners in France, the UK and the Netherlands and industrial partners in France, Canada, the USA and China to combine know-how and compress the schedule by parallelizing assembly of the cables. Besides the complex management that this induces, it has called for revising the fibers' handling to relax tolerances and for a rigorous assessment of the conformity of the products. This paper tells the story of the making of the fiber links, presents the overall organization of the procurement and assembly chains together with the inspection and testing allowing for assessing the conformance of the hardware delivered.

WEAVE is the new wide-field spectroscopy facility for the prime focus of the William Herschel Telescope at La Palma, Spain. Its fibre positioner is essential for the accurate placement of the spectrograph's 960 fibre multiplex. We provide an overview of the final assembly and metrology of the fibre positioner, and results of lab commissioning of its robot gantries. A completely new z-gantry for each positioner robot was acquired, with measurements showing a marked improvement in positioning repeatability. We also present the first results of the configuration software testing, and discuss the metrology procedures that must be repeated after the positioner's arrival at the observatory.

The Atmospheric Remote-Sensing Infrared Exoplanet Large-survey, ARIEL, has been selected to be the next (M4) medium class space mission in the ESA Cosmic Vision programme. From launch in 2028, and during the following 4 years of operation, ARIEL will perform precise spectroscopy of the atmospheres of ~1000 known transiting exoplanets using its metre-class telescope. A three-band photometer and three spectrometers cover the 0.5 µm to 7.8 µm region of the electromagnetic spectrum. This paper gives an overview of the mission payload, including the telescope assembly, the FGS (Fine Guidance System) - which provides both pointing information to the spacecraft and scientific photometry and low-resolution spectrometer data, the ARIEL InfraRed Spectrometer (AIRS), and other payload infrastructure such as the warm electronics, structures and cryogenic cooling systems.

Background Continuing professional development (CPD) activities delivered by simulation to independently practicing physicians are becoming increasingly popular. At present, the educational potential of such simulations is limited by the inability to create effective curricula for the CPD audience. In contrast to medical trainees, CPD activities lack pre-defined learning expectations and, instead, emphasize self-directed learning, which may not encompass true learning needs. We hypothesize that we could generate an interprofessional CPD simulation curriculum for practicing pediatric emergency medicine (PEM) physicians in a single-center tertiary care hospital using a deliberative approach combined with Kern’s six-step method of curriculum development. Methods From a comprehensive core list of 94 possible PEM clinical presentations and procedures, we generated an 18-scenario CPD simulation curriculum. We conducted a comprehensive perceived and unperceived needs assessment on topics to include, incorporating opinions of faculty PEM physicians, hospital leadership, interprofessional colleagues, and expert opinion on patient benefit, simulation feasibility, and value of simulating the case for learning. To systematically rank items while balancing the needs of all stakeholders, we used a prioritization matrix to generate objective “priority scores.” These scores were used by CPD planners to deliberately determine the simulation curriculum contents. Results We describe a novel three-step CPD simulation curriculum design method involving (1) systematic and deliberate needs assessment, (2) systematic prioritization, and (3) curriculum synthesis. Of practicing PEM physicians, 17/20 responded to the perceived learning needs survey, while 6/6 leaders responded to the unperceived needs assessment. These ranked data were input to a five-variable prioritization matrix generating priority scores. Based on local needs, the highest 18 scoring clinical presentations and procedures were selected for final inclusion in a PEM CPD simulation curriculum. An interim survey of PEM physician (21/24 respondents) opinions was collected, with 90% finding educational value with the curriculum. The curriculum includes items not identified by self-directed learning that PEM physicians thought should be included. Conclusions We highlight a novel methodology for PEM physicians that can be adapted by other specialities when designing their own CPD simulation curriculum. This methodology objectively considers and prioritizes the needs of practicing physicians and stakeholders involved in CPD.

Mechanical loading on bone tissue is an important physiological stimulus that plays a key role in bone growth, fracture repair, and treatment of bone diseases. Osteocytes (bone cells embedded in bone matrix) are well accepted as the sensor cells to mechanical loading and play a critical role in regulating the bone structure in response to mechanical loading. To understand the response of osteocytes to differential mechanical stimulation in physiologically relevant arrangements, there is a need for a platform which can locally stimulate bone cells with different levels of fluid shear stress. In this study, we developed a device aiming to achieve non-contact local mechanical stimulation of osteocytes with a magnetically actuated beam that generates the fluid shear stresses encountered in vivo. The stimulating beam was made from a composite of magnetic powder and polymer, where a magnetic field was used to precisely oscillate the beam in the horizontal plane. The beam is placed above a cell-seeded surface with an estimated gap height of 5 μm. Finite element simulations were performed to quantify the shear stress values and to generate a shear stress map in the region of interest. Osteocytes were seeded on the device and were stimulated while their intracellular calcium responses were quantified and correlated with their position and local shear stress value. We observed that cells closer to the oscillating beam respond earlier compared to cells further away from the local shear stress gradient generated by the oscillating beam. We have demonstrated the capability of our device to mimic the propagation of calcium signalling to osteocytes outside of the stimulatory region. This device will allow for future studies of osteocyte network signalling with a physiologically accurate localized shear stress gradient.

Bone metastases occur in 65% to 75% of patients with advanced breast cancer and significantly worsen their survival and quality of life. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced the transendothelial migration of breast cancer cells. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels. In this study, we investigated the specific effects of flow-stimulated osteocytes on the interaction between endothelial cells and breast cancer cells in vitro. We observed that CM from flow-stimulated osteocytes reduced endothelial permeability by 15% and breast cancer cell adhesion onto endothelial monolayers by 18%. The difference in adhesion was abolished with anti-intercellular adhesion molecule 1 (ICAM-1) neutralizing antibodies. Furthermore, CM from endothelial cells conditioned in CM from flow-stimulated osteocytes significantly altered the gene expression in bone-metastatic breast cancer cells, as shown by RNA sequencing. Specifically, breast cancer cell expression of matrix metallopeptidase 9 (MMP-9) was downregulated by 62%, and frizzled-4 (FZD4) by 61%, when the osteocytes were stimulated with flow. The invasion of these breast cancer cells across Matrigel was also reduced by 47%, and this difference was abolished by MMP-9 inhibitors. In conclusion, we demonstrated that flow-stimulated osteocytes downregulate the bone-metastatic potential of breast cancer cells by signaling through endothelial cells. This provides insights into the capability of bone mechanical regulation in preventing bone metastases; and may assist in prescribing exercise or bone-loading regimens to patients with breast cancers.

Bone metastases, the migration of cancers to bone, occur in 65-80% of patients with advanced breast cancer. Metastasized cancer cells interact with cells such as the bone-resorbing osteoclasts to alter bone remodeling. Exercise, often suggested as an intervention for cancer patients, regulates bone remodeling via osteocytes. Osteocytes also signal to endothelial cells, which may affect cancer cell extravasation. Therefore, we hypothesize that mechanically stimulated osteocytes can regulate processes in breast cancer bone metastasis. To test this, we exposed osteocytes to oscillatory fluid flow in vitro using parallel-plate flow chambers. We observed that conditioned medium from flow-stimulated osteocytes increased migration (by 45%) and reduced apoptosis (by 12%) of breast cancer cells. Conditioned medium from osteoclasts conditioned in flowed osteocytes' conditioned medium reduced migration (by 47%) and increased apoptosis (by 55%) of cancer cells. Cancer cell trans-endothelial migration was reduced by 34% toward flowed osteocytes' conditioned medium. This difference was abolished with ICAM-1 or IL-6 neutralizing antibodies. Conditioned medium from endothelial cells conditioned in flowed osteocytes' conditioned medium increased cancer cell apoptosis by 29%. To summarize, this study demonstrated mechanically stimulated osteocytes' potential to affect breast cancer cells not only through direct signaling, but also through osteoclasts and endothelial cells. The anti-metastatic potential of the indirect signalings is particularly exciting since osteocytes are further away from metastasizing cancer cells than osteoclasts and endothelial cells. Future studies into the effect of bone mechanical loading on metastases and its mechanism will assist in designing cancer intervention programs that lowers the risk for bone metastases.

The Atmospheric Remote-sensing Infrared Exoplanet Large-survey mission (ARIEL) is one of the three present candidates for the ESA M4 (the fourth medium mission) launch opportunity. The proposed Payload will perform a large unbiased spectroscopic survey from space concerning the nature of exoplanets atmospheres and their interiors to determine the key factors affecting the formation and evolution of planetary systems. ARIEL will observe a large number (>500) of warm and hot transiting gas giants, Neptunes and super-Earths around a wide range of host star types, targeting planets hotter than 600 K to take advantage of their well-mixed atmospheres. It will exploit primary and secondary transits spectroscopy in the 1.2-8 um spectral range and broad-band photometry in the optical and Near IR (NIR). The main instrument of the ARIEL Payload is the IR Spectrometer (AIRS) providing low-resolution spectroscopy in two IR channels: Channel 0 (CH0) for the 1.95-3.90 um band and Channel 1 (CH1) for the 3.90-7.80 um range. It is located at the intermediate focal plane of the telescope and common optical system and it hosts two IR sensors and two cold front-end electronics (CFEE) for detectors readout, a well defined process calibrated for the selected target brightness and driven by the Payload's Instrument Control Unit (ICU)., Experimental Astronomy, Special Issue on ARIEL, (2017)

Bone cells exist in a complex environment where they are constantly exposed to numerous dynamic biochemical and mechanical stimuli. These stimuli regulate bone cells that are involved in various bone disorders, such as osteoporosis. Knowledge of how these stimuli affect bone cells have been utilised to develop various treatments, such as pharmaceuticals, hormone therapy, and exercise. To investigate the role that bone loading has on these disorders in vitro, bone cell mechanotransduction studies are typically performed using parallel plate flow chambers (PPFC). However, these chambers do not allow for dynamic cellular interactions among different cell populations to be investigated. We present a microfluidic approach that exposes different cell populations, which are located at physiologically relevant distances within adjacent channels, to different levels of fluid shear stress, and promotes cell-cell communication between the different channels. We employed this microfluidic system to assess mechanically regulated osteocyte-osteoclast communication. Osteoclast precursors (RAW264.7 cells) responded to cytokine gradients (e.g., RANKL, OPG, PGE-2) developed by both mechanically stimulated (fOCY) and unstimulated (nOCY) osteocyte-like MLO-Y4 cells simultaneously. Specifically, we observed increased osteoclast precursor cell densities and osteoclast differentiation towards nOCY. We also used this system to show an increased mechanoresponse of osteocytes when in co-culture with osteoclasts. We envision broad applicability of the presented approach for microfluidic perfusion co-culture of multiple cell types in the presence of fluid flow stimulation, and as a tool to investigate osteocyte mechanotransduction, as well as bone metastasis extravasation. This system could also be applied to any multi-cell population cross-talk studies that are typically performed using PPFCs (e.g. endothelial cells, smooth muscle cells, and fibroblasts).

Manipulation of micrometer to millimeter-scale objects is central to biotechnological and medical applications involving small-scale robotic devices. Mobile untethered microgrippers have been developed, which use magnetic fields for motion and activation of grasping. This letter extends the capabilities of such microgrippers by presenting the first example of reliable and autonomous three-dimensional (3-D) micrograsping and cargo delivery of a microgripper using simple control strategies. This endeavor will allow microgrippers to reliably grasp and transfer microobjects, such as cells, with minimal user input, which is ideal for cooperative tasks performed by multiple microgrippers in future work. The proposed controller autonomously manipulates a 3-D magnetic microgripper for pick-and-place tasks in the 3-D space. By regulating the remotely applied force on the microgripper, the 3-D position and velocity of the microgripper are controlled, and the microgripper grasping, i.e., opening and closing, is determined by the magnetic field strength. In experiments, the microgripper successfully grasps cargoes with cubic, irregular, triangular, and beam shapes using at most 5, 8 , 20, and 24 attempts, respectively. The microgripper shown here demonstrates fast grasping due to their complete magnetic actuation method. Moreover, a preliminary cell viability test suggests that the microgripper has no adverse effects on living cells. This study proves the proposed microgripper and controller to be agile and reliable tools for biomedical tasks.

Accurate prediction of the arrival of solar wind phenomena, in particular coronal mass ejections (CMEs), is becoming more important given our ever-increasing reliance on technology. SCOPE is a coronagraph specifically optimised for operational space weather prediction, designed to provide early evidence of Earth-bound CMEs. In this paper, we present results from phase A/B1 of the instrument’s development, which included conceptual design and a program of breadboard testing. We describe the conceptual design of the instrument. In particular, we explain the design and analysis of the straylight rejection baffles and occulter needed to block the image of the solar disc, in order to render the much fainter corona visible. We discuss the development of in-house analysis code to predict the straylight diffraction effects that limit the instrument’s performance, and present results, which we compare against commercially available analysis tools and the results from breadboard testing. In particular, we discuss some of the challenges of predicting straylight effects in this type of instrument and the methods we have developed for overcoming them. We present the test results from an optical breadboard, designed to verify the end-to-end straylight rejection of the instrument. The design and development of both the breadboard and the test facility is presented. We discuss some of the challenges of measuring very low levels of straylight and how these drive the breadboard and test facility design. We discuss the test and analysis procedures developed to ensure a representative, complete characterisation of the instrument’s straylight response.

Objectives: Three-dimensional (3D) printing has emerged as a promising technology in the field of orthopaedic surgery. The purpose of this study was to evaluate the mechanical properties of 3D printed 1/3 tubular plates and cortical screws compared to standard-of-care stainless steel 1/3 tubular plates and cortical screws. Methods: Replication and modification designs were developed for both plates and screws using open-source computer-assisted design (CAD) software. Models were printed in four materials: acrylonitrile butadiene styrene (ABS), carbon fiber reinforced polylactic acid (PLA), polycarbonate (PC), and polyether ether ketone (PEEK). The implants (Figure 1) were tested and compared to surgical steel plates and screws. Plates were tested with three-point bend and torsional loading using an Instron® material testing machine. Screws were analyzed on pull-out strength in a Sawbones® bone model, shear strength, and torsional loading. Each combination of design and material was placed in its own test group with a sample size (n = 5) and compared to a steel control group (n = 5) for each mechanical test. Results: Significant interaction effects between material type and design type were observed for screw shear (p = 0.003), screw torque (p = 0.023), plate 3-point bend (p = 0.002), and plate torque (p = 0.001). A significant interaction effect was not observed for screw pull-out (p = 0.407), however, a statistically significant difference in mean force between material types (p Conclusion: This study demonstrates that desktop 3D printers are capable of printing biocompatible materials that can replicate surgical implants. Although the current materials have significant mechanical variability, they do not approximate the properties of stainless steel. The utility of 3D printed surgical implants for internal fracture fixation provides a potential clinical application in locations where equipment is not as readily available, such as developing countries, forward operating military units, or long duration space flight missions. Furthermore, the cost for 3D printers and 3D printable materials has significantly decreased over recent years. This increase in technology and associated decrease in costs, along with numerous open-source 3D modeling software programs, could provide a low-cost alternative to more expensive and less accessible standard-of-care stainless-steel implants. [Figure: see text]

International audience; ARIEL (the Atmospheric Remote-sensing Infrared Exoplanet Large-survey) has been selected by ESA as the next medium-class science mission (M4), expected to be launched in 2028. The mission will be devoted to observing spectroscopically in the infrared a large population of warm and hot transiting exoplanets (temperatures from 500 K to 3000 K) in our nearby Galactic neighborhood, opening a new discovery space in the field of extrasolar planets and enabling the understanding of the physics and chemistry of these far away worlds. ARIEL was selected for implementation by ESA in March 2018 from three candidate missions that underwent parallel phase A studies. This paper gives an overview of the design at the end of phase A and discusses plans for its evolution during phase B1, in the run-up to mission adoption. ARIEL is based on a 1 m class telescope feeding two instruments: a moderate resolution spectrometer covering the wavelengths from 1.95 to 7.8 microns; and a three-channel photometer (which also acts as a fine guidance sensor) with bands between 0.5 and 1.2 microns combined with a low resolution spectrometer covering 1.25 to 1.9 microns. During its 3.5 years of operation from an L2 orbit, ARIEL will continuously observe exoplanets transiting their host star. This paper presents an overall view of the integrated design of the payload proposed for this mission. The design tightly integrates the various payload elements in order to allow the exacting photometric stability targets to be met, while providing simultaneous spectral and photometric data from the visible to the mid-infrared. We identify and discuss the key requirements and technical challenges for the payload and describe the trade-offs that were assessed during phase A, culminating in the baseline design for phase B1. We show how the design will be taken forward to produce a fully integrated and calibrated payload for ARIEL that can be built within the mission and programmatic constraints and will meet the challenging scientific performance required for transit spectroscopy.

WEAVE is a new wide-field multi-object spectroscopy (MOS) facility proposed for the prime focus of the 4.2m William Herschel Telescope (WHT), situated on the island of La Palma, Canary Islands, Spain. To allow for the compensation of the effects of temperature-induced and gravity-induced image degradation, the WEAVE prime focus assembly will be translated along the telescope optical axis. The assembly comprises the prime focus corrector (PFC), a central mount for the corrector known as FTS[1], an instrument rotator and a twin-focal-plane fibre positioner. SENER, that manufactured and delivered the FTS, is also responsible for the final design, manufacturing, integration, alignment and testing of the PFC and its ancillary equipment. This manuscript describes the final design of the PFC along with the analyses and simulations performed and presents the procedures for the integration and alignment of the lenses in the corrector.

Product Assurance is an essential activity to support the design and construction of complex instruments developed for major scientific programs. The international size of current consortia in astrophysics, the ambitious and challenging developments, make the product assurance issues very important. The objective of this paper is to focus in particular on the application of Product Assurance Activities to a project such as MOSAIC, within an international consortium. The paper will also give a general overview on main product assurance tasks to be implemented during the development from the design study to the validation of the manufacturing, assembly, integration and test (MAIT) process and the delivery of the instrument.

A new prime focus corrector for the WEAVE project for the William Herschel Telescope is being produced. The corrector consists of six lens elements, the largest being 1.1 m in diameter. It also incorporates an Atmospheric Dispersion Corrector. Testing procedures for the WEAVE prime focus corrector lens elements are described here. Critical issues encountered in practice, including the influence of the lens size, wedge and weight on the testing procedure are discussed. Due to large lens dimensions, a dedicated test tower and lens support system has been developed to measure the optical surface form errors of the concave surfaces and the transmitted wavefront of each lens. For some of the lens elements, sub-aperture measurements have been performed using an off-axis Hindle sphere and the resultant OPD maps have been stitched together. The challenge of testing a wedged lens with a combination of a long radius convex surface and a short radius concave surface has been resolved by using another lens from the system as an auxiliary lens. The practice of testing convex surfaces via internal reflection/transmission through the lens element has been avoided entirely in this case and some discussion justifying the choices of metrology approach taken is given. The fabrication and acceptance testing of the lens elements has been completed within the expected time and budget, and all elements have been shown to meet requirements.

International audience; We present an update on the overall construction progress of the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT), now that all the major fabrication contracts are in place. We also present a summary of the current planning behind the 5-year initial phase of survey operations, and some detailed end-to-end science simulations that have been effected to evaluate the final on-sky performance after data processing. WEAVE will provide optical ground-based follow up of ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 integral field units, or a single large IFU for each observation. The fibres are fed to a single (dual-beam) spectrograph, with total of 16k spectral pixels, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R 5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R 20000. The project has experienced some delays in procurement and now has first light expected for the middle of 2019.

The Observation Queue Scheduler (OQS) for WEAVE is described in this paper, with particular emphasis on the scheduling algorithm. WEAVE is the new 2-deg field of view multi-object (1000 multiplex) spectroscopy facility (R5000 and R20000) at the 4.2-m William Herschel Telescope. The OQS helps to maximize the scientific impact of WEAVE observations by optimising the schedule of the observing blocks, taking into account the science priority, required instrument configuration and observing constraints. On a nightly basis the OQS will assist the observer in creating a flexible queue of suitable observing blocks to be executed. It will be also possible to run a version of the OQS for extended periods of time to provide guidance on the longer-term planning of WEAVE surveys.

WEAVE is the new wide field multi-object and integral field survey facility for the prime focus of the 4.2 m William Herschel Telescope. It is located at the Observatorio Roque de los Muchachos, in La Palma, Canary Islands, Spain. WEAVE fiber-fed spectrograph offers two resolutions, R ~ 5000 and 20,000. It has a collimator mirror and two cameras optimized for the wavelength intervals of 366 - 959 nm and 579 - 959 nm, respectively. One of the responsibilities of INAOE within the WEAVE collaboration is the polishing of the collimator mirror, made of OHARA CLEARCERAM®- Z HS. The collimator has a diameter of 660 mm, a central thickness of 44.7 mm and a weight of 56.8 kg. The main specifications are: 2 fringes irregularity in a clear aperture of 624 mm diameter and a radius of curvature of 1224.65 mm +/- 0.15. In this work, we present the polishing process and final results for the collimator. In particular, we describe the tools developed for its manufacturing, the modifications carried out to the conventional polishing machine to support the glass. Additionally, the interferometric optical irregularity measurements are presented. The collimator polishing process is finished fulfilling all the optical specifications.

WEAVE is the new wide field multi-object and integral field survey facility for the prime focus of the 4.2 m William Herschel Telescope. WEAVE fiber-fed spectrograph offers two resolutions, R ~ 5000 and 20,000. The dual-beam spectrograph has two cameras: the blue one optimized for the wavelength interval of 366 - 606 nm and the red one for 579 - 959 nm. Each camera is formed by eight lenses, one aspherical and seven spherical. The lenses of the red camera are identical to the lenses of the blue camera only differentiated by the anti-reflection coating wavelength range. The diameter of the largest surface is 320 mm while of the smallest is 195 mm. INAOE, as a member of the collaboration is responsible of the manufacturing of the 14 spherical lenses and the collimator mirror. Here, we describe the main characteristics of WEAVE high precision cameras lenses, the manufacturing challenges giving the combination of OHARA® glasses properties, dimensions and specifications. We discuss the solutions developed to achieve the very demanding specifications.

WEAVE is the next-generation optical spectroscopy facility for the William Herschel Telescope (WHT). It shows two channels (blue and red) and two working modes, a low-resolution (R=3,000-7,500) and a high-resolution (R=13,000- 25,000). The dispersing elements of the spectrograph are Volume Phase Holographic Gratings (VPHGs), two for the lower resolution mode and three for the higher resolution mode. Such gratings have a large size (clear aperture > 190 mm) and they are characterized by some key features, i.e. diffraction efficiency, wavefront error and dispersion that affect the final performances of the spectrograph. The VPHGs have been produced by KOSI based on the WEAVE design. After that, the VPHGs have been characterized, showing interesting results in terms of diffraction efficiency that reached peak values of 90%. As for the wavefront distortion, which is one of the critical aspect in VPHG technology, a different behavior between medium and high resolution elements was found. A larger wavefront distortion have been measured in the high resolution elements, because of the higher aspect ratio. A polishing process on the assembled VPHGs has been performed in order to reduce the wavefront distortion. Here, the results are presented and the specific issues discussed.

WEAVE is the new wide-field spectroscopy facility for the prime focus of the William Herschel Telescope on La Palma in the Canary Islands, Spain. It is a multi-object "pick-and-place" fibre-fed spectrograph with a 960 fibre multiplex behind a new dedicated 2° prime focus corrector. We provide an update on the fibre positioner's technical progress. The hardware has been fully assembled and integrated with its control system for testing. We have made initial calibrations and are starting to move test fibres. In the near future we will dismantle for final modifications and surface anodising, before final reassembly and full fibre installation.

Metastases, or migration of cancers, are common and severe cancer complications. Although the 5-year survival rates of primary tumors have greatly improved, those of metastasis remain below 30%, highlighting the importance of investigating specific mechanisms and therapeutic approaches for metastasis. Microfluidic devices have emerged as a powerful platform for drug target identification and drug response screening and allow incorporation of complex interactions in the metastatic microenvironment as well as manipulation of individual factors. In this work, we review microfluidic devices that have been developed to study cancer cell migration and extravasation in response to mechanical (section ‘Microfluidic investigation of mechanical factors in cancer cell migration’), biochemical (section ‘Microfluidic investigation of biochemical signals in cancer cell invasion’), and cellular (section ‘Microfluidic metastasis-on-a-chip models for investigation of cancer extravasation’) signals. We highlight the device characteristics, discuss the discoveries enabled by these devices, and offer perspectives on future directions for microfluidic investigations of cancer metastasis, with the ultimate aim of identifying the essential factors for a ‘metastasis-on-a-chip’ platform to pursue more efficacious treatment approaches for cancer metastasis. The stealthy spread of cancer from tumors to other organs is being unraveled with increasing precision thanks to on-chip microfluidics. Yu Sun from the University of Toronto in Canada and colleagues review how high-throughput devices containing 3D cell cultures have intrinsic advantages over mouse models when it comes to pinpointing the mechanical, biochemical, and micro-environmental factors that cause cancers to metastasize. Devices that move cancer cells through variously-shaped channels reveal how geometric confinement can increase migration speeds and alter cell organization. Other systems grow co-cultures of tumors with macrophages or vascular tissue to simulate and identify the chemokine-based agents that signal cancer cells to force their way into secondary sites. Integrating these microfluidic experiments into single ‘metastasis-on-a-chip’ devices is forecast to benefit personalized testing of future cancer medications.

The Atmospheric Remote-sensing Infrared Exoplanet Large-survey (ARIEL) has been recently selected as the next ESA medium-class mission (M4) with a foreseen launch in 2028. During its 3.5 years of scientific operations, ARIEL will observe spectroscopically in the infrared (IR) a large population of known transiting planets in the neighbourhood of the Solar System. ARIEL aims to give a breakthrough in the observation of exoplanet atmospheres and understanding of the physics and chemistry of these far-away worlds. ARIEL is based on a 1-m class telescope feeding a collimated beam into two separate instrument modules: a spectrometer module covering the waveband between 1.95 μm and 7.80 μm; and a combined fine guidance system/visible photometer/NIR spectrometer. The primary payload is the spectrometer, whose scientific observations are supported by the fine guidance system and photometer, which is monitoring the photometric stability of the target and allowing, at the same time, the target to be properly pointed. The telescope configuration is a classic Cassegrain layout used with an eccentric pupil and coupled to a tertiary off-axis paraboloidal mirror; the design has been conceived to satisfy all the mission requirements, and it guarantees the requested “as-built” diffraction limited performance. To constrain the thermo-mechanically induced optical aberrations, the primary mirror (M1) temperature will be monitored and finely tuned using an active thermal control system based on thermistors and heaters. They will be switched on and off to maintain the M1 temperature within ±1 K by the Telescope Control Unit (TCU). The TCU is a payload electronics subsystem also responsible for the thermal control of the main spectrometer detectors as well as the secondary mirror (M2) mechanism and IR calibration source management. The TCU, being a slave subsystem of the Instrument Control Unit (ICU), will collect the housekeeping data from the monitored subsystems and will forward them to the master unit. The latter will run the application software, devoted to the main spectrometer management and to the scientific data on-board processing.

International audience

In this work we present the coatings of the spectrograph red camera of WEAVE -the new multiobject survey facility for the 4.2m William Herschel Telescope. The initial requirements of WEAVE red camera lenses, with reflectances as low as 0.4% through the wavelength interval from 590 nm to 959 nm at angles of incidence of 18° +/- 17° represented a challenge for both design and production. Based on initial requirements, several solutions to the same problem were achieved and tested. The customized designs have been continuously improved through theoretical and experimental approximations. From transmittance measurements at normal incidence we developed a method to determine the reflectance at different angles of incidence. We show the designs and coating transmittance obtained for the four glasses on test runs to guarantee that the designs were achievable experimentally. Additionally, we present the reflectance obtained on the lenses of the the first four lenses of WEAVE red camera.

WEAVE is the next-generation spectroscopic facility for the William Herschel Telescope (WHT) 1,2. WEAVE offers multi-object (1000 fibres) and integral-field spectroscopy at two resolutions (R 5000, 20000) over a 2-deg field of view at prime focus and will mainly provide follow up of ground-based (LOFAR) and space-based (GAIA) surveys. The Observatory Control System (OCS) is responsible for providing the software control and feedback framework through which WEAVE will be operated. This paper summarizes the design of the different OCS subsystems and the interfaces between them and other WEAVE components. In the remainder of this paper, Section 2 outlines the other WEAVE systems with which the OCS interacts, Section 3 describes the system architecture, Section 4 comments on system-architecture decisions, Section 5 describes the main components of the OCS, Section 6 outlines the life-cycle of an OCS Observing Block and, finally, Section 7 gives an overview of the OCS testing plan.

Fluid flow is an important regulator of cell function and metabolism in many tissues. Fluid shear stresses have been used to level the mechanical stimuli applied in vitro with what occurs in vivo. However, these experiments often lack dynamic similarity, which is necessary to ensure the validity of the model. For interstitial fluid flow, the major requirement for dynamic similarity is the Reynolds number (Re), the ratio of inertial to viscous forces, is the same between the system and model. To study the necessity of dynamic similarity for cell mechanotransduction studies, we investigated the response of osteocyte-like MLO-Y4 cells to different Re flows at the same level of fluid shear stress. Osteocytes were chosen for this study as flows applied in vitro and in vivo have Re that are orders of magnitude different. We hypothesize that osteocytes' response to fluid flow is Re dependent. We observed that cells exposed to lower and higher Re flows developed rounded and triangular morphologies, respectively. Lower Re flows also reduced apoptosis rates compared to higher Re flows. Furthermore, MLO-Y4 cells exposed to higher Re flows had stronger calcium responses compared to lower Re flows. However, by also controlling for flow rate, the lower Re flows induced a stronger calcium response; while degradation of components of the osteocyte glycocalyx reversed this effect. This work suggests that osteocytes are highly sensitive to differences in Re, independent of just shear stresses, supporting the need for improved in vitro flow platforms that better recapitulate the physiological environment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:663-671, 2018.

Fluid flow is an important regulator of cell function and metabolism in many tissues. Fluid shear stresses have been used to level the mechanical stimuli applied in vitro with what occurs in vivo. However, these experiments often lack dynamic similarity, which is necessary to ensure the validity of the model. For interstitial fluid flow, the major requirement for dynamic similarity is the Reynolds number (Re), the ratio of inertial to viscous forces, is the same between the system and model. To study the necessity of dynamic similarity for cell mechanotransduction studies, we investigated the response of osteocyte-like MLO-Y4 cells to different Re flows at the same level of fluid shear stress. Osteocytes were chosen for this study as flows applied in vitro and in vivo have Re that are orders of magnitude different. We hypothesize that osteocytes' response to fluid flow is Re dependent. We observed that cells exposed to lower and higher Re flows developed rounded and triangular morphologies, respectively. Lower Re flows also reduced apoptosis rates compared to higher Re flows. Furthermore, MLO-Y4 cells exposed to higher Re flows had stronger calcium responses compared to lower Re flows. However, by also controlling for flow rate, the lower Re flows induced a stronger calcium response; while degradation of components of the osteocyte glycocalyx reversed this effect. This work suggests that osteocytes are highly sensitive to differences in Re, independent of just shear stresses, supporting the need for improved in vitro flow platforms that better recapitulate the physiological environment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:663-671, 2018.

ARIEL (Atmospheric Remote-sensing Infrared Exoplanet Large-survey) is one of the three present candidates for the next ESA medium-class science mission (M4) to be launched in 2026. During its 3.5 years of scientific operations from L2 orbit, this mission will observe spectroscopically in the infrared (IR) a large population of known transiting planets in the neighbourhood of the Solar System. The aim is to enable a deep understanding of the physics and chemistry of these exoplanets. ARIEL is based on a 1-m class telescope ahead of a suite of instruments: two spectrometer channels covering the band 1.95 to 7.80 µm and four photometric channels (two wide and two narrow band) in the range 0.5 to 1.9 μm. The ARIEL optical design is conceived as a fore-module common afocal telescope that will feed the spectrometer and photometric channels. The telescope optical design is based on an eccentric pupil two-mirror classic Cassegrain configuration coupled to a tertiary paraboloidal mirror. An all-aluminum structure has been considered for the telescope layout, and a detailed tolerance analysis has been conducted to assess the telescope feasibility. This analysis has been done including the different parts of the realization and life of the instrument, from integration on-ground to in-flight stability during the scientific acquisitions. The primary mirror (M1) temperature will be monitored and finely tuned via an active thermal control system based on thermistors and heaters. The heaters will be switched on and off to maintain the M1 temperature within ±1K thanks to a proportional-integral-derivative (PID) controller.

ARIEL (Atmospheric Remote-sensing Infrared Exoplanet Large-survey) is one of the three present candidates for the next ESA medium-class science mission (M4) to be launched in 2026. During its 3.5 years of scientific operations from L2 orbit, this mission will observe spectroscopically in the infrared (IR) a large population of known transiting planets in the neighbourhood of the Solar System. The aim is to enable a deep understanding of the physics and chemistry of these exoplanets. ARIEL is based on a 1-m class telescope ahead of a suite of instruments: two spectrometer channels covering the band 1.95 to 7.80 µm and four photometric channels (two wide and two narrow band) in the range 0.5 to 1.9 μm. The ARIEL optical design is conceived as a fore-module common afocal telescope that will feed the spectrometer and photometric channels. The telescope optical design is based on an eccentric pupil two-mirror classic Cassegrain configuration coupled to a tertiary paraboloidal mirror. An all-aluminum structure has been considered for the telescope layout, and a detailed tolerance analysis has been conducted to assess the telescope feasibility. This analysis has been done including the different parts of the realization and life of the instrument, from integration on-ground to in-flight stability during the scientific acquisitions. The primary mirror (M1) temperature will be monitored and finely tuned via an active thermal control system based on thermistors and heaters. The heaters will be switched on and off to maintain the M1 temperature within ±1K thanks to a proportional–integral–derivative (PID) controller.

ARIEL (Atmospheric Remote-sensing Infrared Exoplanet Large-survey) is one of the three candidates for the next ESA medium-class science mission (M4) expected to be launched in 2026. This mission will be devoted to observing spectroscopically in the infrared (IR) a large population of known transiting planets in the neighborhood of the Solar System, opening a new discovery space in the field of extrasolar planets and enabling the understanding of the physics and chemistry of these far away worlds. ARIEL is based on a 1-m class telescope ahead of two spectrometer channels covering the band 1.95 to 7.8 microns. In addition there are four photometric channels: two wide band, also used as fine guidance sensors, and two narrow band. During its 3.5 years of operations from L2 orbit, ARIEL will continuously observe exoplanets transiting their host star. The ARIEL optical design is conceived as a fore-module common afocal telescope that will feed the spectrometer and photometric channels. The telescope optical design is composed of an off-axis portion of a two-mirror classic Cassegrain coupled to a tertiary off-axis paraboloidal mirror. The telescope and optical bench operating temperatures, as well as those of some subsystems, will be monitored and fine tuned/stabilised mainly by means of a thermal control subsystem (TCU-Telescope Control Unit) working in closed-loop feedback and hosted by the main Payload electronics unit, the Instrument Control Unit (ICU). Another important function of the TCU will be to monitor the telescope and optical bench thermistors when the Payload decontamination heaters will be switched on (when operating the instrument in Decontamination Mode) during the Commissioning Phase and cyclically, if required. Then the thermistors data will be sent by the ICU to the On Board Computer by means of a proper formatted telemetry. The latter (OBC) will be in charge of switching on and off the decontamination heaters on the basis of the thermistors readout values.

ARIEL (Atmospheric Remote-sensing Infrared Exoplanet Large-survey) is one of the three present candidates as an M4 ESA mission to be launched in 2026. During its foreseen 3.5 years operation, it will observe spectroscopically in the infrared a large population of known transiting planets in the neighborhood of the Solar System. The aim is to enable a deep understanding of the physics and chemistry of these exoplanets. ARIEL is based on a 1-m class telescope ahead of a suite of instruments: two spectrometer channels covering the band 1.95 to 7.8 μm and four photometric channels (two wide and two narrow band) in the range 0.5 to 1.9 μm. The ARIEL optical design is conceived as a fore-module common afocal telescope that will feed the spectrometer and photometric channels. The telescope optical design is based on an eccentric pupil two-mirror classic Cassegrain configuration coupled to a tertiary paraboloidal mirror. The temperature of the primary mirror (M1) will be monitored and finely tuned by means of an active thermal control system based on thermistors and heaters. They will be switched on and off to maintain the M1 temperature within ±1 K thanks to a proportional-integral-derivative (PID) controller implemented within the Telescope Control Unit (TCU), a Payload electronics subsystem mainly in charge of the active thermal control of the two detectors owning to the spectrometer. TCU will collect the housekeeping data of the controlled subsystems and will forward them to the spacecraft (S/C) by means of the Instrument Control Unit (ICU), the main Payload's electronic Unit linked to the S/C On Board Computer (OBC).

Mechanical stimulation of bone regulates bone remodeling via Wolff's Law, which can be applied to bone disorders (e.g., osteoporosis) to improve bone strength. Tissue level loading of bone transduces to cellular forces in a complex manner. Bone-forming osteoblasts follow bone-resorbing osteoclasts in a bone remodeling unit and are exposed to fluid shear stresses. Mechanosensing osteocytes reside within a lacunar–canalicular space and are exposed to fluid flow, hydrostatic pressure, and strain. Bone marrow stromal cells (BMSCs) reside within the marrow and undergo intramedullary pressures, along with intermedullary and interstitial fluid flow. Understanding bone cell responses to mechanical stimulation helps identify signaling pathways and cellular interactions for bone homeostasis, thus leading to new therapies for bone disorders. Therefore, this chapter explains how to perform in vitro mechanical stimulation tests on bone cells, as well as how to analyze, present, and interpret results.

In this paper, we detail the manufacturing process for the lenses that will constitute the new two-degree field-of-view Prime Focus Corrector (PFC) for the 4.2m William Herschel Telescope (WHT) optimised for the upcoming WEAVE Multi-Object Spectroscopy (MOS) facility. The corrector, including an Atmospheric Dispersion Corrector (ADC), is made of six large lenses, the largest being 1.1-meter diameter. We describe how the prescriptions of the optical design were translated into manufacturing specifications for the blanks and lenses. We explain how the as-built glass blank parameters were fed back into the optical design and how the specifications for the lenses were subsequently modified. We review the critical issues for the challenging manufacturing process and discuss the trade-offs that were necessary to deliver the lenses while maintaining the optimal optical performance. A short description of the lens optical testing is also presented. Finally, the subsequent manufacturing steps, including assembly, integration, and alignment are outlined.

The WAS1(WEAVE Archive System) is a software architecture for archiving and delivering the data releases for the WEAVE7 instrument at WHT (William Herschel Telescope). The WEAVE spectrograph will be mounted at the 4.2-m WHT telescope and will provide millions of spectra in a 5-year program, starting early 2018. The access and retrieval of information will be through its dedicated archive, the WEAVE Archive System (WAS). This will be developed and maintained at the TNG2 premises on the same island as the WHT. Its structure foresees the main axes of scalability, virtualization, and high availability. We present here the first performances on a simulated data set of 20M spectra, using different architectures and hardware choices.

We present an integrated end-end simulation of the spectral images that will be obtained by the weave spectrograph, which aims to include full modelling of all effects from the top of the atmosphere to the detector. These data are based in input spectra from a combination of library spectra and synthetic models, and will be used to provide inputs for an endend test of the full weave data pipeline and archive systems, prior to 1st light of the instrument.

ARIEL (Atmospheric Remote-sensing Infrared Exoplanet Large-survey) is one of the three candidates for the next ESA medium-class science mission (M4) expected to be launched in 2026. This mission will be devoted to observe spectroscopically in the infrared (IR) a large population of known transiting planets in our Galaxy. ARIEL is based on a 1-m class telescope ahead of two spectrometer channels covering the band 1.95 to 7.8 microns. In addition there are four photometric channels: two wide band, also used as fine guidance sensors, and two narrow band. During its 3.5 years operations from L2 orbit, ARIEL will continuously observe exoplanets transiting their host star. The ARIEL design is conceived as a fore-module common afocal telescope that will feed the spectrometer and photometric channels. The telescope optical design is an off-axis portion of a two-mirror classic telescope coupled to a tertiary off-axis paraboloidal mirror providing a collimating output beam. The telescope and optical bench operating temperatures, as well as those of some subsystems, will be monitored and fine tuned/stabilised mainly by means of a thermal control subsystem (TCU - Telescope Control Unit) working in closed-loop feedback and hosted by the main Payload electronics unit, i.e. the Instrument Control Unit (ICU). In this paper the telescope requirements will be given together with the foreseen design. The technical solution chosen to passively cool the telescope unit will be detailed discussed.

WEAVE is a new wide-field spectroscopy facility proposed for the prime focus of the 4.2m William Herschel Telescope. The facility comprises a new 2-degree field of view prime focus corrector with a 1000-multiplex fibre positioner, a small number of individually deployable integral field units, and a large single integral field unit. The IFUs (Integral Field Units) and the MOS (Multi Object Spectrograph) fibres can be used to feed a dual-beam spectrograph that will provide full coverage of the majority of the visible spectrum in a single exposure at a spectral resolution of ~5000 or modest wavelength coverage in both arms at a resolution ~20000. The instrument is expected to be on-sky by the first quarter of 2018 to provide spectroscopic sampling of the fainter end of the Gaia astrometric catalogue, chemical labeling of stars to V~17, and dedicated follow up of substantial numbers of sources from the medium deep LOFAR surveys. After a brief description of the Fibre System, we describe the fibre test bench, its calibration, and some test results. We have to verify 1920 fibres from the MOS bundles and 740 fibres from the mini-IFU bundles with the test bench. In particular, we present the Focal Ratio Degradation of a cable.

WEAVE is the next-generation wide-field optical spectroscopy facility for the William Herschel Telescope (WHT) on La Palma in the Canary Islands, Spain. It is a multi-object "pick-and-place" fibre-fed spectrograph with a 1000 fibre multiplex behind a new dedicated 2° prime focus corrector. The WEAVE positioner concept uses two robots working in tandem in order to reconfigure a fully populated field within the expected 1 hour dwell-time for the instrument (a good match between the required exposure times and the limit of validity for a given configuration due to the effects of differential refraction). In this paper we describe some of the final design decisions arising from the prototyping phase of the instrument design and provide an update on the current manufacturing status of the fibre positioner system.

ARIEL (the Atmospheric Remote-sensing Infrared Exoplanet Large-survey) is one of the three candidates for the next ESA medium-class science mission (M4) expected to be launched in 2026. This mission will be devoted to observing spectroscopically in the infrared a large population of warm and hot transiting exoplanets (temperatures from ~500 K to ~3000 K) in our nearby Galactic neighborhood, opening a new discovery space in the field of extrasolar planets and enabling the understanding of the physics and chemistry of these far away worlds. The three candidate missions for M4 are now in a Phase A study which will run until mid-2017 at which point one mission will be selected for implementation. ARIEL is based on a 1-m class telescope feeding both a moderate resolution spectrometer covering the wavelengths from 1.95 to 7.8 microns, and a four channel photometer (which also acts as a Fine Guidance Sensor) with bands between 0.55 and 1.65 microns. During its 3.5 years of operation from an L2 orbit, ARIEL will continuously observe exoplanets transiting their host star.