A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics with Metabolism, Signaling Networks, and Biomechanics as Plug-In Component Models of a Cancer Digital Twin.

The massive amount of human biological, imaging, and clinical data produced by multiple and diverse sources necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell-signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels, as well as their orchestration and links, are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof-of-concept study cases. Personalized simulations of the actual anatomy of a patient have been conducted. The hypermodel has also been applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin-based clinical decision support system and as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

Socio-economic impact of ecological agriculture at the territorial level

This deliverable investigates the socio-economic effects of ecological approaches to farming through implementing two participatory approaches, namely Delphi exercise and Q-method, at the level of a case study area (CSA). The focus is on how people and other productive assets are employed and remunerated by ecological approaches to agriculture, particularly those aspects that can influence employment, and drive the prosperity and vitality of local communities and some rural businesses. It is based on the collaborative research on Task 4.2 ‘Socio-economic impact of ecological agriculture at the territorial level’ of the LIFT project between UNIKENT (United Kingdom-UK) (Task Leader), BOKU (Austria), INRAE (France), VetAgro Sup (France), DEMETER (Greece), MTA KRTK (Hungary), UNIBO (Italy), IRWiR PAN (Poland), IAE-AR (Romania), SLU (Sweden), SRUC (UK). Beginning with the Delphi exercise, this deliverable presents qualitative information extracted from stakeholders in the following four steps. First, the researchers build a presentation of differences between ecological and conventional farming approaches in each CSA. Second, stakeholders elaborate on how they understand ecological farming approaches to exist in each CSA. Third, stakeholders develop a scenario of adoption of ecological approaches to farming depending on two factors: pattern (ecological farms forming clusters or randomly spread within the territory) and rate of adoption 10 years in the future. After establishing this scenario across two rounds, the stakeholders explore the socio-economic effects of their adoption scenario. The Q-methodology then presents a Q-set of statements that the Delphi has developed and, through factor analysis,studies the key stakeholder perspectives of the socio-economic effects of the perceived adoption of ecological practices in 10 years in the future. Four key results can be derived from the Delphi exercise and the Q-methodology. First, a higher adoption of ecological farming approaches, especially so at a 50% adoption rate, is mostly thought by stakeholders in the Delphi Exercise to lead to an increase in skill level and quality of life in on-farm employment. This is as a result of an increased diversity of farming enterprises on farms using ecological farming approaches, the interest generated from this, the knowledge of natural processes and biology required, engagement with nature and change in machinery that is coming into the industry. Strongly related to this need for skills is a predicted increase in the number of advisers and civil servants to deal with more complicated farms and incentives as well as monitoring of ecological effects on farm. An increase in required skill level is repeated across all Q-studies. Second, especially where farms are clustered together, Delphi Exercise respondents predict an increase in the trade of inputs such as manure and compost replacing synthetic fertiliser, as well as more sharing of capital and labour. Q-methodology highlights that these clusters may support a stronger social movement, more consumers buying local food and increase collaboration between farmers. Supply chains are expected to become shorter as farmers sell more directly and there are fewer intermediaries upstream of the farming sector. As farmers collaborate more with each other on environmental objectives, trading inputs and sharing best practices, farmer relationships should improve in rural communities. Third, Delphi exercise finds that contracting, machinery purchasers, and machinery traders and dealers could increase, decrease or display no change – the anticipated effects are mixed. Stakeholders are in no doubt that machinery use will change and therefore new skills will need to be learnt, but the wider effect on machinery purchase is uncertain. However, stakeholders conclude that a greater specialisation in machinery will occur leading to changes in farm management as well as the suppliers of this machinery. Q-methodology highlights that ecological practices will not mean the end of machinery and a lot more labour – often machinery will be useful in weeding and reducing physical labour as technology has significantly improved and skills are improving too in order to use these technologies. Fourth, Delphi respondents argued that although rural populations might be little affected by ecological farming, a shift in people moving from urban to rural settlements, and thereby a higher rural population density, seeking a more attractive rural environment, might contribute to higher local consumer demand. The Q-methodology highlights that where there is high adoption, rural areas are expected to become more attractive, as landscapes will have a much greater variety of crops instead of fields of monocrops. This variety of crops may include agroforestry (farmers interested in ecological approaches to farming may also be interested in agroforestry as a way of boosting their yields and protecting crops and livestock from the elements) as well as intercropping

A multidisciplinary hyper-modeling scheme in personalized in silico oncology : coupling cell kinetics with metabolism, signaling networks, and biomechanics as plug-in component models of a cancer digital twin

The massive amount of human biological, imaging, and clinical data produced by multiple and diverse sources necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell-signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels, as well as their orchestration and links, are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof-of-concept study cases. Personalized simulations of the actual anatomy of a patient have been conducted. The hypermodel has also been applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin-based clinical decision support system and as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary

GRAVITY: observing the universe in motion

GRAVITY is the second generation VeryLarge Telescope Interferometer instrument for precision narrow-angle as -trometry and interferometric imaging.With its fibre-fed integrated optics,wavefront sensors, fringe tracker, beamstabilisation and a novel metrologyconcept, GRAVITY will push the sensitivity and accuracy of astrometry andinterferometric imaging far beyond whatis offered today. Providing precisionastrometry of order 10 microarcseconds,and imaging with 4-milliarcsecondresolution, GRAVITY will revolutionisedynamical measurements of celestialobjects: it will probe physics close tothe event horizon of the Galactic Centreblack hole; unambiguously detect andmeasure the masses of black holesin massive star clusters throughout theMilky Way; uncover the details of massaccretion and jets in young stellarobjects and active galactic nuclei; andprobe the motion of binary stars, exoplanets and young stellar discs. Theinstrument capabilities of GRAVITY areoutlined and the science opportunitiesthat will open up are summarised

The Athena X-ray Integral Field Unit (X-IFU)

The X-ray Integral Field Unit (X-IFU) is the high resolution X-ray spectrometer of the ESA Athena X-ray observatory. Over a field of view of 5' equivalent diameter, it will deliver X-ray spectra from 0.2 to 12 keV with a spectral resolution of 2.5 eV up to 7 keV on similar to 5 '' pixels. The X-IFU is based on a large format array of super-conducting molybdenum-gold Transition Edge Sensors cooled at similar to 90 mK, each coupled with an absorber made of gold and bismuth with a pitch of 249 mu m. A cryogenic anti-coincidence detector located underneath the prime TES array enables the non X-ray background to be reduced. A bath temperature of similar to 50 mK is obtained by a series of mechanical coolers combining 15K Pulse Tubes, 4K and 2K Joule-Thomson coolers which pre-cool a sub Kelvin cooler made of a He-3 sorption cooler coupled with an Adiabatic Demagnetization Refrigerator. Frequency domain multiplexing enables to read out 40 pixels in one single channel. A photon interacting with an absorber leads to a current pulse, amplified by the readout electronics and whose shape is reconstructed on board to recover its energy with high accuracy. The defocusing capability offered by the Athena movable mirror assembly enables the X-IFU to observe the brightest X-ray sources of the sky (up to Crab-like intensities) by spreading the telescope point spread function over hundreds of pixels. Thus the X-IFU delivers low pile-up, high throughput (> 50%), and typically 10 eV spectral resolution at 1 Crab intensities, i.e. a factor of 10 or more better than Silicon based X-ray detectors. In this paper, the current X-IFU baseline is presented, together with an assessment of its anticipated performance in terms of spectral resolution, background, and count rate capability. The X-IFU baseline configuration will be subject to a preliminary requirement review that is scheduled at the end of 2018. The X-IFU will be provided by an international consortium led by France, the Netherlands and Italy, with further ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Ireland, Poland, Spain, Switzerland and contributions from Japan and the United States.Peer reviewe

The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI

The GRAVITY instrument has been revolutionary for near-infrared interferometry by pushing sensitivity and precision to previously unknown limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) in GRAVITY+, these limits will be pushed even further, with vastly improved sky coverage, as well as faint-science and high-contrast capabilities. This upgrade includes the implementation of wide-field off-axis fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser guide stars in an upgraded facility. GRAVITY+ will open up the sky to the measurement of black hole masses across cosmic time in hundreds of active galactic nuclei, use the faint stars in the Galactic centre to probe General Relativity, and enable the characterisation of dozens of young exoplanets to study their formation, bearing the promise of another scientific revolution to come at the VLTI.Comment: Published in the ESO Messenge

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin