Building invitro 3D human multicellular models of high-grade serous ovarian cancer.

Three-dimensional (3D), multicellular invitro models provide a useful platform for studying human cancer biology, particularly through deconvolution of the tumor microenvironment, or where animal models do not recapitulate the human condition. Here, we detail a protocol for building human multicellular models made of patient-derived primary cells and malignant cell lines, which recapitulate features of the tumor microenvironment. This protocol is optimized for building 3D models of high-grade serous ovarian cancer omental metastasis but can be adapted for modeling other cancers. For complete details on the use and execution of this profile, please refer to Delaine-Smith et al. (2021) and Malacrida et al. (2021)

Modelling TGFbR and Hh pathway regulation of prognostic matrisome molecules in ovarian cancer

In a multi-level ‘deconstruction’ of omental metastases, we previously identified a prognostic matrisome gene expression signature in high-grade serous ovarian cancer (HGSOC) and twelve other malignancies. Here, our aim was to understand how six of these extracellular matrix, ECM, molecules, COL11A1, COMP, FN1, VCAN, CTSB and COL1A1, are up-regulated in cancer. Using biopsies, we identified significant associations between TGFβR activity, Hedgehog signalling and these ECM molecules and then studied the associations in mono-, co- and tri-culture. Activated omental fibroblasts produced more matrix than malignant cells, directed by TGFβR and Hedgehog signalling crosstalk. We ‘reconstructed’ omental metastases in tri-culture of HGSOC cells, omental fibroblasts and adipocytes. This combination was sufficient to generate all six ECM proteins and the matrisome expression signature. TGFβR and Hedgehog inhibitor combinations attenuated fibroblast activation, gel remodelling and ECM remodelling in these models. The tri-culture model reproduces key features of omental metastases and allows study of diseased-associated ECM

nIFTy Galaxy Cluster simulations VI: The dynamical imprint of substructure on gaseous cluster outskirts

Galaxy cluster outskirts mark the transition region from the mildly non-linear cosmic web to the highly non-linear, virialised, cluster interior. It is in this transition region that the intra-cluster medium (ICM) begins to influence the properties of accreting galaxies and groups, as ram pressure impacts a galaxy's cold gas content and subsequent star formation rate. Conversely, the thermodynamical properties of the ICM in this transition region should also feel the influence of accreting substructure (i.e. galaxies and groups), whose passage can drive shocks. In this paper, we use a suite of cosmological hydrodynamical zoom simulations of a single galaxy cluster, drawn from the nIFTy comparison project, to study how the dynamics of substructure accreted from the cosmic web influences the thermodynamical properties of the ICM in the cluster's outskirts. We demonstrate how features evident in radial profiles of the ICM (e.g. gas density and temperature) can be linked to strong shocks, transient and short-lived in nature, driven by the passage of substructure. The range of astrophysical codes and galaxy formation models in our comparison are broadly consistent in their predictions (e.g. agreeing when and where shocks occur, but differing in how strong shocks will be); this is as we would expect of a process driven by large-scale gravitational dynamics and strong, inefficiently radiating, shocks. This suggests that mapping such shock structures in the ICM in a cluster's outskirts (via e.g. radio synchrotron emission) could provide a complementary measure of its recent merger and accretion history

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

nIFTY galaxy cluster simulations - III. The similarity and diversity of galaxies and subhaloes

We examine subhaloes and galaxies residing in a simulated $\Lambda$ cold dark matter galaxy cluster ($M^{crit} _{200}$ = 1.1 × 10$^{15}$ $h^{−1}$ M$_\odot$) produced by hydrodynamical codes ranging from classic smooth particle hydrodynamics (SPH), newer SPH codes, adaptive and moving mesh codes. These codes use subgrid models to capture galaxy formation physics. We compare how well these codes reproduce the same subhaloes/galaxies in gravity-only, non-radiative hydrodynamics and $\textit{full feedback physics}$ runs by looking at the overall subhalo/galaxy distribution and on an individual object basis. We find that the subhalo population is reproduced to within $\lesssim$10 per cent for both dark matter only and non-radiative runs, with individual objects showing code-to-code scatter of $\lesssim$0.1 dex, although the gas in non-radiative simulations shows significant scatter. Including feedback physics significantly increases the diversity. Subhalo mass and $V_{max}$ distributions vary by ≈20 per cent. The galaxy populations also show striking code-to-code variations. Although the Tully–Fisher relation is similar in almost all codes, the number of galaxies with 10$^9$ $h^{−1}$ M$_\odot$ $\lesssim$ $M_∗$ $\lesssim$ 10$^{12}$ $h^{−1}$ M$_\odot$ can differ by a factor of 4. Individual galaxies show code-to-code scatter of ~0.5 dex in stellar mass. Moreover, systematic differences exist, with some codes producing galaxies 70 per cent smaller than others. The diversity partially arises from the inclusion/absence of active galactic nucleus feedback. Our results combined with our companion papers demonstrate that subgrid physics is not just subject to fine-tuning, but the complexity of building galaxies $\textit{in all environments}$ remains a challenge. We argue that even basic galaxy properties, such as stellar mass to halo mass, should be treated with errors bars of ~0.2–0.4 dex

Roadmap of optical communications

© 2016 IOP Publishing Ltd. Lightwave communications is a necessity for the information age. Optical links provide enormous bandwidth, and the optical fiber is the only medium that can meet the modern society's needs for transporting massive amounts of data over long distances. Applications range from global high-capacity networks, which constitute the backbone of the internet, to the massively parallel interconnects that provide data connectivity inside datacenters and supercomputers. Optical communications is a diverse and rapidly changing field, where experts in photonics, communications, electronics, and signal processing work side by side to meet the ever-increasing demands for higher capacity, lower cost, and lower energy consumption, while adapting the system design to novel services and technologies. Due to the interdisciplinary nature of this rich research field, Journal of Optics has invited 16 researchers, each a world-leading expert in their respective subfields, to contribute a section to this invited review article, summarizing their views on state-of-the-art and future developments in optical communications

nIFTY galaxy cluster simulations - III. The similarity and diversity of galaxies and subhaloes

We examine subhaloes and galaxies residing in a simulated $\Lambda$ cold dark matter galaxy cluster ($M^{crit} _{200}$ = 1.1 × 10$^{15}$ $h^{−1}$ M$_\odot$) produced by hydrodynamical codes ranging from classic smooth particle hydrodynamics (SPH), newer SPH codes, adaptive and moving mesh codes. These codes use subgrid models to capture galaxy formation physics. We compare how well these codes reproduce the same subhaloes/galaxies in gravity-only, non-radiative hydrodynamics and $\textit{full feedback physics}$ runs by looking at the overall subhalo/galaxy distribution and on an individual object basis. We find that the subhalo population is reproduced to within $\lesssim$10 per cent for both dark matter only and non-radiative runs, with individual objects showing code-to-code scatter of $\lesssim$0.1 dex, although the gas in non-radiative simulations shows significant scatter. Including feedback physics significantly increases the diversity. Subhalo mass and $V_{max}$ distributions vary by ≈20 per cent. The galaxy populations also show striking code-to-code variations. Although the Tully–Fisher relation is similar in almost all codes, the number of galaxies with 10$^9$ $h^{−1}$ M$_\odot$ $\lesssim$ $M_∗$ $\lesssim$ 10$^{12}$ $h^{−1}$ M$_\odot$ can differ by a factor of 4. Individual galaxies show code-to-code scatter of ~0.5 dex in stellar mass. Moreover, systematic differences exist, with some codes producing galaxies 70 per cent smaller than others. The diversity partially arises from the inclusion/absence of active galactic nucleus feedback. Our results combined with our companion papers demonstrate that subgrid physics is not just subject to fine-tuning, but the complexity of building galaxies $\textit{in all environments}$ remains a challenge. We argue that even basic galaxy properties, such as stellar mass to halo mass, should be treated with errors bars of ~0.2–0.4 dex

nIFTy galaxy cluster simulations – V. Investigation of the cluster infall region

We examine the properties of the galaxies and dark matter haloes residing in the cluster infall region surrounding the simulated $\Lambda$ cold dark matter galaxy cluster studied by Elahi et al. at $z$ = 0. The 1.1 × 10$^{15}$ $h^{−1}$ M$_\odot$ galaxy cluster has been simulated with eight different hydrodynamical codes containing a variety of hydrodynamic solvers and sub-grid schemes. All models completed a dark-matter-only, non-radiative and full-physics run from the same initial conditions. The simulations contain dark matter and gas with mass resolution $m_\text{DM}$ = 9.01 × 10$^8$ $h^{−1}$ M$_\odot$ and $m_\text{gas}$ = 1.9 × 10$^8$ $h^{−1}$ M$_\odot$, respectively. We find that the synthetic cluster is surrounded by clear filamentary structures that contain ~60 per cent of haloes in the infall region with mass ~10$^{12.5}$–10$^{14}$ $h^{−1}$ M$_\odot$, including 2–3 group-sized haloes (>10$^{13}$ $h^{−1}$ M$_\odot$). However, we find that only ~10 per cent of objects in the infall region are sub-haloes residing in haloes, which may suggest that there is not much ongoing pre-processing occurring in the infall region at $z$ = 0. By examining the baryonic content contained within the haloes, we also show that the code-to-code scatter in stellar fraction across all halo masses is typically ~2 orders of magnitude between the two most extreme cases, and this is predominantly due to the differences in sub-grid schemes and calibration procedures that each model uses. Models that do not include active galactic nucleus feedback typically produce too high stellar fractions compared to observations by at least ~1 order of magnitude.The authors would like the acknowledge the Centre for High Performance Computing in Rosebank, Cape Town, for financial support and for hosting the ‘Comparison Cape Town’ workshop in 2016, July. The authors would further like to acknowledge the support of the International Centre for Radio Astronomy Research (ICRAR) node at the University of Western Australia (UWA) in hosting the precursor workshop ‘Perth Simulated Cluster Comparison’ in 2015, March; the financial support of the UWA Research Collaboration Award 2014 and 2015 schemes; the financial support of the ARC Centre of Excellence for All Sky Astrophysics (CAASTRO) CE110001020 and ARC Discovery Projects DP130100117 and DP140100198. We would also like to thank the Instituto de Fisica Teorica (IFT-UAM/CSIC in Madrid) for its support, via the Centro de Excelencia Severo Ochoa Program under Grant No. SEV- 2012-0249, during the three-week workshop ‘nIFTy Cosmology’ in 2014, where the foundation for the whole comparison project was established. JA acknowledges support from a post-graduate award from STFC. PJE is supported by the SSimPL programme and the Sydney Institute for Astronomy (SIfA) and Australian Research Council (ARC) grants DP130100117 and DP140100198. AK is supported by the Ministerio de Econom´ıa y Competitividad (MINECO) in Spain through grant AYA2012-31101 as well as the ConsoliderIngenio 2010 Programme of the Spanish Ministerio de Ciencia e Innovacion (MICINN) under grant MultiDark CSD2009-00064. ´ He also acknowledges support from the ARC grant DP140100198. He further thanks Noonday Underground for surface noise. STK acknowledges support from STFC through grant ST/L000768/1. CP acknowledges the support of the ARC through Future Fellowship FT130100041 and Discovery Project DP140100198. WC and CP acknowledge the support of ARC DP130100117. GY and FS acknowledge support from MINECO (Spain) through the grant AYA 2012-31101. GY thanks also the Red Espanola de Supercomputa- ˜ cion for granting the computing time in the Marenostrum Supercomputer at BSC, where all the MUSIC simulations have been performed. AMB is supported by the DFG Research Unit 1254 ‘Magnetisation of interstellar and intergalactic media’ and by the DFG Cluster of Excellence ‘Universe’. GM acknowledge support from the PRIN-MIUR 2012 Grant ‘The Evolution of Cosmic Baryons’ funded by the Italian Minister of University and Research, by the PRIN-INAF 2012 Grant ‘Multi-scale Simulations of Cosmic Structures’, by the INFN INDARK Grant and by the ‘Consorzio per la Fisica di Trieste’. IGM acknowledges support from an STFC Advanced Fellowship. EP acknowledges support by the ERC grant ‘The Emergence of Structure During the Epoch of Reionization’

nIFTy galaxy cluster simulations II: radiative models

We have simulated the formation of a massive galaxy cluster (M$_{200}^{\rm crit}$ = 1.1$\times$10$^{15}h^{-1}M_{\odot}$) in a $\Lambda$CDM universe using 10 different codes (RAMSES, 2 incarnations of AREPO and 7 of GADGET), modeling hydrodynamics with full radiative subgrid physics. These codes include Smoothed-Particle Hydrodynamics (SPH), spanning traditional and advanced SPH schemes, adaptive mesh and moving mesh codes. Our goal is to study the consistency between simulated clusters modeled with different radiative physical implementations - such as cooling, star formation and AGN feedback. We compare images of the cluster at $z=0$, global properties such as mass, and radial profiles of various dynamical and thermodynamical quantities. We find that, with respect to non-radiative simulations, dark matter is more centrally concentrated, the extent not simply depending on the presence/absence of AGN feedback. The scatter in global quantities is substantially higher than for non-radiative runs. Intriguingly, adding radiative physics seems to have washed away the marked code-based differences present in the entropy profile seen for non-radiative simulations in Sembolini et al. (2015): radiative physics + classic SPH can produce entropy cores. Furthermore, the inclusion/absence of AGN feedback is not the dividing line -as in the case of describing the stellar content- for whether a code produces an unrealistic temperature inversion and a falling central entropy profile. However, AGN feedback does strongly affect the overall stellar distribution, limiting the effect of overcooling and reducing sensibly the stellar fraction