Therapeutic potential of fetal liver cells transplantation in hemophilia A mice

: Hemophilia A (HA) cell therapy approaches in pediatric individuals require suitable factor (F)VIII-producing cells for stable engraftment. Liver sinusoidal endothelial cells (LSEC) and hematopoietic stem cells (HSC) have been demonstrated to be suitable for the treatment of adult HA-mice. However, after transplantation in busulfan (BU)-conditioned newborn mice, adult LSEC/HSC cannot efficiently engraft, while murine fetal liver (FL) hemato/vascular cells from embryonic day 11-13 of gestation (E11-E13), strongly engraft the hematopoietic and endothelial compartments while also secreting FVIII. Our aim was to investigate the engraftment of FL cells in newborn HA mice for obtaining a suitable "proof of concept" for the development of a new HA treatment in neonates. Hence, we transplanted FLE11 or E13 cells and adult bone marrow (BM) cells into newborn HA mice with or without BU preconditioning. The engraftment levels and FVIII activity was assessed starting from 6 weeks after transplantation. FLE11-E13+BU-transplanted newborns reached up to 95% engraftment with stable FVIII activity levels observed for 16 months. FLE13 cells showed engraftment ability even in absence of BU preconditioning, while FLE11 cells did not. BM+BU transplanted newborn HA mice showed high levels of engraftment; nevertheless, in contrast to FL cells, BM cells cannot engraft HA newborns in non-conditioning regimen. Finally, none of the transplanted mice developed anti-FVIII antibodies. Overall, this study sheds some light on the therapeutic potential of healthy FL cells in the cure of HA neonatal/pediatric patients

Skunk River Review 2008-2009, vol 21

https://openspace.dmacc.edu/skunkriver/1014/thumbnail.jp

Dataset for the reporting of carcinoma of renal tubular origin:recommendations from the International Collaboration on Cancer Reporting (ICCR)

AIMS The International Collaboration on Cancer Reporting (ICCR) has provided detailed datasets based upon the published reporting protocols of the Royal College of Pathologists, The Royal College of Pathologists of Australasia and the College of American Pathologists. METHODS AND RESULTS The dataset for carcinomas of renal tubular origin treated by nephrectomy was developed to provide a minimum structured reporting template suitable for international use and incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology and the fourth edition of the World Health Organization Bluebook on tumours of the urinary and male genital systems published in 2016. Reporting elements were divided into those, which are Required and Recommended components of the report. Required elements are; specimen laterality, operative procedure, attached structures, tumour focality, tumour dimension, tumour type, WHO/ISUP grade, sarcomatoid/rhabdoid morphology, tumour necrosis, extent of invasion, lymph node status, surgical margin status, AJCC TNM staging and co-existing pathology. Recommended reporting elements are; pre-operative treatment, details of tissue removed for experimental purposes prior to submission, site of tumour(s) block identification key, extent of sarcomatoid and/or rhabdoid component, extent of necrosis, presence of tumour in renal vein wall, lymphovascular invasion and lymph node status (size of largest focus and extranodal extension). CONCLUSIONS It is anticipated that the implementation of this dataset in routine clinical practise will inform patient treatment as well as provide standardized information relating to outcome prediction. The harmonisation of data reporting should also facilitate international research collaborations. This article is protected by copyright. All rights reserved

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Calibrating an updated SPH scheme within GCD+

We adapt a modern scheme of smoothed particle hydrodynamics (SPH) to our tree N-body/SPH galactic chemodynamics code GCD+. The applied scheme includes imple- mentations of the artificial viscosity switch and artificial thermal conductivity pro- posed by Morris & Monaghan (1997), Rosswog & Price (2007) and Price (2008), to model discontinuities and Kelvin-Helmholtz instabilities more accurately. We first present hydrodynamics test simulations and contrast the results to runs undertaken without artificial viscosity switch or thermal conduction. In addition, we also explore the different levels of smoothing by adopting larger or smaller smoothing lengths, i.e. a larger or smaller number of neighbour particles, Nnb. We demonstrate that the new version of GCD+ is capable of modelling Kelvin-Helmholtz instabilities to a simi- lar level as the mesh code, Athena. From the Gresho vortex, point-like explosion and self-similar collapse tests, we conclude that setting the smoothing length to keep the number of neighbour particles as high as Nnb~58 is preferable to adopting smaller smoothing lengths. We present our optimised parameter sets from the hydrodynamics tests.Comment: 14 pages, 2 tables, 15 figures, MNRAS in pres

Chemical evolution of galaxies. I. A composition-dependent SPH model for chemical evolution and cooling

We describe an SPH model for chemical enrichment and radiative cooling in cosmological simulations of structure formation. This model includes: i) the delayed gas restitution from stars by means of a probabilistic approach designed to reduce the statistical noise and, hence, to allow for the study of the inner chemical structure of objects with moderately high numbers of particles; ii) the full dependence of metal production on the detailed chemical composition of stellar particles by using, for the first time in SPH codes, the Qij matrix formalism that relates each nucleosynthetic product to its sources; and iii) the full dependence of radiative cooling on the detailed chemical composition of gas particles, achieved through a fast algorithm using a new metallicity parameter zeta(T) that gives the weight of each element on the total cooling function. The resolution effects and the results obtained from this SPH chemical model have been tested by comparing its predictions in different problems with known theoretical solutions. We also present some preliminary results on the chemical properties of elliptical galaxies found in self-consistent cosmological simulations. Such simulations show that the above zeta-cooling method is important to prevent an overestimation of the metallicity-dependent cooling rate, whereas the Qij formalism is important to prevent a significant underestimation of the [alpha/Fe] ratio in simulated galaxy-like objects.Comment: 19 pages, 22 figures, 2 tables; accepted for publication in MNRA

Euclid: The importance of galaxy clustering and weak lensing cross-correlations within the photometric Euclid survey

Context. The data from the Euclid mission will enable the measurement of the angular positions and weak lensing shapes of over a billion galaxies, with their photometric redshifts obtained together with ground-based observations. This large dataset, with well-controlled systematic effects, will allow for cosmological analyses using the angular clustering of galaxies (GCph) and cosmic shear (WL). For Euclid, these two cosmological probes will not be independent because they will probe the same volume of the Universe. The cross-correlation (XC) between these probes can tighten constraints and is therefore important to quantify their impact for Euclid. Aims. In this study, we therefore extend the recently published Euclid forecasts by carefully quantifying the impact of XC not only on the final parameter constraints for different cosmological models, but also on the nuisance parameters. In particular, we aim to decipher the amount of additional information that XC can provide for parameters encoding systematic effects, such as galaxy bias, intrinsic alignments (IAs), and knowledge of the redshift distributions. Methods. We follow the Fisher matrix formalism and make use of previously validated codes. We also investigate a different galaxy bias model, which was obtained from the Flagship simulation, and additional photometric-redshift uncertainties; we also elucidate the impact of including the XC terms on constraining these latter. Results. Starting with a baseline model, we show that the XC terms reduce the uncertainties on galaxy bias by ∼17% and the uncertainties on IA by a factor of about four. The XC terms also help in constraining the γ parameter for minimal modified gravity models. Concerning galaxy bias, we observe that the role of the XC terms on the final parameter constraints is qualitatively the same irrespective of the specific galaxy-bias model used. For IA, we show that the XC terms can help in distinguishing between different models, and that if IA terms are neglected then this can lead to significant biases on the cosmological parameters. Finally, we show that the XC terms can lead to a better determination of the mean of the photometric galaxy distributions. Conclusions. We find that the XC between GCph and WL within the Euclid survey is necessary to extract the full information content from the data in future analyses. These terms help in better constraining the cosmological model, and also lead to a better understanding of the systematic effects that contaminate these probes. Furthermore, we find that XC significantly helps in constraining the mean of the photometric-redshift distributions, but, at the same time, it requires more precise knowledge of this mean with respect to single probes in order not to degrade the final “figure of merit”

Euclid: Constraining ensemble photometric redshift distributions with stacked spectroscopy

Context. The ESA Euclid mission will produce photometric galaxy samples over 15 000 square degrees of the sky that will be rich for clustering and weak lensing statistics. The accuracy of the cosmological constraints derived from these measurements will depend on the knowledge of the underlying redshift distributions based on photometric redshift calibrations. Aims. A new approach is proposed to use the stacked spectra from Euclid slitless spectroscopy to augment broad-band photometric information to constrain the redshift distribution with spectral energy distribution fitting. The high spectral resolution available in the stacked spectra complements the photometry and helps to break the colour-redshift degeneracy and constrain the redshift distribution of galaxy samples. Methods. We modelled the stacked spectra as a linear mixture of spectral templates. The mixture may be inverted to infer the underlying redshift distribution using constrained regression algorithms. We demonstrate the method on simulated Vera C. Rubin Observatory and Euclid mock survey data sets based on the Euclid Flagship mock galaxy catalogue. We assess the accuracy of the reconstruction by considering the inference of the baryon acoustic scale from angular two-point correlation function measurements. Results. We selected mock photometric galaxy samples at redshift za>a1 using the self-organising map algorithm. Considering the idealised case without dust attenuation, we find that the redshift distributions of these samples can be recovered with 0.5% accuracy on the baryon acoustic scale. The estimates are not significantly degraded by the spectroscopic measurement noise due to the large sample size. However, the error degrades to 2% when the dust attenuation model is left free. We find that the colour degeneracies introduced by attenuation limit the accuracy considering the wavelength coverage of Euclid near-infrared spectroscopy

Euclid: Forecast constraints on consistency tests of the ∧cDM model

Context. The standard cosmological model is based on the fundamental assumptions of a spatially homogeneous and isotropic universe on large scales. An observational detection of a violation of these assumptions at any redshift would immediately indicate the presence of new physics. Aims. We quantify the ability of the Euclid mission, together with contemporary surveys, to improve the current sensitivity of null tests of the canonical cosmological constant ∧ and the cold dark matter (∧ CDM) model in the redshift range 0 < 1.8. Methods. We considered both currently available data and simulated Euclid and external data products based on a ∧CDM fiducial model, an evolving dark energy model assuming the Chevallier-Polarski-Linder parameterization or an inhomogeneous Lemaître-Tolman-Bondi model with a cosmological constant ∧, and carried out two separate but complementary analyses: A machine learning reconstruction of the null tests based on genetic algorithms, and a theory-Agnostic parametric approach based on Taylor expansion and binning of the data, in order to avoid assumptions about any particular model. Results. We find that in combination with external probes, Euclid can improve current constraints on null tests of the ∧CDM by approximately a factor of three when using the machine learning approach and by a further factor of two in the case of the parametric approach. However, we also find that in certain cases, the parametric approach may be biased against or missing some features of models far from ∧CDM. Conclusions. Our analysis highlights the importance of synergies between Euclid and other surveys. These synergies are crucial for providing tighter constraints over an extended redshift range for a plethora of different consistency tests of some of the main assumptions of the current cosmological paradigm

The PAU Survey & Euclid: Improving broad-band photometric redshifts with multi-task learning

Current and future imaging surveys require photometric redshifts (photo-z) to be estimated for millions of galaxies. Improving the photo-z quality is a major challenge to advance our understanding of cosmology. In this paper, we explore how the synergies between narrow-band photometric data and large imaging surveys can be exploited to improve broad-band photometric redshifts. We use a multi-task learning (MTL) network to improve broad-band photo-z estimates by simultaneously predicting the broad-band photo-z and the narrow-band photometry from the broad-band photometry. The narrow-band photometry is only required in the training field, which enables better photo-z predictions also for the galaxies without narrow-band photometry in the wide field. This technique is tested with data from the Physics of the Accelerating Universe Survey (PAUS) in the COSMOS field. We find that the method predicts photo-z that are 14% more precise down to magnitude i_AB<23, while reducing the outlier rate by 40% with respect to the baseline network mapping broad-band colours to only photo-zs. Furthermore, MTL significantly reduces the photo-z bias for high-redshift galaxies, improving the redshift distributions for tomographic bins with z>1. Applying this technique to deeper samples is crucial for future surveys like \Euclid or LSST. For simulated data, training on a sample with i_AB <23, the method reduces the photo-z scatter by 15% for all galaxies with 24<i_AB<25. We also study the effects of extending the training sample with photometric galaxies using PAUS high-precision photo-zs, which further reduces the photo-z scatter.Comment: 20 pages, 16 figure