ABSTRACT
We present and study a large suite of high-resolution cosmological zoom-in simulations, using the FIRE-2 treatment of mechanical and radiative feedback from massive stars, together with ...explicit treatment of magnetic fields, anisotropic conduction and viscosity (accounting for saturation and limitation by plasma instabilities at high β), and cosmic rays (CRs) injected in supernovae shocks (including anisotropic diffusion, streaming, adiabatic, hadronic and Coulomb losses). We survey systems from ultrafaint dwarf ($M_{\ast }\sim 10^{4}\, \mathrm{M}_{\odot }$, $M_{\rm halo}\sim 10^{9}\, \mathrm{M}_{\odot }$) through Milky Way/Local Group (MW/LG) masses, systematically vary uncertain CR parameters (e.g. the diffusion coefficient κ and streaming velocity), and study a broad ensemble of galaxy properties masses, star formation (SF) histories, mass profiles, phase structure, morphologies, etc.. We confirm previous conclusions that magnetic fields, conduction, and viscosity on resolved ($\gtrsim 1\,$ pc) scales have only small effects on bulk galaxy properties. CRs have relatively weak effects on all galaxy properties studied in dwarfs ($M_{\ast } \ll 10^{10}\, \mathrm{M}_{\odot }$, $M_{\rm halo} \lesssim 10^{11}\, \mathrm{M}_{\odot }$), or at high redshifts (z ≳ 1–2), for any physically reasonable parameters. However, at higher masses ($M_{\rm halo} \gtrsim 10^{11}\, \mathrm{M}_{\odot }$) and z ≲ 1–2, CRs can suppress SF and stellar masses by factors ∼2–4, given reasonable injection efficiencies and relatively high effective diffusion coefficients $\kappa \gtrsim 3\times 10^{29}\, {\rm cm^{2}\, s^{-1}}$. At lower κ, CRs take too long to escape dense star-forming gas and lose their energy to collisional hadronic losses, producing negligible effects on galaxies and violating empirical constraints from spallation and γ-ray emission. At much higher κ CRs escape too efficiently to have appreciable effects even in the CGM. But around $\kappa \sim 3\times 10^{29}\, {\rm cm^{2}\, s^{-1}}$, CRs escape the galaxy and build up a CR-pressure-dominated halo which maintains approximate virial equilibrium and supports relatively dense, cool (T ≪ 106 K) gas that would otherwise rain on to the galaxy. CR ‘heating’ (from collisional and streaming losses) is never dominant.
Abstract
We study the z = 0 gas kinematics, morphology and angular momentum content of isolated galaxies in a suite of cosmological zoom-in simulations from the FIRE project spanning Mstar = 106–11 ...M⊙. Gas becomes increasingly rotationally supported with increasing galaxy mass. In the lowest mass galaxies (Mstar < 108 M⊙), gas fails to form a morphological disc and is primarily dispersion and pressure supported. At intermediate masses (Mstar = 108–10 M⊙), galaxies display a wide range of gas kinematics and morphologies, from thin, rotating discs to irregular spheroids with negligible net rotation. All the high-mass (Mstar = 1010–11 M⊙) galaxies form rotationally supported gas discs. Many of the haloes whose galaxies fail to form discs harbour high angular momentum gas in their circumgalactic medium. The ratio of the specific angular momentum of gas in the central galaxy to that of the dark matter halo increases significantly with galaxy mass, from 〈jgas〉/〈jDM〉 ∼ 0.1 at $M_{\rm star}=10^{6\text{--}7}\, \rm M_{{\odot }}$ to 〈jgas〉/〈jDM〉 ∼ 2 at Mstar = 1010–11 M⊙. The reduced rotational support in the lowest mass galaxies owes to (a) stellar feedback and the UV background suppressing the accretion of high angular momentum gas at late times, and (b) stellar feedback driving large non-circular gas motions. We broadly reproduce the observed scaling relations between galaxy mass, gas rotation velocity, size and angular momentum, but may somewhat underpredict the incidence of disky, high angular momentum galaxies at the lowest observed masses (Mstar = (106–2 × 107) M⊙). Stars form preferentially from low angular momentum gas near the galactic centre and are less rotationally supported than gas. The common assumption that stars follow the same rotation curve as gas thus substantially overestimates the simulated galaxies’ stellar angular momentum, particularly at low masses.
BACKGROUND Female cancer patients are offered ‘banking’ of gametes before starting fertility-threatening cancer therapy. Transplants of fresh and frozen ovarian tissue between healthy fertile and ...infertile women have demonstrated the utility of the tissue banked for restoration of endocrine and fertility function. Additional methods, like follicle culture and isolated follicle transplantation, are in development. METHODS Specialist reproductive medicine scientists and clinicians with complementary expertise in ovarian tissue culture and transplantation presented relevant published literature in their field of expertise and also unpublished promising data for discussion. As the major aims were to identify the current gaps prohibiting advancement, to share technical experience and to orient new research, contributors were allowed to provide their opinioned expert views on future research. RESULTS Normal healthy children have been born in cancer survivors after orthotopic transplantation of their cryopreserved ovarian tissue. Longevity of the graft might be optimized by using new vitrification techniques and by promoting rapid revascularization of the graft. For the in vitro culture of follicles, a successive battery of culture methods including the use of defined media, growth factors and three-dimensional extracellular matrix support might overcome growth arrest of the follicles. Molecular methods and immunoassay can evaluate stage of maturation and guide adequate differentiation. Large animals, including non-human primates, are essential working models. CONCLUSIONS Experiments on ovarian tissue from non-human primate models and from consenting fertile and infertile patients benefit from a multidisciplinary approach. The new discipline of oncofertility requires professionalization, multidisciplinarity and mobilization of funding for basic and translational research.
ABSTRACT
We use a particle tracking analysis to study the origins of the circumgalactic medium (CGM), separating it into (1) accretion from the intergalactic medium (IGM), (2) wind from the central ...galaxy, and (3) gas ejected from other galaxies. Our sample consists of 21 FIRE-2 simulations, spanning the halo mass range Mh ∼ 1010–1012 M⊙, and we focus on z = 0.25 and z = 2. Owing to strong stellar feedback, only ∼L⋆ haloes retain a baryon mass $\gtrsim\! 50\hbox{ per cent}$ of their cosmic budget. Metals are more efficiently retained by haloes, with a retention fraction $\gtrsim\! 50\hbox{ per cent}$. Across all masses and redshifts analysed $\gtrsim \!60\hbox{ per cent}$ of the CGM mass originates as IGM accretion (some of which is associated with infalling haloes). Overall, the second most important contribution is wind from the central galaxy, though gas ejected or stripped from satellites can contribute a comparable mass in ∼L⋆ haloes. Gas can persist in the CGM for billions of years, resulting in well mixed-halo gas. Sightlines through the CGM are therefore likely to intersect gas of multiple origins. For low-redshift ∼L⋆ haloes, cool gas (T < 104.7 K) is distributed on average preferentially along the galaxy plane, however with strong halo-to-halo variability. The metallicity of IGM accretion is systematically lower than the metallicity of winds (typically by ≳1 dex), although CGM and IGM metallicities depend significantly on the treatment of subgrid metal diffusion. Our results highlight the multiple physical mechanisms that contribute to the CGM and will inform observational efforts to develop a cohesive picture.
Abstract
We describe a public data release of the FIRE-2 cosmological zoom-in simulations of galaxy formation (available at
http://flathub.flatironinstitute.org/fire
) from the Feedback In Realistic ...Environments (FIRE) project. FIRE-2 simulations achieve parsec-scale resolution to explicitly model the multiphase interstellar medium while implementing direct models for stellar evolution and feedback, including stellar winds, core-collapse and Type Ia supernovae, radiation pressure, photoionization, and photoelectric heating. We release complete snapshots from three suites of simulations. The first comprises 20 simulations that zoom in on 14 Milky Way (MW)–mass galaxies, five SMC/LMC-mass galaxies, and four lower-mass galaxies including one ultrafaint; we release 39 snapshots across
z
= 0–10. The second comprises four massive galaxies, with 19 snapshots across
z
= 1–10. Finally, a high-redshift suite comprises 22 simulations, with 11 snapshots across
z
= 5–10. Each simulation also includes dozens of resolved lower-mass (satellite) galaxies in its zoom-in region. Snapshots include all stored properties for all dark matter, gas, and star particles, including 11 elemental abundances for stars and gas, and formation times (ages) of star particles. We also release accompanying (sub)halo catalogs, which include galaxy properties and member star particles. For the simulations to
z
= 0, including all MW-mass galaxies, we release the formation coordinates and an “ex situ” flag for all star particles, pointers to track particles across snapshots, catalogs of stellar streams, and multipole basis expansions for the halo mass distributions. We describe publicly available python packages for reading and analyzing these simulations.
Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits ...excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed.
BACKGROUND
In vitro follicle growth is a promising fertility preservation strategy in which ovarian follicles are cultured to produce mature and fertilization-competent oocytes. However, in primates, ...there has been limited success with in vitro follicle growth starting from primordial and primary follicles because adequate isolation methods and culture strategies have not been established. Understanding how to use primordial follicles for fertility preservation has significant implications because these follicles are the most abundant in the ovary, are found in all females and are fairly resistant to cryopreservation and chemotherapeutics.
METHODS
In the primate ovary, primordial follicles are concentrated near the collagen-rich ovarian cortex. To obtain these follicles, we separated the ovarian cortex prior to enzymatic digestion and enriched the primordial follicle concentration by using a novel double filtration system. To test the hypothesis that a rigid physical environment, as found in vivo, is optimal for survival, primordial follicles were cultured in different concentrations of alginate for up to 6 days. Follicle survival and morphology were monitored throughout the culture.
RESULTS
We found that primate ovarian tissue can be maintained for up to 24 h at 4°C without compromising tissue or follicle health. Hundreds of intact and viable primordial follicles were isolated from each ovary independent of animal age. Follicle survival and morphology were more optimal when follicles were cultured in 2% alginate compared with 0.5% alginate.
CONCLUSIONS
By mimicking the rigid ovarian environment through the use of biomaterials, we have established conditions that support primordial follicle culture. These results lay the foundations for studying the basic biology of primordial follicles in a controlled environment and for using primordial follicles for fertility preservation methods.
The gonadotoxic effects of chemotherapy and radiation may result in premature ovarian failure in premenopausal oncology patients. Although autotransplantation of ovarian tissue has led to successful ...live births, reintroduction of latent malignant cells inducing relapse is a significant concern. In this report, we investigated the design of biomaterial grafts for transplantation of isolated ovarian follicles as a means to preserve fertility. Primordial and primary ovarian follicles from young female mice were extracted and encapsulated into biomaterials for subsequent transplantation into adult mice. Among the formulations tested, aggregated follicles encapsulated within fibrin had enhanced survival and integration with the host tissue following transplantation relative to the fibrin-alginate and fibrin-collagen composites. All mice transplanted with fibrin-encapsulated follicles resumed cycling, and live births were achieved only for follicles transplanted within VEGF-loaded fibrin beads. The extent to which these procedures reduce the presence of metastatic breast cancer cells among the isolated follicles was evaluated, with significantly reduced numbers of cancer cells present relative to intact ovaries. This ability to obtain live births by transplanting isolated primordial and primary follicles, while also reducing the risk of re-seeding disease relative to ovarian tissue transplantation, may ultimately provide a means to preserve fertility in premenopausal oncology patients.
In vitro follicle growth in alginate hydrogels is a unique and versatile method for studying ovarian and follicle biology that may also have implications for fertility preservation. Current culture ...systems support the development of isolated mouse follicles from the secondary stage onward. However, it has been a challenge to grow smaller follicles in vitro due to the dissociation of the oocyte from companion somatic cells. Recent work has demonstrated that coculturing primary follicles with mouse embryonic fibroblasts or ovarian stromal cells supports follicle survival and growth. In this study, we demonstrate that follicles themselves can exert a beneficial coculture effect. When primary follicles were cultured in groups of five or ten (multiple follicle culture), there was increased growth and survival. The multiple follicle culture approach maintained follicle integrity and resulted in the formation of antral stage follicles containing meiotically competent gametes. The growth and survival of primary follicles were highly number dependent, with the most significant enhancement observed when the largest number of follicles was grown together. Our data suggest that the follicle unit is necessary to produce the secreted factors responsible for the supportive effects of multiple follicle culture, as neither denuded oocytes, oocyte-secreted factors, nor granulosa cells alone were sufficient to support early follicle growth in vitro. Therefore, there may be signaling from both the oocyte and the follicle that enhances growth but requires both components in a feedback mechanism. This work is consistent with current in vivo models for follicle growth and thus advances the movement to recapitulate the ovarian environment in vitro.