Investigations into the in vitro developmental plasticity of adult mesenchymal stem cells

Bone marrow (BM) derived stem cells contribute to the regeneration of diverse adult tissues including heart, liver and brain following BM transplantation. Trans- differentiation is a mechanism proposed to explain how tissue specific stem cells could generate cells of other organs, thus supporting the emerging concept of enhanced adult stem cell plasticity. New studies have demonstrated that spontaneous cell fusion rather than trans-differentiation is the cause of unexpected cell fate changes in vivo. In contrast, several authors have reported that trans-differentiation can occur in vitro in the absence of cell fusion, including the generation of neural derivatives from non-neural tissues. These findings have profound implications for stem cell biology and cell replacement therapy, and as a result require extensive validation. Mesenchymal stem cells (MSCs) nave been isolated from the postnatal BM and more recently many other sites including adipose tissue, skin and placental cord blood. As such these cells have attracted interest as candidates for cell replacement therapies. This interest follows recent observations both in vitro and in transplant studies that these cells are capable of broader differentiation potential beyond those cell lineages associated with the organ in which they reside. The aim of the present thesis was to examine the developmental plasticity of MSCs in vitro including the capacity of these cells to cross lineage boundaries by differentiating into neuro-ectodermal cell derivatives. There are no universally accepted procedures for the prospective isolation of these cells. In the present thesis, procedures for the isolation of MSCs from rat BM and optimal conditions for the propagation of these cells in culture without loss of multipotent differentiation potential and proliferative capacity are first described. Secondly, the response of cultured MSCs with a consistent immunophenotype to defined culture conditions, previously reported to induce neuronal differentiation of MSCs are evaluated. Thirdly, evidence is presented that suggests that previous claims of trans-differentiation and apparent changes in cell phenotype have been incorrectly interpreted. Evidence is provided that MSCs respond to neural cues in vitro with a stress response, which is characterized by aberrant changes in the expression of constitutive neural proteins, an event previously interpreted as trans-differentiation. MSCs do not have the attributes of early or mature neural derivatives and therefore such changes in protein expression do not equate to true neural differentiation. Finally, evidence is presented that demonstrates that MSCs cultured under defined culture conditions release soluble factors that instruct a neurogenic cell fate decision on neural stem cells (NSCs). In addition, these soluble factors also increase neurite outgrowth of Tuj-1+ differentiating cell progeny. These effects may in part explain the therapeutic benefit of MSG transplantation in animal models of CNS lesions

Development management and localism: Zeitgeist or lasting change?

The spatial planning approach has become accepted as the progressive theoretical and professional currency in England following the 2004 Planning and Compulsory Purchase Act. The reforms which followed sought considerable change in the remit of planning and the approach to community engagement. However, an often overlooked component of the spatial planning approach is development management; and yet it is potentially of most relevance to the challenges of neighbourhood planning and community resilience. Development management focuses upon outcomes (i.e. meeting needs) rather than outputs (the implications of permitting/refusing development - normatively related to the regulatory ‘DC’ function). The methodological approach is based around a more varied and multi-faceted concept than in the reactive past. A key part of this relates to the way in which community participation occurs and decision making takes place. This artcile discusses the concept that empowering communities through early engagement, support for community led initiatives/plans, Local Development Orders, and enhanced delegated decision making at the Parish level are examples of localism before Localism, and highlight the contemporary relevance of the development management approach. It is suggested, therefore, that rather than requiring a planning revolution, the current changes represent an opportunity to firstly recognise and secondly utilise existing tools to support community planning. Implementing further significant change in the planning system may not be in anyone’s best interest, least of all for the resilience of those communities it seeks to empower.This article explores the evolution of the development management approach and its significance in the context of the proposed neighbourhood planning systems, including Neighbourhood Plans and Development Orders, the Community Right to Build, and community engagement and participation methods

Novel Academic Tabletop 2022 (NAT22): A dynamic dice-based emergency medicine education tool

Gamification is an effective teaching tool that improves engagement and knowledge retention. Tabletop role-playing games are dynamic games that use random chance and foster player/leader partnership. To date, there are no teaching tools that mimic dynamic or unpredictable patient presentations. This style of game may work well as a tool for medical education in a simulation-based modality. In this report, we document the rules, materials, and training required to reproduce a hybrid game created to combine facets of simulation and tabletop role-playing games (TRPGs) to create a dynamic medical education tool. After testing the game for flaws and fluidity of gameplay, we plan to collect data evaluating emergency medicine residents\u27 enjoyability and knowledge retention. In this article, we describe a novel TRPG simulation hybrid game that we hypothesize will improve learner enjoyability/engagement and have similar educational benefits to standard medical education

Constraints on Quasar Lifetimes and Beaming from the HeII Lyman-alpha Forest

We show that comparisons of HeII Lyman-alpha forest lines of sight to nearby quasar populations can strongly constrain the lifetimes and emission geometry of quasars. By comparing the HeII and HI Lyman-alpha forests along a particular line of sight, one can trace fluctuations in the hardness of the radiation field (which are driven by fluctuations in the HeII ionization rate). Because this high-energy background is highly variable - thanks to the rarity of the bright quasars that dominate it and the relatively short attenuation lengths of these photons - it is straightforward to associate features in the radiation field with their source quasars. Here we quantify how finite lifetimes and beamed emission geometries affect these expectations. Finite lifetimes induce a time delay that displaces the observed radiation peak relative to the quasar. For beamed emission, geometry dictates that sources invisible to the observer can still create a peak in the radiation field. We show that both these models produce substantial populations of "bare" peaks (without an associated quasar) for reasonable parameter values (lifetimes ~10^6-10^8 yr and beaming angles <90 degrees). A comparison to existing quasar surveys along two HeII Lyman-alpha forest lines of sight rules out isotropic emission and infinite lifetime at high confidence; they can be accommodated either by moderate beaming or lifetimes ~10^7-10^8 yr. We also show that the distribution of radial displacements between peaks and their quasars can unambiguously distinguish these two models, although larger statistical samples are needed.Comment: submitted to ApJ, 8 pages, 2 figure

Detection of fast radio transients with multiple stations: a case study using the Very Long Baseline Array

Recent investigations reveal an important new class of transient radio phenomena that occur on sub-millisecond timescales. Often transient surveys' data volumes are too large to archive exhaustively. Instead, an on-line automatic system must excise impulsive interference and detect candidate events in real-time. This work presents a case study using data from multiple geographically distributed stations to perform simultaneous interference excision and transient detection. We present several algorithms that incorporate dedispersed data from multiple sites, and report experiments with a commensal real-time transient detection system on the Very Long Baseline Array (VLBA). We test the system using observations of pulsar B0329+54. The multiple-station algorithms enhanced sensitivity for detection of individual pulses. These strategies could improve detection performance for a future generation of geographically distributed arrays such as the Australian Square Kilometre Array Pathfinder and the Square Kilometre Array.Comment: 12 pages, 14 figures. Accepted for Ap

A Measurement of Small Scale Structure in the 2.2 < z < 4.2 Lyman-alpha Forest

The amplitude of fluctuations in the Ly-a forest on small spatial scales is sensitive to the temperature of the IGM and its spatial fluctuations. The temperature of the IGM and its spatial variations contain important information about hydrogen and helium reionization. We present a new measurement of the small-scale structure in the Ly-a forest from 40 high resolution, high signal-to-noise, VLT spectra at z=2.2-4.2. We convolve each Ly-a forest spectrum with a suitably chosen wavelet filter, which allows us to extract the amount of small-scale structure in the forest as a function of position across each spectrum. We compare these measurements with high resolution hydrodynamic simulations of the Ly-a forest which track more than 2 billion particles. This comparison suggests that the IGM temperature close to the cosmic mean density (T_0) peaks near z=3.4, at which point it is greater than 20,000 K at 2-sigma confidence. The temperature at lower redshift is consistent with the fall-off expected from adiabatic cooling ($T_0 \propto (1+z)^2$), after the peak temperature is reached near z=3.4. At z=4.2 our results favor a temperature of T_0 = 15-20,000 K. However, owing mostly to uncertainties in the mean transmitted flux at this redshift, a cooler IGM model with T_0 = 10,000 K is only disfavored at the 2-sigma level here, although such cool IGM models are strongly discrepant with the z ~ 3-3.4 measurement. We do not detect large spatial fluctuations in the IGM temperature at any redshift covered by our data set. The simplest interpretation of our measurements is that HeII reionization completes sometime near z ~ 3.4, although statistical uncertainties are still large [Abridged].Comment: Submitted to ApJ. Best printed in colo

Boosting Line Intensity Map Signal-to-Noise with the Ly-α\alpha Forest Cross-Correlation

We forecast the prospects for cross-correlating future line intensity mapping (LIM) surveys with the current and future Ly-$\alpha$ forest data. We use large cosmological hydrodynamic simulations to model the expected emission signal for the CO rotational transition in the COMAP LIM experiment at the 5-year benchmark and the Ly-$\alpha$ forest absorption signal for various surveys, including eBOSS, DESI, and PFS. We show that CO$\times$Ly-$\alpha$ forest can significantly enhance the detection signal-to-noise ratio of CO, with a $200$ to $300 \%$ improvement when cross-correlated with the forest observed in the Prime Focus Spectrograph (PFS) survey and a $50$ to $75\%$ enhancement for the currently available eBOSS or the upcoming DESI observations. We compare to the signal-to-noise improvements expected for a galaxy survey and show that CO$\times$Ly-$\alpha$ is competitive with even a spectroscopic galaxy survey in raw signal-to-noise. Furthermore, our study suggests that the clustering of CO emission is tightly constrained by CO$\times$Ly-$\alpha$ forest, due to the increased signal-to-noise ratio and the simplicity of Ly-$\alpha$ absorption power spectrum modeling. Any foreground contamination or systematics are expected not to be shared between LIM surveys and Ly-$\alpha$ forest observations; this provides an unbiased inference. Our findings highlight the potential benefits of utilizing the Ly-$\alpha$ forest to aid in the initial detection of signals in line intensity experiments. For example, we also estimate that [CII]$\times$Ly-$\alpha$ forest measurements from EXCLAIM and DESI/eBOSS, respectively, should have a larger signal-to-noise ratio than planned [CII]$\times$quasar observations by about an order of magnitude. Our results can be readily applied to actual data thanks to the observed quasar spectra in eBOSS Stripe 82, which overlaps with several LIM surveys.Comment: Codes and the produced data are available at https://github.com/qezlou/lal

The Signatures of Large-scale Temperature and Intensity Fluctuations in the Lyman-alpha Forest

It appears inevitable that reionization processes would have produced large-scale temperature fluctuations in the intergalactic medium. Using toy temperature models and detailed heating histories from cosmological simulations of HeII reionization, we study the consequences of inhomogeneous heating for the Ly-alpha forest. The impact of temperature fluctuations in physically well-motivated models can be surprisingly subtle. In fact, we show that temperature fluctuations at the level predicted by our reionization simulations do not give rise to detectable signatures in the types of statistics that have been employed previously. However, because of the aliasing of small-scale density power to larger scale modes in the line-of-sight Ly-alpha forest power spectrum, earlier analyses were not sensitive to 3D modes with >~ 30 comoving Mpc wavelengths -- scales where temperature fluctuations are likely to be relatively largest. The ongoing Baryon Oscillation Spectroscopic Survey (BOSS) aims to measure the 3D power spectrum of the Ly-alpha forest, P_F, from a large sample of quasars in order to avoid this aliasing. We find that physically motivated temperature models can alter P_F at an order unity level at k <~ 0.1 comoving Mpc^{-1}, a magnitude that should be easily detectable with BOSS. Fluctuations in the intensity of the ultraviolet background can also alter P_F significantly. These signatures will make it possible for BOSS to study the thermal impact of HeII reionization at 2 < z < 3 and to constrain models for the sources of the ionizing background. Future spectroscopic surveys could extend this measurement to even higher redshifts, potentially detecting the thermal imprint of hydrogen reionization.Comment: 14 pages, 17 figures, plus 4 pages of Appendix, matches published versio

Neutrino mass limits from SDSS, 2dFGRS and WMAP

We investigate whether cosmological data suggest the need for massive neutrinos. We employ galaxy power spectrum measurements from the Sloan Digital Sky Survey (SDSS) and the Two Degree Field Galaxy Redshift Survey (2dFGRS), along with cosmic microwave background (CMB) data from the Wilkinson Microwave Anisotropy Probe (WMAP) and 27 other CMB experiments. We also use the measurement of the Hubble parameter from the Hubble Space Telescope (HST) Key Project. We find the sum of the neutrino masses to be smaller than 0.75 eV at 2\sigma (1.1 eV at 3\sigma).Comment: 4 pages, 2 figures. Only unconstrained bias fit included. References adde