403 research outputs found
Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme
The renal endothelium has been debated as arising from resident hemangioblast precursors that transdifferentiate from the nephrogenic mesenchyme (vasculogenesis) and/or from invading vessels (angiogenesis). While the Foxd1-positive renal cortical stroma has been shown to differentiate into cells that support the vasculature in the kidney (including vascular smooth muscle and pericytes) it has not been considered as a source of endothelial cell progenitors. In addition, it is unclear if Foxd1-positive mesenchymal cells in other organs such as the lung have the potential to form endothelium. This study examines the potential for Foxd1-positive cells of the kidney and lung to give rise to endothelial progenitors. We utilized immunofluorescence (IF) and fluorescence-activated cell sorting (FACS) to co-label Foxd1-expressing cells (including permanently lineage-tagged cells) with endothelial markers in embryonic and postnatal mice. We also cultured FACsorted Foxd1-positive cells, performed in vitro endothelial cell tubulogenesis assays and examined for endocytosis of acetylated low-density lipoprotein (Ac-LDL), a functional assay for endothelial cells. Immunofluorescence and FACS revealed that a subset of Foxd1-positive cells from kidney and lung co-expressed endothelial cell markers throughout embryogenesis. In vitro, cultured embryonic Foxd1-positive cells were able to differentiate into tubular networks that expressed endothelial cell markers and were able to endocytose Ac-LDL. IF and FACS in both the kidney and lung revealed that lineage-tagged Foxd1-positive cells gave rise to a significant portion of the endothelium in postnatal mice. In the kidney, the stromal-derived cells gave rise to a portion of the peritubular capillary endothelium, but not of the glomerular or large vessel endothelium. These findings reveal the heterogeneity of endothelial cell lineages; moreover, Foxd1-positive mesenchymal cells of the developing kidney and lung are a source of endothelial progenitors that are likely critical to patterning the vasculature. © 2013 Sims-Lucas et al
Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning
The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma. © 2014 Hum et al
Deletion of Fibroblast Growth Factor Receptor 2 from the Peri-Wolffian Duct Stroma Leads to Ureteric Induction Abnormalities and Vesicoureteral Reflux
Purpose: Pax3cre-mediated deletion of fibroblast growth factor receptor 2 (Fgfr2) broadly in renal and urinary tract mesenchyme led to ureteric bud (UB) induction defects and vesicoureteral reflux (VUR), although the mechanisms were unclear. Here, we investigated whether Fgfr2 acts specifically in peri-Wolffian duct stroma (ST) to regulate UB induction and development of VUR and the mechanisms of Fgfr2 activity. Methods: We conditionally deleted Fgfr2 in ST (Fgfr2 ST-/- ) using Tbx18cre mice. To look for ureteric bud induction defects in young embryos, we assessed length and apoptosis of common nephric ducts (CNDs). We performed 3D reconstructions and histological analyses of urinary tracts of embryos and postnatal mice and cystograms in postnatal mice to test for VUR. We performed in situ hybridization and real-time PCR in young embryos to determine mechanisms underlying UB induction defects. Results: We confirmed that Fgfr2 is expressed in ST and that Fgfr2 was efficiently deleted in this tissue in Fgfr2 ST-/- mice at embryonic day (E) 10.5. E11.5 Fgfr2 ST-/- mice had randomized UB induction sites with approximately 1/3 arising too high and 1/3 too low from the Wolffian duct; however, apoptosis was unaltered in E12.5 mutant CNDs. While ureters were histologically normal, E15.5 Fgfr2 ST-/- mice exhibit improper ureteral insertion sites into the bladder, consistent with the ureteric induction defects. While ureter and bladder histology appeared normal, postnatal day (P) 1 mutants had high rates of VUR versus controls (75% versus 3%, p = 0.001) and occasionally other defects including renal hypoplasia and duplex systems. P1 mutant mice also had improper ureteral bladder insertion sites and shortened intravesicular tunnel lengths that correlated with VUR. E10.5 Fgfr2 ST-/- mice had decreases in Bmp4 mRNA in stromal tissues, suggesting a mechanism underlying the ureteric induction and VUR phenotypes. Conclusion: Mutations in FGFR2 could possibly cause VUR in humans. © 2013 Walker et al
Virtual player design using self-learning via competitive coevolutionary algorithms
The Google Artificial Intelligence (AI) Challenge
is an international contest the objective of which is to program the AI in a two-player real time strategy (RTS) game. This AI is an autonomous computer program that governs the actions that one of the two players executes during the game according to the state of play. The entries
are evaluated via a competition mechanism consisting of two-player rounds where each entry is tested against others.
This paper describes the use of competitive coevolutionary (CC) algorithms for the automatic generation of winning game strategies in Planet Wars, the RTS game associated with the 2010 contest. Three different versions of a prime
algorithm have been tested. Their common nexus is not only the use of a Hall-of-Fame (HoF) to keep note of the winners of past coevolutions but also the employment of an archive of experienced players, termed the hall-of-celebrities
(HoC), that puts pressure on the optimization process and guides the search to increase the strength of the solutions; their differences come from the periodical updating of the HoF on the basis of quality and diversity metrics.
The goal is to optimize the AI by means of a self-learning process guided by coevolutionary search and competitive evaluation. An empirical study on the performance of a number of variants of the proposed algorithms is described and a statistical analysis of the results is conducted. In addition to the attainment of competitive bots we also
conclude that the incorporation of the HoC inside the primary algorithm helps to reduce the effects of cycling caused by the use of HoF in CC algorithms.This work is partially supported by Spanish
MICINN under Project ANYSELF (TIN2011-28627-C04-01),3 by Junta de AndalucÃa under Project P10-TIC-6083 (DNEMESIS) and by Universidad de Málaga, Campus de Excelencia Internacional AndalucÃa Tech
Does Banque de France control inflation and unemployment?
We re-estimate statistical properties and predictive power of a set of
Phillips curves, which are expressed as linear and lagged relationships between
the rates of inflation, unemployment, and change in labour force. For France,
several relationships were estimated eight years ago. The change rate of labour
force was used as a driving force of inflation and unemployment within the
Phillips curve framework. The set of nested models starts with a simplistic
version without autoregressive terms and one lagged term of explanatory
variable. The lag is determined empirically together with all coefficients. The
model is estimated using the Boundary Element Method (BEM) with the least
squares method applied to the integral solutions of the differential equations.
All models include one structural break might be associated with revisions to
definitions and measurement procedures in the 1980s and 1990s as well as with
the change in monetary policy in 1994-1995. For the GDP deflator, our original
model provided a root mean squared forecast error (RMSFE) of 1.0% per year at a
four-year horizon for the period between 1971 and 2004. The rate of CPI
inflation is predicted with RMSFE=1.5% per year. For the naive (no change)
forecast, RMSFE at the same time horizon is 2.95% and 3.3% per year,
respectively. Our model outperforms the naive one by a factor of 2 to 3. The
relationships for inflation were successfully tested for cointegration. We have
formally estimated several vector error correction (VEC) models for two
measures of inflation. At a four year horizon, the estimated VECMs provide
significant statistical improvements on the results obtained by the BEM:
RMSFE=0.8% per year for the GDP deflator and ~1.2% per year for CPI. For a two
year horizon, the VECMs improve RMSFEs by a factor of 2, with the smallest
RMSFE=0.5% per year for the GDP deflator.Comment: 25 pages, 12 figure
The Methodology of Modern Macroeconomics and the Descriptive Approach to Discounting
Critics of modern macroeconomics often raise concerns about unwarranted welfare conclusions and data mining. This paper illustrates these concerns with a thought experiment, based on the debate in environmental economics about the appropriate discount rate in climate change analyses: I set up an economy where a social evaluator wants to determine the optimal time path of emission levels, and seeks advice for this from an old-style neo-classical macroeconomist and a new neo-classical (modern) macroeconomist; I then describe how both economists analyze the economy, their policy advice, and their mistakes. I then use the insights from this thought experiment to point out some pitfalls of the modern macroeconomic methodology
- …