Impact study design

Precise design of impact studies carried out in interaction with WP2 and WP

CD1d expression demarcates CDX4+ hemogenic mesoderm with definitive hematopoietic potential

To achieve efficient, reproducible differentiation of human pluripotent stem cells (hPSCs) towards specific hematopoietic cell-types, a comprehensive understanding of the necessary cell signaling and developmental trajectories involved is required. Previous studies have identified the mesodermal progenitors of extra-embryonic-like and intra-embryonic-like hemogenic endothelium (HE), via stage-specific WNT and ACTIVIN/NODAL, with GYPA/GYPB (CD235a/b) expression serving as a positive selection marker for mesoderm harboring exclusively extra-embryonic-like hemogenic potential. However, a positive mesodermal cell-surface marker with exclusively intra-embryonic-like hemogenic potential has not been identified. Recently, we reported that early mesodermal expression of CDX4 critically regulates definitive HE specification, suggesting that CDX4 may act in a cell-autonomous manner during hematopoietic development. To identify CDX4+ mesoderm, we performed single cell (sc)RNAseq on hPSC-derived mesodermal cultures, revealing CDX

MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation

Macrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between miR-21 and the lipid mediator prostaglandin E2 (PGE2) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE2 and its downstream effectors PKA and Epac inhibit miR-21 expression and enhance expression of M2 genes, and this effect is more pronounced in miR-21-/- cells. Among potential targets involved in macrophage polarization, we found that STAT3 and SOCS1 were enhanced in miR-21-/- cells and further enhanced by PGE2. We found that STAT3 was a direct target of miR-21 in macrophages. Silencing the STAT3 gene abolished PGE2-mediated expression of M2 genes in miR-21-/- macrophages. These data shed light on the molecular brakes involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses

Operative Intervention Does Not Change Pain Perception in Patients With Diabetic Foot Ulcers

Researchers investigated pain perception in patients with diabetic foot ulcers (DFUs) by analyzing pre- and postoperative physical function (PF), pain interference (PI), and depression domains of the Patient-Reported Outcome Measurement Information System (PROMIS). They hypothesized that 1) because of painful diabetic peripheral neuropathy (DPN), a majority of patients with DFUs would have high PROMIS PI scores unchanged by operative intervention, and 2) the initially assessed PI, PF, and depression levels would be correlated with final outcomes. Seventy-five percent of patients with DFUs reported pain, most likely because of painful DPN. Those who reported high PI and low PF were likely to report depression. PF, PI, and depression levels were unchanged after operative intervention or healing of DFUs

Impact of Trucking Network Flow on Preferred Biorefinery Locations in the Southern United States

The impact of the trucking transportation network flow was modeled for the southern United States. The study addresses a gap in existing research by applying a Bayesian logistic regression and Geographic Information System (GIS) geospatial analysis to predict biorefinery site locations. A one-way trucking cost assuming a 128.8 km (80-mile) haul distance was estimated by the Biomass Site Assessment model. The median family income, timberland annual growth-to-removal ratio, and transportation delays were significant in determining mill location. Transportation delays that directly impacted the costs of trucking are presented. A logistic model with Bayesian inference was used to identify preferred site locations, and locations not preferential for a mill location. The model predicted that higher probability locations for smaller biomass mills (feedstock capacity, the size of sawmills) were in southern Alabama, southern Georgia, southeast Mississippi, southern Virginia, western Louisiana, western Arkansas, and eastern Texas. The higher probability locations for large capacity mills (feedstock capacity, the size for pulp and paper mills) were in southeastern Alabama, southern Georgia, central North Carolina, and the Mississippi Delta regions

The UV, Optical, and IR Properties of SDSS Sources Detected by GALEX

We discuss the UV, optical, and IR properties of the SDSS sources detected by GALEX as part of its All-sky Imaging Survey Early Release Observations. Virtually all of the GALEX sources in the overlap region are detected by SDSS. GALEX sources represent ~2.5% of all SDSS sources within these fields and about half are optically unresolved. Most unresolved GALEX/SDSS sources are bright blue turn-off thick disk stars and are typically detected only in the GALEX near-UV band. The remaining unresolved sources include low-redshift quasars, white dwarfs, and white dwarf/M dwarf pairs, and these dominate the optically unresolved sources detected in both GALEX bands. Almost all the resolved SDSS sources detected by GALEX are fainter than the SDSS 'main' spectroscopic limit. These sources have colors consistent with those of blue (spiral) galaxies (u-r<2.2), and most are detected in both GALEX bands. Measurements of their UV colors allow much more accurate and robust estimates of star-formation history than are possible using only SDSS data. Indeed, galaxies with the most recent (<20 Myr) star formation can be robustly selected from the GALEX data by requiring that they be brighter in the far-UV than in the near-UV band. However, older starburst galaxies have UV colors similar to AGN, and thus cannot be selected unambiguously on the basis of GALEX fluxes alone. With the aid of 2MASS data, we construct and discuss median 10 band UV-optical-IR spectral energy distributions for turn-off stars, hot white dwarfs, low-redshift quasars, and spiral and elliptical galaxies. We point out the high degree of correlation between the UV color and the contribution of the UV flux to the UV-optical-IR flux of galaxies detected by GALEX.Comment: 35 pages, 11 figures, 3 tables; to appear in the AJ. PS with better figures available from http://www.astro.washington.edu/agueros/pub

Toward an improved design of the in-situ observing system for ocean reanalysis, analysis and forecasting: design of experiments

This report presents the work plan within the task 1.3 - Observing System Design Studie

XMM-Newton Observations of a Complete Sample of Optically Selected Type 2 Seyfert Galaxies

(abridged)The majority of Active Galactic Nuclei (AGN) suffer from significant obscuration by surrounding dust and gas. X-ray surveys in the 2-10 keV band will miss the most heavily-obscured AGN in which the absorbing column density exceeds $\sim10^{24}$cm$^{-2}$ (the Compton-thick AGN). It is therefore vital to know the fraction of AGN that are missed in such X-rays surveys and to determine if these AGN represent some distinct population in terms of the fundamental properties of AGN and/or their host galaxies. In this paper we present the analysis of \textit{XMM-Newton} X-ray data for a complete sample of 17 low-redshift Type 2 Seyfert galaxies chosen from the Sloan Digital Sky Survey based solely on the high observed flux of the [OIII]$\lambda$5007 emission-line. This line is formed in the Narrow Line Region hundreds of parsecs away from the central engine. Thus, unlike the X-ray emission, it is not affected by obscuration due to the torus surrounding the black hole. It therefore provides a useful isotropic indicator of the AGN luminosity. As additional indicators of the intrinsic AGN luminosity, we use the Spitzer Space Telescope to measure the luminosities of the mid-infrared continuum and the [OIV]25.89$\mu$m narrow emission-line. We then use the ratio of the 2-10 keV X-ray luminosity to the [OIII], [OIV], and mid-infrared luminosities to assess the amount of X-ray obscuration and to distinguish between Compton-thick and Compton-thin objects. We find that the majority of the sources suffer significant amounts of obscuration: the observed 2-10 keV emission is depressed by more than an order-of-magnitude in 11 of the 17 cases (as expected for Compton-thick sources).Comment: accepted for publication to ApJ; 48 pages, 15 figure

Analysis of retinal cell development in chick embryo by immunohistochemistry and in ovo electroporation techniques

<p>Abstract</p> <p>Background</p> <p>Retinal cell development has been extensively investigated; however, the current knowledge of dynamic morphological and molecular changes is not yet complete.</p> <p>Results</p> <p>This study was aimed at revealing the dynamic morphological and molecular changes in retinal cell development during the embryonic stages using a new method of targeted retinal injection, <it>in ovo </it>electroporation, and immunohistochemistry techniques. A plasmid DNA that expresses the green fluorescent protein (GFP) as a marker was delivered into the sub-retinal space to transfect the chick retinal stem/progenitor cells at embryonic day 3 (E3) or E4 with the aid of pulses of electric current. The transfected retinal tissues were analyzed at various stages during chick development from near the start of neurogenesis at E4 to near the end of neurogenesis at E18. The expression of GFP allowed for clear visualization of cell morphologies and retinal laminar locations for the indication of retinal cell identity. Immunohistochemistry using cell type-specific markers (e.g., Visinin, Xap-1, Lim1+2, Pkcα, NeuN, Pax6, Brn3a, Vimentin, etc.) allowed further confirmation of retinal cell types. The composition of retinal cell types was then determined over time by counting the number of GFP-expressing cells observed with morphological characteristics specific to the various retinal cell types.</p> <p>Conclusion</p> <p>The new method of retinal injection and electroporation at E3 - E4 allows the visualization of all retinal cell types, including the late-born neurons, e.g., bipolar cells at a level of single cells, which has been difficult with a conventional method with injection and electroporation at E1.5. Based on data collected from analyses of cell morphology, laminar locations in the retina, immunohistochemistry, and cell counts of GFP-expressing cells, the time-line and dynamic morphological and molecular changes of retinal cell development were determined. These data provide more complete information on retinal cell development, and they can serve as a reference for the investigations in normal retinal development and diseases.</p