Differences in the pattern and regulation of mineral deposition in human cell lines of osteogenic and non-osteogenic origin

Bone marrow-derived mesenchymal stem cells (MSCs) are widely used as a cellular model of bone formation, and can mineralize in vitro in response to osteogenic medium (OM). It is unclear, however, whether this property is specific to cells of mesenchymal origin. We analysed the OM response in 3 non-osteogenic lines, HEK293, HeLa and NTera, compared to MSCs. Whereas HEK293 cells failed to respond to OM conditions, the 2 carcinoma-derived lines NTera and HeLa deposited a calcium phosphate mineral comparable to that present in MSC cultures. However, unlike MSCs, HeLa and NTera cultures did so in the absence of dexamethasone. This discrepancy was confirmed, as bone morphogenetic protein inhibition obliterated the OM response in MSCs but not in HeLa or NTera, indicating that these 2 models can deposit mineral through a mechanism independent of established dexamethasone or bone morphogenetic protein signalling. © 2011 S. Karger AG, Basel

Implementation and sustainment of diverse practices in a large integrated health system: a mixed methods study

Background: One goal of health systems seeking to evolve into learning health systems is to accelerate the implementation and sustainment of evidence-based practices (EBPs). As part of this evolution, the Veterans Health Administration (VHA) developed the Innovation Ecosystem, which includes the Diffusion of Excellence (DoE), a program that identifies and diffuses Gold Status Practices (GSPs) across facilities. The DoE hosts an annual Shark Tank competition in which leaders bid on the opportunity to implement a GSP with 6 months of implementation support. Over 750 diverse practices were submitted in cohorts 2 and 3 of Shark Tank; 23 were designated GSPs and were implemented in 31 VA networks or facilities. As part of a national evaluation of the DoE, we identified factors contributing to GSP implementation and sustainment. Methods: Our sequential mixed methods evaluation of cohorts 2 and 3 of Shark Tank included semi-structured interviews with at least one representative from 30/31 implementing teams (N = 78/105 people invited) and survey responses from 29/31 teams (N = 39/47 invited). Interviews focused on factors influencing implementation and future sustainment. Surveys focused on sustainment 1.5-2 years after implementation. The Consolidated Framework for Implementation Research (CFIR) informed data collection and directed content analysis. Ordinal scales were developed inductively to rank implementation and sustainment outcomes. Results: Over 50% of teams (17/30) successfully implemented their GSP within the 6-month implementation period. Despite extensive implementation support, significant barriers related to centralized decision-making, staffing, and resources led to partial (n = 6) or no (n = 7) implementation for the remaining teams. While 12/17 initially successful implementation teams reported sustained use of their GSP, over half of the initially unsuccessful teams (n = 7/13) also reported sustained GSP use 1.5 years after the initial implementation period. When asked at 6 months, 18/27 teams with complete data accurately anticipated their future sustainability based on reported sustainment an average of 1.5 years later. Conclusions: Most teams implemented within 6 months and/or sustained their GSP 1.5 years later. High levels of implementation and sustainment across diverse practices and teams suggest that VHA\u27s DoE is a successful large-scale model of diffusion. Team predictions about sustainability after the first 6 months of implementation provide a promising early assessment and point of intervention to increase sustainability

Are current dynamic water quality models too complex? A comparison of a new parsimonious phosphorus model, SimplyP, and INCA-P

Catchment-scale water quality models are becoming increasingly popular tools for exploring the potential effects of land management, land use change and climate change on water quality. However, the dynamic, catchment-scale nutrient models in common usage are complex, with many uncertain parameters requiring calibration, limiting their usability and robustness. A key question is whether this complexity is justified. To explore this, we have developed a parsimonious P model, SimplyP, incorporating a coupled rainfall-runoff model and a biogeochemical model able to simulate streamflow, suspended sediment, particulate and dissolved P dynamics. The model’s complexity is compared in a small rural catchment in northeast Scotland. For three land use classes, less than six SimplyP model parameters must be determined through calibration alone, the rest may be based on measurements; INCA-P has around 40 unmeasurable parameters. Despite simpler process-representation, SimplyP produced a slightly better dissolved P simulation during both calibration and validation, and produced similar long-term projections in response to changes in land management. Results support the hypothesis that INCA-P is overly complex for the study catchment. We hope our findings will help prompt wider model comparison exercises, as well as debate amongst the water quality modelling community as to whether today's models are fit for purpose. Simpler models such as SimplyP have the potential to be useful management and research tools, building blocks for future model development (prototype code is freely available), or benchmarks against which more complex models could be evaluated

Target Selection for the Apache Point Observatory Galactic Evolution Experiment (APOGEE)

The Apache Point Observatory Galactic Evolution Experiment (APOGEE) is a high-resolution infrared spectroscopic survey spanning all Galactic environments (i.e., bulge, disk, and halo), with the principal goal of constraining dynamical and chemical evolution models of the Milky Way. APOGEE takes advantage of the reduced effects of extinction at infrared wavelengths to observe the inner Galaxy and bulge at an unprecedented level of detail. The survey's broad spatial and wavelength coverage enables users of APOGEE data to address numerous Galactic structure and stellar populations issues. In this paper we describe the APOGEE targeting scheme and document its various target classes to provide the necessary background and reference information to analyze samples of APOGEE data with awareness of the imposed selection criteria and resulting sample properties. APOGEE's primary sample consists of ~100,000 red giant stars, selected to minimize observational biases in age and metallicity. We present the methodology and considerations that drive the selection of this sample and evaluate the accuracy, efficiency, and caveats of the selection and sampling algorithms. We also describe additional target classes that contribute to the APOGEE sample, including numerous ancillary science programs, and we outline the targeting data that will be included in the public data releases.Comment: Accepted to AJ. 31 pages, 11 figure

Discovery and Characterization of 2-Anilino-4- (Thiazol-5-yl)Pyrimidine Transcriptional CDK Inhibitors as Anticancer Agents

The main difficulty in the development of ATP antagonist kinase inhibitors is target specificity, since the ATP-binding motif is present in many proteins. We introduce a strategy that has allowed us to identify compounds from a kinase inhibitor library that block the cyclin-dependent kinases responsible for regulating transcription, i.e., CDK7 and especially CDK9. The screening cascade employs cellular phenotypic assays based on mitotic index and nuclear p53 protein accumulation. This permitted us to classify compounds into transcriptional, cell cycle, and mitotic inhibitor groups. We describe the characterization of the transcriptional inhibitor class in terms of kinase inhibition profile, cellular mode of action, and selectivity for transformed cells. A structural selectivity rationale was used to optimize potency and biopharmaceutical properties and led to the development of a transcriptional inhibitor, 3,4-dimethyl-5-[2-(4-piperazin-1-yl-phenylamino)-pyrimidin-4-yl]-3H-thiazol-2-one, with anticancer activity in animal models

The INtegrated CAtchment model of phosphorus dynamics (INCA-P): description and demonstration of new model structure and equations

INCA-P is a dynamic, catchment-scale phosphorus model which has been widely applied during the last decade. Since its original release in 2002, the model structure and equations have been significantly altered during several development phases. Here, we provide the first full model description since 2002 and then test the latest version of the model (v1.4.4) in a small rural catchment in northeast Scotland. The particulate phosphorus simulation was much improved compared to previous model versions, whilst the latest sorption equations allowed us to explore the potential time lags between reductions in terrestrial inputs and improvements in surface water quality, an issue of key policy relevance. The model is particularly suitable for use as a research tool, but should only be used to inform policy and land management in data-rich areas, where parameters and processes can be well-constrained. More long-term data is needed to parameterise dynamic models and test their predictions

Catalog of Radio Galaxies with z>0.3. I:Construction of the Sample

The procedure of the construction of a sample of distant ($z>0.3$) radio galaxies using NED, SDSS, and CATS databases for further application in statistical tests is described. The sample is assumed to be cleaned from objects with quasar properties. Primary statistical analysis of the list is performed and the regression dependence of the spectral index on redshift is found.Comment: 9 pages, 6 figures, 2 table

Water abundances in high-mass protostellar envelopes: Herschel observations with HIFI

We derive the dense core structure and the water abundance in four massive star-forming regions which may help understand the earliest stages of massive star formation. We present Herschel-HIFI observations of the para-H2O 1_11-0_00 and 2_02-1_11 and the para-H2-18O 1_11-0_00 transitions. The envelope contribution to the line profiles is separated from contributions by outflows and foreground clouds. The envelope contribution is modelled using Monte-Carlo radiative transfer codes for dust and molecular lines (MC3D and RATRAN), with the water abundance and the turbulent velocity width as free parameters. While the outflows are mostly seen in emission in high-J lines, envelopes are seen in absorption in ground-state lines, which are almost saturated. The derived water abundances range from 5E-10 to 4E-8 in the outer envelopes. We detect cold clouds surrounding the protostar envelope, thanks to the very high quality of the Herschel-HIFI data and the unique ability of water to probe them. Several foreground clouds are also detected along the line of sight. The low H2O abundances in massive dense cores are in accordance with the expectation that high densities and low temperatures lead to freeze-out of water on dust grains. The spread in abundance values is not clearly linked to physical properties of the sources.Comment: 8 pages, 5 figures, accepted for publication the 15/07/2010 by Astronomy&Astrophysics as a letter in the Herschel-HIFI special issu