Acidosis Is a Key Regulator of Osteoblast Ecto-Nucleotidase Pyrophosphatase/Phosphodiesterase 1 (NPP1) Expression and Activity

Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (Pi) to pyrophosphate (PPi) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both Pi and PPi, a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto‐nucleotidases. This study investigated the expression and activity of ecto‐nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto‐nucleotidases including NTPdase 1–6 (ecto‐nucleoside triphosphate diphosphohydrolase) and NPP1‐3 (ecto‐nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1 > NTPdase 4 > NTPdase 6 > NTPdase 5 > alkaline phosphatase > ecto‐5‐nucleotidase > Enpp3 > NTPdase 1 > NTPdase 3 > Enpp2 > NTPdase 2. Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8‐fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto‐nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (P < 0.001). Release of ATP, one of the key substrates for NPP1, from osteoblasts, was unaffected by acidosis. Further studies showed that mineralised bone formation by osteoblasts cultured from NPP1 knockout mice was increased compared with wildtypes (2.5‐fold, P < 0.001) and was partially resistant to the inhibitory effect of acidosis. These results indicate that increased NPP1 expression and activity might contribute to the decreased mineralisation observed when osteoblasts are exposed to acid conditions

Time to publication for NIHR HTA programme-funded research: a cohort study

ObjectiveTo assess the time to publication of primary research and evidence syntheses funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme published as a monograph in Health Technology Assessment and as a journal article in the wider biomedical literature.Study designRetrospective cohort study.SettingPrimary research and evidence synthesis projects funded by the HTA Programme were included in the cohort if they were registered in the NIHR research programmes database and was planned to submit the draft final report for publication in Health Technology Assessment on or before 9 December 2011.Main outcome measuresThe median time to publication and publication at 30?months in Health Technology Assessment and in an external journal were determined by searching the NIHR research programmes database and HTA Programme website.ResultsOf 458 included projects, 184 (40.2%) were primary research projects and 274 (59.8%) were evidence syntheses. A total of 155 primary research projects had a completion date; the median time to publication was 23?months (26.5 and 35.5?months to publish a monograph and to publish in an external journal, respectively) and 69% were published within 30?months. The median time to publication of HTA-funded trials (n=126) was 24?months and 67.5% were published within 30?months. Among the evidence syntheses with a protocol online date (n=223), the median time to publication was 25.5?months (28?months to publication as a monograph), but only 44.4% of evidence synthesis projects were published in an external journal. 65% of evidence synthesis studies had been published within 30.0?months.ConclusionsResearch funded by the HTA Programme publishes promptly. The importance of Health Technology Assessment was highlighted as the median time to publication was 9?months shorter for a monograph than an external journal article

Spacecraft drag-free technology development: On-board estimation and control synthesis

Estimation and control methods for a Drag-Free spacecraft are discussed. The functional and analytical synthesis of on-board estimators and controllers for an integrated attitude and translation control system is represented. The framework for detail definition and design of the baseline drag-free system is created. The techniques for solution of self-gravity and electrostatic charging problems are applicable generally, as is the control system development

Sea ice - atmosphere interaction: Application of multispectral satellite data in polar surface energy flux estimates

In the past six months, work has continued on energy flux sensitivity studies, ice surface temperature retrievals, corrections to Advanced Very High Resolution Radiometer (AVHRR) thermal infrared data, modelling of cloud fraction retrievals, and radiation climatologies. We tentatively conclude that the SSM/I may not provide accurate enough estimates of ice concentration and type to improve our shorter term energy flux estimates. SSM/I derived parameters may still be applicable in longer term climatological flux characterizations. We hold promise for a system coupling observation to a ice deformation model. Such a model may provide information on ice distribution which can be used in energy flux calculations. Considerable variation was found in modelled energy flux estimates when bulk transfer coefficients are modulated by lead fetch. It is still unclear what the optimum formulation is and this will be the subject of further work. Data sets for ice surface temperature retrievals were assembled and preliminary data analysis was started. Finally, construction of a conceptual framework for further modelling of the Arctic radiation flux climatology was started

Atlantic CFC data in CARINA

Water column data of carbon and carbon-relevant parameters have been collected and merged into a new database called CARINA (CARbon IN the Atlantic). In order to provide a consistent data set, all data have been examined for systematic biases and adjusted if necessary (secondary quality control (QC)). The CARINA data set is divided into three regions: the Arctic/Nordic Seas, the Atlantic region and the Southern Ocean. Here we present the CFC data for the Atlantic region, including the chlorofluorocarbons CFC-11, CFC-12 and CFC-113 as well as carbon tetrachloride (CCl4). The methods applied for the secondary quality control, a crossover analyses, the investigation of CFC ratios in the ocean and the CFC surface saturation are presented. Based on the results, the CFC data of some cruises are adjusted by a certain factor or given a “poor” quality flag

Sequential Adaptive Detection for In-Situ Transmission Electron Microscopy (TEM)

We develop new efficient online algorithms for detecting transient sparse signals in TEM video sequences, by adopting the recently developed framework for sequential detection jointly with online convex optimization [1]. We cast the problem as detecting an unknown sparse mean shift of Gaussian observations, and develop adaptive CUSUM and adaptive SSRS procedures, which are based on likelihood ratio statistics with post-change mean vector being online maximum likelihood estimators with $\ell_1$. We demonstrate the meritorious performance of our algorithms for TEM imaging using real data

Initial Results of a Silicon Sensor Irradiation Study for ILC Extreme Forward Calorimetry

Detectors proposed for the International Linear Collider (ILC) incorporate a tungsten sampling calorimeter (`BeamCal') intended to reconstruct showers of electrons, positrons and photons that emerge from the interaction point of the collider with angles between 5 and 50 milliradians. For the innermost radius of this calorimeter, radiation doses at shower-max are expected to reach 100 MRad per year, primarily due to minimum-ionizing electrons and positrons that arise in the induced electromagnetic showers of e+e- `beamstrahlung' pairs produced in the ILC beam-beam interaction. However, radiation damage to calorimeter sensors may be dominated by hadrons induced by nuclear interactions of shower photons, which are much more likely to contribute to the non-ionizing energy loss that has been observed to damage sensors exposed to hadronic radiation. We report here on the results of SLAC Experiment T-506, for which several different types of silicon diode sensors were exposed to doses of radiation induced by showering electrons of energy 3.5-10.6 GeV. By embedding the sensor under irradiation within a tungsten radiator, the exposure incorporated hadronic species that would potentially contribute to the degradation of a sensor mounted in a precision sampling calorimeter. Depending on sensor technology, efficient charge collection was observed for doses as large as 220 MRad.Comment: Talk presented at the International Workshop on Future Linear Colliders (LCWS13), Tokyo, Japan, 11-15 November 201

Exact Polynomial Eigenmodes for Homogeneous Spherical 3-Manifolds

Observational data hints at a finite universe, with spherical manifolds such as the Poincare dodecahedral space tentatively providing the best fit. Simulating the physics of a model universe requires knowing the eigenmodes of the Laplace operator on the space. The present article provides explicit polynomial eigenmodes for all globally homogeneous 3-manifolds: the Poincare dodecahedral space S3/I*, the binary octahedral space S3/O*, the binary tetrahedral space S3/T*, the prism manifolds S3/D_m* and the lens spaces L(p,1).Comment: v3. Final published version. 27 pages, 1 figur

Quality control procedures and methods of the CARINA database

Data on the carbon and carbon relevant hydrographic and hydrochemical parameters from previously not publicly available cruises in the Arctic, Atlantic and Southern Ocean have been retrieved and merged to a new data base: CARINA (CARbon IN the Atlantic). These data have gone through rigorous quality control (QC) procedures to assure the highest possible quality and consistency. All CARINA data were subject to primary QC; a process in which data are studied in order to identify outliers and obvious errors. Additionally, secondary QC was performed for several of the measured parameters in the CARINA data base. Secondary QC is a process in which the data are objectively studied in order to quantify systematic differences in the reported values. This process involved crossover analysis, and as a second step the offsets derived from the crossover analysis were used to calculate corrections of the parameters measured on individual cruises using least square models. Significant biases found in the data have been corrected in the data products, i.e. three merged data files containing measured, calculated and interpolated data for each of the three regions (i.e. Arctic Mediterranean Seas, Atlantic, and Southern Ocean). Here we report on the technical details of the quality control and on tools that have been developed and used during the project, including procedures for crossover analysis and least square models. Furthermore, an interactive website for uploading of results, plots, comments etc. was developed and was of critical importance for the success of the project, this is also described here