CRYP-2/cPTPRO is a neurite inhibitory repulsive guidance cue for retinal neurons in vitro

Receptor protein tyrosine phosphatases (RPTPs) are implicated as regulators of axon growth and guidance. Genetic deletions in the fly have shown that type III RPTPs are important in axon pathfinding, but nothing is known about their function on a cellular level. Previous experiments in our lab have identified a type III RPTP, CRYP-2/cPTPRO, specifically expressed during the period of axon outgrowth in the chick brain; cPTPRO is expressed in the axons and growth cones of retinal and tectal projection neurons. We constructed a fusion protein containing the extracellular domain of cPTPRO fused to the Fc portion of mouse immunoglobulin G-1, and used it to perform in vitro functional assays. We found that the extracellular domain of cPTPRO is an antiadhesive, neurite inhibitory molecule for retinal neurons. In addition, cPTPRO had potent growth cone collapsing activity in vitro, and locally applied gradients of cPTPRO repelled growing retinal axons. This chemorepulsive effect could be regulated by the level of cGMP in the growth cone. Immunohistochemical examination of the retina indicated that cPTPRO has at least one heterophilic binding partner in the retina. Taken together, our results indicate that cPTPRO may act as a guidance cue for retinal ganglion cells during vertebrate development

New freshwater diatom genus, Edtheriotia gen. nov. of the Stephanodiscaceae (Bacillariophyta) from south‐central China

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134437/1/pre12145.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134437/2/pre12145_am.pd

The wall shear rate distribution for flow in random sphere packings

The wall shear rate distribution P(gamma) is investigated for pressure-driven Stokes flow through random arrangements of spheres at packing fractions 0.1 <= phi <= 0.64. For dense packings, P(gamma) is monotonic and approximately exponential. As phi --> 0.1, P(gamma) picks up additional structure which corresponds to the flow around isolated spheres, for which an exact result can be obtained. A simple expression for the mean wall shear rate is presented, based on a force-balance argument.Comment: 4 pages, 3 figures, 1 table, RevTeX 4; significantly revised with significantly extended scop

Bony canal and grooves of the middle meningeal artery: mythic structures in anatomy and neurosurgery?

Background: It has been previously published that the frontal branch of the middle meningeal artery (MMA) is usually embedded in a bony canal (BC). Although the incidence of the BC was over 70%, this structure is currently omitted both in anatomical nomenclature and in most of the literature. We found the same gap pertaining to the grooves for the MMA on the skull base. The aims of our study were to assess the incidence and morphometry of the MMA BC and grooves on the skull base. Materials and methods: Computed tomography (CT) scans of 378 patients, 172 skull bases as well as 120 sphenoidal bones and 168 temporal bones, and 12 histological specimens from 3 men and 3 women and 3 different regions of the MMA course were assessed. Results: Based on CT scans, the incidence of the BC was 85.44% and was significantly higher in females than in males. Most of the canals and grooves were bilateral. The mean canal length was 17.67 mm, the mean transverse diameter 1.33 mm, and the mean distance from the superior orbital fissure (dFOS) was 26.7 mm. In the skull bases, the BC incidence was 70.07%, the mean canal length 10.74 mm, and the mean dFOS was 19.16 mm. The groove for the MMA on the temporal and sphenoidal bones was present in 99.42% and 95.35%, respectively. Histological specimens confirmed the presence of the MMA and accompanying vein/s. Conclusions: Based on our results, we suggest the addition of the BC and grooves for the middle meningeal vessels to the upcoming version of the Terminologia Anatomica

Research Activities for the DORIS Contribution to the Next International Terrestrial Reference Frame

For the preparation of ITRF2008, the IDS processed data from 1993 to 2008, including data from TOPEX/Poseidon, the SPOT satellites and Envisat in the weekly solutions. Since the development of ITRF2008, the IDS has been engaged in a number of efforts to try and improve the reference frame solutions. These efforts include (i) assessing the contribution of the new DORIS satellites, Jason-2 and Cryosat2 (2008-2011), (ii) individually analyzing the DORIS satellite contributions to geocenter and scale, and (iii) improving orbit dynamics (atmospheric loading effects, satellite surface force modeling. . . ). We report on the preliminary results from these research activities, review the status of the IDS combination which is now routinely generated from the contributions of the IDS analysis centers, and discuss the prospects for continued improvement in the DORIS contribution to the next international reference frame

PIK3CA mutations in advanced cancers: characteristics and outcomes.

PIK3CA mutations are frequently diagnosed in diverse cancers and may predict response to PI3K/AKT/mTOR inhibitors. It remains unclear whether they are associated with other characteristics. We analyzed characteristics and outcome of 90 consecutive patients with diverse advanced tumors and PIK3CA mutations and 180 wild-type PIK3CA controls matched by tumor type, gender, and age referred to the Clinical Center for Targeted Therapy. PIK3CA and MAPK mutations (KRAS, NRAS, and BRAF) were analyzed using polymerase chain reaction-based DNA sequencing. The most frequent PIK3CA mutations were E545K (31/90, 34%), E542K (16/90, 18%) in exon 9, and H1047R (20/90, 22%) in exon 20. PIK3CA mutations compared to wild-type PIK3CA were associated with simultaneous KRAS (p=0.047) and MAPK mutations (p=0.03), but only MAPK mutations were confirmed as having an independent association in multivariate analysis. Rates of lung, bone, liver and brain metastases were similar in PIK3CA-mutant and wild-type patients. Patients with PIK3CA mutations treated on trials with PI3K/AKT/mTOR inhibitors had a higher partial/complete response (PR/CR) rate than wild-type PIK3CA patients treated with their best phase I therapy (10/56, 18% vs. 12/152, 8%; p=0.045), but not a prolonged progression-free survival. Patients with H1047R PIK3CA mutations had higher PR/CR rate with PI3K/AKT/mTOR inhibitors compared to wild-type PIK3CA patients treated with their best phase I therapy (6/16, 38% vs. 12/152, 8%; p=0.003). In conclusion, PIK3CA mutations in diverse cancers were not associated with clinical characteristics, but were correlated with MAPK mutations. PIK3CA mutations, especially, H1047R, were associated with attaining a PR/CR to PI3K/AKT/mTOR pathway inhibitors

MOSFET dosimetry for microbeam radiation therapy at the European Synchrotron Radiation Facility

Preclinical experiments are carried out with ~20–30 μm wide, ~10 mm high parallel microbeams of hard, broad-‘‘white’’-spectrum x rays (~50–600 keV) to investigate microbeam radiation therapy (MRT) of brain tumors in infants for whom other kinds of radiotherapy are inadequate and/or unsafe. Novel physical microdosimetry (implemented with MOSFET chips in the ‘‘edge-on’’ mode) and Monte Carlo computer-simulated dosimetry are described here for selected points in the peak and valley regions of a microbeam-irradiated tissue-equivalent phantom. Such microbeam irradiation causes minimal damage to normal tissues, possible because of rapid repair of their microscopic lesions. Radiation damage from an array of parallel microbeams tends to correlate with the range of peak-valley dose ratios (PVDR). This paper summarizes comparisons of our dosimetric MOSFET measurements with Monte Carlo calculations. Peak doses at depths \u3c22 mm are 18% less than Monte Carlo values, whereas those depths \u3e22 mm and valley doses at all depths investigated (2 mm–62 mm) are within 2–13% of the Monte Carlo values. These results lend credence to the use of MOSFET detector systems in edge-on mode for microplanar irradiation dosimetry

Large-scale features of Pliocene climate: results from the Pliocene Model Intercomparison Project

Climate and environments of the mid-Pliocene warm period (3.264 to 3.025 Ma) have been extensively studied. Whilst numerical models have shed light on the nature of climate at the time, uncertainties in their predictions have not been systematically examined. The Pliocene Model Intercomparison Project quantifies uncertainties in model outputs through a coordinated multi-model and multi-model/data intercomparison. Whilst commonalities in model outputs for the Pliocene are clearly evident, we show substantial variation in the sensitivity of models to the implementation of Pliocene boundary conditions. Models appear able to reproduce many regional changes in temperature reconstructed from geological proxies. However, data/model comparison highlights that models potentially underestimate polar amplification. To assert this conclusion with greater confidence, limitations in the time-averaged proxy data currently available must be addressed. Furthermore, sensitivity tests exploring the known unknowns in modelling Pliocene climate specifically relevant to the high latitudes are essential (e.g. palaeogeography, gateways, orbital forcing and trace gasses). Estimates of longer-term sensitivity to CO2 (also known as Earth System Sensitivity; ESS), support previous work suggesting that ESS is greater than Climate Sensitivity (CS), and suggest that the ratio of ESS to CS is between 1 and 2, with a "best" estimate of 1.5

The event generator DECAY4 for simulation of double beta processes and decay of radioactive nuclei

The computer code DECAY4 is developed to generate initial energy, time and angular distributions of particles emitted in radioactive decays of nuclides and nuclear (atomic) deexcitations. Data for description of nuclear and atomic decay schemes are taken from the ENSDF and EADL database libraries. The examples of use of the DECAY4 code in several underground experiments are described.Comment: 8 pages, 1 fi