Fos co-operation with PTEN loss elicits keratoacanthoma not carcinoma due to p53/p21^WAF-induced differentiation triggered by GSK3b inactivation and reduced AKT activity

To investigate gene synergism in multistage skin carcinogenesis, the RU486-inducible cre/lox system was employed to ablate PTEN function [K14.cre/D5PTENflx] in mouse epidermis expressing activated v-fos [HK1.fos]. RU486-treated HK1.fos/D5PTENflx mice exhibited hyperplasia, hyperkeratosis and tumours that progressed to highly differentiated keratoacanthomas rather than carcinomas, due to re-expression of high p53 and p21WAF levels. Despite elevated MAP kinase activity, cyclin D1/E2 over expression and increased AKT activity forming areas of highly proliferative, papillomatous keratinocytes, increasing levels of GSK3b inactivation exceeded a threshold that induced p53/p21WAF expression to halt proliferation and accelerate differentiation, giving the hallmark keratosis of keratoacanthomas. A pivotal facet to this GSK3b-triggered mechanism centred on increasing p53 expression in basal layer keratinocytes. This reduced activated AKT expression and released inhibition of p21WAF, which accelerated keratinocyte differentiation, as indicated by unique basal layer expression of differentiation-specific keratin K1, alongside premature filaggrin and loricrin expression. Thus, fos synergism with PTEN loss elicited a benign tumour context where GSK3b-induced, p53/p21WAF expression continually switched AKT-associated proliferation into one of differentiation, preventing further progression. This putative compensatory mechanism required the critical availability of normal p53 and/or p21WAF otherwise deregulated fos, Akt and GSK3b associate with malignant progression

Rate of undesirable events at beginning of academic year: retrospective cohort study.

OBJECTIVE: To determine whether an increase in the rate of undesirable events occurs after care provided by trainees at the beginning of the academic year. DESIGN: Retrospective cohort study using administrative and patient record data. SETTING: University affiliated hospital in Melbourne, Australia. PARTICIPANTS: 19,560 patients having an anaesthetic procedure carried out by first to fifth year trainees starting work for the first time at the hospital over a period of five years (1995-2000). MAIN OUTCOME MEASURES: Absolute event rates, absolute rate reduction, and rate ratios of undesirable events. RESULTS: The rate of undesirable events was higher at the beginning of the academic year compared with the rest of the year (absolute event rate 137 v 107 per 1000 patient hours, relative rate reduction 28%, P<0.001). The overall adjusted rate ratio for undesirable events was 1.40, 95% confidence interval 1.24 to 1.58. This excess risk was seen for all residents, regardless of their level of seniority. The excess risk decreased progressively after the first month, and the trend disappeared fully after the fourth month of the year (rate ratio for fourth month 1.21, 0.93 to 1.57). The most important decreases were for central and peripheral nerve injuries (relative difference 82%), inadequate oxygenation of the patient (66%), vomiting/aspiration in theatre (53%), and technical failures of tracheal tube placement (49%). CONCLUSIONS: The rate of undesirable events was greater among trainees at the beginning of the academic year regardless of their level of clinical experience. This suggests that several additional factors, such as knowledge of the working environment, teamwork, and communication, may contribute to the increase

Gene-flow between populations of cotton bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) is highly variable between years

Both large and small scale migrations of Helicoverpa armigera Hübner in Australia were investigated using AMOVA analysis and genetic assignment tests. Five microsatellite loci were screened across 3142 individuals from 16 localities in eight major cotton and grain growing regions within Australia, over a 38-month period (November 1999 to January 2003). From November 1999 to March 2001 relatively low levels of migration were characterized between growing regions. Substantially higher than average gene-flow rates and limited differentiation between cropping regions characterized the period from April 2001 to March 2002. A reduced migration rate in the year from April 2002 to March 2003 resulted in significant genetic structuring between cropping regions. This differentiation was established within two or three generations. Genetic drift alone is unlikely to drive genetic differentiation over such a small number of generations, unless it is accompanied by extreme bottlenecks and/or selection. Helicoverpa armigera in Australia demonstrated isolation by distance, so immigration into cropping regions is more likely to come from nearby regions than from afar. This effect was most pronounced in years with limited migration. However, there is evidence of long distance dispersal events in periods of high migration (April 2001–March 2002). The implications of highly variable migration patterns for resistance management are considered.K.D. Scott, K.S. Wilkinson, N. Lawrence, C.L. Lange, L.J. Scott, M.A. Merritt, A.J. Lowe and G.C Graha

Interaction of CO2 laser-modified nylon with osteoblast cells in relation to wettability

It has been amply demonstrated previously that CO2 lasers hold the ability to surface modify various polymers. In addition, it has been observed that these surface enhancements can augment the biomimetic nature of the laser irradiated materials. This research has employed a CO2 laser marker to produce trench and hatch topographical patterns with peak heights of around 1 μm on the surface of nylon 6,6. The patterns generated have been analysed using white light interferometery, optical microscopy and X-ray photoelectron spectroscopy was employed to determine the surface oxygen content. Contact angle measurements were used to characterize each sample in terms of wettability. Generally, it was seen that as a result of laser processing the contact angle, surface roughness and surface oxygen content increased whilst the apparent polar and total surface energies decreased. The increase in contact angle and reduction in surface energy components was found to be on account of a mixed intermediate state wetting regime owing to the change in roughness due to the induced topographical patterns. To determine the biomimetic nature of the modified and as-received control samples each one was seeded with 2×104 cells/ml normal human osteoblast cells and observed after periods of 24 hours and 4 days using optical microscopy and SEM to determine mean cell cover densities and variations in cell morphology. In addition a haeymocytometer was used to show that the cell count for the laser patterned samples had increased by up to a factor of 1.5 compared to the as-received control sample after 4 days of incubation. Significantly, it was determined that all laser-induced patterns gave rise to better cell response in comparison to the as-received control sample studied due to increased preferential cell growth on those surfaces with increased surface roughness

Generalized conductance sum rule in atomic break junctions

When an atomic-size break junction is mechanically stretched, the total conductance of the contact remains approximately constant over a wide range of elongations, although at the same time the transmissions of the individual channels (valence orbitals of the junction atom) undergo strong variations. We propose a microscopic explanation of this phenomenon, based on Coulomb correlation effects between electrons in valence orbitals of the junction atom. The resulting approximate conductance quantization is closely related to the Friedel sum rule.Comment: 4 pages, 1 figure, appears in Proceedings of the NATO Advanced Research Workshop ``Size dependent magnetic scattering'', Pecs, Hungary, May 28 - June 1, 200

D-optimal designs via a cocktail algorithm

A fast new algorithm is proposed for numerical computation of (approximate) D-optimal designs. This "cocktail algorithm" extends the well-known vertex direction method (VDM; Fedorov 1972) and the multiplicative algorithm (Silvey, Titterington and Torsney, 1978), and shares their simplicity and monotonic convergence properties. Numerical examples show that the cocktail algorithm can lead to dramatically improved speed, sometimes by orders of magnitude, relative to either the multiplicative algorithm or the vertex exchange method (a variant of VDM). Key to the improved speed is a new nearest neighbor exchange strategy, which acts locally and complements the global effect of the multiplicative algorithm. Possible extensions to related problems such as nonparametric maximum likelihood estimation are mentioned.Comment: A number of changes after accounting for the referees' comments including new examples in Section 4 and more detailed explanations throughou

The structure of superheavy elements newly discovered in the reaction of 86^{86}Kr with 208^{208}Pb

The structure of superheavy elements newly discovered in the $^{208}$Pb($^{86}$Kr,n) reaction at Berkeley is systematically studied in the Relativistic Mean Field (RMF) approach. It is shown that various usually employed RMF forces, which give fair description of normal stable nuclei, give quite different predictions for superheavy elements. Among the effective forces we tested, TM1 is found to be the good candidate to describe superheavy elements. The binding energies of the $^{293}$118 nucleus and its $\alpha-$decay daughter nuclei obtained using TM1 agree with those of FRDM within 2 MeV. Similar conclusion that TM1 is the good interaction is also drawn from the calculated binding energies for Pb isotopes with the Relativistic Continuum Hartree Bogoliubov (RCHB) theory. Using the pairing gaps obtained from RCHB, RMF calculations with pairing and deformation are carried out for the structure of superheavy elements. The binding energy, shape, single particle levels, and the Q values of the $\alpha-$decay $Q_{\alpha}$ are discussed, and it is shown that both pairing correlation and deformation are essential to properly understand the structure of superheavy elements. A good agreement is obtained with experimental data on $Q_{\alpha}$. %Especially, the atomic number %dependence of $Q_{\alpha}$ %seems to match with the experimental observationComment: 19 pages, 5 figure

Updated Bounds on Sum of Neutrino Masses in Various Cosmological Scenarios

We present strong bounds on the sum of three active neutrino masses ($\sum m_{\nu}$) in various cosmological models. We use the following baseline datasets: CMB temperature data from Planck 2015, BAO measurements from SDSS-III BOSS DR12, the newly released SNe Ia dataset from Pantheon Sample, and a prior on the optical depth to reionization from 2016 Planck Intermediate results. We constrain cosmological parameters in $\Lambda CDM$ model with 3 massive active neutrinos. For this $\Lambda CDM+\sum m_{\nu}$ model we find a upper bound of $\sum m_{\nu} <$ 0.152 eV at 95$\%$ C.L. Adding the high-$l$ polarization data from Planck strengthens this bound to $\sum m_{\nu} <$ 0.118 eV, which is very close to the minimum required mass of $\sum m_{\nu} \simeq$ 0.1 eV for inverted hierarchy. This bound is reduced to $\sum m_{\nu} <$ 0.110 eV when we also vary r, the tensor to scalar ratio ($\Lambda CDM+r+\sum m_{\nu}$ model), and add an additional dataset, BK14, the latest data released from the Bicep-Keck collaboration. This bound is further reduced to $\sum m_{\nu} <$ 0.101 eV in a cosmology with non-phantom dynamical dark energy ($w_0 w_a CDM+\sum m_{\nu}$ model with $w(z)\geq -1$ for all $z$). Considering the $w_0 w_a CDM+r+\sum m_{\nu}$ model and adding the BK14 data again, the bound can be even further reduced to $\sum m_{\nu} <$ 0.093 eV. For the $w_0 w_a CDM+\sum m_{\nu}$ model without any constraint on $w(z)$, the bounds however relax to $\sum m_{\nu} <$ 0.276 eV. Adding a prior on the Hubble constant ($H_0 = 73.24\pm 1.74$ km/sec/Mpc) from Hubble Space Telescope (HST), the above mentioned bounds further improve to $\sum m_{\nu} <$ 0.117 eV, 0.091 eV, 0.085 eV, 0.082 eV, 0.078 eV and 0.247 eV respectively. This substantial improvement is mostly driven by a more than 3$\sigma$ tension between Planck 2015 and HST measurements of $H_0$ and should be taken cautiously. (abstract abridged)Comment: 31 pages, 19 figures, matches published version in JCA

Exploring morphological correlations among H2CO, 12CO, MSX and continuum mappings

There are relatively few H2CO mappings of large-area giant molecular cloud (GMCs). H2CO absorption lines are good tracers for low-temperature molecular clouds towards star formation regions. Thus, the aim of the study was to identify H2CO distributions in ambient molecular clouds. We investigated morphologic relations among 6-cm continuum brightness temperature (CBT) data and H2CO (111-110; Nanshan 25-m radio telescope), 12CO (1--0; 1.2-m CfA telescope) and midcourse space experiment (MSX) data, and considered the impact of background components on foreground clouds. We report simultaneous 6-cm H2CO absorption lines and H110\alpha radio recombination line observations and give several large-area mappings at 4.8 GHz toward W49 (50'\times50'), W3 (70'\times90'), DR21/W75 (60'\times90') and NGC2024/NGC2023 (50'\times100') GMCs. By superimposing H2CO and 12CO contours onto the MSX color map, we can compare correlations. The resolution for H2CO, 12CO and MSX data was about 10', 8' and 18.3", respectively. Comparison of H2CO and 12CO contours, 8.28-\mu m MSX colorscale and CBT data revealed great morphological correlation in the large area, although there are some discrepancies between 12CO and H2CO peaks in small areas. The NGC2024/NGC2023 GMC is a large area of HII regions with a high CBT, but a H2CO cloud to the north is possible against the cosmic microwave background. A statistical diagram shows that 85.21% of H2CO absorption lines are distributed in the intensity range from -1.0 to 0 Jy and the \Delta V range from 1.206 to 5 km/s.Comment: 18 pages, 22 figures, 5 tables. Accepted to be published in Astrophysics and Space Scienc