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

A New Meghimatium Slug (Pulmonata: Philomycidae) from Taiwan

Chi-Li Tsai and Shi-Kuei Wu (2008) A new Meghimatium slug (Pulmonata: Philomycidae) from Taiwan. Zoological Studies 47(6): 759-766. Meghimatium burchi sp. nov. is described based on its small size (12-16.5 mm in body length), and its genitalia with a uniquely expanded proximal end of the vas deferens. DNA sequence analysis within the family Philomycidae indicated that M. burchi belongs to the Taiwanese clade. Specimens of this new species were collected from the watershed of Koan-Tau Mt. of Huei-Sun Agriculture Farm in Taiwan's Central Mountain Range. The holotype is deposited at the National Museum of Natural Science, Taichung, Taiwan (catalog no. NMNS-4609-001). http://zoolstud.sinica.edu.tw/Journals/47.6/759.pd

Annealing Effect on the Microstructure and Mechanical Properties of a Thin Titanium Nitride Film

Titanium nitride (TiN) films were deposited by the D.C. magnetron sputtering process on a SUS 304 steel substrate. The effect of postdeposition annealing on the microstructure and mechanical properties of thin TiN films was studied in detail using atomic force microscopy, a potentiostat and nano-indentation tests. The TiN films were annealed at temperatures ranging from 100 to 300C. Surface roughnesses of TiN films estimated by atomic force microscopy decreased from 3.83 to 2.43 nm as the annealing temperatures increased from 100 to 300°C. The corrosion rates of the films measured by a potentionstat in a 0.5-molar H₂SO₄ solution decreased from 8.57•10⁻² to 4.59•10⁻² mmPY as the annealing temperatures increased from 100 to 300°C. An increase in corrosion resistance was attributed to an increase in hardness and a modulus of the film with the annealing temperature. Atomic force microscopy images of the film revealed fine-grained morphology for TiN films annealed at higher temperature. Experimental results show that the mechanical properties of TiN films could be significantly improved by annealing. The control of the annealing process was proved to be critical for the improvement of TiN film properties.Методом магнетронного напыления при постоянном токе на стальную подложку SUS 304 наносили нитрид-титановые пленки. Детально исследовано влияние отжига после нанесения пленок на микроструктуру и их механические свойства с помощью метода атомно-силовой микроскопии, стабилизатора напряжения и наноиндентирования. Нитрид-титановые пленки обжигали при температуре 100…300С. Шероховатость их поверхности, исследуемая методом атомно-силовой микроскопии, уменьшилась с 3,83 до 2,43 нм при повышении температуры отжига в интервале 100…300°С. Скорость коррозии пленок, измеренная с помощью стабилизатора напряжений в 0,5%-ном молярном растворе H₂SO₄, снизилась с 8,57•10⁻² до 4,59•10⁻² мм, тогда как температура отжига повысилась с 100 до 300°С. Рост коррозионной стойкости зависит от увеличения твердости и модуля упругости пленки с температурой отжига. Исследование пленки посредством метода атомно-силовой микроскопии показало, что нитрид титана, который обжигался при более высокой температуре, имеет мелкозернистую структуру. Установлено, что механические свойства нитрид-титановых пленок можно значительно улучшить путем отжига. Получил подтверждение тот факт, что контроль процесса отжига крайне необходим для усовершенствования свойств нитридтитановых пленок.Методом магнетронного напилення під дією постійного струму на стальну підкладку SUS 304 наносили нітрид-титанові плівки. Детально досліджено вплив відпалу після нанесення плівок на мікроструктуру та їх механічні властивості за допомогою методу атомно-силової мікроскопії, стабілізатора напруги і наноіндентування. Нітрид-титанові плівки випалювали за температури 100...300C. Шорсткість їхньої поверхні, що досліджувалася методом атомно-силової мікроскопії, зменшилася з 3,83 до 2,43 нм із підвищенням температури відпалу в інтервалі 100...300°С. Швидкість корозії плівок, яку вимірювали за допомогою стабілізатора напруги в 0,5%-ному молярному розчині H₂SO₄, зменшилася з 8,57•10⁻² до 4,59 •0⁻² мм, у той час як температура відпалу підвищилась із 100 до 300°C. Зростання корозійної стійкості залежить від збільшення твердості і модуля пружності плівки з температурою відпалу. Дослідження плівки за допомогою методу атомно-силової мікроскопії показало, що нітрид титану, який випалювався за більш високої температури, має дрібнозеренну структуру. Установлено, що механічні властивості нітрид-титанових плівок можна значно покращити шляхом відпалу. Отримав підтвердження той факт, що контроль процесу відпалу необхідний для удосконалення властивостей нітрид-титанових плівок