Cell lineage-specific mitochondrial resilience during mammalian organogenesis

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments

Incidence of metachronous contralateral breast cancer in the Canton of Zurich: a population-based study of the cancer registry

PURPOSE To examine the incidence and characteristics of metachronous contralateral breast cancer (CBC) among women in the Canton of Zurich, Switzerland. METHODS For 1980-2006, patients with unilateral invasive breast cancer (UBC) were analysed for metachronous CBC. Poisson's regression was used to estimate incidence rates of metachronous CBC according to age, year of diagnosis, follow-up period since first breast cancer and morphology. RESULTS Of 16,323 patients with UBC, 700 (4.3 %) developed a second malignant tumour of the opposite breast. Median age at first breast cancer was lower in the CBC group than in the full cohort. Median interval time between first and second breast cancer was 5.5 (interquartile range 2.6-10.1) years. Incidence rate at age 20-29 was 1006 (95 % confidence interval, CI, 452-2238) cases per 100,000 person-years and decreased to 299 (199-450) at 80-84. Age-adjusted incidence rates according to period of diagnosis decreased from 618 (530-721) for 1980-1984 to 329 (217-500) cases per 100,000 person-years for 2005-2006. Incidence rate ratio of CBC for lobular carcinoma was 1.28 (95 % CI 0.99-1.67) adjusted by age group and period of diagnosis compared to ductal carcinoma. CONCLUSIONS In our study, incidence rates for CBC are comparable with findings from the literature. A reduction in the incidence of metachronous CBC, thought to be due to adjuvant therapies, is seen in our data. In our cohort, younger age and lobular carcinoma were associated with an increased risk of CBC

Micro-structuring of glassy carbon for precision glass molding of binary diffractive optical elements

Precision glass molding is a more cost efficient process for the large volume manufacturing of highly complex optical surfaces than direct manufacturing. Glassy carbon (GC) molds are used for precision glass molding, because they can be operated at temperatures up to 2000°C. Used today mainly for manufacturing aspheric lenses, we consider here material technology for diffractive optical element (DOE). For diffractive optics the surface structuring is in the micrometer range and a surface roughness Ra lower than 20 nm is required. We introduce a reactive ion etching process with a titanium hard mask. Fused silica (FS) molds with identical optical functionality were fabricated for comparison. All molds were used for precision glass molding of a low Tg glass L-BAL42. We will compare GC and FS as mold materials in terms of quality and robustness. Optical performance measurements of the molded glass DOEs are shown and are in good agreement with the theoretical predictions. The results confirm that precision glass molding based on GC molds is a very promising technology to economically fabricate small structures in glass for DOEs.OP

Multilevel micro-structuring of glassy carbon for precision glass molding of diffractive optical elements

A consumer market for diffractive optical elements in glass can only be created if high efficient elements are available at affordable prices. In diffractive optics the efficiency and optical properties increases with the number of levels used, but in the same way the costs are multiplied by the number if fabrication steps. Replication of multilevel diffractive optical elements in glass would allow cost efficient fabrication but a suitable mold material is needed. Glassy carbon shows a high mechanical strength, thermal stability and non-sticking adhesion properties, which makes it an excellent candidate as mold material for precision compression molding of low and high glass-transition temperature materials. We introduce an 8 level micro structuring process for glassy carbon molds with standard photolithography and a Ti layer as hard mask for reactive ion etching. The molds were applied to thermal imprinting onto low and high transition temperature glass. Optical performance was tested for the molded samples with different designs for laser beamsplitters. The results show a good agreement to the design specification. Our result allow us to show limitations of our fabrication technique and we discussed the suitability of precision glass molding for cost efficient mass production with a high quality

Cell lineage-specific mitochondrial resilience during mammalian organogenesis.

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments

Behavioral Response in the Immediate Aftermath of Shaking: Earthquakes in Christchurch and Wellington, New Zealand, and Hitachi, Japan

This study examines people’s response actions in the first 30 min after shaking stopped following earthquakes in Christchurch and Wellington, New Zealand, and Hitachi, Japan. Data collected from 257 respondents in Christchurch, 332 respondents in Hitachi, and 204 respondents in Wellington revealed notable similarities in some response actions immediately after the shaking stopped. In all four events, people were most likely to contact family members and seek additional information about the situation. However, there were notable differences among events in the frequency of resuming previous activities. Actions taken in the first 30 min were weakly related to: demographic variables, earthquake experience, contextual variables, and actions taken during the shaking, but were significantly related to perceived shaking intensity, risk perception and affective responses to the shaking, and damage/infrastructure disruption. These results have important implications for future research and practice because they identify promising avenues for emergency managers to communicate seismic risks and appropriate responses to risk area populations