Influence of Yttrium on the Thermal Stability of Ti-Al-N Thin Films

Ti(1-x)Al(x)N coated tools are commonly used in high-speed machining, where the cutting edge of an end-mill or insert is exposed to temperatures up to 1100 degrees C. Here, we investigate the effect of Yttrium addition on the thermal stability of Ti(1-x)Al(x)N coatings. Reactive DC magnetron sputtering of powder metallurgically prepared Ti(0.50)Al(0.50), Ti(0.49)Al(0.49)Y(0.02), and Ti(0.46)Al(0.46)Y(0.08) targets result in the formation of single-phase cubic (c) Ti(0.45)Al(0.55)N, binary cubic/wurtzite c/w-Ti(0.41)Al(0.57)Y(0.02)N and singe-phase w-Ti(0.38)Al(0.54)Y(0.08)N coatings. Using pulsed DC reactive magnetron sputtering for the Ti(0.49)Al(0.49)Y(0.02) target allows preparing single-phase c-Ti(0.46)Al(0.52)Y(0.02)N coatings. By employing thermal analyses in combination with X-ray diffraction and transmission electron microscopy investigations of as deposited and annealed (in He atmosphere) samples, we revealed that Y effectively retards the decomposition of the Ti(1-x-y)Al(x)Y(y)N solid-solution to higher temperatures and promotes the precipitation of c-TiN, c-YN, and w-AlN. Due to their different microstructure and morphology already in the as deposited state, the hardness of the coatings decreases from similar to 35 to 22 GPa with increasing Y-content and increasing wurtzite phase fraction. Highest peak hardness of similar to 38 GPa is obtained for the Y-free c-Ti(0.45)Al(0.55)N coating after annealing at T(a) = 950 degrees C, due to spinodal decomposition. After annealing above 1000 degrees C the highest hardness is obtained for the 2 mol % YN containing c-Ti(0.46)Al(0.52)Y(0.02)N coating with similar to 29 and 28 GPa for T(a) = 1150 and 1200 degrees C, respectively

The transformer2 gene in Musca domestica is required for selecting and maintaining the female pathway of development

We present the isolation and functional analysis of a transformer2 homologue Mdtra2 in the housefly Musca domestica. Compromising the activity of this gene by injecting dsRNA into embryos causes complete sex reversal of genotypically female individuals into fertile males, revealing an essential function of Mdtra2 in female development of the housefly. Mdtra2 is required for female-specific splicing of Musca doublesex (Mddsx) which structurally and functionally corresponds to Drosophila dsx, the bottom-most regulator in the sex-determining pathway. Since Mdtra2 is expressed in males and females, we propose that Mdtra2 serves as an essential co-factor of F, the key sex-determining switch upstream of Mddsx. We also provide evidence that Mdtra2 acts upstream as a positive regulator of F supporting genetic data which suggest that F relies on an autocatalytic activity to select and maintain the female path of development. We further show that repression of male courtship behavior by F requires Mdtra2. This function of F and Mdtra2 appears not to be mediated by Mddsx, suggesting that bifurcation of the pathway at this level is a conserved feature in the genetic architecture of Musca and Drosophil

High susceptibility to fatty liver disease in two-pore channel 2-deficient mice

Endolysosomal organelles play a key role in trafficking, breakdown and receptor-mediated recycling of different macromolecules such as low-density lipoprotein (LDL)-cholesterol, epithelial growth factor (EGF) or transferrin. Here we examine the role of two-pore channel (TPC) 2, an endolysosomal cation channel, in these processes. Embryonic mouse fibroblasts and hepatocytes lacking TPC2 display a profound impairment of LDL-cholesterol and EGF/EGF-receptor trafficking. Mechanistically, both defects can be attributed to a dysfunction of the endolysosomal degradation pathway most likely on the level of late endosome to lysosome fusion. Importantly, endolysosomal acidification or lysosomal enzyme function are normal in TPC2-deficient cells. TPC2-deficient mice are highly susceptible to hepatic cholesterol overload and liver damage consistent with non-alcoholic fatty liver hepatitis. These findings indicate reduced metabolic reserve of hepatic cholesterol handling. Our results suggest that TPC2 plays a crucial role in trafficking in the endolysosomal degradation pathway and, thus, is potentially involved in the homoeostatic control of many macromolecules and cell metabolites

Measurement of the Non-Common Vertex Error of a Double Corner Cube

ABSTRACT The Space Interferometry Mission (SIM) requires the control of the optical path of each interferometer with picometer accuracy. Laser metrology gauges are used to measure the path lengths to the fiiducial corner cubes at the siderostats. Due to the geometry of SIM a single corner cube does not have sufficient acceptance angle to work with all the gauges. Therefore SIM employs a double corner cube. Current fabrication methods are in fact not capable of producing such a double corner cube with vertices having sufficient commonality. The plan for SIM is to measure the non-commonalty of the vertices and correct for the error in orbit. SIM requires that the non-common vertex error (NCVE) of the double corner cube to be less than 6 µm. The required accuracy for the knowledge of the NCVE is less than 1 µm. This paper explains a method of measuring non-common vertices of a brassboard double corner cube with sub-micron accuracy. The results of such a measurement will be presented

Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice

ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts