An approximate spin design criterion for monoplanes, 1 May 1939

An approximate empirical criterion, based on the projected side area and the mass distribution of the airplane, was formulated. The British results were analyzed and applied to American designs. A simpler design criterion, based solely on the type and the dimensions of the tail, was developed; it is useful in a rapid estimation of whether a new design is likely to comply with the minimum requirements for safety in spinning

Direct Measurement of 2D and 3D Interprecipitate Distance Distributions from Atom-Probe Tomographic Reconstructions

Edge-to-edge interprecipitate distance distributions are critical for predicting precipitation strengthening of alloys and other physical phenomena. A method to calculate this 3D distance and the 2D interplanar distance from atom-probe tomographic data is presented. It is applied to nanometer-sized Cu-rich precipitates in an Fe-1.7 at.% Cu alloy. Experimental interprecipitate distance distributions are discussed

Differential Effects of the Hormonal and Copper Intrauterine Device on the Endometrial Transcriptome.

The contraceptive effectiveness of intrauterine devices (IUDs) has been attributed in part to a foreign body reaction in the endometrium. We performed this study to better understand mechanisms of action of contraceptives of by studying their effects on endometrial and cervical transcriptomes. We collected endometrial and cervical biopsies from women using the levonorgestrel-releasing intrauterine system (LNG-IUS, n = 11), copper intrauterine device (cu-IUD, n = 13) or levonorgestrel-containing combined oral contraceptives (COC, n = 12), and from women not using contraceptives (control group, n = 11). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. In endometrial samples from cu-IUD users, there were no genes with statistically significant differential expression compared to controls. In LNG-IUS users, 2509 genes were differentially expressed and mapped predominantly onto immune and inflammatory pathways. The cervical samples showed no statistically significant differential gene expression compared to controls. Hormonal and copper IUDs have significantly different effects on the endometrial transcriptome, with the LNG-IUS transcriptome showing pronounced inflammation and immune activation compared to controls whereas the cu-IUD transcriptome was indistinguishable from luteal phase endometrium. These findings argue against a foreign body reaction as a common mechanism of action of IUDs

Structure and Growth of Core–shell Nanoprecipitates in Al–Er–Sc–Zr–V–Si High-temperature Alloys

Lightweight Sc-containing aluminum alloys exhibit superior mechanical performance at high temperatures due to core–shell, L12-ordered trialuminide nanoprecipitates. In this study, the structure of these nanoprecipitates was studied, using different transmission electron microscopy (TEM) techniques, for an Al–Er– Sc–Zr–V–Si alloy that was subjected to a two-stage overaging heat treatment. Energy-dispersive X-ray spectroscopy of the spherical Al3(Sc, Zr, Er ,V) nanoprecipitates revealed a core–shell structure with an Sc- and Er-enriched core and a Zr-enriched shell, without a clear V outer shell. This structure is stable up to 72% of the absolute melting temperature of Al for extended periods of time. High-angle annular dark-field scanning TEM was used to image the {100} planes of the nanoprecipitates, demonstrating a homogeneous L12-ordered superlattice structure for the entire nanoprecipitates, despite the variations in the concentrations of solute atoms within the unit cells. A possible growth path and compositional trajectory for these nanoprecipitates was proposed using high-resolution TEM observations, where different rod-like structural defects were detected, which are considered to be precursors to the spherical L12-ordered nanoprecipitates. It is also hypothesized that the structural defects could consist of segregated Si; however, this was not possible to verify with HAADF-STEM because of the small differences in Al and Si atomic numbers. The results herein allow a better understanding of how the Al–Sc alloys’ core–shell nanoprecipitates form and evolve temporally, thereby providing a better physical picture for future atomistic structural mappings and simulations

Piecewise smooth systems near a co-dimension 2 discontinuity manifold: can one say what should happen?

We consider a piecewise smooth system in the neighborhood of a co-dimension 2 discontinuity manifold $\Sigma$. Within the class of Filippov solutions, if $\Sigma$ is attractive, one should expect solution trajectories to slide on $\Sigma$. It is well known, however, that the classical Filippov convexification methodology is ambiguous on $\Sigma$. The situation is further complicated by the possibility that, regardless of how sliding on $\Sigma$ is taking place, during sliding motion a trajectory encounters so-called generic first order exit points, where $\Sigma$ ceases to be attractive. In this work, we attempt to understand what behavior one should expect of a solution trajectory near $\Sigma$ when $\Sigma$ is attractive, what to expect when $\Sigma$ ceases to be attractive (at least, at generic exit points), and finally we also contrast and compare the behavior of some regularizations proposed in the literature. Through analysis and experiments we will confirm some known facts, and provide some important insight: (i) when $\Sigma$ is attractive, a solution trajectory indeed does remain near $\Sigma$, viz. sliding on $\Sigma$ is an appropriate idealization (of course, in general, one cannot predict which sliding vector field should be selected); (ii) when $\Sigma$ loses attractivity (at first order exit conditions), a typical solution trajectory leaves a neighborhood of $\Sigma$; (iii) there is no obvious way to regularize the system so that the regularized trajectory will remain near $\Sigma$ as long as $\Sigma$ is attractive, and so that it will be leaving (a neighborhood of) $\Sigma$ when $\Sigma$ looses attractivity. We reach the above conclusions by considering exclusively the given piecewise smooth system, without superimposing any assumption on what kind of dynamics near $\Sigma$ (or sliding motion on $\Sigma$) should have been taking place.Comment: 19 figure

Effects of Nb and Ta additions on the strength and coarsening resistance of precipitation-strengthened Al-Zr-Sc-Er-Si alloys

A dilute Al-0.07Zr-0.02Sc-0.005Er-0.06Si (at.%) alloy was microalloyed with 0.08 at.% Nb or Ta. Atom-probe tomography reveals that, upon aging, Nb and Ta partition to the coherent L12-Al3(Zr,Sc,Er) nanoprecipitates (with average concentrations of 0.2 and 0.08 at.%, respectively), with both segregating at the matrix/nanoprecipitate heterophase interface. This is consistent with the Nb- and Ta-modified alloys exhibiting, as compared to the unmodified alloy: (i) higher peak microhardness, from a higher nanoprecipitate volume fraction and/or lattice parameter mismatch; and (ii) improved aging resistance, from slower nanoprecipitate coarsening due to the small diffusivities of niobium and tantalum in aluminum. Analogous results were previously reported for a V-modified alloy

Functional Effects of the TMEM43 Ser358Leu Mutation in the Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy

Background: The Ser358Leu mutation in TMEM43, encoding an inner nuclear membrane protein, has been implicated in arrhythmogenic right ventricular cardiomyopathy (ARVC). The pathogenetic mechanisms of this mutation are poorly understood. Methods: To determine the frequency of TMEM43 mutations as a cause of ARVC, we screened 11 ARVC families for mutations in TMEM43 and five desmosomal genes previously implicated in the disease. Functional studies were performed in COS-7 cells transfected with wildtype, mutant, and 1:2 wildtype:mutant TMEM43 to determine the effect of the Ser358Leu mutation on the stability and cellular localization of TMEM43 and other nuclear envelope and desmosomal proteins, assessed by solubility assays and immunofluorescence imaging. mRNA expression was assessed of genes potentially affected by dysfunction of the nuclear lamina. Results: Three novel mutations in previously documented desmosomal genes, but no mutations in TMEM43, were identified. COS-7 cells transfected with mutant TMEM43 exhibited no change in desmosomal stability. Stability and nuclear membrane localization of mutant TMEM43 and of lamin B and emerin were normal. Mutant TMEM43 did not alter the expression of genes located on chromosome 13, previously implicated in nuclear envelope protein mutations leading to skeletal muscular dystrophies. Conclusions: Mutant TMEM43 exhibits normal cellular localization and does not disrupt integrity and localization of other nuclear envelope and desmosomal proteins. The pathogenetic role of TMEM43 mutations in ARVC remains uncertain

EM-mosaic detects mosaic point mutations that contribute to congenital heart disease.

BackgroundThe contribution of somatic mosaicism, or genetic mutations arising after oocyte fertilization, to congenital heart disease (CHD) is not well understood. Further, the relationship between mosaicism in blood and cardiovascular tissue has not been determined.MethodsWe developed a new computational method, EM-mosaic (Expectation-Maximization-based detection of mosaicism), to analyze mosaicism in exome sequences derived primarily from blood DNA of 2530 CHD proband-parent trios. To optimize this method, we measured mosaic detection power as a function of sequencing depth. In parallel, we analyzed our cohort using MosaicHunter, a Bayesian genotyping algorithm-based mosaic detection tool, and compared the two methods. The accuracy of these mosaic variant detection algorithms was assessed using an independent resequencing method. We then applied both methods to detect mosaicism in cardiac tissue-derived exome sequences of 66 participants for which matched blood and heart tissue was available.ResultsEM-mosaic detected 326 mosaic mutations in blood and/or cardiac tissue DNA. Of the 309 detected in blood DNA, 85/97 (88%) tested were independently confirmed, while 7/17 (41%) candidates of 17 detected in cardiac tissue were confirmed. MosaicHunter detected an additional 64 mosaics, of which 23/46 (50%) among 58 candidates from blood and 4/6 (67%) of 6 candidates from cardiac tissue confirmed. Twenty-five mosaic variants altered CHD-risk genes, affecting 1% of our cohort. Of these 25, 22/22 candidates tested were confirmed. Variants predicted as damaging had higher variant allele fraction than benign variants, suggesting a role in CHD. The estimated true frequency of mosaic variants above 10% mosaicism was 0.14/person in blood and 0.21/person in cardiac tissue. Analysis of 66 individuals with matched cardiac tissue available revealed both tissue-specific and shared mosaicism, with shared mosaics generally having higher allele fraction.ConclusionsWe estimate that ~ 1% of CHD probands have a mosaic variant detectable in blood that could contribute to cardiac malformations, particularly those damaging variants with relatively higher allele fraction. Although blood is a readily available DNA source, cardiac tissues analyzed contributed ~ 5% of somatic mosaic variants identified, indicating the value of tissue mosaicism analyses