Gender’s Wider Stakes: Lay Attitudes to Legal Gender Reform

The Future of Legal Gender (FLaG) project is interested in examining the implications, for a wide range of stakeholders, of changing how legal sex/gender is regulated in England and Wales. In this article, we explore the views of ‘the wider public’ as manifest in responses to our ‘Attitudes to Gender’ survey (n=3,101), which ran in October to December 2018. Generally, respondents were invested in the status quo regarding a binary two-sex registration of gender close to birth. We discuss this finding with reference to cisgenderism and endosexism, focusing particularly on being critical of ‘gender’ and foregrounding biological sex, and views for and against self-identifying gender. In tandem, we also provide a critical commentary on the methodological positives and pitfalls associated with online survey research on a ‘topical’ issue. We suggest that cisgenderism could provide a less individualised framework for understanding different people’s hopes and worries with regard to both the current legal gender framework, and the possibility of reform.    &nbsp

Gene expression in BMPR2 mutation carriers with and without evidence of Pulmonary Arterial Hypertension suggests pathways relevant to disease penetrance

<p>Abstract</p> <p>Background</p> <p>While BMPR2 mutation strongly predisposes to pulmonary arterial hypertension (PAH), only 20% of mutation carriers develop clinical disease. This finding suggests that modifier genes contribute to FPAH clinical expression. Since modifiers are likely to be common alleles, this problem is not tractable by traditional genetic approaches. Furthermore, examination of gene expression is complicated by confounding effects attributable to drugs and the disease process itself.</p> <p>Methods</p> <p>To resolve these problems, B-cells were isolated, EBV-immortalized, and cultured from familial PAH patients with BMPR2 mutations, mutation positive but disease-free family members, and family members without mutation. This allows examination of differences in gene expression without drug or disease-related effects. These differences were assayed by Affymetrix array, with follow-up by quantitative RT-PCR and additional statistical analyses.</p> <p>Results</p> <p>By gene array, we found consistent alterations in multiple pathways with known relationship to PAH, including actin organization, immune function, calcium balance, growth, and apoptosis. Selected genes were verified by quantitative RT-PCR using a larger sample set. One of these, CYP1B1, had tenfold lower expression than control groups in female but not male PAH patients. Analysis of overrepresented gene ontology groups suggests that risk of disease correlates with alterations in pathways more strongly than with any specific gene within those pathways.</p> <p>Conclusion</p> <p>Disease status in BMPR2 mutation carriers was correlated with alterations in proliferation, GTP signaling, and stress response pathway expression. The estrogen metabolizing gene CYP1B1 is a strong candidate as a modifier gene in female PAH patients.</p

Do logarithmic proximity measures outperform plain ones in graph clustering?

We consider a number of graph kernels and proximity measures including commute time kernel, regularized Laplacian kernel, heat kernel, exponential diffusion kernel (also called "communicability"), etc., and the corresponding distances as applied to clustering nodes in random graphs and several well-known datasets. The model of generating random graphs involves edge probabilities for the pairs of nodes that belong to the same class or different predefined classes of nodes. It turns out that in most cases, logarithmic measures (i.e., measures resulting after taking logarithm of the proximities) perform better while distinguishing underlying classes than the "plain" measures. A comparison in terms of reject curves of inter-class and intra-class distances confirms this conclusion. A similar conclusion can be made for several well-known datasets. A possible origin of this effect is that most kernels have a multiplicative nature, while the nature of distances used in cluster algorithms is an additive one (cf. the triangle inequality). The logarithmic transformation is a tool to transform the first nature to the second one. Moreover, some distances corresponding to the logarithmic measures possess a meaningful cutpoint additivity property. In our experiments, the leader is usually the logarithmic Communicability measure. However, we indicate some more complicated cases in which other measures, typically, Communicability and plain Walk, can be the winners.Comment: 11 pages, 5 tables, 9 figures. Accepted for publication in the Proceedings of 6th International Conference on Network Analysis, May 26-28, 2016, Nizhny Novgorod, Russi

A Novel BMPR2 Mutation Associated with Pulmonary Arterial Hypertension in an Octogenarian

We describe the case of an 83-year-old man with a family history of pulmonary hypertension (PH) who presented with severe pulmonary arterial hypertension (PAH) and later tested positive for a novel bone morphogenetic protein receptor 2 (BMPR2) gene mutation. To our knowledge, this may be the oldest reported patient with PAH in whom a BMPR2 mutation was initially identified

Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

Background: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. Methods: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually or as a group across an entire gene for association to aging phenotypes using family based tests. Results: We found significant associations to three genes and nine single variants. Most notably, we found a novel variant significantly associated with exceptional survival in the 3' UTR OBFC1 in 13 individuals from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL). Conclusions: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants

Static fracture and modal analysis simulation of a gas turbine compressor blade and bladed disk system

This paper presents a methodology for conducting a 3-D static fracture analysis with applications to a gas turbine compressor blade. An open crack model is considered in the study and crack-tip driving parameters are estimated by using 3-D singular crack-tip elements in ANSYS. The static fracture analysis is verified with a special purpose fracture code (FRANC3D). Once the crack front is perfectly defined and validated, a free vibration study is conducted by analyzing the natural frequencies and modeshapes for both a single blade and bladed disk system. Taking advantage of high performance computing resources, a high fidelity finite element model is considered in the parametric investigation. In the fracture simulation, the influence of the size of a single edged crack as well as the rotational velocity on fracture parameters (stress intensity factors and J-Integral) are evaluated. Results demonstrate that for the applied loading condition, a mixed mode crack propagation is expected. In the modal analysis study, increasing the depth of the crack leads to a decrease in the natural frequencies of both the single blade and bladed disk system, while increasing the rotational velocity increases the natural frequencies. The presence of a crack also leads to mode localization for all mode families, a phenomenon that cannot be captured by a single blade analysis.The authors gratefully acknowledge the support of the Qatar National Research Fund through Grant number NPRP 7-1153-2-432. The authors also thank Texas A&M at Qatar?s Advanced Scientific Computing (TASC) for access to the RAAD Supercomputer.Scopu