The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Genetic variants in anti-Müllerian hormone-related genes and breast cancer risk: results from the AMBER consortium

Purpose: Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women. Methods: In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression. Results: After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89–0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85–0.90 for breast cancer overall and after menopause (p ≤ 0.02). Conclusions: The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies

Volunteerism, social context and health impacts: a qualitative study of Glasgow Commonwealth Games event volunteers

Volunteer engagement is crucial to the effective delivery of mega-sporting events. While evidence points to reported motivations and wellbeing benefits for individual participants during and post event, there is less evidence on how this type of civic participation relates to the social context in which it occurs and the wider social determinants of health. This qualitative study sought to understand impacts on wellbeing and the determinants of health resulting from the experience of volunteering at the Glasgow 2014 Commonwealth Games. Focus groups and interviews were conducted one-year post-Games to gather the perspectives of 46 volunteers and 7 unsuccessful applicants on their experiences. Participants provided insight into the volunteer journey, contributions and associated outcomes. Wider social impacts were also reported including a renewed sense of pride in the city. The qualitative analysis suggested an important non-linear relationship between volunteer contributions, impacts and rewards, and the outcome of enhanced social connections. The emergent ‘people and place’ framework identifies some critical factors around city life and volunteer assets that planners could consider in developing and evaluating sustainable volunteering and its wider impacts beyond a mega-event

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Nitric oxide and cyclic nucleotides: Their roles in junction dynamics and spermatogenesis

Spermatogenesis is a highly complicated process in which functional spermatozoa (haploid, 1n) are generated from primitive mitotic spermatogonia (diploid, 2n). This process involves the differentiation and transformation of several types of germ cells as spermatocytes and spermatids undergo meiosis and differentiation. Due to its sophistication and complexity, testis possesses intrinsic mechanisms to modulate and regulate different stages of germ cell development under the intimate and indirect cooperation with Sertoli and Leydig cells, respectively. Furthermore, developing germ cells must translocate from the basal to the apical (adluminal) compartment of the seminiferous epithelium. Thus, extensive junction restructuring must occur to assist germ cell movement. Within the seminiferous tubules, three principal types of junctions are found namely anchoring junctions, tight junctions, and gap junctions. Other less studied junctions are desmosome-like junctions and hemidesmosome junctions. With these varieties of junction types, testes are using different regulators to monitor junction turnover. Among the uncountable junction modulators, nitric oxide (NO) is a prominent candidate due to its versatility and extensive downstream network. NO is synthesized by nitric oxide synthase (NOS). Three traditional NOS, specified as endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS), and one testis-specific nNOS (TnNOS) are found in the testis. For these, eNOS and iNOS were recently shown to have putative junction regulation properties. More important, these two NOSs likely rely on the downstream soluble guanylyl cyclase/cGMP/protein kinase G signaling pathway to regulate the structural components at the tight junctions and adherens junctions in the testes. Apart from the involvement in junction regulation, NOS/NO also participates in controlling the levels of cytokines and hormones in the testes. On the other hand, NO is playing a unique role in modulating germ cell viability and development, and indirectly acting on some aspects of male infertility and testicular pathological conditions. Thus, NOS/NO bears an irreplaceable role in maintaining the homeostasis of the microenvironment in the seminiferous epithelium via its different downstream signaling pathways

Energetic particle influence on the Earth's atmosphere

This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society