Technology requirements of exploration beyond Neptune by solar sail propulsion

This paper provides a set of requirements for the technology development of a solar sail propelled Interstellar Heliopause Probe mission. The mission is placed in the context of other outer solar systems missions, ranging from a Kuiper Belt mission through to an Oort cloud mission. Mission requirements are defined and a detailed parametric trajectory analysis and launch date scan performed. Through analysis of the complete mission trade space a set of critical technology development requirements are identified which include an advanced lightweight composite High-Gain Antenna, a high-efficiency Ka-band travelling-wave tube amplifier and a radioisotope thermoelectric generator with power density of approximately 12 W/kg. It is also shown that the Interstellar Heliopause Probe mission necessitates the use of a spinning sail, limiting the direct application of current hardware development activities. A Kuiper Belt mission is then considered as a pre-curser to the Interstellar Heliopause Probe, while it is also shown through study of an Oort cloud mission that the Interstellar Heliopause Probe mission is the likely end-goal of any future solar sail technology development program. As such, the technology requirements identified to enable the Interstellar Heliopause Probe must be enabled through all prior missions, with each mission acting as an enabling facilitator towards the next

My care manager, my computer therapy and me: the relationship triangle in computerized cognitive behavioural therapy

Previous research has reported mixed findings regarding the relationship between therapeutic alliance, engagement and outcomes in e-mental health. This study aims to overcome some of the methodological limitations of previous research and extend our understanding of alliance-outcome relationships in e-mental health by exploring the nature of the relationship triangle between the patient, their care manager and their computerized cognitive behavioural therapy (CCBT) program, accessed with or without an Internet Support Group (ISG). Positive patient-rated alliance with both their care manager and the CCBT program itself was found and these were significantly associated with measures of engagement and clinical outcome. The magnitude of this association was moderate, and within the range of that reported for traditional face-to-face psychotherapies in recent meta-analyses. Limitations of the study, including the reliance on completer data and a cross-sectional design, and directions for future research are presented. Our findings suggest that both the training and supervision of support staff and the optimization of CCBT interventions themselves to enhance alliance and experience may lead to improved engagement and outcomes

Why highly expressed proteins evolve slowly

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we hypothesize that selection to reduce the burden of protein misfolding will favor protein sequences with increased robustness to translational missense errors. Pressure for translational robustness increases with expression level and constrains sequence evolution. Using several sequenced yeast genomes, global expression and protein abundance data, and sets of paralogs traceable to an ancient whole-genome duplication in yeast, we rule out several confounding effects and show that expression level explains roughly half the variation in Saccharomyces cerevisiae protein evolutionary rates. We examine causes for expression's dominant role and find that genome-wide tests favor the translational robustness explanation over existing hypotheses that invoke constraints on function or translational efficiency. Our results suggest that proteins evolve at rates largely unrelated to their functions, and can explain why highly expressed proteins evolve slowly across the tree of life.Comment: 40 pages, 3 figures, with supporting informatio

Ultralight Structures for Space Solar Power Satellites

The design of a deployable spacecraft, measuring 60 m × 60 m, and with an areal density 100 g m^(−2) , is described. This spacecraft can be packaged into a cylinder measuring 1.5 m in height and 1 m in diameter. It can be deployed to a flat configuration, where it acts as a stiff, lightweight support framework for multifunctional tiles that collect sunlight, generate electric power, and transmit to a ground station on Earth

Association Study of Common Genetic Variants and HIV- 1 Acquisition in 6,300 Infected Cases and 7,200 Controls

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10−11). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception ofCCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size

Oxytocin: co-evolution of human and domesticated animals

The neuropeptide oxytocin (OT) and its homologues are produced in specialized neurons located in Vertebrates exclusively in a deep and evolutionarily old part of the forebrain, the hypothalamus. The axons of OT neurons form the classical hypothalamic-neurohypophyseal tract terminating on blood vessels of the neurohypothysis to release OT into the systemic blood circulation. However, as was recently demonstrated in mammals, collaterals of OT axons concomitantly project to various forebrain regions to modulate the activity of local networks. At the behavioral level, OT facilitates intraspecific social contacts in mammals via various mechanisms ranging from the suppression of neuroendocrine stress responses to the direct OT action on neurons of socially relevant brain regions. Recent reports indicated possible contribution of OT to the formation of the social bond between domesticated mammals (dog, sheep, cattle) and humans. Indeed, social interaction between humans and a domesticated animal resulted in the elevation of peripheral OT levels (in blood, saliva or urine) and, in congruence, exogenous (intranasal) OT application led to more frequent contacts between the owner and the domesticated animal. It has been known for decades that domesticated animals exhibit profound socio-communicative abilities accompanied by suppressed aggression and stress responsiveness. These peculiarities of their behavior and physiology may be influenced by the activity of the central OT system. Therefore, in the present mini-review we focus on the role of OT in the orchestration of distinct forms of social behavior, including the monogamous bond, maternal care, social memory and recognition, aggression, and anxiety. As a conclusion, we propose possible directions for exploration of the OT contribution to empathy between humans and domesticated animals, which was likely established in the course of their co-evolution during last 10.000– 15.000 years

Hippocampal glucocorticoid receptor and microRNA gene expression and serum cortisol concentration in foxes selected for behavior toward humans

In many cases, stress reactivity is one of the important bases of aggressive behavior. It appears as if reduced stress reactivity underlies an abrupt decrease in aggression towards man in domesticated animals. However, the mechanisms of this reduction have yet to be resolved. In this work, we used an experimental domestication model, the silver fox selected for many years for the response to humans to study cortisol stress reactivity in tame and aggressive foxes in response to immobilization in human arms. Additionally, these behavioral fox groups were explored for one of the important mechanisms of glucocorticoid negative feedback, the expression of the glucocorticoid receptor gene (NR3C1) in a portion of the dorsal hippocampus. In recent years, attention has been paid to differences in miRNA expression patterns between animals with different behavior and stress reactivity, as well as to miRNA regulation under stress. The same applies to NR3C1 mRNA as well. That is why we performed a miRNA-seq analysis on a portion of the fox dorsal hippocampus. It has been demonstrated that immobilization in human arms leads to significantly higher stressinduced cortisol levels in aggressive than tame foxes. At the same time, no differences have been found between hippocampal NR3C1 gene expression and the pattern of miRNA expression. Thus, reduced stress reactivity in foxes during selection for the absence of aggressive responses and for the presence of emotionally positive responses to humans does not seem to be associated with important mechanisms of regulation such as alterations in hippocampal NR3C1 gene expression or microRNA-mediated silencing

Intra- and inter-subtype HIV diversity between 1994 and 2018 in southern Uganda: a longitudinal population-based study

There is limited data on human immunodeficiency virus (HIV) evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a 24-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from people living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994–2018) and four hyperendemic Lake Victoria fishing communities (2011–2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was evaluated using the Shannon diversity index, and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Demographic history of HIV was inferred using a coalescent-based Bayesian Skygrid model. Evolutionary dynamics were assessed among demographic and behavioral population subgroups, including by migration status. 9931 HIV sequences were available from 4999 PLHIV, including 3060 and 1939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (P < .001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (P < .001). The proportion of viruses classified as recombinants significantly increased by nearly four-fold from 12.2% in 1995 to 44.8% in 2017. Inter-subtype HIV diversity has generally increased. While intra-subtype p24 genetic diversity and divergence leveled off after 2014, intra-subtype gp41 diversity, effective population size, and divergence increased through 2017. Intra- and inter-subtype viral diversity increased across all demographic and behavioral population subgroups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development

Is the general time-reversible model bad for molecular phylogenetics?

The general time reversible model (GTR) is presently the most popular model used in phylogentic studies. However, GTR has an undesirable mathematical property that is potentially of significant concern. It is the purpose of this article to give examples that demonstrate why this deficit may pose a problem for phylogenetic analysis and interpretation.Comment: 10 pages, 2 figure