Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes.

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function

E-learning and health inequality aversion : A questionnaire experiment

In principle, questionnaire data on public views about hypothetical trade-offs between improving total health and reducing health inequality can provide useful normative health inequality aversion parameter benchmarks for policymakers faced with real trade-offs of this kind. However, trade-off questions can be hard to understand, and one standard type of question finds that a high proportion of respondents-sometimes a majority-appear to give exclusive priority to reducing health inequality. We developed and tested two e-learning interventions designed to help respondents understand this question more completely. The interventions were a video animation, exposing respondents to rival points of view, and a spreadsheet-based questionnaire that provided feedback on implied trade-offs. We found large effects of both interventions in reducing the proportion of respondents giving exclusive priority to reducing health inequality, though the median responses still implied a high degree of health inequality aversion and-unlike the video-the spreadsheet-based intervention introduced a substantial new minority of non-egalitarian responses. E-learning may introduce as well as avoid biases but merits further research and may be useful in other questionnaire studies involving trade-offs between conflicting values

SOFIA FORCAST Grism Study of the Mineralogy of Dust in the Winds of Proto-planetary Nebulae: RV Tauri Stars and SRd Variables

We present a SOFIA FORCAST grism spectroscopic survey to examine the mineralogy of the circumstellar dust in a sample of post-asymptotic giant branch (post-AGB) yellow supergiants that are believed to be the precursors of planetary nebulae. Our mineralogical model of each star indicates the presence of both carbon-rich and oxygenrich dust species—contrary to simple dredge-up models—with a majority of the dust in the form of amorphous carbon and graphite. The oxygen-rich dust is primarily in the form of amorphous silicates. The spectra do not exhibit any prominent crystalline silicate emission features. For most of the systems, our analysis suggests that the grains are relatively large and have undergone significant processing, supporting the hypothesis that the dust is confined to a Keplerian disk and that we are viewing the heavily processed, central regions of the disk from a nearly face-on orientation. These results help to determine the physical properties of the post-AGB circumstellar environment and to constrain models of post-AGB mass loss and planetary nebula formatio

Robert Nozick on nonhuman animals : rights, value and the meaning of life

In his chapter, Josh Milburn argues that Robert Nozick considers nonhuman animals in his philosophical writings, but that these discussions are downplayed in animal ethics and Nozick scholarship. This is regrettable, Milburn proposes, as Nozick is far more sympathetic to animal rights than many other libertarians. Milburn thus offers an analysis of Nozick’s animal ethics. Nozick’s arguments concerning vegetarianism and speciesism are considered, and Milburn argues that tensions in Nozick’s political philosophy potentially open the door to animal rights. Whatever their place in his political philosophy, Milburn contends, nonhuman animals find a comfortable home in Nozick’s axiology and ethics, with their value and the significance of our duties towards them affirmed. Milburn concludes that animal ethicists could learn from Nozick’s distinctive arguments and approaches and find an unexpected ally

On Justification, Idealization, and Discursive Purchase

Conceptions of acceptability-based moral or political justification take it that authoritative acceptability, widely conceived, constitutes, or contributes to, validity, or justification. There is no agreement as to what bar for authoritativeness such justification may employ. The paper engages the issue in relation to (i) the level of idealization that a bar for authoritativeness, ψ, imparts to a standard of acceptability-based justification, S, and (ii) the degree of discursive purchase of the discursive standing that S accords to people when it builds ψ. I argue that (i) and (ii) are interdependent: high idealization values entail low discursive purchase, while high degrees of purchase require low idealization values. I then distinguish between alethic conceptions of justification that prioritize ends that commit to high idealization values, and recognitive conceptions that favor high discursive purchase. On this basis, I argue for a moderately recognitivist constraint on idealization. To render the recognitive discursive minimum available to relevant people at the site of justification, S should set ψ low enough so that it is a genuine option for actual people to reject relevant views in ways that S recognizes as authoritative. (The Appendix applies this to a Forst-type view of reciprocity of reasons to draw out some limitations of this view.) [Draft available from author on request.

Scalable Parallel DFPN Search

Abstract. We present Scalable Parallel Depth-First Proof Number Search, a new shared-memory parallel version of depth-first proof number search. Based on the serial DFPN 1+ε method of Pawlewicz and Lew, SPDFPN searches effectively even as the transposition table becomes almost full, and so can solve large prob-lems. To assign jobs to threads, SPDFPN uses proof and disproof numbers and two parameters. SPDFPN uses no domain-specific knowledge or heuristics, so it can be used in any domain. Our experiments show that SPDFPN scales well and performs well on hard problems. We tested SPDFPN on problems from the game of Hex. On a 24-core machine and a 4.2-hour single-thread task, parallel efficiency ranges from 0.8 on 4 threads to 0.74 on 16 threads. SPDFPN solved all previously intractable 9×9 Hex open-ing moves; the hardest opening took 111 days. Also, in 63 days, it solved one 10×10 Hex opening move. This is the first time a computer or human has solved a 10×10 Hex opening move.

Universal DNA methylation age across mammalian tissues

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals

A mammalian methylation array for profiling methylation levels at conserved sequences

Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures up to 36k CpGs per species that are well conserved across many mammalian species. We designed a set of probes that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development of epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others

Educating for Autonomy: Liberalism and Autonomy in the Capabilities Approach

Martha Nussbaum grounds her version of the capabilities approach in political liberalism. In this paper, we argue that the capabilities approach, insofar as it genuinely values the things that persons can actually do and be, must be grounded in a hybrid account of liberalism: in order to show respect for adults, its justification must be political; in order to show respect for children, however, its implementation must include a commitment to comprehensive autonomy, one that ensures that children develop the skills necessary to make meaningful choices about whether or not to exercise their basic capabilities. Importantly, in order to show respect for parents who do not necessarily recognize autonomy as a value, we argue that the liberal state, via its system of public education, should take on the role of ensuring that all children within the state develop a sufficient degree of autonomy