The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

MATISSE, perspective of imaging in the mid-infrared at the VLTI

International audienceMATISSE is foreseen as a mid-infrared spectro-interferometer combining the beams of up to four UTs/ATs of the Very Large Telescope Interferometer (VLTI) of the European Southern Observatory. The related science case study demonstrates the enormous capability of a new generation mid-infrared beam combiner. MATISSE will constitute an evolution of the two-beam interferometric instrument MIDI. MIDI is a very successful instrument which offers a perfect combination of spectral and angular resolution. New characteristics present in MATISSE will give access to the mapping and the distribution of the material (typically dust) in the circumstellar environments by using a wide mid-infrared band coverage extended to L, M and N spectral bands. The four beam combination of MATISSE provides an efficient UV-coverage : 6 visibility points are measured in one set and 4 closure phase relations which can provide aperture synthesis images in the mid-infrared spectral regime

Widespread horse-based mobility arose around 2200 BCE in Eurasia.

Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and their widespread integration as a means of transport remains contentious2-4. Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 BCE, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai around 3500 BCE, a settlement from central Asia associated with corrals and a subsistence economy centred on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

The isolated human umbilical vein as a bioassay for kinin-generating proteases : an in vitro model for therapeutic angioedema agents

Aims: The isolated human umbilical vein is a robust contractile bioassay for ligands of the bradykinin (BK) B2 receptor (B2R), also extendable to B1 receptor (B1R) pharmacology. We hypothesized that, as a freshly isolated vessel, it also contains traces of plasma proteins that may confer responses to exogenous proteases via the formation of kinins. Main methods : Rings of human umbilical veins were mounted in organ baths containing Krebs buffer maintained at 37 °C and purified proteases were introduced in the bathing fluid along with additional drugs/proteins that permit mechanistic analysis of effects. Key findings: The previously described contractile response to human recombinant tissue kallikrein (KLK-1, 1–10 nM) is not influenced by metabolic inhibitors, suggesting its dependence on a preexisting reservoir of low molecular weight-kininogen (LK). Active plasma kallikrein (apK, ≤ 5 nM) was inactive in fresh tissues, unless high molecular weight-kininogen (HK, 39–197 nM) replenishment was applied. The effects of KLK-1 and HK + apK are abolished by pretreating tissues with icatibant, but not with tranexamic acid. C1-esterase inhibitor inhibited only HK + apK. Purified plasmin and neutrophil proteinase-3 produced small contractions in the presence of HK only, and tissue plasminogen activator, none. B1R stimulation was pharmacologically evidenced in response to KLK-1 if LK was supplied. Significance: The pharmacology of KLK-1 and HK + apK in the human isolated umbilical vein is essentially based on the activity of locally generated kinins and this assay models the inhibitory action of some therapeutic agents active in angioedema states. Proteases that indirectly generate kinins have little activity in the system

A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome

In chronic lymphocytic leukemia (CLL), an elevated glycosyltransferase UGT2B17 expression (UGT2B17HI) identifies a subgroup of patients with shorter survival and poor drug response. We uncovered a mechanism, possibly independent of its enzymatic function, characterized by an enhanced expression and signaling of the proximal effectors of the pro-survival B cell receptor (BCR) pathway and elevated Bruton tyrosine kinase (BTK) phosphorylation in B-CLL cells from UGT2B17HI patients. A prominent feature of B-CLL cells is the strong correlation of UGT2B17 expression with the adverse marker ZAP70 encoding a tyrosine kinase that promotes B-CLL cell survival. Their combined high expression levels in the treatment of naïve patients further defined a prognostic group with the highest risk of poor survival. In leukemic cells, UGT2B17 knockout and repression of ZAP70 reduced proliferation, suggesting that the function of UGT2B17 might involve ZAP70. Mechanistically, UGT2B17 interacted with several kinases of the BCR pathway, including ZAP70, SYK, and BTK, revealing a potential therapeutic vulnerability. The dual SYK and JAK/STAT6 inhibitor cerdulatinib most effectively compromised the proliferative advantage conferred by UGT2B17 compared to the selective BTK inhibitor ibrutinib. Findings point to an oncogenic role for UGT2B17 as a novel constituent of BCR signalosome also connected with microenvironmental signaling

Synthèse. L'épopée, moteur de l'imaginaire scientifique collectif ?

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Synthèse. L'épopée, moteur de l'imaginaire scientifique collectif ?

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Synthèse. La technologie est-elle impérialiste ?

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La hard science fiction, scientisme, rationalisme ou humanisme ?

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