On Robustness in Cosmological Simulations

The Cold Dark Matter model faces many controversies at small scales, as simulations fail to reproduce the observed properties of dark matter (DM) haloes. Since rival DM models differ on their predictions about the structure of DM haloes, understanding their mass distribution is crucial for determining the nature of dark matter. However, only numerical approaches to determining what a hypothesis implies for the mass distribution are possible. Hence, simulations are a crucial part of evaluating DM rival models, as is assessing their reliability. I argue that robustness analysis is not a sufficient criterion for the trustworthiness of cosmological simulations

On Robustness in Cosmological Simulations

The Cold Dark Matter model faces many controversies at small scales, as simulations fail to reproduce the observed properties of dark matter (DM) haloes. Since rival DM models differ on their predictions about the structure of DM haloes, understanding their mass distribution is crucial for determining the nature of dark matter. However, only numerical approaches to determining what a hypothesis implies for the mass distribution are possible. Hence, simulations are a crucial part of evaluating DM rival models, as is assessing their reliability. I argue that robustness analysis is not a sufficient criterion for the trustworthiness of cosmological simulations

On Robustness in Cosmological Simulations

The Cold Dark Matter model faces many controversies at small scales, as simulations fail to reproduce the observed properties of dark matter (DM) haloes. Since rival DM models differ on their predictions about the structure of DM haloes, understanding their mass distribution is crucial for determining the nature of dark matter. However, only numerical approaches to determining what a hypothesis implies for the mass distribution are possible. Hence, simulations are a crucial part of evaluating DM rival models, as is assessing their reliability. I argue that robustness analysis is not a sufficient criterion for the trustworthiness of cosmological simulations

A crack in the track of the Hubble constant

Measuring the rate at which the universe expands at a given time--the "Hubble constant"-- has been a topic of controversy since the first measure of its expansion by Edwin Hubble in the 1920's. As early as the 1970's, Sandage et de Vaucouleurs have been arguing about the adequate methodology for such a measurement. Should astronomers focus only on their best indicators, e.g., the Cepheids, and improve the precision of this measurement based on a unique object to the best possible? Or should they “spread the risks”, i.e., multiply the indicators and methodologies before averaging over their results? Is a robust agreement across several uncertain measures, as is currently argued to defend the existence of a "Hubble crisis" more telling than a single 1 % precision measurement? This controversy, I argue, stems from a misconception of what managing the uncertainties associated with such experimental measurements require. Astrophysical measurements, such as the measure of the Hubble constant, require a methodology that permits both to reduce the known uncertainties and to track the unknown unknowns. Based on the lessons drawn from the so-called Hubble crisis, I sketch a methodological guide for identifying, quantifying and reducing uncertainties in astrophysical measurements, hoping that such a guide can not only help to re-frame the current Hubble tension, but serve as a starting point for future fruitful discussions between astrophysicists, astronomers and philosophers

On Separating the Wheat from the Chaff: Surplus Structure and Artifacts in Scientific Theories

Although logical empiricism is now mostly decried, their naturalist claim that the content of a theory can be read off from its structure, without any philosophical considerations needed, still supports traditional strategies to escape cases of underdetermination. The appeal to theoretical equivalence or to theoretical virtues, for instance, both assume that there is a neutral standpoint from which the structure of the theories can be analyzed, the physically relevant from the superfluous separated, and a comparison made between their theoretical content and virtues. In my dissertation, I examine the presuppositions upon which such strategies depend. I argue that the methodological principle underlying them, according to which theories with no superfluous structure should be preferred, is unpractical, for what constitutes relevant structure is determined by epistemic considerations about the aim of scientific theories. In chapter 1, I analyze the claim that theories with ordinary bosons and fermions are theoretically equivalent to theories with exotic `paraparticles\u27. I argue that this claim does not do justice to the latter, as the proof is formulated in a vocabulary parochial to the former and thus favors one of the theory while giving an impoverished version of the second. In chapter 2, I examine recent arguments to the effects that any interpretation of Quantum Mechanics that can offer a no-go theorem against paraparticles possesses an explanatory advantage over other interpretations and should, as such, be favored over others. Given that most physicists consider paraparticles as surplus structure whose non-observation does not require an explanation, I evaluate arguments of both sides and suggest a third way to approach the question. Finally, in chapter 3, I turn my attention to methods for excluding another kind of unphysical structure, mathematical artifacts, from rival dark matter models. Simulations are our only window into what rival models predict about the universe’s structure. But for them to play a useful role in generating knowledge, we need to distinguish reliably between real predictions and artifacts. I argue that robustness analysis fails to fulfill this task. I propose in its place another methodology, that of crucial simulations

On Robustness in Cosmological Simulations

The Cold Dark Matter model faces many controversies at small scales, as simulations fail to reproduce the observed properties of dark matter (DM) haloes. Since rival DM models differ on their predictions about the structure of DM haloes, understanding their mass distribution is crucial for determining the nature of dark matter. However, only numerical approaches to determining what a hypothesis implies for the mass distribution are possible. Hence, simulations are a crucial part of evaluating DM rival models, as is assessing their reliability. I argue that robustness analysis is not a sufficient criterion for the trustworthiness of cosmological simulations

Use of a LiESP/QA-21 Vaccine (CaniLeish) Stimulates an Appropriate Th1-Dominated Cell-Mediated Immune Response in Dogs

Canine leishmaniasis is an important zoonotic disease of dogs. The clinical outcome of infection is variable, with the efficiency of the immune response being the key determining factor. There is now a general consensus that a predominant Th1 immune profile in an overall mixed Th1/Th2 response is associated with resistance in dogs, and the absence of a strong Th1 influence is associated with a progression to clinical disease. As a result, there has been a growing demand for vaccines that can induce a specific, strong Th1 response. In this study, we measured the impact of a primary course of a newly available LiESP/QA-21 vaccine on selected humoral and cellular markers of the canine immune response during the onset of immunity. All vaccinated dogs developed a humoral response characterised by IgG2 production. More importantly, vaccinated dogs developed significantly stronger cell-mediated immunity responses than did control dogs. Vaccination induced specific cellular reactivity to soluble Leishmania antigens, with a Leishmania-specific lymphoproliferation (p = 0.0072), characterised by an increased population of T lymphocytes producing IFN-γ (p = 0.0021) and a significant ability of macrophages to reduce intracellular parasite burdens in vitro after co-culture with autologous lymphocytes (p = 0.0014). These responses were correlated with induction of the NOS pathway and production of NO derivatives, which has been shown to be an important leishmanicidal mechanism. These results confirm that vaccination with LiESP/QA-21 induces an appropriate Th1-profile cell-mediated response within three weeks of completing the primary course, and that this response effectively reduces the parasite load in pre-infected macrophages in vitro

Activation of an endothelial Notch1-Jagged1 circuit induces VCAM1 expression, an effect amplified by interleukin-1β

The Notch1 and Notch4 signaling pathways regulate endothelial cell homeostasis. Inflammatory cytokines induce the expression of endothelial adhesion molecules, including VCAM1, partly by downregulating Notch4 signaling. We investigated the role of endothelial Notch1 in this IL-1β-mediated process. Brief treatment with IL-1β upregulated endothelial VCAM1 and Notch ligand Jagged1. IL-1β decreased Notch1 mRNA levels, but levels of the active Notch1ICD protein remained constant. IL-1β-mediated VCAM1 induction was downregulated in endothelial cells subjected to pretreatment with a pharmacological inhibitor of the γ-secretase, which activates Notch receptors, producing NotchICD. It was also downregulated in cells in which Notch1 and/or Jagged1 were silenced.Conversely, the forced expression of Notch1ICD in naïve endothelial cells upregulated VCAM1 per se and amplified IL-1β-mediated VCAM1 induction. Jagged1 levels increased and Notch4 signaling was downregulated in parallel. Finally, Notch1ICD and Jagged1 expression was upregulated in the endothelium of the liver in a model of chronic liver inflammation.In conclusion, we describe here a cell-autonomous, pro-inflammatory endothelial Notch1-Jagged1 circuit (i) triggering the expression of VCAM1 even in the absence of inflammatory cytokines and (ii) enhancing the effects of IL-1β. Thus, IL-1β regulates Notch1 and Notch4 activity in opposite directions, consistent with a selective targeting of Notch1 in inflamed endothelium

Multimethod Characterization of the French-Pyrenean Valley of Bagnères-de-Bigorre for Seismic-Hazard Evaluation: Observations and Models

International audienceA narrow rectilinear valley in the French Pyrenees, affected in the past by damaging earthquakes, has been chosen as a test site for soil response characteriza- tion. The main purpose of this initiative was to compare experimental and numerical approaches. A temporary network of 10 stations has been deployed along and across the valley during two years; parallel various experiments have been conducted, in particular ambient noise recording, and seismic profiles with active sources for struc- ture determination at the 10 sites. Classical observables have been measured for site amplification evaluation, such as spectral ratios of horizontal or vertical motions between site and reference stations using direct S waves and S coda, and spectral ratios between horizontal and vertical (H/V) motions at single stations using noise and S-coda records. Vertical shear-velocity profiles at the stations have first been obtained from a joint inversion of Rayleigh wave dispersion curves and ellipticity. They have subsequently been used to model the H/V spectral ratios of noise data from synthetic seismograms, the H/V ratio of S-coda waves based on equipartition theory, and the 3D seismic response of the basin using the spectral element method. General good agreement is found between simulations and observations. The 3D simulation reveals that topography has a much lower contribution to site effects than sedimentary filling, except at the narrow ridge crests. We find clear evidence of a basin edge effect, with an increase of the amplitude of ground motion at some distance from the edge inside the basin and a decrease immediately at the slope foot