A framework for proof certificates in finite state exploration

Model checkers use automated state exploration in order to prove various properties such as reachability, non-reachability, and bisimulation over state transition systems. While model checkers have proved valuable for locating errors in computer models and specifications, they can also be used to prove properties that might be consumed by other computational logic systems, such as theorem provers. In such a situation, a prover must be able to trust that the model checker is correct. Instead of attempting to prove the correctness of a model checker, we ask that it outputs its "proof evidence" as a formally defined document--a proof certificate--and that this document is checked by a trusted proof checker. We describe a framework for defining and checking proof certificates for a range of model checking problems. The core of this framework is a (focused) proof system that is augmented with premises that involve "clerk and expert" predicates. This framework is designed so that soundness can be guaranteed independently of any concerns for the correctness of the clerk and expert specifications. To illustrate the flexibility of this framework, we define and formally check proof certificates for reachability and non-reachability in graphs, as well as bisimulation and non-bisimulation for labeled transition systems. Finally, we describe briefly a reference checker that we have implemented for this framework.Comment: In Proceedings PxTP 2015, arXiv:1507.0837

A proof theory for model checking

International audienceWhile model checking has often been considered as a practical alternative to building formal proofs, we argue here that the theory of sequent calculus proofs can be used to provide an appealing foundation for model checking. Since the emphasis of model checking is on establishing the truth of a property in a model, we rely on additive inference rules since these provide a natural description of truth values via inference rules. Unfortunately, using these rules alone can force the use of inference rules with an infinite number of premises. In order to accommodate more expressive and finitary inference rules, we also allow multiplicative rules but limit their use to the construction of additive synthetic inference rules: such synthetic rules are described using the proof-theoretic notions of polarization and focused proof systems. This framework provides a natural, proof-theoretic treatment of reachability and non-reachability problems, as well as tabled deduction, bisimulation, and winning strategies

The 6dF Galaxy Survey: Dependence of halo occupation on stellar mass

In this paper we study the stellar-mass dependence of galaxy clustering in the 6dF Galaxy Survey. The near-infrared selection of 6dFGS allows more reliable stellar mass estimates compared to optical bands used in other galaxy surveys. Using the Halo Occupation Distribution (HOD) model, we investigate the trend of dark matter halo mass and satellite fraction with stellar mass by measuring the projected correlation function, $w_p(r_p)$. We find that the typical halo mass ($M_1$) as well as the satellite power law index ($\alpha$) increase with stellar mass. This indicates, (1) that galaxies with higher stellar mass sit in more massive dark matter halos and (2) that these more massive dark matter halos accumulate satellites faster with growing mass compared to halos occupied by low stellar mass galaxies. Furthermore we find a relation between $M_1$ and the minimum dark matter halo mass ($M_{\rm min}$) of $M_1 \approx 22\,M_{\rm min}$, in agreement with similar findings for SDSS galaxies. The satellite fraction of 6dFGS galaxies declines with increasing stellar mass from 21% at $M_{\rm stellar} = 2.6\times10^{10}h^{-2}\,M_{\odot}$ to 12% at $M_{\rm stellar} = 5.4\times10^{10}h^{-2}\,M_{\odot}$ indicating that high stellar mass galaxies are more likely to be central galaxies. We compare our results to two different semi-analytic models derived from the Millennium Simulation, finding some disagreement. Our results can be used for placing new constraints on semi-analytic models in the future, particularly the behaviour of luminous red satellites. Finally we compare our results to studies of halo occupation using galaxy-galaxy weak lensing. We find good overall agreement, representing a valuable crosscheck for these two different tools of studying the matter distribution in the Universe.Comment: 17 pages, 11 figures. arXiv admin note: text overlap with arXiv:1104.2447 by other author

The 6dF Galaxy Survey: Baryon Acoustic Oscillations and the Local Hubble Constant

We analyse the large-scale correlation function of the 6dF Galaxy Survey (6dFGS) and detect a Baryon Acoustic Oscillation (BAO) signal. The 6dFGS BAO detection allows us to constrain the distance-redshift relation at z_{\rm eff} = 0.106. We achieve a distance measure of D_V(z_{\rm eff}) = 456\pm27 Mpc and a measurement of the distance ratio, r_s(z_d)/D_V(z_{\rm eff}) = 0.336\pm0.015 (4.5% precision), where r_s(z_d) is the sound horizon at the drag epoch z_d. The low effective redshift of 6dFGS makes it a competitive and independent alternative to Cepheids and low-z supernovae in constraining the Hubble constant. We find a Hubble constant of H_0 = 67\pm3.2 km s^{-1} Mpc^{-1} (4.8% precision) that depends only on the WMAP-7 calibration of the sound horizon and on the galaxy clustering in 6dFGS. Compared to earlier BAO studies at higher redshift, our analysis is less dependent on other cosmological parameters. The sensitivity to H_0 can be used to break the degeneracy between the dark energy equation of state parameter w and H_0 in the CMB data. We determine that w = -0.97\pm0.13, using only WMAP-7 and BAO data from both 6dFGS and \citet{Percival:2009xn}. We also discuss predictions for the large scale correlation function of two future wide-angle surveys: the WALLABY blind H{\sc I} survey (with the Australian SKA Pathfinder, ASKAP), and the proposed TAIPAN all-southern-sky optical galaxy survey with the UK Schmidt Telescope (UKST). We find that both surveys are very likely to yield detections of the BAO peak, making WALLABY the first radio galaxy survey to do so. We also predict that TAIPAN has the potential to constrain the Hubble constant with 3% precision.Comment: 18 pages, 17 figures, 3 table

The 6dF Galaxy Survey: z \approx 0 measurement of the growth rate and sigma_8

We present a detailed analysis of redshift-space distortions in the two-point correlation function of the 6dF Galaxy Survey (6dFGS). The K-band selected sub-sample which we employ in this study contains 81971 galaxies distributed over 17000deg^2 with an effective redshift z = 0.067. By modelling the 2D galaxy correlation function, xi(r_p,pi), we measure the parameter combination f(z)sigma_8(z) = 0.423 +/- 0.055. Alternatively, by assuming standard gravity we can break the degeneracy between sigma_8 and the galaxy bias parameter, b. Combining our data with the Hubble constant prior from Riess et al (2011), we measure sigma_8 = 0.76 +/- 0.11 and Omega_m = 0.250 +/- 0.022, consistent with constraints from other galaxy surveys and the Cosmic Microwave Background data from WMAP7. Combining our measurement of fsigma_8 with WMAP7 allows us to test the relationship between matter and gravity on cosmic scales by constraining the growth index of density fluctuations, gamma. Using only 6dFGS and WMAP7 data we find gamma = 0.547 +/- 0.088, consistent with the prediction of General Relativity. We note that because of the low effective redshift of 6dFGS our measurement of the growth rate is independent of the fiducial cosmological model (Alcock-Paczynski effect). We also show that our conclusions are not sensitive to the model adopted for non-linear redshift-space distortions. Using a Fisher matrix analysis we report predictions for constraints on fsigma_8 for the WALLABY survey and the proposed TAIPAN survey. The WALLABY survey will be able to measure fsigma_8 with a precision of 4-10%, depending on the modelling of non-linear structure formation. This is comparable to the predicted precision for the best redshift bins of the Baryon Oscillation Spectroscopic Survey (BOSS), demonstrating that low-redshift surveys have a significant role to play in future tests of dark energy and modified gravity.Comment: 17 pages, 13 figures, 1 tabl

International Network for Comparison of HIV Neutralization Assays: The NeutNet Report II

BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s) can provide measures of protective immunity. An international collaboration (NeutNet) involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs) and soluble CD4 (Phase I study). METHODS: In the present study (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or green fluorescent protein (GFP) reporter gene expression. FINDINGS: Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014). Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus. Consistent with the Phase I study, we recommend parallel use of PSV and VIA for vaccine evaluation

International Network for Comparison of HIV Neutralization Assays: The NeutNet Report

BACKGROUND: Neutralizing antibody assessments play a central role in human immunodeficiency virus type-1 (HIV-1) vaccine development but it is unclear which assay, or combination of assays, will provide reliable measures of correlates of protection. To address this, an international collaboration (NeutNet) involving 18 independent participants was organized to compare different assays. METHODS: Each laboratory evaluated four neutralizing reagents (TriMab, 447-52D, 4E10, sCD4) at a given range of concentrations against a panel of 11 viruses representing a wide range of genetic subtypes and phenotypes. A total of 16 different assays were compared. The assays utilized either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (virus infectivity assays, VI assays), or their Env-pseudotyped (gp160) derivatives produced in 293T cells (PSV assays) from molecular clones or uncloned virus. Target cells included PBMC and genetically-engineered cell lines in either a single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs that included extracellular or intracellular p24 antigen detection, RNA quantification and luciferase and beta-galactosidase reporter gene expression. FINDINGS: PSV assays were generally more sensitive than VI assays, but there were important differences according to the virus and inhibitor used. For example, for TriMab, the mean IC50 was always lower in PSV than in VI assays. However, with 4E10 or sCD4 some viruses were neutralized with a lower IC50 in VI assays than in the PSV assays. Inter-laboratory concordance was slightly better for PSV than for VI assays with some viruses, but for other viruses agreement between laboratories was limited and depended on both the virus and the neutralizing reagent. CONCLUSIONS: The NeutNet project demonstrated clear differences in assay sensitivity that were dependent on both the neutralizing reagent and the virus. No single assay was capable of detecting the entire spectrum of neutralizing activities. Since it is not known which in vitro assay correlates with in vivo protection, a range of neutralization assays is recommended for vaccine evaluation

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population