Mortensen Observer for a class of variational inequalities -Lost equivalence with stochastic filtering approaches

We address the problem of deterministic sequential estimation for a nonsmooth dynamics in R governed by a variational inequality, as illustrated by the Skorokhod problem with a reflective boundary condition at 0. For smooth dynamics, Mortensen introduced an energy for the likelihood that the state variable produces-up to perturbations disturbances-a given observation in a finite time interval, while reaching a given target state at the final time. The Mortensen observer is the minimiser of this energy. For dynamics given by a variational inequality and therefore not reversible in time, we study the definition of a Mortensen estimator. On the one hand, we address this problem by relaxing the boundary constraint of the synthetic variable and then proposing an approximated variant of the Mortensen estimator that uses the resulting nonlinear smooth dynamics. On the other hand, inspired by the smooth dynamics approach, we study the vanishing viscosity limit of the Hamilton-Jacobi equation satisfied by the Hopf-Cole transform of the solution of the robust Zakai equation. We prove a stability result that allows us to interpret the limiting solution as the value function associated with a control problem rather than an estimation problem. In contrast to the case of smooth dynamics, here the zero-noise limit of the robust form of the Zakai equation cannot be understood from the Bellman equation of the value function arising in Mortensen's deterministic estimation. This may unveil a violation of equivalence for non-reversible dynamics between the Mortensen approach and the low noise stochastic approach for nonsmooth dynamics

Ivy : un bus logiciel au service du développement de prototypes de systèmes interactifs

Ce document présente l'expérience acquise au cours du développement et de l'utilisation du bus logiciel Ivy, dans un cadre de prototypage de systèmes interactifs pour le contrôle du trafic aérien. Après une description du principe de fonctionnement de ce système, nous verrons comment cet outil a pu influer sur notre approche de problématiques IHM spécifiques comme la multimodalité, l'interaction répartie ou la mobilité. L'accent est porté sur les services rendus par ce bus pour le développement rapide de systèmes interactifs " légers ", facilement intégrables dans un banc de démonstration et basés sur la logique des langages de script. En présentant cet outil que nous utilisons depuis maintenant cinq ans, nous espérons partager ici une expérience utile pour la conception de futures architectures de systèmes interactifs à des fins de recherche prospective

Mortensen observer for a class of variational inequalities – lost equivalence with stochastic filtering approaches

We address the problem of deterministic sequential estimation for a nonsmooth dynamics governed by a variational inequality. An example of such dynamics is the Skorokhod problem with a reflective boundary condition. For smooth dynamics, Mortensen introduced in 1968 a nonlinear estimator based on likelihood maximisation. Then, starting with Hijab in 1980, several authors established a connection between Mortensen’s approach and the vanishing noise limit of the robust form of the so-called Zakai equation. In this paper, we investigate to what extent these methods can be developed for dynamics governed by a variational inequality. On the one hand, we address this problem by relaxing the inequality constraint by penalization: this yields an approximate Mortensen estimator relying on an approximating smooth dynamics. We verify that the equivalence between the deterministic and stochastic approaches holds through a vanishing noise limit. On the other hand, inspired by the smooth dynamics approach, we study the vanishing viscosity limit of the Hamilton-Jacobi equation satisfied by the Hopf-Cole transform of the solution of the robust Zakai equation. In contrast to the case of smooth dynamics, the zero-noise limit of the robust form of the Zakai equation cannot be understood in our case from the Bellman equation on the value function arising in Mortensen’s procedure. This unveils a violation of equivalence for dynamics governed by a variational inequality between the Mortensen approach and the low noise stochastic approach for nonsmooth dynamics

Dual Suppression of the Cyclin-Dependent Kinase Inhibitors CDKN2C and CDKN1A in Human Melanoma

Resistance to BRAFV600E inhibitors is associated with reactivation of mitogen-activated protein kinase (MAPK) signaling at different levels in melanoma. To identify downstream effectors of MAPK signaling that could be used as potential additional therapeutic targets for BRAFV600E inhibitors, we used hTERT/CDK4R24C/p53DD-immortalized primary human melanocytes genetically modified to ectopically express BRAF V600E or NRAS G12D and observed induction of the AP-1 transcription factor family member c-Jun. Using a dominant negative approach, in vitro cell proliferation assays, western blots, and flow cytometry showed that MAPK signaling via BRAFV600E promotes melanoma cell proliferation at G1 through AP-1-mediated negative regulation of the INK4 family member, cyclin-dependent kinase inhibitor 2C (CDKN2C), and the CIP/KIP family member, cyclin-dependent kinase inhibitor 1A (CDKN1A). These effects were antagonized by pharmacological inhibition of CDKN2C and CDKN1A targets CDK2 and CDK4 in vitro. In contrast to BRAF V600E or NRAS G12D-expressing melanocytes, melanoma cells have an inherent resistance to suppression of AP-1 activity by BRAFV600E- or MEK-inhibitors. Here, CDK2/4 inhibition statistically significantly augmented the effects of BRAFV600E- or MEK-inhibitors on melanoma cell viability in vitro and growth in athymic nude Foxn1 nu mice (P = .03 when mean tumor volume at day 13 was compared for BRAFV600E inhibitor vs BRAFV600E inhibitor plus CDK2/4 inhibition; P = .02 when mean tumor volume was compared for MEK inhibitor vs MEK inhibitor plus CDK2/4 inhibition; P values were calculated by a two-sided Welch t test; n = 4–8 mice per group)

No-cloning theorem and teleportation criteria for quantum continuous variables

We discuss the criteria presently used for evaluating the efficiency of quantum teleportation schemes for continuous variables. Using an argument based upon the difference between 1-to-2 quantum cloning (quantum duplication) and 1-to-infinity cloning (classical measurement), we show that a fidelity value larger than 2/3 is required for successful quantum teleportation of coherent states. This value has not been reached experimentally so far.Comment: 4 pages, 1 figure, submitted to Phys. Rev.

Fatigue is independently associated with disease activity assessed using the Physician Global Assessment but not the SLEDAI in patients with systemic lupus erythematosus

Objectives To analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global Assessment (PGA). Methods Patients from the Lupus BioBank of the upper Rhein database, a cross-sectional multicentre collection of detailed clinical and biological data from patients with SLE, were included. Patients had to fulfil the 1997 American College of Rheumatology criteria for SLE and the PGA (0-3 scale) at the time of inclusion had to be available. Fatigue was assessed according to the Fatigue Scale for Motor and Cognitive Functions. Univariate and multivariate regression models were built to determine which variables were associated with the PGA. Results A total of 350 patients (89% female; median age: 42 years, IQR: 34-52) were included. The median Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 4 (IQR: 2-6). Of these 350 patients, 257 (73%) reported significant fatigue. The PGA (p=0.004) but not the SELENA-SLEDAI (p=0.43) was significantly associated with fatigue. Both fatigue and SELENA-SLEDAI were independently associated with the PGA in two different multivariate models. Conclusion Fatigue is independently associated with disease activity assessed using the PGA but not the SLEDAI. These findings highlight the fact that the PGA should capture only objectively active disease manifestations in order to improve its reliability

Episodic Therapy for Genital Herpes in Sub-Saharan Africa: A Pooled Analysis from Three Randomized Controlled Trials

BACKGROUND: A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations. METHODOLOGY/PRINCIPAL FINDINGS: Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98-1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm(2)), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors. CONCLUSIONS/SIGNIFICANCE: There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing

The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice.

Colorectal cancer (CRC) develops through a multistep process and is modulated by inflammation. However, the inflammatory pathways that support intestinal tumors at different stages remain incompletely understood. Interleukin (IL)-33 signaling plays a role in intestinal inflammation, yet its contribution to the pathogenesis of CRC is unknown. Using immunohistochemistry on 713 resected human CRC specimens, we show here that IL-33 and its receptor ST2 are expressed in low-grade and early-stage human CRCs, and to a lesser extent in higher-grade and more advanced-stage tumors. In a mouse model of CRC, ST2-deficiency protects from tumor development. Moreover, bone marrow (BM) chimera studies indicate that engagement of the IL-33/ST2 pathway on both the radio-resistant and radio-sensitive compartment is essential for CRC development. Mechanistically, activation of IL-33/ST2 signaling compromises the integrity of the intestinal barrier and triggers the production of pro-tumorigenic IL-6 by immune cells. Together, this data reveals a tumor-promoting role of IL-33/ST2 signaling in CRC

Bacterial Colonization of Low‐Wettable Surfaces is Driven by Culture Conditions and Topography

Effect of surface low‐wettability on bacterial colonization has become a prominent subject for the development of antibacterial coatings. However, bacteria's fate on such surfaces immersed in liquid as well as causal factors is poorly understood. This question is addressed by using a range of coatings with increasing hydrophobicity, to superhydrophobic, obtained by an atmospheric plasma polymer method allowing series production. Chemistry, wettability, and topography are thoroughly described, as well as bacterial colonization by in situ live imaging up to 24 h culture time in different liquid media. In the extreme case of superhydrophobic coating, substrates are significantly less colonized in biomolecule‐poor liquids and for short‐term culture only. Complex statistical analysis demonstrates that bacterial colonization on these low‐wettable substrates is predominantly controlled by the culture conditions and only secondary by topographic coating's properties (variation in surface structuration with almost constant mean height). Wettability is less responsible for bacterial colonization reduction in these conditions, but allows the coatings to preserve colonization‐prevention properties in nutritive media when topography is masked by fouling. Even after long‐term culture in rich medium, many large places of the superhydrophobic coating are completely free of bacteria in relation to their capacity to preserve air trapping