794 research outputs found
Rearranged Stochastic Heat Equation
The purpose of this work is to provide an explicit construction of a strong
Feller semigroup on the space of probability measures over the real line that
additionally maps bounded measurable functions into Lipschitz continuous
functions, with a Lipschitz constant that blows up in an integrable manner in
small time. Our construction relies on a rearranged version of the stochastic
heat equation on the circle driven by a coloured noise. Formally, this
stochastic equation writes as a reflected equation in infinite dimension, a
topic that is known to be challenging. Under the action of the rearrangement,
the solution is forced to live in a space of quantile functions that is
isometric to the space of probability measures on the real line. We prove the
equation to be solvable by means of an Euler scheme in which we alternate flat
dynamics in the space of random variables on the circle with a rearrangement
operation that projects back the random variables onto the subset of quantile
functions. A first challenge is to prove that this scheme is tight. A second
one is to provide a consistent theory for the limiting reflected equation and
in particular to interpret in a relevant manner the reflection term. The last
step in our work is to establish the aforementioned Lipschitz property of the
semigroup by adapting earlier ideas from the Bismut-Elworthy-Li formula in
stochastic analysis
EczemaPred: a computational framework for personalised prediction of eczema severity dynamics
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease leading to substantial quality of life impairment with heterogeneous treatment responses. People with AD would benefit from personalised treatment strategies, whose design requires predicting how AD severity evolves for each individual. Objective: This study aims to develop a computational framework for personalised prediction of AD severity dynamics. Methods: We introduced EczemaPred, a computational framework to predict patient-dependent dynamic evolution of AD severity using Bayesian state-space models that describe latent dynamics of AD severity items and how they are measured. We used EczemaPred to predict the dynamic evolution of validated patient-oriented scoring atopic dermatitis (PO-SCORAD) by combining predictions from the models for the nine severity items of PO-SCORAD (six intensity signs, extent of eczema, and two subjective symptoms). We validated this approach using longitudinal data from two independent studies: a published clinical study in which PO-SCORAD was measured twice weekly for 347 AD patients over 17 weeks, and another one in which PO-SCORAD was recorded daily by 16 AD patients for 12 weeks. Results: EczemaPred achieved good performance for personalised predictions of PO-SCORAD and its severity items daily to weekly. EczemaPred outperformed standard time-series forecasting models such as a mixed effect autoregressive model. The uncertainty in predicting PO-SCORAD was mainly attributed to that in predicting intensity signs (75% of the overall uncertainty). Conclusions: EczemaPred serves as a computational framework to make a personalised prediction of AD severity dynamics relevant to clinical practice. EczemaPred is available as an R package
Structural Basis for Potentiation by Alcohols and Anaesthetics in a Ligand-gated Ion Channel
Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. A recent series of mutagenesis experiments on Gloeobacter violaceus ligand-gated ion channel, a prokaryotic member of this family, identified a single-site variant that is potentiated by pharmacologically relevant concentrations of ethanol. Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. Structural and mutagenesis studies defined overlapping mechanisms of potentiation by alcohols and anaesthetics via the inter-subunit cavity. Furthermore, homology modelling show this cavity to be conserved in human ethanol-sensitive glycine and GABA(A) receptors, and to involve residues previously shown to influence alcohol and anaesthetic action on these proteins. These results suggest a common structural basis for ethanol potentiation of an important class of targets for neurological actions of ethanol
Large Deviations Analysis for Distributed Algorithms in an Ergodic Markovian Environment
We provide a large deviations analysis of deadlock phenomena occurring in
distributed systems sharing common resources. In our model transition
probabilities of resource allocation and deallocation are time and space
dependent. The process is driven by an ergodic Markov chain and is reflected on
the boundary of the d-dimensional cube. In the large resource limit, we prove
Freidlin-Wentzell estimates, we study the asymptotic of the deadlock time and
we show that the quasi-potential is a viscosity solution of a Hamilton-Jacobi
equation with a Neumann boundary condition. We give a complete analysis of the
colliding 2-stacks problem and show an example where the system has a stable
attractor which is a limit cycle
Probabilistic analysis of the upwind scheme for transport
We provide a probabilistic analysis of the upwind scheme for
multi-dimensional transport equations. We associate a Markov chain with the
numerical scheme and then obtain a backward representation formula of
Kolmogorov type for the numerical solution. We then understand that the error
induced by the scheme is governed by the fluctuations of the Markov chain
around the characteristics of the flow. We show, in various situations, that
the fluctuations are of diffusive type. As a by-product, we prove that the
scheme is of order 1/2 for an initial datum in BV and of order 1/2-a, for all
a>0, for a Lipschitz continuous initial datum. Our analysis provides a new
interpretation of the numerical diffusion phenomenon
Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.
Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted
Verticalization of bacterial biofilms
Biofilms are communities of bacteria adhered to surfaces. Recently, biofilms
of rod-shaped bacteria were observed at single-cell resolution and shown to
develop from a disordered, two-dimensional layer of founder cells into a
three-dimensional structure with a vertically-aligned core. Here, we elucidate
the physical mechanism underpinning this transition using a combination of
agent-based and continuum modeling. We find that verticalization proceeds
through a series of localized mechanical instabilities on the cellular scale.
For short cells, these instabilities are primarily triggered by cell division,
whereas long cells are more likely to be peeled off the surface by nearby
vertical cells, creating an "inverse domino effect". The interplay between cell
growth and cell verticalization gives rise to an exotic mechanical state in
which the effective surface pressure becomes constant throughout the growing
core of the biofilm surface layer. This dynamical isobaricity determines the
expansion speed of a biofilm cluster and thereby governs how cells access the
third dimension. In particular, theory predicts that a longer average cell
length yields more rapidly expanding, flatter biofilms. We experimentally show
that such changes in biofilm development occur by exploiting chemicals that
modulate cell length.Comment: Main text 10 pages, 4 figures; Supplementary Information 35 pages, 15
figure
- …