519 research outputs found
Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases.
The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials. These include the BAFF/APRIL dual inhibitor, atacicept, and the BAFF inhibitor, belimumab, which is approved as an add-on therapy for patients with active SLE. Post hoc analyses of these trials indicate that baseline serum levels of BAFF and BAFF/APRIL correlate with treatment response to belimumab and atacicept, respectively, suggesting a role for the two molecules as predictive biomarkers. It will, however, be important to refine future testing to identify active forms of BAFF and APRIL in the circulation, as well as to distinguish between homotrimer and heteromer configurations. In this review, we discuss the rationale for dual BAFF/APRIL inhibition versus single BAFF inhibition in autoimmune disease, by focusing on the similarities and differences between the physiological and pathogenic roles of the two molecules. A summary of the preclinical and clinical data currently available is also presented
The Excursion Set Theory of Halo Mass Functions, Halo Clustering, and Halo Growth
I review the excursion set theory (EST) of dark matter halo formation and
clustering. I recount the Press-Schechter argument for the mass function of
bound objects and review the derivation of the Press-Schechter mass function in
EST. The EST formalism is powerful and can be applied to numerous problems. I
review the EST of halo bias and the properties of void regions. I spend
considerable time reviewing halo growth in the EST. This section culminates
with descriptions of two Monte Carlo methods for generating halo mass accretion
histories. In the final section, I emphasize that the standard EST approach is
the result of several simplifying assumptions. Dropping these assumptions can
lead to more faithful predictions and a more versatile formalism. One such
assumption is the constant height of the barrier for nonlinear collapse. I
review implementations of the excursion set approach with arbitrary barrier
shapes. An application of this is the now well-known improvement to standard
EST that follows from the ellipsoidal-collapse barrier. Additionally, I
emphasize that the statement that halo accretion histories are independent of
halo environments is a simplifying assumption, rather than a prediction of the
theory. I review the method for constructing correlated random walks of the
density field in more general cases. I construct a simple toy model with
correlated walks and I show that excursion set theory makes a qualitatively
simple and general prediction for the relation between halo accretion histories
and halo environments: regions of high density preferentially contain
late-forming halos and conversely for regions of low density. I conclude with a
brief discussion of this prediction in the context of recent numerical studies
of the environmental dependence of halo properties. (Abridged)Comment: 62 pages, 19 figures. Review article based on lectures given at the
Sixth Summer School of the Helmholtz Institute for Supercomputational
Physics. Accepted for Publication in IJMPD. Comments Welcom
Penetration depth of low-coherence enhanced backscattered light in sub-diffusion regime
The mechanisms of photon propagation in random media in the diffusive
multiple scattering regime have been previously studied using diffusion
approximation. However, similar understanding in the low-order (sub-diffusion)
scattering regime is not complete due to difficulties in tracking photons that
undergo very few scatterings events. Recent developments in low-coherence
enhanced backscattering (LEBS) overcome these difficulties and enable probing
photons that travel very short distances and undergo only a few scattering
events. In LEBS, enhanced backscattering is observed under illumination with
spatial coherence length L_sc less than the scattering mean free path l_s. In
order to understand the mechanisms of photon propagation in LEBS in the
subdiffusion regime, it is imperative to develop analytical and numerical
models that describe the statistical properties of photon trajectories. Here we
derive the probability distribution of penetration depth of LEBS photons and
report Monte Carlo numerical simulations to support our analytical results. Our
results demonstrate that, surprisingly, the transport of photons that undergo
low-order scattering events has only weak dependence on the optical properties
of the medium (l_s and anisotropy factor g) and strong dependence on the
spatial coherence length of illumination, L_sc, relative to those in the
diffusion regime. More importantly, these low order scattering photons
typically penetrate less than l_s into the medium due to low spatial coherence
length of illumination and their penetration depth is proportional to the
one-third power of the coherence volume (i.e. [l_s \pi L_sc^2 ]^1/3).Comment: 32 pages(including 7 figures), modified version to appear in Phys.
Rev.
An exact analytical solution for generalized growth models driven by a Markovian dichotomic noise
Logistic growth models are recurrent in biology, epidemiology, market models,
and neural and social networks. They find important applications in many other
fields including laser modelling. In numerous realistic cases the growth rate
undergoes stochastic fluctuations and we consider a growth model with a
stochastic growth rate modelled via an asymmetric Markovian dichotomic noise.
We find an exact analytical solution for the probability distribution providing
a powerful tool with applications ranging from biology to astrophysics and
laser physics
Brownian Simulations and Uni-Directional Flux in Diffusion
Brownian dynamics simulations require the connection of a small discrete
simulation volume to large baths that are maintained at fixed concentrations
and voltages. The continuum baths are connected to the simulation through
interfaces, located in the baths sufficiently far from the channel. Average
boundary concentrations have to be maintained at their values in the baths by
injecting and removing particles at the interfaces. The particles injected into
the simulation volume represent a unidirectional diffusion flux, while the
outgoing particles represent the unidirectional flux in the opposite direction.
The classical diffusion equation defines net diffusion flux, but not
unidirectional fluxes. The stochastic formulation of classical diffusion in
terms of the Wiener process leads to a Wiener path integral, which can split
the net flux into unidirectional fluxes. These unidirectional fluxes are
infinite, though the net flux is finite and agrees with classical theory. We
find that the infinite unidirectional flux is an artifact caused by replacing
the Langevin dynamics with its Smoluchowski approximation, which is classical
diffusion. The Smoluchowski approximation fails on time scales shorter than the
relaxation time of the Langevin equation. We find the unidirectional
flux (source strength) needed to maintain average boundary concentrations in a
manner consistent with the physics of Brownian particles. This unidirectional
flux is proportional to the concentration and inversely proportional to
to leading order. We develop a BD simulation that maintains
fixed average boundary concentrations in a manner consistent with the actual
physics of the interface and without creating spurious boundary layers
Random paths and current fluctuations in nonequilibrium statistical mechanics
An overview is given of recent advances in nonequilibrium statistical
mechanics about the statistics of random paths and current fluctuations.
Although statistics is carried out in space for equilibrium statistical
mechanics, statistics is considered in time or spacetime for nonequilibrium
systems. In this approach, relationships have been established between
nonequilibrium properties such as the transport coefficients, the thermodynamic
entropy production, or the affinities, and quantities characterizing the
microscopic Hamiltonian dynamics and the chaos or fluctuations it may generate.
This overview presents results for classical systems in the escape-rate
formalism, stochastic processes, and open quantum systems
Algorithm for normal random numbers
We propose a simple algorithm for generating normally distributed pseudo
random numbers. The algorithm simulates N molecules that exchange energy among
themselves following a simple stochastic rule. We prove that the system is
ergodic, and that a Maxwell like distribution that may be used as a source of
normally distributed random deviates follows when N tends to infinity. The
algorithm passes various performance tests, including Monte Carlo simulation of
a finite 2D Ising model using Wolff's algorithm. It only requires four simple
lines of computer code, and is approximately ten times faster than the
Box-Muller algorithm.Comment: 5 pages, 3 encapsulated Postscript Figures. Submitted to
Phys.Rev.Letters. For related work, see http://pipe.unizar.es/~jf
Theory of Adiabatic fluctuations : third-order noise
We consider the response of a dynamical system driven by external adiabatic
fluctuations. Based on the `adiabatic following approximation' we have made a
systematic separation of time-scales to carry out an expansion in , where is the strength of fluctuations and is the
damping rate. We show that probability distribution functions obey the
differential equations of motion which contain third order terms (beyond the
usual Fokker-Planck terms) leading to non-Gaussian noise. The problem of
adiabatic fluctuations in velocity space which is the counterpart of Brownian
motion for fast fluctuations, has been solved exactly. The characteristic
function and the associated probability distribution function are shown to be
of stable form. The linear dissipation leads to a steady state which is stable
and the variances and higher moments are shown to be finite.Comment: Plain Latex, no figures, 28 pages; to appear in J. Phys.
Probing Ion-Ion and Electron-Ion Correlations in Liquid Metals within the Quantum Hypernetted Chain Approximation
We use the Quantum Hypernetted Chain Approximation (QHNC) to calculate the
ion-ion and electron-ion correlations for liquid metallic Li, Be, Na, Mg, Al,
K, Ca, and Ga. We discuss trends in electron-ion structure factors and radial
distribution functions, and also calculate the free-atom and metallic-atom
form-factors, focusing on how bonding effects affect the interpretation of
X-ray scattering experiments, especially experimental measurements of the
ion-ion structure factor in the liquid metallic phase.Comment: RevTeX, 19 pages, 7 figure
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"Engaging with birth stories in pregnancy: a hermeneutic phenomenological study of women's experiences across two generations"
BACKGROUND: The birth story has been widely understood as a crucial source of knowledge about childbirth. What has not been reported is the effect that birth stories may have on primigravid women's understandings of birth. Findings are presented from a qualitative study exploring how two generations of women came to understand birth in the milieu of other's stories. The prior assumption was that birth stories must surely have a positive or negative influence on listeners, steering them towards either medical or midwifery-led models of care.
METHODS: A Heideggerian hermeneutic phenomenological approach was used. Twenty UK participants were purposively selected and interviewed. Findings from the initial sample of 10 women who were pregnant in 2012 indicated that virtual media was a primary source of birth stories. This led to recruitment of a second sample of 10 women who gave birth in the 1970s-1980s, to determine whether they were more able to translate information into knowledge via stories told through personal contact and not through virtual technologies
RESULTS: Findings revealed the experience of 'being-in-the-world' of birth and of stories in that world. From a Heideggerian perspective, the birth story was constructed through 'idle talk' (the taken for granted assumptions of things, which come into being through language). Both oral stories and those told through technology were described as the 'modern birth story'. The first theme 'Stories are difficult like that', examines the birth story as problematic and considers how stories shape meaning. The second 'It's a generational thing', considers how women from two generations came to understand what their experience might be. The third 'Birth in the twilight of certainty,' examines women's experience of Being in a system of birth as constructed, portrayed and sustained in the stories being shared.
CONCLUSIONS: The women pregnant in 2012 framed their expectations in the language of choice, whilst the women who birthed in the 1970s-1980s framed their experience in the language of safety. For both, however, the world of birth was the same; saturated with, and only legitimised by the birth of a healthy baby. Rather than creating meaningful understanding, the 'idle talk' of birth made both cohorts fearful of leaving the relative comfort of the 'system', and of claiming an alternative birth
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