747 research outputs found
A solvable model of the genesis of amino-acid sequences via coupled dynamics of folding and slow genetic variation
We study the coupled dynamics of primary and secondary structure formation
(i.e. slow genetic sequence selection and fast folding) in the context of a
solvable microscopic model that includes both short-range steric forces and and
long-range polarity-driven forces. Our solution is based on the diagonalization
of replicated transfer matrices, and leads in the thermodynamic limit to
explicit predictions regarding phase transitions and phase diagrams at genetic
equilibrium. The predicted phenomenology allows for natural physical
interpretations, and finds satisfactory support in numerical simulations.Comment: 51 pages, 13 figures, submitted to J. Phys.
IL-6-induced anaemia in rats:Possible pathogenetic implications for anaemia observed in chronic inflammations
Anaemia of chronic disease (ACD) is frequently found in rheumatoid arthritis (RA). In the pathogenesis of ACD both cytokines, such as tumour necrosis factor-alpha (TNF-α), IL-1 and IL-6 as well as a relative deficiency of erythropoietin (EPO), are thought to play a key role. In the present study the role of IL-6 in the pathogenesis of this anaemia was investigated. IL-6 was administered intraperitoneally to rats for 14 sequential days. It appeared that IL-6 was able to induce anaemia. No evidence for suppression of bone marrow erythropoiesis or enhanced sequestration of erythrocytes in the liver was found. However, decreased plasma and bone marrow iron contents were observed in anaemic rats. Blood loss in intestinal tissue was demonstrated using erythrocyte labelling with 99mtechnetium. Histologically this was associated with inflammatory cell infiltration, oedema and bleeding in the intestinal wall. In conclusion, IL-6 induced anaemia in rats. This anaemia was caused by intestinal blood loss.</p
Slowly evolving geometry in recurrent neural networks I: extreme dilution regime
We study extremely diluted spin models of neural networks in which the
connectivity evolves in time, although adiabatically slowly compared to the
neurons, according to stochastic equations which on average aim to reduce
frustration. The (fast) neurons and (slow) connectivity variables equilibrate
separately, but at different temperatures. Our model is exactly solvable in
equilibrium. We obtain phase diagrams upon making the condensed ansatz (i.e.
recall of one pattern). These show that, as the connectivity temperature is
lowered, the volume of the retrieval phase diverges and the fraction of
mis-aligned spins is reduced. Still one always retains a region in the
retrieval phase where recall states other than the one corresponding to the
`condensed' pattern are locally stable, so the associative memory character of
our model is preserved.Comment: 18 pages, 6 figure
Comparison of preferences of healthcare professionals and MS patients for attributes of disease-modifying drugs:A best-worst scaling
Background The choice between disease-modifying drugs (DMDs) for the treatment of multiple sclerosis (MS) becomes more often a shared decision between the patient and the neurologist and MS nurse. This study aimed to assess which DMD attributes are most important for the healthcare professionals in selecting a DMD for a patient. Subsequently, within this perspective, the neurologists' and nurses' perspectives were compared. Lastly, the healthcare professionals' perspective was compared with the patients' perspective to detect any differences that may need attention in the communication about DMDs. DesignA best-worst scaling (BWS) was conducted among 27 neurologists and 33 MS nurses treating patients with MS to determine the importance of 27 DMD attributes. These attributes were identified through three focus groups with MS patients in a previous study (N=19). Relative importance scores (RISs) were estimated for each attribute. Multivariable linear regression analyses were used to compare the different perspectives. ResultsAccording to the neurologists and nurses, safety of the DMD was the most important DMD attribute in the treatment decision, closely followed by effect on disability progression, quality of life and relapse rate. Patients with MS agreed with the importance of the last three attributes, but valued safety significantly lower (b=-2.59, P ConclusionsThis study suggests that, overall, neurologists and nurses regard the same DMD attributes as important as MS patients with the notable exception of safety. This study provides valuable information for the development of interventions to support shared decision making and highlights which attributes of DMDs may need additional attention
Modelling topical photodynamic therapy treatment including the continuous production of Protoporphyrin IX
C L Campbell acknowledges financial support from an UK EPSRC PhD studentship (EP/K503162/1) and the Alfred Stewart Trust.Most existing theoretical models of photodynamic therapy (PDT) assume a uniform initial distribution of the photosensitive molecule, Protoporphyrin IX (PpIX). This is an adequate assumption when the prodrug is systematically administered; however for topical PDT this is no longer a valid assumption. Topical application and subsequent diffusion of the prodrug results in an inhomogeneous distribution of PpIX, especially after short incubation times, prior to light illumination. In this work a theoretical simulation of PDT where the PpIX distribution depends on the incubation time and the treatment modality is described. Three steps of the PpIX production are considered. The first is the distribution of the topically applied prodrug, the second in the conversion from the prodrug to PpIX and the third is the light distribution which affects the PpIX distribution through photobleaching. The light distribution is modelled using a Monte Carlo radiation transfer model and indicates treatment depths of around 2 mm during daylight PDT and approximately 3 mm during conventional PDT. The results suggest that treatment depths are not only limited by the light penetration but also by the PpIX distributionPostprintPeer reviewe
Diagonalization of replicated transfer matrices for disordered Ising spin systems
We present an alternative procedure for solving the eigenvalue problem of
replicated transfer matrices describing disordered spin systems with (random)
1D nearest neighbor bonds and/or random fields, possibly in combination with
(random) long range bonds. Our method is based on transforming the original
eigenvalue problem for a matrix (where ) into an
eigenvalue problem for integral operators. We first develop our formalism for
the Ising chain with random bonds and fields, where we recover known results.
We then apply our methods to models of spins which interact simultaneously via
a one-dimensional ring and via more complex long-range connectivity structures,
e.g. dimensional neural networks and `small world' magnets.
Numerical simulations confirm our predictions satisfactorily.Comment: 24 pages, LaTex, IOP macro
Orbital order in the low-dimensional quantum spin system TiOCl probed by ESR
We present electron spin resonance data of Ti (3) ions in single
crystals of the novel layered quantum spin magnet TiOCl. The analysis of the g
tensor yields direct evidence that the d_{xy} orbital from the t_{2g} set is
predominantly occupied and owing to the occurrence of orbital order a linear
spin chain forms along the crystallographic b axis. This result corroborates
recent theoretical LDA+U calculations of the band structure. The temperature
dependence of the parameters of the resonance signal suggests a strong coupling
between spin and lattice degrees of freedom and gives evidence for a transition
to a nonmagnetic ground state at 67 K.Comment: revised version, accepted for publication in Phys. Rev. B, Rapid Com
The prognostic performance of Adjuvant! Online and Nottingham Prognostic Index in young breast cancer patients: an international multicentre hospital-based retrospective cohort study
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