Structural Properties of Self-Attracting Walks

Self-attracting walks (SATW) with attractive interaction u > 0 display a swelling-collapse transition at a critical u_{\mathrm{c}} for dimensions d >= 2, analogous to the \Theta transition of polymers. We are interested in the structure of the clusters generated by SATW below u_{\mathrm{c}} (swollen walk), above u_{\mathrm{c}} (collapsed walk), and at u_{\mathrm{c}}, which can be characterized by the fractal dimensions of the clusters d_{\mathrm{f}} and their interface d_{\mathrm{I}}. Using scaling arguments and Monte Carlo simulations, we find that for u<u_{\mathrm{c}}, the structures are in the universality class of clusters generated by simple random walks. For u>u_{\mathrm{c}}, the clusters are compact, i.e. d_{\mathrm{f}}=d and d_{\mathrm{I}}=d-1. At u_{\mathrm{c}}, the SATW is in a new universality class. The clusters are compact in both d=2 and d=3, but their interface is fractal: d_{\mathrm{I}}=1.50\pm0.01 and 2.73\pm0.03 in d=2 and d=3, respectively. In d=1, where the walk is collapsed for all u and no swelling-collapse transition exists, we derive analytical expressions for the average number of visited sites and the mean time to visit S sites.Comment: 15 pages, 8 postscript figures, submitted to Phys. Rev.

Quenched Averages for self-avoiding walks and polygons on deterministic fractals

We study rooted self avoiding polygons and self avoiding walks on deterministic fractal lattices of finite ramification index. Different sites on such lattices are not equivalent, and the number of rooted open walks W_n(S), and rooted self-avoiding polygons P_n(S) of n steps depend on the root S. We use exact recursion equations on the fractal to determine the generating functions for P_n(S), and W_n(S) for an arbitrary point S on the lattice. These are used to compute the averages $, ,$ and $<log W_n(S)>$ over different positions of S. We find that the connectivity constant $\mu$, and the radius of gyration exponent $\nu$ are the same for the annealed and quenched averages. However, $~ n log \mu + (\alpha_q -2) log n$, and $~ n log \mu + (\gamma_q -1)log n$, where the exponents $\alpha_q$ and $\gamma_q$ take values different from the annealed case. These are expressed as the Lyapunov exponents of random product of finite-dimensional matrices. For the 3-simplex lattice, our numerical estimation gives $\alpha_q \simeq 0.72837 \pm 0.00001$; and $\gamma_q \simeq 1.37501 \pm 0.00003$, to be compared with the annealed values $\alpha_a = 0.73421$ and $\gamma_a = 1.37522$.Comment: 17 pages, 10 figures, submitted to Journal of Statistical Physic

Targeting lyn kinase in chorea-acanthocytosis: A translational treatment approach in a rare disease

Background: Chorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms in this disease, and therefore represents a promising drug target. Methods: We evaluated an individual off-label treatment with the tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8–50.4 weeks) of three ChAc patients. Alongside thorough safety monitoring, we assessed motor and non-motor scales (e.g., MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g., serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells). Results: Dasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels, and acanthocyte count did not reveal consistent effects. However, a reduction of initially elevated Lyn kinase activity and accumulated autophagy markers, as well as a partial restoration of the actin cytoskeleton, was found in red blood cells. Conclusions: We report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for “clinical trial readiness”. We suggest a panel of outcome parameters for future clinical trials in ChA

Swelling-collapse transition of self-attracting walks

We study the structural properties of self-attracting walks in d dimensions using scaling arguments and Monte Carlo simulations. We find evidence for a transition analogous to the \Theta transition of polymers. Above a critical attractive interaction u_c, the walk collapses and the exponents \nu and k, characterising the scaling with time t of the mean square end-to-end distance ~ t^{2 \nu} and the average number of visited sites ~ t^k, are universal and given by \nu=1/(d+1) and k=d/(d+1). Below u_c, the walk swells and the exponents are as with no interaction, i.e. \nu=1/2 for all d, k=1/2 for d=1 and k=1 for d >= 2. At u_c, the exponents are found to be in a different universality class.Comment: 6 pages, 5 postscript figure

Polymers in long-range-correlated disorder

We study the scaling properties of polymers in a d-dimensional medium with quenched defects that have power law correlations ~r^{-a} for large separations r. This type of disorder is known to be relevant for magnetic phase transitions. We find strong evidence that this is true also for the polymer case. Applying the field-theoretical renormalization group approach we perform calculations both in a double expansion in epsilon=4-d and delta=4-a up to the 1-loop order and secondly in a fixed dimension (d=3) approach up to the 2-loop approximation for different fixed values of the correlation parameter, 2=<a=<3. In the latter case the numerical results need appropriate resummation. We find that the asymptotic behavior of self-avoiding walks in three dimensions and long-range-correlated disorder is governed by a set of separate exponents. In particular, we give estimates for the 'nu' and 'gamma' exponents as well as for the correction-to-scaling exponent 'omega'. The latter exponent is also calculated for the general m-vector model with m=1,2,3.Comment: 13 pages, 5 figure

Weak quenched disorder and criticality: resummation of asymptotic(?) series

In these lectures, we discuss the influence of weak quenched disorder on the critical behavior in condensed matter and give a brief review of available experimental and theoretical results as well as results of MC simulations of these phenomena. We concentrate on three cases: (i) uncorrelated random-site disorder, (ii) long-range-correlated random-site disorder, and (iii) random anisotropy. Today, the standard analytical description of critical behavior is given by renormalization group results refined by resummation of the perturbation theory series. The convergence properties of the series are unknown for most disordered models. The main object of these lectures is to discuss the peculiarities of the application of resummation techniques to perturbation theory series of disordered models.Comment: Lectures given at the Second International Pamporovo Workshop on Cooperative Phenomena in Condensed Matter (28th July - 7th August 2001, Pamporovo, Bulgaria). 51 pages, 12 figures, 1 style files include

Multifractal behavior of linear polymers in disordered media

The scaling behavior of linear polymers in disordered media modelled by self-avoiding random walks (SAWs) on the backbone of two- and three-dimensional percolation clusters at their critical concentrations p_c is studied. All possible SAW configurations of N steps on a single backbone configuration are enumerated exactly. We find that the moments of order q of the total number of SAWs obtained by averaging over many backbone configurations display multifractal behavior, i.e. different moments are dominated by different subsets of the backbone. This leads to generalized coordination numbers \mu_q and enhancement exponents \gamma_q, which depend on q. Our numerical results suggest that the relation \mu_1 = p_ c \mu between the first moment \mu_1 and its regular lattice counterpart \mu is valid.Comment: 11 pages, 12 postscript figures, to be published in Phys. Rev.

Aging Impairs Recipient T Cell Intrinsic and Extrinsic Factors in Response to Transplantation

As increasing numbers of older people are listed for solid organ transplantation, there is an urgent need to better understand how aging modifies alloimmune responses. Here, we investigated whether aging impairs the ability of donor dendritic cells or recipient immunity to prime alloimmune responses to organ transplantation.Using murine experimental models, we found that aging impaired the host environment to expand and activate antigen specific CD8(+) T cells. Additionally, aging impaired the ability of polyclonal T cells to induce acute allograft rejection. However, the alloimmune priming capability of donor dendritic cells was preserved with aging.Aging impairs recipient responses, both T cell intrinsic and extrinsic, in response to organ transplantation

International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium

Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed on by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multicenter clinical trials. We developed guidelines through international expert consensus opinion to standardize the diagnosis and clinical staging of GVHD for use in a large international GVHD research consortium. During the first year of use, the guidance followed discussion of complex clinical phenotypes by experienced transplant physicians and data managers. These guidelines increase the uniformity of GVHD symptom capture, which may improve the reproducibility of GVHD clinical trials after further prospective validation