Bronchial reactivity to cigarette smoke; relation to lung function, respiratory symptoms, serum-immunoglobulin E and blood eosinophil and leukocyte counts

AbstractStudy objectives: The aim of the study was to investigate the relationship between the immediate bronchial response to inhaled cigarette smoke [cigarette smoke bronchial reactivity (CBR)] and lung function, respiratory symptoms and markers of allergy and inflammation.Design, participants and measurements: This cross-sectional study included 98 smokers. Their lung function and reversibility to inhaled terbutaline was measured. Their clinical history was obtained, an allergological examination was done, and bronchial reactivity to methacholine and inhaled cigarette smoke was measured. Questionnaires about respiratory symptoms, smoking history and drug usage were completed and a blood sample was obtained. Participants were divided into three groups: with asthma, chronic bronchitis and persons without asthma or chronic bronchitis (the respiratory healthy).Results: Forced expiratory volume in 1sec (FEV1) residuals were independently related to the % fall in FEV1after 12 cigarette smoke inhalations (DFEV%) in all participants (P<0·01), in asthmatic smokers (P<0·01) and in smokers with chronic bronchitis (P<0·05). In smokers with asthma and chronic bronchitis FEV1residuals explained 51% and 13% of the variation in DFEV%, respectively, but only 8% (P<0·05) and 1% (N.S.) of the variation in the methacholine bronchial reactivity. In the total population the presence of wheeze (P<0·01), attacks of breathlessness (P<0·05) and daily expectoration (P<0·001) were related to higher DFEV% readings. Serum immunonoglobulin (ES-IgE) was independently related to DFEV% in all participants (P<0·01), in smokers with chronic bronchitis (P<0·01) and in the respiratory healthy (0·05<P<0·1). The eosinophil blood count was, in similar analyses, related to DFEV% in all participants (P<0·05) and in persons with chronic bronchitis (0·05<P<0·1).Conclusion: Cigarette smoke bronchial reactivity was strongly associated to actual FEV1in smokers with asthma and bronchitis, overall to most respiratory symptoms and in smokers without asthma to S-IgE. Cigarette smoke bronchial reactivity might be suitable to test further how cigarette smoke influences the pathophysiology of the bronchial wall, especially in smokers with asthma

Rooted Spiral Trees on Hyper-cubical lattices

We study rooted spiral trees in 2,3 and 4 dimensions on a hyper cubical lattice using exact enumeration and Monte-Carlo techniques. On the square lattice, we also obtain exact lower bound of 1.93565 on the growth constant $\lambda$. Series expansions give $\theta=-1.3667\pm 0.001$ and $\nu = 1.3148\pm0.001$ on a square lattice. With Monte-Carlo simulations we get the estimates as $\theta=-1.364\pm0.01$, and $\nu = 1.312\pm0.01$. These results are numerical evidence against earlier proposed dimensional reduction by four in this problem. In dimensions higher than two, the spiral constraint can be implemented in two ways. In either case, our series expansion results do not support the proposed dimensional reduction.Comment: replaced with published versio

Efficiency of the Incomplete Enumeration algorithm for Monte-Carlo simulation of linear and branched polymers

We study the efficiency of the incomplete enumeration algorithm for linear and branched polymers. There is a qualitative difference in the efficiency in these two cases. The average time to generate an independent sample of $n$ sites for large $n$ varies as $n^2$ for linear polymers, but as $exp(c n^{\alpha})$ for branched (undirected and directed) polymers, where $0<\alpha<1$. On the binary tree, our numerical studies for $n$ of order $10^4$ gives $\alpha = 0.333 \pm 0.005$. We argue that $\alpha=1/3$ exactly in this case.Comment: replaced with published versio

Computational and experimental druggability assessment of human DNA glycosylases

Due to a polar or even charged binding interface, DNA-binding proteins are considered extraordinarily difficult targets for development of small-molecule ligands and only a handful of proteins have been targeted successfully to date. Recently, however, it has been shown that development of selective and efficient inhibitors of 8-oxoguanine DNA glycosylase is possible. Here, we describe the initial druggability assessment of DNA glycosylases in a computational setting and experimentally investigate several methods to target endonuclease VIII-like 1 (NEIL1) with small-molecule inhibitors. We find that DNA glycosylases exhibit good predicted druggability in both DNA-bound and -unbound states. Furthermore, we find catalytic sites to be highly flexible, allowing for a range of interactions and binding partners. One flexible catalytic site was rationalized for NEIL1 and further investigated experimentally using both a biochemical assay in the presence of DNA and a thermal shift assay in the absence of DNA

RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements

The CD11a/CD18 (leukocyte functionassociated antigen 1 [LFA-1]) integrin mediates critical leukocyte adhesive interactions during immune and inflammatory responses. The CD11a promoter directs CD11a/CD18 integrin expression, and its activity in lymphoid cells depends on a functional RUNX1/AML-1–binding site (AML-110) within the MS7 sequence. We now report that MS7 contains a C/EBPbinding site (C/EBP-100), which overlaps with AML-110 and is bound by C/EBP factors in myeloid cells. C/EBP and RUNX/ AML factors compete for binding to their respective cognate elements and bind to the CD11a promoter MS7 sequence in a cell lineage- and differentiation-dependent manner. In myeloid cells MS7 is primarily recognized by C/EBP factors in proliferating cells whereas RUNX/AMLfactors (especially RUNX3/AML-2) bind to MS7 in differentiated cells. RUNX3/AML-2 binding to the CD11a promoter correlates with increased RUNX3/AML-2 protein levels and enhanced CD11a/CD18 cell surface expression. The relevance of the AML-110 element is underscored by the ability of AML-1/ETO to inhibit CD11a promoter activity, thus explaining the low CD11a/CD18 expression in t(8;21)–containing myeloid leukemia cells. Therefore, the expression of the CD11a/CD18 integrin in myeloid cells is determined through the differential occupancy of the CD11a proximal promoter by transcription factors implicated in the pathogenesis of myeloid leukemia

Demagnetization via Nucleation of the Nonequilibrium Metastable Phase in a Model of Disorder

We study both analytically and numerically metastability and nucleation in a two-dimensional nonequilibrium Ising ferromagnet. Canonical equilibrium is dynamically impeded by a weak random perturbation which models homogeneous disorder of undetermined source. We present a simple theoretical description, in perfect agreement with Monte Carlo simulations, assuming that the decay of the nonequilibrium metastable state is due, as in equilibrium, to the competition between the surface and the bulk. This suggests one to accept a nonequilibrium "free-energy" at a mesoscopic/cluster level, and it ensues a nonequilibrium "surface tension" with some peculiar low-T behavior. We illustrate the occurrence of intriguing nonequilibrium phenomena, including: (i) Noise-enhanced stabilization of nonequilibrium metastable states; (ii) reentrance of the limit of metastability under strong nonequilibrium conditions; and (iii) resonant propagation of domain walls. The cooperative behavior of our system may also be understood in terms of a Langevin equation with additive and multiplicative noises. We also studied metastability in the case of open boundaries as it may correspond to a magnetic nanoparticle. We then observe burst-like relaxation at low T, triggered by the additional surface randomness, with scale-free avalanches which closely resemble the type of relaxation reported for many complex systems. We show that this results from the superposition of many demagnetization events, each with a well- defined scale which is determined by the curvature of the domain wall at which it originates. This is an example of (apparent) scale invariance in a nonequilibrium setting which is not to be associated with any familiar kind of criticality.Comment: 26 pages, 22 figure

Search for the Rare Decay KL --> pi0 ee

The KTeV/E799 experiment at Fermilab has searched for the rare kaon decay KL--> pi0ee. This mode is expected to have a significant CP violating component. The measurement of its branching ratio could support the Standard Model or could indicate the existence of new physics. This letter reports new results from the 1999-2000 data set. One event is observed with an expected background at 0.99 +/- 0.35 events. We set a limit on the branching ratio of 3.5 x 10^(-10) at the 90% confidence level. Combining the results with the dataset taken in 1997 yields the final KTeV result: BR(KL --> pi0 ee) < 2.8 x 10^(-10) at 90% CL.Comment: 4 pages, three figure

Sparse Multi-Shell Diffusion Imaging

Abstract. Diffusion magnetic resonance imaging (dMRI) is an impor-tant tool that allows non-invasive investigation of neural architecture of the brain. The data obtained from these in-vivo scans provides important information about the integrity and connectivity of neural fiber bundles in the brain. A multi-shell imaging (MSI) scan can be of great value in the study of several psychiatric and neurological disorders, yet its usabil-ity has been limited due to the long acquisition times required. A typical MSI scan involves acquiring a large number of gradient directions for the 2 (or more) spherical shells (several b-values), making the acquisition time significantly long for clinical application. In this work, we propose to use results from the theory of compressive sampling and determine the minimum number of gradient directions required to attain signal re-construction similar to a traditional MSI scan. In particular, we propose a generalization of the single shell spherical ridgelets basis for sparse rep-resentation of multi shell signals. We demonstrate its efficacy on several synthetic and in-vivo data sets and perform quantitative comparisons with solid spherical harmonics based representation. Our preliminary re-sults show that around 20-24 directions per shell are enough for robustly recovering the diffusion propagator.

Стратегічне планування як основний інструмент ефективності підприємства

Наук. кер.: А.Ю. Жулавськи

A review of Monte Carlo simulations of polymers with PERM

In this review, we describe applications of the pruned-enriched Rosenbluth method (PERM), a sequential Monte Carlo algorithm with resampling, to various problems in polymer physics. PERM produces samples according to any given prescribed weight distribution, by growing configurations step by step with controlled bias, and correcting "bad" configurations by "population control". The latter is implemented, in contrast to other population based algorithms like e.g. genetic algorithms, by depth-first recursion which avoids storing all members of the population at the same time in computer memory. The problems we discuss all concern single polymers (with one exception), but under various conditions: Homopolymers in good solvents and at the $\Theta$ point, semi-stiff polymers, polymers in confining geometries, stretched polymers undergoing a forced globule-linear transition, star polymers, bottle brushes, lattice animals as a model for randomly branched polymers, DNA melting, and finally -- as the only system at low temperatures, lattice heteropolymers as simple models for protein folding. PERM is for some of these problems the method of choice, but it can also fail. We discuss how to recognize when a result is reliable, and we discuss also some types of bias that can be crucial in guiding the growth into the right directions.Comment: 29 pages, 26 figures, to be published in J. Stat. Phys. (2011