351 research outputs found
Calibration of the Particle Density in Cellular-Automaton Models for Traffic Flow
We introduce density dependence of the cell size in cellular-automaton models
for traffic flow, which allows a more precise correspondence between real-world
phenomena and what observed in simulation. Also, we give an explicit
calibration of the particle density particularly for the asymmetric simple
exclusion process with some update rules. We thus find that the present method
is valid in that it reproduces a realistic flow-density diagram.Comment: 2 pages, 2 figure
Studies on terrein as a new class of proteasome inhibitors
The proteasome is an intracellular multicatalytic protease involved in the cell cycle regulation, signaling response, antigen presentation and apoptosis. Since proteasome inhibitors promote cell death by apoptosis, they have been proposed as new anti-tumoral drugs. Terrein, a secondary metabolite secreted by the fungus Aspergillus terreus, was firstly described in 1935. In the present work we report that terrein isolated through the screening for inhibitors of the 20S proteasome showed inhibitory effect upon both chymotrypsin- and trypsin-like activities of the multicatalytic core particle, the 20S proteasome. Despite of the high inhibitory concentration determined in vitro, that verified by incubating cells (fibroblasts and a pulmonary tumor cell line) in the presence of terrein was 4-fold lower indicating the proteasome as a selective intracellular target. Moreover, terrein promoted apoptotic cell death on both fibroblasts and pulmonary tumor cell line tested. Although terrein concentrations (mM range) necessary to elicit apoptosis in the cellular models herein tried were high when compared to those (μM and nM range) of other inhibitors recently described, its chemical structure is not correlated to any other inhibitor reported thus far. Therefore, the present results point out for the possibility of exploring terrein as a new molecular fragment for the development of synthetic proteasome inhibitors
Band structure of ZnO from resonant x-ray emission spectroscopy
Soft x-ray emission and absorption spectroscopy of the O K-edge are employed
to investigate the electronic structure of wurtzite ZnO(0001). A quasiparticle
band structure calculated within the GW approximation agrees well with the
data, most notably with the energetic location of the Zn3d - O2p hybridized
state and the anisotropy of the absorption spectra. Dispersion in the band
structure is mapped using the coherent k-selective part of the resonant x-ray
emission spectra. We show that a more extensive mapping of the bands is
possible in the case of crystalline anisotropy such as that found in ZnO.Comment: 5 pages, 5 figure
Final results of the telaprevir access program: Fibroscan values predict safety and efficacy in hepatitis c patients with advanced fibrosis or cirrhosis
Background: Liver stiffness determined by transient elastography is correlated with hepatic fibrosis stage and has high accuracy for detecting severe fibrosis and cirrhosis in chronic hepatitis C patients. We evaluated the clinical value of baseline FibroScan values for the prediction of safety and efficacy of telaprevir-based therapy in patients with advanced fibrosis and cirrhosis in the telaprevir Early Access Program HEP3002. Methods: 1,772 patients with HCV-1 and bridging fibrosis or cirrhosis were treated with telaprevir plus pegylated interferon-α and ribavirin (PR) for 12 weeks followed by PR alone, the total treatment duration depending on virological response and previous response type. Liver fibrosis stage was determined either by liver biopsy or by non-invasive markers. 1,282 patients (72%) had disease stage assessed by FibroScan; among those 46% were classified as Metavir F3 at baseline and 54% as F4. Results: Overall, 1,139 patients (64%) achieved a sustained virological response (SVR) by intentionto- treat analysis. Baseline FibroScan values were tested for association with SVR and the occurrence of adverse events. By univariate analysis, higher baseline FibroScan values were predictive of lower sustained virological response rates and treatment-related anemia. By multivariate analysis, FibroScan was no longer statistically significant as an independent predictor, but higher FibroScan values were correlated with the occurrence of infections and serious adverse events. Conclusions: FibroScan has a limited utility as a predictor of safety and efficacy in patients treated with telaprevir-based triple therapy. Nevertheless it can be used in association with other clinical and biological parameters to help determine patients who will benefit from the triple regiments. © 2015 Lepida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis
Increased glucose uptake mediated by glucose
transporters and reliance on glycolysis are common features
of malignant cells. Hypoxia-inducible factor-1α supports the
adaptation of hypoxic cells by inducing genes related to
glucose metabolism. The contribution of glucose transporter
(GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to
tumor behavior and their prognostic value in head and neck
cancers remains unclear. The aim of this study was to examine
the predictive value of GLUT1, GLUT3, and HIF-1α messenger
RNA (mRNA)/protein expression as markers of tumor
aggressiveness and prognosis in laryngeal cancer. The level of
hypoxia/metabolic marker genes was determined in 106 squamous
cell laryngeal cancer (SCC) and 73 noncancerous
matched mucosa (NCM) controls using quantitative realtime
PCR. The related protein levels were analyzed by
Western blot. Positive expression of SLC2A1, SLC2A3, and
HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC
specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer
samples. Higher levels of mRNA/protein for GLUT1 and
HIF-1α were noted in SCC compared to NCM (p<0.05).
SLC2A1 was found to have a positive relationship with grade,
tumor front grading (TFG) score, and depth and mode of
invasion (p<0.05). SLC2A3 was related to grade and invasion
type (p<0.05). There were also relationships of HIF-1α with
pTNM, TFG scale, invasion depth and mode, tumor recurrences,
and overall survival (p<0.05). In addition, more advanced
tumors were found to be more likely to demonstrate
positive expression of these proteins. In conclusion, the
hypoxia/metabolic markers studied could be used as molecular
markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory
fund of the Department of Cytobiochemistry, University of Łódź, Poland
(506/811), and by grant fromtheNational Science Council, Poland (N403
043 32/2326)
Non equilibrium steady states: fluctuations and large deviations of the density and of the current
These lecture notes give a short review of methods such as the matrix ansatz,
the additivity principle or the macroscopic fluctuation theory, developed
recently in the theory of non-equilibrium phenomena. They show how these
methods allow to calculate the fluctuations and large deviations of the density
and of the current in non-equilibrium steady states of systems like exclusion
processes. The properties of these fluctuations and large deviation functions
in non-equilibrium steady states (for example non-Gaussian fluctuations of
density or non-convexity of the large deviation function which generalizes the
notion of free energy) are compared with those of systems at equilibrium.Comment: 35 pages, 9 figure
A pedestrian's view on interacting particle systems, KPZ universality, and random matrices
These notes are based on lectures delivered by the authors at a Langeoog
seminar of SFB/TR12 "Symmetries and universality in mesoscopic systems" to a
mixed audience of mathematicians and theoretical physicists. After a brief
outline of the basic physical concepts of equilibrium and nonequilibrium
states, the one-dimensional simple exclusion process is introduced as a
paradigmatic nonequilibrium interacting particle system. The stationary measure
on the ring is derived and the idea of the hydrodynamic limit is sketched. We
then introduce the phenomenological Kardar-Parisi-Zhang (KPZ) equation and
explain the associated universality conjecture for surface fluctuations in
growth models. This is followed by a detailed exposition of a seminal paper of
Johansson that relates the current fluctuations of the totally asymmetric
simple exclusion process (TASEP) to the Tracy-Widom distribution of random
matrix theory. The implications of this result are discussed within the
framework of the KPZ conjecture.Comment: 52 pages, 4 figures; to appear in J. Phys. A: Math. Theo
Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation
Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia
An efficient C0 FE model for the analysis of composites and sandwich laminates with general layup
- …