Competition between Antiferromagnetism and Superconductivity in High TcT_c Cuprates

Using variational cluster perturbation theory we study the competition between d-wave superconductivity (dSC) and antiferromagnetism (AF) in the the t-t'-t''-U Hubbard model. Large scale computer calculations reproduce the overall ground state phase diagram of the high-temperature superconductors as well as the one-particle excitation spectra for both hole- and electron-doping. We identify clear signatures of the Mott gap as well as of AF and of dSC that should be observable in photoemission experiments.Comment: 4 pages, 4 figure

A non-hybrid method for the PDF equations of turbulent flows on unstructured grids

In probability density function (PDF) methods of turbulent flows, the joint PDF of several flow variables is computed by numerically integrating a system of stochastic differential equations for Lagrangian particles. A set of parallel algorithms is proposed to provide an efficient solution of the PDF transport equation, modeling the joint PDF of turbulent velocity, frequency and concentration of a passive scalar in geometrically complex configurations. An unstructured Eulerian grid is employed to extract Eulerian statistics, to solve for quantities represented at fixed locations of the domain (e.g. the mean pressure) and to track particles. All three aspects regarding the grid make use of the finite element method (FEM) employing the simplest linear FEM shape functions. To model the small-scale mixing of the transported scalar, the interaction by exchange with the conditional mean model is adopted. An adaptive algorithm that computes the velocity-conditioned scalar mean is proposed that homogenizes the statistical error over the sample space with no assumption on the shape of the underlying velocity PDF. Compared to other hybrid particle-in-cell approaches for the PDF equations, the current methodology is consistent without the need for consistency conditions. The algorithm is tested by computing the dispersion of passive scalars released from concentrated sources in two different turbulent flows: the fully developed turbulent channel flow and a street canyon (or cavity) flow. Algorithmic details on estimating conditional and unconditional statistics, particle tracking and particle-number control are presented in detail. Relevant aspects of performance and parallelism on cache-based shared memory machines are discussed.Comment: Accepted in Journal of Computational Physics, Feb. 20, 200

Lysosomal rupture induced by structurally distinct chitosans either promotes a type 1 IFN response or activates the inflammasome in macrophages

Chitosan is a family of glucosamine and N-acetyl glucosamine polysaccharides with poorly understood immune modulating properties. Here, functional U937 macrophage responses were analyzed in response to a novel library of twenty chitosans with controlled degree of deacetylation (DDA, 60-98%), molecular weight (1 to >100 kDa), and acetylation pattern (block vs. random). Specific chitosan preparations (10 or 190 kDa 80% block DDA and 3, 5, or 10 kDa 98% DDA) either induced macrophages to release CXCL10 and IL-1ra at 5-50 mug/mL, or activated the inflammasome to release IL-1beta and PGE2 at 50-150 mug/mL. Chitosan induction of these factors required lysosomal acidification. CXCL10 production was preceded by lysosomal rupture as shown by time-dependent co-localization of galectin-3 and chitosan and slowed autophagy flux, and specifically depended on IFN-beta paracrine activity and STAT-2 activation that could be suppressed by PGE2. Chitosan induced a type I IFN paracrine response or inflammasome response depending on the extent of lysosomal rupture and cytosolic foreign body invasion. This study identifies the structural motifs that lead to chitosan-driven cytokine responses in macrophages and indicates that lysosomal rupture is a key mechanism that determines the endogenous release of either IL-1ra or IL-1beta

Intra-arterial chemoradiation for T3-4 oral cavity cancer: Treatment outcomes in comparison to oropharyngeal and hypopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Surgery followed by radiotherapy is the standard of care for resectable locally advanced oral cavity squamous cell carcinoma (SCC). We report the treatment outcomes of patients with T3-T4 SCC of the oral cavity treated with chemoradiation, an alternative approach.</p> <p>Patients and methods</p> <p>From a series of 240 patients with stage III-IV carcinoma of the upper aerodigestive tract who were treated consecutively according to the RADPLAT protocol, a subset analysis of 155 patients with T3-T4 SCC (Oral cavity SCC N = 22, oropharynx SCC N = 94 and hypopharynx SCC N = 39), was performed. The goal was to test the hypothesis that oral cavity SCC treated with chemoradiation has similar outcomes to the two comparison sites.</p> <p>Results</p> <p>With a median follow-up of 58 months, local disease control was 69% and the overall survival was 37%. In comparison, local disease control for the oropharynx and hypopharynx groups was 86% and 79% respectively. The overall survival rate for the oropharyngeal and hypopharyngeal groups were 41% and 6% respectively</p> <p>Conclusion</p> <p>Patients with locally advanced oral cavity cancer treated with the chemoradiation protocol RADPLAT have outcomes that are equal or better compared to patients with similar disease involving the oropharynx and hypopharynx</p

Enhanced Gene Delivery Mediated by Low Molecular Weight Chitosan/DNA Complexes: Effect of pH and Serum

This study was designed to systematically evaluate the influence of pH and serum on the transfection process of chitosan-DNA complexes, with the objective of maximizing their efficiency. The hydrodynamic diameter of the complexes, measured by dynamic light scattering (DLS), was found to increase with salt and pH from 243 nm in water to 1244 nm in PBS at pH 7.4 and aggregation in presence of 10% serum. The cellular uptake of complexes into HEK 293 cells assessed by flow cytometry and confocal fluorescent imaging was found to increase at lower pH and serum. Based on these data, new methodology were tested and high levels of transfection (>40%) were achieved when transfection was initiated at pH 6.5 with 10% serum for 8-24 h to maximize uptake and then the media was changed to pH 7.4 with 10% serum for an additional 24-40 h period. Cytotoxicity of chitosan/DNA complexes was also considerably lower than Lipofectamine. Our study demonstrates that the evaluation of the influence of important parameters in the methodology of transfection enables the understanding of crucial physicochemical and biological mechanisms which allows for the design of methodologies maximising transgene expression

Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells

Cancer gene therapy requires the design of non-viral vectors that carry genetic material and selectively deliver it with minimal toxicity. Non-viral vectors based on cationic natural polymers can form electrostatic complexes with negatively-charged polynucleotides such as microRNAs (miRNAs). Here we investigated the physicochemical/biophysical properties of chitosan–hsa-miRNA-145 (CS–miRNA) nanocomplexes and the biological responses of MCF-7 breast cancer cells cultured in vitro. Self-assembled CS–miRNA nanocomplexes were produced with a range of (+/−) charge ratios (from 0.6 to 8) using chitosans with various degrees of acetylation and molecular weight. The Z-average particle diameter of the complexes was <200 nm. The surface charge increased with increasing amount of chitosan. We observed that chitosan induces the base-stacking of miRNA in a concentration dependent manner. Surface plasmon resonance spectroscopy shows that complexes formed by low degree of acetylation chitosans are highly stable, regardless of the molecular weight. We found no evidence that these complexes were cytotoxic towards MCF-7 cells. Furthermore, CS–miRNA nanocomplexes with degree of acetylation 12% and 29% were biologically active, showing successful downregulation of target mRNA expression in MCF-7 cells. Our data, therefore, shows that CS–miRNA complexes offer a promising non-viral platform for breast cancer gene therapy

Ki-67 expression predicts locoregional recurrence in stage I oral tongue carcinoma

Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer associated with poor prognosis. Methods for determining the aggressiveness of OTSCC from analysis of the primary tumour specimen are thus highly desirable. We investigated whether genomic instability and proliferative activity (by means of Ki-67 activity) could be of clinical use for prediction of locoregional recurrence in 76 pretreatment OTSCC paraffin samples (stage I, n=22; stage II, n=33; stage III, n=8; stage IV, n=13). Eleven surgical tumour specimens were also analysed for remnants of proliferative activity after preoperative radiotherapy. Ninety-seven percent of cases (n=72) were characterised as being aneuploid as measured by means of image cytometry. Preoperative radiotherapy (50–68 Gy) resulted in significant reduction of proliferative activity in all patients for which post-treatment biopsies were available (P-value=0.001). Proliferative activity was not associated with response to radiation in stage II patients. However, we report a significant correlation between high proliferation rates and locoregional recurrences in stage I OTSCC patients (P-value=0.028). High-proliferative activity is thus related to an elevated risk of recurrence after surgery alone. We therefore conclude that Ki-67 expression level is a potentially useful clinical marker for predicting recurrence in surgically treated stage I OTSCC

Treatment results for hypopharyngeal cancer by different treatment strategies and its secondary primary- an experience in Taiwan

<p>Abstract</p> <p>Purpose</p> <p>The aim of this study was to evaluate treatment results in our hypopharyngeal cancer patients.</p> <p>Patients and Methods</p> <p>A total of three hundred and ninety five hypopharyngeal cancer patients received radical treatment at our hospital; 96% were male. The majority were habitual smokers (88%), alcohol drinkers (73%) and/or betel quid chewers (51%). All patients received a CT scan or MRI for tumor staging before treatment. The stage distribution was stage I: 2 (0.5%); stage II: 22 (5.6%); stage III: 57 (14.4%) and stage IV: 314 (79.5%). Radical surgery was used first in 81 patients (20.5%), and the remaining patients (79.5%) received organ preservation-intended treatment (OPIT). In the OPIT group, 46 patients received radiotherapy alone, 156 patients received chemotherapy followed by radiotherapy (CT/RT) and 112 patients received concomitant chemo-radiotherapy (CCRT).</p> <p>Results</p> <p>The five-year overall survival rates for stages I/II, III and IV were 49.5%, 47.4% and 18.6%, respectively. There was no significant difference in overall and disease-specific survival rates between patients who received radical surgery first and those who received OPIT. In the OPIT group, CCRT tended to preserve the larynx better (p = 0.088), with three-year larynx preservation rates of 44.8% for CCRT and 27.2% for CT/RT. Thirty-seven patients developed a second malignancy, with an annual incidence of 4.6%.</p> <p>Conclusions</p> <p>There was no survival difference between OPIT and radical surgery in hypopharyngeal cancer patients at our hospital. CCRT may offer better laryngeal preservation than RT alone or CT/RT. However, prospective studies are still needed to confirm this finding. Additionally, second primary cancers are another important issue for hypopharyngeal cancer management.</p