Critical Casimir forces and adsorption profiles in the presence of a chemically structured substrate

Motivated by recent experiments with confined binary liquid mixtures near demixing, we study the universal critical properties of a system, which belongs to the Ising universality class, in the film geometry. We employ periodic boundary conditions in the two lateral directions and fixed boundary conditions on the two confining surfaces, such that one of them has a spatially homogeneous adsorption preference while the other one exhibits a laterally alternating adsorption preference, resembling locally a single chemical step. By means of Monte Carlo simulations of an improved Hamiltonian, so that the leading scaling corrections are suppressed, numerical integration, and finite-size scaling analysis we determine the critical Casimir force and its universal scaling function for various values of the aspect ratio of the film. In the limit of a vanishing aspect ratio the critical Casimir force of this system reduces to the mean value of the critical Casimir force for laterally homogeneous ++ and +- boundary conditions, corresponding to the surface spins on the two surfaces being fixed to equal and opposite values, respectively. We show that the universal scaling function of the critical Casimir force for small but finite aspect ratios displays a linear dependence on the aspect ratio which is solely due to the presence of the lateral inhomogeneity. We also analyze the order-parameter profiles at criticality and their universal scaling function which allows us to probe theoretical predictions and to compare with experimental data.Comment: revised version, section 5.2 expanded; 53 pages, 12 figures, iopart clas

Novel autoantigens immunogenic in COPD patients

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients.</p> <p>Methods</p> <p>An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera.</p> <p>Results</p> <p>By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By <it>in silico </it>sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity.</p> <p>Conclusion</p> <p>The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.</p

Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma

<p>Abstract</p> <p>Background</p> <p>The SRY-related HMG-box family of transcription factors member <it>SOX2 </it>has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients.</p> <p>Methods</p> <p>Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for <it>SOX2</it>, <it>NANOG </it>and <it>OCT4 </it>gene expression by real-time PCR.</p> <p>Results</p> <p>SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432).</p> <p>Conclusions</p> <p>In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.</p

Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics

The evolution of proteins with novel function is thought to start from precursor proteins that are conformationally heterogeneous. The corresponding genes may be duplicated and then mutated to select and optimize a specific conformation. However, testing this idea has been difficult because of the challenge of quantifying protein flexibility and conformational heterogeneity as a function of evolution. Here, we report the characterization of protein heterogeneity and dynamics as a function of evolution for the antifluorescein antibody 4-4-20. Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular dynamics simulations, we demonstrate that evolution localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein. This study demonstrates how protein dynamics may be tailored by evolution and has important implications for our understanding of how novel protein functions are evolved