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Search Results: 1 - 10 of 319109 matches for " Robert J. Binder "
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Immunotherapy of Tumors with α2-Macroglobulin-Antigen Complexes Pre-Formed In Vivo
Sudesh Pawaria, Laura E. Kropp, Robert J. Binder
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050365
Abstract: The cell surface receptor CD91/LRP-1 binds to immunogenic heat shock proteins (HSP) and α2M ligands to elicit T cell immune responses. In order to generate specific immune responses, the peptides chaperoned by HSPs or α2M are cross-presented on MHC molecules to T cells. While the immunogenic HSPs naturally chaperone peptides within cells and can be purified as an intact HSP-peptide complex, the peptides have had to be complexed artificially to α2M in previous studies. Here, we show that immunogenic α2M-peptide complexes can be isolated from the blood of tumor-bearing mice without further experimental manipulation in vitro demonstrating the natural association of tumor antigens with α2M. The naturally formed immunogenic α2M-peptide complexes are effective in prophylaxis and therapy of cancer in mouse models. We investigate the mechanisms of cross-presentation of associated peptides and co-stimulation by APCs that interact with α2M. These data have implications for vaccine design in immunotherapy of cancer and infectious disease.
CD91-Dependent Modulation of Immune Responses by Heat Shock Proteins: A Role in Autoimmunity
Robert J. Binder,Yu Jerry Zhou,Michelle N. Messmer,Sudesh Pawaria
Autoimmune Diseases , 2012, DOI: 10.1155/2012/863041
Abstract: Heat shock proteins (HSPs) have been known for decades for their ability to protect cells under stressful conditions. In the 1980s a new role was ascribed for several HSPs given their ability to elicit specific immune responses in the setting of cancer and infectious disease. These immune responses have primarily been harnessed for the immunotherapy of cancer in the clinical setting. However, because of the ability of HSPs to prime diverse immune responses, they have also been used for modulation of immune responses during autoimmunity. The apparent dichotomy of immune responses elicited by HSPs is discussed here on a molecular and cellular level. The potential clinical application of HSP-mediated immune responses for therapy of autoimmune diseases is reviewed. 1. Introduction: HSPs in Immunity Expression of HSPs is generally upregulated in cells in response to a variety of stressful conditions including nonphysiological temperature, nutrient deprivation, and hypoxia [1]. It is the inherent chaperoning function of HSPs that allows them to provide their cytoprotective function in assisting correct protein/polypeptide folding and preventing further protein denaturation. It has become evident over the past two decades that the chaperoning function of HSPs also plays a key role in several processes during the development of immune responses [2]. Within the cell, several HSPs act as chaperones of peptides that are ultimately presented by MHC I and MHC II molecules. Thus, the HSPs in the cytosol and in the endoplasmic reticulum form a relay line for the transport of peptides from their formation by the proteasome to the MHC I heavy chain (HC). This is discussed in the next subheading. As the HSPs are some of the most abundant proteins in cells, their liberation into the extracellular environment has been shown to be a key indicator of loss of cellular integrity and they are rapidly recognized by the cellular sentinels of the immune system. Such recognition allows for cross-priming of the potential antigens that the HSPs chaperone. The efficiency of this pathway predicted a cell surface receptor on the cross-presenting cells and that receptor has now been shown to be CD91. These events are discussed in the next two subheadings. The isolation of HSPs (and the associated peptides) from tumor cells or cells infected with pathogens therefore provides a single entity that primes immune responses specific for the chaperoned peptides and thus for the cell that harbored these antigens. This application has been tested in a vast number of rodent models of cancer and
Ethylene Receptors Function as Components of High-Molecular-Mass Protein Complexes in Arabidopsis
Yi-Feng Chen,Zhiyong Gao,Robert J. Kerris III,Wuyi Wang,Brad M. Binder,G. Eric Schaller
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008640
Abstract: The gaseous plant hormone ethylene is perceived in Arabidopsis thaliana by a five-member receptor family composed of ETR1, ERS1, ETR2, ERS2, and EIN4.
Superparamagnetic Ironoxide Nanoparticles via Ligand Exchange Reactions: Organic 1,2-Diols as Versatile Building Blocks for Surface Engineering
Wolfgang H. Binder,Harald Weinstabl,Robert Sachsenhofer
Journal of Nanomaterials , 2008, DOI: 10.1155/2008/383020
Abstract: A method for the preparation of ligand-covered superparamagnetic iron oxide nanoparticles via exchange reactions is described. 1,2-diol-ligands are used to provide a stable binding of the terminally modified organic ligands onto the surface of -Fe2O3-nanoparticles (~4 nm). The 1,2-diol-ligands are equipped with variable terminal functional groups (i.e., hydrogen bonding moieties, azido- bromo-, fluorescent moieties) and can be easily prepared via osmium tetroxide-catalyzed 1,2-dihydroxylation reactions of the corresponding terminal alkenes. Starting from octylamine-covered -Fe2O3-nanoparticles, ligand exchange was effected at 50°C over 24–48 hours, whereupon complete ligand exchange is taking place as proven by thermogravimetric (TGA)- and IR-spectroscopic measurements. A detailed kinetic analysis of the ligand exchange reaction was performed via TGA analysis, demonstrating a complete ligand exchange after 24 hours. The method offers a simple approach for the generation of various -Fe2O3-nanoparticles with functional organic shells in a one-step procedure.
Physico-chemical modelling of target depletion during hybridisation on oligonulceotide microarrays
Conrad J. Burden,Hans Binder
Quantitative Biology , 2009,
Abstract: The effect of target molecule depletion from the supernatant solution is incorporated into a physico-chemical model of hybridisation on oligonucleotide microarrays. Two possible regimes are identified: local depletion, in which depletion by a given probe feature only affects that particular probe, and global depletion, in which all features responding to a given target species are affected. Examples are given of two existing spike-in data sets experiencing measurable effects of target depletion. The first of these, from an experiment by Suzuki et al. using custom built arrays with a broad range of probe lengths and mismatch positions, is verified to exhibit local and not global depletion. The second dataset, the well known Affymetrix HGU133a latin square experiment is shown to be very well explained by a global depletion model. It is shown that microarray calibrations relying on Langmuir isotherm models which ignore depletion effects will significantly underestimate specific target concentrations. It is also shown that a combined analysis of perfect match and mismatch probe signals in terms of a simple graphical summary, namely the hook curve method, can discriminate between cases of local and global depletion.
Reversible and Irreversible Binding of Nanoparticles to Polymeric Surfaces
Wolfgang H. Binder,Marina Lomoschitz,Robert Sachsenhofer,Gernot Friedbacher
Journal of Nanomaterials , 2009, DOI: 10.1155/2009/613813
Abstract: Reversible and irreversible binding of CdSe-nanoparticles and nanorods to polymeric surfaces via a strong, multiple hydrogen bond (= Hamilton-receptor/barbituric acid) is described. Based on ROMP-copolymers, the supramolecular interaction on a thin polymer film is controlled by living polymerization methods, attaching the Hamilton-receptor in various architectures, and concentrations. Strong binding is observed with CdSe-nanoparticles and CdSe-nanorods, whose surfaces are equipped with matching barbituric acid-moieties. Addition of polar solvents, able to break the hydrogen bonds leads to the detachment of the nanoparticles from the polymeric film. Irreversible binding is observed if an azide/alkine-“click”-reaction is conducted after supramolecular recognition of the nanoparticles on the polymeric surface. Thus reversible or irreversible attachment of the nanosized objects can be achieved.
Ab Initio Path to Heavy Nuclei
Sven Binder,Joachim Langhammer,Angelo Calci,Robert Roth
Physics , 2013, DOI: 10.1016/j.physletb.2014.07.010
Abstract: We present the first ab initio calculations of nuclear ground states up into the domain of heavy nuclei, spanning the range from 16-O to 132-Sn based on two- plus three-nucleon interactions derived within chiral effective field theory. We employ the similarity renormalization group for preparing the Hamiltonian and use coupled-cluster theory to solve the many-body problem for nuclei with closed sub-shells. Through an analysis of theoretical uncertainties resulting from various truncations in this framework, we identify and eliminate the technical hurdles that previously inhibited the step beyond medium-mass nuclei, allowing for reliable validations of nuclear Hamiltonians in the heavy regime. Following this path we show that chiral Hamiltonians qualitatively reproduce the systematics of nuclear ground-state energies up to the neutron-rich Sn isotopes.
Evolved Chiral NN+3N Hamiltonians for Ab Initio Nuclear Structure Calculations
Robert Roth,Angelo Calci,Joachim Langhammer,Sven Binder
Physics , 2013, DOI: 10.1103/PhysRevC.90.024325
Abstract: We discuss the building blocks for a consistent inclusion of chiral three-nucleon (3N) interactions into ab initio nuclear structure calculations beyond the lower p-shell. We highlight important technical developments, such as the similarity renormalization group (SRG) evolution in the 3N sector, a JT-coupled storage scheme for 3N matrix elements with efficient on-the-fly decoupling, and the importance truncated no-core shell model with 3N interactions. Together, these developments make converged ab initio calculations with explicit 3N interactions possible also beyond the lower p-shell. We analyze in detail the impact of various truncations of the SRG-evolved Hamiltonian, in particular the truncation of the harmonic-oscillator model space used for solving the SRG flow equations and the omission of the induced beyond-3N contributions of the evolved Hamiltonian. Both truncations lead to sizable effects in the upper p-shell and beyond and we present options to remedy these truncation effects. The analysis of the different truncations is a first step towards a systematic uncertainty quantification of all stages of the calculation.
Multiple Kernel Learning for Brain-Computer Interfacing
Wojciech Samek,Alexander Binder,Klaus-Robert Müller
Statistics , 2013, DOI: 10.1109/EMBC.2013.6611181
Abstract: Combining information from different sources is a common way to improve classification accuracy in Brain-Computer Interfacing (BCI). For instance, in small sample settings it is useful to integrate data from other subjects or sessions in order to improve the estimation quality of the spatial filters or the classifier. Since data from different subjects may show large variability, it is crucial to weight the contributions according to importance. Many multi-subject learning algorithms determine the optimal weighting in a separate step by using heuristics, however, without ensuring that the selected weights are optimal with respect to classification. In this work we apply Multiple Kernel Learning (MKL) to this problem. MKL has been widely used for feature fusion in computer vision and allows to simultaneously learn the classifier and the optimal weighting. We compare the MKL method to two baseline approaches and investigate the reasons for performance improvement.
Washing scaling of GeneChip microarray expression
Hans Binder, Knut Krohn, Conrad J Burden
BMC Bioinformatics , 2010, DOI: 10.1186/1471-2105-11-291
Abstract: We conducted experiments on GeneChip microarrays with altered protocols for washing, scanning and staining to study the probe-level intensity changes as a function of the number of washing cycles. For calibration and analysis of the intensity data we make use of the 'hook' method which allows intensity contributions due to non-specific and specific hybridization of perfect match (PM) and mismatch (MM) probes to be disentangled in a sequence specific manner. On average, washing according to the standard protocol removes about 90% of the non-specific background and about 30-50% and less than 10% of the specific targets from the MM and PM, respectively. Analysis of the washing kinetics shows that the signal-to-noise ratio doubles roughly every ten stringent washing cycles. Washing can be characterized by time-dependent rate constants which reflect the heterogeneous character of target binding to microarray probes. We propose an empirical washing function which estimates the survival of probe bound targets. It depends on the intensity contribution due to specific and non-specific hybridization per probe which can be estimated for each probe using existing methods. The washing function allows probe intensities to be calibrated for the effect of washing. On a relative scale, proper calibration for washing markedly increases expression measures, especially in the limit of small and large values.Washing is among the factors which potentially distort expression measures. The proposed first-order correction method allows direct implementation in existing calibration algorithms for microarray data. We provide an experimental 'washing data set' which might be used by the community for developing amendments of the washing correction.Gene expression profiling using microarrays has become a standard technique for the large scale estimation of transcript abundance [1]. The method is based on the hybridization of RNA prepared from samples of interest with gene-specific oligonucleoti
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