Immunoscreening of the extracellular proteome of colorectal cancer cells

<p>Abstract</p> <p>Background</p> <p>The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome.</p> <p>Methods</p> <p>For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest.</p> <p>Results</p> <p>From 281 secretome proteins stained with autoantibodies in total we first defined the "background patterns" of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities.</p> <p>Conclusions</p> <p>Our findings suggest, first, that autoantibody responses may be due, in large part, to cross-presentation of antigens to the immune system via exosomes, membrane vesicles released by tumor cells and constituting a significant fraction of the secretome. In addition, this immunosecretomics approach has revealed novel biomarker candidates, some of them secretome-specific, and thus serves as a promising complementary tool to the frequently reported immunoproteomic studies for biomarker discovery.</p

Validation of the Dutch Comprehensive Inventory of Mindfulness Experiences (CHIME) and development of a short form (CHIME-SF)

Contains fulltext : 206966.pdf (publisher's version ) (Open Access)Objectives: In recent years, there has been a growing interest in the assessment of mindfulness skills. The present study describes the validation of the Dutch Comprehensive Inventory of Mindfulness Experiences (CHIME) and the development of a short form. Methods: The original scale was translated into Dutch. The psychometric properties of the CHIME were examined, including its factor structure, internal consistency, and convergent and discriminant validity in a group of 481 participants consisting of clinical and non-clinical samples. In addition, a 24-item short form (CHIME-SF) was developed and its psychometric properties were assessed in the same sample. Results: Confirmatory factor analyses showed an acceptable model fit of an 8-factor structure of the CHIME with the following subscales: awareness of internal experiences, awareness of external experiences, acting with awareness, accepting and non-judgmental attitude, nonreactive decentering, openness to experiences, awareness of thought’s relativity, and insightful understanding (X2 = 1534.90, df = 601, X2/df = 2.55, CFI = 0.90, RMSEA = 0.057 [90% CI 0.053, 0.060], SRMR = 0.06). The CHIME-SF showed a good model fit (X2 = 486.13, df = 224, X2/df = 0.17, CFI = 0.95, RMSEA = 0.049 [90% CI 0.043, 0.055], SRMR = 0.05.) and the subscales of the CHIME and CHIME-SF showed high corrected correlations (rc = .69-.88). The CHIME and the CHIME-SF proved to be sensitive to change. Conclusions: The results indicate that the Dutch version of the CHIME and CHIME-SF are valid instruments to assess mindfulness skills in clinical and non-clinical populations. The psychometric properties of the CHIME-SF should be further evaluated in an independent sample.12 p

Bessere Ausnutzung von Fernwaermeanlagen. Teilprojekt Hannover-Hamburg: 'Analyse des Regelverhaltens von Fernwaermenetzen'. T. 1: Optimieren einer automatischen Pumpensteuerung auf schnelle Lastwechsel. T. 2: Darstellen der Automatisierungseinrichtungen von Fernwaermepumpen an der Mensch-Maschine-Kommunikationsschnittstelle (MMK). T. 3: Installation und Anpassung des Programmsystems BoFiT (nur Hannover) Abschlussbericht

The general target of the interconnection research intention is discovering margins for optimizing the heat consumption by fast and ensured variation between producers with CHP generation plants and plants for primary heat and reverse. The project is subdivided in three parts: In part 1 the usefulness of automated operation of the communal distributed heating net-work was determined by: Comparison of real measurements with simulated processes calculations of the differential control processes, development and analysis of a control process concept and improvement of the existing controler action in the Hamburg and the Hannover model, investigations of the effects of closed loop control on safety and portrayal of the processes during optimised and automated operation. The advantage of this system can be demonstrated to be both economical and ecological. Safety analysis showed that a higher degree of automation does not compromise safe operation. In Hamburg these findings led to the development of a training simulator for the operating personnel. The optimisation techniques presented in part 1 can therefore be implemented in a model, which provides a very good analogy to the real network. In part 2 innovative forms of presentation of hydraulic relations of the controled District Heating network where developed. They where realised in a computer program. This program was installed in the District Heating control room. The target of part 3 is the practical application of BoFit for the generation of optimized propositions for operation mode of the District Heating net-work. The consideration of the actual condition of the District Heating network was realized by online-connection to the process data processing. The situation of costs of heat supply is found out by simulations for the present moment and for a prognosted period. (orig.)Published in two separate volumesSIGLEAvailable from TIB Hannover: F01B306+a: F01B307+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman