Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex^® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.     

Photo-vulcanization using thiol-ene chemistry: Film formation,morphology and network characteristics of UV crosslinked rubber latices

The photo-vulcanization with versatile thiol-ene chemistry represents an innovative approach to crosslink diene-rubber materials both in latex and in solid film state. In this work, the structure of elastomer-based thiol-ene networks and the morphology after film formation are studied in detail using electron microscopic techniques, atomic force microscopy and multiple-quantum solid-state NMR spectroscopy. Additionally, film formation properties and corresponding macroscopic properties of photo-vulcanized natural rubber (NR) latex and its synthetic counterpart, isoprene rubber (IR) latex, are determined in dependence on the curing procedure (pre- and post-vulcanization). The results reveal that thiol-ene cured elastomers comprise homogenously distributed crosslinks with a low amount of short chain defects. Whilst photochemically pre-cured NR latex particles provide coherent films, the film formation and mechanical properties of IR are strongly governed by the crosslink density of the latex particles. In film state, photo-vulcanization promotes narrow crosslink distributions and excellent tensile properties of both NR and IR.     

On the settling of a bidisperse suspension with particles having different sizes and densities

The settling of a bidisperse suspension with small particles having different sizes and densities can be described by an initial value problem for a system of two non-linear, first-order conservation laws. Solutions to this problem are in general discontinuous and exhibit kinematic shocks that separate areas of different composition. The solution requires the construction of so-called elementary curves in phase space, which are determined from eigenvector fields of the Jacobian of the flux function. Differences in solution behavior to the previously analyzed equal-density case are due to an umbilic point, which appears for different densities only. The initial value problem is eventually solved by the front tracking method, which generates a series of Riemann problems. It turns out that the solution of the problem predicts a fairly complex process of sediment formation, and that the stationary solution can consist of non-constant smooth transitions. This observation is of interest for manufacturing of functionally graded materials.     

Intermittent Fasting Primes the Tumor Microenvironment and Improves Nanomedicine Delivery in Hepatocellular Carcinoma

Fasting has many health benefits, including reduced chemotherapy toxicity and improved efficacy. It is unclear how fasting affects the tumor microenvironment (TME) and tumor-targeted drug delivery. Here the effects of intermittent (IF) and short-term (STF) fasting are investigated on tumor growth, TME composition, and liposome delivery in allogeneic hepatocellular carcinoma (HCC) mouse models. To this end, mice are inoculated either subcutaneously or intrahepatically with Hep-55.1C cells and subjected to IF for 24 d or to STF for 1 d. IF but not STF significantly slows down tumor growth. IF increases tumor vascularization and decreases collagen density, resulting in improved liposome delivery. In vitro, fasting furthermore promotes the tumor cell uptake of liposomes. These results demonstrate that IF shapes the TME in HCC towards enhanced drug delivery. Finally, when combining IF with liposomal doxorubicin treatment, the antitumor efficacy of nanochemotherapy is found to be increased, while systemic side effects are reduced. Altogether, these findings exemplify that the beneficial effects of fasting on anticancer therapy outcomes go beyond modulating metabolism at the molecular level.     

Towards a comprehensive proteome of normal and malignant human colon tissue by 2-D-LC-ESI-MS and 2-DE proteomics and identification of S100A12 as potential cancer biomarker

The aim of this study was to characterize the proteome of normal and malignant colonic tissue. We previously studied the colon proteome using 2‐DE and MALDI‐MS and identified 734 proteins (Roeßler, M., Rollinger, W., Palme S., Hagmann, M.‐L., et al.., Clin. Cancer Res. 2005, 11, 6550–6557). Here we report the identification of additional colon proteins from the same set of tissue samples using a complementary nano‐flow 2‐D‐LC‐ESI‐MS. In total, 484 proteins were identified in colon. Of these, 252 had also been identified by the 2‐DE/MALDI‐MS approach, whereas 232 proteins were unique to the 2‐D‐LC‐ESI‐MS analysis. Comparing protein expression in neoplastic and normal colon tissue indicated elevated expression of several proteins in colorectal cancer, among them the well established tumor marker carcinoembryonic antigen, as well as calnexin, 40S ribosomal protein S15a, serpin H1, and S100A12. Overexpression of these proteins was confirmed by immunoblotting. Serum levels of S100A12 were determined by ELISA and were found to be strongly elevated in colorectal cancer patients compared to healthy individuals. We conclude, that 2‐D‐LC‐ESI‐MS is a powerful approach to identify and compare protein profiles of tissue samples, that it is complementary to 2‐DE/MALDI‐MS approaches and has the potential to identify novel biomarkers.     

Dye and polymer based light sensor for tag integration

In this work we present a light sensor for tag integration based on the principle of a dye sensitized solar cell, using a flexible substrate and a polymer electrolyte. These features make an integration of the light sensor into current smart label fabrication processes possible. A printable light sensor combined with novel conductive polymers could solve reliability issues resulting from bonding processes. The components of the light sensor were chosen in a way to enable screen print production. The dye Ruthenium 535-bis-TBA has been used as active dye and Iodolyte AN-50 by Solaronix and PEDOT/PSS by H.C. Starck have been used as liquid and polymer electrolyte respectively. In order to prepare the liquid electrolyte for tag integration it has been gelatinized by addition of silica gel. Depending on the amount of silica gel different stiffness levels have been achieved. The functional layers have been deposited first on glass substrate and then on KAPTON foil by Du Pont. The polymer has been used as flexible substrate. Special care has been taken regarding the preparation of the transparent electrode. The transparent conductive oxide (TCO) indium tin oxide (ITO), which has been used as transparent electrode, has to be cured at elevated temperatures on the polymer substrate. A complete process flow for an integrated light sensor is being described in this work.     

Web accessibility implementation in private sector organizations: motivations and business impact

Despite the prominence of the World Wide Web in people’s everyday lives, most Web presences in private sector organizations still fail to comply with contemporary accessibility standards. As a consequence, a large group of users—i.e., people with impairments—are excluded from accessing these Web presences. In order to explain the managerial rationale, an exploratory case study was conducted in three industry sectors. The results of the analysis shed light on organizations’ motivations to implement or reject Web accessibility standards, reveal positive and negative consequences of implementation, and provide in-depth insights into the determinants for successful and unsuccessful Web accessibility implementation. This study supports organizations in making better decisions on the implementation of Web accessibility.     

Norms for change in episodic memory as a prerequisite for the diagnosis of mild cognitive impairment (MCI).

The new diagnostic criteria for mild cognitive impairment (MCI) from the International Working Group on Mild Cognitive Impairment (Winblad et al., 2004, p. 243) list “evidence of decline over time in objective cognitive tasks” as one diagnostic sign, implying the repeated neuropsychological testing. This study aimed to compare different assessment methods of longitudinal change based on the performances of 366 cognitively healthy participants (237 men, 129 women) examined with a German version of the California Verbal Learning Test (Delis, Kramer, Kaplan, & Ober, 1987) at baseline and 2 years later. Age, education, gender, and baseline performance were taken into account. Results revealed marked practice effects after 2 years. Normal ranges for change that controls for practice effects and regression to the mean proved to be superior to other reliable change indexes. This new method allows for more valid interpretation of change in neuropsychological functioning and thus diagnosis of MCI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)