Titaniumcarboxonitride layer increased biocompatibility of medical polyetherurethanes.

Polyetherurethane (PEU) is in use for blood-contacted devices because of its excellent mechanical properties. However, poor hemocompatibility of the hydrophobic material required surface modification or endothelialization. To increase the biocompatibility of PEU, the polymer was coated with a titaniumcarboxonitride [Ti(C,N,O)] layer by a plasma-activated chemical vapor deposition (PACVD) process. Biocompatibility of titaniferously coated PEU was verified using static and dynamic cell culture techniques. Titaniferous coating significantly improved proliferation and mitochondrial activity of human endothelial cells on PEU. These cells captured significantly less mononuclear cells and platelets. Under shear stress for up to 72 hours, titaniferous coating increased endothelial cell adhesion, spreading, and cell density to form an organized monolayer covering the whole luminal surface of vascular PEU grafts. In summary, coating of PEU surfaces with Ti(C,N,O) might be a promising strategy to improve the biocompatibility of biomedical biomaterials.

In vitro Endothelialization and Platelet Adhesion on Titaniferous Upgraded Polyether and Polycarbonate Polyurethanes.

Polycarbonateurethanes (PCU) and polyetherurethanes (PEU) are used for medical devices, however their bio- and haemocompatibility is limited. In this study, the effect of titaniferous upgrading of different polyurethanes on the bio- and haemocompatibility was investigated by endothelial cell (EC) adhesion/proliferation and platelet adhesion (scanning electron microscopy), respectively. There was no EC adhesion/proliferation and only minor platelet adhesion on upgraded and pure PCU (Desmopan). PEUs (Texin 985, Tecothane 1085, Elastollan 1180A) differed in their cyto- and haemocompatibility. While EC adhesion depended on the type of PEU, any proliferative activity was inhibited. Additional titaniferous upgrading of PEU induced EC proliferation and increased metabolic activity. However, adherent ECs were significantly activated. While Texin was highly thrombotic, only small amounts of platelets adhered onto Tecothane and Elastollan. Additional titaniferous upgrading reduced thrombogenicity of Texin, preserved haemocompatibility of Elastollan, and increased platelet activation/aggregation on Tecothane. In conclusion, none of the PUs was cytocompatible; only titaniferous upgrading allowed EC proliferation and metabolism on PEUs. Haemocompatibility depended on the type of PU.

Identifying redundancy and exposing provenance in crowdsourced data analysis.

We present a system that lets analysts use paid crowd workers to explore data sets and helps analysts interactively examine and build upon workers' insights. We take advantage of the fact that, for many types of data, independent crowd workers can readily perform basic analysis tasks like examining views and generating explanations for trends and patterns. However, workers operating in parallel can often generate redundant explanations. Moreover, because workers have different competencies and domain knowledge, some responses are likely to be more plausible than others. To efficiently utilize the crowd's work, analysts must be able to quickly identify and consolidate redundant responses and determine which explanations are the most plausible. In this paper, we demonstrate several crowd-assisted techniques to help analysts make better use of crowdsourced explanations: (1) We explore crowd-assisted strategies that utilize multiple workers to detect redundant explanations. We introduce color clustering with representative selection--a strategy in which multiple workers cluster explanations and we automatically select the most-representative result--and show that it generates clusterings that are as good as those produced by experts. (2) We capture explanation provenance by introducing highlighting tasks and capturing workers' browsing behavior via an embedded web browser, and refine that provenance information via source-review tasks. We expose this information in an explanation-management interface that allows analysts to interactively filter and sort responses, select the most plausible explanations, and decide which to explore further.

Vitamin D receptor activation improves allergen-triggered eczema in mice.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has increased in prevalence over the last several decades in industrialized countries. AD is a multifactorial, heterogenous disease with a variety of defects in the immune system, in antimicrobial defense mechanisms and epidermal barrier integrity, which collectively contribute to the risk and severity of AD development. Vitamin D receptor (VDR) signaling has been shown to be important not only in the immune system but also in the skin and in particular keratinocytes to regulate skin homeostasis and epidermal barrier function. However, this work aimed to analyze the role and clinical efficiency of VDR activation by a VDR agonist without calcium-mobilizing activity in a mouse model of allergen-triggered eczema. We show that the systemic administration of the low-calcemic VDR agonist significantly improved the allergen-triggered eczema. Thereby, forkhead box P3 (Foxp3)-expressing regulatory T cells, revealed to have a role in AD, were selectively increased in the skin of VDR agonist-treated mice. Moreover, our results demonstrate a marked induction of skin barrier gene and antimicrobial peptide gene expression in skin lesions of VDR agonist-treated mice. Thus, our study provides evidence that systemic VDR agonist treatment may improve allergen-triggered eczema in vivo.

1,25-dihydroxyvitamin D3 impairs NF-κB activation in human naïve B cells.

1α,25-dihydroxyvitamin D(3) (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-κB p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-κB mediated activation of human naïve B cells. Naïve B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naïve B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-κB activation by interference with NF-κB p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naïve B cells, namely by reducing CD40 signaling.

Liver X receptors control IgE expression in B cells.

B lymphocytes play a fundamental role in the development of IgE-dependent allergic immune reactions. Upon appropriate activation, IgE class switch recombination is initiated in B cells, followed by terminal differentiation to IgE-secreting plasmablasts. This process is controlled by different nuclear receptors, including receptors for vitamin D, retinoids, and peroxisome proliferator-activated receptor-gamma ligands. In this study, we show constitutive expression of the nuclear liver X receptor (LXR)alpha and LXRbeta in peripheral human B cells. Activation of LXRs reduced secreted IgE (-68% +/- 11) in CD40 and IL-4 activated B cells. The production of other isotypes, including IgG, IgM, IgA and B cell homeostatic parameters were not significantly altered by LXR activation. We identified inhibitory action of LXR activation on IgE production involving reduced phosphorylation of JNK and increased membrane CD23 expression (38% +/- 11). The biological significance of our findings was validated by showing that systemic treatment of type I-sensitized BALB/c mice with LXR ligands reduced the serum concentrations of Ag-specific IgE in a dose-dependent manner (maximum, -52% +/- 14). Thus, our data indicates that LXRs are involved in the control of IgE secretion by differentiating B cells.