Deriving a joint risk estimate from dynamic data collected at motorcycle rides.

Making motorcycle rides safer by advanced technology is an ongoing challenge in the context of developing driving assistant systems and safety infrastructure. Determining which section of a road and which driving behaviour is "safe" or "unsafe" is rarely possible due to the individual differences in driving experience, driving style, fitness and potentially available assistant systems. This study investigates the feasibility of a new approach to quantify motorcycle riding risk for an experimental sample of bikers by collecting motorcycle-specific dynamic data of several riders on selected road sections.

Experimental glioma with high bHLH expression harbor increased replicative stress and are sensitive toward ATR inhibition.

Background: The overexpression of (basic)helix-loop-helix ((b)HLH) transcription factors (TFs) is frequent in malignant glioma. We investigated molecular effects upon disruption of the (b)HLH network by a dominant-negative variant of the E47 protein (dnE47). Our goal was to identify novel molecular subgroup-specific therapeutic strategies.

TNF Receptor-Associated Factor 1 is a Major Target of Soluble TWEAK.

Soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), in contrast to membrane TWEAK and TNF, is only a weak activator of the classical NFκB pathway. We observed that soluble TWEAK was regularly more potent than TNF with respect to the induction of TNF receptor-associated factor 1 (TRAF1), a NFκB-controlled signaling protein involved in the regulation of inflammatory signaling pathways. TNF-induced TRAF1 expression was efficiently blocked by inhibition of the classical NFκB pathway using the IKK2 inhibitor, TPCA1.

TWEAK inhibits TRAF2-mediated CD40 signaling by destabilization of CD40 signaling complexes.

We found recently that TNF-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible-14 (Fn14) by virtue of their strong capability to reduce the freely available cytoplasmic pool of TNFR-associated factor (TRAF)2 and cellular inhibitors of apoptosis (cIAPs) antagonize the functions of these molecules in TNFR1 signaling, resulting in sensitization for apoptosis and inhibition of classical NF-κB signaling. In this study, we demonstrate that priming of cells with TWEAK also interferes with activation of the classical NF-κB pathway by CD40. Likewise, there was strong inhibition of CD40 ligand (CD40L)-induced activation of MAPKs in TWEAK-primed cells.

Electronic structure and soft-X-ray-induced photoreduction studies of iron-based magnetic polyoxometalates of type {(M)M5}12Fe(III)30 (M = Mo(VI), W(VI)).

Giant Keplerate-type molecules with a {Mo72Fe30} core show a number of very interesting properties, making them particularly promising for various applications. So far, only limited data on the electronic structure of these molecules from X-ray spectra and electronic structure calculations have been available. Here we present a combined electronic and magnetic structure study of three Keplerate-type nanospheres--two with a {Mo72Fe30} core and one with a {W72Fe30} core by means of X-ray absorption spectroscopy, X-ray magnetic circular dichroism (XMCD), SQUID magnetometry, and complementary theoretical approaches.

Preparation of monolayers of [MnIII6CrIII]3+ single-molecule magnets on HOPG, mica and silicon surfaces and characterization by means of non-contact AFM.

We report on the characterization of various salts of [MnIII6CrIII]3+ complexes prepared on substrates such as highly oriented pyrolytic graphite (HOPG), mica, SiO2, and Si3N4. [MnIII6CrIII]3+ is a single-molecule magnet, i.e.

Spin resolved photoelectron spectroscopy of [Mn6(III)Cr(III)]3+ single-molecule magnets and of manganese compounds as reference layers.

Properties of the manganese-based single-molecule magnet [Mn(6)(III)Cr(III)](3+) are studied. It contains six Mn(III) ions arranged in two bowl-shaped trinuclear triplesalen building blocks linked by a hexacyanochromate and exhibits a large spin ground state of S(t) = 21/2. The dominant structures in the electron emission spectra of [Mn(6)(III)Cr(III)](3+) resonantly excited at the L(3)-edge are the L(3)M(2, 3)M(2, 3), L(3)M(2, 3)V and L(3)VV Auger emission groups following the decay of the primary p(3/2) core hole state.

Cellular FLICE-inhibitory protein (cFLIP) isoforms block CD95- and TRAIL death receptor-induced gene induction irrespective of processing of caspase-8 or cFLIP in the death-inducing signaling complex.

Death receptors (DRs) induce apoptosis but also stimulate proinflammatory "non-apoptotic" signaling (e.g. NF-κB and mitogen-activated protein kinase (MAPK) activation) and inhibit distinct steps of DR-activated maturation of procaspase-8.

Photocycloaddition of anthracene-functionalized monolayers on silicon(100) surface.

Here we present detailed investigations of UV-photoinduced dimerization of anthracene substructures without solvent environment at the level of molecular monolayers prepared on a surface. Monolayers prepared on silicon(100) substrates were analyzed by means of X-ray photoelectron spectroscopy (XPS) in the valence band region revealing significant changes in the carbon C 2s region (11-20 eV). SVWN DFT calculations were performed to understand the influence of the structural changes by dimerization.

Experimental and theoretical studies of the structure of tellurate-borate glasses network.

The structural properties of the xTeO(2) x (1-x)B(2)O(3) glasses (x = 0.6; 0.7) were investigated by FT-IR spectroscopy.

A star-shaped heteronuclear Cr(III)Mn(II)3 species and its precise electronic and magnetic structure: spin frustration studied by X-ray spectroscopic, magnetic, and theoretical methods.

Molecular magnets incorporate transition-metal ions with organic groups providing a bridge to mediate magnetic exchange interactions between the ions. Among them are star-shaped molecules in which antiferromagnetic couplings between the central and peripheral atoms are predominantly present. Those configurations lead to an appreciable spin moment in the nonfrustrated ground state.

Star-shaped molecule of MnII4O6 core with an St=10 high-spin state. A theoretical and experimental study with XPS, XMCD, and other magnetic methods.

We report a comprehensive study of the electronic and magnetic properties of a star-shaped molecule comprising a MnII4O6 core. One feature of this compound is weak magnetic coupling constants compared to other similar polyoxo compounds. This leads to complicated low-lying magnetic states in which the ground state is not well separated from the upper-lying states, yielding a high-spin molecule with a giant magnetic moment of up to 20 microB/formula unit.

Mitochondrial dysfunction and redox signaling in atrial tachyarrhythmia.

Accumulating evidence links calcium-overload and oxidative stress to atrial remodeling during atrial fibrillation (AF). Furthermore, atrial remodeling appears to increase atrial thrombogeneity, characterized by increased expression of adhesion molecules. The aim of this study was to assess mitochondrial dysfunction and oxidative stress-activated signal transduction (nuclear factor-kappaB [NF-kappa B], lectin-like oxidized low-density lipoprotein receptor [LOX-1], intercellular adhesion molecule-1 [ICAM-1], and hemeoxgenase-1 [HO-1]) in atrial tissue during AF.

NF-kappaB inhibition reveals differential mechanisms of TNF versus TRAIL-induced apoptosis upstream or at the level of caspase-8 activation independent of cIAP2.

Death ligands not only activate a death program but also regulate inflammatory signalling pathways, for example, through NF-kappaB induction. Although tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TNF both activate NF-kappaB in human keratinocytes, only TRAIL potently induces apoptosis. However, when induction of NF-kappaB was inhibited with a kinase dead IKK2 mutant (IKK2-KD), TNF- but not TRAIL-induced apoptosis was dramatically enhanced.

Beyond IkappaBs: alternative regulation of NF-kappaB activity.

The transcription factor nuclear factor-kappa B (NF-kappaB) is a crucial regulator of many physiological and patho-physiological processes, including control of the adaptive and innate immune responses, inflammation, proliferation, tumorigenesis, and apoptosis. Thus, the tight regulation of NF-kappaB activity within a cell is extremely important. The central mechanism of NF-kappaB regulation is the signal-induced proteolytic degradation of a family of cytoplasmic inhibitors of NF-kappaB, the IkappaBs.

Peroxisome proliferator-activated receptor-gamma agonists inhibit respiratory syncytial virus-induced expression of intercellular adhesion molecule-1 in human lung epithelial cells.

Respiratory syncytial virus (RSV) is the major causative agent of severe lower respiratory tract disease and death in infants worldwide. The epithelial cells of the airways are the target cells for RSV infection and the site of the majority of the inflammation associated with the disease. However, despite five decades of intensive RSV research there exist neither an effective active vaccine nor a promising antiviral and anti-inflammatory therapy.

The PAK1 autoregulatory domain is required for interaction with NIK in Helicobacter pylori-induced NF-kappaB activation.

Helicobacter pylori, the etiological agent of various human gastric diseases, induces the transcription factor nuclear factor kappaB (NF-kappaB) and proinflammatory cytokines/chemokines. We have characterised the direct interaction between p21-activated kinase 1 (PAK1) and NF-kappaB-inducing kinase (NIK) in H. pylori-infected epithelial cells.

Gene transfer of tissue inhibitor of metalloproteinases-3 reverses the inhibitory effects of TNF-alpha on Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts.

Apart from counteracting matrix metalloproteinases, tissue inhibitor of metalloproteinases-3 (TIMP-3) has proapoptotic properties. These features have been attributed to the inhibition of metalloproteinases involved in the shedding of cell surface receptors such as the TNFR. However, little is known about effects of TIMP-3 in cells that are not susceptible to apoptosis by TNF-alpha.

Inhibition of RICK/nuclear factor-kappaB and p38 signaling attenuates the inflammatory response in a murine model of Crohn disease.

Nuclear factor-kappaB (NF-kappaB) is the main target of anti-inflammatory therapies in human chronic inflammatory bowel diseases (IBD), Crohn disease, and ulcerative colitis. This study investigates the molecular anti-inflammatory mechanisms of SB203580, an inhibitor of the mitogen-activated protein kinase p38. The murine trinitrobenzene sulfonic acid (TNBS)-induced colitis was used as an established model of human Crohn disease.

Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are the two entities of chronic inflammatory bowel diseases (IBD). One of the main pathogenic mechanisms is probably a dysregulated immune response triggered by products of the enteric bacterial flora. The goal of this study was to evaluate the effects of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 on inflammatory responses using the DSS-induced experimental colitis model in mice reflecting human IBD.

Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM-1.

Background: Leukocyte recruitment to areas of inflammation depends on Integrin-VCAM/ICAM interaction. Blocking the vascular cell adhesion molecule (VCAM-1) and the intracellular adhesion molecule (ICAM-1) may have therapeutic benefit for the inflammatory component of bowel disease. Notably, the induction of ICAM and VCAM is mediated by a nuclear factor kappaB (NF-kappaB)-dependent mechanism.

Curcumin blocks NF-kappaB and the motogenic response in Helicobacter pylori-infected epithelial cells.

Infection of epithelial cells by the microbial pathogen Helicobacter pylori leads to activation of the transcription factor nuclear factor kappaB (NF-kappaB), the induction of pro-inflammatory cytokine/chemokine genes, and the motogenic response (cell scattering). Here we report that H. pylori-induced NF-kappaB activation and the subsequent release of interleukin 8 (IL-8) are inhibited by curcumin (diferuloylmethane), a yellow pigment in turmeric (Curcuma longa L.

TRAIL-induced apoptosis and gene induction in HaCaT keratinocytes: differential contribution of TRAIL receptors 1 and 2.

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) exerts a potent cytotoxic activity especially against many tumor cell types such as transformed keratinocytes. The specific role of the different TRAIL receptors in this process, however, is unknown. In this report we examine the role the TRAIL receptors play in both the apoptotic and nonapoptotic responses of HaCaT keratinocytes to leucine zipper TRAIL (LZ-TRAIL).

RelB forms transcriptionally inactive complexes with RelA/p65.

RelB is an unusual member of the NF-kappaB transcription factor family that acts as both a transcriptional activator as well as a repressor of NF-kappaB-dependent gene expression. Although RelB promotes gene expression when it associates with p50/NF-kappaB1 or p52/NF-kappaB2, the precise molecular mechanisms through which it represses NF-kappaB remain unclear. To examine this inhibitory function in more detail, we employed reporter gene assays and found that RelB represses at the level of RelA.