Structure of the silicon vacancy in 6H-SiC after annealing identified as the carbon vacancy–carbon antisite pair

We investigated radiation-induced defects in neutron-irradiated and subsequently annealed 6H-silicon carbide (SiC) with electron paramagnetic resonance (EPR), the magnetic circular dichroism of the absorption (MCDA), and MCDA-detected EPR (MCDA-EPR). In samples annealed beyond the annealing temperature of the isolated silicon vacancy we observed photoinduced EPR spectra of spin S=1 centers that occur in orientations expected for nearest neighbor pair defects. EPR spectra of the defect on the three inequivalent lattice sites were resolved and attributed to optical transitions between photon energies of 999 and 1075 meV by MCDA-EPR. The resolved hyperfine structure indicates the presence of one single carbon nucleus and several silicon ligand nuclei. These experimental findings are interpreted with help of total energy and spin density data obtained from the standard local-spin density approximation of the density-functional theory, using relaxed defect geometries obtained from the self-consistent charge density-functional theory based tight binding scheme. We have checked several defect models of which only the photoexcited spin triplet state of the carbon antisite–carbon vacancy pair (CSi-VC) in the doubly positive charge state can explain all experimental findings. We propose that the (CSi-VC) defect is formed from the isolated silicon vacancy as an annealing product by the movement of a carbon neighbor into the vacancy

The Role of the Mucus Barrier in Digestion

Mucus forms a protective layer across a variety of epithelial surfaces. In the gastrointestinal (GI) tract, the barrier has to permit the uptake of nutrients, while excluding potential hazards, such as pathogenic bacteria. In this short review article, we look at recent literature on the structure, location, and properties of the mammalian intestinal secreted mucins and the mucus layer they form over a wide range of length scales. In particular, we look at the structure of the gel-forming glycoprotein MUC2, the primary intestinal secreted mucin, and the influence this has on the properties of the mucus layer. We show that, even at the level of the protein backbone, MUC2 is highly heterogeneous and that this is reflected in the networks it forms. It is evident that a combination of charge and pore size determines what can diffuse through the layer to the underlying gut epithelium. This information is important for the targeted delivery of bioactive molecules, including nutrients and pharmaceuticals, and for understanding how GI health is maintained

Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy

Background: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. Methods: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. Results: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia 30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. Conclusion: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions

The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients

Recent advances in brain imaging have contributed to our understanding of the neural activity associated with acupuncture treatment. In this study, we investigated functional connectivity across longitudinal acupuncture treatments in older patients with knee osteoarthritis (OA). Over a period of 4 weeks (six treatments), we collected resting state functional magnetic resonance imaging (fMRI) scans from 30 patients before and after their first, third and sixth treatments. Clinical outcome showed a significantly greater pain subscore on the Knee Injury and Osteoarthritis Outcome Score (KOOS) (indicative of improvement) with verum acupuncture than with sham acupuncture. Independent component analysis (ICA) of the resting state fMRI data showed that the right frontoparietal network (rFPN) and the executive control network (ECN) showed enhanced functional connectivity (FC) with the rostral anterior cingulate cortex/medial prefrontal cortex, a key region in the descending pain modulatory system, in the verum groups as compared to the sham group after treatments. We also found that the rFPN connectivity with the left insula is (1) significantly associated with changes in KOOS pain score after treatments, and (2) significantly enhanced after verum acupuncture treatments as compared to sham treatment. Analysis of the acupuncture needle stimulation scan showed that compared with sham treatment, verum acupuncture activated the left operculum/insula, which also overlaps with findings observed in resting state analysis. Our results suggest that acupuncture may achieve its therapeutic effect on knee OA pain by modulating functional connectivity between the rFPN, ECN and the descending pain modulatory pathway. Clinical trial number: NCT0107939

Neutron-diffraction studies of amorphous CNx materials

The results of neutron-diffraction experiments performed on two samples of amorphous CNx, with nitrogen concentrations of 5 and 30 at. %, prepared by a combination of filtered cathodic are and Kaufman-type ion source, are presented. Increasing the N content of the samples is seen to cause a decrease of the average bond length and the first coordination number. An increase in the average bond angle from 113 degrees to 121 degrees is also observed. The pair-distribution functions indicate that N incorporation results in some transformation of sp(3) C sites to sp(2) sites, but there is no evidence for N inducing the formation of crystalline graphitic clusters, and the overall structure remains amorphous. A direct subtraction of the two data sets emphasizes the loss of sp(3) bonds and the increasing sp(2) character of the higher-N-content sample, and shows the occurrence of a variety of bonding environments for N. More limited information on second neighbor correlations involving N is also revealed

NOX4-dependent ROS production by stromal mammary cells modulates epithelial MCF-7 cell migration

BACKGROUND: The influence of the stromal microenvironment on the progression of epithelial cancers has been demonstrated. Unravelling the mechanisms by which stromal cells affect epithelial behaviour will contribute in understanding cellular malignancy. It has been proposed that redox environment has a role in the acquisition of malignancy. In this work, we studied the influence of epithelial cells on the stromal redox status and the consequence of this phenomenon on MCF-7 cell motility. METHODS: We analysed in a co-culture system, the effect of RMF-EG mammary stromal cells on the migratory capacity of MCF-7 cell line. To test whether the NOX-dependent stromal redox environment influences the epithelial migratory behaviour, we knocked down the expression of NOX4 using siRNA strategy. The effect of TGF-b1 on NOX4 expression and activity was analysed by qPCR, and intracellular ROS production was measured by a fluorescent method. RESULTS: Migration of MCF-7 breast epithelial cells was stimulated when co-cultured with RMF-EG cells. This effect depends on stromal NOX4 expression that, in turn, is enhanced by epithelial soluble factors. Pre-treatment of stromal cells with TGF-b1 enhanced this migratory stimulus by elevating NOX4 expression and intracellular ROS production. TGF-b1 seems to be a major component of the epithelial soluble factors that stimulate NOX4 expression. CONCLUSIONS: Our results have identified that an increased stromal oxidative status, mainly provided by an elevated NOX4 expression, is a permissive element in the acquisition of epithelial migratory properties. The capacity of stromal cells to modify their intracellular ROS production, and accordingly, to increase epithelial motility, seems to depend on epithelial soluble factors among which TGF-b1 have a decisive role.This work was supported by the grant (1080196 to JM) from the Fondo Nacional de Ciencia y Tecnologı´a (FONDECYT) of Chile