Contribution of a Disk Component to Single Peaked Broad Lines of Active Galactic Nuclei

We study the disk emission component hidden in the single-peaked Broad Emission Lines (BELs) of Active Galactic Nuclei (AGN). We compare the observed broad lines from a sample of 90 Seyfert 1 spectra taken from the Sloan Digital Sky Survey with simulated line profiles. We consider a two-component Broad Line Region (BLR) model where an accretion disk and a surrounding non-disk region with isotropic cloud velocities generate the simulated BEL profiles. The analysis is mainly based in measurements of the full widths (at 10%, 20% and 30% of the maximum intensity) and of the asymmetries of the line profiles. Comparing these parameters for the simulated and observed H$\alpha$ broad lines, we {found} that the hidden disk emission {may} be present in BELs even if the characteristic {of two peaked line profiles is} absent. For the available sample of objects (Seyfert 1 galaxies with single-peaked BELs), our study indicates that, {in the case of the hidden disk emission in single peaked broad line profiles}, the disk inclination tends to be small (mostly $i<25^\circ$) and that the contribution of the disk emission to the total flux should be smaller than the contribution of the surrounding region.Comment: 18 Figures, 1 Table, MNRAS-accepted. MNRAS-accepte

The Cytoplasmic Tail of the Notch Ligand Jagged-1: Intrinsic Disorder, Induced Order and Molecular Interactions

Notch signaling plays a key role in cell differentiation in all metazoans. As both receptors and ligands are cell-surface proteins, Notch signaling is restricted to nearby interacting cells. Notch ligands are membrane-spanning proteins made of a large extracellular region, a transmembrane segment, and a 100\u2013200 residue cytoplasmic tail. The sequence of the intracellular region of Jagged-1, one of the five ligands to Notch receptors in man, is very well conserved throughout evolution but does not encode any globular domain. The cytoplasmic tail of Jagged-1 mediates protein\u2013protein interactions through the C-terminal PDZ binding motif, is involved in ligand endocytosis triggered by mono-ubiquitination, and, as a consequence of regulated intramembrane proteolysis, can be released into the cytosol as a signaling fragment. The intracellular region of Jagged-1 may then exist in at least two forms: as a membrane-tethered protein located at the interface between the membrane and the cytoplasm, and as a soluble nucleocytoplasmic protein. To investigate its structural properties, a recombinant protein corresponding to the human Jagged-1 intracellular region (J1_tmic) was expressed, purified, and characterized in different environments using various biophysical methods such as circular dichroism, tryptophan fluorescence, size-exclusion chromatography, and NMR. In solution, J1_tmic behaves as an intrinsically disordered protein, but displays a significant helical propensity. In the presence of SDS micelles or negatively charged phospholipid micelles and vesicles, used to mimick the interface between the plasma membrane and the cytosol, J1_tmic gains partial helical structure. The partial folding and association of the intracellular region of Jagged-1 with the membrane is expected to reduce its \u201ccapture radius\u201d towards target proteins and to make selected residues unavailable for post-translational modifications or binding. Binding of Jagged-1 intracellular region to the PDZ domain of afadin, a protein located at cell-cell adherens junctions, couples Notch signaling with the adhesion system and the cytoskeleton. The interaction between the PDZ domain of afadin (AF6_PDZ) and a series of polypeptides comprising the Jagged-1 PDZ-binding motif (EYIV) was investigated using NMR chemical shift perturbation and surface plasmon resonance. It was shown that binding of Jagged-1 intracellular region to AF6_PDZ is strictly local, involving only the last six residues of the binding motif and the PDZ binding groove, and that it does not trigger global folding of J1_tmic. In the C-terminal region of Jagged-1 cytoplasmic tail, four potential phosphorylation sites can be identified, one of them (Y1216) located in the PDZbinding motif. It was found that, while phosphorylation at any of these sites disrupts binding of the C-terminal peptides to lipid micelles, phosphorylation at (Y1216) also affects the interaction with AF6_PDZ, with a reduction in the binding affinity. Phosphorylation thus provides a potential way to modulate the interaction of Jagged-1 C-terminal region not only with the membrane but also with the partner PDZ. It was also shown that the R1213Q mutation in the PDZ binding motif associated with a congenital obstruction of the bile ducts, increases the affinity for AF6_PDZ. In summary, this work presents the first biochemical and structural characterization of Jagged-1 cytoplasmic tail in solution and in environments that mimic the membrane/cytoplasm interface, and the first biophysical study on its interaction with the afadin PDZ domain

Tools and Guidelines for Principled Machine Translation Development

This work addresses the need to aid Machine Translation (MT) development cycles with a complete workflow of MT evaluation methods. Our aim is to assess, compare and improve MT system variants. We hereby report on novel tools and practices that support various measures, developed in order to support a principled and informed approach of MT developmen

SUSTAINABLE LAND MANAGEMENT IN AGRICULTURE -OBRENOVAC MUNICIPALITY (SERBIA) CASE STUDY

Abstract According to proposed E

Hyaluronic acid treatment outcome on the post-extraction wound healing in patients with poorly controlled type 2 diabetes : a randomized controlled split-mouth study

Hyaluronic acid is widely used in the medical field. However, there is a lack of research about its effect on patients with certain risks, such as compromised wound healing commonly found in patients with poorly controlled type 2 diabetes. The aim of this study is to investigate the efficacy of hyaluronic acid on the post-extraction wound healing and pain in patients with poorly controlled type 2 diabetes. The randomized controlled split-mouth study was designed, which included 30 patients with poorly controlled type 2 diabetes with a bilaterally same teeth in the lower jaw for extraction. The sockets treated with 0.8% hyaluronic acid represented the study group, while the sockets where hyaluronic acid was not applied represented the control group. Wound closure rate (WCR), clinical scores in wound healing scale (WHS) and pain intensity in Visual analogue scale (VAS) were recorded. Patients were followed up on 5th, 10th, 15th, 20th, 25th day after tooth extraction. The results showed a higher WCR at the extraction site where hyaluronic acid was applied. Also, statistically significant difference was found (p< 0.001). In regards to WHS, the sockets treated with hyaluronic acid showed better healing, especially on day 10 (p=0.006) and day 15 (p=0.021). However, there were no statistically significant differences in VAS scores between groups. Hyaluronic acid placed in post-extraction socket in patients with poorly controlled diabetes may improve wound healing, especially in the first days after application

Descriptions. A Special Program for Least pth Approximation Including Interpolation

PURPOSE: Minimization of a least pth objective function of k variables using gradient methods. Interpolation brings thediscrete problem closer to the continuous minimsx approximation problem