Warping the young stellar disc in the Galactic Centre

We examine influence of the circum-nuclear disc (CND) upon the orbital evolution of young stars in the Galactic Centre. We show that gravity of the CND causes precession of the orbits which is highly sensitive upon the semi-major axis and inclination. We consider such a differential precession within the context of an ongoing discussion about the origin of the young stars and suggest a possibility that all of them have originated in a thin disc which was partially destroyed due to the influence of the CND during the period of ~6Myr.Comment: proc. conf. "The Universe Under the Microscope - Astrophysics at High Angular Resolution", 21-25 April 2008, Bad Honnef, German

Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

INTRODUCTION: Members of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2) than of rhPAD4 were required for citrullination of fibrinogen. PAD activity was detected in four of five synovial fluid samples from RA patients and correlated with PAD2 concentrations in the samples (r = 0.98, P = 0.003). The calcium requirement for half-maximal activities of PAD2 and PAD4 were found in a range from 0.35 to 1.85 mM, and synovial fluid was found to contain sufficient calcium levels for the citrullination process to occur. CONCLUSIONS: We present an assay with high specificity for PAD2 activity and show that citrullination of fibrinogen can occur in cell-free synovial fluid from RA patients

Identification of potential autoantigens in anti-CCP-positive and anti-CCP-negative rheumatoid arthritis using citrulline-specific protein arrays

Abstract The presence or absence of autoantibodies against citrullinated proteins (ACPAs) distinguishes two main groups of rheumatoid arthritis (RA) patients with different etiologies, prognoses, disease severities, and, presumably, disease pathogenesis. The heterogeneous responses of RA patients to various biologics, even among ACPA-positive patients, emphasize the need for further stratification of the patients. We used high-density protein array technology for fingerprinting of ACPA reactivity. Identification of the proteome recognized by ACPAs may be a step to stratify RA patients according to immune reactivity. Pooled plasma samples from 10 anti-CCP-negative and 15 anti-CCP-positive RA patients were assessed for ACPA content using a modified protein microarray containing 1631 different natively folded proteins citrullinated in situ by protein arginine deiminases (PADs) 2 and PAD4. IgG antibodies from anti-CCP-positive RA plasma showed high-intensity binding to 87 proteins citrullinated by PAD2 and 99 proteins citrullinated by PAD4 without binding significantly to the corresponding native proteins. Curiously, the binding of IgG antibodies in anti-CCP-negative plasma was also enhanced by PAD2- and PAD4-mediated citrullination of 29 and 26 proteins, respectively. For only four proteins, significantly more ACPA binding occurred after citrullination with PAD2 compared to citrullination with PAD4, while the opposite was true for one protein. We demonstrate that PAD2 and PAD4 are equally efficient in generating citrullinated autoantigens recognized by ACPAs. Patterns of proteins recognized by ACPAs may serve as a future diagnostic tool for further subtyping of RA patients

Identification of Novel Native Autoantigens in Rheumatoid Arthritis

The majority of patients diagnosed with rheumatoid arthritis (RA) have developed autoantibodies against neoepitopes in proteins that have undergone post-translational modification, e.g., citrullination or carbamylation. There is growing evidence of their molecular relevance and their potential utility to improve diagnosis, patient stratification, and prognosis for precision medicine. Autoantibodies reacting to native proteins may also have a role in RA pathogenesis, however, their reactivity patterns remain much less studied. We hypothesized that a high-density protein array technology could shed light onto the normal and disease-related autoantibodies produced in healthy and RA patient subgroups. In an exploratory study, we investigated the global reactivity of autoantibodies in plasma pools from 15 anti-cyclic citrullinated peptide (CCP)-positive and 10 anti-CCP-negative RA patients and 10 healthy donors against more than 1600 native and unmodified human proteins using a high-density protein array. A total of 102 proteins recognized by IgG autoantibodies were identified, hereof 86 were recognized by antibodies from CCP-positive RA patients and 76 from anti-CCP-negative RA patients, but not by antibodies from healthy donors. Twenty-four of the identified autoantigens have previously been identified in synovial fluid. Multiple human proteins in their native conformation are recognized by autoantibodies from anti-CCP-positive as well as anti-CCP-negative RA patients

Equilibrium long-ranged charge correlations at the interface between media coupled to the electromagnetic radiation

We continue studying long-ranged quantum correlations of surface charge densities on the interface between two media of distinct dielectric functions which are in thermal equilibrium with the radiated electromagnetic field. Two regimes are considered: the non-retarded one with the speed of light $c$ taken to be infinitely large and the retarded one with finite value of $c$. The analysis is based on results obtained by using fluctuational electrodynamics in [L. \v{S}amaj and B. Jancovici, Phys. Rev. E {\bf 78}, 051119 (2008)]. Using an integration method in the complex plane and the general analytic properties of dielectric functions in the frequency upper half-plane, we derive explicit forms of prefactors to the long-range decay of the surface charge correlation functions for all possible media (conductor, dielectric, vacuum) configurations. The main result is that the time-dependent quantum prefactor in the retarded regime takes its static classical form, for any temperature.Comment: 9 pages, 3 figure

Entanglement generation in continuously coupled parametric generators

We investigate a compact source of entanglement. This device is composed of a pair of linearly coupled nonlinear waveguides operating by means of degenerate parametric downconversion. For the vacuum state at the input the generalized squeeze variance and logarithmic negativity are used to quantify the amount of nonclassicality and entanglement of output beams. Squeezing and entanglement generation for various dynamical regimes of the device are discussed.Comment: 6 pages, 7 figure