Binding of thrombin to glycoprotein Ib accelerates the hydrolysis of Par-1 on intact platelets

The activation of human platelets by α-thrombin is mediated at least in part by cleavage of protease-activated G-protein-coupled receptors, PAR-1 and PAR-4. Platelet glycoprotein Ibα also has a high affinity binding site for α-thrombin, and this interaction contributes to platelet activation through a still unknown mechanism. In the present study the hypothesis that GpIbα may contribute to platelet activation by modulating the hydrolysis of PAR-1 on the platelet membrane was investigated. Gel-filtered platelets from normal individuals were stimulated by α-thrombin, and the kinetics of PAR-1 hydrolysis by enzyme was followed with flow cytometry using an anti-PAR-1 monoclonal antibody (SPAN 12) that recognizes only intact PAR-1 molecules. This strategy allowed measurement of the apparentk cat/K m value for thrombin hydrolysis of PAR-1 on intact platelets, which was equal to 1.5 ± 0.1 × 107 m −1sec−1. The hydrolysis rate of PAR-1 by thrombin was measured under conditions in which thrombin binding to GpIb was inhibited by different strategies, with the following results. 1) Elimination of GpIbα on platelet membranes by mocarhagin treatment reduced the k cat/K m value by about 6-fold. 2) A monoclonal anti-GpIb antibody reduced the apparent k cat/K m value by about 5-fold. 3) An oligonucleotide DNA aptamer, HD22, which binds to the thrombin heparin-binding site (HBS) and inhibits thrombin interaction with GpIbα, reduced the apparentk cat/K m value by about 5-fold. 4) Displacement of α-thrombin from the binding site on GpIb using PPACK-thrombin reduced the apparentk cat/K m value by about 5-fold, and 5) mutation at the HBS of thrombin (R98A) caused a 5-fold reduction of the apparentk cat/K m value of PAR-1 hydrolysis. Altogether these results show that thrombin interaction with GpIb enhances the specificity of thrombin cleavage of PAR-1 on intact platelets, suggesting that GpIb may function as a “cofactor” for PAR-1 activation by thrombin

Acoustic characteristics evaluation of an innovative metamaterial obtained through 3D printing technique

The reduction of interior noise level in the transportation sector is a big problem to cope with in view to increase the comfort of passengers. For this reason a great emphasis from the research community is devoted to develop new technology which are able to satisfy the mechanical requirements with concrete benefits from the acoustic point of view. Currently, it does not exist a solution for wideband range of frequency. Indeed, porous materials are characterized by outstanding dissipation in the high frequency range but they exhibit poor performance in the low and medium frequency range, where instead resonant cavities systems have the best performances but with narrow-band sound absorption. For this reason, the design and development of new materials which offers a good acoustic absorption over a wide range of frequencies is requested. In this paper, a hybrid metamaterial is designed, by coupling resonant cavities with micro-porous material and obtained through additive manufacturing technique which enables to model complex geometries that could not be feasible with classical manufacturing. Numerical and experimental studies have been conducted on the manufactured samples of PLA, with an interesting focus on the effect of each parameter which affects the absorption properties

New label-free methods for protein relative quantification applied to the investigation of an animal model of Huntington Disease

Spectral Counts approaches (SpCs) are largely employed for the comparison of protein expression profiles in label-free (LF) differential proteomics applications. Similarly, to other comparative methods, also SpCs based approaches require a normalization procedure before Fold Changes (FC) calculation. Here, we propose new Complexity Based Normalization (CBN) methods that introduced a variable adjustment factor (f), related to the complexity of the sample, both in terms of total number of identified proteins (CBN(P)) and as total number of spectral counts (CBN(S)). Both these new methods were compared with the Normalized Spectral Abundance Factor (NSAF) and the Spectral Counts log Ratio (Rsc), by using standard protein mixtures. Finally, to test the robustness and the effectiveness of the CBNs methods, they were employed for the comparative analysis of cortical protein extract from zQ175 mouse brains, model of Huntington Disease (HD), and control animals (raw data available via ProteomeXchange with identifier PXD017471). LF data were also validated by western blot and MRM based experiments. On standard mixtures, both CBN methods showed an excellent behavior in terms of reproducibility and coefficients of variation (CVs) in comparison to the other SpCs approaches. Overall, the CBN(P) method was demonstrated to be the most reliable and sensitive in detecting small differences in protein amounts when applied to biological samples

New label-free methods for protein relative quantification applied to the investigation of an animal model of Huntington Disease

Spectral Counts approaches (SpCs) are largely employed for the comparison of protein expression profiles in label-free (LF) differential proteomics applications. Similarly, to other comparative methods, also SpCs based approaches require a normalization procedure before Fold Changes (FC) calculation. Here, we propose new Complexity Based Normalization (CBN) methods that introduced a variable adjustment factor (f), related to the complexity of the sample, both in terms of total number of identified proteins (CBN(P)) and as total number of spectral counts (CBN(S)). Both these new methods were compared with the Normalized Spectral Abundance Factor (NSAF) and the Spectral Counts log Ratio (Rsc), by using standard protein mixtures. Finally, to test the robustness and the effectiveness of the CBNs methods, they were employed for the comparative analysis of cortical protein extract from zQ175 mouse brains, model of Huntington Disease (HD), and control animals (raw data available via ProteomeXchange with identifier PXD017471). LF data were also validated by western blot and MRM based experiments. On standard mixtures, both CBN methods showed an excellent behavior in terms of reproducibility and coefficients of variation (CVs) in comparison to the other SpCs approaches. Overall, the CBN(P) method was demonstrated to be the most reliable and sensitive in detecting small differences in protein amounts when applied to biological samples

Conformally parametrized surfaces associated with CP^(N-1) sigma models

Two-dimensional conformally parametrized surfaces immersed in the su(N) algebra are investigated. The focus is on surfaces parametrized by solutions of the equations for the CP^(N-1) sigma model. The Lie-point symmetries of the CP^(N-1) model are computed for arbitrary N. The Weierstrass formula for immersion is determined and an explicit formula for a moving frame on a surface is constructed. This allows us to determine the structural equations and geometrical properties of surfaces in R^(N^2-1). The fundamental forms, Gaussian and mean curvatures, Willmore functional and topological charge of surfaces are given explicitly in terms of any holomorphic solution of the CP^2 model. The approach is illustrated through several examples, including surfaces immersed in low-dimensional su(N) algebras.Comment: 32 page

Analysis of hydrogen-rich magnetic white dwarfs detected in the Sloan Digital Sky Survey

We model the structure of the surface magnetic fields of the hydrogen-rich white dwarfs in the SDSS. We have calculated a grid of state-of-the-art theoretical optical spectra of hydrogen-rich magnetic white dwarfs with magnetic field strengths between 1 MG and 1200 MG for different angles, and for effective temperatures between 7000 K and 50000 K. We used a least-squares minimization scheme with an evolutionary algorithm in order to find the magnetic field geometry best fitting the observed data. We used simple centered dipoles or dipoles which were shifted along the dipole axis to model the coadded SDSS fiber spectrum of each object. We have analysed the spectra of all known magnetic DAs from the SDSS (97 previously published plus 44 newly discovered) and also investigated the statistical properties of magnetic field geometries of this sample. The total number of known magnetic white dwarfs already more than tripled by the SDSS and more objects are expected from a more systematic search. The magnetic fields span a range between ~1 and 900 MG. Our results further support the claim that Ap/Bp population is insufficient in generating the numbers and field strength distributions of the observed MWDs, and either another source of progenitor types or binary evolution is needed. Moreover clear indications for non-centered dipoles exist in about ~50% of the objects which is consistent with the magnetic field distribution observed in Ap/Bp stars.Comment: 15 pages, accepted for publication in A&A. For online version with full appendix figures, see http://www.ari.uni-heidelberg.de/mitarbeiter/bkulebi/papers/12570_online.pd

Novel approach to the study of quantum effects in the early universe

We develop a theoretical frame for the study of classical and quantum gravitational waves based on the properties of a nonlinear ordinary differential equation for a function $\sigma(\eta)$ of the conformal time $\eta$, called the auxiliary field equation. At the classical level, $\sigma(\eta)$ can be expressed by means of two independent solutions of the ''master equation'' to which the perturbed Einstein equations for the gravitational waves can be reduced. At the quantum level, all the significant physical quantities can be formulated using Bogolubov transformations and the operator quadratic Hamiltonian corresponding to the classical version of a damped parametrically excited oscillator where the varying mass is replaced by the square cosmological scale factor $a^{2}(\eta)$. A quantum approach to the generation of gravitational waves is proposed on the grounds of the previous $\eta-$dependent Hamiltonian. An estimate in terms of $\sigma(\eta)$ and $a(\eta)$ of the destruction of quantum coherence due to the gravitational evolution and an exact expression for the phase of a gravitational wave corresponding to any value of $\eta$ are also obtained. We conclude by discussing a few applications to quasi-de Sitter and standard de Sitter scenarios.Comment: 20 pages, to appear on PRD. Already published background material has been either settled up in a more compact form or eliminate

Extramedullary hematopoiesis presenting as a compressive cord and cerebral lesion in a patient without a significant hematologic disorder: a case report

<p>Abstract</p> <p>Introduction</p> <p>Intracranial or spinal compressive lesions due to extramedullary hematopoiesis have been reported in the medical literature. Most of the reported cases are extradural lesions or, on rare occasions, foci within another neoplasm such as hemangioblastoma, meningioma or pilocytic astrocytoma. Often these cases occur in patients with an underlying hematological disorder such as acute myelogenic leukemia, myelofibrosis, or other myelodysplastic syndromes. Such lesions have also been reported in thalassemia major.</p> <p>Case presentation</p> <p>We report the case of a 43-year-old Iranian woman in whom extramedullary hematopoiesis presented as a compressive cord lesion and then later as an intracranial lesion.</p> <p>Conclusions</p> <p>To the best of our knowledge, we document the first reported case of sacral, lumbar, thoracic and cranial involvement in the same patient with extramedullary hematopoiesis, which seems both rare and remarkable.</p

Acoustic Power Absorption and its Relation with Vector Magnetic Field of a Sunspot

The distribution of acoustic power over sunspots shows an enhanced absorption near the umbra--penumbra boundary. Earlier studies revealed that the region of enhanced absorption coincides with the region of strongest transverse potential field. The aim of this paper is to (i) utilize the high-resolution vector magnetograms derived using Hinode SOT/SP observations and study the relationship between the vector magnetic field and power absorption and (ii) study the variation of power absorption in sunspot penumbrae due to the presence of spine-like radial structures. It is found that (i) both potential and observed transverse fields peak at a similar radial distance from the center of the sunspot, and (ii) the magnitude of the transverse field, derived from Hinode observations, is much larger than the potential transverse field derived from SOHO/MDI longitudinal field observations. In the penumbra, the radial structures called spines (intra-spines) have stronger (weaker) field strength and are more vertical (horizontal). The absorption of acoustic power in the spine and intra-spine shows different behaviour with the absorption being larger in the spine as compared to the intra-spine.Comment: 18 pages, 7 figures, In Press Solar Physics, Topical Issue on Helio-and-Astroseismolog