Non-Relativistic Gravitation: From Newton to Einstein and Back

We present an improvement to the Classical Effective Theory approach to the non-relativistic or Post-Newtonian approximation of General Relativity. The "potential metric field" is decomposed through a temporal Kaluza-Klein ansatz into three NRG-fields: a scalar identified with the Newtonian potential, a 3-vector corresponding to the gravito-magnetic vector potential and a 3-tensor. The derivation of the Einstein-Infeld-Hoffmann Lagrangian simplifies such that each term corresponds to a single Feynman diagram providing a clear physical interpretation. Spin interactions are dominated by the exchange of the gravito-magnetic field. Leading correction diagrams corresponding to the 3PN correction to the spin-spin interaction and the 2.5PN correction to the spin-orbit interaction are presented.Comment: 10 pages, 3 figures. v2: published version. v3: Added a computation of Einstein-Infeld-Hoffmann in higher dimensions within our improved ClEFT which partially confirms and partially corrects a previous computation. See notes added at end of introductio

Canonical formulation of self-gravitating spinning-object systems

Based on the Arnowitt-Deser-Misner (ADM) canonical formulation of general relativity, a canonical formulation of gravitationally interacting classical spinning-object systems is given to linear order in spin. The constructed position, linear momentum and spin variables fulfill standard Poisson bracket relations. A spatially symmetric time gauge for the tetrad field is introduced. The achieved formulation is of fully reduced form without unresolved constraints, supplementary, gauge, or coordinate conditions. The canonical field momentum is not related to the extrinsic curvature of spacelike hypersurfaces in standard ADM form. A new reduction of the tetrad degrees of freedom to the Einstein form of the metric field is suggested.Comment: 6 pages. v2: extended version; identical to the published one. v3: corrected misprints in (24) and (39); improved notation; added note regarding a further reference

Use of spin labels to study membrane proteins by high-frequency electron nuclear double resonance spectroscopy

The applicability of spin labels to study membrane proteins by high-frequency electron nuclear double resonance spectroscopy is demonstrated. With the use of bacteriorhodopsin embedded in a lipid membrane as an example, the spectra of protons of neighboring amino acids are recorded, electric field gradients at the membrane surface are detected, and the constant of hyperfine interaction with the chlorine nucleus at the site of ion trapping is measured. © 2007 Pleiades Publishing, Ltd

Proteomic analysis of the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

So far, only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) has been accepted as diagnostic criterion for Creutzfeldt-Jakob disease (CJD). However, this assay cannot be used for screening because of the high rate of false-positive results, whereas patients with variant CJD are often negative for 14-3-3 proteins. The aim of this study was to compare the spot patterns of CSF by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to search for a CJD-specific spot pattern. We analyzed the CSF of 28 patients {[}11 CJD, 9 Alzheimer's disease ( AD), 8 nondemented controls (NDC)] employing 2D-PAGE which was optimized for minimal volumes of CSF (0.1 ml; 7-cm strips). All samples were run at least three times, gels were silver stained and analyzed by an analysis software and manually revised. We could consistently match 268 spots which were then compared between all groups. By the use of 5 spots, we were able to differentiate CJD from AD or NDC with a sensitivity of 100%. CJD could also be distinguished from both groups by using a heuristic clustering algorithm of 2 spots. We conclude that this proteomic approach can differentiate CJD from other diseases and may serve as a model for other neurodegenerative diseases. Copyright (C) 2007 S. Karger AG, Basel

Next to leading order spin-orbit effects in the motion of inspiralling compact binaries

Using effective field theory (EFT) techniques we calculate the next-to-leading order (NLO) spin-orbit contributions to the gravitational potential of inspiralling compact binaries. We use the covariant spin supplementarity condition (SSC), and explicitly prove the equivalence with previous results by Faye et al. in arXiv:gr-qc/0605139. We also show that the direct application of the Newton-Wigner SSC at the level of the action leads to the correct dynamics using a canonical (Dirac) algebra. This paper then completes the calculation of the necessary spin dynamics within the EFT formalism that will be used in a separate paper to compute the spin contributions to the energy flux and phase evolution to NLO.Comment: 25 pages, 4 figures, revtex4. v2: minor changes, refs. added. To appear in Class. Quant. Gra

Creutzfeldt-Jacob Disease: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Role of Extracellular Vesicles as Modulators of the Tumor Microenvironment, Metastasis and Drug Resistance in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with high morbidity and mortality rates. A number of factors including modulation of the tumor microenvironment, high metastatic capability, and resistance to treatment have been associated with CRC disease progression. Recent studies have documented that tumor-derived extracellular vesicles (EVs) play a significant role in intercellular communication in CRC via transfer of cargo lipids, proteins, DNA and RNAs to the recipient tumor cells. This transfer influences a number of immune-related pathways leading to activation/differentiation/expression of immune cells and modulation of the tumor microenvironment that plays a significant role in CRC progression, metastasis, and drug resistance. Furthermore, tumor-derived EVs are secreted in large amounts in biological fluids of CRC patients and as such the expression analysis of EV cargoes have been associated with prognosis or response to therapy and may be a source of therapeutic targets. This review aims to provide a comprehensive insight into the role of EVs in the modulation of the tumor microenvironment and its effects on CRC progression, metastasis, and drug resistance. On the other hand, the potential role of CRC derived EVs as a source of biomarkers of response and therapeutic targets will be discussed in detail to understand the dynamic role of EVs in CRC diagnosis, treatment, and management

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling

Sanguinarine (SNG), a benzophenanthridine alkaloid, has displayed various anticancer abilities in several vivo and in vitro studies. However, the anticancer potential of SNG is yet to be established in multiple myeloma (MM), a mostly incurable malignancy of plasma cells. In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppression of the constitutively active STAT3 with a concomitant increase in expression of protein tyrosine phosphatase (SHP-1). SNG treatment of MM cells leads to down-regulation of the anti-apoptotic proteins including cyclin D, Bcl-2, Bclxl, and XIAP. In addition, it also upregulates pro-apoptotic protein, Bax. SNG mediated cellular DNA damage in MM cell lines by induction of oxidative stress through the generation of reactive oxygen species and depletion of glutathione. Finally, the subtoxic concentration of SNG enhanced the cytotoxic effects of anticancer drugs bortezomib (BTZ) by suppressing the viability of MM cells via induction of caspase-mediated apoptosis. Altogether our findings demonstrate that SNG induces mitochondrial and caspase-dependent apoptosis, generates oxidative stress, and suppresses MM cell lines proliferation. In addition, co-treatment of MM cell lines with sub-toxic doses of SNG and BTZ potentiated the cytotoxic activity. These results would suggest that SNG could be developed into therapeutic agent either alone or in combination with other anticancer drugs in MM

Reverse Engineering Gene Networks with ANN: Variability in Network Inference Algorithms

Motivation :Reconstructing the topology of a gene regulatory network is one of the key tasks in systems biology. Despite of the wide variety of proposed methods, very little work has been dedicated to the assessment of their stability properties. Here we present a methodical comparison of the performance of a novel method (RegnANN) for gene network inference based on multilayer perceptrons with three reference algorithms (ARACNE, CLR, KELLER), focussing our analysis on the prediction variability induced by both the network intrinsic structure and the available data. Results: The extensive evaluation on both synthetic data and a selection of gene modules of "Escherichia coli" indicates that all the algorithms suffer of instability and variability issues with regards to the reconstruction of the topology of the network. This instability makes objectively very hard the task of establishing which method performs best. Nevertheless, RegnANN shows MCC scores that compare very favorably with all the other inference methods tested. Availability: The software for the RegnANN inference algorithm is distributed under GPL3 and it is available at the corresponding author home page (http://mpba.fbk.eu/grimaldi/regnann-supmat

Spin and quadrupole contributions to the motion of astrophysical binaries

Compact objects in general relativity approximately move along geodesics of spacetime. It is shown that the corrections to geodesic motion due to spin (dipole), quadrupole, and higher multipoles can be modeled by an extension of the point mass action. The quadrupole contributions are discussed in detail for astrophysical objects like neutron stars or black holes. Implications for binaries are analyzed for a small mass ratio situation. There quadrupole effects can encode information about the internal structure of the compact object, e.g., in principle they allow a distinction between black holes and neutron stars, and also different equations of state for the latter. Furthermore, a connection between the relativistic oscillation modes of the object and a dynamical quadrupole evolution is established.Comment: 43 pages. Proceedings of the 524. WE-Heraeus-Seminar "Equations of Motion in Relativistic Gravity". v2: fixed reference. v3: corrected typos in eqs. (1), (57), (85