Is erythropoietin a worthy candidate for traumatic brain injury or are we heading the wrong way?

Traumatic brain injury (TBI) is a leading cause of death and disability in the modern society. Although primary prevention is the only strategy that can counteract the primary brain damage, numerous preclinical studies have been accumulated in order to find therapeutic strategies against the secondary damage. In this scenario erythropoietin (EPO) has been shown to be a promising candidate as neuroprotective agent. A recent clinical trial, however, has shown that EPO has not an overall effect on outcomes following TBI thus renewing old concerns. However, the results of a prespecified sensitivity analysis indicate that the effect of EPO on mortality remains still unclear. In the light of these observations, further investigations are needed to resolve doubts on EPO effectiveness in order to provide a more solid base for tailoring conclusive clinical trials

MORPH: A Reference Architecture for Configuration and Behaviour Self-Adaptation

An architectural approach to self-adaptive systems involves runtime change of system configuration (i.e., the system's components, their bindings and operational parameters) and behaviour update (i.e., component orchestration). Thus, dynamic reconfiguration and discrete event control theory are at the heart of architectural adaptation. Although controlling configuration and behaviour at runtime has been discussed and applied to architectural adaptation, architectures for self-adaptive systems often compound these two aspects reducing the potential for adaptability. In this paper we propose a reference architecture that allows for coordinated yet transparent and independent adaptation of system configuration and behaviour

Transumbilical versus transvaginal retrieval of surgical specimens at laparoscopy: a randomized trial.

Objective We sought to compare transumbilical (TU) and transvaginal (TV) route for retrieval of surgical specimens at laparoscopy. Study design Women scheduled for a laparoscopic resection of an adnexal mass were randomized to have their surgical specimen removed either through a posterior colpotomy (n = 34) or the umbilical port site (n = 32). Group allocation was concealed from patients and bedside clinicians. The primary outcome was postoperative incisional pain assessed by a 10-cm visual analog scale at 1, 3, and 24 hours after surgery. Results TV retrieval caused less postoperative pain than TU specimen extraction at each time point (visual analog scale score at 1 hour: 2.6 \ub1 2.9 vs 1.2 \ub1 2.0, P = .03; at 3 hours: 2.4 \ub1 2.0 vs 1.4 \ub1 2.0, P = .02; and at 24 hours: 1.1 \ub1 1.5 vs 0.5 \ub1 1.4, P = .02). A higher proportion of women in the TU group than in the TV group indicated the umbilicus as the most painful area at 1 and 3 hours postoperatively. Two months after surgery, the participants scored similarly as to their overall satisfaction, cosmetic outcome, and dyspareunia upon resumption of intercourse. Conclusion A TV approach for specimen removal after laparoscopic resection of adnexal masses offers the advantage of less postoperative pain than TU retrieva

Anisotropic dark energy stars

A model of compact object coupled to inhomogeneous anisotropic dark energy is studied. It is assumed a variable dark energy that suffers a phase transition at a critical density. The anisotropic Lambda-Tolman-Oppenheimer-Volkoff equations are integrated to know the structure of these objects. The anisotropy is concentrated on a thin shell where the phase transition takes place, while the rest of the star remains isotropic. The family of solutions obtained depends on the coupling parameter between the dark energy and the fermion matter. The solutions share several features in common with the gravastar model. There is a critical coupling parameter that gives non-singular black hole solutions. The mass-radius relations are studied as well as the internal structure of the compact objects. The hydrodynamic stability of the models is analyzed using a standard test from the mass-radius relation. For each permissible value of the coupling parameter there is a maximum mass, so the existence of black holes is unavoidable within this model.Comment: 12 pages, 6 figures, final manuscript, Accepted for publication in Astrophysics & Space Scienc

Sharp bounds on the critical stability radius for relativistic charged spheres

In a recent paper by Giuliani and Rothman \cite{GR}, the problem of finding a lower bound on the radius $R$ of a charged sphere with mass M and charge Q<M is addressed. Such a bound is referred to as the critical stability radius. Equivalently, it can be formulated as the problem of finding an upper bound on M for given radius and charge. This problem has resulted in a number of papers in recent years but neither a transparent nor a general inequality similar to the case without charge, i.e., M\leq 4R/9, has been found. In this paper we derive the surprisingly transparent inequality $$\sqrt{M}\leq\frac{\sqrt{R}}{3}+\sqrt{\frac{R}{9}+\frac{Q^2}{3R}}.$$ The inequality is shown to hold for any solution which satisfies $p+2p_T\leq\rho,$ where $p\geq 0$ and $p_T$ are the radial- and tangential pressures respectively and $\rho\geq 0$ is the energy density. In addition we show that the inequality is sharp, in particular we show that sharpness is attained by infinitely thin shell solutions.Comment: 20 pages, 1 figur

Inhibitor binding mode and allosteric regulation of Na+-glucose symporters.

Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due to their role in renal sugar reabsorption, SGLTs are targets for the treatment of type 2 diabetes. Current therapeutics are phlorizin derivatives that contain a sugar moiety bound to an aromatic aglycon tail. Here, we develop structural models of human SGLT1/2 in complex with inhibitors by combining computational and functional studies. Inhibitors bind with the sugar moiety in the sugar pocket and the aglycon tail in the extracellular vestibule. The binding poses corroborate mutagenesis studies and suggest a partial closure of the outer gate upon binding. The models also reveal a putative Na+ binding site in hSGLT1 whose disruption reduces the transport stoichiometry to the value observed in hSGLT2 and increases inhibition by aglycon tails. Our work demonstrates that subtype selectivity arises from Na+-regulated outer gate closure and a variable region in extracellular loop EL5

Interleukin-1 Induces Tumor Necrosis Factor (TNF) in Human Peripheral Blood Mononuclear Cells In Vitro and a Circulating TNF-like Activity in Rabbits

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A Proposal of Business Model Design Parameters for Future Internet Carriers

Future Internet evolution requires innovative strategic stances and the design of original business models from actors involved in the ecosystem. The study focuses on Internet Carriers, recently striving to make their business sustainable, and proposes to enclose in a single reference framework all the critical levers, either consolidated or innovative, such actors can employ in order to design their value proposition, value network integration, and financial configuration. The framework grounds its findings on multiple case studies, and, by presenting an insightful list of business model parameters for Carriers, sheds light on key emerging strategic and tactical trends in the Internet interconnections market

Response of microchannel plates to single particles and to electromagnetic showers

We report on the response of microchannel plates (MCPs) to single relativistic particles and to electromagnetic showers. Particle detection by means of secondary emission of electrons at the MCP surface has long been proposed and is used extensively in ion time-of-flight mass spectrometers. What has not been investigated in depth is their use to detect the ionizing component of showers. The time resolution of MCPs exceeds anything that has been previously used in calorimeters and, if exploited effectively, could aid in the event reconstruction at high luminosity colliders. Several prototypes of photodetectors with the amplification stage based on MCPs were exposed to cosmic rays and to 491 MeV electrons at the INFN-LNF Beam-Test Facility. The time resolution and the efficiency of the MCPs are measured as a function of the particle multiplicity, and the results used to model the response to high-energy showers.Comment: Paper submitted to NIM

Direct measurements of the effects of salt and surfactant on interaction forces between colloidal particles at water-oil interfaces

The forces between colloidal particles at a decane-water interface, in the presence of low concentrations of a monovalent salt (NaCl) and of the surfactant sodium dodecylsulfate (SDS) in the aqueous subphase, have been studied using laser tweezers. In the absence of electrolyte and surfactant, particle interactions exhibit a long-range repulsion, yet the variation of the interaction for different particle pairs is found to be considerable. Averaging over several particle pairs was hence found to be necessary to obtain reliable assessment of the effects of salt and surfactant. It has previously been suggested that the repulsion is consistent with electrostatic interactions between a small number of dissociated charges in the oil phase, leading to a decay with distance to the power -4 and an absence of any effect of electrolyte concentration. However, the present work demonstrates that increasing the electrolyte concentration does yield, on average, a reduction of the magnitude of the interaction force with electrolyte concentration. This implies that charges on the water side also contribute significantly to the electrostatic interactions. An increase in the concentration of SDS leads to a similar decrease of the interaction force. Moreover the repulsion at fixed SDS concentrations decreases over longer times. Finally, measurements of three-body interactions provide insight into the anisotropic nature of the interactions. The unique time-dependent and anisotropic interactions between particles at the oil-water interface allow tailoring of the aggregation kinetics and structure of the suspension structure.Comment: Submitted to Langmui