26 research outputs found
A Grid Information Service Based on Peer-to-Peer
No full textInformation Services are fundamental blocks of the Grid infrastructure. They are responsible for collecting and distributing information about resource availability and status to users: the quality of these data may have a strong impact on scheduling algorithms and overall performance. Many popular information services have a centralized structure. This clearly introduces problems related to information updating and fault tolerance. Also, in very large configurations, scalability may be an issue. In this work, we present a Grid Information Service based on the peer-to-peer technology. Our system offers a fast propagation of information and has high scalability and reliability. We implemented our system complying to the OGSA standard using the Globus Toolkit 3. Our system can run on Linux and Windows systems, with different network configurations, so to trade off between redundancy (reliability) and cost. © Springer-Verlag Berlin Heidelberg 2005
A new approach to detect and study ion channel formation in microBLMs
No full textIn this paper, an innovative and versatile approach to detect pore formation in microBLMs and to investigate their ion selectivity is described. For the first time, both electrochemical impedance spectroscopy and conductivity measurements are performed on the same membrane, providing a simple, long-lasting and cheap method which can find applications in various ion channel-involving research fields. We make use of this improved experimental procedure to obtain for the first time a range of values to characterize homogeneous polycarbonate-supported microBLMs. To test the validity of our method, the well-known. channel-forming peptide gramicidin D was first employed. Then, we applied our approach to the study of the still unclear membrane interaction mechanisms of the peptides trichogin GA IV and phospholamban, finding that both can form ion channels in biomimetic models. The phospholamban-generated ion channels could be a promising therapeutic target in heart failures and other cardiac diseases. Our methodology might also be useful for detecting new drugs with ion-channel blocking action. (C) 2011 Elsevier B.V. All rights reserved
Ivabradine, coronary artery disease, and heart failure: beyond rhythm control
No full textPietro Scicchitano,1 Francesca Cortese,1 Gabriella Ricci,1 Santa Carbonara,1 Michele Moncelli,1 Massimo Iacoviello,1 Annagrazia Cecere,1 Michele Gesualdo,1 Annapaola Zito,1 Pasquale Caldarola,2 Domenico Scrutinio,3 Rocco Lagioia,3 Graziano Riccioni,4 Marco Matteo Ciccone1 1Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Bari, Italy; 2Section of Cardiovascular Diseases, Policlinic, San Paolo Hospital, Bari, Italy; 3Section of Cardiovascular Diseases, Fondazione Maugeri, Cassano Murge, Italy; 4Intensive Cardiology Care Unit, San Camillo de Lellis Hospital, Manfredonia, Foggia, Italy Abstract: Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies. Keywords: chronic heart failure, heart rate reduction, cardiac ischemic disease, heart-rate lowering drugs, funny curren
A Novel Cardiac Bio-Marker: ST2: A Review
No full textCardiovascular diseases (CVD) are the major cause of death worldwide. The identification of markers able to detect the early stages of such diseases and/or their progression is fundamental in order to adopt the best actions in order to reduce the worsening of clinical condition. Brain natriuretic peptide (BNP) and NT-proBNP are the best known markers of heart failure (HF), while troponins ameliorated the diagnosis of acute and chronic coronary artery diseases. Nevertheless, many limitations reduce their accuracy. Physicians have tried to develop further detectable molecules in order to improve the detection of the early moments of CVD and prevent their development. Soluble ST2 (suppression of tumorigenicity 2) is a blood protein confirmed to act as a decoy receptor for interleukin-33. It seems to be markedly induced in mechanically overloaded cardiac myocytes. Thus, HF onset or worsening of a previous chronic HF status, myocardial infarct able to induce scars that make the myocardium unable to stretch well, etc, are all conditions that could be detected by measuring blood levels of soluble ST2. The aim of this review is to explore the possible role of ST2 derived-protein as an early marker of cardiovascular diseases, above all in heart failure and ischemic heart diseases
Characterization of hybrid bilayer membranes on silver electrodes as biocompatible SERS substrates to study membrane-protein interactions
No full textHybrid bilayer lipid membranes (HBMs) were built on roughened silver electrodes exhibiting surface-enhanced Raman scattering (SERS) activity. The HBM consisted of a first layer of octadecanethiol (ODT) directly bound to the electrode surface, on which a second layer of 1.2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) was obtained by self-assembled phospholipid vesicle fusion. The electrochemical properties of the HBM were investigated in situ by cyclic voltammetry (CV), AC voltammetry and electrochemical impedance spectroscopy (EIS). The results indicate that our HBMs are well-formed, and their insulating properties are comparable to those observed for HBM supported by smooth metal substrates. The interaction between the bilayer and the human enzyme cytochrome P450 2D6 (CYP2D6) was investigated. Surface-enhanced resonance Raman scattering (SERRS) measurements in combination with AC and EIS, performed on the same electrode sample, proved that the CYP2D6 is immobilized on the HBM without evident alterations of its active site and without significant perturbations of the bilayer architecture. This study yields novel insights into the properties of HBMs built on roughened surfaces, providing in situ electrochemical characterization of a substrate which is suitable for studying peripheral membrane proteins with SERRS spectroscopy
SEAS (Software Energetico per Audit Semplificati - Simplified Energy Auditing Software), versione 2.0
No full textSoftware con interfaccia grafica per l'audit energetico negli edifici ad uso residenziale, uffici e scuole, sviluppato in collaborazione con ENEA. Basato sul linguaggio Java, con database MySQL
Lipoic-Based TRPA1/TRPV1 Antagonist to Treat Orofacial Pain
No full textInflammation of the
trigeminal nerve is considered one of the most
painful conditions known to humankind. The diagnosis is often difficult;
moreover, safe and effective pharmacological treatments are lacking.
A new molecule, ADM_12, formed by a lipoic and omotaurine residues
covalently linked, is here reported. In vitro and in vivo tests showed
that ADM_12 is a very attractive original compound presenting (i)
a remarkable safety profile; (ii) a high binding constant versus TRPA1;
(iii) an intriguing behavior versus TRPV1; and (iv) the ability to
significantly and persistently reduce mechanical facial allodynia
in rats. Noteworthy, by testing ADM_12, we shed light on the unprecedented
involvement of TRPA1 and TRPV1 channels in orofacial pain
Mimicking the Intramolecular Hydrogen Bond: Synthesis, Biological Evaluation, and Molecular Modeling of Benzoxazines and Quinazolines as Potential Antimalarial Agents.
No full textThe intramolecular hydrogen bond formed between a protonated amine and a
neighbouring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to
play an important role in their antimalarial activities. Here we describe isoquine-based
compounds in which the intramolecular H-bond is mimicked by a methylene linker. The
antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline
derivatives, and febrifugine-based 1,3-quinazolin-4-ones were examined in vitro (against
Plasmodium falciparum) and in vivo (against P. berghei). Compounds 6b,c caused modest
inhibition of chloroquine transport via the parasite’s ‘chloroquine resistance transporter’
(PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental
evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound
6c emerged from this work as the most promising scaffold of the series; it possessed low toxicity
and good antimalarial activity when administered orally to P. berghei-infected mice
Mimicking the Intramolecular Hydrogen Bond: Synthesis, Biological Evaluation, and Molecular Modeling of Benzoxazines and Quinazolines as Potential Antimalarial Agents
No full textThe intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to play an important role in their antimalarial activities. Here we describe isoquine-based compounds in which the intramolecular H-bond is mimicked by a methylene linker. The antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3-quinazolin-4-ones were examined in vitro (against Plasmodium falciparum) and in vivo (against Plasmodium berghei). Compounds 6b,c caused modest inhibition of chloroquine transport via the parasite's chloroquine resistance transporter (PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound 6c emerged from this work as the most promising analogue of the series; it possessed low toxicity and good antimalarial activity when administered orally to P. berghei-infected mice. © 2012 American Chemical Society
The Final Frontier of pH and the Undiscovered Country Beyond
No full textThe comparison of volumes of cells and subcellular structures with the pH values reported for them leads to a conflict with
the definition of the pH scale. The pH scale is based on the ionic product of water, Kw = [H+]6[OH2].We used Kw [in a
reversed way] to calculate the number of undissociated H2O molecules required by this equilibrium constant to yield at
least one of its daughter ions, H+ or OH2 at a given pH. In this way we obtained a formula that relates pH to the minimal
volume VpH required to provide a physical meaning to Kw, VpH~10DpH{pKw=2D|
10pKw=2
NA
(where NA is Avogadro’s number).
For example, at pH 7 (neutral at 25uC) VpH = 16.6 aL. Any deviation from neutral pH results in a larger VpH value. Our results indicate that many subcellular structures, including coated vesicles and lysosomes, are too small to contain free H+ ions at equilibrium, thus the definition of pH based on Kw is no longer valid. Larger subcellular structures, such as mitochondria, apparently contain only a few free H+ ions. These results indicate that pH fails to describe intracellular conditions, and that water appears to be dissociated too weakly to provide free H+ ions as a general source for biochemical reactions. Consequences of this finding are discussed
