Non-functional variants of yeast mitochondrial ATP synthase subunit 8 that assemble into the complex

Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2- propanol (S-1'-[18F]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We have determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C18) followed by reversed-phase HPLC and (2) direct injection of untreated plasma samples on an internal-surface reversed-phase (ISRP) column. The two methods were in good agreement. Unmodified I decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and human volunteers, respectively. Protein binding in sheep and human plasma was determined by ultrafiltration. The fraction of total plasma radioactivity bound to protein and the fraction representing unmodified radioligand were linearly correlated, suggesting that fluorocarazolol was more than 70% protein-bound, whereas its metabolites showed negligible protein binding. Direct injection of plasma on an ISRP column seems a convenient method for quantification of lipophilic radioligands such as fluorocarazolol.     

The TSIMMIS Approach to Mediation: Data Models and Languages

TSIMMIS—The Stanford-IBM Manager of Multiple InformationSources—is a system for integrating information. It offers a datamodel and a common query language that are designed to support thecombining of information from many different sources. It also offerstools for generating automatically the components that are needed tobuild systems for integrating information. In this paper we shalldiscuss the principal architectural features and their rationale.     

Spatio-Temporal Short-Term Urban Traffic Volume Forecasting Using Genetically Optimized Modular Networks

Abstract:   Current interest in short-term traffic volume forecasting focuses on incorporating temporal and spatial volume characteristics in the forecasting process. This article addresses the problem of integrating and optimizing predictive information from multiple locations of an urban signalized arterial and proposes a modular neural predictor consisting of temporal genetically optimized structures of multilayer perceptrons (MLP) that are fed with volume data from sequential locations to improve the accuracy of short-term forecasts. The results show that the proposed methodology provides more accurate forecasts compared to the conventional statistical methodologies applied, as well as to the static forms of neural networks.     

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism,Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.     

The mechanical property and phase structures of wheat proteins/polyvinyl alcohol blends studied by high-resolution solid-state NMR

The phase structures of thermally processed wheat proteins (WP) and polyvinyl alcohol (PVOH) blends were studied by solid-state high-resolution NMR spectroscopy. The intermolecular interactions among the multi-component systems and the behavior of each component in the blends on scales of nanometers were examined. The mechanical properties of the blends were also measured and related to the phase structure studies. The results indicated that the polymer chains of WP could be homogeneously mobilized when thermally processed with glycerol and water as plasticisers, but the glycerol predominately associated with WP rather than PVOH in the blends. The intermolecular hydrogen bonding interactions between WP and PVOH caused some extent of miscibility in the system on scales of nanometers especially when the PVOH content was low. The tensile strength and modulus of the blends were improved as compared to WP. However, the intermolecular interactions were relatively weak and could not be further enhanced by increasing PVOH component in the blends. The particle miscible WP/PVOH blends contained plasticised WP and PVOH phases in conjunction with the miscible WP/PVOH phase. Increasing the PVOH content in the blends did not result in an increase of the percentage of the miscible phase and the blends tented to be immiscible while the elongation of the blends was reduced when increasing the PVOH content in the blends.     

High resolution XPS characterization of chemical functionalised MWCNTs and SWCNTs

High resolution XPS analysis of chemical functionalised multi-wall carbon nanotubes (MWCNTs) and single wall carbon nanotubes (SWCNT) was done with ESCA300 (overall instrument resolution of 0.35 eV). Information to the degree of functionalisation was ascertained by argon ion bombardment of the samples followed by XPS analysis to detect the functional groups, the percentage atomic concentration of various elements present and whether or not the detected functional groups imposed a chemical shift on the CNT atoms. The results show that true chemical functionalisation was achieved and by argon ion bombardment these functional groups can be altered relative to the C 1s carbon atoms of the CNT. The choice of chemicals used for functionalisation, the techniques employed and the types of nanotubes treated are important factors in chemical characterisation. The carbon atom on the nanotube ring to which the functional group (atom) is bonded, the chirality of the CNT, the electronegativity of the functional group, the bond type and whether the CNT is single-wall or multi-wall, or cut (short) could play a role in determining the chemical shift on the CNTs atoms. These investigations are relevant to chemical functionalisation of carbon nanotubes for various applications for example DNA sensors and other biomedical sensors.     

Oxidative functionalization of carbon nanotubes in atmospheric pressure filamentary dielectric barrier discharge (APDBD)

The surface compositional and any structural changes that occur on carbon nanotubes using air-atmospheric pressure dielectric barrier discharge (APDBD) for functionalization are investigated employing Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), and neutron diffraction techniques. Atmospheric pressure plasmas (APP) are suggested to be particularly suitable for functionalization of aligned nanotubes, where wet chemical manipulation could damage or even destroy the highly desirable vertical alignment. In this work a detailed experimental study elucidating the effects of APDBD plasma treatment parameters (e.g. power density, discharge composition, inter-electrode gap and treatment time) on the electronic structure, physical, and chemical behaviour of carbon nanotubes has been conducted. In an atmospheric air we find an optimal oxidative functionalization of CNTs in our DBD system within few seconds (<5 s) at a discharge power of ∼0.5 kW. This investigation may find useful application as functionalization technique for CNT engineered devices and sensors.     

Applying storm water management in Greek cities: learning from the European experience

This paper is based on the studies forming part of the European research project DayWater, which aims at the promotion of stormwater source control (participating countries: UK, France, Sweden, Denmark, Germany, The Netherlands and Greece). Source control techniques include all techniques (e.g. retention, infiltration, reuse) of stormwater treatment near its source, in contrast to end-of-pipe. In this paper we present: the different stormwater management issues across Europe; the specific stormwater management issues in Greece; source control techniques applied in European cities; Public policies for promoting source control techniques; Strategies of application of the aforementioned techniques and policies in Greek cities. In Greece, the question of stormwater treatment has not yet attracted a lot of attention. Wastewater management, flood prevention and fresh water scarcity issues are given priority instead. However source control stormwater management can contribute to the solution of all these problems. In many European cities source control techniques have been chosen for stormwater treatment because: a) they are less expensive than massive end-of-pipe treatment installations, b) they are more compatible with the natural water cycle, c) they reduce the overall stormwater flow and thus permit the expansion of cities without requesting reconstruction of the existing sewer networks. Different policy instruments (taxes, specific regulations and controls, information campaigns) have been applied in order to promote source control techniques. The main objective of this work is to discuss the possibility of applying similar techniques and policies in Greek cities.     

Enhancing self-scheduling algorithms via synchronization and weighting

Existing dynamic self-scheduling algorithms, used to schedule independent tasks on heterogeneous clusters, cannot handle tasks with dependencies because they lack the support for internode communication. To compensate for this deficiency we introduce a synchronization mechanism that provides inter-processor communication, thus, enabling self-scheduling algorithms to handle efficiently nested loops with dependencies. We also present a weighting mechanism that significantly improves the performance of dynamic self-scheduling algorithms. These algorithms divide the total number of tasks into chunks and assign them to processors. The weighting mechanism adapts the chunk sizes to the computing power and current run-queue state of the processors. The synchronization and weighting mechanisms are orthogonal, in the sense that they can simultaneously be applied to loops with dependencies. Thus, they broaden the application spectrum of dynamic self-scheduling algorithms and improve their performance. Extensive testing confirms the efficiency of the synchronization and weighting mechanisms and the significant improvement of the synchronized–weighted versions of the algorithms over the synchronized-only versions.     

Aberrant protein expression in plasma and kidney tissue during experimental obstructive nephropathy

Kidney failure is a major health problem worldwide. Patients with end-stage renal disease require intensive medical support by dialysis or kidney transplantation. Current methods for diagnosis of kidney disease are either invasive or insensitive, and renal function may decline by as much as 50% before it can be detected using current techniques. The goal of this study was, therefore, to identify biomarkers of kidney disease (associated with renal fibrosis) that can be used for the development of a non-invasive clinical test for early disease detection. We utilized two protein-profiling technologies (SELDI-TOF MS and 2-D) to screen the plasma and kidney proteome for aberrantly expressed proteins in an experimental mouse model of unilateral uretric obstruction, which mimics the pathology of human renal disease. Several differentially regulated proteins were detected at the plasma level of day-3-obstructed animals, which included serum amyloid A1, fibrinogen α, haptoglobin precursor protein, haptoglobin and major urinary proteins 11 and 8. Differentially expressed proteins detected at the tissue level included ras-like activator protein 2, haptoglobin precursor protein, malate dehydrogenase, α enolase and murine urinary protein (all p<0.05 versus controls). Immunohistochemistry was used to confirm the up-regulation of fibrinogen. Interestingly, these proteins are largely separated into four major classes: (i) acute-phase reactants (ii) cell-signaling molecules (iii) molecules involved in cell growth and metabolism and (iv) urinary proteins. These results provide new insights into the pathology of obstructive nephropathy and may facilitate the development of specific assay(s) to detect and monitor renal fibrosis.