A Method to Monitor the NAD+ Metabolome—From Mechanistic to Clinical Applications

Nicotinamide adenine dinucleotide (NAD⁺) and its reduced form (NADH) are coenzymes employed in hundreds of metabolic reactions. NAD⁺ also serves as a substrate for enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs) and ADP-ribosyl cyclases. Given the pivotal role of NAD(H) in health and disease, studying NAD⁺ metabolism has become essential to monitor genetic- and/or drug-induced perturbations related to metabolic status and diseases (such as ageing, cancer or obesity), and its possible therapies. Here, we present a strategy based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the analysis of the NAD⁺ metabolome in biological samples. In this method, hydrophilic interaction chromatography (HILIC) was used to separate a total of 18 metabolites belonging to pathways leading to NAD⁺ biosynthesis, including precursors, intermediates and catabolites. As redox cofactors are known for their instability, a sample preparation procedure was developed to handle a variety of biological matrices: cell models, rodent tissues and biofluids, as well as human biofluids (urine, plasma, serum, whole blood). For clinical applications, quantitative LC-MS/MS for a subset of metabolites was demonstrated for the analysis of the human whole blood of nine volunteers. Using this developed workflow, our methodology allows studying NAD⁺ biology from mechanistic to clinical applications.     

Epigenetic Regulation by microRNAs in Hyperhomocysteinemia-Accelerated Atherosclerosis

Increased serum levels of homocysteine (Hcy) is a risk factor for cardiovascular disease and is specifically linked to various diseases of the vasculature such as atherosclerosis. However, the precise mechanisms by which Hcy contributes to this condition remain elusive. During the development of atherosclerosis, epigenetic modifications influence gene expression. As such, epigenetic modifications are an adaptive response to endogenous and exogenous factors that lead to altered gene expression by methylation and acetylation reactions of different substrates and the action of noncoding RNA including microRNAs (miRNAs). Epigenetic remodeling modulates cell biology in both physiological and physiopathological conditions. DNA and histone modification have been identified to have a crucial role in the progression of atherosclerosis. However, the potential role of miRNAs in hyperHcy (HHcy)-related atherosclerosis disease remains poorly explored and might be essential as well. There is no review available yet summarizing the contribution of miRNAs to hyperhomocystein-mediated atherogenicity or their potential as therapeutic targets even though their important role has been described in numerous studies. Specifically, downregulation of miR-143 or miR-125b has been shown to regulate VSCMs proliferation in vitro. In preclinical studies, downregulation of miR-92 or miR195-3p has been shown to increase the accumulation of cholesterol in foam cells and increase macrophage inflammation and atherosclerotic plaque formation, respectively. Another preclinical study found that there is a reciprocal regulation between miR-148a/152 and DNMT1 in Hcy-accelerated atherosclerosis. Interestingly, a couple of studies have shown that miR-143 or miR-217 may be used as potential biomarkers in patients with HHcy that may develop atherosclerosis. Moreover, the current review will also update current knowledge on miRNA-based therapies, their challenges, and approaches to deal with Hcy-induced atherosclerosis.     

Photovoltaic system simulation using a standard electronic circuit simulator

An approach to photovoltaic (PV) system simulation is presented based on the use of SPICE instead of using a specifically developed software package. SPICE models for PV cells, PV modules, lead-acid batteries and the rest of the main components of a PV system have been developed. A simulation example of a stand-alone PV system including measured irradiance data as an input is used to show some of the possibilities inherent in such an approach. Greater flexibility, quick access to all voltages and currents within the system and a simpler way of interfacing with standard electronic components are the main conclusions to be drawn from this work.     

Experimental study of the vapour–liquid equilibria of HI–I2–H2O ternary mixtures,Part 2: Experimental results at high temperature and pressure

In order to assess the choice of the sulphur–iodine thermochemical cycle for massive hydrogen production, a precise knowledge of the concentrations of the gaseous species (HI, I₂, and H₂O) in thermodynamic equilibrium with the liquid phase of the HI–I₂–H₂O ternary mixture is required, in a wide range of concentrations and for temperatures and pressures up to 300 °C and 50 bar.     

Multiproject–multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy

Justification  Automatic brain tumor classification by MRS has been under development for more than a decade. Nonetheless, to our knowledge, there are no published evaluations of predictive models with unseen cases that are subsequently acquired in different centers. The multicenter eTUMOUR project (2004–2009), which builds upon previous expertise from the INTERPRET project (2000–2002) has allowed such an evaluation to take place. Materials and Methods  A total of 253 pairwise classifiers for glioblastoma, meningioma, metastasis, and low-grade glial diagnosis were inferred based on 211 SV short TE INTERPRET MR spectra obtained at 1.5 T (PRESS or STEAM, 20–32 ms) and automatically pre-processed. Afterwards, the classifiers were tested with 97 spectra, which were subsequently compiled during eTUMOUR. Results  In our results based on subsequently acquired spectra, accuracies of around 90% were achieved for most of the pairwise discrimination problems. The exception was for the glioblastoma versus metastasis discrimination, which was below 78%. A more clear definition of metastases may be obtained by other approaches, such as MRSI + MRI. Conclusions  The prediction of the tumor type of in-vivo MRS is possible using classifiers developed from previously acquired data, in different hospitals with different instrumentation under the same acquisition protocols. This methodology may find application for assisting in the diagnosis of new brain tumor cases and for the quality control of multicenter MRS databases.     

Hydropeaking effects on movement patterns of brown trout (Salmo trutta L.)

Radiotelemetry was used to investigate seasonal movement and home range of brown trout Salmo trutta (size range 188–420 mm fork length, N = 30) in two reaches of the Noguera Pallaresa River (Ebro Basin, north‐east Spain) subjected to different flow regulation schemes. NP‐1 reach is a bypassed section with near natural flow conditions, whereas the downstream reach NP‐2 is subjected to daily pulsed flow discharge (i.e., hydropeaking) from an upstream hydropower station. Significant differences in home range size (95% kernel estimates) and seasonal movement pattern between study reaches were found. Mean home range size was (μ ± SE) 112.1 ± 11.5 m in the bypassed reach NP‐1 and increased significantly in the hydropeaking reach NP‐2 up to 237.9 ± 37.2 m. There was a large individual variability in fish home range size within reaches. Most of the seasonal differences in fish movement among reaches were associated with the spawning season. Pulsed discharge events in NP‐2 during daytime in summer (lasting about 3 hr and increasing water flow from 1 to 20 m³/s) did not cause significant displacements in either upstream or downstream direction during the duration of the event. Our results highlight the importance of habitat connectivity in hydropeaking streams due to the need of brown trout to move large distances among complementary habitats, necessary to complete their life cycle, compared with unregulated or more stable streams.     

Review of Robust Cooperative Spectrum Sensing Techniques for Cognitive Radio Networks

Cognitive radio networks sense spectrum occupancy and manage themselves to operate in unused bands without disturbing licensed users. The detection capability of a radio system can be enhanced if the sensing process is performed jointly by a group of nodes so that the effects of wireless fading and shadowing can be minimized. However, taking a collaborative approach poses new security threats to the system as nodes can report false sensing data to reach a wrong decision. This paper makes a review of secure cooperative spectrum sensing in cognitive radio networks. The main objective of these protocols is to provide an accurate resolution about the availability of some spectrum channels, ensuring the contribution from incapable users as well as malicious ones is discarded. Issues, advantages and disadvantages of such protocols are investigated and summarized.     

Predicting availability functions in time-dependent complex systems with SAEDES simulation algorithms

In this paper, we propose the use of discrete-event simulation (DES) as an efficient methodology to obtain estimates of both survival and availability functions in time-dependent real systems—such as telecommunication networks or distributed computer systems. We discuss the use of DES in reliability and availability studies, not only as an alternative to the use of analytical and probabilistic methods, but also as a complementary way to: (i) achieve a better understanding of the system internal behavior and (ii) find out the relevance of each component under reliability/availability considerations. Specifically, this paper describes a general methodology and two DES algorithms, called SAEDES, which can be used to analyze a wide range of time-dependent complex systems, including those presenting multiple states, dependencies among failure/repair times or non-perfect maintenance policies. These algorithms can provide valuable information, specially during the design stages, where different scenarios can be compared in order to select a system design offering adequate reliability and availability levels. Two case studies are discussed, using a C/C++ implementation of the SAEDES algorithms, to show some potential applications of our approach.     

FRUIT: An operational tool for multisphere neutron spectrometry in workplaces

FRUIT (Frascati Unfolding Interactive Tool) is an unfolding code for Bonner sphere spectrometers (BSS) developed, under the Labview environment, at the INFN-Frascati National Laboratory. It models a generic neutron spectrum as the superposition of up to four components (thermal, epithermal, fast and high energy), fully defined by up to seven positive parameters. Different physical models are available to unfold the sphere counts, covering the majority of the neutron spectra encountered in workplaces. The iterative algorithm uses Monte Carlo methods to vary the parameters and derive the final spectrum as limit of a succession of spectra fulfilling the established convergence criteria. Uncertainties on the final results are evaluated taking into consideration the different sources of uncertainty affecting the input data. Relevant features of FRUIT are (1) a high level of interactivity, allowing the user to follow the convergence process, (2) the possibility to modify the convergence tolerances during the run, allowing a rapid achievement of meaningful solutions and (3) the reduced dependence of the results from the initial hypothesis. This provides a useful instrument for spectrometric measurements in workplaces, where detailed a priori information is usually unavailable. This paper describes the characteristics of the code and presents the results of performance tests over a significant variety of reference and workplace neutron spectra ranging from thermal up to hundreds MeV neutrons.