Matteo Conti - Academia.edu (original) (raw)
Papers by Matteo Conti
Hepato-gastroenterology
ABSTRACT
Rapid communications in mass spectrometry : RCM, Jan 15, 2015
Surface-Activated Chemical Ionization/Electrospray Ionization mass spectrometry (SACI/ESI-MS) is ... more Surface-Activated Chemical Ionization/Electrospray Ionization mass spectrometry (SACI/ESI-MS) is a technique with high sensitivity and low noise that allows accurate biomarker discovery studies. We developed a dedicated SACI/ESI software, named SANIST, for both biomarker fingerprint data acquisition and as a diagnostic tool, using prostate cancer (PCa) as the disease of interest. Liquid chromatography (LC)/SACI/ESI-MS technology was employed to detect a potential biomarker panel for PCa disease prediction. Serum from patients with histologically confirmed or negative prostate biopsies for PCa was employed. The biomarker data (m/z or Thompson value, retention time and extraction mass chromatogram peak area) were stored in an ascii database. SANIST software allowed identification of potential biomarkers. A Bayesian scoring algorithm developed in house allowed sample separation based on comparison with samples in the database. Biomarker candidates from the carnitine family were detecte...
Journal of Parenteral and Enteral Nutrition, 2015
Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by... more Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by-product of vegetable and animal oil during the refining processes. Likewise, other lipid-soluble vitamins may be present in IVFE. No data, however, exist about phytonadione (vitamin K1) concentration in IVFE information leaflets. Therefore, our aim was to evaluate the phytonadione content in different IVFE. Analyses were carried out in triplicate on 6 branded IVFE as follows: 30% soybean oil (100%), 20% olive-soybean oil (80%-20%), 20% soybean-medium-chain triglycerides (MCT) coconut oil (50%-50%), 20% soybean-olive-MCT-fish oil (30%-25%-30%-15%), 20% soybean-MCT-fish oil (40%-50%-10%), and 10% pure fish oil (100%). Phytonadione was analyzed and quantified by a quali-quantitative liquid chromatography-mass spectrometry (LC-MS) method after its extraction from the IVFE by an isopropyl alcohol-hexane mixture, reverse phase-liquid chromatography, and specific multiple-reaction monitoring for phytonadione and vitamin d3 (as internal standard). This method was validated through specificity, linearity, and accuracy. Average vitamin K1 content was 500, 100, 90, 100, 95, and 70 µg/L in soybean oil, olive-soybean oil, soybean-MCT coconut oil, soybean-olive-MCT-fish oil, soybean-MCT-fish oil, and pure fish oil intravenous lipid emulsions (ILEs), respectively. The analytical LC-MS method was extremely effective in terms of specificity, linearity (r = 0.99), and accuracy (coefficient of variation <5%). Phytonadione is present in IVFE, and its intake varies according to IVFE type and the volume administered. It can contribute to daily requirements and become clinically relevant when simultaneously infused with multivitamins during long-term parenteral nutrition. LC-MS seems adequate in assessing vitamin K1 intake in IVFE.
International Journal of Electrical Power & Energy Systems, 2014
ABSTRACT Existing commercial battery charging posts for electric vehicles (EV) offer limited cont... more ABSTRACT Existing commercial battery charging posts for electric vehicles (EV) offer limited controllability and flexibility. These chargers are not designed to allow users to specify important criteria such as desired energy for next trip and waiting time whilst charging. In addition, the charging regime is not set to take into consideration the impact of charging (e.g. rate of charge) on the battery cycle life and the grid supply. With increased penetration of EVs and distributed generators (DG), complying with grid regulations will become more challenging, e.g. network voltage levels may deviate from the statutory limits. Moreover, as the battery is the most expensive part of an EV, consideration should be given to extending battery life and reduce the effective EV cost. Therefore, there is a need to develop a smart EV charge controller that can meet users’ requirements, extend battery cycle life and have minimum impact on the grid supply. In this paper, a smart controller is proposed which determines the optimal charging current based on grid voltage, battery state of health and user’s trip requirements. Models of a typical UK power distribution network and an EV battery (that allows simulation of battery aging process) are developed to investigate the performance of the “smart” charging system. Simulation and experimental results are presented to demonstrate the effectiveness of the proposed controller.
Lecture Notes in Mobility, 2014
ABSTRACT There is an increasing awareness, policies and an incentive landscape, which are encoura... more ABSTRACT There is an increasing awareness, policies and an incentive landscape, which are encouraging and starting to shape future transport as part of a wider ecosystem of infrastructure, use, behaviour and sustainability. However, one of the main barriers for the wider uptake by both fleet and individual users of electric vehicles is the concern of the uncertainties of Total Cost of Ownership (TCO). This contribution is based on a mix of original modelling, simulation and laboratory experimentation studies as well as a review of the academic and policy literature. It focuses on vehicle design and the battery and energy management in electric and plug-in hybrid electric vehicles (EV/PHEV). EV users express concerns about the longevity of the electric battery and hence the life cycle (especially with frequent fast charging), which amounts to a major part of the costs and value of the vehicle. Using the battery to provide ancillary services will add more value to the EV and reduce the effective TCO.
4th International Conference on Power Engineering, Energy and Electrical Drives, 2013
ABSTRACT The electric vehicle (EV) is targeted as an efficient method of decreasing CO2 emission ... more ABSTRACT The electric vehicle (EV) is targeted as an efficient method of decreasing CO2 emission and reducing dependence on fossil fuel. Compared with filling up the internal combustion engine (ICE) vehicle, the EV power charging time is usually long. However, to the best of our knowledge, the current charging strategy does not consider the battery state of health (SOH). It is noted that a high charging current rate may damage the battery life. Motivated by this, an optimal charging strategy is proposed in the present paper, providing several optimal charging options taking into account the EV battery health, trying to prevent 'abused battery utilization' happening.
Rapid Communications in Mass Spectrometry, 2011
Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identif... more Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identification of drugs of abuse and their metabolites in biological samples. However, the sensitivity and selectivity of this technique are commonly inadequate for the analysis of tetrahydrocannabinol (THC) and its metabolites at very low levels, such as those sometimes required in forensic and clinical-legal applications. We coupled electrospray ionization and surface-activated chemical ionization (ESI-SACI) to various types of mass analyzers (ion trap, triple quadrupole and orbitrap) (ESI-SACI-MS) to improve the detection of 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), the most common marker of THC abuse. The benefits of this approach in terms of sensitivity and selectivity compared with a common ESI-MS approach are clearly demonstrated.
Rapid Communications in Mass Spectrometry, 2013
Drug stability is an important quality-control issue for pharmaceutical and clinical practices. A... more Drug stability is an important quality-control issue for pharmaceutical and clinical practices. Among the analytical techniques that address this issue, liquid chromatography/mass spectrometry (LC/MS) can be very useful, especially when assessing the quality of liquid formulations, because it is intrinsically sensitive, selective, and a rapid analytical technique. However, LC/MS suffers from technical drawbacks, e.g., matrix effects, and the production of in-source degradation products, which can limit its usefulness. To overcome the aforementioned drawbacks associated with LC/MS, we introduce an innovative approach (2D-LC/SACI-ESI-MS/MS) that incorporates two-dimensional liquid chromatography (2D-LC) in conjunction with an MS system consisting of a surface-activated chemical ionization-electrospray ionization chamber (SACI-ESI), an ion trap MS analyzer, and tandem mass spectrometry. To validate our 2D-LC/SACI-ESI-MS/MS system stability studies were performed on the computerized tomography contrast agents, iohexol, iodixanol, iopamidol, iomeprol, iopromide, and iobitridol, either alone or in binary combination. The matrix effects, in-source analyte degradation, and analytical performance were compared with those obtained using a one-dimensional LC/MS configuration. The accuracy coefficient of variance (CV) = 1-4%, and degradation (loss of water and other chemical moieties) was greatly reduced, attesting to the usefulness of this system for drug stability measurements. Our new approach improves the performance (sensitivity, accuracy, and signal stability) of LC/MS instrumentation for drug stability measurements by reducing signal suppression effects and in-source chemical reactions.
Proceedings of the National Academy of Sciences, 2003
Similar to many other types of cell-protein adhesion, the binding between Fn and S. epidermidis t... more Similar to many other types of cell-protein adhesion, the binding between Fn and S. epidermidis takes place under physiological shear rates. We investigated the dynamics of the interaction between individual living S. epidermidis cells and single Fn molecules under mechanical force by using the scanning force microscope. The mechanical strength of this interaction and the binding site in the Fn molecule were determined. The energy landscape of the binding͞unbinding process was mapped, and the force spectrum and the association and dissociation rate constants of the binding pair were measured.
Journal of Separation Science, 2007
Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma A liquid... more Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma A liquid chromatographic method with diode array detection (DAD) has been developed for the analysis of the antiepileptic agent lamotrigine (LTG) and its metabolites, lamotrigine 2-N-glucuronide and 2-N-methylated in plasma samples. The analytes were separated on a C8 RP column, using a mobile phase composed of methanol and a 0.45 mM, pH 3.5 phosphate buffer containing 0.17% triethylamine (24:76 v/v). Melatonin was used as the internal standard (IS). The DAD detector was set at 220 nm for the detection of all the analytes. A simple protein precipitation with methanol guaranteed high extraction yield values (A90%) and good purification from matrix interference. Good linearity was obtained in the 0.1 -15.0 lg/mL range for LTG and lamotrigine 2-N-glucuronide and in the 0.1 -2.0 lg/mL range for lamotrigine 2-N-methylated. The analytical method was validated in terms of precision, extraction yield, and accuracy. These assays gave RSD% values for precision always lower than 4.3% and mean accuracy higher than 80%. The method seems to be suitable for the analysis of plasma samples from patients treated with Lamictal.
Journal of Pharmaceutical and Biomedical Analysis, 2008
Cocaine is currently one of the most widespread abuse drugs in the world. Since hair cocaine conc... more Cocaine is currently one of the most widespread abuse drugs in the world. Since hair cocaine concentrations are a reliable marker of exposition to the drug, an original liquid chromatographic method has been developed for the determination of cocaine in human hair. The chromatographic analysis was carried out on a Hydro-RP C18 column, using a mobile phase containing a phosphate buffer (pH 3.0)-acetonitrile-methanol (75:15:10, v/v/v). Native cocaine fluorescence was monitored at 315 nm while exciting at 230 nm. Mirtazapine was used as the internal standard. Sample pre-treatment was carried out by incubative extraction with 0.1 M HCl followed by solid-phase extraction with C2 cartridges. Good linearity was obtained over a working range of 0.3-100.0 ng/mg. Both extraction yield (>89%) and precision values (R.S.D. < 6.2%) were highly satisfactory. The method was successfully applied to hair samples collected from cocaine users.
Journal of Pharmaceutical and Biomedical Analysis, 2008
Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identif... more Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identification of drugs of abuse and their metabolites in biological samples. However, the sensitivity and selectivity of this technique are commonly inadequate for the analysis of tetrahydrocannabinol (THC) and its metabolites at very low levels, such as those sometimes required in forensic and clinical-legal applications. We coupled electrospray ionization and surface-activated chemical ionization (ESI-SACI) to various types of mass analyzers (ion trap, triple quadrupole and orbitrap) (ESI-SACI-MS) to improve the detection of 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), the most common marker of THC abuse. The benefits of this approach in terms of sensitivity and selectivity compared with a common ESI-MS approach are clearly demonstrated.
Journal of Chromatography B, 2007
Methadone and buprenorphine are two of the drugs most frequently used for abstinence from illicit... more Methadone and buprenorphine are two of the drugs most frequently used for abstinence from illicit opioids and in the treatment of pain. A sensitive and selective high-performance liquid chromatographic method with diode array detection for the simultaneous determination of methadone, buprenorphine and norbuprenorphine has been developed. Separation of the three analytes was obtained by using a reversed-phase column (C8, 250mmx4.6mm i.d., 5microm) and a mobile phase composed of 40% phosphate buffer containing triethylamine, 50% methanol and 10% acetonitrile (final apparent pH 6.0). Loxapine was used as the internal standard. An accurate pre-treatment procedure of biological samples was developed, using solid-phase extraction with C8 cartridges (100mg, 1mL) and needing small amounts of plasma or urine (300microL). The calibration curves were linear over a working range of 10.0-1500.0ng/mL for methadone and of 5.0-500.0ng/mL for buprenorphine and norbuprenorphine in both matrices. The limit of quantitation (LOQ) and the limit of detection (LOD) were 1.0 and 0.4ng/mL for methadone and 0.5 and 0.2ng/mL for both buprenorphine and norbuprenorphine, respectively. The method was successfully applied to the analysis of plasma and urine samples from patients undergoing treatment with these drugs. Precision and accuracy results were satisfactory and no interference from endogenous or exogenous compounds was found. The method is suitable for the simultaneous determination of methadone and buprenorphine in human plasma and urine for therapeutic drug monitoring purposes.
Journal of Biomedical Materials Research, 2002
A mechanochemical study of the process of adhesion of plasma proteins to the surface of dialysis ... more A mechanochemical study of the process of adhesion of plasma proteins to the surface of dialysis membranes was carried out with a scanning force microscope (SFM) in the force spectroscopy mode. Three representative blood plasma proteins (fibronectin, fibrinogen, and albumin) covalently were grafted to a SFM probe, and the adhesion forces of these proteins to cellulosic and synthetic dialysis membranes were measured. The experiment was tailored to apply a controlled load on the protein molecules adsorbed onto the surface in order to simulate the squeezing forces exerted on them during blood filtration. The de-adhesion forces, measured using this new approach for studying the interaction between a protein and dialysis membranes, suggest that the membrane&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s topography, at a nanometer scale, plays a critical role in the adhesion process. This result was strongly supported by parallel experiments performed on a flattened glass surface with the same dominant hydrophilic character as dialysis membranes. In contrast, a hydrophobic polystyrene surface led to de-adhesion forces at least one order of magnitude greater, overwhelming any possible shape recognition process between the protein molecules and the surface.
Journal of Biological Chemistry, 2008
One of the defining properties of beta2-adrenergic receptor (beta(2)AR) signaling is the transien... more One of the defining properties of beta2-adrenergic receptor (beta(2)AR) signaling is the transient and rapidly reversed accumulation of cAMP. Here we have investigated the contribution of different PDE4 proteins to the generation of this transient response. To this aim, mouse embryonic fibroblasts deficient in PDE4A, PDE4B, or PDE4D were generated, and the regulation of PDE activity, the accumulation of cAMP, and CREB phosphorylation in response to isoproterenol were monitored. Ablation of PDE4D, but not PDE4A or PDE4B, had a major effect on the beta-agonist-induced PDE activation, with only a minimal increase in PDE activity being retained in PDE4D knock-out (KO) cells. Accumulation of cAMP was markedly enhanced, and the kinetics of cAMP accumulation were altered in their properties in PDE4DKO but not PDE4BKO cells. Modest effects were observed in PDE4AKO mouse embryonic fibroblasts. The return to basal levels of both cAMP accumulation and CREB phosphorylation was greatly delayed in the PDE4DKO cells, suggesting that PDE4D is critical for dissipation of the beta2AR stimulus. This effect of PDE4D ablation was in large part due to inactivation of a negative feedback mechanism consisting of the PKA-mediated activation of PDE4D in response to elevated cAMP levels, as indicated by experiments using the cAMP-dependent protein kinase inhibitors H89 and PKI. Finally, PDE4D ablation affected the kinetics of beta2AR desensitization as well as the interaction of the receptor with Galphai. These findings demonstrate that PDE4D plays a major role in shaping the beta2AR signal.
Journal of Biological Chemistry, 2007
Disorganized ion transport caused by hypo- or hyperfunctioning of the cystic fibrosis transmembra... more Disorganized ion transport caused by hypo- or hyperfunctioning of the cystic fibrosis transmembrane conductance regulator (CFTR) can be detrimental and may result in life-threatening diseases such as cystic fibrosis or secretory diarrhea. Thus, CFTR is controlled by elaborate positive and negative regulations for an efficient homeostasis. It has been shown that expression and activity of CFTR can be regulated either positively or negatively by PDZ (PSD-95/discs large/ZO-1) domain-based adaptors. Although a positive regulation by PDZ domain-based adaptors such as EBP50/NHERF1 is established, the mechanisms for negative regulation of the CFTR by Shank2, as well as the effects of multiple adaptor interactions, are not known. Here we demonstrate a physical and physiological competition between EBP50-CFTR and Shank2-CFTR associations and the dynamic regulation of CFTR activity by these positive and negative interactions using the surface plasmon resonance assays and consecutive patch clamp experiments. Furthermore whereas EBP50 recruits a cAMP-dependent protein kinase (PKA) complex to CFTR, Shank2 was found to be physically and functionally associated with the cyclic nucleotide phosphodiesterase PDE4D that precludes cAMP/PKA signals in epithelial cells and mouse brains. These findings strongly suggest that balanced interactions between the membrane transporter and multiple PDZ-based adaptors play a critical role in the homeostatic regulation of epithelial transport and possibly the membrane transport in other tissues.
International Journal of Cancer, 2012
The small, water soluble molecule Dichloroacetate (DCA) is recently arousing lively interests in ... more The small, water soluble molecule Dichloroacetate (DCA) is recently arousing lively interests in the field of cancer therapy for it has been shown to be able to inhibit the growth of human tumors acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells. Neuroblastoma was one of the tumor types on which DCA was considered ineffective as it is composed of cells with few recognized mitochondrial anomalies. Neuroblastoma, however, is composed of different cell types in terms of metabolism, phenotype and malignant potential. Despite the above prediction, in this work, we show that (i) DCA exhibits an unexpected anticancer effect on NB tumor cells and (ii) this effect is selectively directed to very malignant NB cells, whereas the more differentiated/less malignant NB cells are refractory to DCA treatment. This result supports the need of a detailed investigation of DCA anticancer properties against this tumor type with the final aim of its possible use as therapeutic agent.
Current Medicinal Chemistry, 2005
The serotonergic system plays a critical role in a wide variety of physiological and behavioral p... more The serotonergic system plays a critical role in a wide variety of physiological and behavioral processes. Dysregulation of the tightly controlled extracellular concentration of serotonin (5hydroxytryptamine, 5-HT) appears to be at the origin of a host of metabolic and psychiatric disorders. Since the plasma membrane 5-HT transporter (SERT) is the major protagonist in regulating extracellular 5-HT concentration, SERT is the target of most drugs interacting with the serotonergic system. Unfortunately, some of the drugs towards SERT (e.g. amphetamine derivatives) interfere with cell homeostasis leading to cell toxicity. Developing new SERT ligands devoid of any side-effect represents a major priority in the treatment of 5-HT-associated pathologies. Here, we report structure-activity relationships (SAR) and three-dimensional QSAR (3D-QSAR) studies of a library of 121 compounds including 5-HT analogs, harmanes, benzothiazoles, indanones, amphetamine derivatives and substrate-type 5-HT releasers, with the goal of identifying the structural determinants crucial for SERT uptake. In the absence of data about the bioactive form of 5-HT, conformational analysis of 5-HT was performed using quantum chemistry calculations. This led to three 5-HT stable conformers with anti, -gauche and +gauche side-chain conformation. These conformers, used as templates for superimposition with all the library compounds, enabled the design of a reliable 6-points pharmacophore representative of SERT uptake activity. Molecular dynamics (MD) simulations performed with compounds that are efficiently, moderately, poorly or not transported by SERT allowed to assess the validity of our pharmacophore. Altogether, our data provide for the first time a reliable pharmacophore of SERT uptake activity, which may help to the design of new drugs targeting SERT.
Biomaterials, 2003
Staphylococcus epidermidis is able to adhere onto biomaterials and to cause implant infections. R... more Staphylococcus epidermidis is able to adhere onto biomaterials and to cause implant infections. Recently, host matrix proteins, which in vivo cover the implants, have been indicated as substrates for adhesion by specific bacterial adhesins. Here, the binding of S. epidermidis to fibronectin, a main protein of the extracellular matrix, and the effect of heparin on this interaction were studied by dynamic force spectroscopy (DFS). Novelties are that S. epidermidis strains analysed by DFS were clinical isolates from prosthesisassociated infections, genotyped and phenotyped for their adhesion properties to fibronectin and examined as living cells. Thus, fibronectin-binding staphylococci adhered to the fibronectin-coated substratum and formed a continuous layer assuring their contact with the fibronectin-coated cantilever tip during the approach-retraction cycles of the DFS measurements. Results show that only a single molecular binding site of fibronectin is involved in the interaction with S. epidermidis, that it takes place at the domain near the C-terminus and that it is specifically inhibited by heparin. r
Abstract This paper describes the development of a generic model suitable for emulating Photovolt... more Abstract This paper describes the development of a generic model suitable for emulating Photovoltaic (PV) system characteristics in order to study its impacts on the performance power networks. This model can accurately emulate the dynamic behaviour of the PV ...
Hepato-gastroenterology
ABSTRACT
Rapid communications in mass spectrometry : RCM, Jan 15, 2015
Surface-Activated Chemical Ionization/Electrospray Ionization mass spectrometry (SACI/ESI-MS) is ... more Surface-Activated Chemical Ionization/Electrospray Ionization mass spectrometry (SACI/ESI-MS) is a technique with high sensitivity and low noise that allows accurate biomarker discovery studies. We developed a dedicated SACI/ESI software, named SANIST, for both biomarker fingerprint data acquisition and as a diagnostic tool, using prostate cancer (PCa) as the disease of interest. Liquid chromatography (LC)/SACI/ESI-MS technology was employed to detect a potential biomarker panel for PCa disease prediction. Serum from patients with histologically confirmed or negative prostate biopsies for PCa was employed. The biomarker data (m/z or Thompson value, retention time and extraction mass chromatogram peak area) were stored in an ascii database. SANIST software allowed identification of potential biomarkers. A Bayesian scoring algorithm developed in house allowed sample separation based on comparison with samples in the database. Biomarker candidates from the carnitine family were detecte...
Journal of Parenteral and Enteral Nutrition, 2015
Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by... more Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by-product of vegetable and animal oil during the refining processes. Likewise, other lipid-soluble vitamins may be present in IVFE. No data, however, exist about phytonadione (vitamin K1) concentration in IVFE information leaflets. Therefore, our aim was to evaluate the phytonadione content in different IVFE. Analyses were carried out in triplicate on 6 branded IVFE as follows: 30% soybean oil (100%), 20% olive-soybean oil (80%-20%), 20% soybean-medium-chain triglycerides (MCT) coconut oil (50%-50%), 20% soybean-olive-MCT-fish oil (30%-25%-30%-15%), 20% soybean-MCT-fish oil (40%-50%-10%), and 10% pure fish oil (100%). Phytonadione was analyzed and quantified by a quali-quantitative liquid chromatography-mass spectrometry (LC-MS) method after its extraction from the IVFE by an isopropyl alcohol-hexane mixture, reverse phase-liquid chromatography, and specific multiple-reaction monitoring for phytonadione and vitamin d3 (as internal standard). This method was validated through specificity, linearity, and accuracy. Average vitamin K1 content was 500, 100, 90, 100, 95, and 70 µg/L in soybean oil, olive-soybean oil, soybean-MCT coconut oil, soybean-olive-MCT-fish oil, soybean-MCT-fish oil, and pure fish oil intravenous lipid emulsions (ILEs), respectively. The analytical LC-MS method was extremely effective in terms of specificity, linearity (r = 0.99), and accuracy (coefficient of variation &amp;amp;amp;lt;5%). Phytonadione is present in IVFE, and its intake varies according to IVFE type and the volume administered. It can contribute to daily requirements and become clinically relevant when simultaneously infused with multivitamins during long-term parenteral nutrition. LC-MS seems adequate in assessing vitamin K1 intake in IVFE.
International Journal of Electrical Power & Energy Systems, 2014
ABSTRACT Existing commercial battery charging posts for electric vehicles (EV) offer limited cont... more ABSTRACT Existing commercial battery charging posts for electric vehicles (EV) offer limited controllability and flexibility. These chargers are not designed to allow users to specify important criteria such as desired energy for next trip and waiting time whilst charging. In addition, the charging regime is not set to take into consideration the impact of charging (e.g. rate of charge) on the battery cycle life and the grid supply. With increased penetration of EVs and distributed generators (DG), complying with grid regulations will become more challenging, e.g. network voltage levels may deviate from the statutory limits. Moreover, as the battery is the most expensive part of an EV, consideration should be given to extending battery life and reduce the effective EV cost. Therefore, there is a need to develop a smart EV charge controller that can meet users’ requirements, extend battery cycle life and have minimum impact on the grid supply. In this paper, a smart controller is proposed which determines the optimal charging current based on grid voltage, battery state of health and user’s trip requirements. Models of a typical UK power distribution network and an EV battery (that allows simulation of battery aging process) are developed to investigate the performance of the “smart” charging system. Simulation and experimental results are presented to demonstrate the effectiveness of the proposed controller.
Lecture Notes in Mobility, 2014
ABSTRACT There is an increasing awareness, policies and an incentive landscape, which are encoura... more ABSTRACT There is an increasing awareness, policies and an incentive landscape, which are encouraging and starting to shape future transport as part of a wider ecosystem of infrastructure, use, behaviour and sustainability. However, one of the main barriers for the wider uptake by both fleet and individual users of electric vehicles is the concern of the uncertainties of Total Cost of Ownership (TCO). This contribution is based on a mix of original modelling, simulation and laboratory experimentation studies as well as a review of the academic and policy literature. It focuses on vehicle design and the battery and energy management in electric and plug-in hybrid electric vehicles (EV/PHEV). EV users express concerns about the longevity of the electric battery and hence the life cycle (especially with frequent fast charging), which amounts to a major part of the costs and value of the vehicle. Using the battery to provide ancillary services will add more value to the EV and reduce the effective TCO.
4th International Conference on Power Engineering, Energy and Electrical Drives, 2013
ABSTRACT The electric vehicle (EV) is targeted as an efficient method of decreasing CO2 emission ... more ABSTRACT The electric vehicle (EV) is targeted as an efficient method of decreasing CO2 emission and reducing dependence on fossil fuel. Compared with filling up the internal combustion engine (ICE) vehicle, the EV power charging time is usually long. However, to the best of our knowledge, the current charging strategy does not consider the battery state of health (SOH). It is noted that a high charging current rate may damage the battery life. Motivated by this, an optimal charging strategy is proposed in the present paper, providing several optimal charging options taking into account the EV battery health, trying to prevent 'abused battery utilization' happening.
Rapid Communications in Mass Spectrometry, 2011
Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identif... more Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identification of drugs of abuse and their metabolites in biological samples. However, the sensitivity and selectivity of this technique are commonly inadequate for the analysis of tetrahydrocannabinol (THC) and its metabolites at very low levels, such as those sometimes required in forensic and clinical-legal applications. We coupled electrospray ionization and surface-activated chemical ionization (ESI-SACI) to various types of mass analyzers (ion trap, triple quadrupole and orbitrap) (ESI-SACI-MS) to improve the detection of 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), the most common marker of THC abuse. The benefits of this approach in terms of sensitivity and selectivity compared with a common ESI-MS approach are clearly demonstrated.
Rapid Communications in Mass Spectrometry, 2013
Drug stability is an important quality-control issue for pharmaceutical and clinical practices. A... more Drug stability is an important quality-control issue for pharmaceutical and clinical practices. Among the analytical techniques that address this issue, liquid chromatography/mass spectrometry (LC/MS) can be very useful, especially when assessing the quality of liquid formulations, because it is intrinsically sensitive, selective, and a rapid analytical technique. However, LC/MS suffers from technical drawbacks, e.g., matrix effects, and the production of in-source degradation products, which can limit its usefulness. To overcome the aforementioned drawbacks associated with LC/MS, we introduce an innovative approach (2D-LC/SACI-ESI-MS/MS) that incorporates two-dimensional liquid chromatography (2D-LC) in conjunction with an MS system consisting of a surface-activated chemical ionization-electrospray ionization chamber (SACI-ESI), an ion trap MS analyzer, and tandem mass spectrometry. To validate our 2D-LC/SACI-ESI-MS/MS system stability studies were performed on the computerized tomography contrast agents, iohexol, iodixanol, iopamidol, iomeprol, iopromide, and iobitridol, either alone or in binary combination. The matrix effects, in-source analyte degradation, and analytical performance were compared with those obtained using a one-dimensional LC/MS configuration. The accuracy coefficient of variance (CV) = 1-4%, and degradation (loss of water and other chemical moieties) was greatly reduced, attesting to the usefulness of this system for drug stability measurements. Our new approach improves the performance (sensitivity, accuracy, and signal stability) of LC/MS instrumentation for drug stability measurements by reducing signal suppression effects and in-source chemical reactions.
Proceedings of the National Academy of Sciences, 2003
Similar to many other types of cell-protein adhesion, the binding between Fn and S. epidermidis t... more Similar to many other types of cell-protein adhesion, the binding between Fn and S. epidermidis takes place under physiological shear rates. We investigated the dynamics of the interaction between individual living S. epidermidis cells and single Fn molecules under mechanical force by using the scanning force microscope. The mechanical strength of this interaction and the binding site in the Fn molecule were determined. The energy landscape of the binding͞unbinding process was mapped, and the force spectrum and the association and dissociation rate constants of the binding pair were measured.
Journal of Separation Science, 2007
Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma A liquid... more Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma A liquid chromatographic method with diode array detection (DAD) has been developed for the analysis of the antiepileptic agent lamotrigine (LTG) and its metabolites, lamotrigine 2-N-glucuronide and 2-N-methylated in plasma samples. The analytes were separated on a C8 RP column, using a mobile phase composed of methanol and a 0.45 mM, pH 3.5 phosphate buffer containing 0.17% triethylamine (24:76 v/v). Melatonin was used as the internal standard (IS). The DAD detector was set at 220 nm for the detection of all the analytes. A simple protein precipitation with methanol guaranteed high extraction yield values (A90%) and good purification from matrix interference. Good linearity was obtained in the 0.1 -15.0 lg/mL range for LTG and lamotrigine 2-N-glucuronide and in the 0.1 -2.0 lg/mL range for lamotrigine 2-N-methylated. The analytical method was validated in terms of precision, extraction yield, and accuracy. These assays gave RSD% values for precision always lower than 4.3% and mean accuracy higher than 80%. The method seems to be suitable for the analysis of plasma samples from patients treated with Lamictal.
Journal of Pharmaceutical and Biomedical Analysis, 2008
Cocaine is currently one of the most widespread abuse drugs in the world. Since hair cocaine conc... more Cocaine is currently one of the most widespread abuse drugs in the world. Since hair cocaine concentrations are a reliable marker of exposition to the drug, an original liquid chromatographic method has been developed for the determination of cocaine in human hair. The chromatographic analysis was carried out on a Hydro-RP C18 column, using a mobile phase containing a phosphate buffer (pH 3.0)-acetonitrile-methanol (75:15:10, v/v/v). Native cocaine fluorescence was monitored at 315 nm while exciting at 230 nm. Mirtazapine was used as the internal standard. Sample pre-treatment was carried out by incubative extraction with 0.1 M HCl followed by solid-phase extraction with C2 cartridges. Good linearity was obtained over a working range of 0.3-100.0 ng/mg. Both extraction yield (>89%) and precision values (R.S.D. < 6.2%) were highly satisfactory. The method was successfully applied to hair samples collected from cocaine users.
Journal of Pharmaceutical and Biomedical Analysis, 2008
Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identif... more Recently, electrospray ionization mass spectroscopy (ESI-MS) has been widely used for the identification of drugs of abuse and their metabolites in biological samples. However, the sensitivity and selectivity of this technique are commonly inadequate for the analysis of tetrahydrocannabinol (THC) and its metabolites at very low levels, such as those sometimes required in forensic and clinical-legal applications. We coupled electrospray ionization and surface-activated chemical ionization (ESI-SACI) to various types of mass analyzers (ion trap, triple quadrupole and orbitrap) (ESI-SACI-MS) to improve the detection of 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), the most common marker of THC abuse. The benefits of this approach in terms of sensitivity and selectivity compared with a common ESI-MS approach are clearly demonstrated.
Journal of Chromatography B, 2007
Methadone and buprenorphine are two of the drugs most frequently used for abstinence from illicit... more Methadone and buprenorphine are two of the drugs most frequently used for abstinence from illicit opioids and in the treatment of pain. A sensitive and selective high-performance liquid chromatographic method with diode array detection for the simultaneous determination of methadone, buprenorphine and norbuprenorphine has been developed. Separation of the three analytes was obtained by using a reversed-phase column (C8, 250mmx4.6mm i.d., 5microm) and a mobile phase composed of 40% phosphate buffer containing triethylamine, 50% methanol and 10% acetonitrile (final apparent pH 6.0). Loxapine was used as the internal standard. An accurate pre-treatment procedure of biological samples was developed, using solid-phase extraction with C8 cartridges (100mg, 1mL) and needing small amounts of plasma or urine (300microL). The calibration curves were linear over a working range of 10.0-1500.0ng/mL for methadone and of 5.0-500.0ng/mL for buprenorphine and norbuprenorphine in both matrices. The limit of quantitation (LOQ) and the limit of detection (LOD) were 1.0 and 0.4ng/mL for methadone and 0.5 and 0.2ng/mL for both buprenorphine and norbuprenorphine, respectively. The method was successfully applied to the analysis of plasma and urine samples from patients undergoing treatment with these drugs. Precision and accuracy results were satisfactory and no interference from endogenous or exogenous compounds was found. The method is suitable for the simultaneous determination of methadone and buprenorphine in human plasma and urine for therapeutic drug monitoring purposes.
Journal of Biomedical Materials Research, 2002
A mechanochemical study of the process of adhesion of plasma proteins to the surface of dialysis ... more A mechanochemical study of the process of adhesion of plasma proteins to the surface of dialysis membranes was carried out with a scanning force microscope (SFM) in the force spectroscopy mode. Three representative blood plasma proteins (fibronectin, fibrinogen, and albumin) covalently were grafted to a SFM probe, and the adhesion forces of these proteins to cellulosic and synthetic dialysis membranes were measured. The experiment was tailored to apply a controlled load on the protein molecules adsorbed onto the surface in order to simulate the squeezing forces exerted on them during blood filtration. The de-adhesion forces, measured using this new approach for studying the interaction between a protein and dialysis membranes, suggest that the membrane&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s topography, at a nanometer scale, plays a critical role in the adhesion process. This result was strongly supported by parallel experiments performed on a flattened glass surface with the same dominant hydrophilic character as dialysis membranes. In contrast, a hydrophobic polystyrene surface led to de-adhesion forces at least one order of magnitude greater, overwhelming any possible shape recognition process between the protein molecules and the surface.
Journal of Biological Chemistry, 2008
One of the defining properties of beta2-adrenergic receptor (beta(2)AR) signaling is the transien... more One of the defining properties of beta2-adrenergic receptor (beta(2)AR) signaling is the transient and rapidly reversed accumulation of cAMP. Here we have investigated the contribution of different PDE4 proteins to the generation of this transient response. To this aim, mouse embryonic fibroblasts deficient in PDE4A, PDE4B, or PDE4D were generated, and the regulation of PDE activity, the accumulation of cAMP, and CREB phosphorylation in response to isoproterenol were monitored. Ablation of PDE4D, but not PDE4A or PDE4B, had a major effect on the beta-agonist-induced PDE activation, with only a minimal increase in PDE activity being retained in PDE4D knock-out (KO) cells. Accumulation of cAMP was markedly enhanced, and the kinetics of cAMP accumulation were altered in their properties in PDE4DKO but not PDE4BKO cells. Modest effects were observed in PDE4AKO mouse embryonic fibroblasts. The return to basal levels of both cAMP accumulation and CREB phosphorylation was greatly delayed in the PDE4DKO cells, suggesting that PDE4D is critical for dissipation of the beta2AR stimulus. This effect of PDE4D ablation was in large part due to inactivation of a negative feedback mechanism consisting of the PKA-mediated activation of PDE4D in response to elevated cAMP levels, as indicated by experiments using the cAMP-dependent protein kinase inhibitors H89 and PKI. Finally, PDE4D ablation affected the kinetics of beta2AR desensitization as well as the interaction of the receptor with Galphai. These findings demonstrate that PDE4D plays a major role in shaping the beta2AR signal.
Journal of Biological Chemistry, 2007
Disorganized ion transport caused by hypo- or hyperfunctioning of the cystic fibrosis transmembra... more Disorganized ion transport caused by hypo- or hyperfunctioning of the cystic fibrosis transmembrane conductance regulator (CFTR) can be detrimental and may result in life-threatening diseases such as cystic fibrosis or secretory diarrhea. Thus, CFTR is controlled by elaborate positive and negative regulations for an efficient homeostasis. It has been shown that expression and activity of CFTR can be regulated either positively or negatively by PDZ (PSD-95/discs large/ZO-1) domain-based adaptors. Although a positive regulation by PDZ domain-based adaptors such as EBP50/NHERF1 is established, the mechanisms for negative regulation of the CFTR by Shank2, as well as the effects of multiple adaptor interactions, are not known. Here we demonstrate a physical and physiological competition between EBP50-CFTR and Shank2-CFTR associations and the dynamic regulation of CFTR activity by these positive and negative interactions using the surface plasmon resonance assays and consecutive patch clamp experiments. Furthermore whereas EBP50 recruits a cAMP-dependent protein kinase (PKA) complex to CFTR, Shank2 was found to be physically and functionally associated with the cyclic nucleotide phosphodiesterase PDE4D that precludes cAMP/PKA signals in epithelial cells and mouse brains. These findings strongly suggest that balanced interactions between the membrane transporter and multiple PDZ-based adaptors play a critical role in the homeostatic regulation of epithelial transport and possibly the membrane transport in other tissues.
International Journal of Cancer, 2012
The small, water soluble molecule Dichloroacetate (DCA) is recently arousing lively interests in ... more The small, water soluble molecule Dichloroacetate (DCA) is recently arousing lively interests in the field of cancer therapy for it has been shown to be able to inhibit the growth of human tumors acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells. Neuroblastoma was one of the tumor types on which DCA was considered ineffective as it is composed of cells with few recognized mitochondrial anomalies. Neuroblastoma, however, is composed of different cell types in terms of metabolism, phenotype and malignant potential. Despite the above prediction, in this work, we show that (i) DCA exhibits an unexpected anticancer effect on NB tumor cells and (ii) this effect is selectively directed to very malignant NB cells, whereas the more differentiated/less malignant NB cells are refractory to DCA treatment. This result supports the need of a detailed investigation of DCA anticancer properties against this tumor type with the final aim of its possible use as therapeutic agent.
Current Medicinal Chemistry, 2005
The serotonergic system plays a critical role in a wide variety of physiological and behavioral p... more The serotonergic system plays a critical role in a wide variety of physiological and behavioral processes. Dysregulation of the tightly controlled extracellular concentration of serotonin (5hydroxytryptamine, 5-HT) appears to be at the origin of a host of metabolic and psychiatric disorders. Since the plasma membrane 5-HT transporter (SERT) is the major protagonist in regulating extracellular 5-HT concentration, SERT is the target of most drugs interacting with the serotonergic system. Unfortunately, some of the drugs towards SERT (e.g. amphetamine derivatives) interfere with cell homeostasis leading to cell toxicity. Developing new SERT ligands devoid of any side-effect represents a major priority in the treatment of 5-HT-associated pathologies. Here, we report structure-activity relationships (SAR) and three-dimensional QSAR (3D-QSAR) studies of a library of 121 compounds including 5-HT analogs, harmanes, benzothiazoles, indanones, amphetamine derivatives and substrate-type 5-HT releasers, with the goal of identifying the structural determinants crucial for SERT uptake. In the absence of data about the bioactive form of 5-HT, conformational analysis of 5-HT was performed using quantum chemistry calculations. This led to three 5-HT stable conformers with anti, -gauche and +gauche side-chain conformation. These conformers, used as templates for superimposition with all the library compounds, enabled the design of a reliable 6-points pharmacophore representative of SERT uptake activity. Molecular dynamics (MD) simulations performed with compounds that are efficiently, moderately, poorly or not transported by SERT allowed to assess the validity of our pharmacophore. Altogether, our data provide for the first time a reliable pharmacophore of SERT uptake activity, which may help to the design of new drugs targeting SERT.
Biomaterials, 2003
Staphylococcus epidermidis is able to adhere onto biomaterials and to cause implant infections. R... more Staphylococcus epidermidis is able to adhere onto biomaterials and to cause implant infections. Recently, host matrix proteins, which in vivo cover the implants, have been indicated as substrates for adhesion by specific bacterial adhesins. Here, the binding of S. epidermidis to fibronectin, a main protein of the extracellular matrix, and the effect of heparin on this interaction were studied by dynamic force spectroscopy (DFS). Novelties are that S. epidermidis strains analysed by DFS were clinical isolates from prosthesisassociated infections, genotyped and phenotyped for their adhesion properties to fibronectin and examined as living cells. Thus, fibronectin-binding staphylococci adhered to the fibronectin-coated substratum and formed a continuous layer assuring their contact with the fibronectin-coated cantilever tip during the approach-retraction cycles of the DFS measurements. Results show that only a single molecular binding site of fibronectin is involved in the interaction with S. epidermidis, that it takes place at the domain near the C-terminus and that it is specifically inhibited by heparin. r
Abstract This paper describes the development of a generic model suitable for emulating Photovolt... more Abstract This paper describes the development of a generic model suitable for emulating Photovoltaic (PV) system characteristics in order to study its impacts on the performance power networks. This model can accurately emulate the dynamic behaviour of the PV ...