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Plasma initiation in ITER will be critical, since low electric field will be available, and a reduction of field lines connection length may occur due to the presence of stray fields. A number of studies have been performed to assess the impact of different stray field sources, but they mostly use equivalent 2D models to assess effects of intrinsically 3D fields, or were performed on other machines run in “ITER-relevant” modes. Magnet tolerances will provide local contributions to stray field at breakdown in the order of some mT. The toroidally averaged figures are much smaller (in the order of fractions of mT), but the impact of localized field map deformations on the connection lengths may provide deeper understanding of ITER behavior at breakdown. In this paper, starting from a waveform scenario optimized using an axisymmetric model for nominal coils and vessel, a full 3D numerical model is used to analyze the contribution to the magnetic field in the breakdown region generated by tolerances on the toroidal field coils, and the effects of stray fields on the connection lengths are analyzed. [ABSTRACT FROM AUTHOR]

Control of a Tokamak requires operating many sophisticated control loops in a dynamic sequence of activities. To take appropriate actions in case technical or physics conditions occur unexpectedly, the continuous control must be backed up by Exception Handling (EH) logic. To mature the Conceptual Design of the ITER Plasma Control System (PCS) with such logic for the Preliminary Design, we studied, in a formal process, how the plasma will be controlled during the 1 st plasma and early operation phases of ITER and analysed the required control and EH functions and dependencies: Three classes of Exception Handling were identified which cover all use cases: modification of the control behaviour of a single control function, modification of the control structure of connected controllers, and change of the control goal which modifies the overall control system. The three classes form a EH hierarchy from low to high impact responses that can be implemented as local EH in the Pulse Continuous Control layer and as central EH in the Pulse Supervision layer of the PCS. [ABSTRACT FROM AUTHOR]

The biofilm matrix is a complex of secreted polymers, absorbed nutrients and metabolites, cell lysis products, and even particulate material. Being polyanionic in nature, this matrix plays a crucial role in the biosorption of metal cations. In this work, the adsorption process of heavy metals in biofilms is modeled in one space dimension. The mathematical model is a free-boundary value problem for nonlinear hyperbolic and parabolic partial differential equations. Biomass and extracellular polymeric substances (EPS) growth is governed by hyperbolic equations, and substrate evolution by parabolic equations. All equations are mutually connected. The model is general and can work for any number of microbial species, EPS, and substrates. In numerical analysis, heterotrophic-autotrophic competition for space with oxygen as common substrate is considered. The model can describe biofilm growth dynamics including spatial distribution of microbial species, substrate concentrations, EPS formation, and, in particular, is able to simulate heavy metal diffusion and adsorption into biofilm. Numerical simulations for representative examples are obtained by the method of characteristics. Results indicate that model is able to capture the main features of heavy metal adsorption process on EPS. [ABSTRACT FROM AUTHOR]

Through the assistance of trace element and petrographic analyses on 14 samples of mortar aggregates from Roman monuments, including the Porticus Aemilia, the Temple of Concordia, the Temple of the Dioscuri, Temple B and other structures of the Area Sacra di Largo Argentina, and the Villa di Livia, we establish the source area and we investigate the chronological employment of the volcanic materials used in ancient Rome's masonry. In contrast to previous inferences, the petrochemical data presented here show that systematic exploitation of the local ' Pozzolane Rosse' pyroclastic deposit has occurred since the early development of concrete masonry, at the beginning of the second century bc, through the early Imperial age. Subsequently, exploitation was extended to the overlying Pozzolane Nere and Pozzolanelle deposits. Only during the early phase of development of the concrete masonry in Rome, volcaniclastic sediments outcropping near the construction sites were mixed with the sieved remains of the tuff employed as the coarse aggregate, to produce the fine aggregate. The results of the study on the investigated monuments suggest the possibility of establishing the chronological identification of three different types of mortars, as a function of the composition of the volcanic material employed in the fine aggregate, which, when implemented by future studies, may contribute to the dating of monuments and archaeological structures. [ABSTRACT FROM AUTHOR]

To prepare the DEMO conceptual design phase a number of physics and engineering assessments were carried out in recent years in the frame of EFDA concluding in an initial design configuration of a DEMO tokamak. This paper gives an insight into the identified engineering requirements and constraints and describes their impact on the selection of the technologies and design principles of the main tokamak components. The EU DEMO program aims at making best use of the technologies developed for ITER (e.g., magnets, vessel, cryostat, and to some degree also the divertor). However, other systems in particular the breeding blanket require design solutions and advanced technologies that will only partially be tested in ITER. The main differences from ITER include the requirement to breed, to extract, to process and to recycle the tritium needed for plasma operation, the two orders of magnitude larger lifetime neutron fluence, the consequent radiation dose levels, which limit remote maintenance options, and the requirement to use low-activation steel for in-vessel components that also must operate at high temperature for efficient energy conversion. [ABSTRACT FROM AUTHOR]

The Plasma Control System Simulation Platform (PCSSP) is a highly flexible, modular, time-dependent simulation environment developed primarily to support development of the ITER Plasma Control System (PCS). It has been under development since 2011 and is scheduled for first release to users in the ITER Organization (IO) and at selected additional sites in 2015. Modules presently implemented in PCSSP enable exploration of axisymmetric evolution and control, basic kinetic control, and tearing mode suppression. A basic capability for generation of control-relevant events is included, enabling study of exception handling in the PCS, continuous controllers, and PCS architecture. While the control design focus of PCSSP applications tends to require only a moderate level of accuracy and complexity in modules, more complex codes can be embedded or connected to access higher accuracy if needed. This paper describes the background and motivation for PCSSP, provides an overview of the capabilities, architecture, and features of PCSSP, and discusses details of the PCSSP vision and its intended goals and application. Completed work, including architectural design, prototype implementation, reference documents, and IO demonstration of PCSSP, is summarized and example use of PCSSP is illustrated. Near-term high-level objectives are summarized and include preparation for release of an “alpha” version of PCSSP and preparation for the next development phase. High-level objectives for future work are also discussed. [ABSTRACT FROM AUTHOR]

This paper gives an overview of the scope and context of the CODAC high-level real-time applications (Supervision and Plasma Control) and presents the strategy and current state of design of the tools to support the implementation. A real-time framework, which is currently under development with strong support of the worldwide fusion community will not only support the implementation of plasma control strategies with the extensive exception handling and forecasting functionality foreseen for ITER, but also integrated commissioning, orchestration and supervision as well as the real-time needs of ITER plant system developers. A second cornerstone in the implementation strategy is the development of a powerful simulation environment (Plasma Control System Simulation Platform – PCSSP) to design and verify control strategies, event handling and orchestration and automation. The development of PCSSP is currently under contract and this paper will also give an overview of its current state of development. [ABSTRACT FROM AUTHOR]

The plasma design point during stationary phase operation of EU-DEMO has been described extensively in the past, and the assumptions employed for its definition have been supported by various investigations. However, a stationary snapshot is by far not sufficient to ensure the actual operability of the plasma scenario. On the contrary, both normal and off-normal transients have a strong impact on the machine design, providing the most challenging requirements to the actuators. This has to be accounted for in the design from the early phases on. In this paper, the main requirements originating from plasma operation, studied during the Pre-Concept Design Phase, are briefly reviewed. These encompass the so-called planned transients, e.g. plasma current ramps, access and termination of the burn phase or plasma fueling with pellets, but also the mitigation of off-normal events which may lead to a disruption, e.g. the divertor reattachment or an uncontrolled increase of radiation after a sudden W influx from the wall. [ABSTRACT FROM AUTHOR]

Ring finger protein 11 (RNF11) is a RING (really interesting new gene)-H2 E3 ligase that is overexpressed in several human tumor tissues. The mature protein, which is anchored to membranes via a double acylation, localizes to early endosome and recycling compartments. Apart from its subcellular localization, additional lines of evidence implicate RNF11 in the mechanisms underlying vesicle traffic. Here we identify two acidic-cluster dileucine (Ac-LL) motifs, which are recognized by the VHS domains of Golgi-localized, gamma adaptin era-containing, ADP-ribosylation factor-binding protein (GGA) adaptors, as the molecular determinants governing RNF11 sorting at the trans-Golgi network and its internalization from the plasma membrane. We also show that RNF11 recruits itch to drive the ubiquitination of GGA3. This function is experimentally detectable only in cells overexpressing an RNF11 variant that is inactivated in the RING domain, indicating that RNF11 recruits GGA3 and controls its ubiquitination by regulating itch activity. Accordingly, our data demonstrate the involvement of itch in regulating GGA3 stability. Indeed, we observe that the endogenous levels of GGA3 are increased in cells knocked down for itch and endogenous GGA3 is hyperubiquitinated in an itch-dependent manner in a cell line expressing catalytically inactive RNF11. Our data are consistent with a model whereby the RING E3 ligase RNF11 is a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. The results that we are presenting put RNF11 at the center of a finally regulated system where it acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. [ABSTRACT FROM AUTHOR]

Anisotropy of magnetic susceptibility (AMS) techniques are applied to Permo-Triassic red beds from the Castilian Branch (Iberian Range, NE Spain) that were deposited in an extensional basin inverted during Cenozoic times. The main goal of this work is to characterize the tectonic evolution of the basinal stage by differentiating synsedimentary to early diagenetic magnetic fabrics from the secondary tectonic fabrics related to compression, which are scarcely developed because no penetrative structures related to compression have been recognized. Oblate magnetic fabrics, with k min axes perpendicular to bedding ,are observed in most cases. Magnetic lineations are variable, showing a dominant ENE-WSW maximum, which fits with a dextral transtensional regime acting on NW-SE master faults during the Triassic. We propose that variations in the orientation of the magnetic lineation are associated with transfer faults which fragment the basin and trigger strain partitioning in different areas. Magnetic fabrics are locally modified by Cenozoic compression, with intermediate and minimum axes distributed along girdles perpendicular to fold axes. Comparing all these results with macrostructures and mesostructural kinematic indicators, we conclude that the fine-grained hematite-bearing rocks carry a consistent magnetic fabric which can be used to reconstruct the basin history. [ABSTRACT FROM AUTHOR]

In view of the preparation for the operation of the ITER tokamak it is necessary to develop the plasma scenarios taking into account all engineering constraints coming from the plant and including a realistic control system. It is important to consider that, due to the high energy of ITER plasmas, much more stringent requirements are posed on the control of transients in order to avoid machine damage. Several activities are performed in the EU focusing on one side on the scenario optimization from a physics point of view and on the other side on the design and modeling of a realistic plasma control system driving the plasma configuration throughout the whole pulse and suitable for implementation on a real machine. The issues related to the computation of the control feed-forward component are addressed. In particular, the possibility to trigger a feed-forward component to solve controllability problems arising in the transitions from plasma L to H and H to L modes is studied in detail with the support of linear and non-linear simulations. A control strategy is designed and tested on non-linear simulations of the whole pulse, including linear and non-linear effects due to controller switching, plasma shape reconstruction and power supplies. The paper reports on the results of the studies performed and discuss the proposed design of the plasma control system. [ABSTRACT FROM AUTHOR]

Electrochemotherapy (ECT) is a local anticancer treatment for superficial tumors which involves the administration of a chemotherapeutic drug followed by short, highvoltage pulses. Incipient clinical experience with breast cancer patients are encouraging, with a local complete response rate ranging from 50 to 90%. However, since many patients present with multiple or widespread metastases, ECT, despite its high local antitumor efficacy, need to be applied several times in order to complete treatment delivery or maintain tumor control during the follow-up. In this paper, we propose the prototype of a new grid electrode aimed at the improvement of ECT application. The device is suitable for treating large, tumor-infiltrated skin surfaces as in breast cancer patients with chest wall metastases after mastectomy. According to our tests in different in vitro models, the new device allows to apply the voltage pulses more quickly and homogeneously when compared with standard pulse applicators. This technical advancement holds promise for improving ECT outcome and, hopefully, for sparing a number of patients from the need of multiple treatments. [ABSTRACT FROM AUTHOR]

Abstract: ITER is targeting Q =10 with 500MW of fusion power. To meet this target, the plasma needs to be controlled and shaped for a period of hundreds of seconds, avoiding contact with internal components, and acting against instabilities that could result in the loss of control of the plasma and in its disruptive termination. Axisymmetric magnetic control is a well-understood area being the basic control for any tokamak device. ITER adds more stringent constraints to the control primarily due to machine protection and engineering limits. The limits on the actuators by means of the maximum current and voltage at the coils and the few hundred ms time response of the vacuum vessel requires optimization of the control strategies and the validation of the capabilities of the machine in controlling the designed scenarios. Scenarios have been optimized with realistic control strategies able to guarantee robust control against plasma behavior and engineering limits due to recent changes in the ITER design. Technological issues such as performance changes associated with the optimization of the final design of the central solenoid, control of fast transitions like H to L mode to avoid plasma-wall contact, and optimization of the plasma ramp-down have been modeled to demonstrate the successful operability of ITER and compatibility with the latest refinements in the magnetic system design. Validation and optimization of the scenarios refining the operational space available for ITER and associated control strategies will be proposed. The present capabilities of magnetic control will be assessed and the remaining critical aspects that still need to be refined will be presented. The paper will also demonstrate the capabilities of the diagnostic system for magnetic control as a basic element for control. In fact, the noisy environment (affecting primarily vertical stability), the non-axisymmetric elements in the machine structure (affecting the accuracy of the identification of the plasma boundary), and the strong component of eddy current at the start-up (resulting in a poor S/N ratio for plasma reconstruction for I p <2MA requiring a robust plasma control) make the ITER magnetic diagnostic system a demanding part of the magnetic control and investment protection systems. Finally the paper will illustrate the identified roles of magnetic control in the PCS (plasma control system) as formally defined in the recent first step of the design and development of the system. [Copyright &y& Elsevier]

Abstract: The plasma control system simulation platform (PCSSP) for ITER shall support the analysis and development of methods to be used by the ITER plasma control system (PCS) for handling exceptions to optimize pulses and assist in machine protection. PCSSP will permit to investigate physical and technical events, such as component failures, control degradation, operation domain excess, plasma state bifurcation or instabilities, and interlock activity. Serving that purpose, the plasma, actuator, diagnostics and PCS simulation modules in PCSSP will be enhanced to compute nominal and off-normal data. Configured by an event schedule, an event generator will orchestrate the activation and manipulate the characteristics of such off-normal computation. In the simulated PCS exceptions will be handled in a pulse supervision layer operating on top of the pulse continuous control (PCC) feedback loops. It will monitor events, decide on which exceptions to respond, and compute new control references to modify PCC behavior. We discuss basic concepts for the event generation in PCSSP, and a preliminary architecture for exception handling in PCS, and show how these will be configured with event and pulse schedules. [Copyright &y& Elsevier]

Highlights: [•] Describes task to develop simulation tool to aid development/testing of ITER PCS. [•] Requirements and use cases and preliminary architecture have been delivered. [•] Detailed design is now being developed. [•] Provides overview of use cases and requirements. [•] Provides overview of architecture and status of development. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX), one of the important pillars in the treatment of different forms of cancer, is associated with the development of hepatotoxicity. The 677C>T variant (rs1801133) in the methylenetetrahydrofolate reductase (MTHFR) gene might affect the development of hepatotoxicity. Results in literature are, however, contradictive. The aim of this study was to evaluate the role of the MTHFR 677C>T polymorphism in MTX-induced hepatotoxicity by analyzing a Dutch cohort of pediatric patients treated with high doses of MTX and subsequently performing a meta-analysis. Ninety-eight patients receiving 542 courses of high-dose MTX were genotyped for the MTHFR 677C>T variant. Hepatotoxicity was evaluated retrospectively according to common terminology criteria for adverse events-National Cancer Institute criteria. The influence of MTHFR 677C>T on hepatotoxicity was examined using a generalized estimating equation (GEE) analysis. A fixed-effect meta-analysis based on this and previous studies investigating the association between the MTHFR 677C>T polymorphism and uniformly coded hepatotoxicity was performed. The GEE analysis showed an increased risk of developing hepatotoxicity for T versus C allele (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.0-3.2, P=0.04). This finding was not supported by the meta-analysis including seven studies and 1044 patients; the OR for the 677T versus C allele was 1.1 (95% CI 0.84-1.5, P=0.25). Heterogeneity between studies was observed, possibly related to differences in MTX dose and leucovorin rescue. In conclusion, in patients with cancer, the MTHFR 677T allele has only a minor role in the development of MTX-induced hepatotoxicity. Observed heterogeneity between studies warrants further study into (tailored) leucovorin rescue. [ABSTRACT FROM AUTHOR]

Submarine felsic volcanoes are dominated by hyaloclastic piles hundreds of meters thick, the origin of which, in terms of how and when they form, is far from being completely understood. Here we present a study of the thermal remanent magnetization of the Miocene high-K dacitic El Barronal hyaloclastites (Cabo de Gata, Spain), showing that their formation is dominated by in situ fragmentation with small or negligible transportation and/or rotation of different clasts after their formation. Data indicate that fragmentation progressed down to 210-390 °C, well below the glass-transition temperature estimated at 560-750 ºC depending on the water content of the high-K dacite. Hence, hyaloclastite fragmentation in thick lavas may occur over most of the cooling history, as a result of the progressive access of sea water toward the lava interior by development of a complex network of contraction fractures. [ABSTRACT FROM AUTHOR]

Self-consistent transport simulation of ITER scenarios is a very important tool for the exploration of the operational space and for scenario optimization. It also provides an assessment of the compatibility of developed scenarios (which include fast transient events) with machine constraints, in particular with the poloidal field coil system, heating and current drive, fuelling and particle and energy exhaust systems. This paper discusses results of predictive modelling of all reference ITER scenarios and variants using two suites of linked transport and equilibrium codes. The first suite consisting of the 1.5D core/2D SOL code JINTRAC (Wiesen S. et al 2008 JINTRAC-JET modelling suite JET ITC-Report) and the free-boundary equilibrium evolution code CREATE-NL (Albanese R. et al 2003 ISEM 2003 (Versailles, France); Albanese R. et al 2004 Nucl. Fusion44 999), was mainly used to simulate the inductive D–T reference Scenario-2 with fusion gain Q = 10 and its variants in H, D and He (including ITER scenarios with reduced current and toroidal field). The second suite of codes was used mainly for the modelling of hybrid and steady-state ITER scenarios. It combines the 1.5D core transport code CRONOS (Artaud J.F. et al 2010 Nucl. Fusion50 043001) and the free-boundary equilibrium evolution code DINA-CH (Kim S.H. et al 2009 Plasma Phys. Control. Fusion51 105007). [ABSTRACT FROM AUTHOR]

Abstract: The active control of plasma discharges in present Tokamak devices must be prompt and accurate to guarantee expected performance. As a consequence, the identification step, calculating plasma parameters from diagnostics, should provide in a very short time reliable estimates of the relevant quantities, such as plasma centroid position, plasma-wall distances at given points called gaps, and other geometrical parameters as elongation and triangularity. To achieve the desired response promptness, a number of simplifying assumptions are usually made in the identification algorithms. Among those clearly affecting the quality of the plasma parameters reconstruction, one of the most relevant is the precise knowledge of the magnetic field produced by active coils. Since uncertainties in their manufacturing and assembly process may cause misalignments between the actual and expected geometry and position of magnets, an analysis on the effect of possible wrong information about magnets on the plasma shape identification is documented in this paper. [Copyright &y& Elsevier]

Abstract: The aim of the PFX Operating Early Task (POET) was to obtain a highly shaped plasma and x-point formation in the early phases of the discharge. The PFX is an amplifier which feeds the central pancakes of the JET primary circuit. In the past it was possible to energize the PFX circuit only when the PFGC current, which feeds all the coils of the primary circuit, was already flowing in the same direction as the PFX current would have flowed, to avoid repulsive vertical forces which would tend to lift the top pancakes of the central solenoid, balanced only by the net weight of the upper part of the JET machine. In this paper the modeling activity performed to provide a more accurate estimate of the ejection forces acting on the upper coils in order to safely widen the operational space, by using two dimensional finite element electromagnetic models and the simulation of the performances of the actual controller algorithm on tracking the desired references of current are described. Finally will be presented the results of the implemented POET system, routinely used in JET in the 2011/2012 experimental campaigns, in terms of anticipation of x-point formation and enhanced system flexibility. [Copyright &y& Elsevier]

Abstract: Many adhesion test techniques have been developed to measure the adhesion energy of thin films but they are hard to implement in the case of submicron organic thin films deposited on a flexible substrate. Recently the feasibility and repeatability of the scratch test technique as a tool for testing the adhesion and the damage behaviour of ultra-thin films on polymer substrates has been demonstrated. However, direct comparison of the critical load between samples was not straightforward since different failure mechanisms were induced. In the present work, we have performed nanoscratch experiments on submicron thin films deposited on a flexible substrate. The use of a tip radius of 5μm enabled a unique delamination mechanism to be induced by localizing and maximizing the stress closer to the interface. We have observed an increase of the critical load on samples processed with an adhesive plasma treatment prior to thin film deposition, confirming the effectiveness of this treatment. We have also performed mechanical ageing tests on specimens and proved that the scratch test technique is sensitive enough to monitor the degradation of the interface properties. Finally, we have discussed some existing energy models. Taking into account some limitations, Laugier''s model gives an upper bound for the adhesion energy. [Copyright &y& Elsevier]

This paper describes an integrated procedure for the reconstruction of halo currents expected in ITER. The procedure is based on simulation and reconstruction codes, partially adapted from existing codes and partly developed specifically for this purpose. The ultimate goal of this integrated procedure is the assessment of the performance and the possible optimization of the halo current diagnostic system foreseen in ITER. The preliminary results indicate that an alternative distribution of the present layout of halo current sensors could improve the reconstruction capability of this diagnostic system. [ABSTRACT FROM PUBLISHER]

Experiments and modelling have been carried out to optimize the magnetic field null during breakdown at JET. Such optimization may prove to be essential for reliable plasma initiation at low voltages, e.g. in ITER where the value of the electric field available will be limited to 0.33Vm-1. A two-dimensional FE Melectromagnetic model has been employed to predict the stray field configuration during JET breakdown. This model includes the active poloidal field circuits, a description of the passive structure and the JET magnetic circuit. In particular, the model includes the gap at the top of the iron circuit (but not at the bottom), which introduces a perturbing field, with radial and vertical components, not previously considered. A number of experiments were run using the optimized magnetic null configuration, allowing one to achieve a more robust breakdown at a low electric field. The model calculation to adjust the magnetic null position was validated using the recordings from a fast visible camera. The optimized position and dynamics of the plasma start lead to a smoother behaviour of the JET radial field control system, far from the amplifier limits. Finally, an important indication was obtained on the precision needed for the active current measurements during the low electric field breakdown relevant from the perspective of the ITER real-time acquisition system. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is the methylation status of the methylenetetrahydrofolate reductase (MTHFR) promoter region in semen samples associated with ‘recurrent spontaneous abortion’ (RSA)? SUMMARY ANSWER MTHFR promoter hypermethylation is more frequent in semen samples from RSA couples than in semen samples from infertile couples with no history of RSA (NRSA) and affects the whole sperm population significantly more often. WHAT IS KNOWN ALREADY Modifications to the MTHFR gene such as polymorphisms and promoter methylations are associated with male infertility. STUDY DESIGN, SIZE AND DURATION Retrospective cohort study of semen samples from 20 RSA couples, 147 NRSA couples and 20 fertile men between 2011 and 2012. MATERIALS, SETTING AND METHODS DNA from the semen samples of RSA, NRSA and fertile men were analyzed by methylation-specific PCR amplification using primers which anneal to the methylated or unmethylated cytosine-phosphodiester bond guanine (CpG) islands within the promoter region of MTHFR. The specificity of the PCR products was assessed by DNA sequencing. MAIN RESULTS AND THE ROLE OF CHANCE The methylated MTHFR epigenotype (including samples where it co-existed with unmethylated MTHFR epigenotypes) was detected in 75% of RSA men, 54% of NRSA men and 15% of fertile men. MTHFR methylation was observed in the whole sperm population in semen samples from 55% of RSA men compared with 8% in NRSA men (P < 0.05) and 0% in fertile men (P < 0.05). DNA sequencing analysis was fully concordant with the PCR results and revealed that when MTHFR methylation occurred, CpG islands within the promoter region were 100% methylated (hypermethylation of MTHFR promoter). LIMITATIONS, REASONS FOR CAUTION The relatively small sample size of RSA infertile couples. WIDER IMPLICATIONS OF THE FINDINGS The hypermethylation of the MTHFR gene promoter should be taken into consideration as a novel putative risk factor in RSA etiology. STUDY FUNDING/COMPETING INTEREST(S) Our institution has received an FAR research grant from the University of Ferrara, Ferrara, Italy. No competing interests declared. [ABSTRACT FROM PUBLISHER]

Synovial fibroblasts (SFs) contribute to the development of osteoarthritis (OA) by the secretion of a wide range of pro-inflammatory mediators, including cytokines and lipid mediators of inflammation. Previous studies suggest that electromagnetic fields (EMFs) may represent a potential therapeutic approach to limit cartilage degradation and control inflammation associated to OA, and that they may act through the adenosine pathway. Therefore, we investigated whether EMFs might modulate inflammatory activities of human SFs from OA patients (OASFs) treated with interleukin-1β (IL-1β), and the possible involvement of adenosine receptors (ARs) in mediating EMF effects. EMF exposure induced a selective increase in A2A and A3 ARs. These increases were associated to changes in cAMP levels, indicating that ARs were functionally active also in EMF-exposed cells. Functional data obtained in the presence of selective A2A and A3 adenosine agonists and antagonists showed that EMFs inhibit the release of prostaglandin E2 (PGE2) and the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), while stimulating the release of interleukin-10 (IL-10), an antinflammatory cytokine. These effects seem to be mediated by the EMF-induced upregulation of A2A and A3 ARs. No effects of EMFs or ARs have been observed on matrix degrading enzyme production. In conclusion, this study shows that EMFs display anti-inflammatory effects in human OASFs, and that these EMF-induced effects are in part mediated by the adenosine pathway, specifically by the A2A and A3 AR activation. Taken together, these results open new clinical perspectives to the control of inflammation associated to joint diseases. J. Cell. Physiol. 227: 2461-2469, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: The JET enhancement project Plasma Control Upgrade (PCU) aimed at increasing the capabilities of the plasma vertical stabilization (VS) system. One of the activities of this project was devoted to the development of simple but sufficiently accurate models of the VS system so as to address the main design choices, use the simulation tools as reliable test-beds, and provide an adequate support to the engineering design and commissioning of the new Enhanced Radial Field Amplifier (ERFA). This paper illustrates some of the main achievements of the modelling activity, which gave rise to a closed loop model of the VS system, including plasma, PF coils and passive structures. In particular the paper deals with the selection of the set of turns to be used in the control coils and with the estimation of the eddy current effects on the VS system. The latter analysis addressed an upgrade of the converter units of ERFA, successfully implemented during its commissioning on plasma in August 2009. [Copyright &y& Elsevier]

Abstract: In the framework of the ITER project, an investigation has been conducted on an alternative vessel and blanket design, aimed at reducing cost and production risk. The modifications proposed have a strong impact on plasma control since they affect the main conducting structures surrounding the plasma column, providing passive stabilization but at the same time shielding the field generated by the active coils to control the plasma motion and shape. An extensive analysis was performed to assess the plasma vertical controllability and the modified requirements to the in-vessel vertical stability coils system as well as to the external Poloidal Field coils system. A similar analysis was aimed at assessing the performance of the shape control system in presence of the modified structures. The effect on plasma breakdown was also evaluated in terms of maximum initial loop voltage, quality of magnetic null and the flux loss related to the breakdown delay that was quantified under the same hypothesis employed by ITER for the baseline design. Furthermore, the modified design presents issues for the magnetic diagnostic system, related to the shielding of the probes by the eddy currents, which were analysed with a 3D model. The results of the analyses performed have some general interest in particular regarding the influence on plasma stability of 3D structures with close proximity to the plasma. The present paper aims at giving an overview of the analyses that have been carried out and a summary of the results in terms of impact of the modified design on plasma control and scenario, and in general an evaluation of the role of passive structure in plasma vertical stability and shape control. [ABSTRACT FROM AUTHOR]

Background and Purpose: Adenosine is an endogenous modulator, interacting with four G-protein coupled receptors (A(1), A(2A), A(2B) and A(3)) and acts as a potent inhibitor of inflammatory processes in several tissues. So far, the functional effects modulated by adenosine receptors on human synoviocytes have not been investigated in detail. We evaluated mRNA, the protein levels, the functional role of adenosine receptors and their pharmacological modulation in human synoviocytes.Experimental Approach: mRNA, Western blotting, saturation and competition binding experiments, cyclic AMP, p38 mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-kappaB activation, tumour necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) release were assessed in human synoviocytes isolated from patients with osteoarthritis.Key Results: mRNA and protein for A(1), A(2A), A(2B) and A(3) adenosine receptors are expressed in human synoviocytes. Standard adenosine agonists and antagonists showed affinity values in the nanomolar range and were coupled to stimulation or inhibition of adenylyl cyclase. Activation of A(2A) and A(3) adenosine receptors inhibited p38 MAPK and NF-kappaB pathways, an effect abolished by selective adenosine antagonists. A(2A) and A(3) receptor agonists decreased TNF-alpha and IL-8 production. The phosphoinositide 3-kinase or G(s) pathways were involved in the functional responses of A(3) or A(2A) adenosine receptors. Synoviocyte A(1) and A(2B) adenosine receptors were not implicated in the inflammatory process whereas stimulation of A(2A) and A(3) adenosine receptors was closely associated with a down-regulation of the inflammatory status.Conclusions and Implications: These results indicate that A(2A) and A(3) adenosine receptors may represent a potential target in therapeutic modulation of joint inflammation. [ABSTRACT FROM AUTHOR]

Abstract: The Fusion Advanced Studies Torus (FAST) conceptual study has been proposed [A. Pizzuto on behalf of the Italian Association, The Fusion Advanced Studies Torus (FAST): a proposal for an ITER Satellite facility in support of the development of fusion energy, in: Proceedings of 22nd IAEA Fusion Energy Conference, Geneva, Switzerland, October 13–18, 2008; Nucl. Fusion, submitted for publication] as possible European ITER Satellite facility with the aim of preparing ITER operation scenarios and helping DEMO design and R&D. Insights into ITER regimes of operation in deuterium plasmas can be obtained from investigations of non linear dynamics that are relevant for the understanding of alpha particle behaviours in burning plasmas by using fast ions accelerated by heating and current drive systems. FAST equilibrium configurations have been designed in order to reproduce those of ITER with scaled plasma current, but still suitable to fulfil plasma conditions for studying burning plasma physics issues in an integrated framework. In this paper we report the plasma scenarios that can be studied on FAST, with emphasis on the aspect of its flexibility in terms of both performance and physics that can be investigated. All plasma equilibria satisfy the following constraints: (a) minimum distance of 3 energy e-folding length (assumed to be 1cm on the equatorial plane) between plasma and first wall to avoid interaction between plasma and main chamber; (b) maximum current density in the poloidal field coils, transiently, up to around 30MA/m2. The discharge duration is always limited by the heating of the toroidal field coils that are inertially cooled by helium gas at 30K. The location of the poloidal field coils has been optimized in order to: minimize the magnetic energy; produce enough magnetic flux (up to 35Wb stored) for the formation and sustainment of each scenario; produce a good field null at the plasma break-down (B P/B T <2×10−4 at low field, i.e. B T =4T and E T =2V/m for at least 40ms). Plasma position and shape control studies will also be presented. The optimization of the passive shell position slows the vertical stability growth time down to 100ms. [Copyright &y& Elsevier]

Abstract: The Tyrrhenian coastal sector of North Calabria, stretching between Torre S. Nicola and the Lao river, belongs to the inner extensional sector of the Neogene Apennines thrust belt. It is characterised by a stair of Quaternary marine and fluvial terraces representing the geomorphic response to the interaction between the Quaternary sea level fluctuations and the regional trend of tectonic uplift experienced by the margins of the Tyrrhenian back-arc basin. Since the last century, several authors studied the North Calabria coasts, where the flight of terraces preserves significant marine and continental successions, and proposed several paleo-geomorphological and tectonic reconstructions. In this paper we present a new stratigraphic and morphostructural setting of the North Calabria coasts based on both chronostratigraphical constraints obtained from marine deposits and detailed geomorphological analysis. A ten order stair of marine terraces, stepping between 240 and 0 m a.s.l., was recognized and time-constrained by the age of the Fornaci S. Nicola marine succession which was ascribed by integrated paleoecological, biostratigraphical and paleomagentic analyses to the early Middle Pleistocene (MIS 19–15). In particular, the 240, 200 and 160 m a.s.l. high strandlines were ascribed to the Early Pleistocene and the ones between 100 and 15 m a.s.l. to the Middle Pleistocene. The total amount of the vertical motion experienced by the studied area was estimated, and evaluation of the average rates of uplift for the Middle and Late Pleistocene times were also given. Considering the elevation a.s.l. of the oldest terraces, a tectonic uplift of at least 240 m was calculated for the North Calabria coasts since the Early Pleistocene times, 100 m of which gained from the beginning of the Middle Pleistocene. On the other hand, the 8-m high Late Pleistocene strandlines display a negligible vertical displacement affecting the area during the last 130 ka. The entire staircase of terraces preserves a record of slowing down in the rate of uplift, which attained an average value of 0.15 mm/year during the Middle Pleistocene. [Copyright &y& Elsevier]

Abstract: As part of the ITER design review, a reassessment of the specifications underlying the design of the vertical stabilization system (VS) was performed. Recent results from experiments, aimed at the evaluation of the feasibility of the ITER reference scenarios, have raised several concerns regarding mostly the ramp-up and ramp-down phases of the pulse. The main issue is the value of the internal inductance li which may reach values outside the range 0.7–1, considered as reference for the ITER control system design. Similar concerns apply to the low current L-mode plasmas, needed to the exploitation of the machine towards the development of the 15MA pulse. The performance of the reference vertical stabilization system, under the revised conditions may be marginal, in particular if the effect of plasma generated noise on the velocity measurement is considered. A reliable and robust VS is mandatory to guarantee the operation of ITER at the reference elongation and plasma current values. To avoid de-scoping of the machine mission, several solutions have been proposed to improve the VS performances, ranging from an upgrade of the maximum voltage available to the present external coils system, to the introduction of in-vessel passive and/or active conductors. The paper presents an overview of the modelling and experimental effort aimed at the assessment of the baseline ITER VS and analyses the proposed solutions to improve the system performance. [Copyright &y& Elsevier]

• A new strategy for the sweeping control on DEMO device is developed. • The possibility to improve the sweeping control performance with in-vessel coils is investigated. • The compatibility of the sweeping control with vertical stability and shape control is investigated. • The sweeping performance has been validated by numerical simulations. In this paper, the sweeping control strategy is applied to DEMO single null configuration as possible solution for the power exhaust problem. Firstly, a possible sweeping control strategy is proposed to impose a periodic movement of the plasma divertor legs at a desired frequency with an almost fixed plasma shape. Then, the performance of the sweeping control using ex-vessel coils is analyzed in terms of current, voltage and maximum sweeping frequency. Finally, the possibility to implement the sweeping with the in-vessel coils is considered. Two possible solutions for the in-vessel coils have been adopted: a preliminary solution compatible with the actual DEMO port locations and an optimized solution that is more performing for the sweeping but needs to be validated for the compatibility with the remote handling. Numerical simulations demonstrate the effectiveness of the proposed approach coupling the sweeping control with the feedback control strategies for the plasma shape and position. [ABSTRACT FROM AUTHOR]

Liver resection is a standard treatment for liver tumours. Intra-operative blood loss remains a major concern during liver resection due to its association with higher postoperative complications and shorter long-term survival. To perform bloodless hepatic resection we realized an apparatus consisting of an incremental, bipolar radiofrequency generator and a probe with six in-line needles (SURTRON SB). Several ex-vivo and in-vivo pig liver experiments and a first-phase clinical study allowed the realization of a prototype radiofrequency (RF) generator that works at 470 kHz, 150 watts maximum power delivered. The probe consists of six needle electrodes of 1.5 mm diameter, with 4.5 mm free space, 6.0 mm centre to centre, between each. We obtained a coagulation of 35 mm length and 12 mm width. The transection was performed with a common scalpel after coagulation of liver parenchyma. We observed good healing of the liver edge both in animal model and in ongoing pilot clinical study. Coagulation with SURTRON SB allows a feasible, easy and safe bloodless liver resection. This method is tolerated with no systemic complication or adverse reaction. This technique offers a method for a bloodless hepatic transection without the need for sutures, ties, staples or tissue glue. [ABSTRACT FROM AUTHOR]

Abstract: High-resolution (HR) γ-ray detector 99mTc Bombesin (99mTcBN) and 99mTc sestamibi (99mTcSM), have been used to drive Mammotome biopsy after fusion of scintigraphic with digital X-ray images. We studied eight patients with class V microcalcifications. An HR detector with spatial resolution of 3mm was matched with Mammotome biopsy system provided with Fisher digital X-ray device: images were fused to use the pointer indifferently on X-ray, scintigraphic and fused images. Fusion between X-ray and HR image has previously been reported. The 12 Mammotome samples/patient were weighted and counted in a well counter. Tumour/bkg (T/B) ratio was measured on HR images as well as on biopsy samples. Axilla was also explored with the portable HR device in order to diagnose node invasion. Conventional histology assessment and immunohystochemical study with anti BN receptor antibody was blindly performed on samples. All the patients studied with 99mTcSM showed T1b cancer, 99mTcBN detected one T1a and two T1b cancers. HR scan of axilla detected node metastases in two patients, both studied with 99mTcBN. All the biopsies showed cancer on at least one of the 12 samples. Histology found node metastases in three patients: the two 99mTcBN positive and one studied with 99mTcSM whose axilla was negative at HR scan. Samples showed T/B ratio of 6.6±0.4 for 99mTcSM and 11.3±0.9 for 99mTcBN (p<0.01). Note that also the patient with T1a cancer, showing 10.4 T/B ratio was included in the 99mTcBN series. Not only 99mTcBN HR is able to show breast cancer and to guide biopsy, but also detects node metastases. Our is the first ex vivo measurement of T/B ratio of 99mTcBN on humans. [Copyright &y& Elsevier]

Abstract: Dikes provide important information on the structure, state of stress and activity of a volcano. Mt. Somma borders part of the Vesuvio cone (Italy), displaying ∼100 dikes emplaced between ∼18 and 30ka. Field, AMS (anisotropy of magnetic susceptibility) and thin section analyses are used to characterize their geometry and kinematics (direction and sense of flow). The dikes mostly have a NNW–SSE to NE–SW strike. Approximately 57% are radial to the older Somma edifice, ∼27% are oblique and ∼16% tangential. Among the latter two groups, ∼32% are outward dipping and ∼11% inward dipping. The dike thickness varies between 0.2 and 3m, with a mean value of 1.17m. The kinematics of 19 dikes is determined through a combination of field (8 dikes), AMS (16 dikes) and thin section analyses (15 dikes). Thirteen dikes have a vertical upward flow, whereas six have an oblique-subhorizontal flow, suggesting a lateral propagation from the summit or eccentric vents of the former Somma edifice. These propagation paths differ from those deducible from the recent activity, as all the seven major fissure eruptions between 1631 and 1944 were related to the lateral propagation of radial dikes. We propose that these different behaviours in dike propagation may be mainly related to the opening conditions of the summit conduit. The laterally propagating dikes in 1631–1944 formed with an open conduit. Conversely, the vertically propagating dikes may have formed, between 18 and 30ka, with a closed conduit. [Copyright &y& Elsevier]

Abstract: The assessment of JET magnetics has been carried out using a statistical technique on a large set of sensor data. The results highlight that improved accuracy in the magnetic field reconstruction can be obtained by making an efficient use of the information brought in by the available sensors, in conjunction with the new magnetics that will be installed during the 2004 shutdown (JET Enhancement on Magnetic Diagnostics). Moreover, the better estimation of the magnetic configuration provides an improved capability to locate the plasma boundary and determine its shape. [Copyright &y& Elsevier]

Abstract: A new model-based plasma current and shape controller has been set up and tested on the JET Tokamak with the existing active circuits and control. The installation has been carried out without causing any interference to the plasma operation and without requiring a long commissioning time. Eventually, the new controller was used on really extremely shaped internal transport barrier experiments at high poloidal beta and in the presence of quite large variations of the plasma current density profile (variation range Δβ pol up to 1.5 and Δl i up to 0.5). The extreme shape controller (XSC) controller architecture and philosophy also offer new interesting opportunities, e.g., the separatrix sweeping on the divertor plates without significantly affecting the overall plasma shape, and the possibility of improving the overall tokamak performance via combined control of plasma shape, current and profile. The adopted methodology constitutes also an important test bed for feedback control strategies of ITER relevance. [Copyright &y& Elsevier]

Abstract: In this study we derive linear models describing the dynamics of the n =0 plasma displacements around the main ITER equilibrium configurations. The models derived are consistent with the MHD equilibrium constraint as well as with the 3D geometry of the vacuum vessel and blanket outer triangular support where the main eddy currents flow takes place. Particular emphasis is placed on the analysis of the stability margin, growth time and minimum stabilization voltage. The performances of the present ITER control system (single loop) are compared to those of an upgraded system (double-loop) that is here proposed to improve the stability domain of the ITER plasmas forecast. [Copyright &y& Elsevier]

Abstract: A new model-based shape controller (XSC, i.e., eXtreme Shape Controller) able to operate with high elongation and triangularity plasmas has been designed and implemented at JET in 2003. The use of the XSC needs a number of steps, which at present are not automated and therefore imply the involvement of several experts. To help the session leader in preparing an experiment, a number of software tools are needed. The paper describes the SW tools that are currently in the developing phase, and describes the new framework for the preparation of a JET experiment. [Copyright &y& Elsevier]

The development of linear model of the present JET (Joint European Torus) electromagnetic system has allowed the design of an optimized Plasma Shape Controller. Quite extreme plasma boundaries (elongation k=1.9 and triangularity 〈δ〉=0.6) are shown to be controllable also in the presence of large variations of the values of poloidal beta (0.1<βp<0.6) and/or internal magnetic inductance (0.8

This study was designed to improve the removal efficiency of COD, SS, and microorganism at the S. Giovanni a Teduccio municipal wastewater treatment plant, Naples, Italy. The plant consists of screen, sand grinder, oil removal, coagulation, flocculation and sedimentation units, hypochlorite disinfection, mechanical dewatering, and thermal sludge conditioning. A series of Jar-test was conducted on twelve samples taken after screen using FeSO4 alone or together with Ca(OH)2 at 100 rpm rapid mixing for 1 min, 30 rpm for slow mixing for 20 min and 30 min for settling. 150 mg L-1 and 450 mg/L doses of FeSO4 were used at a pH interval in between 6 and 9. The removals of COD, TSS, Escherichia coli and total coliforms were measured ranging from 40 to 70%, 70 to 90%, 96 to 99% and 97 to 99%, respectively when FeSO4 was used alone at 150 mg L-1 and 450 mg L-1 doses and at pH 6, 7 and 8. Wastewater discharge standards could be safely obtained at 150 mg L-1 dose of FeSO4 with the use of 220 mg L-1 Ca(OH)2 at pH 8 in terms of COD and E. coli removals resulted in 65% and 98%, respectively, with less sludge production to be disposed. Additionally, none of influent and supernatant samples tested in this study was found to be acute toxic on 24 h-born Daphnia magna at 50% dilution. [ABSTRACT FROM AUTHOR]

The age of spreading of the Liguro–Provenc¸al Basin is still poorly constrained due to the lack of boreholes penetrating the whole sedimentary sequence above the oceanic crust and the lack of a clear magnetic anomaly pattern. In the past, a consensus developed over a fast (20.5–19 Ma) spreading event, relying on old paleomagnetic data from Oligo–Miocene Sardinian volcanics showing a drift-related 30° counterclockwise (CCW) rotation. Here we report new paleomagnetic data from a 10-m-thick lower–middle Miocene marine sedimentary sequence from southwestern Sardinia. Ar/Ar dating of two volcanoclastic levels in the lower part of the sequence yields ages of 18.94±0.13 and 19.20±0.12 Ma (lower–mid Burdigalian). Sedimentary strata below the upper volcanic level document a 23.3±4.6° CCW rotation with respect to Europe, while younger strata rapidly evolve to null rotation values. A recent magnetic overprint can be excluded by several lines of evidence, particularly by the significant difference between the in situ paleomagnetic and geocentric axial dipole (GAD) field directions. In both the rotated and unrotated part of the section, only normal polarity directions were obtained. As the global magnetic polarity time scale (MPTS) documents several geomagnetic reversals in the Burdigalian, a continuous sedimentary record would imply that (unrealistically) the whole documented rotation occurred in few thousands years only. We conclude that the section contains one (or more) hiatus(es), and that the minimum age of the unrotated sediments above the volcanic levels is unconstrained. Typical back-arc basin spreading rates translate to a duration ≥3 Ma for the opening of the Liguro–Provenc¸al Basin. Thus, spreading and rotation of Corsica–Sardinia ended no earlier than 16 Ma (early Langhian). A 16–19 Ma, spreading is corroborated by other evidences, such as the age of the breakup unconformity in Sardinia, the age of igneous rocks dredged west of Corsica, the heat flow in the Liguro–Provenc¸al Basin, and recent paleomagnetic data from Sardinian sediments and volcanics. Since Corsica was still rotating/drifting eastward at 16 Ma, it presumably induced significant shortening to the east, in the Apennine belt. Therefore, the lower Miocene extensional basins in the northern Tyrrhenian Sea and margins can be interpreted as synorogenic “intra-wedge” basins due to the thickening and collapse of the northern Apennine wedge. [Copyright &y& Elsevier]

We report here the genomic and transcriptional characterization in mouse and man of a novel transporter of the ABCA subclass,named ABCA7.As it is the case for other ABCA genes,the predicted protein encoded by ABCA7 is a full symmetric transporter,highly conserved across species.The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10. The preferential expression of ABCA7 in the spleen,thymus, and fetal liver is consistent with the finding,in both human and mouse promoter,of sites targeted by lymphomyeloid-specific transcription factors.This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoiet- ic cell lineages. [ABSTRACT FROM AUTHOR]

To date, transcription factors of the NFAT family (nuclear factors of activated T cells) have been described for mouse and man. Recently, we mapped the human NFAT5 gene to chromosome 16 by PCR using DNA from hybrid cell lines. Here we report the exact position of the human gene between D16S496 and WI5254 within the 16q22.1 subband, the localization of the murine gene at chromosome 8D, and the identification and mapping of the porcine counterpart to chromosome 6p1.4. Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]