A molecular basis for selective antagonist destabilization of dopamine D3 receptor quaternary organization

The dopamine D3 receptor (D3R) is a molecular target for both first-generation and several recently-developed antipsychotic agents. Following stable expression of this mEGFP-tagged receptor, Spatial Intensity Distribution Analysis indicated that a substantial proportion of the receptor was present within dimeric/oligomeric complexes and that increased expression levels of the receptor favored a greater dimer to monomer ratio. Addition of the antipsychotics, spiperone or haloperidol, resulted in re-organization of D3R quaternary structure to promote monomerization. This action was dependent on ligand concentration and reversed upon drug washout. By contrast, a number of other antagonists with high affinity at the D3R, did not alter the dimer/monomer ratio. Molecular dynamics simulations following docking of each of the ligands into a model of the D3R derived from the available atomic level structure, and comparisons to the receptor in the absence of ligand, were undertaken. They showed that, in contrast to the other antagonists, spiperone and haloperidol respectively increased the atomic distance between reference α carbon atoms of transmembrane domains IV and V and I and II, both of which provide key interfaces for D3R dimerization. These results offer a molecular explanation for the distinctive ability of spiperone and haloperidol to disrupt D3R dimerization

Rapporto sulle misure di Mercurio effettuate sull’Etna nel periodo Novembre 2005 – Marzo 2006 e loro raffronto con altri parametri geochimici

traccia nella troposfera, tende ad accumularsi nei processi biologici che seguono la sua deposizione. Il suo lungo tempo di residenza in atmosfera (circa 1 anno) combinato con la sua elevata tossicità, rendono tale elemento di primaria importanza per l’impatto ambientale, soprattutto nelle aree di maggiore emissione. Le emissioni di mercurio da aree vulcaniche attive sono considerate una delle principali sorgenti di mercurio verso l’atmosfera terrestre, insieme con le emissioni antropogeniche legate all’attività mineraria per l’estrazione del cinabro. L’entità del contributo vulcanico a scala regionale e globale rimane tuttavia altamente incerto. Le emissioni vulcaniche possono essere ricche in mercurio elementare gassoso (Hg0), mercurio gassoso reattivo (HgII) presente soprattutto come solfuro ed altre forme di mercurio che devono essere ancora determinate (Symonds et al., 1992; Nicholson, 1993; Barnes & Seward, 1997). L’Etna rappresenta una delle maggiori sorgenti potenzialmente in grado di fornire grandi quantità di Hg in atmosfera, grazie alle sue notevoli emissioni gassose dal plume craterico e dai fianchi (e.g., Ferrara et al., 2000). A partire dalla metà di Novembre 2005 si è reso disponibile un analizzatore portatile della concentrazione di mercurio in fase gassosa Lumex RA-915+ (Figura 1), in visione temporanea grazie all’accordo tra il distributore per l’Italia (Loccioni srl, Ancona) e la sezione di Catania dell’INGV ottenuto su interessamento personale di M. Burton. L’analizzatore si basa sul principio della spettrometria differenziale Zeeman di assorbimento atomico, ed utilizza la modulazione ad alta frequenza della polarizzazione della luce. Lo strumento è in grado di misurare concentrazioni di Hg in aria o in fase gassosa da 0 a 20.000 ng m-3 nella modalità a cella multi-percorso (limite di rilevabilità = 2 ng m-3), oppure da 500 a 200.000 ng m-3 nella modalità a cella singolo-percorso (limite di rilevabilità = 500 ng m-3). La misura viene effettuata mediante aspirazione del campione di aria o di gas all’interno dello strumento attraverso un tubo che, nel caso di gas del suolo o gorgogliante in acqua, viene opportunamente collegato, rispettivamente, ad una sonda inserita nel suolo o ad un imbuto posto sul punto di campionamento. Nel corso degli ultimi due mesi lo strumento è stato utilizzato sull’Etna per misure di Hg nell’aria in varie zone del vulcano, in gas del suolo emessi in due siti ubicati presso Santa Venerina e presso Paternò, in gas fumarolici presso la Torre del Filosofo e in gas gorgoglianti emessi dalle polle d’acqua delle Salinelle dello Stadio di Paternò. Purtroppo, le spesso avverse condizioni meteorologiche che hanno caratterizzato questo periodo, hanno impedito un più esteso utilizzo dell’analizzatore, così come era stato inizialmente preventivat

SO2 flux from Stromboli during the 2007 eruption: Results from the FLAME network and traverse measurements

SO2 fluxes emitted by Stromboli during the 27th February – 2nd April 2007 effusive eruption were regularly measured both by an automatic network of scanning ultraviolet spectrometers and by traverse easurements conducted by boat and helicopter. The results from both methodologies agree reasonably well, providing a validation for the automatic flux calculations produced by the network. Approximately 22,000 tonnes of SO2 were degassed during the course of the 35 day eruption at an average rate of 620 tonnes per day. Such a degassing rate is much higher than that normally observed (150-200 t/d), because the cross-sectional area occupied by ascending degassed magma is much greater than normal during the effusion, as descending, degassed magma that would normally occupy a large volume of the conduit is absent. We propose that the hydrostatically controlled magma level within Stromboli’s conduit is the main control on eruptive activity, and that a high effusion rate led to the depressurisation of an intermediate magma reservoir, creating a decrease in the magma level until it dropped beneath the eruptive fissure, causing the rapid end of the eruption. A significant decrease in SO2 flux was observed prior to a paroxysm on 15th March 2007, suggesting that choking of the gas flowing in the conduit may have induced a coalescence event, and consequent rapid ascent of gas and magma that produced the explosion

Three-years of SO2 flux measurements of Mt. Etna using an automated UV scanner array: comparison with conventional traverses and uncertainties in flux retrieval

Routine measurements of SO2 flux using the traverse method on Mt. Etna (Italy) were augmented in late 2004 when an array of automatic scanning ultraviolet spectrometers was installed. Each instrument allows one SO2 scan to be recorded every ~6 min. Here we report the methods that we developed to automatically and robustly transform SO2 profiles into SO2 flux data. Radian geometry and Fast Fourier Transform algorithm were used for reducing plume cross sections and for discriminating between volcanic plumes from those produced by water vapour clouds. Uncertainty in flux measurements depends on the accuracy of plume-height estimation, on assumptions concerning plume-geometry, and on the quality of the retrieved SO2 amounts. We compare 3 years of flux measurements made using both the automated network and “conventional” traverse methods beneath the plume. We found a good agreement between the datasets, both in terms of magnitude and in temporal variations. These results validate the Etna SO2 flux monitoring system. Emission rates are available to the 24-hour manned operations room via intranet, providing real-time information on degassing rates and plume location

Cervical neurenteric cyst and Klippel-Feil syndrome: An abrupt onset of myelopathic signs in a young patient

Neurenteric cysts (NECs), also called enterogenous cysts or enterogenic cysts, are congenital malformative anomalies of endodermal origin that manifest with a variety of disorders, including spine anomalies. Neurenteric cysts are uncommon developmental disorders reported in 0.7%–1.3% of all spinal tumors. Klippel-Feil syndrome (KFS) defines a malformative spine disorder presenting with congenital fusion of cervical vertebrae and/or other parts of the spine. In patients with KFS, NECs are rarely reported; they may be silent for long periods of time, showing a slow progressive course or manifesting with an acute, severe neurological presentation or with fluctuating myelopathic symptoms. We report a young patient affected by KFS associated with a NEC which, in a short period of time, progressively caused myelopathic symptomatology. Surgical intervention resulted in resolution of the neurological signs. Keywords: Neurenteric cyst, Klippel-Feil syndrome, Intramedullary cys

Novel retrieval of volcanic SO2 abundance from ultraviolet spectra

The recent development of fixed networks of scanning ultraviolet spectrometers for automatic determination of volcanic SO2 fluxes has created tremendous opportunities for monitoring volcanoes but has brought new challenges in processing of the substantial data flow they produce. A particular difficulty in standard implantation of differential optical absorption (DOAS) methods is the requirement for a clear-sky (plume-free) background spectrum. Our experience after four years of measurements with two UV scanner networks on Etna and Stromboli shows that wide plumes are frequently observed precluding simple selection of clear-sky spectra. We have therefore developed a retrieval approach based on simulation of the background spectrum. We describe the method here and tune it empirically by collecting clear, zenith sky spectra using calibration cells containing known amounts of SO2. We then test the performance of this optimised retrieval using clear-sky spectra collected with the same calibration cells but for variable scan angles, time of day, and season (through the course of 1 year). We find in all cases acceptable results (maximum ~12% error) for SO2 column amounts. The method is therefore very suitable for automated SO2-plume monitoring

Semantic technologies for the production and publication of open data in ACI - Automobile club d’Italia

Semantic technologies combine knowledge representation techniques with artificial intelligence in order to achieve a more effective management of enterprise knowledge bases, thanks to the separation of the conceptual level of the applications from the logical and physical ones, and to the automatic reasoning services they deploy for data access and control. In this context, Ontology-based Data Management (OBDM) [3] has consolidated itself as a paradigm for data integration and governance, based on a three-tier architecture: the ontology, the data sources, and the mappings, which declaratively link the ontology predicates to the data in the sources. In this talk1 we present a joint project by Sapienza University of Rome, the Automobile Club d’Italia (ACI), and OKKAM S.r.l.2, a spinoff of the University of Trento. The objectives of the project were the definition of an ontology of ACI’s Public Vehicle Register (PRA) and car tax domains, the development of an OBDM system to access the data through such ontology, and the creation of a web portal for the publication of ACI’s car parc data in Linked Open format

A monolithic ASIC demonstrator for the Thin Time-of-Flight PET scanner

Time-of-flight measurement is an important advancement in PET scanners to improve image reconstruction with a lower delivered radiation dose. This article describes the monolithic ASIC for the TT-PET project, a novel idea for a high-precision PET scanner for small animals. The chip uses a SiGe Bi-CMOS process for timing measurements, integrating a fully-depleted pixel matrix with a low-power BJT-based front-end per channel, integrated on the same 100 µm thick die. The target timing resolution of the scanner is 30 ps RMS for electrons from the conversion of 511 keV photons. The system will include 1.6 million channels across almost 2000 different chips. A full-featured demonstrator chip with a 3×10 matrix of 500×500 µm2 pixels was fabricated to validate each block. Its design and experimental results are presented here. © 2019 CERN

Degassing behavior of Mt. Etna volcano (Italy) during 2007-2008, inferred

Studies on volcanic degassing have recently shown the important role of volatile release from active volcanoes in understanding magmatic processes prior to eruptions. Here we present and discuss the evolution of magmatic degassing that preceded and accompanied the 2008 Mt. Etna eruption. We tracked the ascent of magma bodies by high-temporal resolution measurements of SO2 emission rates and discrete sampling of SO2/HCl and SO2/HF molar ratios in the crater plume, as well as by periodic measurement of soil CO2 emission rates. Our data suggest that the first signs of upward migration of gas-rich magma before the 2008 eruption were observed in June 2007, indicated by a strong increase in soil CO2 efflux followed by a slow declining trend in SO2 flux and halogens. This degassing behavior preceded the mid-August 2007 summit activity culminated with the September 4th paroxysmal event. Five months later, a new increase in both soil CO2 and SO2 emission rates occurred before the November 23rd paroxysm, to drop down in late December. In the following months, geochemical parameters showed high variability, characterized by isolated sudden increases occurred in early December 2007 and late March 2008. In early May soil CO2, SO2 emission rates and S/Cl molar ratio gradually increased. Crater degassing peaked on May 13th marking the onset of the eruption. Eruptive activity was accompanied by a general steady-state of SO2 flux characterized by two main degassing cycles. These cycles preceded explosive activity at the eruptive vents, indicating terminal new-arrival of deep gas-rich magma bodies in the shallow plumbing system of Mt Etna. Conversely, halogens described a slight increasing trend till the end of 2008. These observations suggest an impulsive syn-eruptive dynamics of magma transfer from depth to the surface. Differently from the SO2 emission rates, the S/Cl ratio and the soil CO2 efflux values showed an increasing trend from mid-April to mid-July 2008, indicating steady-increasing input of deeper, gas-rich magma. Since August, geochemical parameters decreased, suggesting that new magma has not arrived from depth. According to our interpretation, both the CO2 efflux and the S/Cl ratio increases observed in early November may indicate a new input of fresh magma form depth. Finally, the estimated volume of degassing magma showed substantial equilibrium between degassed and erupted magma suggesting an “eruptive” steady-state of the volcano