Properties of Some Variants of Human β2-Microglobulin and Amyloidogenesis

Three variants of human beta(2)-microglobulin (beta(2)-m) were compared with wild-type protein. For two variants, namely the mutant R3Abeta(2)-m and the form devoid of the N-terminal tripeptide (DeltaN3beta(2)-m), a reduced unfolding free energy was measured compared with wild-type beta(2)-m, whereas an increased stability was observed for the mutant H31Ybeta(2)-m. The solution structure could be determined by (1)H NMR spectroscopy and restrained modeling only for R3Abeta(2)-m that showed the same conformation as the parent species, except for deviations at the interstrand loops. Analogous conclusions were reached for H31Ybeta(2)-m and DeltaN3beta(2)-m. Precipitation and unfolding were observed over time periods shorter than 4-6 weeks with all the variants and, sometimes, with wild-type protein. The rate of structured protein loss from solution as a result of precipitation and unfolding always showed pseudo-zeroth order kinetics. This and the failure to observe an unfolded species without precipitation suggest that a nucleated conformational conversion scheme should apply for beta(2)-m fibrillogenesis. The mechanism is consistent with the previous and present results on beta(2)-m amyloid transition, provided a nucleated oligomeric species be considered the stable intermediate of fibrillogenesis, the monomeric intermediate being the necessary transition step along the pathway from the native protein to the nucleated oligomer

Exploring energy performance certificates through visualization

Energy Performance Certificates (EPCs) provide interesting information on the standard-based calculation of energy performance, thermo-physical and geometrical related properties of a building. Because of the volume of available data (issued as open data) and the heterogeneity of the attributes, the exploration of these energy-related data collections is challenging. This paper presents INDICE (INformative DynamiC dashboard Engine), a new data visualization framework able to automatically explore large collections of EPCs. INDICE explores EPCs through both querying and analytics tasks, and intuitively presents the output through informative dashboards. The latter include dynamic and interactive maps along with different informative charts allowing different stakeholders (e.g., domain and non-domain expert users) to explore and interpret the extracted knowledge at different spatial granularity levels. The objective of INDICE is to create energy maps useful for the characterization of the energy performance of buildings located in different areas. The experimental evaluation, performed on a real set of EPCs related to a major Italian region in the North West of Italy, demonstrates the effectiveness of INDICE in exploring an EPC dataset through different data and knowledge visualization techniques

Modification of the electrical and optical Properties of Single Crystal Diamond with Focused MeV Ion Beams

AbstractIn this paper an overview is given on recent results obtained in the framework of an Italian/Croatian collaboration aimed to explore the potential of techniques based on focused MeV ion beams to locally modify the structural, electrical and optical features of diamond.Experiments were carried out using light (H, He, C) ion beams with energies of the order of MeV, focused to micrometer-size spot and raster scanned onto the surface of monocrystalline (IIa or Ib) diamond samples. Different energies, ion species and fluences were used, in conjunction with variable thickness masks and post annealing processes, to define three-dimensional structures in diamond, whose electrical/optical/structural properties have been suitably characterized. Finite element numerical methods have been employed in the modeling of the material modification and in device design

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients

Background: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. Methods: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. Results: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. Discussion: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting

Dependence of immunoglobulin class switch recombination in B Cells on vesicular release of ATP and CD73 ectonucleotidase activity

Immunoglobulin (Ig) isotype diversification by class switch recombination (CSR) is an essential process for mounting a protective humoral immune response. Ig CSR deficiencies in humans can result from an intrinsic B cell defect; however, most of these deficiencies are still molecularly undefined and diagnosed as common variable immunodeficiency (CVID). Here, we show that extracellular adenosine critically contributes to CSR in human naive and IgM memory B cells. In these cells, coordinate stimulation of B cell receptor and toll-like receptors results in the release of ATP stored in Ca2+-sensitive secretory vesicles. Plasma membrane ectonucleoside triphosphate diphosphohydrolase 1 CD39 and ecto-5′-nucleotidase CD73 hydrolyze ATP to adenosine, which induces CSR in B cells in an autonomous fashion. Notably, CVID patients with impaired class-switched antibody responses are selectively deficient in CD73 expression in B cells, suggesting that CD73-dependent adenosine generation contributes to the pathogenesis of this disease

Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial.

OBJECTIVE  To test the optimal antithrombotic regimen in patients with acute coronary syndrome. DESIGN  Randomised controlled trial. SETTING  Patients with acute coronary syndrome with and without ST segment elevation in 78 centres in Italy, the Netherlands, Spain, and Sweden. PARTICIPANTS  7213 patients with acute coronary syndrome and planned percutaneous coronary intervention: 4010 with ST segment elevation and 3203 without ST segment elevation. The primary study results in the overall population have been reported previously. INTERVENTIONS  Patients were randomly assigned, in an open label fashion, to one of two regimens: bivalirudin with glycoprotein IIb/IIIa inhibitors restricted to procedural complications or heparin with or without glycoprotein IIb/IIIa inhibitors. MAIN OUTCOME MEASURES  Primary endpoints were the occurrence of major adverse cardiovascular events, defined as death, myocardial infarction or stroke; and net adverse clinical events, defined as major bleeding or major adverse cardiovascular events, both assessed at 30 days. Analyses were performed by the principle of intention to treat. RESULTS  Use of a glycoprotein IIb/IIIa inhibitor in patients assigned to heparin was planned at baseline in 30.7% of patients with ST segment elevation, in 10.9% without ST segment elevation, and in no patients assigned to bivalirudin. In patients with ST segment elevation, major adverse cardiovascular events occurred in 118 (5.9%) assigned to bivalirudin and 129 (6.5%) assigned to heparin (rate ratio 0.90, 95% confidence interval 0.70 to 1.16; P=0.43), whereas net adverse clinical events occurred in 139 (7.0%) patients assigned to bivalirudin and 163 (8.2%) assigned to heparin (0.84, 0.67 to 1.05; P=0.13). In patients without ST segment elevation, major adverse cardiovascular events occurred in 253 (15.9%) assigned to bivalirudin and 262 (16.4%) assigned to heparin (0.97, 0.80 to 1.17; P=0.74), whereas net adverse clinical events occurred in 262 (16.5%) patients assigned to bivalirudin and 281 (17.6%) assigned to heparin (0.93, 0.77 to 1.12; P=0.43). CONCLUSIONS  A bivalirudin monotherapy strategy compared with heparin with or without glycoprotein IIb/IIIa inhibitors, did not result in reduced major adverse cardiovascular events or net adverse clinical events in patients with or without ST segment elevation.Trial Registration ClinicalTrials.gov NCT01433627

Characterization of monolithic SDD arrays and SFERA ASIC for the SIDDHARTA experiment

This work deals with the first characterization results of an X-ray detection module developed within the scope of SIDDHARTA experiment. SIDDHARTA is a nuclear physics experiment aimed at the study of strong nuclear interactions using exotic atoms. This is achieved using monolithic arrays of Silicon Drift Detectors (SDDs), each consisting of eight SDD elements arranged in a 2×4 format (total area 18×34 mm2). A total of 48 SDD arrays arranged on a gantry structure are required to perform the experiment. Each SDD element is coupled to a CUBE pre-amplifier with the consequent shaping amplifier and complementary analog electronic stages implemented in a custom developed 16-channel SFERA chip. During the experiment, SDD arrays must be cooled down to cryogenic temperature below 120 K to perform X-ray spectroscopy to assess spread/shift of energy levels of exotic kaonic atoms. Alongside the cryogenic operation, the X-ray spectrometer needs to operate with a linearity of around 10/00 with an output stability of a few eV/day. This work describes the preliminary characterization results of cryogenically cooled 2×4 SDD arrays readout by SFERA chip. These include X-ray spectroscopy, stability and linearity performances

Characterization of monolithic SDD arrays and SFERA ASIC for the SIDDHARTA experiment

This work deals with the first characterization results of an X-ray detection module developed within the scope of SIDDHARTA experiment. SIDDHARTA is a nuclear physics experiment aimed at the study of strong nuclear interactions using exotic atoms. This is achieved using monolithic arrays of Silicon Drift Detectors (SDDs), each consisting of eight SDD elements arranged in a 2×4 format (total area 18×34 mm2). A total of 48 SDD arrays arranged on a gantry structure are required to perform the experiment. Each SDD element is coupled to a CUBE pre-amplifier with the consequent shaping amplifier and complementary analog electronic stages implemented in a custom developed 16-channel SFERA chip. During the experiment, SDD arrays must be cooled down to cryogenic temperature below 120 K to perform X-ray spectroscopy to assess spread/shift of energy levels of exotic kaonic atoms. Alongside the cryogenic operation, the X-ray spectrometer needs to operate with a linearity of around 1‰ with an output stability of a few eV/day. This work describes the preliminary characterization results of cryogenically cooled 2×4 SDD arrays readout by SFERA chip. These include X-ray spectroscopy, stability and linearity performances

Metrological features of the Large Piston Prover at INRIM

INRIM realizes its flow rate standard using three distinct facilities, aimed at measuring different flow rate ranges; in particular, for the largest flow range rate (10–2600 L/min) a piston prover is used. This machine is of the volumetric type, therefore its traceability can be obtained through dimensional calibration of the piston, which has a nominal diameter of 1000 mm and a nominal stroke of 1200 mm. The present paper describes in detail the features of the standard, its traceability chain and the uncertainty budget of the measurements it can perform. The uncertainty budget directly determines the Calibration and Measurement Capabilities claim in the range available to the test rig. A detailed analysis of the various uncertainty components will be presented and discussed. Special attention will be dedicated to the dimensional calibration of the piston, since it is of paramount importance for the determination of the main uncertainty component. This calibration is particularly challenging since, due to the large size of the piston, it must be carried on in-situ, thereby requiring a set of special adaptations with respect to a standard calibration of a cylinder. It will be shown that the calibration of the piston recently performed is in good accordance with the one that was carried out at the piston initial installation in 1999, thus confirming the stability of the standard