The ASTRI Mini-Array is an international collaboration led by the Italian National Institute for Astrophysics (INAF) that will operate nine telescopes to perform Cherenkov and optical stellar ...intensity interferometry (SII) observations. At the focal plane of these telescopes, we are planning to install a stellar intensity interferometry instrument. Here we present the selected design, based on Silicon Photomultiplier (SiPM) detectors matching the telescope point spread function together with dedicated front-end electronics.
Abstract
We report a detailed study of a cohort of sporadic Creutzfeldt-Jakob disease (sCJD) VV1–2 type-mixed cases (valine homozygosity at codon 129 of the prion protein, PrP, gene harboring ...disease-related PrP, PrP
D
, types 1 and 2). Overall, sCJDVV1–2 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrP
D
type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrP
D
type exceeded 20–25%. Overall, original features of types 1 (T1) and 2 (T2) in sCJDVV1 and -VV2, including rostrocaudal relative distribution and conformational indicators, were maintained in sCJDVV1–2 except for one of the two components of T1 identified by electrophoretic mobility as T1
21
. The T1
21
conformational characteristics shifted in the presence of T2, inferring a conformational effect of PrP
D
T2 on T1
21
. The prevalence of sCJDVV1–2 was 23% or 57% of all sCJDVV cases, depending on whether standard or highly sensitive type-detecting procedures were adopted. This study, together with previous data from sCJDMM1–2 (methionine homozygosity at PrP gene codon 129) establishes the type-mixed sCJD variants as an important component of sCJD, which cannot be identified with current non-tissue based diagnostic tests of prion disease.
To evaluate interstitial lung disease associated with systemic sclerosis (SSc-ILD) and its changes during treatment by using quantitative analysis (QA) compared to semi-quantitative analysis (semiQA) ...of chest computed tomography (CT) scans. To assess the prognostic value of QA in predicting functional changes.
We retrospectively selected 35 consecutive patients with SSc-ILD with complete pulmonary functional evaluation, Doppler-echocardiography, immunological tests, and chest CT scan at both baseline and follow-up after immunosuppressive therapy. CT images were analyzed by two chest radiologists for semiQA and by a computational platform for texture analysis of ILD patterns (CALIPER) for QA. Concordance between semiQA and QA was tested. Traction bronchiectasis severity was scored. Analysis of ROC curves was performed.
Seventy CT scans were analyzed and QA failed in 4/70 scans. Thus, the final population included 31/35 patients (51.3±12.1 years). QA had a weak-to-good concordance with semiQA (ICC reticular:0.275; ICC ground-glass:0.667) and QA correlated better than semiQA (r = -0.3 to -0.74 vs r = -0.3 to -0.4) with functional parameters. Both methods correlated with traction bronchiectases score and pulmonary artery diameter at CT. A pulmonary artery diameter ≥29mm distinguished patients with lower lung volumes and ILD extent greater than 39% (p<0.001). Changes in QA patterns during treatment were not accurate (AUC: 0.50 to 0.70; p>0.05) in predicting disease progression as assessed by functional parameters, whereas variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco% (AUC = 0.74; 95%CI: 0.54 to 0.93; p = 0.03).
Pulmonary QA of CT images can objectively quantify specific patterns of ILD changes during treatment in patients with SSc-ILD. Changes in QA patterns do not correlate with functional changes, but variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco%. Pulmonary artery diameter at CT reflects the interstitial involvement, identifying patients with more severe prognosis.
The insertion of additional 168‐base pair containing seven octapeptide repeats in the prion protein (PrP) gene region spanning residues 51 to 91 is associated with inherited prion disease. In 2008, ...we reported the clinical features of a novel de novo seven-octapeptide repeat insertion (7-OPRI) mutation coupled with codon 129 methionine (M) homozygosity in the PrP gene of a 19-year-old man presenting with psychosis and atypical dementia, and 16-year survival. Here, we describe the histopathological and PrP molecular properties in the autopsied brain of this patient. Histopathological examination revealed widespread brain atrophy, focal spongiform degeneration, cortical PrP plaques, and elongated PrP formations in the cerebellum. Overall, these histopathological features resemble those described in a Belgian pedigree with 7-OPRI mutation except for the presence of PrP plaques in our case, which are morphologically different from the multicore plaques described in some OPRI mutations and in Gerstmann-Sträussler-Scheinker syndrome. The comparative characterization of the detergent- soluble and -insoluble PrP in our patient and in sporadic Creutzfeldt-Jakob disease revealed distinct molecular signatures. Proteinase K digestion of the pathogenic, disease-associated PrP (PrPD), revealed PrPD type 1 in the cerebral cortex and mixed PrPD types 1 and 2 in the cerebellum. Altogether, the present study outlines the importance of assessing the phenotypical and PrP biochemical properties of these rare conditions, thereby widening the spectrum of the phenotypic heterogeneity of the 7-OPRI insertion mutations. Further studies are needed to determine whether distinct conformers of PrPD are associated with two major clinico-histopathological phenotypes in prion disease with 7-OPRI.
Aurora kinases were recently identified as a potential target in anticancer therapy and, amongst their available inhibitors, Tozasertib (VX-680) and Danusertib (PHA-739358) have been indicated as ...possible substrates of human flavin-containing monooxygenase 3 (hFMO3). Here we report the in vitro rate of oxidation of these drugs by wild-type hFMO3 and its polymorphic variant V257M. The conversion of Tozasertib and Danusertib to their corresponding metabolites, identified by LC-MS, by the purified wild-type and V257M hFMO3 show significant differences. In the case of Tozasertib, the V257M variant shows a catalytic efficiency, expressed as k(cat)/K(m), similar to the wild-type: 0.39 ± 0.06 min-1µM-1 for V257M compared to 0.33 ± 0.04 min-1µM-1 for the wild type. On the other hand, in the case of Danusertib, V257M shows a 3.4× decrease in catalytic efficiency with k(cat)/K(m) values of 0.05 ± 0.01 min-1µM-1 for V257M and 0.17 ± 0.03 min-1µM-1 for the wild type. These data reveal how a simple V257M substitution ascribed to a single nucleotide polymorphism affects the N-oxidation of relevant anticancer drugs, with important outcome in their therapeutic effects. These findings demonstrate that codon 257 is important for activity of the hFMO3 gene and the codon change V to M has an effect on the catalytic efficiency of this enzyme.
We report a detailed study of a cohort of sporadic Creutzfeldt-Jakob disease (sCJD) VV1-2 type-mixed cases (valine homozygosity at codon 129 of the prion protein, PrP, gene harboring disease-related ...PrP, PrP
, types 1 and 2). Overall, sCJDVV1-2 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrP
type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrP
type exceeded 20-25%. Overall, original features of types 1 (T1) and 2 (T2) in sCJDVV1 and -VV2, including rostrocaudal relative distribution and conformational indicators, were maintained in sCJDVV1-2 except for one of the two components of T1 identified by electrophoretic mobility as T1
. The T1
conformational characteristics shifted in the presence of T2, inferring a conformational effect of PrP
T2 on T1
. The prevalence of sCJDVV1-2 was 23% or 57% of all sCJDVV cases, depending on whether standard or highly sensitive type-detecting procedures were adopted. This study, together with previous data from sCJDMM1-2 (methionine homozygosity at PrP gene codon 129) establishes the type-mixed sCJD variants as an important component of sCJD, which cannot be identified with current non-tissue based diagnostic tests of prion disease.
The purpose of this project is to improve the techniques of Quantum Cryptography, to realize a Quantum Key Distribution (QKD) in free space with an orbiting satellite using nowadays technology. With ...this experiment we characterize the properties of a single photon communication channel from an orbiting satellite in space to a ground based station. We used the facilities of the ASI laser ranging station MLRO (Matera) and the satellite for geodesy Lageos I, equipped with corner-cube retroreflectors, to simulate a single photon transmission from an orbiting satellite.
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