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1.
  • Soffitta, Paolo, et al. (author)
  • XIPE : the X-ray imaging polarimetry explorer
  • 2013
  • In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 36:3, s. 523-567
  • Journal article (peer-reviewed)abstract
    • X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017. The proposal was, unfortunately, not selected. To be compliant with this schedule, we designed the payload mostly with existing items. The XIPE proposal takes advantage of the completed phase A of POLARIX for an ASI small mission program that was cancelled, but is different in many aspects: the detectors, the presence of a solar flare polarimeter and photometer and the use of a light platform derived by a mass production for a cluster of satellites. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus. Two additional GPDs filled with a 3-bar Ar-DME mixture always face the Sun to detect polarization from solar flares. The Minimum Detectable Polarization of a 1 mCrab source reaches 14 % in the 2-10 keV band in 10(5) s for pointed observations, and 0.6 % for an X10 class solar flare in the 15-35 keV energy band. The imaging capability is 24 arcsec Half Energy Width (HEW) in a Field of View of 14.7 arcmin x 14.7 arcmin. The spectral resolution is 20 % at 6 keV and the time resolution is 8 mu s. The imaging capabilities of the JET-X optics and of the GPD have been demonstrated by a recent calibration campaign at PANTER X-ray test facility of the Max-Planck-Institut fur extraterrestrische Physik (MPE, Germany). XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil). The data policy is organized with a Core Program that comprises three months of Science Verification Phase and 25 % of net observing time in the following 2 years. A competitive Guest Observer program covers the remaining 75 % of the net observing time.
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2.
  • Abelev, Betty, et al. (author)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Journal article (peer-reviewed)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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3.
  • Abelev, Betty, et al. (author)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :11
  • Journal article (peer-reviewed)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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4.
  • Abelev, Betty, et al. (author)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :7
  • Journal article (peer-reviewed)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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  • Adriani, Andrea, et al. (author)
  • Asymptotic Spectra of Large (Grid) Graphs with a Uniform Local Structure (Part I) : Theory
  • 2020
  • In: Milan Journal of Mathematics. - : Springer Science and Business Media LLC. - 1424-9286 .- 1424-9294. ; 88:2, s. 409-454
  • Journal article (peer-reviewed)abstract
    • We are mainly concerned with sequences of graphs having a grid geometry, with a uniform local structure in a bounded domain omega subset of Rd, d >= 1. When omega=[0,1] , such graphs include the standard Toeplitz graphs and, for omega=[0,1](d), the considered class includesd-level Toeplitz graphs. In the general case, the underlying sequence of adjacency matrices has a canonical eigenvalue distribution, in the Weyl sense, and we show that we can associate to it a symbol f. The knowledge of the symbol and of its basic analytical features provides many information on the eigenvalue structure, of localization, spectral gap, clustering, and distribution type.Few generalizations are also considered in connection with the notion of generalized locally Toeplitz sequences and applications are discussed, stemming e.g. from the approximation of differential operators via numerical schemes. Nevertheless, more applications can be taken into account, since the results presented here can be applied as well to study the spectral properties of adjacency matrices and Laplacian operators of general large graphs and networks
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7.
  • Adriani, Andrea, et al. (author)
  • Asymptotic spectra of large (grid) graphs with a uniform local structure, Part II : Numerical applications
  • 2024
  • In: Journal of Computational and Applied Mathematics. - : Elsevier. - 0377-0427 .- 1879-1778. ; 437
  • Journal article (peer-reviewed)abstract
    • In the current work we are concerned with sequences of graphs having a grid geometry, with a uniform local structure in a bounded domain Ω ⊂ Rd , d ≥ 1. When Ω = [0, 1], such graphs include the standard Toeplitz graphs and, for Ω = [0,1]d, the considered class includes d-level Toeplitz graphs. In the general case, the underlying sequence of adjacency matrices has a canonical eigenvalue distribution, in the Weyl sense, and it has been shown in the theoretical part of this work that we can associate to it a symbol f. The knowledge of the symbol and of its basic analytical features provides key information on the eigenvalue structure in terms of localization, spectral gap, clustering, and global distribution. In the present paper, many different applications are discussed and various numerical examples are presented in order to underline the practical use of the developed theory. Tests and applications are mainly obtained from the approximation of differential operators via numerical schemes such as Finite Differences, Finite Elements, and Isogeometric Analysis. Moreover, we show that more applications can be taken into account, since the results presented here can be applied as well to study the spectral properties of adjacency matrices and Laplacian operators of general large graphs and networks, whenever the involved matrices enjoy a uniform local structure.
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8.
  • Ahuja, Vasudha, et al. (author)
  • Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults : A Meta-analysis
  • 2021
  • In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:4, s. 1062-1069
  • Research review (peer-reviewed)abstract
    • OBJECTIVE: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA1c. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.
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  • Bianchi, Michele, et al. (author)
  • Poly(3,4‐ethylenedioxythiophene)‐Based Neural Interfaces for Recording and Stimulation: Fundamental Aspects and In Vivo Applications
  • 2022
  • In: Advanced Science. - : John Wiley & Sons. - 2198-3844. ; 9:12
  • Research review (peer-reviewed)abstract
    • Next‐generation neural interfaces for bidirectional communication with the central nervous system aim to achieve the intimate integration with the neural tissue with minimal neuroinflammatory response, high spatio‐temporal resolution, very high sensitivity, and readout stability. The design and manufacturing of devices for low power/low noise neural recording and safe and energy‐efficient stimulation that are, at the same time, conformable to the brain, with matched mechanical properties and biocompatibility, is a convergence area of research where neuroscientists, materials scientists, and nanotechnologists operate synergically. The biotic–abiotic neural interface, however, remains a formidable challenge that prompts for new materials platforms and innovation in device layouts. Conductive polymers (CP) are attractive materials to be interfaced with the neural tissue and to be used as sensing/stimulating electrodes because of their mixed ionic‐electronic conductivity, their low contact impedance, high charge storage capacitance, chemical versatility, and biocompatibility. This manuscript reviews the state‐of‐the‐art of poly(3,4‐ethylenedioxythiophene)‐based neural interfaces for extracellular recording and stimulation, focusing on those technological approaches that are successfully demonstrated in vivo. The aim is to highlight the most reliable and ready‐for‐clinical‐use solutions, in terms of materials technology and recording performance, other than spot major limitations and identify future trends in this field.
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13.
  • Bianchi, Stefano, et al. (author)
  • Increase of Ventricular Interval During Atrial Fibrillation by Atrioventricular Node Vagal Stimulation : Chronic Clinical Atrioventricular-Nodal Stimulation Download Study
  • 2015
  • In: Circulation. - 1941-3149 .- 1941-3084. ; 8:3, s. 562-568
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: -Patients with a high ventricular rate during atrial fibrillation (AF) are at increased risk of receiving inappropriate implantable cardioverter defibrillator (ICD) shocks. The objective was to demonstrate the feasibility of high frequency atrioventricular-nodal stimulation (AVNS) to reduce the ventricular rate during AF to prevent inappropriate ICD shocks.METHODS AND RESULTS: -Patients with a new atrial lead placement as part of a CRT-D implant and a history of paroxysmal or persistent AF were eligible. If proper atrial lead position was confirmed, AVNS software was uploaded to the CRT device, tested and optimized. AVNS was delivered via a right atrial pacing lead positioned in the posterior right atrium. Software allowed initiation of high frequency bursts triggered on rapidly conducted AF. Importantly, the efficacy was evaluated during spontaneous AF episodes between 1 and 6 months after implant. Forty-four patients were enrolled in 4 centers. Successful atrial lead placement occurred in 74%. Median implant time of the AVNS lead was 37 minutes. In 26 (81%) patients, manual AVNS tests increased the ventricular interval by > 25%. Between 1 and 6 months, automatic AVNS activations occurred in 4 patients with rapidly conducted AF, and in 3 patients, AVNS slowed the ventricular rate out of the ICD shock zone. No adverse events were associated with the AVNS software.CONCLUSIONS: -The present study demonstrated the feasibility of implementation of AVNS in a CRT-D system. AVNS increased ventricular interval > 25% in 81% of patients. AVNS did not influence the safety profile of the CRT-D system.
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  • Cai, Jing, et al. (author)
  • Elucidating the mechanisms of atmospheric new particle formation in the highly polluted Po Valley, Italy
  • 2024
  • In: Atmospheric Chemistry and Physics. - 1680-7316 .- 1680-7324. ; 24:4, s. 2423-2441
  • Journal article (peer-reviewed)abstract
    • New particle formation (NPF) is a major source of aerosol particles and cloud condensation nuclei in the troposphere, playing an important role in both air quality and climate. Frequent NPF events have been observed in heavily polluted urban environments, contributing to the aerosol number concentration by a significant amount. The Po Valley region in northern Italy has been characterized as a hotspot for high aerosol loadings and frequent NPF events in southern Europe. However, the mechanisms of NPF and growth in this region are not completely understood. In this study, we conducted a continuous 2-month measurement campaign with state-of-the-art instruments to elucidate the NPF and growth mechanisms in northern Italy. Our results demonstrate that frequent NPF events (66% of all days during the measurement campaign) are primarily driven by abundant sulfuric acid (8.5×106cm-3) and basic molecules in this area. In contrast, oxygenated organic molecules from the atmospheric oxidation of volatile organic compounds (VOCs) appear to play a minor role in the initial cluster formation but contribute significantly to the consecutive growth process. Regarding alkaline molecules, amines are insufficient to stabilize all sulfuric acid clusters in the Po Valley. Ion cluster measurements and kinetic models suggest that ammonia (10ppb) must therefore also play a role in the nucleation process. Generally, the high formation rates of sub-2nm particles (87cm-3s-1) and nucleation-mode growth rates (5.1nmh-1) as well as the relatively low condensational sink (8.9×10-3s-1) will result in a high survival probability for newly formed particles, making NPF crucial for the springtime aerosol number budget. Our results also indicate that reducing key pollutants, such as SO2, amine and NH3, could help to substantially decrease the particle number concentrations in the Po Valley region.
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  • DAddio, Francesca, et al. (author)
  • The IGFBP3/TMEM219 pathway regulates beta cell homeostasis
  • 2022
  • In: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • In this new study the Authors demonstrated that the IGFBP3/TMEM219 pathway is a physiological regulator of pancreatic beta cell homeostasis and it is dysregulated in diabetes. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes. Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
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  • Engert, Andreas, et al. (author)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • In: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Journal article (peer-reviewed)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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  • Ercan, Ayse Bahar, et al. (author)
  • Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
  • 2024
  • In: The Lancet. Oncology. - 1474-5488. ; 25:5, s. 668-682
  • Journal article (peer-reviewed)abstract
    • Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
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  • Juneau, Stéphanie, et al. (author)
  • The Black Hole-Galaxy Connection : Interplay between Feedback, Obscuration, and Host Galaxy Substructure
  • 2022
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 925:2
  • Journal article (peer-reviewed)abstract
    • There is growing evidence for physical influence between supermassive black holes and their host galaxies. We present a case study of the nearby galaxy NGC 7582, for which we find evidence that galactic substructure plays an important role in affecting the collimation of ionized outflows as well as contributing to the heavy active galactic nucleus (AGN) obscuration. This result contrasts with a simple, small-scale AGN torus model, according to which AGN-wind collimation may take place inside the torus itself, at subparsec scales. Using 3D spectroscopy with the Multi Unit Spectroscopic Explorer instrument, we probe the kinematics of the stellar and ionized gas components as well as the ionization state of the gas from a combination of emission-line ratios. We report for the first time a kinematically distinct core (KDC) in NGC 7582, on a scale of ∼600 pc. This KDC coincides spatially with dust lanes and starbursting complexes previously observed. We interpret it as a circumnuclear ring of stars and dusty, gas-rich material. We obtain a clear view of the outflowing cones over kiloparsec scales and demonstrate that they are predominantly photoionized by the central engine. We detect the back cone (behind the galaxy) and confirm previous results of a large nuclear obscuration of both the stellar continuum and H II regions. While we tentatively associate the presence of the KDC with a large-scale bar and/or a minor galaxy merger, we stress the importance of gaining a better understanding of the role of galaxy substructure in controlling the fueling, feedback, and obscuration of AGNs.
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  • Lopergolo, D., et al. (author)
  • Familial Alzheimer's disease associated with heterozygous NPC1 mutation
  • 2024
  • In: Journal of medical genetics. - 0022-2593. ; 61:4, s. 332-339
  • Journal article (peer-reviewed)abstract
    • Introduction NPC1 mutations are responsible for Niemann-Pick disease type C (NPC), a rare autosomal recessive neurodegenerative disease. Patients harbouring heterozygous NPC1 mutations may rarely show parkinsonism or dementia. Here, we describe for the first time a large family with an apparently autosomal dominant late-onset Alzheimer's disease (AD) harbouring a novel heterozygous NPC1 mutation.Methods All the five living siblings belonging to the family were evaluated. We performed clinical evaluation, neuropsychological tests, assessment of cerebrospinal fluid markers of amyloid deposition, tau pathology and neurodegeneration (ATN), structural neuroimaging and brain amyloid-positron emission tomography. Oxysterol serum levels were also tested. A wide next-generation sequencing panel of genes associated with neurodegenerative diseases and a whole exome sequencing analysis were performed.Results We detected the novel heterozygous c.3034G>T (p.Gly1012Cys) mutation in NPC1, shared by all the siblings. No other point mutations or deletions in NPC1 or NPC2 were found. In four siblings, a diagnosis of late-onset AD was defined according to clinical characterisation and ATN biomarkers (A+, T+, N+) and serum oxysterol analysis showed increased 7-ketocholesterol and cholestane-3 beta,5 alpha,6 beta-triol.Discussion We describe a novel NPC1 heterozygous mutation harboured by different members of a family with autosomal dominant late-onset amnesic AD without NPC-associated features. A missense mutation in homozygous state in the same aminoacidic position has been previously reported in a patient with NPC with severe phenotype. The alteration of serum oxysterols in our family corroborates the pathogenic role of our NPC1 mutation. Our work, illustrating clinical and biochemical disease hallmarks associated with NPC1 heterozygosity in patients affected by AD, provides relevant insights into the pathogenetic mechanisms underlying this possible novel association.
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  • Magistretti, Stefano, et al. (author)
  • The contribution of Design Thinking to the R of R&D in technological innovation
  • 2022
  • In: R&D Management. - : Wiley: 24 months. - 1467-9310 .- 0033-6807. ; 52:1, s. 108-125
  • Journal article (peer-reviewed)abstract
    • Literature on Design Thinking has mainly focused on whether its key principles enhance performance in the development phase (the D of R&D) of the technological innovation process. However, it has dedicated scant attention to the earlier research phase (the R of R&D). This aspect is surprising, given that many innovations fail as a result of early research actions and decisions. This article examines how it is possible and desirable to apply Design Thinking to the research phase of the technological innovation process. How can Design Thinking support innovation, even when advanced breakthrough technologies are at stake, the market is distant, and product applications and specific user needs have not been identified yet? To respond to this question, we investigate the research work of the design center of a global electronics company that uses a design approach called Proxemics to envision future interactions between bodies (people), objects (technology), and spaces (context). Although Proxemics is consistent with and implements the human centeredness and experimentation principles of Design Thinking, results of this study show that its logics and tools are different from those used in Design Thinking in the D of R&D due to the more abstract nature of the tasks in the R of R&D. © 2021 The Authors. R&D Management published by RADMA and John WileyXX1Sons Ltd.
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  • Schouten, Stefan, et al. (author)
  • An interlaboratory study of TEX86 and BIT analysis of sediments, extracts, and standard mixtures
  • 2013
  • In: Geochemistry Geophysics Geosystems. - 1525-2027. ; 14:12, s. 5263-5285
  • Journal article (peer-reviewed)abstract
    • Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility +/- 3-4 degrees C when translated to temperature) but a large spread in BIT measurements (reproducibility +/- 0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0 degrees C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the true (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values.
  •  
24.
  • Stigliani, Ileana, et al. (author)
  • Framing the multifaceted nature of design thinking in addressing different innovation purposes
  • 2022
  • In: Long Range Planning. - : Elsevier. - 1873-1872 .- 0024-6301. ; 55:5
  • Journal article (peer-reviewed)abstract
    • Scholars and practitioners acknowledge the role of design, and specifically design thinking, as a driver of innovation and change. Design thinking is gaining attention in the business community beyond the traditional product innovation realm and is increasingly promoted as an engine for the creation of novel user experiences, new businesses, strategic transformation, organizational and cultural change. Is it reasonable to assume that the same set of practices fits such a broad range of applications equally well? This study addresses how design thinking applications are differently framed when addressing diverse innovation purposes. Specifically, we compare two purposes: innovation of solutions, encompassing traditional product and service development projects, and innovation of direction, encompassing strategic and organizational renewal projects. Based on data collected from 146 design thinking projects conducted by European consulting firms we investigate the relationships between the design thinking practices adopted and the value generated by the projects. We then analyze how these relationships vary depending on the purpose of the innovation project, namely whether focused on innovating solutions or direction. The results show that different purposes indeed call for different practices. In projects aimed at innovating solutions, market value is positively related to capturing current user needs and envisioning future society. Conversely, in projects aimed at innovating direction, market value is positively related to challenging current assumptions. © 2021 Elsevier Ltd
  •  
25.
  • Svoboda, Jiří, et al. (author)
  • Dramatic Drop in the X-Ray Polarization of Swift J1727.8–1613 in the Soft Spectral State
  • 2024
  • In: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 966:2
  • Journal article (peer-reviewed)abstract
    • Black hole X-ray binaries exhibit different spectral and timing properties in different accretion states. The X-ray outburst of a recently discovered and extraordinarily bright source, Swift J1727.8–1613, has enabled the first investigation of how the X-ray polarization properties of a source evolve with spectral state. The 2–8 keV polarization degree was previously measured by the Imaging X-ray Polarimetry Explorer (IXPE) to be ≈4% in the hard and hard intermediate states. Here we present new IXPE results taken in the soft state, with the X-ray flux dominated by the thermal accretion disk emission. We find that the polarization degree has dropped dramatically to ≲1%. This result indicates that the measured X-ray polarization is largely sensitive to the accretion state and the polarization fraction is significantly higher in the hard state when the X-ray emission is dominated by upscattered radiation in the X-ray corona. The combined polarization measurements in the soft and hard states disfavor a very high or low inclination of the system.
  •  
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