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Showing papers by "University of Siena published in 2019"


Journal ArticleDOI
Andrea Cossarizza1, Hyun-Dong Chang, Andreas Radbruch, Andreas Acs2  +459 moreInstitutions (160)
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

698 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigated the drug retention rate of interleukin (IL)-1 inhibitors on systemic JIA (sJIA) patients and evaluated predictive factors of drug survival based on data from a real-world setting concerning sJIA.
Abstract: Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA. Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers. Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to adverse events (AEs) occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341-8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186-7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002). Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.

615 citations


Journal ArticleDOI
TL;DR: The OpenMolcas environment is described and features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism and properties are described.
Abstract: In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.

559 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3  +1215 moreInstitutions (134)
TL;DR: In this paper, the mass, spin, and redshift distributions of binary black hole (BBH) mergers with LIGO and Advanced Virgo observations were analyzed using phenomenological population models.
Abstract: We present results on the mass, spin, and redshift distributions with phenomenological population models using the 10 binary black hole (BBH) mergers detected in the first and second observing runs completed by Advanced LIGO and Advanced Virgo. We constrain properties of the BBH mass spectrum using models with a range of parameterizations of the BBH mass and spin distributions. We find that the mass distribution of the more massive BH in such binaries is well approximated by models with no more than 1% of BHs more massive than 45 M and a power-law index of (90% credibility). We also show that BBHs are unlikely to be composed of BHs with large spins aligned to the orbital angular momentum. Modeling the evolution of the BBH merger rate with redshift, we show that it is flat or increasing with redshift with 93% probability. Marginalizing over uncertainties in the BBH population, we find robust estimates of the BBH merger rate density of R= (90% credibility). As the BBH catalog grows in future observing runs, we expect that uncertainties in the population model parameters will shrink, potentially providing insights into the formation of BHs via supernovae, binary interactions of massive stars, stellar cluster dynamics, and the formation history of BHs across cosmic time.

464 citations


Journal ArticleDOI
F. Kyle Satterstrom1, Jack A. Kosmicki1, Jiebiao Wang2, Michael S. Breen3  +150 moreInstitutions (45)
TL;DR: Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, 102 risk genes are identified at a false discovery rate of ≤ 0.1, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.
Abstract: We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

461 citations


Journal ArticleDOI
TL;DR: 5-year follow-up surveillance shows that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since the authors' first report.
Abstract: The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009-2011. Here we show a five-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. Further phylogenetic analyses on more than 10,000 sequences obtained from the national ARCA cohort was performed in parallel. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e the Italian origin, young age at HIV diagnosis (median 24 years; range 18-37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in UK in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Furthermore, this study allowed to identify 13 additional sequences from a clinical center in central Italy (Ancona) that shared a B/C recombination pattern distinct from that detected for CRF60_BC, likely representing a new Italian CRF. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy.

452 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Fausto Acernese3  +1237 moreInstitutions (131)
TL;DR: In this paper, the authors place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime of a binary neutron star inspiral.
Abstract: The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in the presence of matter. In this Letter, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polarization content of the gravitational wave signal is studied. The results of all tests performed here show good agreement with GR.

430 citations


Journal ArticleDOI
TL;DR: Continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo in patients with TRD in stable remission.
Abstract: Importance Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. Objective To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant. Design, Setting, and Participants In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, to February 15, 2018, at outpatient referral centers, 705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84 mg) plus an oral antidepressant. After 16 weeks of esketamine treatment, 297 who achieved stable remission or stable response entered the randomized withdrawal phase. Interventions Patients who achieved stable remission and those who achieved stable response (without remission) were randomized 1:1 to continue esketamine nasal spray or discontinue esketamine treatment and switch to placebo nasal spray, with oral antidepressant treatment continued in each group. Main Outcomes and Measures Time to relapse was examined in patients who achieved stable remission, as assessed using a weighted combination log-rank test. Results Among the 297 adults (mean age [SD], 46.3 [11.13] years; 197 [66.3%] female) who entered the randomized maintenance phase, 176 achieved stable remission; 24 (26.7%) in the esketamine and antidepressant group and 39 (45.3%) in the antidepressant and placebo group experienced relapse (log-rankP = .003, number needed to treat [NNT], 6). Among the 121 who achieved stable response, 16 (25.8%) in the esketamine and antidepressant group and 34 (57.6%) in the antidepressant and placebo group experienced relapse (log-rankP Conclusions and Relevance For patients with TRD who experienced remission or response after esketamine treatment, continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo. Trial Registration ClinicalTrials.gov identifier:NCT02493868

284 citations


Journal ArticleDOI
TL;DR: This review aims to bring together these multidisciplinary and interdisciplinary features of MDR cancers by deciphering the molecular mechanisms underlying anticancer drug resistance, to pave the way towards the development of novel precision medicine treatment modalities that are able to surmount distinct and well-defined mechanisms of antic cancer drug resistance.

281 citations


Journal ArticleDOI
01 Jul 2019-Brain
TL;DR: A practical guide to the proper recognition of multiple sclerosis lesions is provided, including a thorough description and illustration of typical MRI features, as well as a discussion of red flags suggestive of alternative diagnoses.
Abstract: MRI has improved the diagnostic work-up of multiple sclerosis, but inappropriate image interpretation and application of MRI diagnostic criteria contribute to misdiagnosis. Some diseases, now recognized as conditions distinct from multiple sclerosis, may satisfy the MRI criteria for multiple sclerosis (e.g. neuromyelitis optica spectrum disorders, Susac syndrome), thus making the diagnosis of multiple sclerosis more challenging, especially if biomarker testing (such as serum anti-AQP4 antibodies) is not informative. Improvements in MRI technology contribute and promise to better define the typical features of multiple sclerosis lesions (e.g. juxtacortical and periventricular location, cortical involvement). Greater understanding of some key aspects of multiple sclerosis pathobiology has allowed the identification of characteristics more specific to multiple sclerosis (e.g. central vein sign, subpial demyelination and lesional rims), which are not included in the current multiple sclerosis diagnostic criteria. In this review, we provide the clinicians and researchers with a practical guide to enhance the proper recognition of multiple sclerosis lesions, including a thorough definition and illustration of typical MRI features, as well as a discussion of red flags suggestive of alternative diagnoses. We also discuss the possible place of emerging qualitative features of lesions which may become important in the near future.

270 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of heavy metal-induced reactive oxygen species (ROS) on plant cell wall-related processes and the stimulatory/inhibitory effects of ROS on plant secondary metabolism were investigated.

Journal ArticleDOI
TL;DR: Eurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity and shows a high accuracy in an independent data set of 1018 patients.
Abstract: Background Different diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)—familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)—and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA. Methods Step 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients’ diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of the best candidate classification criteria; step 4: nominal group technique consensus conference with 33 panellists for the discussion and selection of the final classification criteria; step 5: cross-sectional validation of the novel criteria. Results The panellists achieved consensus to classify 281 of 360 (78%) patients (32 CAPS, 36 FMF, 56 MKD, 37 PFAPA, 39 TRAPS, 81 undefined recurrent fever). Consensus was reached for two sets of criteria for each HRF, one including genetic and clinical variables, the other with clinical variables only, plus new criteria for PFAPA. The four HRF criteria demonstrated sensitivity of 0.94–1 and specificity of 0.95–1; for PFAPA, criteria sensitivity and specificity were 0.97 and 0.93, respectively. Validation of these criteria in an independent data set of 1018 patients shows a high accuracy (from 0.81 to 0.98). Conclusion Eurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity.


Journal ArticleDOI
TL;DR: An updated account on the current knowledge concerning periodontal disease and the adverse effects exerted on the cardiovascular system health and diabetes is provided, informing readers on the most recent preclinical studies and epidemiological evidence.
Abstract: Periodontitis is a chronic inflammatory disease, initiated by the presence of a bacterial biofilm, called dental plaque, which affects both the periodontal ligaments and bone surrounding teeth. In the last decades, several lines of evidence have supported the existence of a relationship between periodontitis and systemic health. For instance, as periodontitis acts within the same chronic inflammatory model seen in cardiovascular disease (CVD), or other disorders, such as diabetes, several studies have suggested the existence of a bi-directional link between periodontal health and these pathologies. For instance, people with diabetes are more susceptible to infections and are more likely to suffer from periodontitis than people without this syndrome. Analogously, it is now evident that cardiac disorders are worsened by periodontitis, both experimentally and in humans. For all these reasons, it is very plausible that preventing periodontitis has an impact on the onset or progression of CVD and diabetes. On these grounds, in this review, we have provided an updated account on the current knowledge concerning periodontal disease and the adverse effects exerted on the cardiovascular system health and diabetes, informing readers on the most recent preclinical studies and epidemiological evidence.

Journal ArticleDOI
TL;DR: It is hypothesized that the effects of microplastics on mucosal epithelium integrity and immune response could potentially reduce the organism defense against pathogens, and lead to a different utilization of energy stores.
Abstract: Microplastics have become pervasive environmental pollutants in both freshwater and marine ecosystems. The presence of microplastics have been recorded in the tissues of many wild fish species, and laboratory studies have demonstrated that microplastics can exert adverse health effects. To further investigate the biological mechanisms underlying microplastics toxicity we applied an integrated approach, analyzing the effects of microplastics at transcriptomic, histological and behavioral level. Adult zebrafish have been exposed to two concentrations of high-density polyethylene and polystyrene microplastics for twenty days. Transcriptomic results indicate alterations in the expression of immune system genes and the down-regulation of genes correlated with epithelium integrity and lipid metabolism. The transcriptomic findings are supported by tissue alterations and higher occurrence of neutrophils observed in gills and intestinal epithelium. Even the daily rhythm of activity of zebrafish appears to be affected, although the regular pattern of activity is recovered over time. Considering the transcriptomic and histological findings reported, we hypothesize that the effects on mucosal epithelium integrity and immune response could potentially reduce the organism defense against pathogens, and lead to a different utilization of energy stores.

Journal ArticleDOI
Maya Fishbach1, R. Gray2, I. Magaña Hernandez3, H. Qi3  +322 moreInstitutions (52)
TL;DR: In this paper, a statistical standard siren analysis of GW170817 is presented, which considers all galaxies brighter than 0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger.
Abstract: We perform a statistical standard siren analysis of GW170817. Our analysis does not utilize knowledge of NGC 4993 as the unique host galaxy of the optical counterpart to GW170817. Instead, we consider each galaxy within the GW170817 localization region as a potential host; combining the redshifts from all of the galaxies with the distance estimate from GW170817 provides an estimate of the Hubble constant, H 0. Considering all galaxies brighter than $0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger, we find ${H}_{0}={77}_{-18}^{+37}$ km s−1 Mpc−1 (maximum a posteriori and 68.3% highest density posterior interval; assuming a flat H 0 prior in the range $\left[10,220\right]$ km s−1 Mpc−1). We explore the dependence of our results on the thresholds by which galaxies are included in our sample, and we show that weighting the host galaxies by stellar mass or star formation rate provides entirely consistent results with potentially tighter constraints. By applying the method to simulated gravitational-wave events and a realistic galaxy catalog we show that, because of the small localization volume, this statistical standard siren analysis of GW170817 provides an unusually informative (top 10%) constraint. Under optimistic assumptions for galaxy completeness and redshift uncertainty, we find that dark binary neutron star measurements of H 0 will converge as $40 \% /\sqrt{(N)}$, where N is the number of sources. While these statistical estimates are inferior to the value from the counterpart standard siren measurement utilizing NGC 4993 as the unique host, ${H}_{0}={76}_{-13}^{+19}$ km s−1 Mpc−1 (determined from the same publicly available data), our analysis is a proof-of-principle demonstration of the statistical approach first proposed by Bernard Schutz over 30 yr ago.

Journal ArticleDOI
TL;DR: This paper presents a steganographic scheme with a novel operation called adversarial embedding (ADV-EMB), which achieves the goal of hiding a stego message while at the same time fooling a convolutional neural network (CNN)-based steganalyzer.
Abstract: Steganographic schemes are commonly designed in a way to preserve image statistics or steganalytic features. Since most of the state-of-the-art steganalytic methods employ a machine learning (ML)-based classifier, it is reasonable to consider countering steganalysis by trying to fool the ML classifiers. However, simply applying perturbations on stego images as adversarial examples may lead to the failure of data extraction and introduce unexpected artifacts detectable by other classifiers. In this paper, we present a steganographic scheme with a novel operation called adversarial embedding (ADV-EMB), which achieves the goal of hiding a stego message while at the same time fooling a convolutional neural network (CNN)-based steganalyzer. The proposed method works under the conventional framework of distortion minimization. In particular, ADV-EMB adjusts the costs of image elements modifications according to the gradients back propagated from the target CNN steganalyzer. Therefore, modification direction has a higher probability to be the same as the inverse sign of the gradient. In this way, the so-called adversarial stego images are generated. Experiments demonstrate that the proposed steganographic scheme achieves better security performance against the target adversary-unaware steganalyzer by increasing its missed detection rate. In addition, it deteriorates the performance of other adversary-aware steganalyzers, opening the way to a new class of modern steganographic schemes capable of overcoming powerful CNN-based steganalysis.

Journal ArticleDOI
TL;DR: Looking at the mechanisms underlying exosome action, it is found that T lymphocyte exosomes trigger apoptosis and the expression of genes involved in chemokine signaling, including Ccl2, Ccl7, and Cxcl10, exclusively in β cells, which point to exosomal-miRNA transfer as a communication mode between immune and insulin-secreting cells.

Journal ArticleDOI
TL;DR: Metasurfaces are thin two-dimensional metamaterial layers that allow or inhibit the propagation of electromagnetic waves in desired directions as discussed by the authors, and have been demonstrated to be able to p...
Abstract: Metasurfaces are thin two-dimensional metamaterial layers that allow or inhibit the propagation of electromagnetic waves in desired directions. For example, metasurfaces have been demonstrated to p ...

Journal ArticleDOI
Marcelle Soares-Santos1, Antonella Palmese2, W. G. Hartley3, J. Annis2  +1285 moreInstitutions (156)
TL;DR: In this article, a multi-messenger measurement of the Hubble constant H 0 using the binary-black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES), is presented.
Abstract: We present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in ${H}_{0}={75}_{-32}^{+40}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$, which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find ${H}_{0}={78}_{-24}^{+96}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$ (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0.

Journal ArticleDOI
TL;DR: It is experimentally shown for the first time that metasurface antennas constituted by subwavelength elements printed on a grounded dielectric slab can have aperture efficiency up to 70%, a bandwidth up to 30%, and produce two different direction beams of high-gain and similar beams at two different frequencies, showing performances never reached before.
Abstract: This paper presents new designs, implementation and experiments of metasurface (MTS) antennas constituted by subwavelength elements printed on a grounded dielectric slab These antennas exploit the interaction between a cylindrical surface wave (SW) wavefront and an anisotropic impedance boundary condition (BC) to produce an almost arbitrary aperture field They are extremely thin and excited by a simple in-plane monopole By tailoring the BC through the shaping of the printed elements, these antennas can be largely customized in terms of beam shape, bandwidth and polarization In this paper, we describe new designs and their implementation and measurements It is experimentally shown for the first time that these antennas can have aperture efficiency up to 70%, a bandwidth up to 30%, they can produce two different direction beams of high-gain and similar beams at two different frequencies, showing performances never reached before

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2382 moreInstitutions (209)
TL;DR: In this paper, a search for supersymmetric particles in the final state with multiple jets and large missing transverse momentum was performed using a sample of proton-proton collisions collected with the CMS detector.
Abstract: Results are reported from a search for supersymmetric particles in the final state with multiple jets and large missing transverse momentum. The search uses a sample of proton-proton collisions at $ \sqrt{s} $ = 13 TeV collected with the CMS detector in 2016–2018, corresponding to an integrated luminosity of 137 fb$^{−1}$, representing essentially the full LHC Run 2 data sample. The analysis is performed in a four-dimensional search region defined in terms of the number of jets, the number of tagged bottom quark jets, the scalar sum of jet transverse momenta, and the magnitude of the vector sum of jet transverse momenta. No significant excess in the event yield is observed relative to the expected background contributions from standard model processes. Limits on the pair production of gluinos and squarks are obtained in the framework of simplified models for supersymmetric particle production and decay processes. Assuming the lightest supersymmetric particle to be a neutralino, lower limits on the gluino mass as large as 2000 to 2310 GeV are obtained at 95% confidence level, while lower limits on the squark mass as large as 1190 to 1630 GeV are obtained, depending on the production scenario.

Journal ArticleDOI
TL;DR: Treatment of adenomyosis requires a lifelong management plan as the disease has a negative impact on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome and has a high risk of miscarriage and obstetric complications.
Abstract: Adenomyosis is a benign uterine disorder in which endometrial glands and stroma are pathologically demonstrated in the uterine myometrium and it is considered a specific entity in the PALM-COEIN FIGO (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified – International Federation of Gynecology and Obstetrics) classification of causes of abnormal uterine bleeding (AUB). Although it has always been considered the classic condition of multiparous women over 40 years old who have pain and heavy menstrual bleeding, diagnosed at hysterectomy, the epidemiological scenario has completely changed. Adenomyosis is increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging point of view, and the diagnosis remains difficult and unclear. A uniform and shared reporting system needs to be implemented in order to improve our understanding on imaging features, their relationship with pathogenic theories, and their importance in terms of clinical symptoms and response to treatment. In fact, adenomyosis pathogenesis remains elusive and not a single theory can explain all of the different phenotypes of the disease. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. Treatment requires a lifelong management plan as the disease has a negative impact on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome and has a high risk of miscarriage and obstetric complications.

Journal ArticleDOI
TL;DR: Preliminary results represent a baseline for the implementation of the Marine Strategy Framework Directive descriptor 10 in Italy as well as an important step for detecting microplastics in bioindicator species from different GSAs.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3  +1222 moreInstitutions (135)
TL;DR: In this article, the results of an all-sky search for continuous gravitational waves (CWs), which can be produced by fast spinning neutron stars with an asymmetry around their rotation axis, were presented.
Abstract: We present results of an all-sky search for continuous gravitational waves (CWs), which can be produced by fast spinning neutron stars with an asymmetry around their rotation axis, using data from the second observing run of the Advanced LIGO detectors. Three different semicoherent methods are used to search in a gravitational-wave frequency band from 20 to 1922 Hz and a first frequency derivative from -1×10-8 to 2×10-9 Hz/s. None of these searches has found clear evidence for a CW signal, so upper limits on the gravitational-wave strain amplitude are calculated, which for this broad range in parameter space are the most sensitive ever achieved.

Journal ArticleDOI
TL;DR: The TOTEM collaboration measured the proton-proton total cross section at the LHC with a luminosity-independent method as discussed by the authors using dedicated beam optics, the Roman Pots were inserted very close to the beam.
Abstract: The TOTEM collaboration has measured the proton–proton total cross section at $$\sqrt{s}=13~\hbox {TeV}$$ with a luminosity-independent method. Using dedicated $$\beta ^{*}=90~\hbox {m}$$ beam optics, the Roman Pots were inserted very close to the beam. The inelastic scattering rate has been measured by the T1 and T2 telescopes during the same LHC fill. After applying the optical theorem the total proton–proton cross section is $$\sigma _\mathrm{tot}=(110.6~\pm ~3.4$$ ) mb, well in agreement with the extrapolation from lower energies. This method also allows one to derive the luminosity-independent elastic and inelastic cross sections: $$\sigma _\mathrm{el}=(31.0~\pm ~1.7)~\hbox {mb}$$ and $$\sigma _\mathrm{inel}=(79.5~\pm ~1.8)~\hbox {mb}$$ .

Journal ArticleDOI
TL;DR: The obtained results suggest that plastics can serve as vectors for the spread of multiple resistances to antibiotics across Antarctic marine environments and underline the relevance of future studies on this topic.

Journal ArticleDOI
TL;DR: The number of rare likely deleterious variants in functionally intolerant genes (“other hits”) correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with their carrier family members.

Journal ArticleDOI
O. Adriani1, Y. Akaike2, Y. Akaike3, Katsuaki Asano4, Yoichi Asaoka5, Yoichi Asaoka6, Maria Grazia Bagliesi7, Eugenio Berti1, Gabriele Bigongiari7, W. R. Binns8, S. Bonechi7, M. Bongi1, Paolo Brogi7, A. Bruno2, J. H. Buckley8, N. Cannady9, G. Castellini10, C. Checchia11, Michael Cherry9, G. Collazuol11, V. Di Felice12, K. Ebisawa6, H. Fuke6, T. G. Guzik9, T. Hams2, T. Hams3, N. Hasebe5, K. Hibino13, M. Ichimura14, Kunihito Ioka15, W. Ishizaki4, M. H. Israel8, K. Kasahara5, Jun Kataoka5, Ryuho Kataoka16, Y. Katayose17, Chihiro Kato18, Norita Kawanaka19, Y. Kawakubo20, Y. Kawakubo9, Kazunori Kohri, Henric Krawczynski8, John F. Krizmanic2, John F. Krizmanic3, Teimuraz Lomtadze, Paolo Maestro7, P. S. Marrocchesi7, Alberto Messineo21, John Mitchell2, S. Miyake, A. A. Moiseev2, A. A. Moiseev22, K. Mori5, K. Mori6, Masaki Mori23, N. Mori, Holger Motz5, Kazuoki Munakata18, H. Murakami5, Satoshi Nakahira, Jun Nishimura6, G. A. de Nolfo2, S. Okuno13, J. F. Ormes24, S. Ozawa5, L. Pacini1, L. Pacini10, F. Palma12, P. Papini, A. V. Penacchioni7, A. V. Penacchioni25, Brian Rauch8, S. B. Ricciarini10, K. Sakai3, K. Sakai2, T. Sakamoto20, Manami Sasaki2, Manami Sasaki22, Y. Shimizu13, A. Shiomi26, R. Sparvoli12, P. Spillantini1, F. Stolzi7, J. E. Suh7, A. Sulaj7, I. Takahashi27, Masahiro Takayanagi6, Masato Takita4, T. Tamura13, Toshio Terasawa, H. Tomida6, Shoji Torii5, Y. Tsunesada28, Y. Uchihori, Shinji Ueno6, E. Vannuccini, J. P. Wefel9, Kazutaka Yamaoka29, Shohei Yanagita30, A. Yoshida20, Kenji Yoshida31 
TL;DR: The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index, thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ.
Abstract: In this paper, we present the analysis and results of a direct measurement of the cosmic-ray proton spectrum with the CALET instrument onboard the International Space Station, including the detailed assessment of systematic uncertainties. The observation period used in this analysis is from October 13, 2015 to August 31, 2018 (1054 days). We have achieved the very wide energy range necessary to carry out measurements of the spectrum from 50 GeV to 10 TeV covering, for the first time in space, with a single instrument the whole energy interval previously investigated in most cases in separate subranges by magnetic spectrometers (BESS-TeV, PAMELA, and AMS-02) and calorimetric instruments (ATIC, CREAM, and NUCLEON). The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index from -2.81±0.03 (50-500 GeV) neglecting solar modulation effects (or -2.87±0.06 including solar modulation effects in the lower energy region) to -2.56±0.04 (1-10 TeV), thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ.

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TL;DR: The ability of PS-COOH NPs to interact with EPS as shown for other nanomaterials is confirmed, and altered nanoparticle surface charge and hydrodynamic diameter following algal EPS exposure is supported, supporting the hypothesis of a protein corona formation.