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| 5. |
- Panuzzo, P., et al.
(author)
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Discovery of a dormant 33 solar-mass black hole in pre-release Gaia astrometry
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 686
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Journal article (peer-reviewed)abstract
- Context. Gravitational waves from black-hole (BH) merging events have revealed a population of extra-galactic BHs residing in short-period binaries with masses that are higher than expected based on most stellar evolution models-And also higher than known stellar-origin black holes in our Galaxy. It has been proposed that those high-mass BHs are the remnants of massive metal-poor stars.Aims. Gaia astrometry is expected to uncover many Galactic wide-binary systems containing dormant BHs, which may not have been detected before. The study of this population will provide new information on the BH-mass distribution in binaries and shed light on their formation mechanisms and progenitors.Methods. As part of the validation efforts in preparation for the fourth Gaia data release (DR4), we analysed the preliminary astrometric binary solutions, obtained by the Gaia Non-Single Star pipeline, to verify their significance and to minimise false-detection rates in high-mass-function orbital solutions.Results. The astrometric binary solution of one source, Gaia BH3, implies the presence of a 32.70a ±a 0.82aM- BH in a binary system with a period of 11.6 yr. Gaia radial velocities independently validate the astrometric orbit. Broad-band photometric and spectroscopic data show that the visible component is an old, very metal-poor giant of the Galactic halo, at a distance of 590 pc.Conclusions. The BH in the Gaia BH3 system is more massive than any other Galactic stellar-origin BH known thus far. The low metallicity of the star companion supports the scenario that metal-poor massive stars are progenitors of the high-mass BHs detected by gravitational-wave telescopes. The Galactic orbit of the system and its metallicity indicate that it might belong to the Sequoia halo substructure. Alternatively, and more plausibly, it could belong to the ED-2 stream, which likely originated from a globular cluster that had been disrupted by the Milky Way.
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| 6. |
- Bousquet, Jean, et al.
(author)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Journal article (peer-reviewed)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 7. |
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| 8. |
- Bousquet, J, et al.
(author)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Journal article (peer-reviewed)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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| 9. |
- Menditto, Enrica, et al.
(author)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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In: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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Journal article (peer-reviewed)abstract
- Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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| 13. |
- Bousquet, J, et al.
(author)
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MASK 2017 : ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence.
- 2018
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In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 8
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Journal article (peer-reviewed)abstract
- mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.
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| 14. |
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| 15. |
- Cervero, A. G., et al.
(author)
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Green Wired Networks
- 2015
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In: Large-scale Distributed Systems and Energy Efficiency. - Hoboken, NJ, USA : Wiley-Blackwell. - 9781118981122 - 9781118864630 ; , s. 41-80
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Book chapter (other academic/artistic)abstract
- This chapter first highlights the significant energy consumption of existing wired communication networks. It considers various means of operating such networks more efficiently. Then, the chapter examines the components that make up a wired communications network and their differing characteristics between the access and core, as well as patterns of traffic behavior. The chapter focuses on static (network planning) and dynamic (traffic-engineering) schemes that can be used to reduce the energy consumption of networks. It also pays attention to a number of challenges/open research questions that need to be resolved before the implementation of such schemes. These include issues with migration and resilience. The chapter then deals with economic-, regulatory-, and business-related methods. Finally, it focuses on the architecture of communication networks and the corresponding relationship with energy usage.
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| 16. |
- Gurgel-Giannetti, J., et al.
(author)
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A novel complex neurological phenotype due to a homozygous mutation in FDX2
- 2018
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141, s. 2289-2298
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Journal article (peer-reviewed)abstract
- Defects in iron-sulphur [Fe-S] cluster biogenesis are increasingly recognized as causing neurological disease. Mutations in a number of genes that encode proteins involved in mitochondrial [Fe-S] protein assembly lead to complex neurological phenotypes. One class of proteins essential in the early cluster assembly are ferredoxins. FDX2 is ubiquitously expressed and is essential in the de novo formation of [2Fe-2S] clusters in humans. We describe and genetically define a novel complex neurological syndrome identified in two Brazilian families, with a novel homozygous mutation in FDX2. Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. To define the genetic aetiology, a combination of homozygosity mapping and whole exome sequencing was performed. We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. Sensory-motor axonal neuropathy led to progressive distal weakness. MRI disclosed a reversible or partially reversible leukoencephalopathy. Muscle biopsy demonstrated an unusual pattern of regional succinate dehydrogenase and cytochrome c oxidase deficiency with iron accumulation. The phenotype was mapped in both families to the same homozygous missense mutation in FDX2 (c. 431C > T, p. P144L). The deleterious effect of the mutation was validated by real-time reverse transcription polymerase chain reaction and western blot analysis, which demonstrated normal expression of FDX2 mRNA but severely reduced expression of FDX2 protein in muscle tissue. This study describes a novel complex neurological phenotype with unusual MRI and muscle biopsy features, conclusively mapped to a mutation in FDX2, which encodes a ubiquitously expressed mitochondrial ferredoxin essential for early [Fe-S] cluster biogenesis.
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| 17. |
- Müser, M. H., et al.
(author)
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Meeting the Contact-Mechanics Challenge
- 2017
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In: Tribology letters. - : Springer New York LLC. - 1023-8883 .- 1573-2711. ; 65:4
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Journal article (peer-reviewed)abstract
- This paper summarizes the submissions to a recently announced contact-mechanics modeling challenge. The task was to solve a typical, albeit mathematically fully defined problem on the adhesion between nominally flat surfaces. The surface topography of the rough, rigid substrate, the elastic properties of the indenter, as well as the short-range adhesion between indenter and substrate, were specified so that diverse quantities of interest, e.g., the distribution of interfacial stresses at a given load or the mean gap as a function of load, could be computed and compared to a reference solution. Many different solution strategies were pursued, ranging from traditional asperity-based models via Persson theory and brute-force computational approaches, to real-laboratory experiments and all-atom molecular dynamics simulations of a model, in which the original assignment was scaled down to the atomistic scale. While each submission contained satisfying answers for at least a subset of the posed questions, efficiency, versatility, and accuracy differed between methods, the more precise methods being, in general, computationally more complex. The aim of this paper is to provide both theorists and experimentalists with benchmarks to decide which method is the most appropriate for a particular application and to gauge the errors associated with each one..
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| 18. |
- Bédard, A., et al.
(author)
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Treatment of allergic rhinitis during and outside the pollen season using mobile technology : A MASK study
- 2020
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In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 10:1
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Research review (peer-reviewed)abstract
- BackgroundThe analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users.MethodsThe Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis.Results9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines.ConclusionsThis study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.
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| 19. |
- Bousquet, Jean, et al.
(author)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Research review (peer-reviewed)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 20. |
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| 21. |
- Ardighieri, L, et al.
(author)
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Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
- 2021
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In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 690201-
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Journal article (peer-reviewed)abstract
- Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.
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| 22. |
- Bacalini, MG, et al.
(author)
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Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer's disease and longevity in an Italian population
- 2022
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In: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 44:2, s. 881-896
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Journal article (peer-reviewed)abstract
- Many physiological processes in the human body follow a 24-h circadian rhythm controlled by the circadian clock system. Light, sensed by retina, is the predominant “zeitgeber” able to synchronize the circadian rhythms to the light-dark cycles. Circadian rhythm dysfunction and sleep disorders have been associated with aging and neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In the present study, we aimed at investigating the genetic variability of clock genes in AD patients compared to healthy controls from Italy. We also included a group of Italian centenarians, considered as super-controls in association studies given their extreme phenotype of successful aging. We analyzed the exon sequences of eighty-four genes related to circadian rhythms, and the most significant variants identified in this first discovery phase were further assessed in a larger independent cohort of AD patients by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The results identified a significant association between the rs3027178 polymorphism in the PER1 circadian gene with AD, the G allele being protective for AD. Interestingly, rs3027178 showed similar genotypic frequencies among AD patients and centenarians. These results collectively underline the relevance of circadian dysfunction in the predisposition to AD and contribute to the discussion on the role of the relationship between the genetics of age-related diseases and of longevity.
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| 23. |
- Bousquet, J. Jean, et al.
(author)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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In: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
-
Research review (peer-reviewed)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 24. |
- Codenotti, S, et al.
(author)
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Hyperactive Akt1 Signaling Increases Tumor Progression and DNA Repair in Embryonal Rhabdomyosarcoma RD Line and Confers Susceptibility to Glycolysis and Mevalonate Pathway Inhibitors
- 2022
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In: Cells. - : MDPI AG. - 2073-4409. ; 11:18
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Journal article (peer-reviewed)abstract
- In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling.
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| 25. |
- Esposito, B., et al.
(author)
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Progress of Design and Development for the ITER Radial Neutron Camera
- 2022
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In: Journal of fusion energy. - : Springer. - 0164-0313 .- 1572-9591. ; 41:2
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Journal article (peer-reviewed)abstract
- The paper presents an overview of the design status of the Radial Neutron Camera (RNC), that, together with the Vertical Neutron Camera, will provide, through reconstruction techniques applied to the measured line-integrated neutron fluxes, the time resolved measurement of the ITER neutron and alpha-source profile (i.e. neutron emissivity, neutrons emitted per unit time and volume). The RNC is composed of two subsystems, the In-Port RNC and Ex-Port RNC located, respectively, inside and outside the Plug of Equatorial Port #01. The In-Port subsystem is in a more advanced design stage since it has recently undergone the Final Design Review in the ITER procurement process. The paper describes the diagnostic layout, the interfaces, the measurement capabilities and the main challenges in its realization. Prototyping and testing of neutron detectors and electronics components were carried out and led to the choice of the component solutions that can match the environmental and operational constraints in terms radiation hardness, high temperature and electromagnetic compatibility. The performance of the RNC in terms of neutron emissivity measurement capability was assessed through 1D and 2D reconstruction analysis. It is proven that the neutron emissivity can be reconstructed in real-time within the measurement requirements: 10% accuracy, 10 ms time resolution and a/10 (a = plasma minor radius) space resolution.
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| 26. |
- Fiorani, Matteo, et al.
(author)
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On the design of 5G transport networks
- 2015
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In: Photonic network communications. - : Springer-Verlag New York. - 1387-974X .- 1572-8188. ; 30:3, s. 403-415
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Journal article (peer-reviewed)abstract
- Future 5G systems will pave the way to a completely new societal paradigm where access to information will be available anywhere, anytime, and to anyone or anything. Most of the ongoing research and debate around 5G systems are focusing on the radio network segment (e.g., how to offer high peak-rates per subscriber, and how to handle a very large number of simultaneously connected devices without compromising on coverage, outage probability, and latency). On the other hand, understanding the impact that 5G systems will have on the transport network (i.e., the segment in charge of the backhaul of radio base stations and/or the fronthaul of remote radio units) is also very important. This paper provides an analysis of the key architectural challenges for the design of a flexible 5G transport infrastructure able to adapt in a cost-efficient way to the plethora of requirements coming from the large number of envisioned future 5G services.
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| 27. |
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| 28. |
- Guerzoni, R., et al.
(author)
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Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures : An architectural survey
- 2017
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In: Transactions on Emerging Telecommunications Technologies. - : Wiley-Blackwell. - 2161-5748 .- 2161-3915. ; 28:4
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Journal article (peer-reviewed)abstract
- Over the last couple of years, industry operators' associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This article provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi-operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisation.
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| 29. |
- Mandelli, GE, et al.
(author)
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Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer
- 2020
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In: Cells. - : MDPI AG. - 2073-4409. ; 9:2
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Journal article (peer-reviewed)abstract
- Background: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy. Methods: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b+ tumor-associated-neutrophils (TAN) and CD3+ T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed. Results: Basal type BC contained a significantly higher density of CD66b+ TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T cells and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model. Conclusions: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.
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| 30. |
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| 31. |
- Natalino, Carlos, et al.
(author)
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Optimal lifetime-aware operation of green optical backbone networks
- 2016
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In: IEEE Journal on Selected Areas in Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0733-8716 .- 1558-0008. ; 34:12, s. 3915-3926
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Journal article (peer-reviewed)abstract
- This paper targets the lifetime-aware management of a set of optical line amplifiers (OLAs) in an optical network exploiting sleep mode (SM) in order to save energy. We first present a simple model to predict the OLA lifetime. We then provide different mixed-integer linear programming (MILP) formulations, which jointly consider energy saving and lifetime. The proposed MILP formulations are then solved on different realistic scenarios, by taking into account the spatial and temporal variations of traffic demands. Results show that our lifetime-aware approach outperforms classical energy saving ILP formulations, which instead tend to notably decrease the OLA lifetime. More important, the proposed approaches can achieve a good lifetime performance without consuming significantly more energy than purely energy-aware strategies.
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| 32. |
- Ravaioli, F, et al.
(author)
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DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome
- 2022
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In: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 13, s. 792165-
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Journal article (peer-reviewed)abstract
- Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome.
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| 33. |
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| 35. |
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| 36. |
- Araujo, Igor M., et al.
(author)
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Availability-Guaranteed Service Function Chain Provisioning with Optional Shared Backups
- 2020
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In: 2020 16TH INTERNATIONAL CONFERENCE ON THE DESIGN OF RELIABLE COMMUNICATION NETWORKS DRCN 2020. - : IEEE.
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Conference paper (peer-reviewed)abstract
- The dynamic provisioning of Service Function Chain (SFC) using Virtual Network Functions (VNFs) is a challenging problem, especially for availability-constrained services. The provisioning of backup resources is often used to ensure that availability requirements are fulfilled. However, the assignment of backup resources should be carefully designed to avoid resource inefficiencies as much as possible. This paper proposes the Optional Backup with Shared Path and Shared Function (OBSPSF) strategy, which aims at improving resource efficiency while fulfilling the availability requirements of SFC requests. The strategy uses optional backup provisioning to ensure that backup resources are assigned only when strictly needed (i.e., when the SFC alone does not meet the availability constraint). Moreover, OBSPSF encourages backup sharing (among both connectivity and backup VNFs) to reduce the backup resource overhead. Results show that the strategy can accommodate orders-of-magnitude more services than benchmark heuristics from the literature.
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| 37. |
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| 38. |
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| 39. |
- Brandt, L., et al.
(author)
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Uptake of thymidine in lymphoma cells obtained through fine-needle aspiration biopsy. Relation to prognosis in non-hodgkin's lymphomas
- 1981
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In: European Journal of Cancer and Clinical Oncology. - 0277-5379. ; 17:11, s. 1229-1233
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Journal article (peer-reviewed)abstract
- In vitro uptake of tritiated thymidine was studied in autoradiographic preparations of lymphoma cell suspensions obtained through fine-needle aspiration biopsy from 28 patients with non-Hodgkin's lymphoma. The labelling indices (LI ) were highest in patients with histiocytic or poorly differentiated lymphocytic lymphoma. During a two-year period there was a significant correlation between LI and survival, i.e., high LI were associated with a poor prognosis. The results indicate that, in addition to morphology, estimation of the proliferative activity of lymphoma cells may be of clinical significance. © 1981, Pergamon Press Ltd.. All rights reserved.
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| 40. |
- Cardoso, Evelin, et al.
(author)
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A Heuristic Approach for the Design of UAV-Based Disaster Relief in Optical Metro Networks
- 2020
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In: International Conference on Transparent Optical Networks. - 2162-7339. - 9781728184234 ; 2020-July, s. 1-5
-
Conference paper (peer-reviewed)abstract
- We propose a novel algorithm to dimension the backup elements in an optical metro network, by considering the adoption of Unmanned Aerial Vehicles (UAVs) and wireless interfaces to realize backup wireless links. Our key idea is to efficiently find the set of node pairs that have to be connected by means of multi-hop UAV-based wireless links, which are selected based on the simulation of multiple disaster events. Results, obtained over a set of meaningful scenarios, demonstrate that our solution can greatly reduce the total installation costs compared to a naive approach, which is instead solely tailored to the restoration of the disrupted links in a given disaster scenario.
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| 41. |
- Cavdar, Cicek, et al.
(author)
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Design of green optical networks with signal quality guarantee
- 2012
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In: IEEE International Conference on Communications. - : IEEE. - 9781457720529 ; , s. 3025-3030
-
Conference paper (peer-reviewed)abstract
- Energy consumption of communication networks is growing very fast due to the rapidly increasing traffic demand. Consequently, design of green communication networks gained a lot of attention. In this paper we focus on optical Wavelength Division Multiplexing (WDM) networks, able to support this growing traffic demand. Several energy-aware routing and wavelength assignment (EA-RWA) techniques have been proposed for WDM networks in order to minimize their operational cost. These techniques aim at minimizing the number of active links by packing the traffic as much as possible, thus avoiding the use of lightly loaded links. As a result, EA-RWA techniques may lead to longer routes and to a high utilization on some specific links. This has a detrimental effect on the signal quality of the optical connections, i.e., lightpaths. In this study we quantify the impact of power consumption minimization on the optical signal quality. and address this problem by proposing a combined impairment and energy-aware RWA (IEA-RWA) approach. Towards this goal we developed a complete mathematical model that incorporates both linear and non-linear physical impairments together with an energy efficiency objective. The IEA-RWA problem is formulized as a Mixed Integer Linear Programming (MILP) model where both energy efficiency and signal quality considerations are jointly optimized. By comparing the proposed IEA-RWA approach with existing RWA (IA-RWA and EA-RWA) schemes, we demonstrate that our solution allows for a reduction of energy consumption close to the one obtained by EA-RWA approaches, while still guaranteeing a sufficient level of the optical signal quality.
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| 42. |
- Chiaraviglio, L., et al.
(author)
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Impact of energy-efficient techniques on a device lifetime
- 2014
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In: 2014 IEEE Online Conference on Green Communications, OnlineGreenComm 2014. - : IEEE conference proceedings. - 9781479973842
-
Conference paper (peer-reviewed)abstract
- This paper focuses on the impact that energyefficient techniques have on the component lifetime in optical backbone networks. The study presented in the paper considers in particular the influence that green routing strategies have on the failure rate of Erbium Doped Fiber Amplifiers (EDFAs), i.e., if their lifetime is positively or negatively impacted when putting them into sleep mode in order to reduce their energy consumption. To this end, the paper proposes a model that estimates the failure rate acceleration factor as a function of: (i) for how long and how frequently a device is switched into sleep mode, and (ii) hardware parameters that characterize the device. The proposed model is then evaluated by considering an energyefficient Routing and Wavelength Assignment (RWA) strategy that targets saving energy by putting EDFAs into sleep mode. The results presented in the paper show that energy-efficient techniques may have the potential to lower the failure rate of EDFAs. However, this is true only under specific conditions, i.e., an energy-efficient strategy needs to be carefully planned in order to avoid frequent power state transitions, which result in shortening the lifetime of an EDFA.
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| 43. |
- Chiaraviglio, L., et al.
(author)
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Towards sustainable and reliable networks with LIFETEL
- 2015
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In: Proceedings - IEEE INFOCOM. - : IEEE conference proceedings. - 9781467371315 ; , s. 39-40
-
Conference paper (peer-reviewed)abstract
- We present the LIFETEL project, whose aim is trying to increase the device lifetime in telecommunication networks by exploiting energy-efficient techniques. In particular, we show that the lifetime of a device might increase when it is put in sleep mode. However, the device lifetime might decrease when power state variations (from sleep mode to full power) occur very frequently. Thus, there is a trade-off between the duration of sleep mode and its frequency. Moreover, we report a lifetime analysis for cellular and backbone devices, showing that the electricity saving may be exceeded by the costs due to the fact that devices fail more frequently compared to the situation in which they are always powered on. Thus, we claim that energy-aware network algorithms should be redesigned in order not to impact and to increase (when possible) the lifetime of network devices.
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| 44. |
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| 45. |
- D'Assante, R., et al.
(author)
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Myocardial expression of somatotropic axis, adrenergic signalling, and calcium handling genes in heart failure with preserved ejection fraction and heart failure with reduced ejection fraction
- 2021
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:2, s. 1681-1686
-
Journal article (peer-reviewed)abstract
- Aims Limited data are available regarding cardiac expression of molecules involved in heart failure (HF) pathophysiology. The majority of the studies have focused on end-stage HF with reduced ejection fraction (HFrEF) without comparison with healthy subjects, while no data are available with regard to HF with preserved ejection fraction (HFpEF). HFpEF is a condition whose multiple pathophysiological mechanisms are still not fully defined, with many proposed hypotheses remaining speculative due to limited access to human heart tissue. This study aimed at evaluating cardiac expression levels of key genes of interest in human biopsy samples from patients affected with HFrEF and HFpEF in order to possibly point out distinct phenotypes. Methods and results Total RNA was extracted from left ventricular cardiac biopsies collected from stable patients with HFrEF (n = 6) and HFpEF (n = 7) and healthy subjects (n = 9) undergoing elective cardiac surgery for valvular replacement, mitral valvuloplasty, aortic surgery, or coronary artery bypass. Real-time PCR was performed to evaluate the mRNA expression levels of genes involved in somatotropic axis regulation [IGF-1, IGF-1 receptor (IGF-1R), and GH receptor (GHR)], in adrenergic signalling (GRK2, GRK5, ADRB1, and ADRB2), in myocardial calcium handling (SERCA2), and in TNF-alpha. Patients with HFrEF and HFpEF showed reduced serum IGF-1 circulating levels when compared with controls (102 +/- 35.6, 138 +/- 11.5, and 160 +/- 13.2 ng/mL, P < 0.001, respectively). At myocardial level, HFrEF showed significant decreased GHR and increased IGF-1R expressions when compared with HFpEF and controls (0.54 +/- 0.27, 0.94 +/- 0.25, and 0.84 +/- 0.2, P < 0.05 and 1.52 +/- 0.9, 1.06 +/- 0.21, and 0.72 +/- 0.12, P < 0.05, respectively), while no differences in the local expression of IGF-1 mRNA were detected among the groups (0.80 +/- 0.45, 0.97 +/- 0.18, and 0.63 +/- 0.23, P = 0.09, respectively). With regard to calcium handling and adrenergic signalling, HFrEF displayed significant decreased levels of SERCA2 (0.19 +/- 0.39, 0.82 +/- 0.15, and 0.87 +/- 0.32, P < 0.01) and increased levels of GRK2 (3.45 +/- 2.94, 0.93 +/- 0.12, and 0.80 +/- 0.14, P < 0.01) and GRK5 (1.32 +/- 0.70, 0.71 +/- 0.14, and 0.77 +/- 0.15, P < 0.05), while no significant difference was found in ADRB1 (0.66 +/- 0.4, 0.83 +/- 0.3, and 0.86 +/- 0.4) and ADRB2 mRNA expression (0.65 +/- 0.3, 0.66 +/- 0.2, and 0.68 +/- 0.1) when compared with HFpEF and controls. Finally, no changes in the local expression of TNF-alpha were detected among groups. Conclusions Heart failure with reduced ejection fraction and HFpEF patients with stable clinical condition display a distinct molecular milieu of genes involved in somatotropic axis regulation, calcium handling, and adrenergic derangement at a myocardial level. The unique opportunity to compare these results with a control group, as reference population, may contribute to better understand HF pathophysiology and to identify novel potential therapeutic targets that could be modulated to improve ventricular function in patients with HF.
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| 46. |
- Dec, E, et al.
(author)
-
Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity
- 2023
-
In: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715.
-
Journal article (peer-reviewed)abstract
- Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated (r = 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.
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| 47. |
- Dec, E, et al.
(author)
-
Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity
- 2023
-
In: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 45:43, s. 1817-1835
-
Journal article (peer-reviewed)abstract
- Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated (r = 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.
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| 48. |
- Fernandes, Andre L.P., et al.
(author)
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A Cost Assessment Methodology for User-Centric Distributed Massive MIMO Architectures
- 2024
-
In: IEEE Open Journal of the Communications Society. - 2644-125X. ; 5, s. 3517-3543
-
Journal article (peer-reviewed)abstract
- User-centric (UC) distributed massive multiple-input multiple-output (D-mMIMO), also known as cell-free mMIMO, is a pivotal technology for enabling future mobile communication systems. While UC D-mMIMO intrinsically follows a distributed architecture, its processing can be implemented in a distributed or centralized fashion. This paper proposes a comprehensive cost assessment methodology for UC D-mMIMO, capturing its total cost of ownership and factoring in the deployment configuration, processing implementation, computational demands, and fronthaul signaling. The methodology considers two transmission reception point (TRP) deployment strategies. The first focuses only on supporting user equipment (UE) demands, while the other fulfills these requirements and also actively strives to provide a fairer service among UEs. The proposed methodology is then used to perform a techno-economic assessment of the feasibility of centralized versus distributed processing functional splits while varying key costs and TRP capabilities, like antenna and served UE count. Results suggest that with the TRP deployment that only supports the required UE rate, distributed processing is usually the most feasible option for UE demands of up to 50 Mbps, and centralized processing is more cost-effective in other cases. Additionally, when considering the actively fairer TRP deployment, centralized processing becomes cheaper for any UE demands.
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| 49. |
- Fiorani, Matteo, 1984-, et al.
(author)
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Energy performance of C-RAN with 5G-NX radio networks and optical transport
- 2016
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In: 2016 IEEE International Conference on Communications, ICC 2016. - : IEEE conference proceedings. - 9781479966646
-
Conference paper (peer-reviewed)abstract
- Each mobile network architecture able to meet the traffic requirements of future 5G services comes with its own set of benefits vs. requirements for the radio and the transport segments. This paper focuses on the energy performance of four mobile network architectures, each one with different splitting options for the baseband processing functions. The radio segment under exam is based on a new radio access technology referred to as 5G-NX, while the transport segment is based on wavelength division multiplexing (WDM). The energy consumption of each mobile network architecture is weighted against (i) the benefits for the radio segment as a function of the level of centralization of the baseband processing resources and (ii) the required transport capacity and consequently the power consumption levels needed to accommodate the backhaul, midhaul, and/or fronthaul traffic generated at each base station. Our results show that a fully centralized radio access network (C-RAN) with centralization of all the baseband functions is not a practical approach for 5G mobile networks, while a partially centralized C-RAN architecture in which the physical layer baseband processing is performed at the base station site represents a promising solution.
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| 50. |
- Gauld, Jethro G., et al.
(author)
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Hotspots in the grid : Avian sensitivity and vulnerability to collision risk from energy infrastructure interactions in Europe and North Africa
- 2022
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In: Journal of Applied Ecology. - : John Wiley & Sons. - 0021-8901 .- 1365-2664. ; 59:6, s. 1496-1512
-
Journal article (peer-reviewed)abstract
- Wind turbines and power lines can cause bird mortality due to collision or electrocution. The biodiversity impacts of energy infrastructure (EI) can be minimised through effective landscape-scale planning and mitigation. The identification of high-vulnerability areas is urgently needed to assess potential cumulative impacts of EI while supporting the transition to zero carbon energy. We collected GPS location data from 1,454 birds from 27 species susceptible to collision within Europe and North Africa and identified areas where tracked birds are most at risk of colliding with existing EI. Sensitivity to EI development was estimated for wind turbines and power lines by calculating the proportion of GPS flight locations at heights where birds were at risk of collision and accounting for species' specific susceptibility to collision. We mapped the maximum collision sensitivity value obtained across all species, in each 5 x 5 km grid cell, across Europe and North Africa. Vulnerability to collision was obtained by overlaying the sensitivity surfaces with density of wind turbines and transmission power lines. Results: Exposure to risk varied across the 27 species, with some species flying consistently at heights where they risk collision. For areas with sufficient tracking data within Europe and North Africa, 13.6% of the area was classified as high sensitivity to wind turbines and 9.4% was classified as high sensitivity to transmission power lines. Sensitive areas were concentrated within important migratory corridors and along coastlines. Hotspots of vulnerability to collision with wind turbines and transmission power lines (2018 data) were scattered across the study region with highest concentrations occurring in central Europe, near the strait of Gibraltar and the Bosporus in Turkey. Synthesis and applications. We identify the areas of Europe and North Africa that are most sensitive for the specific populations of birds for which sufficient GPS tracking data at high spatial resolution were available. We also map vulnerability hotspots where mitigation at existing EI should be prioritised to reduce collision risks. As tracking data availability improves our method could be applied to more species and areas to help reduce bird-EI conflicts.
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