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- 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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- 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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- 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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- 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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- 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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15. |
- 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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16. |
- 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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17. |
- 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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18. |
- 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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- Sørensen, Lasse K., et al.
(author)
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Thermal degradation of optical resonances in plasmonic nanoparticles
- 2022
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 14:2, s. 433-447
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Journal article (peer-reviewed)abstract
- The dependence of plasmon resonance excitations in ultrafine (3-7 nm) gold nanoparticles on heating and melting is investigated. An integrated approach is adopted, where molecular dynamics simulations of the spatial and temporal development of the atoms constituting the nanoparticles generate trajectories out of which system conformations are sampled and extracted for calculations of plasmonic excitation cross sections which then are averaged over the sample configurations for the final result. The calculations of the plasmonic excitations, which take into account the temperature- and size-dependent relaxation of the plasmons, are carried out with a newly developed Extended Discrete Interaction Model (Ex-DIM) and complemented by multilayered Mie theory. The integrated approach clearly demonstrates the conditions for suppression of the plasmons starting at temperatures well below the melting point. We have found a strong inhomogeneous dependence of the atom mobility in the particle crystal lattice increasing from the center to its surface upon the temperature growth. The plasmon resonance suppression is associated with an increase of the mobility and in the amplitude of phonon vibrations of the lattice atoms accompanied by electron-phonon scattering. This leads to an increase in the relaxation constant impeding the plasmon excitation as the major source of the suppression, while the direct contribution from the increase in the lattice constant and its chaotization at melting is found to be minor. Experimental verification of the suppression of surface plasmon resonance is demonstrated for gold nanoparticles on a quartz substrate heated up to the melting temperature and above.
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- 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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- Sperduti, Andrea, et al.
(author)
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Results of the first user program on the HOmogeneous Thermal NEutron Source HOTNES (ENEA/INFN)
- 2017
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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Journal article (peer-reviewed)abstract
- The HOmogeneous Thermal NEutron Source (HOTNES) is a new type of thermal neutron irradiation assembly developed by the ENEA-INFN collaboration. The facility is fully characterized in terms of neutron field and dosimetric quantities, by either computational and experimental methods. This paper reports the results of the first "HOTNES users program", carried out in 2016, and covering a variety of thermal neutron active detectors such as scintillators, solid-state, single crystal diamond and gaseous detectors.
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25. |
- 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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- 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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- 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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29. |
- 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
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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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32. |
- Gensous, N, et al.
(author)
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A Targeted Epigenetic Clock for the Prediction of Biological Age
- 2022
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In: Cells. - : MDPI AG. - 2073-4409. ; 11:24
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Journal article (peer-reviewed)abstract
- Epigenetic clocks were initially developed to track chronological age, but accumulating evidence indicates that they can also predict biological age. They are usually based on the analysis of DNA methylation by genome-wide methods, but targeted approaches, based on the assessment of a small number of CpG sites, are advisable in several settings. In this study, we developed a targeted epigenetic clock purposely optimized for the measurement of biological age. The clock includes six genomic regions mapping in ELOVL2, NHLRC1, AIM2, EDARADD, SIRT7 and TFAP2E genes, selected from a re-analysis of existing microarray data, whose DNA methylation is measured by EpiTYPER assay. In healthy subjects (n = 278), epigenetic age calculated using the targeted clock was highly correlated with chronological age (Spearman correlation = 0.89). Most importantly, and in agreement with previous results from genome-wide clocks, epigenetic age was significantly higher and lower than expected in models of increased (persons with Down syndrome, n = 62) and decreased (centenarians, n = 106; centenarians’ offspring, n = 143; nutritional intervention in elderly, n = 233) biological age, respectively. These results support the potential of our targeted epigenetic clock as a new marker of biological age and open its evaluation in large cohorts to further promote the assessment of biological age in healthcare practice.
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34. |
- Kandoth, N., et al.
(author)
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Two-photon fluorescence imaging and bimodal phototherapy of epidermal cancer cells with biocompatible self-assembled polymer nanoparticles
- 2014
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 15:5, s. 1768-1776
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Journal article (peer-reviewed)abstract
- We have developed herein an engineered polymer-based nanoplatform showing the convergence of two-photon fluorescence imaging and bimodal phototherapeutic activity in a single nanostructure. It was achieved through the appropriate choice of three different components: a β-cyclodextrin-based polymer acting as a suitable carrier, a zinc phthalocyanine emitting red fluorescence simultaneously as being a singlet oxygen (1O2) photosensitizer, and a tailored nitroaniline derivative, functioning as a nitric oxide (NO) photodonor. The self-assembly of these components results in photoactivable nanoparticles, approximately 35 nm in diameter, coencapsulating a multifunctional cargo, which can be delivered to carcinoma cells. The combination of steady-state and time-resolved spectroscopic and photochemical techniques shows that the two photoresponsive guests do not interfere with each other while being enclosed in their supramolecular container and can thus be operated in parallel under control of light stimuli. Specifically, two-photon fluorescence microscopy allows mapping of the nanoassembly, here applied to epidermal cancer cells. By detecting the red emission from the phthalocyanine fluorophore it was also possible to investigate the tissue distribution after topical delivery onto human skin ex vivo. Irradiation of the nanoassembly with visible light triggers the simultaneous delivery of cytotoxic 1O 2 and NO, resulting in an amplified cell photomortality due to a combinatory effect of the two cytotoxic agents. The potential of dual therapeutic photodynamic action and two-photon fluorescence imaging capability in a single nanostructure make this system an appealing candidate for further studies in biomedical research. © 2014 American Chemical Society.
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35. |
- Kilper, Dan, et al.
(author)
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INGR Roadmap
- 2022
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In: Proceedings - 2022 IEEE Future Networks World Forum, FNWF 2022.
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Conference paper (peer-reviewed)abstract
- Optical networks have long played a central role in telecommunication networks, forming the fiber backbone of the Internet. Over time fiber optic systems have evolved and found deployment increasingly closer to the network edge. Today, optical systems extend to the server network interface cards and home access networks. New application areas have emerged such as the use of free space communications using LiFi technologies, space communication networks between satellites and ground stations. Looking ahead, optical systems in many areas will continue to be driven by the need for higher speeds and capacity in order to keep up with traffic demands. In addition to faster interfaces speeds, parallel fiber or spatial division multiplexing will be used for future capacity growth. In several application areas, new functionality is expected such as low latency in Xhaul networks and optical switching and co-packaged optics in data centers. LiFi will become critical for mitigating RF interference for in-building networks. Intense research is underway to develop quantum networks to connect quantum computers. This general trend toward new functionalities for optical systems, moving beyond capacity growth in fiber networks, is driven in large part by the increasing performance and demands of today's user equipment and applications. From the network edge to the data centers, components are reliant on optics. The integration of optics into these new applications and the higher levels of functionality demanded of optics motivate the use of roadmaps to guide research and development and overcome future roadblocks.
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36. |
- Kilper, Dan, et al.
(author)
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Optics
- 2023
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In: Proceedings - 2023 IEEE Future Networks World Forum: Future Networks: Imagining the Network of the Future, FNWF 2023.
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Conference paper (peer-reviewed)abstract
- Optical networks have long played a central role in telecommunication networks, forming the fiber backbone of the internet. Over time, fiber optic systems have evolved and found deployment increasingly closer to the network edge. Today, optical systems extend to the server network interface cards and home access networks. New application areas have emerged, such as the use of free space communications using LiFi technologies, space communication networks between satellites, and ground stations. Looking ahead, optical systems in many areas will continue to be driven by the need for higher speeds and capacity to keep up with traffic demands. In addition to faster interface speeds, parallel fibers or spatial division multiplexing will be used for future capacity growth. In several application areas, new functionality is expected, such as low latency in XHaul networks and optical switching and co-packaged optics in data centers. LiFi will become critical for mitigating RF interference for in-building networks. Intense research is underway to develop quantum networks to connect quantum computers. This general trend toward new functionalities for optical systems, moving beyond capacity growth in fiber networks, is driven in large part by the increasing performance and demands of today's user equipment and applications. From the network edge to the data centers, components are reliant on optics. However, many of these developments are occurring quite independently and this situation carries the risk of creating problems down the road when eventually all of these components need to be seamlessly connected to maximaze efficiency. Therefore, integration of optics into these new applications and the higher levels of functionality demanded of optics motivate the use of roadmaps to guide research and development to overcome future roadblocks.
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37. |
- 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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38. |
- 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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39. |
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40. |
- Abeywickrama, S., et al.
(author)
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Dual-homing based protection for enhanced network availability and resource efficiency
- 2014
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In: Asia Communications and Photonics Conference, ACP. - Washington, D.C. : Optica Publishing Group.
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Conference paper (peer-reviewed)abstract
- An approach to enhance core network survivability by utilizing dual-homing capabilities of the access network. Results reveal significant improvements in core network resource utilization and connection availability, suggesting benefits to network operators and service providers.
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41. |
- Abeywickrama, S., et al.
(author)
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Energy-efficient survivability for core networks using dual-homing
- 2015
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In: Asia Communications and Photonics Conference, ACPC 2015. - Washington, D.C. : OSA. - 9781943580064
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Conference paper (peer-reviewed)abstract
- This paper studies the energy efficiency of exploiting dual-homing in access network to provide core network survivability. Simulation results show reduced number of utilized wavelengths, suggesting significant energy saving opportunities in the core network.
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42. |
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43. |
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44. |
- Carravetta, V., et al.
(author)
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PH-dependent X-ray Photoelectron Chemical Shifts and Surface Distribution of Cysteine in Aqueous Solution
- 2019
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 123:17, s. 3776-3785
-
Journal article (peer-reviewed)abstract
- The distribution and protonation states of amino acids in water droplets are of considerable concern in studies on the formation of clouds in the atmosphere as well as in many biological contexts. In the present work we use the amino acid cysteine as a prototypical example and explore the protonation states of this molecule in aqueous solution, which are strongly affected by the acidity of the environment and also can show different distributions between surface and bulk. We use a combination of X-ray photoelectron chemical shift measurements, density functional theory calculations of the shifts, and reactive force field molecular dynamics simulations of the underlying structural dynamics. We explore how the photoelectron spectra distinctly reflect the different protonation states that are generated by variation of the solution acidity and how the distribution of these protonation states can differ between bulk and surface regions. At specific pH values, we find that the distribution of the cysteine species at the surface is quite different from that in bulk, in particular, for the appearance in the surface region of species which do not exist in bulk. Some ramifications of this finding are discussed.
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45. |
- 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
-
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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46. |
- Dec, E, et al.
(author)
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Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity
- 2023
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In: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715.
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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)
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Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity
- 2023
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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. |
- Farias, Fabricio S., et al.
(author)
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Green backhauling for heterogeneous mobile access networks : What are the challenges?
- 2013
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In: 2013 9th International Conference on Information, Communications and Signal Processing (ICICS). - : IEEE Computer Society. - 9781479904334 ; , s. 6782868-
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Conference paper (peer-reviewed)abstract
- Heterogeneous network (HetNet) deployment strategies have the potential to improve the energy efficiency of mobile access networks. One key aspect to consider in HetNets is the impact of the power consumption of the backhaul, i.e., the overall energy efficiency of a HetNet deployment is affected by the backhaul technology and architecture. This paper presents a preliminary assessment of the design challenges of a future green backhaul segment for a HetNet deployment. The study is based on the analysis of the medium term future outlook (i.e., between now and the year 2025) of the main technologies used in todays'* backhaul networks (i.e., fiber, microwave and copper). It can be concluded that, even if there arc no doubts that both microwave and fiber will be predominately used in the future, the possible migration paths leading to such fiber- and microwave-dominated scenarios might be different, depending on factors such as spectrum and license costs, time to deployment, availability of equipment, and required Quality of Service (QoS) levels.
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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. |
- Fiorani, Matteo, et al.
(author)
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Joint Design of Radio and Transport for Green Residential Access 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. ; 34:4, s. 812-822
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Journal article (peer-reviewed)abstract
- d Mobile networks are the largest contributor to the carbon footprint of the telecom sector and their contribution is expected to rapidly increase in the future due to the foreseen traffic growth. Therefore, there is an increasing urgency in the definition of green mobile network deployment strategies. This paper proposes a four-step design and power assessment methodology for mobile networks, taking into consideration both radio and transport segments. A number of mobile network deployment architectures for urban residential areas based on different radio (i.e., macro base station, distributed indoor radio, femto cell) and transport (i.e., microwave, copper, optical fiber) technologies are proposed and evaluated to identify the most energy efficient solution. The results show that with low traffic the conventional macro base station deployment with microwave based backhaul is the best option. However, with higher traffic values heterogeneous networks withmacro base stations and indoor small cells are more energy efficient. The best small cell solution highly depends on the transport network architecture. In particular, our results show that a femto cell based deployment with optical fiber backhaul is the most energy efficient, even if a distributed indoor radio architecture (DRA) deployment with fiber fronthaul is also a competitive approach.
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