| 1. |
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| 2. |
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
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| 7. |
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| 8. |
- Marconi, A., et al.
(författare)
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ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
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Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
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Konferensbidrag (refereegranskat)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
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| 9. |
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| 10. |
- Marconi, Alessandro, et al.
(författare)
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ELT-HIRES, the high resolution spectrograph for the ELT : Phase A study and path to construction
- 2020
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Ingår i: Ground-based and Airborne Instrumentation for Astronomy VIII. - : SPIE - International Society for Optical Engineering. - 9781510636828 - 9781510636811
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Konferensbidrag (refereegranskat)abstract
- HIRES is the high-resolution spectrograph of the European Extremely Large Telescope at optical and near-infrared wavelengths. It consists of three fibre-fed spectrographs providing a wavelength coverage of 0.4-1.8 µm (goal 0.35-2.4 µm) at a spectral resolution of 100,000. The fibre-feeding allows HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU in the NIR. Therefore, it will be able to operate both in seeing- and diffraction-limited modes. Its modularity will ensure that HIRES can be placed entirely on the Nasmyth platform, if enough mass and volume is available, or part on the Nasmyth and part in the Coud`e room. ELT-HIRES has a wide range of science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars (PopIII), tests on the stability of Nature’s fundamental couplings, and the direct detection of the cosmic acceleration. The HIRES consortium is composed of more than 30 institutes from 14 countries, forming a team of more than 200 scientists and engineers.
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| 11. |
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| 13. |
- Adriani, O., et al.
(författare)
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Design of an Antimatter Large Acceptance Detector In Orbit (ALADInO)
- 2022
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Ingår i: Instruments. - : MDPI AG. - 2410-390X. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- A new generation magnetic spectrometer in space will open the opportunity to inves-tigate the frontiers in direct high-energy cosmic ray measurements and to precisely measure the amount of the rare antimatter component in cosmic rays beyond the reach of current missions. We propose the concept for an Antimatter Large Acceptance Detector In Orbit (ALADInO), designed to take over the legacy of direct measurements of cosmic rays in space performed by PAMELA and AMS-02. ALADInO features technological solutions conceived to overcome the current limi-tations of magnetic spectrometers in space with a layout that provides an acceptance larger than 10 m2 sr. A superconducting magnet coupled to precision tracking and time-of-flight systems can provide the required matter–antimatter separation capabilities and rigidity measurement resolution with a Maximum Detectable Rigidity better than 20 TV. The inner 3D-imaging deep calorimeter, designed to maximize the isotropic acceptance of particles, allows for the measurement of cosmic rays up to PeV energies with accurate energy resolution to precisely measure features in the cosmic ray spectra. The operations of ALADInO in the Sun–Earth L2 Lagrangian point for at least 5 years would enable unique revolutionary observations with groundbreaking discovery poten-tials in the field of astroparticle physics by precision measurements of electrons, positrons, and antiprotons up to 10 TeV and of nuclear cosmic rays up to PeV energies, and by the possible unam-biguous detection and measurement of low-energy antideuteron and antihelium components in cosmic rays.
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| 14. |
- Di Marcantonio, P., et al.
(författare)
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ANDES, the high resolution spectrograph for the ELT : project management and system engineering approaches for mastering its preliminary design phase
- 2022
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Ingår i: MODELING, SYSTEMS ENGINEERING, AND PROJECT MANAGEMENT FOR ASTRONOMY X. - : SPIE - International Society for Optical Engineering. - 9781510653566 - 9781510653559
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- At the end of 2021, the ESO council approved the start of the construction phase for a High Resolution Spectrograph for the ELT, formerly known as ELT-HIRES, renamed recently as ANDES (ArmazoNes high Dispersion Echelle Spectrograph). The current initial schedule foresees a 9-years development aimed to bring the instrument on-sky soon after the first-generation ELT instruments. ANDES combines high spectral resolution (up to 100,000), wide spectral range (0.4 mu m to 1.8 mu m with a goal from 0.35 mu m to 2.4 mu m) and extreme stability in wavelength calibration accuracy (better than 0.02 m/s rms over a 10-year period in a selected wavelength range) with massive optical collecting power of the ELT thus enabling to achieve possible breakthrough groundbreaking scientific discoveries. The main science cases cover a possible detection of life signatures in exoplanets, the study of the stability of Nature's physical constants along the universe lifetime and a first direct measurement of the cosmic acceleration. The reference design of this instrument in its extended version (with goals included) foresees 4 spectrographic modules fed by fibers, operating in seeing and diffraction limited (adaptive optics assisted) mode carried out by an international consortium composed by 24 institutes from 13 countries which poses big challenges in several areas. In this paper we will describe the approach we intend to pursue to master management and system engineering aspects of this challenging instrument focused mainly on the preliminary design phase, but looking also ahead towards its final construction.
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| 15. |
- Dorn, R. J., et al.
(författare)
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CRIRES+ on sky at the ESO Very Large Telescope : Observing the Universe at infrared wavelengths and high spectral resolution
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671
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Tidskriftsartikel (refereegranskat)abstract
- The CRyogenic InfraRed Echelle Spectrograph (CRIRES) Upgrade project CRIRES+ extended the capabilities of CRIRES. It transformed this VLT instrument into a cross-dispersed spectrograph to increase the wavelength range that is covered simultaneously by up to a factor of ten. In addition, a new detector focal plane array of three Hawaii 2RG detectors with a 5.3 mu m cutoff wavelength replaced the existing detectors. Amongst many other improvements, a new spectropolarimetric unit was added and the calibration system has been enhanced. The instrument was installed at the VLT on Unit Telescope 3 at the beginning of 2020 and successfully commissioned and verified for science operations during 2021, partly remotely from Europe due to the COVID-19 pandemic. The instrument was subsequently offered to the community from October 2021 onwards. This article describes the performance and capabilities of the upgraded instrument and presents on sky results.
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| 16. |
- Noske, G. D., et al.
(författare)
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A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process : SARS-CoV-2 Mpro maturation
- 2021
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 433:18
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous N and C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.
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| 17. |
- von Doetinchem, P., et al.
(författare)
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Cosmic-ray antinuclei as messengers of new physics : status and outlook for the new decade
- 2020
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :8
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Tidskriftsartikel (refereegranskat)abstract
- The precise measurement of cosmic-ray antinuclei serves as an important means for identifying the nature of dark matter and other new astrophysical phenomena, and could be used with other cosmic-ray species to understand cosmic-ray production and propagation in the Galaxy. For instance, low-energy antideuterons would provide a "smoking gun" signature of dark matter annihilation or decay, essentially free of astrophysical background. Studies in recent years have emphasized that models for cosmic-ray antideuterons must be considered together with the abundant cosmic antiprotons and any potential observation of antihelium. Therefore, a second dedicated Antideuteron Workshop was organized at UCLA in March 2019, bringing together a community of theorists and experimentalists to review the status of current observations of cosmic-ray antinuclei, the theoretical work towards understanding these signatures, and the potential of upcoming measurements to illuminate ongoing controversies. This review aims to synthesize this recent work and present implications for the upcoming decade of antinuclei observations and searches. This includes discussion of a possible dark matter signature in the AMS-02 antiproton spectrum, the most recent limits from BESS Polar-II on the cosmic antideuteron flux, and reports of candidate antihelium events by AMS-02; recent collider and cosmic-ray measurements relevant for antinuclei production models; the state of cosmic-ray transport models in light of AMS-02 and Voyager data; and the prospects for upcoming experiments, such as GAPS. This provides a roadmap for progress on cosmic antinuclei signatures of dark matter in the coming years.
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| 18. |
- Lensink, Marc F., et al.
(författare)
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Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
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Ingår i: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
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Tidskriftsartikel (refereegranskat)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
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| 19. |
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| 20. |
- Ramos-Michel, A., et al.
(författare)
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Improving Metaheuristic Algorithm Design Through Inequality and Diversity Analysis : A Novel Multi-Population Differential Evolution
- 2023
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Ingår i: 2023 IEEE Symposium Series on Computational Intelligence (SSCI). - : IEEE. - 9781665430654 ; , s. 1547-1552
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Konferensbidrag (refereegranskat)abstract
- In evolutionary algorithms and metaheuristics, defining when applying a specific operator is important. Besides, in complex optimization problems, multiple populations can be used to explore the search space simultaneously. However, one of the main problems is extracting information from the populations and using it to evolve the solutions. This article presents the inequality-based multi-population differential evo-lution (IMDE). This algorithm uses the K-means to generate subpopulations (settlements). Two variables are extracted from the settlements, the diversity and the Gini index, which measure the solutions' distribution and the solutions' inequality regarding fitness. The Gini index and the diversity are used in the IMDE to dynamically modify the scalation factor and the crossover rate. Experiments over a set of benchmark functions with different degrees of complexity validate the performance of the IMDE. Besides comparisons, statistical and ranking average validate the search capabilities of the IMDE.
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| 21. |
- Tristao-Pereira, C., et al.
(författare)
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Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study
- 2023
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Ingår i: Lancet Healthy Longevity. - 2666-7568. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals. Methods The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [18F]fluorodeoxyglucose ([18F]FDG)-PET, and annual percentage change in [18F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach. Findings This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49 & BULL;8 years [IQR 46 & BULL;1-52 & BULL;2]; 309 [84%] men, 61 [16%] women; median follow-up 4 & BULL;7 years [IQR 4 & BULL;2-5 & BULL;2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [18F]FDG uptake compared with low risk (& beta;=-0 & BULL;008 [95% CI -0 & BULL;013 to -0 & BULL;002]; pFDR=0 & BULL;040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (& beta;=0 & BULL;198 [0 & BULL;008 to 0 & BULL;740]; pFDR=0 & BULL;050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [18F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (& beta;=-0 & BULL;269 [95% CI -0 & BULL;509 to -0 & BULL;027]; p=0 & BULL;029). Interpretation Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life.
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| 22. |
- van Rheenen, PF, et al.
(författare)
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The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update
- 2021
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Ingår i: Journal of Crohn's & colitis. - : Oxford University Press (OUP). - 1876-4479 .- 1873-9946. ; 15:2, s. 171-194
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveWe aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn’s disease [CD].MethodsWe formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained.ResultsWe established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone.ConclusionsWe present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.
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| 23. |
- Wolzak, K., et al.
(författare)
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Protein disulfide isomerases as CSF biomarkers for the neuronal response to tau pathology
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:8, s. 3563-3574
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionCerebrospinal fluid (CSF) biomarkers for specific cellular disease processes are lacking for tauopathies. In this translational study we aimed to identify CSF biomarkers reflecting early tau pathology-associated unfolded protein response (UPR) activation. MethodsWe employed mass spectrometry proteomics and targeted immunoanalysis in a combination of biomarker discovery in primary mouse neurons in vitro and validation in patient CSF from two independent large multicentre cohorts (EMIF-AD MBD, n = 310; PRIDE, n = 771). ResultsFirst, we identify members of the protein disulfide isomerase (PDI) family in the neuronal UPR-activated secretome and validate secretion upon tau aggregation in vitro. Next, we demonstrate that PDIA1 and PDIA3 levels correlate with total- and phosphorylated-tau levels in CSF. PDIA1 levels are increased in CSF from AD patients compared to controls and patients with tau-unrelated frontotemporal and Lewy body dementia (LBD). HighlightsNeuronal unfolded protein response (UPR) activation induces the secretion of protein disulfide isomerases (PDIs) in vitro.PDIA1 is secreted upon tau aggregation in neurons in vitro.PDIA1 and PDIA3 levels correlate with total and phosphorylated tau levels in CSF.PDIA1 levels are increased in CSF from Alzheimer's disease (AD) patients compared to controls.PDIA1 levels are not increased in CSF from tau-unrelated frontotemporal dementia (FTD) and Lewy body dementia (LBD) patients.
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| 28. |
- Genoni, M., et al.
(författare)
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End to end simulators : a flexible and scalable cloud-based architecture Application to high resolution spectrographs ESPRESSO and ELT-HIRES
- 2020
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Ingår i: Experimental astronomy. - : SPRINGER. - 0922-6435 .- 1572-9508. ; 50:2-3, s. 215-232
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Tidskriftsartikel (refereegranskat)abstract
- Simulations of frames from existing and upcoming high-resolution spectrographs, targeted for high accuracy radial velocity measurements, are computationally demanding (both in time and space). We present in this paper an innovative approach based on both parallelization and distribution of the workload. By using NVIDIA CUDA custom-made kernels and state-of-the-art cloud-computing architectures in a Platform as a Service (PaaS) approach, we implemented a modular and scalable end-to-end simulator that is able to render synthetic frames with an accuracy of the order of few cm/sec, while keeping the computational time low. We applied our approach to two spectrographs. For VLT-ESPRESSO we give a sound comparison between the actual data and the simulations showing the obtained spectral formats and the recovered instrumental profile. We also simulate data for the upcoming HIRES at the ELT and investigate the overall performance in terms of computational time and scalability against the size of the problem. In addition we demonstrate the interface with data-reduction systems and we preliminary show that the data can be reduced successfully by existing methods.
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| 29. |
- Bijavara Seshashayana, Shilpa, et al.
(författare)
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Stellar Population Astrophysics (SPA) with TNG
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. The age, evolution, and chemical properties of the Galactic disk can be effectively ascertained using open clusters. Within the large program Stellar Populations Astrophysics at the Telescopio Nazionale Galileo, we specifically focused on stars in open clusters, to investigate various astrophysical topics, from the chemical content of very young systems to the abundance patterns of lesser studied intermediate-age and old open clusters.Aims. We investigate the astrophysically interesting element fluorine (F), which has an uncertain and intriguing cosmic origin. We also determine the abundance of cerium (Ce), as F abundance is expected to correlate with the s-process elements. We intend to determine the trend of F abundance across the Galactic disk as a function of metallicity and age. This will offer insights into Galactic chemical evolution models, potentially enhancing our comprehension of this element’s cosmic origin.Methods. High-resolution near-infrared spectra were obtained using the GIANO-B spectrograph. The Python version of Spectroscopy Made Easy (PySME), was used to derive atmospheric parameters and abundances. The stellar parameters were determined using OH, CN, and CO molecular lines along with Fe I lines. The F and Ce abundances were inferred using two K-band HF lines (λλ 2.28, 2.33 µm) and two atomic H-band lines (λλ 1.66, and 1.71 µm), respectively.Results. Of all the clusters in our sample, only King 11 had not been previously studied through medium- to high-resolution spectroscopy, and our stellar parameter and metallicity findings align well with those documented in the literature. We have successfully inferred F and Ce abundances in all seven open clusters and probed the radial and age distributions of abundance ratios. This paper presents the first F Galactic radial abundance gradient. Our results are also compared with literature estimates and with Galactic chemical evolution models that have been generated using different F production channels.Conclusions. Our results indicate a constant, solar pattern in the [F/Fe] ratios across clusters of different ages, supporting the latest findings that fluorine levels do not exhibit any secondary behavior for stars with solar or above-solar metallicity. However, an exception to this trend is seen in NGC 6791, a metal-rich, ancient cluster whose chemical composition is distinct due to its enhanced fluorine abundance. This anomaly strengthens the hypothesis that NGC 6791 originated in the inner regions of the Galaxy before migrating to its present position. By comparing our sample stars with the predictions of Galactic chemical evolution models, we came to the conclusion that both asymptotic giant branch stars and massive stars, including a fraction of fast rotators that increase with decreasing metallicity, are needed to explain the cosmic origin of F.
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| 30. |
- Espinosa-Oliva, Ana M., et al.
(författare)
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Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain
- 2024
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Ingår i: Neuropathology and Applied Neurobiology. - 0305-1846. ; 50:1
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Tidskriftsartikel (refereegranskat)abstract
- Aims: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. Methods: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. Results: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. Conclusion: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.
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| 31. |
- Giannetta, H. M. R., et al.
(författare)
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Study of the electrical parameters drift due to mechanical stress in coupled conductors path on flexible polymeric substrate
- 2022
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Ingår i: 2022 Argentine Conference on Electronics (CAE). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781728173351 - 9781728192659 ; , s. 37-40
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Konferensbidrag (refereegranskat)abstract
- In this work, the behavior of the drift in electrical impedance values of a coupled device constituting a flat rectangular inductor surrounded by a coupled antenna while subjected to mechanical stresses of over 10,000 bending-stretching cycles has been studied. It has shown correlation with mechanical aging and also is influenced by temperature variations on the device surface. The impact of the mechanical stress was studied separately for the bending-stretching and relaxation phases, considering in both cases the effect of temperature changes and mechanical stress, in order to obtain an adjustment equation for the measured experimental data.. From the fit, it was observed that when using an exponential function for the drift effect due to mechanical stress, the experimental curve was fitted with R-2=0.91 for the bending-stretching phase and R-2=0.79 for the relaxation phase.
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| 32. |
- Landi, Antonio, et al.
(författare)
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Antithrombotic therapy in patients with acute coronary syndrome : similarities and differences between a European expert consensus document and the 2023 European Society of Cardiology guidelines
- 2024
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Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 13:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients.
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| 33. |
- Navarese, Eliano Pio, et al.
(författare)
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Within and beyond 12-month efficacy and safety of antithrombotic strategies in patients with established coronary artery disease : two companion network meta-analyses of the 2022 joint clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute CardioVascular Care (ACVC), and European Association of Preventive Cardiology (EAPC)
- 2023
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 9:3, s. 271-290
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Tidskriftsartikel (refereegranskat)abstract
- Aims To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses. Methods and results Forty-three (N = 189 261 patients) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.49-0.88], aspirin and ticagrelor 90 mg (HR, 0.85; 95% CI, 0.76-0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR, 0.66; 95% CI, 0.51-0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality; compared with aspirin; the greatest reductions of myocardial infarction (MI) were found with aspirin and clopidogrel (HR, 0.68; 95% CI, 0.55-0.85) or P2Y(12) inhibitor monotherapy (HR, 0.76; 95% CI: 0.61-0.95), especially ticagrelor 90 mg (HR, 0.54; 95% CI, 0.32-0.92), and of stroke with VKA (HR, 0.56; 95% CI, 0.44-0.76) or aspirin and rivaroxaban 2.5 mg (HR, 0.58; 95% CI, 0.44-0.76). All treatments increased bleeding except P2Y(12) monotherapy, compared with aspirin. Conclusion Within 12 months, ticagrelor 90 mg monotherapy was the only treatment associated with lower mortality, without bleeding risk trade-off compared with aspirin and clopidogrel. Beyond 12 months, P2Y(12) monotherapy, especially ticagrelor 90 mg, was associated with lower MI without bleeding trade-off; aspirin and rivaroxaban 2.5 mg most effectively reduced stroke, with a more acceptable bleeding risk than VKA, compared with aspirin. Registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifiers: CRD42021243985 and CRD42021252398. [GRAPHICS] .
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| 34. |
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| 35. |
- Papp, Zoltan, et al.
(författare)
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Levosimendan Efficacy and Safety : 20 Years of SIMDAX in Clinical Use
- 2020
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Ingår i: Journal of Cardiovascular Pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446 .- 1533-4023. ; 76:1, s. 4-22
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
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| 36. |
- Rodríguez-Gómez, José A, et al.
(författare)
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Microglia : Agents of the CNS Pro-Inflammatory Response.
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though the research of microglia spans over a century, the last two decades have increased our understanding exponentially. Here, we discuss the phenotypic transformation from homeostatic microglia towards reactive microglia, initiated by specific ligand binding to pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering receptors expressed on myeloid cells-2 (TREM2), as well as pro-inflammatory signaling pathways triggered such as the caspase-mediated immune response. Additionally, new research disciplines such as epigenetics and immunometabolism have provided us with a more holistic view of how changes in DNA methylation, microRNAs, and the metabolome may influence the pro-inflammatory response. This review aimed to discuss our current knowledge of pro-inflammatory microglia from different angles, including recent research highlights such as the role of exosomes in spreading neuroinflammation and emerging techniques in microglia research including positron emission tomography (PET) scanning and the use of human microglia generated from induced pluripotent stem cells (iPSCs). Finally, we also discuss current thoughts on the impact of pro-inflammatory microglia in neurodegenerative diseases.
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| 37. |
- Seshashayana, S. Bijavara, et al.
(författare)
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Stellar Population Astrophysics (SPA) with TNG : Fluorine abundances in seven open clusters
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. The age, evolution, and chemical properties of the Galactic disk can be effectively ascertained using open clusters. Within the large program Stellar Populations Astrophysics at the Telescopio Nazionale Galileo, we specifically focused on stars in open clusters, to investigate various astrophysical topics, from the chemical content of very young systems to the abundance patterns of lesser studied intermediate-age and old open clusters. Aims. We investigate the astrophysically interesting element fluorine (F), which has an uncertain and intriguing cosmic origin. We also determine the abundance of cerium (Ce), as F abundance is expected to correlate with the s-process elements. We intend to determine the trend of F abundance across the Galactic disk as a function of metallicity and age. This will offer insights into Galactic chemical evolution models, potentially enhancing our comprehension of this element's cosmic origin. Methods. High-resolution near-infrared spectra were obtained using the GIANO-B spectrograph. The Python version of Spectroscopy Made Easy (PySME), was used to derive atmospheric parameters and abundances. The stellar parameters were determined using OH, CN, and CO molecular lines along with Fe I lines. The F and Ce abundances were inferred using two K-band HF lines (λλ 2.28, 2.33 μm) and two atomic H-band lines (λλ 1.66, and 1.71 μm), respectively. Results. Of all the clusters in our sample, only King 11 had not been previously studied through medium-to high-resolution spectroscopy, and our stellar parameter and metallicity findings align well with those documented in the literature. We have successfully inferred F and Ce abundances in all seven open clusters and probed the radial and age distributions of abundance ratios. This paper presents the first F Galactic radial abundance gradient. Our results are also compared with literature estimates and with Galactic chemical evolution models that have been generated using different F production channels. Conclusions. Our results indicate a constant, solar pattern in the [F/Fe] ratios across clusters of different ages, supporting the latest findings that fluorine levels do not exhibit any secondary behavior for stars with solar or above-solar metallicity. However, an exception to this trend is seen in NGC 6791, a metal-rich, ancient cluster whose chemical composition is distinct due to its enhanced fluorine abundance. This anomaly strengthens the hypothesis that NGC 6791 originated in the inner regions of the Galaxy before migrating to its present position. By comparing our sample stars with the predictions of Galactic chemical evolution models, we came to the conclusion that both asymptotic giant branch stars and massive stars, including a fraction of fast rotators that increase with decreasing metallicity, are needed to explain the cosmic origin of F.
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| 38. |
- Valgimigli, Marco, et al.
(författare)
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Antithrombotic treatment strategies in patients with established coronary atherosclerotic disease
- 2023
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 9:5, s. 462-496
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Tidskriftsartikel (refereegranskat)abstract
- Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the authors undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.
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| 39. |
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| 40. |
- Bennett, Jennifer A., et al.
(författare)
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A Distinctive Adnexal (Usually Paratubal) Neoplasm Often Associated with Peutz-Jeghers Syndrome and Characterized by STK11 Alterations (STK11 Adnexal Tumor) : A Report of 22 Cases
- 2021
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Ingår i: American Journal of Surgical Pathology. - 0147-5185. ; 45:8, s. 1061-1074
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Tidskriftsartikel (refereegranskat)abstract
- We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39 y) and the tumors from 4.5 to 25.5 cm (median=11 cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median=9/10 HPFs). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2-40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive, while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphologic, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.
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| 47. |
- Macfarlane, N. B. W., et al.
(författare)
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Direct and indirect impacts of synthetic biology on biodiversity conservation
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:11
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Tidskriftsartikel (refereegranskat)abstract
- The world's biodiversity is in crisis. Synthetic biology has the potential to transform biodiversity conservation, both directly and indirectly, in ways that are negative and positive. However, applying these biotechnology tools to environmental questions is fraught with uncertainty and could harm cultures, rights, livelihoods, and nature. Decisions about whether or not to use synthetic biology for conservation should be understood alongside the reality of ongoing biodiversity loss. In 2022, the 196 Parties to the United Nations Convention on Biological Diversity are negotiating the post-2020 Global Biodiversity Framework that will guide action by governments and other stakeholders for the next decade to conserve the worlds' biodiversity. To date, synthetic biologists, conservationists, and policy makers have operated in isolation. At this critical time, this review brings these diverse perspectives together and emerges out of the need for a balanced and inclusive examination of the potential application of these technologies to biodiversity conservation.
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| 48. |
- Maffulli, N., et al.
(författare)
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Free tendon grafts for surgical management of chronic tears of the main body of the Achilles tendon: a systematic review
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - 0942-2056. ; 31:10, s. 4526-38
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Tidskriftsartikel (refereegranskat)abstract
- PurposeAfter four weeks from injury, tears of the Achilles tendon are considered chronic. Their management is challenging, and the use of a graft is suggested when the gap between proximal and distal stumps is greater than 6 cm. The present study systematically reviews the outcome of free tendon grafts in chronic ruptures of the Achilles tendon, evaluating clinical outcomes, complications and return to sport.MethodsThe present study was conducted according to the PRISMA 2020 guidelines. PubMed, Google Scholar, Embase, and Web of Science databases were accessed in February 2023. All the published clinical studies reporting clinical outcome, return to sport and complications of free tendon grafts used the treatment of chronic rupture of the midportion of the Achilles Tendon were accessed. The mean CMS (Coleman Methodology Score) of 65.7 suggested an overall good quality of the available published articles, attesting to the low risk of bias.ResultsData from 22 articles (368 patients with a mean age of 47 years) were retrieved. The average time from rupture to surgery was 25.1 week. At last follow-up, the AOFAS (American Orthopaedic Foot and Ankle Surgery) and ATRS (Achilles Tendon Total Rupture Score) scores improved of 33.8 (P = 0.0004), and 45.1 points (P = 0.0001) respectively. Return to activity was reported in 105 patients, and 82 (78.1%) had no activity limitations, while 19 (18.1%) had limited recreational but not daily activity limitations, and 4 (3.8%) reported limitations in daily activities. Return to sport data was reported in six studies, and 45 of 93 (48.4%) patients returned to sport at an average of 22.6 weeks.ConclusionIn chronic tears of the Achilles tendon, with a gap of at least 6 cm, free tendon grafts allow predictable return to sport and acceptable recovery function.
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| 49. |
- Morales-Castañeda, Bernardo, et al.
(författare)
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A Novel Diversity-Aware Inertia Weight and Velocity Control for Particle Swarm Optimization
- 2023
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Ingår i: 2023 IEEE Congress on Evolutionary Computation (CEC). - : IEEE Press. - 9798350314588 - 9798350314588
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Konferensbidrag (refereegranskat)abstract
- Particle Swarm Optimization (PSO) has efficiently solved several real-world applications and optimization problems. However, it has shortcomings, such as premature convergence and stagnation at local minima. Inertia weight is a parameter of this algorithm that controls the global and local exploration and exploitation capability by determining the influence of the previous velocity on its current motion. Therefore, this article proposes a PSO with a Diversity-aware Inertia and Velocity Control (PSOIVC) algorithm to improve the PSO performance. The PSOIVC employs a novel diversity-aware inertia weight and velocity control approach to tune the parameters to produce a trade-off between exploration and exploitation of the algorithm using the dimension-wise diversity. The PSOIVC algorithm is compared with eight algorithms, including variants of the PSO, on a set of 30 benchmark functions for a single objective real parameter in 30 and 50 dimensions. Based on the results, the proposal presents significant outcomes according to the average values obtained for both comparisons; because it performed similarly or better than the other algorithms in 23/30 and 16/30 for 30 and 50 dimensions, respectively.
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| 50. |
- Morales-Castañeda, Bernardo, et al.
(författare)
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Improving the Convergence of the PSO Algorithm with a Stagnation Variable and Fuzzy Logic
- 2023
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Ingår i: 2023 IEEE Congress on Evolutionary Computation (CEC). - : IEEE Press. - 9798350314588 - 9798350314588
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Konferensbidrag (refereegranskat)abstract
- Particle swarm optimization (PSO) is essential to evolutionary computation algorithms (ECA). The PSO has some drawbacks as premature convergence and stagnation at local minima. Inertia weight is a parameter that controls the global and local exploration and exploitation capability in the PSO by determining the influence of the previous velocity on its current motion. This article proposes using a stagnation counter that verifies the times the PSO is stuck in the same fitness value. In the proposed fuzzy controlled PSO with stagnation coefficient (FCPSO), a fuzzy controller is designed to tune the inertia weight based on the population's diversity and the search's stagnation. This modification allows the PSO to escape from suboptimal values enhancing its search capabilities. The FCPSO is tested over 28 benchmark functions in 50 dimensions. Besides, it has been compared with nine optimization algorithms from the state-of-the-art. The experiments and comparisons suggest that the FCPSO is an interesting tool for solving complex optimization problems.
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