| 1. |
- Walker, Anthony P, et al.
(författare)
-
Horizon 2020 EuPRAXIA design study
- 2017
-
Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 874:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020.
|
|
| 2. |
- Botticella, M. T., et al.
(författare)
-
Supernova rates from the SUDARE VST-omegacam search II. Rates in a galaxy sample
- 2017
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 598
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. This is the second paper of a series in which we present measurements of the supernova (SN) rates from the SUDARE survey. The aim of this survey is to constrain the core collapse (CC) and Type Ia SN progenitors by analysing the dependence of their explosion rate on the properties of the parent stellar population averaging over a population of galaxies with different ages in a cosmic volume and in a galaxy sample. In this paper, we study the trend of the SN rates with the intrinsic colours, the star formation activity and the masses of the parent galaxies. To constrain the SN progenitors we compare the observed rates with model predictions assuming four progenitor models for SNe Ia with different distribution functions of the time intervals between the formation of the progenitor and the explosion, and a mass range of 8-40 M for CC SN progenitors. Methods. We considered a galaxy sample of approximately 130 000 galaxies and a SN sample of approximately 50 events. The wealth of photometric information for our galaxy sample allows us to apply the spectral energy distribution (SED) fitting technique to estimate the intrinsic rest frame colours, the stellar mass and star formation rate (SFR) for each galaxy in the sample. The galaxies have been separated into star-forming and quiescent galaxies, exploiting both the rest frame U-V vs. V-J colour-colour diagram and the best fit values of the specific star formation rate (sSFR) from the SED fitting. Results. We found that the SN Ia rate per unit mass is higher by a factor of six in the star-forming galaxies with respect to the passive galaxies, identified as such both on the U-V vs. V-J colour-colour diagram and for their sSFR. The SN Ia rate per unit mass is also higher in the less massive galaxies that are also younger. These results suggest a distribution of the delay times (DTD) less populated at long delay times than at short delays. The CC SN rate per unit mass is proportional to both the sSFR and the galaxy mass, confirming that the CC SN progenitors explode soon after the end of the star formation activity. The trends of the Type Ia and CC SN rates as a function of the sSFR and the galaxy mass that we observed from SUDARE data are in agreement with literature results at different redshifts suggesting that the ability of the stellar populations to produce SN events does not vary with cosmic time. The expected number of SNe Ia is in agreement with that observed for all four DTD models considered both in passive and star-forming galaxies so we can not discriminate between different progenitor scenarios. The expected number of CC SNe is higher than that observed, suggesting a higher limit for the minimum progenitor mass. However, at least part of this discrepancy between expected and observed number of CC SNe may reflect a fluctuation due to the relatively poor statistics. We also compare the expected and observed trends of the SN Ia rate with the intrinsic U-J colour of the parent galaxy, assumed to be a tracer of the age distribution. While the slope of the relation between the SN Ia rate and the U-J colour in star-forming galaxies can be well-reproduced by all four DTD models considered, only the steepest of them is able to account for the rates and colour in star-forming and passive galaxies with the same value of the SN Ia production efficiency. The agreement between model predictions and data could be found for the other DTD models, but with a productivity of SN Ia higher in passive galaxies compared to star-forming galaxies.
|
|
| 3. |
- De Cicco, D., et al.
(författare)
-
Optically variable AGN in the three-year VST survey of the COSMOS field
- 2019
-
Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 627
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The analysis of the variability of active galactic nuclei (AGN) at different wavelengths and the study of possible correlations of different spectral windows are a current main field of inquiry. Optical variability has been largely used to identify AGN in multivisit surveys. The strength of a selection based on optical variability lies in the opportunity of analyzing data from surveys of large sky areas by ground-based telescopes. However, the effectiveness of optical variability selection with respect to other multiwavelength techniques has been poorly studied down to the depth that is expected from next-generation surveys. Aims. Here we present the results of our r-band analysis of a sample of 299 optically variable AGN candidates in the VST survey of the COSMOS field, counting 54 visits spread over three observing seasons spanning more than three years. This dataset is more than three times larger than the dataset presented in our previous analysis, and the observing baseline is about eight times longer. Methods. We push toward deeper magnitudes (r(AB) similar to 23.5 mag) than were reached in past studies. We made wide use of ancillary multiwavelength catalogs in order to confirm the nature of our AGN candidates, and constrained the accuracy of the method based on spectroscopic and photometric diagnostics. We also performed tests aimed at assessing the relevance of dense sampling in view of future wide-field surveys. Results. We demonstrate that the method allows the selection of high-purity (> 86%) samples. We take advantage of the longer observing baseline to achieve great improvement in the completeness of our sample with respect to X-ray and spectroscopically confirmed samples of AGN (59% vs. similar to 15% in our previous work), as well as in the completeness of unobscured and obscured AGN. The effectiveness of the method confirms the importance of developing future more refined techniques for the automated analysis of larger datasets.
|
|
| 4. |
- Tschandl, P., et al.
(författare)
-
Comparison of the accuracy of human readers versus machine-learning algorithms for pigmented skin lesion classification: an open, web-based, international, diagnostic study
- 2019
-
Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 20:7, s. 938-947
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Whether machine-learning algorithms can diagnose all pigmented skin lesions as accurately as human experts is unclear. The aim of this study was to compare the diagnostic accuracy of state-of-the-art machine-learning algorithms with human readers for all clinically relevant types of benign and malignant pigmented skin lesions. Methods: For this open, web-based, international, diagnostic study, human readers were asked to diagnose dermatoscopic images selected randomly in 30-image batches from a test set of 1511 images. The diagnoses from human readers were compared with those of 139 algorithms created by 77 machine-learning labs, who participated in the International Skin Imaging Collaboration 2018 challenge and received a training set of 10 015 images in advance. The ground truth of each lesion fell into one of seven predefined disease categories: intraepithelial carcinoma including actinic keratoses and Bowen's disease; basal cell carcinoma; benign keratinocytic lesions including solar lentigo, seborrheic keratosis and lichen planus-like keratosis; dermatofibroma; melanoma; melanocytic nevus; and vascular lesions. The two main outcomes were the differences in the number of correct specific diagnoses per batch between all human readers and the top three algorithms, and between human experts and the top three algorithms. Findings: Between Aug 4, 2018, and Sept 30, 2018, 511 human readers from 63 countries had at least one attempt in the reader study. 283 (55·4%) of 511 human readers were board-certified dermatologists, 118 (23·1%) were dermatology residents, and 83 (16·2%) were general practitioners. When comparing all human readers with all machine-learning algorithms, the algorithms achieved a mean of 2·01 (95% CI 1·97 to 2·04; p<0·0001) more correct diagnoses (17·91 [SD 3·42] vs 19·92 [4·27]). 27 human experts with more than 10 years of experience achieved a mean of 18·78 (SD 3·15) correct answers, compared with 25·43 (1·95) correct answers for the top three machine algorithms (mean difference 6·65, 95% CI 6·06–7·25; p<0·0001). The difference between human experts and the top three algorithms was significantly lower for images in the test set that were collected from sources not included in the training set (human underperformance of 11·4%, 95% CI 9·9–12·9 vs 3·6%, 0·8–6·3; p<0·0001). Interpretation: State-of-the-art machine-learning classifiers outperformed human experts in the diagnosis of pigmented skin lesions and should have a more important role in clinical practice. However, a possible limitation of these algorithms is their decreased performance for out-of-distribution images, which should be addressed in future research. Funding: None. © 2019 Elsevier Ltd
|
|
| 5. |
- Sipeky, C, et al.
(författare)
-
4th ESPT Conference: pharmacogenomics and personalized medicine - research progress and clinical implementation
- 2019
-
Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 20:15, s. 1063-1069
-
Tidskriftsartikel (refereegranskat)abstract
- The Fourth European Society of Pharmacogenomics and Personalized Therapy biennial conference was organized in collaboration with the Italian Society of Personalized Medicine (SIMeP) and was held at Benedictine Monastery of San Nicolò l’Arena in Catania, Sicily (Italy) on 4–7 October 2017. The congress addressed the research progress and clinical implementation in pharmacogenomics and personalized medicine. The Fourth European Society of Pharmacogenomics and Personalized Therapy congress brought together leading international scientists and healthcare professionals actively working in the fields of pharmacogenomics and personalized therapy. Altogether, 25 speakers in 15 session comprehensively covered broad spectrum of pharmacogenetics and pharmacogenomics research, clinical applications in different clinical disciplines attended by 270 delegates.
|
|
| 6. |
- Trabelsi, M. S., et al.
(författare)
-
Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Bile acids are signalling molecules, which activate the transmembrane receptor TGR5 and the nuclear receptor FXR. BA sequestrants (BAS) complex bile acids in the intestinal lumen and decrease intestinal FXR activity. The BAS-BA complex also induces glucagon-like peptide-1 (GLP-1) production by L cells which potentiates beta-cell glucose-induced insulin secretion. Whether FXR is expressed in L cells and controls GLP-1 production is unknown. Here, we show that FXR activation in L cells decreases proglucagon expression by interfering with the glucose-responsive factor Carbohydrate-Responsive Element Binding Protein (ChREBP) and GLP-1 secretion by inhibiting glycolysis. In vivo, FXR deficiency increases GLP-1 gene expression and secretion in response to glucose hence improving glucose metabolism. Moreover, treatment of ob/ob mice with the BAS colesevelam increases intestinal proglucagon gene expression and improves glycaemia in a FXR-dependent manner. These findings identify the FXR/GLP-1 pathway as a new mechanism of BA control of glucose metabolism and a pharmacological target for type 2 diabetes.
|
|
| 7. |
- Marchetti, M., et al.
(författare)
-
Which patients with myelofibrosis should receive ruxolitinib therapy? : ELN-SIE evidence-based recommendations
- 2017
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:4, s. 882-888
-
Tidskriftsartikel (refereegranskat)abstract
- Ruxolitinib is an oral Janus-activated kinase 1 (JAK1)/JAK2 inhibitor approved for the treatment of patients with myelofibrosis based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of the three clinical outcomes: (a) splenomegaly, (b) disease-related symptoms, and (c) survival. Ruxolitinib was strongly recommended for improving symptomatic or severe (415 cm below the costal margin) splenomegaly in patients with an International Prognostic Scoring System (IPSS)/dynamic IPSS risk intermediate 2 or high. Ruxolitinib was also strongly recommended for improving systemic symptoms in patients with an MPN10 score 444, refractory severe itching, unintended weight loss not attributable to other causes or unexplained fever. Because of weak evidence, the panel does not recommend ruxolitinib therapy for improving survival. Also, the recommendations given above do not necessarily apply to patients who are candidates for allogeneic stem cell transplant.
|
|
| 8. |
- Taubenberger, S., et al.
(författare)
-
Spectroscopy of the Type Ia supernova 2011fe past 1000 d
- 2015
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966 .- 1745-3925 .- 1745-3933. ; 448:1, s. L48-L52
-
Tidskriftsartikel (refereegranskat)abstract
- In this Letter we present an optical spectrum of SN 2011fe taken 1034 d after the explosion, several hundred days later than any other spectrum of a Type Ia supernova (disregarding light-echo spectra and Local Group remnants). The spectrum is still dominated by broad emission features, with no trace of a light echo or interaction of the supernova ejecta with surrounding interstellar material. Comparing this extremely late spectrum to an earlier one taken 331 d after the explosion, we find that the most prominent feature at 331 d - [Fe III] emission around 4700 angstrom - has entirely faded away, suggesting a significant change in the ionization state. Instead, [Fe II] lines are probably responsible for most of the emission at 1034 d. An emission feature at 6300-6400 angstrom has newly developed at 1034 d, which we tentatively identify with Fe I lambda 6359, [Fe I] lambda lambda 6231, 6394 or [O I] lambda lambda 6300, 6364. Interestingly, the features in the 1034 d spectrum seem to be collectively redshifted, a phenomenon that we currently have no convincing explanation for. We discuss the implications of our findings for explosion models, but conclude that sophisticated spectral modelling is required for any firm statement.
|
|
| 9. |
- Bugliani, Marco, et al.
(författare)
-
DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes
- 2018
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 473, s. 186-193
-
Tidskriftsartikel (refereegranskat)abstract
- It has been reported that the incretin system, including regulated GLP-1 secretion and locally expressed DPP-4, is present in pancreatic islets. In this study we comprehensively evaluated the expression and role of DPP-4 in islet alpha and beta cells from non-diabetic (ND) and type 2 diabetic (T2D) individuals, including the effects of its inhibition on beta cell function and survival. Isolated islets were prepared from 25 ND and 18 T2D organ donors; studies were also performed with the human insulin-producing EndoC-βH1 cells. Morphological (including confocal microscopy), ultrastructural (electron microscopy, EM), functional (glucose-stimulated insulin secretion), survival (EM and nuclear dyes) and molecular (RNAseq, qPCR and western blot) studies were performed under several different experimental conditions. DPP-4 co-localized with glucagon and was also expressed in human islet insulin-containing cells. Furthermore, DPP-4 was expressed in EndoC-βH1 cells. The proportions of DPP-4 positive alpha and beta cells and DPP-4 gene expression were significantly lower in T2D islets. A DPP-4 inhibitor protected ND human beta cells and EndoC-βH1 cells against cytokine-induced toxicity, which was at least in part independent from GLP1 and associated with reduced NFKB1 expression. Finally, DPP-4 inhibition augmented glucose-stimulated insulin secretion, reduced apoptosis and improved ultrastructure in T2D beta cells. These results demonstrate the presence of DPP-4 in human islet alpha and beta cells, with reduced expression in T2D islets, and show that DPP-4 inhibition has beneficial effects on human ND and T2D beta cells. This suggests that DPP-4, besides playing a role in incretin effects, directly affects beta cell function and survival.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- L'Episcopo, F, et al.
(författare)
-
GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease : involvement of astrocyte-neuron interactions
- 2016
-
Ingår i: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 7, s. 1-14
-
Tidskriftsartikel (refereegranskat)abstract
- Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3β expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2-4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3β were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3β mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3β-Tyr(216) being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3β-Tyr(216) was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3β in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3β in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3β as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD.
|
|
| 13. |
|
|
| 14. |
- Peterlongo, Paolo, et al.
(författare)
-
FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5345-5355
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.
|
|
| 15. |
- Avolio, G., et al.
(författare)
-
A procedure for the extraction of a nonlinear microwave GaN FET model
- 2017
-
Ingår i: International Journal of Numerical Modelling: Electronic Networks, Devices and Fields. - : Wiley. - 0894-3370 .- 1099-1204. ; 30:1, s. UNSP e2151-
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, we describe an extraction procedure of nonlinear models for microwave field-effect transistor (FET). We use a nonlinear model available in commercial CAD tools, and we extract the parameters by combining direct extraction and numerical optimization. We determine a first estimate of the model parameters by few DC and S-parameter measurements. Next, we refine the parameters by optimization against low-frequency and high-frequency vector-calibrated large-signal measurements gathered with a Large-Signal-Network Analyzer (LSNA). As case study we consider a 0.25x200 mu m(2) GaN FET on SiC for power amplifier applications. Ultimately, we want to show that a good accuracy level can be achieved while minimizing the extraction effort and that an accurate model can be built and suitably tailored depending on the final application.
|
|
