| 1. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 2. |
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| 3. |
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| 4. |
- Ankowski, A., et al.
(författare)
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Energy reconstruction of electromagnetic showers from Ν0 decays with the ICARUS T600 liquid argon TPC
- 2010
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Ingår i: Acta Physica Polonica, Series B.. - 1509-5770 .- 0587-4254. ; 41:1, s. 103-125
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the ICARUS T600 detector capabilities in electromagnetic shower reconstruction through the analysis of a sample of 212 events, coming from the 2001 Pavia surface test run, of hadronic interactions leading to the production of π 0 mesons. Methods of shower energy and shower direction measurements were developed and the invariant mass of the photon pairs was reconstructed. The (γγ) invariant mass was found to be consistent with the value of the π 0 mass. The resolution of the reconstructed π 0 mass was found to be equal to 27.3%. An improved analysis, carried out in order to clean the full event sample from the events measured in the crowded environment, mostly due to the trigger conditions, gave a π 0 mass resolution of 16.1%, significantly better than the one evaluated for the full event sample. The trigger requirement of the coincidence of at least four photo-multiplier signals favored the selection of events with a strong pile up of cosmic ray tracks and interactions. Hence a number of candidate π 0 events were heavily contaminated by other tracks and had to be rejected. Monte Carlo simulations of events with π 0 production in hadronic and neutrino interactions confirmed the validity of the shower energy and shower direction reconstruction methods applied to the real data.
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| 5. |
- Ankowski, A, et al.
(författare)
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Energy reconstruction of electromagnetic showers from π0 decays with the ICARUS T600 liquid argon TPC
- 2010
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Ingår i: Acta Physica Polonica B. - : Jagellonian University. - 0587-4254 .- 1509-5770. ; 41:1, s. 103-125
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the ICARUS T600 detector capabilities in electromagnetic shower reconstruction through the analysis of a sample of 212 events, coming from the 2001 Pavia surface test run, of hadronic interactions leading to the production of π0 mesons. Methods of shower energy and shower direction measurements were developed and the invariant mass of the photon pairs was reconstructed. The (γ,γ) invariant mass was found to be consistent with the value of the π0 mass. The resolution of the reconstructed π0 mass was found to be equal to 27.3%. An improved analysis, carried out in order to clean the full event sample from the events measured in the crowded environment, mostly due to the trigger conditions, gave a π0 mass resolution of 16.1%, significantly better than the one evaluated for the full event sample. The trigger requirement of the coincidence of at least four photo-multiplier signals favored the selection of events with a strong pile up of cosmic ray tracks and interactions. Hence a number of candidate π0 events were heavily contaminated by other tracks and had to be rejected. Monte Carlo simulations of events with π0 production in hadronic and neutrino interactions confirmed the validity of the shower energy and shower direction reconstruction methods applied to the real data.
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| 6. |
- Rubbia, C, et al.
(författare)
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Underground operation of the ICARUS T600 LAr-TPC : first results
- 2011
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Ingår i: Journal of Instrumentation. ; 6:07
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Tidskriftsartikel (refereegranskat)abstract
- Important open questions are still present in fundamental Physics and Cosmology, like the nature of Dark Matter, the matter-antimatter asymmetry and the validity of the Standard Model of particle interactions. Addressing these questions requires a new generation of massive particle detectors to explore the subatomic and astrophysical worlds. ICARUS T600 is the first large mass (760 tons) example of a new generation of detectors able to combine the imaging capabilities of the old famous “bubble chamber” with the excellent energy measurement of huge electronic detectors. ICARUS T600 now operates at the Gran Sasso underground laboratory and is used to study cosmic rays, neutrino oscillations and the proton decay. The potential for doing physics of this novel telescope is presented through a few examples of neutrino interactions reconstructed with unprecedented detail. Detector design and early operation are also reported.
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| 7. |
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| 8. |
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| 9. |
- Fiorillo, A., et al.
(författare)
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How to improve clinical practice on involuntary hospital admissions of psychiatric patients : suggestions from the EUNOMIA study
- 2011
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Ingår i: European psychiatry. - : Elsevier. - 0924-9338 .- 1778-3585. ; 26:4, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- Number and procedures of involuntary hospital admissions vary in Europe according to the different socio-cultural contexts. The European Commission has funded the EUNOMIA study in 12 European countries in order to develop European recommendations for good clinical practice in involuntary hospital admissions. The recommendations have been developed with the direct and active involvement of national leaders and key professionals, who worked out national recommendations, subsequently summarized into a European document, through the use of specific categories. The need for standardizing the involuntary hospital admission has been highlighted by all centers. In the final recommendations, it has been stressed the need to: providing information to patients about the reasons for hospitalization and its presumable duration; protecting patients’ rights during hospitalization; encouraging the involvement of family members; improving the communication between community and hospital teams; organizing meetings, seminars and focus-groups with users; developing training courses for involved professionals on the management of aggressive behaviors, clinical aspects of major mental disorders, the legal and administrative aspects of involuntary hospital admissions, on communication skills. The results showed the huge variation of involuntary hospital admissions in Europe and the importance of developing guidelines on this procedure.
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| 10. |
- Heier, C. R., et al.
(författare)
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Multi-Omics Identifies Circulating miRNA and Protein Biomarkers for Facioscapulohumeral Dystrophy
- 2020
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Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- The development of therapeutics for muscle diseases such as facioscapulohumeral dystrophy (FSHD) is impeded by a lack of objective, minimally invasive biomarkers. Here we identify circulating miRNAs and proteins that are dysregulated in early-onset FSHD patients to develop blood-based molecular biomarkers. Plasma samples from clinically characterized individuals with early-onset FSHD provide a discovery group and are compared to healthy control volunteers. Low-density quantitative polymerase chain reaction (PCR)-based arrays identify 19 candidate miRNAs, while mass spectrometry proteomic analysis identifies 13 candidate proteins. Bioinformatic analysis of chromatin immunoprecipitation (ChIP)-seq data shows that the FSHD-dysregulated DUX4 transcription factor binds to regulatory regions of several candidate miRNAs. This panel of miRNAs also shows ChIP signatures consistent with regulation by additional transcription factors which are up-regulated in FSHD (FOS, EGR1, MYC, and YY1). Validation studies in a separate group of patients with FSHD show consistent up-regulation of miR-100, miR-103, miR-146b, miR-29b, miR-34a, miR-454, miR-505, and miR-576. An increase in the expression of S100A8 protein, an inflammatory regulatory factor and subunit of calprotectin, is validated by Enzyme-Linked Immunosorbent Assay (ELISA). Bioinformatic analyses of proteomics and miRNA data further support a model of calprotectin and toll-like receptor 4 (TLR4) pathway dysregulation in FSHD. Moving forward, this panel of miRNAs, along with S100A8 and calprotectin, merit further investigation as monitoring and pharmacodynamic biomarkers for FSHD.
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| 11. |
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| 12. |
- Fiorillo, A., et al.
(författare)
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Patient characteristics and symptoms associated with perceived coercion during hospital treatment
- 2012
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Ingår i: Acta Psychiatrica Scandinavica. - Malden, USA : Wiley-Blackwell. - 0001-690X .- 1600-0447. ; 125:6, s. 460-467
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Large numbers of psychiatric patients either are involuntarily admitted to hospital treatment or feel coerced despite a legally voluntary admission. For ethical and clinical reasons, their perceived coercion should be reduced as far as possible. There is however limited evidence on patient characteristics associated with perceived coercion during hospital treatment. This study aimed to identify i) sociodemographic and clinical characteristics associated with perceived coercion at admission and ii) changes in symptoms and global functioning associated with changes in perceived coercion over time.Method: Three thousand and ninety three in-patients who were involuntarily admitted or felt coerced to hospital treatment despite a legally voluntary admission were recruited in the European evaluation of coercion in psychiatry and harmonization of best clinical practice EUNOMIA project in 11 European countries. Perceived coercion, global functioning and symptoms were assessed after admission and at a 3-month follow-up.Results: Involuntary admission, female gender, poorer global functioning and more positive symptoms were associated with higher levels of perceived coercion at admission. Perceived coercion significantly decreased over time, and the improvements in global functioning and positive symptoms were associated with reduction in perceived coercion.Conclusion: Female patients perceive more coercion in psychiatric hospital treatment. Effective treatment for positive symptoms and improving patients global functioning may lead to a reduction in perceived coercion.
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| 13. |
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| 14. |
- Winick-Ng, W, et al.
(författare)
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Cell-type specialization is encoded by specific chromatin topologies
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 599:7886, s. 684-
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Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1–3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4–6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive ‘melting’ of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.
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| 15. |
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| 16. |
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| 17. |
- Donkervoort, S., et al.
(författare)
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Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores
- 2020
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 107:6, s. 1078-1095
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Tidskriftsartikel (refereegranskat)abstract
- The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization.
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| 18. |
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| 19. |
- Brittlebank, A, et al.
(författare)
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Training in psychiatry throughout Europe
- 2016
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Ingår i: European archives of psychiatry and clinical neuroscience. - : Springer Science and Business Media LLC. - 1433-8491 .- 0940-1334. ; 266:2, s. 155-164
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Tidskriftsartikel (refereegranskat)
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Fiorillo, Alyson A., et al.
(författare)
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Estrogen Receptor, Inflammatory, and FOXO Transcription Factors Regulate Expression of Myasthenia Gravis-Associated Circulating microRNAs
- 2020
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate important intracellular biological processes. In myasthenia gravis (MG), a disease-specific pattern of elevated circulating miRNAs has been found, and proposed as potential biomarkers. These elevated miRNAs include miR-150-5p, miR-21-5p, and miR-30e-5p in acetylcholine receptor antibody seropositive (AChR+) MG and miR-151a-3p, miR-423-5p, let-7a-5p, and let-7f-5p in muscle-specific tyrosine kinase antibody seropositive (MuSK+) MG. In this study, we examined the regulation of each of these miRNAs using chromatin immunoprecipitation sequencing (ChIP-seq) data from the Encyclopedia of DNA Elements (ENCODE) to gain insight into the transcription factor pathways that drive their expression in MG. Our aim was to look at the transcription factors that regulate miRNAs and then validate some of those in vivo with cell lines that have sufficient expression of these transcription factors This analysis revealed several transcription factor families that regulate MG-specific miRNAs including the Forkhead box or the FOXO proteins (FoxA1, FoxA2, FoxM1, FoxP2), AP-1, interferon regulatory factors (IRF1, IRF3, IRF4), and signal transducer and activator of transcription proteins (Stat1, Stat3, Stat5a). We also found binding sites for nuclear factor of activated T-cells (NFATC1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), early growth response factor (EGR1), and the estrogen receptor 1 (ESR1). AChR+ MG miRNAs showed a stronger overall regulation by the FOXO transcription factors, and of this group, miR-21-5p, let-7a, and let 7f were found to possess ESR1 binding sites. Using a murine macrophage cell line, we found activation of NF-kappa B -mediated inflammation by LPS induced expression of miR-21-5p, miR-30e-5p, miR-423-5p, let-7a, and let-7f. Pre-treatment of cells with the anti-inflammatory drugs prednisone or deflazacort attenuated induction of inflammation-induced miRNAs. Interestingly, the activation of inflammation induced packaging of the AChR+-specific miRNAs miR-21-5p and miR-30e-5p into exosomes, suggesting a possible mechanism for the elevation of these miRNAs in MG patient serum. In conclusion, our study summarizes the regulatory transcription factors that drive expression of AChR+ and MuSK+ MG-associated miRNAs. Our findings of elevated miR-21-5p and miR-30e-5p expression in immune cells upon inflammatory stimulation and the suppressive effect of corticosteroids strengthens the putative role of these miRNAs in the MG autoimmune response.
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| 25. |
- Kalisova, Lucie, et al.
(författare)
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Do patient and ward-related characteristics influence the use of coercive measures? : Results from the EUNOMIA international study
- 2014
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer. - 0933-7954 .- 1433-9285. ; 49:10, s. 1619-1629
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to identify whether selected patient and ward-related factors are associated with the use of coercive measures. Data were collected as part of the EUNOMIA international collaborative study on the use of coercive measures in ten European countries.Involuntarily admitted patients (N = 2,027) were divided into two groups. The first group (N = 770) included patients that had been subject to at least one of these coercive measures during hospitalization: restraint, and/or seclusion, and/or forced medication; the other group (N = 1,257) included patients who had not received any coercive measure during hospitalization. To identify predictors of use of coercive measures, both patients' sociodemographic and clinical characteristics and centre-related characteristics were tested in a multivariate logistic regression model, controlled for countries' effect.The frequency of the use of coercive measures varied significantly across countries, being higher in Poland, Italy and Greece. Patients who received coercive measures were more frequently male and with a diagnosis of psychotic disorder (F20-F29). According to the regression model, patients with higher levels of psychotic and hostility symptoms, and of perceived coercion had a higher risk to be coerced at admission. Controlling for countries' effect, the risk of being coerced was higher in Poland. Patients' sociodemographic characteristics and ward-related factors were not identifying as possible predictors because they did not enter the model.The use of coercive measures varied significantly in the participating countries. Clinical factors, such as high levels of psychotic symptoms and high levels of perceived coercion at admission were associated with the use of coercive measures, when controlling for countries' effect. These factors should be taken into consideration by programs aimed at reducing the use of coercive measures in psychiatric wards.
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| 26. |
- Mastrototaro, L., et al.
(författare)
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Constraining axion-like particles with the diffuse gamma-ray flux measured by the Large High Altitude Air Shower Observatory
- 2022
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:11
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Tidskriftsartikel (refereegranskat)abstract
- The detection of very high-energy neutrinos by IceCube experiment supports the existence of a comparable gamma-ray counterpart from the same cosmic accelerators. Under the likely assumption that the sources of these particles are of extragalactic origin, the emitted photon flux would be significantly absorbed during its propagation over cosmic distances. However, in the presence of photon mixing with ultra-light axion-like-particles (ALPs), this expectation would be strongly modified. Notably, photon-ALP conversions in the host galaxy would produce an ALP flux which propagates unimpeded in the extragalactic space. Then, the back-conversion of ALPs in the Galactic magnetic field leads to a diffuse high-energy photon flux. In this context, the recent detection of the diffuse high-energy photon flux by the Large High Altitude Air Shower Observatory (LHAASO) allows us to exclude at the 95%95% CL an ALP-photon coupling gaγ>rsim3.9–7.8×10−11 GeV−1 for ma≲4×10−7 eV, depending on the assumptions on the magnetic fields and on the original gamma-ray spectrum. This new bound is complementary with other ALP constraints from very-high-energy gamma-ray experiments and sensitivities of future experiments.
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| 27. |
- Orrú, Valeria, et al.
(författare)
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A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:3, s. 569-579
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Tidskriftsartikel (refereegranskat)abstract
- A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.
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| 28. |
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| 29. |
- Petkari, Eleni, et al.
(författare)
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Acute psychopathology as a predictor of global functioning in patients with ICD-10 non-affective psychosis : a prospective study in 11 European countries
- 2011
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 131:1-3, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- This prospective analysis aimed to study the influence of psychopathological dimensions on the global functioning of persons suffering from psychotic disorders, taking into account the role of a broad range of potential confounders. A large international cohort (n = 1888) with ICD-10 non-affective psychosis was evaluated both at baseline during a hospital admission and three months after discharge. Trained interviewers administered a global functioning scale (GAF) and a psychopathological scale (BPRS) at baseline and follow-up). Baseline BPRS psychopathological dimensions were extracted using Principal Component Analysis. Results of multiple linear regression analyses demonstrated that affective symptoms (depressive or manic) prospectively predict a better global functioning, whilst agitation/cognitive symptoms determined poorer global functioning. Other predictors showing an independent effect on better global functioning were medication compliance, country of residence, female gender, married or coupled status, younger age and having a diagnosis of schizoaffective disorder rather than schizophrenia or other ICD-10 psychosis. A predicting model for global functioning in patients with psychosis is provided, showing that assessment of affective and agitation/cognitive symptoms should be emphasised during admission as they can be more informative than positive/negative symptoms in prospectively planning follow-up care that is geared towards a better functional recovery. (C) 2011 Elsevier B.V. All rights reserved.
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| 30. |
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