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| 3. |
- Abazov, V. M., et al.
(author)
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The upgraded DO detector
- 2006
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Journal article (peer-reviewed)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 4. |
- Elhai, M, et al.
(author)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Journal article (peer-reviewed)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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| 8. |
- Polettini, M., et al.
(author)
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Decay studies in the A∼225 Po-Fr region from the DESPEC campaign at GSI in 2021
- 2022
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In: Il Nuovo Cimento. - : Società Italiana di Fisica. - 2037-4909. ; 45:5
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Journal article (peer-reviewed)abstract
- The HISPEC-DESPEC collaboration aims at investigating the structure of exotic nuclei formed in fragmentation reactions with decay spectroscopy measurements, as part of the FAIR Phase-0 campaign at GSI. This paper reports on first results of an experiment performed in spring 2021, with a focus on beta-decaystudies in the Po-Fr nuclei in the 220 < A <230 island of octupole deformation exploiting the DESPEC setup. Ion-beta correlations and fast-timing techniques are being employed, giving an insight into this difficult-to-reach region.
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| 9. |
- Solmi, M, et al.
(author)
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- 2022
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In: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
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Journal article (peer-reviewed)
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| 10. |
- Alcorn, J, et al.
(author)
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Basic instrumentation for Hall A at Jefferson Lab
- 2004
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 522:3, s. 294-346
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Journal article (peer-reviewed)abstract
- The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved.
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| 11. |
- Campo, E, et al.
(author)
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The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee
- 2022
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 140:11, s. 1229-1253
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Journal article (peer-reviewed)abstract
- Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.
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| 12. |
- Recchia, F., et al.
(author)
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Isomer spectroscopy in odd–even Ti isotopes : Approaching n = 40
- 2019
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In: Acta Physica Polonica B. - : Jagellonian University. - 0587-4254 .- 1509-5770. ; 50:3, s. 669-674
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Journal article (peer-reviewed)abstract
- Our understanding of the evolution of the shell structure in nuclei far from stability is based on the study of some key nuclei. Nuclei at or next to double shell closures play a special role in this. Presently, a lot of discussion is concentrated on the neutron-rich calcium isotopes, which provide a rich testing ground for various nuclear models with several traditional and new magic numbers. 60 Ca is now almost within reach with the most advanced radioactive beam facilities. In order to investigate the evolution of the shell gap at N = 40, the configuration of states in the odd–even titanium isotopes up to N = 37 ( 59 Ti) have been studied. In order to experimentally access the shell gap at N = 40, it is nowadays within the reach of the most advanced facility the investigation of neutron hole configuration states in odd–even titanium isotopes up to N = 37, in the 59 Ti nucleus. Such states correspond to relatively simple configurations that constitute a challenging testing ground for effective nuclear interactions. The new data obtained in our experiment allows to place the present predictions concerning the shell closure at N = 40 in the calcium region on a more solid ground.
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| 13. |
- Wimmer, K., et al.
(author)
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First spectroscopy of Ti-61 and the transition to the Island of Inversion at N=40
- 2019
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In: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 792, s. 16-20
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Journal article (peer-reviewed)abstract
- Isomeric states in Ti-59,Ti-61 have been populated in the projectile fragmentation of a 345 AMeV( 238)U beam at the Radioactive Isotope Beam Factory. The decay lifetimes and delayed gamma-ray transitions were measured with the EURICA array. Besides the known isomeric state in Ti-59, two isomeric states in Ti-61 are observed for the first time. Based on the measured lifetimes, transition multipolarities as well as tentative spins and parities are assigned. Large-scale shell model calculations based on the modified LNPS interaction show that both Ti-59 and Ti-61 belong to the Island of Inversion at N = 40 with ground state configurations dominated by particle-hole excitations to the g(9/2 )and d(5/2) orbits.
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| 14. |
- Wimmer, K., et al.
(author)
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Isomeric states in neutron-rich nuclei near N=40
- 2021
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In: Physical Review C. - : American Physical Society (APS). - 2469-9985 .- 2469-9993. ; 104:1
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Journal article (peer-reviewed)abstract
- Neutron-rich nuclei in the vicinity of the N = 40 island of inversion are characterized by shell evolution and exhibit deformed ground states. In several nuclei isomeric states have been observed and attributed to excitations to the intruder neutron 1g(9/2) orbital. In the present paper we searched for isomeric states in nuclei around N = 40, Z = 22 produced by projectile fragmentation at the Radioactive Isotope Beam Factory. Delayed. rays were detected by the Euroball RIKEN Cluster Array germanium detector array gamma High statistics data allowed for an updated decay scheme of V-60. The lifetime of an isomeric state in V-64 was measured for the first time in the present experiment. A previously unobserved isomeric state was discovered in Sc-58. The measured lifetime suggests a parity changing transition, originating from an odd number of neutrons in the 1g(9/2) orbital. The nature of the isomeric state in Sc-58 is, thus, different from isomers in the less exotic V and Sc nuclei.
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| 16. |
- Hakansson, H, et al.
(author)
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Training of risk assessors in Europe
- 2011
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In: TOXICOLOGY LETTERS. - : Elsevier BV. - 0378-4274. ; 205, s. S34-S34
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Conference paper (other academic/artistic)
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| 22. |
- Pinese, Mark, et al.
(author)
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The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly
- 2020
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.
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| 23. |
- Stegmayr, John, et al.
(author)
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Extracellular and intracellular small-molecule galectin-3 inhibitors
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- Galectin-3 is a carbohydrate binding protein which has important roles in cancer and immunity. Potent galectin-3 inhibitors have been synthesized, for experimental purposes and potential clinical use. As galectin-3 is implicated in both intra- and extracellular activities, permeability of galectin-3 inhibitors is an important parameter determining biological effects. We compared the cellular uptake of galectin-3 inhibitors and their potency in the intracellular or extracellular space. The inhibitors differed in their polar surface area (PSA), but had similar affinities for galectin-3. Using a well-established permeability assay, we confirmed that the uptake was significantly higher for the inhibitor with the lowest PSA, as expected. To analyze intracellular activity of the inhibitors, we developed a novel assay based on galectin-3 accumulation around damaged intracellular vesicles. The results show striking differences between the inhibitors intracellular potency, correlating with their PSAs. To test extracellular activity of the inhibitors, we analyzed their potency to block binding of galectin-3 to cell surfaces. All inhibitors were equally able to block galectin-3 binding to cells and this was proportional to their affinity for galectin-3. These inhibitors may serve as useful tools in exploring biological roles of galectin-3 and may further our understanding of intracellular versus extracellular roles of galectin-3.
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| 24. |
- Sörme, Pernilla, et al.
(author)
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Design and Synthesis of Galectin Inhibitors
- 2003
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In: Recognition of Carbohydrates in Biological Systems, Part B: Specific Applications (Methods in Enzymology; 263). - 0121822664 ; 363, s. 157-169
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Doctoral thesis (other academic/artistic)abstract
- Galectins, a lectin family, have shown binding affinities towards b-galactosides. Galectins have been proposed to be involved in a wide range of functions like for example, cell growth, adhesion, migration, chemo taxis and apoptosis. They have also been associated with various cancer types. However, the detailed functions of galectins are still very much unknown. High affinity inhibitors towards the galectins would thus be of value as research tools, as well as possible future pharmaceutical agents. Existing inhibitors have undesirable properties, for example high molecular weight and instability. This thesis concerns the synthesis of small high affinity galectin inhibitors. A previously published X-ray structure of galectin-3 together with LacNAc revealed an extended binding pocket close to 3´-C of the galactoside residue. Filling this pocket with additional chemical entities was hypothesized to allow for further interactions and hence creating higher affinity ligands as compared to the naturally occurring ligand. The hypothesis was probed by substituting the 3´-hydroxyl group on the galactose unit of LacNAc with an amine, which enables the introduction of functional groups under mild reaction conditions. We synthesised a collection of more than 60 LacNAc derivatives with various functional groups at 3´-C of the galactose unit. The measurements of inhibitor potencies towards galectins were made in a novel fluorescence polarisation (FP) assay, which is a solution phase method, as well as a general technique that do not need major re-optimisation to enable the study of other galectins. Hence, it enabled us to study the panel of synthetic inhibitors towards galectin-1, -3 and –4. Selective and high affinity inhibitors were discovered, which is of value as often more than one galectin is present in one and the same system. We found that aromatic amides in particular showed high affinity towards galectin-3. In addition, the X-ray structure of one of the best inhibitors (Kd 0.9 mM) revealed that Arg-144 on galectin-3 had moved 3.5 Å to enable a face-to-face stacking interaction with a 4-methoxy-2,3,5,6-tetrafluorobenzamido substituent. The best inhibitor synthesised as of yet, carried a 2-naphthamido functionality at 3´of the galactose residue. This inhibitor had a Kd of 0.3 mM, which the strongest binding affinity achieved as compared to any monovalent inhibitor. It shows over 200 times higher affinity towards galectin-3 than the unfunctionalised LacNAc.
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| 27. |
- Zetterberg, Fredrik R., et al.
(author)
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Discovery of the Selective and Orally Available Galectin-1 Inhibitor GB1908 as a Potential Treatment for Lung Cancer
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In: Journal of Medicinal Chemistry. - 1520-4804.
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Journal article (peer-reviewed)abstract
- We have previously described a new series of selective and orally available galectin-1 inhibitors resulting in the thiazole-containing glycomimetic GB1490. Here, we show that the introduction of polar substituents to the thiazole ring results in galectin-1-specific compounds with low nM affinities. X-ray structural analysis of a new ligand-galectin-1 complex shows changes in the binding mode and ligand-protein hydrogen bond interactions compared to the GB1490-galectin-1 complex. These new high affinity ligands were further optimized with respect to affinity and ADME properties resulting in the galectin-1-selective GB1908 (Kd galectin-1/3 0.057/6.0 μM). In vitro GB1908 inhibited galectin-1-induced apoptosis in Jurkat cells (IC50 = 850 nM). Pharmacokinetic experiments in mice revealed that a dose of 30 mg/kg b.i.d. results in free levels of GB1908 in plasma over galectin-1 Kd for 24 h. GB1908 dosed with this regimen reduced the growth of primary lung tumor LL/2 in a syngeneic mouse model.
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