| 1. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 2. |
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| 3. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 4. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 5. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 6. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 7. |
- Di Martino, Elena
(författare)
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Neonatal hypoxic ischemic encephalopathy : inflammation and therapies
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neonatal hypoxic ischemia (HI) is a severe condition characterized by a complex pathophysiology. The lack of oxygen (hypoxia) and blood flow (ischemia) leads to neuronal cell death via necrosis and apoptosis, and a consequent post-ischemic inflammation. HI brain injury may lead to seizures, cognitive and motor impairments, and death. Worse neurodevelopmental outcomes have been observed in male than in female survivors, thus underlining sex-dependent differences. To date, hypothermia is the only available evidence-based treatment for neonatal HI that shows neuroprotection if applied within six hours after the insult. Although hypothermia reduces production of cytokines and metabolic stress, it was shown to not be effective in severe cases of neonatal HI. Additional therapies meant to alleviate the HI outcomes are therefore needed. In the present thesis we investigated the role of two key players involved in post-ischemic inflammation, namely resident microglia and infiltrating macrophages, and studied the effects of drug- and cell-based treatments aimed at reducing injury. HI was induced by occluding the common carotid artery in mouse pups that were then subjected to hypoxia. By investigating the dynamics of inflammatory cells in the hippocampus of injured mice, sex-specific differences were observed in microglia and infiltrating peripheral-macrophages. Sequencing data revealed that macrophages are the drivers of the post-ischemic inflammation through significant upregulation of cytokine, chemokine and sensome markers, as well as activation genes. In addition, microglial cells, which were shown to downregulate unique signature genes upon inflammation, restored their homeostatic role within three days after injury in males, suggesting a different mechanistic effect in response to the neuroinflammatory cascade. The role of resident microglia was further investigated in a Tamoxifen-based depletion model in which HI was then performed. While no difference in the speed of microglial repopulation was observed between males and females, the injury progression and cytokine production changed in a sex-dependent fashion. Specifically, depletion aggravated neuronal damage and apoptosis in male mice following HI. In order to reduce inflammation and to induce neuroprotection, therapies involving caffeine or bone marrow-derived macrophage administration were assessed in this thesis. Caffeine, which is an adenosine-receptor competitor, is currently used in the clinic as treatment for neonatal apnea. As long-term follow-up studies of apneic babies treated with caffeine showed a reduced incident of cerebral palsy, this drug was administered at different time points after HI. Our results revealed a reduced lesion and improved behavioral outcomes after a single dose of 5 mg/kg caffeine immediately post-HI, with a reduction of the lesion and glial scar extent, and modulation of microglia activation and pro-inflammatory genes. ii Bone marrow-derived macrophages were adoptively transferred 5 days after HI to investigate their immunomodulatory and wound healing properties. Our results showed a clear difference when anti-inflammatory macrophages (M2) or unpolarized control cells (M0) were administered. While M2 cell therapy led to functional recovery, we observed that M0 macrophages worsened behavioral outcomes and increased the injury size. In addition, in vitro studies in organotypic hippocampal slices co-cultured with these macrophages showed that, while M2 maintained memory of their phenotype, the M0 cells became polarized towards a pro-inflammatory state, thus suggesting how unpolarized cells could lead to exacerbation of the inflammation and the consequent worsening of injury extent and behavioral performance observed in vivo. In summary, in this thesis I highlight the importance of microglia and infiltrating macrophages in the post-ischemic inflammatory cascade, and how caffeine and bone-marrow derived macrophages may be of potential therapeutic interest in future studies.
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| 8. |
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| 9. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 10. |
- Kohler, Annegret, et al.
(författare)
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Convergent losses of decay mechanisms and rapid turnover of symbiosis genes in mycorrhizal mutualists.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:4, s. 176-410
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic bases of mycorrhizal lifestyle evolution, we sequenced new fungal genomes, including 13 ectomycorrhizal (ECM), orchid (ORM) and ericoid (ERM) species, and five saprotrophs, which we analyzed along with other fungal genomes. Ectomycorrhizal fungi have a reduced complement of genes encoding plant cell wall-degrading enzymes (PCWDEs), as compared to their ancestral wood decayers. Nevertheless, they have retained a unique array of PCWDEs, thus suggesting that they possess diverse abilities to decompose lignocellulose. Similar functional categories of nonorthologous genes are induced in symbiosis. Of induced genes, 7-38% are orphan genes, including genes that encode secreted effector-like proteins. Convergent evolution of the mycorrhizal habit in fungi occurred via the repeated evolution of a 'symbiosis toolkit', with reduced numbers of PCWDEs and lineage-specific suites of mycorrhiza-induced genes.
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| 11. |
- Martufi, Giampaolo, et al.
(författare)
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Case Study : Intra-Patient Heterogeneity of Aneurysmal Tissue Properties
- 2018
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Current recommendations for surgical treatment of abdominal aortic aneurysms (AAAs) rely on the assessment of aortic diameter as a marker for risk of rupture. The use of aortic size alone may overlook the role that vessel heterogeneity plays in aneurysmal progression and rupture risk. The aim of the current study was to investigate intra-patient heterogeneity of mechanical and fluid mechanical stresses on the aortic wall and wall tissue histopathology from tissue collected at the time of surgical repair. Methods: Finite element analysis (FEA) and computational fluid dynamics (CFD) simulations were used to predict the mechanical wall stress and the wall shear stress fields for a non-ruptured aneurysm 2 weeks prior to scheduled surgery. During open repair surgery one specimen partitioned into different regions was collected from the patient's diseased aorta according to a pre-operative map. Histological analysis and mechanical testing were performed on the aortic samples and the results were compared with the predicted stresses. Results: The preoperative simulations highlighted the presence of altered local hemodynamics particularly at the proximal segment of the left anterior area of the aneurysm. Results from the post-operative assessment on the surgical samples revealed a considerable heterogeneity throughout the aortic wall. There was a positive correlation between elastin fragmentation and collagen content in the media. The tensile tests demonstrated a good prediction of the locally varying constitutive model properties predicted using geometrical variables, i.e., wall thickness and thrombus thickness. Conclusions: The observed large regional differences highlight the local response of the tissue to both mechanical and biological factors. Aortic size alone appears to be insufficient to characterize the large degree of heterogeneity in the aneurysmal wall. Local assessment of wall vulnerability may provide better risk of rupture predictions.
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| 12. |
- Martufi, Giampaolo, et al.
(författare)
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Three-Dimensional Geometrical Characterization of Abdominal Aortic Aneurysms : Image-Based Wall Thickness Distribution
- 2009
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Ingår i: Journal of Biomechanical Engineering. - : ASME International. - 0148-0731 .- 1528-8951. ; 131:6, s. 061015-
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Tidskriftsartikel (refereegranskat)abstract
- The clinical assessment of abdominal aortic aneurysm (AAA) rupture risk is based on the quantification of AAA size by measuring its maximum diameter from computed tomography (CT) images and estimating the expansion rate of the aneurysm sac over time. Recent findings have shown that geometrical shape and size, as well as local wall thickness may be related to this risk; thus, reliable noninvasive image-based methods to evaluate AAA geometry have a potential to become valuable clinical tools. Utilizing existing CT data, the three-dimensional geometry of nine unruptured human AAAs was reconstructed and characterized quantitatively. We propose and evaluate a series of 1D size, 2D shape, 3D size, 3D shape, and second-order curvature-based indices to quantify AAA geometry, as well as the geometry of a size-matched idealized fusiform aneurysm and a patient-specific normal abdominal aorta used as controls. The wall thickness estimation algorithm, validated in our previous work, is tested against discrete point measurements taken from a cadaver tissue model, yielding an average relative difference in AAA wall thickness of 7.8%. It is unlikely that any one of the proposed geometrical indices alone would be a reliable index of rupture risk or a threshold for elective repair. Rather, the complete geometry and a positive correlation of a set of indices should be considered to assess the potential for rupture. With this quantitative parameter assessment, future research can be directed toward statistical analyses correlating the numerical values of these parameters with the risk of aneurysm rupture or intervention (surgical or endovascular). While this work does not provide direct insight into the possible clinical use of the geometric parameters, we believe it provides the foundation necessary for future efforts in that direction.
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| 13. |
- Sherina, Natalia, et al.
(författare)
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Persistence of SARS-CoV-2-specific B and T cell responses in convalescent COVID-19 patients 6-8 months after the infection
- 2021
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Ingår i: Med. - : Elsevier BV. - 2666-6340. ; 2:3, s. 281-295
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monitoring the adaptive immune responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection provides useful information for the development of vaccination strategies against this virus and its emerging variants. We thus profiled the serum anti-SARS-CoV-2 antibody (Ab) levels and specific memory B and T cell responses in convalescent coronavirus disease 2019 (COVID-19) patients.Methods: A total of 119 samples from 88 convalescent donors who experienced mild to critical disease were tested for the presence of elevated anti-spike and anti-receptor binding domain Ab levels over a period of 8 months. In addition, the levels of SARS-CoV-2 neutralizing Abs and specific memory B and T cell responses were tested in a subset of samples.Findings: Anti-SARS-CoV-2 Abs were present in 85% of the samples collected within 4 weeks after the onset of symptoms in COVID-19 patients. Levels of specific immunoglobulin M (IgM)/IgA Abs declined after 1 month, while levels of specific IgG Abs and plasma neutralizing activities remained relatively stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG Abs were still present, although at a significantly lower level, in 80% of the samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B and T cell responses developed with time and were persistent in all of the patients followed up for 6-8 months.Conclusions: Our data suggest that protective adaptive immunity following natural infection of SARS-CoV-2 may persist for at least 6-8 months, regardless of disease severity. Development of medium- or long-term protective immunity through vaccination may thus be possible.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Shum, Judy, et al.
(författare)
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Quantitative Assessment of Abdominal Aortic Aneurysm Geometry
- 2011
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 39:1, s. 277-286
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that the maximum transverse diameter of an abdominal aortic aneurysm (AAA) and expansion rate are not entirely reliable indicators of rupture potential. We hypothesize that aneurysm morphology and wall thickness are more predictive of rupture risk and can be the deciding factors in the clinical management of the disease. A non-invasive, image-based evaluation of AAA shape was implemented on a retrospective study of 10 ruptured and 66 unruptured aneurysms. Three-dimensional models were generated from segmented, contrast-enhanced computed tomography images. Geometric indices and regional variations in wall thickness were estimated based on novel segmentation algorithms. A model was created using a J48 decision tree algorithm and its performance was assessed using ten-fold cross validation. Feature selection was performed using the chi(2)-test. The model correctly classified 65 datasets and had an average prediction accuracy of 86.6% (kappa = 0.37). The highest ranked features were sac length, sac height, volume, surface area, maximum diameter, bulge height, and intra-luminal thrombus volume. Given that individual AAAs have complex shapes with local changes in surface curvature and wall thickness, the assessment of AAA rupture risk should be based on the accurate quantification of aneurysmal sac shape and size.
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| 18. |
- Shum, Judy, et al.
(författare)
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Quantitative assessment of abdominal aortic aneurysm geometry and rupture potential
- 2009
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Ingår i: PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2009, PT A AND B. - 9780791848913 ; , s. 1303-1304
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Konferensbidrag (refereegranskat)abstract
- Recent biomechanics studies have shown that the maximum transverse diameter of an abdominal aortic aneurysm (AAA) and its expansion rate are not reliable indicators of rupture potential. We hypothesize that geometrical shape and size, as well as wall thickness may be related to rupture risk and can therefore be deciding factors in the clinical management of the disease. A non-invasive, image-based evaluation of AAA size and geometry was implemented on a retrospective study of twenty subjects. The contrast enhanced, computed tomography (CT) scans of 10 patients who suffered AAA rupture within 1 month of the scan were compared to those of 10 patients who received elective repair. The images were segmented and three-dimensional models were generated. Twenty-eight geometry-based indices were calculated to characterize the size and shape of each AAA and regional variations in wall thickness were estimated. A multivariate analysis of variance was performed for all indices comparing the ruptured and non-ruptured data sets to determine which indices are statistically significant. Receiving Operating Characteristic (ROC) curves were generated to determine the indices' potential as predictors of rupture risk. In addition to maximum diameter, five other geometry-based indices were found to be statistically significant, with the minimum wall thickness being the best discriminator between ruptures and non-ruptured AAAs.
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| 19. |
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| 20. |
- Shum, Judy, et al.
(författare)
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Semiautomatic vessel wall detection and quantification of wall thickness in computed tomography images of human abdominal aortic aneurysms
- 2010
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Ingår i: Medical physics (Lancaster). - : Wiley. - 0094-2405. ; 37:2, s. 638-648
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Quantitative measurements of wall thickness in human abdominal aortic aneurysms (AAAs) may lead to more accurate methods for the evaluation of their biomechanical environment. Methods: The authors describe an algorithm for estimating wall thickness in AAAs based on intensity histograms and neural networks involving segmentation of contrast enhanced abdominal computed tomography images. The algorithm was applied to ten ruptured and ten unruptured AAA image data sets. Two vascular surgeons manually segmented the lumen, inner wall, and outer wall of each data set and a reference standard was defined as the average of their segmentations. Reproducibility was determined by comparing the reference standard to lumen contours generated automatically by the algorithm and a commercially available software package. Repeatability was assessed by comparing the lumen, outer wall, and inner wall contours, as well as wall thickness, made by the two surgeons using the algorithm. Results: There was high correspondence between automatic and manual measurements for the lumen area (r=0.978 and r=0.996 for ruptured and unruptured aneurysms, respectively) and between vascular surgeons (r=0.987 and r=0.992 for ruptured and unruptured aneurysms, respectively). The authors' automatic algorithm showed better results when compared to the reference with an average lumen error of 3.69%, which is less than half the error between the commercially available application Simpleware and the reference (7.53%). Wall thickness measurements also showed good agreement between vascular surgeons with average coefficients of variation of 10.59% (ruptured aneurysms) and 13.02% (unruptured aneurysms). Ruptured aneurysms exhibit significantly thicker walls (1.78±0.39 mm) than unruptured ones (1.48±0.22 mm), p=0.044. Conclusions: While further refinement is needed to fully automate the outer wall segmentation algorithm, these preliminary results demonstrate the method's adequate reproducibility and low interobserver variability.
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| 21. |
- Visentin, Cristina, et al.
(författare)
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Glycosylation Tunes Neuroserpin Physiological and Pathological Properties
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:9
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Tidskriftsartikel (refereegranskat)abstract
- Neuroserpin (NS) is a member of the serine protease inhibitors superfamily. Specific point mutations are responsible for its accumulation in the endoplasmic reticulum of neurons that leads to a pathological condition named familial encephalopathy with neuroserpin inclusion bodies (FENIB). Wild-type NS presents two N-glycosylation chains and does not form polymers in vivo, while non-glycosylated NS causes aberrant polymer accumulation in cell models. To date, all in vitro studies have been conducted on bacterially expressed NS, de facto neglecting the role of glycosylation in the biochemical properties of NS. Here, we report the expression and purification of human glycosylated NS (gNS) using a novel eukaryotic expression system, LEXSY. Our results confirm the correct N-glycosylation of wild-type gNS. The fold and stability of gNS are not altered compared to bacterially expressed NS, as demonstrated by the circular dichroism and intrinsic tryptophan fluorescence assays. Intriguingly, gNS displays a remarkably reduced polymerisation propensity compared to non-glycosylated NS, in keeping with what was previously observed for wild-type NS in vivo and in cell models. Thus, our results support the relevance of gNS as a new in vitro tool to study the molecular bases of FENIB.
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| 22. |
- Zanni, Giulia, et al.
(författare)
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Lithium increases proliferation of hippocampal neural stem/progenitor cells and rescues irradiation-induced cell cycle arrest in vitro.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy in children causes debilitating cognitive decline, partly linked to impaired neurogenesis. Irradiation targets primarily cancer cells but also endogenous neural stem/progenitor cells (NSPCs) leading to cell death or cell cycle arrest. Here we evaluated the effects of lithium on proliferation, cell cycle and DNA damage after irradiation of young NSPCs in vitro.NSPCs were treated with 1 or 3 mM LiCl and we investigated proliferation capacity (neurosphere volume and bromodeoxyuridine (BrdU) incorporation). Using flow cytometry, we analysed apoptosis (annexin V), cell cycle (propidium iodide) and DNA damage (γH2AX) after irradiation (3.5 Gy) of lithium-treated NSPCs.Lithium increased BrdU incorporation and, dose-dependently, the number of cells in replicative phase as well as neurosphere growth. Irradiation induced cell cycle arrest in G1 and G2/M phases. Treatment with 3 mM LiCl was sufficient to increase NSPCs in S phase, boost neurosphere growth and reduce DNA damage. Lithium did not affect the levels of apoptosis, suggesting that it does not rescue NSPCs committed to apoptosis due to accumulated DNA damage.Lithium is a very promising candidate for protection of the juvenile brain from radiotherapy and for its potential to thereby improve the quality of life for those children who survive their cancer.
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| 23. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 24. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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