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1.
  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
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7.
  • Gregson, J., et al. (author)
  • Cardiovascular Risk Factors Associated With Venous Thromboembolism
  • 2019
  • In: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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8.
  • Kobel, M., et al. (author)
  • p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
  • 2023
  • In: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222
  • Journal article (peer-reviewed)abstract
    • Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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9.
  • Abbafati, Cristiana, et al. (author)
  • 2020
  • Journal article (peer-reviewed)
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10.
  • Ademuyiwa, Adesoji O., et al. (author)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Journal article (peer-reviewed)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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11.
  • Kang, E. Y., et al. (author)
  • Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses
  • 2021
  • In: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 34:1, s. 194-206
  • Journal article (peer-reviewed)abstract
    • TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (INC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
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12.
  • Santoro, V., et al. (author)
  • HighNESS conceptual design report: Volume I
  • 2024
  • In: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 85-314
  • Journal article (peer-reviewed)abstract
    • The European Spallation Source, currently under construction in Lund, Sweden, is a multidisciplinary international laboratory. Once completed to full specifications, it will operate the world’s most powerful pulsed neutron source. Supported by a 3 million Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) has been completed to develop a second neutron source located below the spallation target. Compared to the first source, designed for high cold and thermal brightness, the new source has been optimized to deliver higher intensity, and a shift to longer wavelengths in the spectral regions of cold (CN, 2–20 Å), very cold (VCN, 10–120 Å), and ultracold (UCN, >500 Å) neutrons. The second source comprises a large liquid deuterium moderator designed to produce CN and support secondary VCN and UCN sources. Various options have been explored in the proposed designs, aiming for world-leading performance in neutronics. These designs will enable the development of several new instrument concepts and facilitate the implementation of a high-sensitivity neutron-antineutron oscillation experiment (NNBAR). This document serves as the Conceptual Design Report for the HighNESS project, representing its final deliverable.
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13.
  • Santoro, V., et al. (author)
  • HighNESS conceptual design report: Volume II. the NNBAR experiment.
  • 2024
  • In: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 315-406
  • Journal article (peer-reviewed)abstract
    • A key aim of the HighNESS project for the European Spallation Source is to enable cutting-edge particle physics experiments. This volume presents a conceptual design report for the NNBAR experiment. NNBAR would exploit a new cold lower moderator to make the first search in over thirty years for free neutrons converting to anti-neutrons. The observation of such a baryon-number-violating signature would be of fundamental significance and tackle open questions in modern physics, including the origin of the matter-antimatter asymmetry. This report shows the design of the beamline, supermirror focusing system, magnetic and radiation shielding, and anti-neutron detector necessary for the experiment. A range of simulation programs are employed to quantify the performance of the experiment and show how background can be suppressed. For a search with full background suppression, a sensitivity improvement of three orders of magnitude is expected, as compared with the previous search. Civil engineering studies for the NNBAR beamline are also shown, as is a costing model for the experiment.
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  • Bhattacharya, S. K., et al. (author)
  • 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: A cluster-randomised, double-blind, placebo-controlled trial
  • 2013
  • In: Lancet. Infectious Diseases. - 1473-3099 .- 1474-4457. ; 13:12, s. 1050-1056
  • Journal article (peer-reviewed)abstract
    • Background: Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. Methods: In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. Findings: 69 of 31932 recipients of vaccine and 219 of 34968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Interpretation: Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Funding: Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. © 2013 Elsevier Ltd.
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16.
  • Calder, S., et al. (author)
  • Neutron scattering and mu SR investigations of the low temperature state of LuCuGaO4
  • 2013
  • In: Journal of Physics: Condensed Matter. - : IOP Publishing. - 1361-648X .- 0953-8984. ; 25:35
  • Journal article (peer-reviewed)abstract
    • LuCuGaO4 has magnetic Cu2+ and diamagnetic Ga3+ ions distributed on a triangular bilayer and is suggested to undergo a spin glass transition at T-g similar to 0.4 K. Using mu SR (muon spin rotation) and neutron scattering measurements, we show that at low temperature the spins form a short range correlated state with spin fluctuations detectable over a wide range of timescales: at 0.05 K magnetic fluctuations can be detected in both the mu SR time window and also extending beyond 7 meV in the inelastic neutron scattering response, indicating magnetic fluctuations spanning timescales between similar to 10(-5) and similar to 10(-10) s. The dynamical susceptibility scales according to the form chi '' (omega)T-alpha, with alpha = 1, throughout the measured temperature range (0.05-50 K). These effects are associated with quantum fluctuations and some degree of structural disorder in ostensibly quite different materials, including certain heavy fermion alloys, kagome spin liquids, quantum spin glasses, and valence bond glasses. We therefore suggest that LuCuGaO4 is an interesting model compound for the further examination of disorder and quantum magnetism.
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17.
  • Portnichenko, P. Y., et al. (author)
  • Momentum-space structure of quasielastic spin fluctuations in Ce3Pd20Si6
  • 2015
  • In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 91:9
  • Journal article (peer-reviewed)abstract
    • Among heavy-fermion metals, Ce3Pd20Si6 is one of the heaviest-electron systems known to date. Here we used high-resolution neutron spectroscopy to observe low-energy magnetic scattering from a single crystal of this compound in the paramagnetic state. We investigated its temperature dependence and distribution in momentum space, which was not accessible in earlier measurements on polycrystalline samples. At low temperatures, a quasielastic magnetic response with a half-width Gamma approximate to 0.1 meV persists with varying intensity all over the Brillouin zone. It forms a broad hump centered at the (111) scattering vector, surrounded by minima of intensity at (002), (220), and equivalent wave vectors. The momentum-space structure distinguishes this signal from a simple crystal-field excitation at 0.31 meV, suggested previously, and rather lets us ascribe it to short-range dynamical correlations between the neighboring Ce ions, mediated by the itinerant heavy f electrons via the Ruderman-Kittel-Kasuya-Yosida mechanism. With increasing temperature, the energy width of the signal follows the conventional T-1/2 law, Gamma(T) = Gamma(0) + A root T. The momentum-space symmetry of the quasielastic response suggests that it stems from the simple-cubic Ce sublattice occupying the 8c Wyckoff site, whereas the crystallographically inequivalent 4a site remains magnetically silent in this material.
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18.
  • Bhattacharya, S, et al. (author)
  • Public health. The cholera crisis in Africa.
  • 2009
  • In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 324:5929
  • Research review (peer-reviewed)abstract
    • Long-lasting cholera outbreaks in Africa suggest limitations in the current strategy of disease control.
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19.
  • Adroja, D. T., et al. (author)
  • Competing 4 f-electron dynamics in Ce(Ru1-xFex)(2)Al-10 (0
  • 2013
  • In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 87:22
  • Journal article (peer-reviewed)abstract
    • We have carried out muon spin relaxation (mu SR), neutron diffraction, and inelastic neutron scattering (INS) investigations on polycrystalline samples of Ce(Ru1-xFex)(2)Al-10 (x = 0, 0.3, 0.5, 0.8, and 1) to investigate the nature of the ground state (magnetic ordered versus paramagnetic) and the origin of the spin-gap formation as evident from the bulk measurements in the end members. Our zero-field mu SR spectra clearly reveal coherent two-frequency oscillations at low temperature in x = 0, 0.3, and 0.5 samples, which confirm the long-range magnetic ordering of the Ce moment with Neel temperature T-N = 27, 26, and 21 K, respectively. On the other hand, the mu SR spectra of x = 0.8 and x = 1 down to 1.4 K and 0.045 K, respectively, exhibit a temperature-independent Kubo-Toyabe term, confirming a paramagnetic ground state. The long-range magnetic ordering in x = 0.5 below 21 K has been confirmed through the neutron diffraction study. INS measurements of x = 0 clearly reveal the presence of a sharp inelastic excitation near 8 meV between 5 K and 26 K, due to an opening of a gap in the spin excitation spectrum, which transforms into a broad response at and above 30 K. Interestingly, at 4.5 K, the spin-gap excitation broadens in x = 0.3 and exhibits two clear peaks at 8.4(3) and 12.0(5) meV in x = 0.5. In the x = 0.8 sample, which remains paramagnetic down to 1.2 K, there is a clear signature of a spin gap of 10-12 meV at 7 K, with a strong wave-vector-dependent intensity. Evidence of a spin gap of 12.5(5) meV has also been found in x = 1. The observation of a spin gap in the paramagnetic samples (x = 0.8 and 1) is an interesting finding in this study, and it challenges our understanding of the origin of the semiconducting gap in CeT2Al10 (T = Ru and Os) compounds in terms of a hybridization gap opening only a small part of the Fermi surface, gapped spin waves, or a spin-dimer gap.
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20.
  • Anastasopoulos, M., et al. (author)
  • Multi-Grid detector for neutron spectroscopy : Results obtained on time-of-flight spectrometer CNCS
  • 2017
  • In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12:4
  • Journal article (peer-reviewed)abstract
    • The Multi-Grid detector technology has evolved from the proof-of-principle and characterisation stages. Here we report on the performance of the Multi-Grid detector, the MG.CNCS prototype, which has been installed and tested at the Cold Neutron Chopper Spectrometer, CNCS at SNS. This has allowed a side-by-side comparison to the performance of 3He detectors on an operational instrument. The demonstrator has an active area of 0.2 m2. It is specifically tailored to the specifications of CNCS. The detector was installed in June 2016 and has operated since then, collecting neutron scattering data in parallel to the He-3 detectors of CNCS. In this paper, we present a comprehensive analysis of this data, in particular on instrument energy resolution, rate capability, background and relative efficiency. Stability, gamma-ray and fast neutron sensitivity have also been investigated. The effect of scattering in the detector components has been measured and provides input to comparison for Monte Carlo simulations. All data is presented in comparison to that measured by the 3He detectors simultaneously, showing that all features recorded by one detector are also recorded by the other. The energy resolution matches closely. We find that the Multi-Grid is able to match the data collected by 3He, and see an indication of a considerable advantage in the count rate capability. Based on these results, we are confident that the Multi-Grid detector will be capable of producing high quality scientific data on chopper spectrometers utilising the unprecedented neutron flux of the ESS.
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21.
  • Backis, A., et al. (author)
  • Time- and energy-resolved effects in the boron-10 based multi-grid and helium-3 based thermal neutron detectors
  • 2021
  • In: Measurement science and technology. - : IOP PUBLISHING LTD. - 0957-0233 .- 1361-6501. ; 32:3
  • Journal article (peer-reviewed)abstract
    • The boron-10 based multi-grid detector is being developed as an alternative to helium-3 based neutron detectors. At the European Spallation Source, the detector will be used for time-of-flight neutron spectroscopy at cold to thermal neutron energies. The objective of this work is to investigate fine time- and energy-resolved effects of the Multi-Grid detector, down to a few mu eV, while comparing it to the performance of a typical helium-3 tube. Furthermore, it is to characterize differences between the detector technologies in terms of internal scattering, as well as the time reconstruction of similar to mu s short neutron pulses. The data were taken at the Helmholtz Zentrum Berlin, where the Multi-Grid detector and a helium-3 tube were installed at the ESS test beamline, V20. Using a Fermi-chopper, the neutron beam of the reactor was chopped into a few tens of mu s wide pulses before reaching the detector, located a few tens of cm downstream. The data of the measurements show an agreement between the derived and calculated neutron detection efficiency curve. The data also provide fine details on the effect of internal scattering, and how it can be reduced. For the first time, the chopper resolution was comparable to the timing resolution of the Multi-Grid detector. This allowed a detailed study of time- and energy resolved effects, as well as a comparison with a typical helium-3 tube.
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24.
  • El-Serafi, Ahmed Taher, 1977-, et al. (author)
  • Dysregulation of male sex hormones in chronic hepatitis C patients
  • 2016
  • In: Andrologia. - Berlin, Germany : Wiley-Blackwell. - 0303-4569 .- 1439-0272. ; 48:1, s. 82-86
  • Journal article (peer-reviewed)abstract
    • Chronic hepatitis C (HCV) infection is a serious problem all over the world and has a special importance in Egypt, where the prevalence of infection is 14.7% of population. In males, HCV is associated with sexual dysfunction and changes in the semen parameters. This study aimed at estimation of a panel of the most important related hormones in the serum of patients and illustration of their correlation to the routine laboratory investigations. The four studied hormones showed alteration in the patients in comparison with the controls. While androstenedione, prolactin and testosterone were significantly increased in patients, dehydroepiandrosterone sulphate was decreased. These changes in the hormones were not related to the liver functions, pathological grade or even viral load. We hypothesised a model of how HCV can induce these hormonal changes and recommended to add these hormones to the follow-up panel of male patients with HCV.
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25.
  • Itel, F., et al. (author)
  • CO2 permeability of cell membranes is regulated by membrane cholesterol and protein gas channels
  • 2012
  • In: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 26:12, s. 5182-5191
  • Journal article (peer-reviewed)abstract
    • Recent observations that some membrane proteins act as gas channels seem surprising in view of the classical concept that membranes generally are highly permeable to gases. Here, we study the gas permeability of membranes for the case of CO2, using a previously established mass spectrometric technique. We first show that biological membranes lacking protein gas channels but containing normal amounts of cholesterol (30-50 mol% of total lipid), e.g., MDCK and tsA201 cells, in fact possess an unexpectedly low CO2 permeability (PCO2) of similar to 0.01 cm/s, which is 2 orders of magnitude lower than the PCO2 of pure planar phospholipid bilayers (similar to 1 cm/s). Phospholipid vesicles enriched with similar amounts of cholesterol also exhibit PCO2 approximate to 0.01 cm/s, identifying cholesterol as the major determinant of membrane PCO2. This is confirmed by the demonstration that MDCK cells depleted of or enriched with membrane cholesterol show dramatic increases or decreases in PCO2, respectively. We demonstrate, furthermore, that reconstitution of human AQP-1 into cholesterol-containing vesicles, as well as expression of human AQP-1 in MDCK cells, leads to drastic increases in PCO2, indicating that gas channels are of high functional significance for gas transfer across membranes of low intrinsic gas permeability.-Itel, F., Al-Samir, S., Oberg, F., Chami, M., Kumar, M., Supuran, C. T., Deen, P. M. T., Meier, W., Hedfalk, K., Gros, G., Endeward, V. CO2 permeability of cell membranes is regulated by membrane cholesterol and protein gas channels. FASEB J. 26, 5182-5191 (2012). www.fasebj.org
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26.
  • Jacobsen, Henrik, et al. (author)
  • Spin dynamics of the director state in frustrated hyperkagome systems
  • 2021
  • In: Physical Review B. - : American Physical Society. - 2469-9969 .- 2469-9950. ; 104:5
  • Journal article (peer-reviewed)abstract
    • We present an experimental study of the magnetic structure and dynamics of two frustrated hyperkagome compounds, Gd3Ga5O12 and Gd3Al5O12. It has previously been shown that Gd3Ga5O12 exhibits long-range correlations of multipolar directors that are formed from antiferromagnetic spins on loops of ten ions. Using neutron diffraction and reverse Monte Carlo simulations we prove the existence of similar magnetic correlations in Gd3Al5O12, showing the ubiquity of these complex structures in frustrated hyperkagome materials. Using inelastic neutron scattering we shed further light on the director state and the associated low-lying magnetic excitations. In addition, we have measured quasielastic dynamics that show evidence of spin diffusion. Finally, we present AC susceptibility measurements on both Gd3Ga5O12 and Gd3Al5O12, revealing a large difference in the low-frequency dynamics between the two otherwise similar compounds.
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27.
  • Melero-Fernandez de Mera, R. M., et al. (author)
  • Effects of mutations in the post-translational modification sites on the trafficking of hyaluronan synthase 2 (HAS2)
  • 2019
  • In: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 80, s. 85-103
  • Journal article (peer-reviewed)abstract
    • Vesicular trafficking of hyaluronan synthases (HAS1-3) from endoplasmic reticulum (ER) through Golgi to plasma membrane (PM), and either back to endosomes and lysosomes, or out into extracellular vesicles, is important for their activities. We studied how post-translational modifications affect the trafficking of HAS2 by mutagenesis of the sites of ubiquitination (K190R), phosphorylation (T110A) and 0-GIcNAcylation (S221A), using Dendra2- and EGFP-HAS2 transfected into COS1 cells. Confocal microscopy showed HAS2 wild type (wt) and its K19OR and S221A mutants in ER, Golgi and extracellular vesicles, while the T110A mutant remained mostly in the ER. HA synthesis was reduced by S221A, while completely blocked by K19OR and T110A. Cell-surface biotinylation indicated that T110A was absent from PM, while S221A was close to the level of wt, and K190R was increased in PM. TIRF microscopy analysis gave similar results. Rabl 0 silencing increased HA secretion by HAS2, likely by inhibiting endocytosis of the enzyme from PM, as reported before for HAS3. Green-to-red photo-conversion of Dendra2-HAS2 constructs suggested slower decay of K190R and S221A than HAS2 wt, while T110A was barely degraded at all. S221D and S221E, the phosphomimetic mutants of this site, decayed faster and blocked hyaluronan synthesis, suggesting alternative 0-GIcNAci-PO4 substitution to regulate the stability of the enzyme. Probing the role of dynamic 0-GIcNAcylation at S221 by adding glucosamine increased the half-life of only HAS2 wt. The Dendra2 " HAS2 disappearance from Golgi was slower for K190R. Of the two inactive constructs, K190R co-transfected with HAS2 wt suppressed, whereas T110A had no effect on HA synthesis. Interestingly, the HAS2stimulated shedding of extracellular vesicles was dependent on HAS residence in PM but independent of HA synthesis. The results indicate that post-translational modifications control the trafficking of HAS2, and that trafficking is an integral part of the post-translational regulation of HAS2 activity.
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29.
  • Sandberg, Lise Orduk, et al. (author)
  • Emergent magnetic behavior in the frustrated Yb3Ga5O12 garnet
  • 2021
  • In: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 104:6
  • Journal article (peer-reviewed)abstract
    • We report neutron scattering, magnetic susceptibility and Monte Carlo theoretical analysis to verify the short-range nature of the magnetic structure and spin-spin correlations in a Yb3Ga5O12 single crystal. The quantum spin state of Yb3+ in Yb3Ga5O12 is verified. The quantum spins organize into a short-ranged emergent director state for T < 0.6 K derived from anisotropy and near-neighbor exchange. We derive the magnitude of the nearneighbor exchange interactions 0.6 < J(1) < 0.7 K, J(2) = 0.12 K and the magnitude of the dipolar exchange interaction, D, in the range 0.18 < D < 0.21 K. Certain aspects of the broad experimental dataset can be modeled using a J(1)D model with ferromagnetic near-neighbor spin-spin correlations while other aspects of the data can be accurately reproduced using a J(1)J(2)D model with antiferromagnetic near-neighbor spin-spin correlation. As such, although we do not quantify all the relevant exchange interactions, we nevertheless provide a strong basis for the understanding of the complex Hamiltonian required to fully describe the magnetic state of Yb3Ga5O12.
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30.
  • Seiler, Roland, et al. (author)
  • Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy
  • 2017
  • In: European Urology. - : Elsevier BV. - 0302-2838. ; 72:4, s. 544-554
  • Journal article (peer-reviewed)abstract
    • Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Design, setting, and participants: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Intervention: Gene expression analysis was used to assign subtypes. Outcome measurements and statistical analysis: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. Results and limitations: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Conclusions: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Patient summary: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation. Molecular subtypes in muscle-invasive bladder cancer appear have an impact on patient response to neoadjuvant chemotherapy (NAC); namely, patients with basal tumors showed the most benefit from NAC and should be prioritized for NAC. Moreover, these subtypes can be identified in a single sample by our discovered classifier.
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31.
  • Soliveres, S., et al. (author)
  • Excess low frequency noise in single-wall carbon nanotube
  • 2006
  • In: Fluctuation and Noise Letters. - : WORLD SCIENTIFIC PUBL CO PTE LTD. - 0219-4775 .- 1793-6780. ; 6:1, s. L45-L55
  • Journal article (peer-reviewed)abstract
    • Low frequency noise measurements have been performed on a single-wall carbon nanotube connected by Ti/Au electrodes. It has been found that the 1/f noise decreases when the measurements are undertaken under vacuum and when the nanotube is partially degassed, showing a correlation between the fluctuation inducing the 1/f noise and the presence of gases. We show that the 1/f noise sources are located at the metal/nanotube contacts. When the device is annealed under vacuum at 450K, some Lorentzian shapes are observable and can be related to nanotube defects or to strongly bound molecules. © World Scientific Publishing Company.
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32.
  • Telling, M. T. F., et al. (author)
  • Pressure-dependent spin fluctuations and magnetic structure in the topologically frustrated spin glass alloy Y(Mn0.95Al0.05)(2)
  • 2012
  • In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 85:18
  • Journal article (peer-reviewed)abstract
    • Longitudinal field (LF = 110 G) muon spin relaxation (mu SR) has been used to investigate the pressure dependence (P < 4.5 kbar) of paramagnetic spin fluctuations in the spin glass alloy Y(Mn0.95Al0.05)(2) via observation of the mu(+) spin depolarization. External mechanical force is seen to counteract the Al-induced chemical pressure, fully delocalizing the Mn moment and altering the nature of the spin fluctuation spectrum sensed by the muon. A qualitative change in the functional form of the mu(+) spin depolarization is observed. Complementary ambient and high-pressure neutron diffraction measurements suggest not only pressure-dependent structural transitions but also the instability of the localized manganese moment. The ambient and high-pressure mu(+) spin depolarization results from Y(Mn0.95Al0.05)(2) are likened to P = 0 results reported for other Y(Mn1-xAlx)(2) alloys. Finally, the possibility of using mu(+) spin depolarization rates to predict experimental inelastic neutron scattering (INS) line widths is considered; the muon having the potential to provide information equivalent to that obtained via INS but with greatly reduced data collection times.
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33.
  • Zanatta, M., et al. (author)
  • A large-area double rotating-crystal monochromator for time-focusing neutron instruments
  • 2016
  • In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 746:1
  • Journal article (peer-reviewed)abstract
    • We present the principle and the first prototypes of a double rotating-crystal monochromator, based on an assembly of smaller rotating elements. Such a device was developed as the key element to implement a parallel-beam modification of the time-focusing technique for neutron spectrometers. This concept is particularly promising for long-pulse sources and can bring specific advantages on continuous sources as well. Neutron tests performed on the first prototypes validate the mechanical reliability of the proposed design and the feasibility of a large-area double rotating-crystal monochromator based on this technology.
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