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  • Thomas, HS, et al. (författare)
  • 2019
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  • Gregson, J., et al. (författare)
  • Cardiovascular Risk Factors Associated With Venous Thromboembolism
  • 2019
  • Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
  • Tidskriftsartikel (refereegranskat)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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  • Kobel, M., et al. (författare)
  • p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
  • 2023
  • Ingår i: Journal of Pathology Clinical Research. - : Wiley. - 2056-4538. ; 9:3, s. 208-222
  • Tidskriftsartikel (refereegranskat)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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  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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  • Santoro, V., et al. (författare)
  • HighNESS conceptual design report: Volume I
  • 2024
  • Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 85-314
  • Tidskriftsartikel (refereegranskat)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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  • Santoro, V., et al. (författare)
  • HighNESS conceptual design report: Volume II. the NNBAR experiment.
  • 2024
  • Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 315-406
  • Tidskriftsartikel (refereegranskat)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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  • Adroja, D. T., et al. (författare)
  • Competing 4 f-electron dynamics in Ce(Ru1-xFex)(2)Al-10 (0
  • 2013
  • Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 87:22
  • Tidskriftsartikel (refereegranskat)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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  • Itel, F., et al. (författare)
  • CO2 permeability of cell membranes is regulated by membrane cholesterol and protein gas channels
  • 2012
  • Ingår i: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 26:12, s. 5182-5191
  • Tidskriftsartikel (refereegranskat)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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  • Anastasopoulos, M., et al. (författare)
  • Multi-Grid detector for neutron spectroscopy : Results obtained on time-of-flight spectrometer CNCS
  • 2017
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12:4
  • Tidskriftsartikel (refereegranskat)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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  • Backis, A., et al. (författare)
  • Time- and energy-resolved effects in the boron-10 based multi-grid and helium-3 based thermal neutron detectors
  • 2021
  • Ingår i: Measurement science and technology. - : IOP PUBLISHING LTD. - 0957-0233 .- 1361-6501. ; 32:3
  • Tidskriftsartikel (refereegranskat)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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  • Bhattacharya, S. K., et al. (författare)
  • 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: A cluster-randomised, double-blind, placebo-controlled trial
  • 2013
  • Ingår i: Lancet. Infectious Diseases. - 1473-3099 .- 1474-4457. ; 13:12, s. 1050-1056
  • Tidskriftsartikel (refereegranskat)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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20.
  • Calder, S., et al. (författare)
  • Neutron scattering and mu SR investigations of the low temperature state of LuCuGaO4
  • 2013
  • Ingår i: Journal of Physics: Condensed Matter. - : IOP Publishing. - 1361-648X .- 0953-8984. ; 25:35
  • Tidskriftsartikel (refereegranskat)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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  • Cherkashyna, Nataliia, et al. (författare)
  • High energy particle background at neutron spallation sources and possible solutions
  • 2014
  • Ingår i: International Workshop on Neutron Optics and Detectors (NOP&D 2013) 2–5 July 2013, Munich, Germany. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 528, s. 012013-012013
  • Konferensbidrag (refereegranskat)abstract
    • Modern spallation neutron sources are driven by proton beams similar to GeV energies. Whereas low energy particle background shielding is well understood for reactors sources of neutrons (similar to 20 MeV), for high energies (100s MeV to multiple GeV) there is potential to improve shielding solutions and reduce instrument backgrounds significantly. We present initial measured data on high energy particle backgrounds, which illustrate the results of particle showers caused by high energy particles from spallation neutron sources. We use detailed physics models of different materials to identify new shielding solutions for such neutron sources, including laminated layers of multiple materials. In addition to the steel and concrete, which are used traditionally, we introduce some other options that are new to the neutron scattering community, among which there are copper alloys as used in hadronic calorimeters in high energy physics laboratories. These concepts have very attractive energy absorption characteristics, and simulations predict that the background suppression could be improved by one or two orders of magnitude. These solutions are expected to be great benefit to the European Spallation Source, where the majority of instruments are potentially affected by high energy backgrounds, as well as to existing spallation sources.
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  • Edberg, Richard, et al. (författare)
  • Dipolar spin ice under uniaxial pressure
  • 2019
  • Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 100:14
  • Tidskriftsartikel (refereegranskat)abstract
    • The magnetically frustrated spin ice family of materials is host to numerous exotic phenomena such as magnetic monopole excitations and macroscopic residual entropy extending to low temperature. A finite-temperature ordering transition in the absence of applied fields has not been experimentally observed in the classical spin ice materials Dy2Ti2O7 and Ho2Ti2O7. Such a transition could be induced by the application of pressure, and in this work we consider the effects of uniaxial pressure on classical spin ice systems. Theoretically, we find that the pressure-induced ordering transition in Dy2Ti2O7 is strongly affected by the dipolar interaction. We also report measurements of the neutron structure factor of Ho2Ti2O7 under pressure and compare the experimental results to the predictions of our theoretical model.
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  • Edberg, Richard, et al. (författare)
  • Effects of uniaxial pressure on the spin ice Ho2Ti2O7
  • 2020
  • Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 102:18
  • Tidskriftsartikel (refereegranskat)abstract
    • The spin ice materials Ho2Ti2O7 and Dy2Ti2O7 are experimental and theoretical exemplars of highly frustrated magnetic materials. However, the effects of applied uniaxial pressure are not well studied, and here we report magnetization measurements of Ho2Ti2O7 under uniaxial pressure applied in the [001], [111], and [110] crystalline directions. The basic features are captured by an extension of the dipolar spin ice model. We find a good match between our model and measurements with pressures applied along two of the three directions, and we extend the framework to discuss the influence of crystal misalignment for the third direction. The parameters determined from the magnetization measurements reproduce neutron scattering measurements that we perform under uniaxial pressure applied along the [110] crystalline direction. In the detailed analysis, we include the recently verified susceptibility dependence of the demagnetizing factor. Our work demonstrates the application of a moderate applied pressure to modify the magnetic interaction parameters. The knowledge can be used to predict critical pressures needed to induce new phases and transitions in frustrated materials, and in the case of Ho2Ti2O7 we expect a transition to a ferromagnetic ground state for uniaxial pressures above 3.3 GPa.
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25.
  • Frick, Anna, 1982, et al. (författare)
  • X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking.
  • 2014
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:17, s. 6305-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 Å resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal α-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein-protein interactions involved in cellular sorting of AQP2. Two Cd(2+)-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking.
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