| 1. |
- Aguilar, J. A., et al.
(författare)
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Triboelectric backgrounds to radio-based polar ultra-high energy neutrino (UHEN) experiments
- 2023
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- In the hopes of observing the highest-energy neutrinos (E> 1 EeV) populating the Universe, both past (RICE, AURA, ANITA) and current (RNO-G, ARIANNA, ARA and TAROGE-M) polar-sited experiments exploit the impulsive radio emission produced by neutrino interactions. In such experiments, rare single event candidates must be unambiguously identified above backgrounds. Background rejection strategies to date primarily target thermal noise fluctuations and also impulsive radio-frequency signals of anthropogenic origin. In this paper, we consider the possibility that 'fake' neutrino signals may also be generated naturally via the `triboelectric effect' This broadly describes any process in which force applied at a boundary layer results in displacement of surface charge, leading to the production of an electrostatic potential difference AV. Wind blowing over granular surfaces such as snow can induce such a potential difference, with subsequent coronal discharge. Discharges over timescales as short as nanoseconds can then lead to radio-frequency emissions at characteristic MHz-GHz frequencies. Using data from various past (RICE, AURA, SATRA, ANITA) and current (RNO G, ARIANNA and ARA) neutrino experiments, we find evidence for such backgrounds, which are generally characterized by: (a) a threshold wind velocity which likely depends on the experimental trigger criteria and layout; for the experiments considered herein, this value is typically O(10 m/s), (b) frequency spectra generally shifted to the low-end of the frequency regime to which current radio experiments are typically sensitive (100-200 MHz), (c) for the strongest background signals, an apparent preference for discharges from above-surface structures, although the presence of more isotropic, lower amplitude triboelectric discharges cannot be excluded.
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| 2. |
- Alcorn, J, et al.
(författare)
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Basic instrumentation for Hall A at Jefferson Lab
- 2004
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 522:3, s. 294-346
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Tidskriftsartikel (refereegranskat)abstract
- The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved.
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| 3. |
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| 4. |
- Chirapatpimol, K, et al.
(författare)
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Precision Measurement of the p(e,e′p)π0 Reaction at Threshold
- 2015
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Ingår i: Physical Review Letters. - 1079-7114. ; 114:19
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Tidskriftsartikel (refereegranskat)abstract
- New results are reported from a measurement of π^{0} electroproduction near threshold using the p(e,e^{'}p)π^{0} reaction. The experiment was designed to determine precisely the energy dependence of s- and p-wave electromagnetic multipoles as a stringent test of the predictions of chiral perturbation theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the ϕ_{π}^{*} and θ_{π}^{*} angles in the pπ^{0} center of mass was obtained for invariant energies above threshold from 0.5 up to 15 MeV. The 4-momentum transfer Q^{2} coverage ranges from 0.05 to 0.155 (GeV/c)^{2} in fine steps. A simple phenomenological analysis of our data shows strong disagreement with p-wave predictions from ChPT for Q^{2}>0.07 (GeV/c)^{2}, while the s-wave predictions are in reasonable agreement.
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| 5. |
- Puckett, A. J. R., et al.
(författare)
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Final analysis of proton form factor ratio data at Q(2)=4.0, 4.8, and 5.6 GeV2
- 2012
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 85:4
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Tidskriftsartikel (refereegranskat)abstract
- Precise measurements of the proton electromagnetic form factor ratio R = mu(p)G(E)(p)/G(M)(p) using the polarization transfer method at Jefferson Lab have revolutionized the understanding of nucleon structure by revealing the strong decrease of R with momentum transfer Q(2) for Q(2) greater than or similar to 1 GeV2, in strong disagreement with previous extractions of R from cross-section measurements. In particular, the polarization transfer results have exposed the limits of applicability of the one-photon-exchange approximation and highlighted the role of quark orbital angular momentum in the nucleon structure. The GEp-II experiment in Jefferson Lab's Hall A measured R at four Q(2) values in the range 3.5 GeV2 <= Q(2) <= 5.6 GeV2. A possible discrepancy between the originally published GEp-II results and more recent measurements at higher Q(2) motivated a new analysis of the GEp-II data. This article presents the final results of the GEp-II experiment, including details of the new analysis, an expanded description of the apparatus, and an overview of theoretical progress since the original publication. The key result of the final analysis is a systematic increase in the results for R, improving the consistency of the polarization transfer data in the high-Q(2) region. This increase is the result of an improved selection of elastic events which largely removes the systematic effect of the inelastic contamination, underestimated by the original analysis.
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| 6. |
- Khoury, J. D., et al.
(författare)
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The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
- 2022
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36, s. 1703-1719
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Tidskriftsartikel (refereegranskat)abstract
- The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
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| 7. |
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| 8. |
- Wijesooriya, K, et al.
(författare)
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Polarization measurements in high-energy deuteron photodisintegration
- 2001
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 86:14, s. 2975-2979
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the recoil proton polarization for the d(γ⃗,p⃗)n reaction at θc.m. = 90° for photon energies up to 2.4 GeV. These are the first data in this reaction for polarization transfer with circularly polarized photons. The induced polarization py vanishes above 1 GeV, contrary to meson-baryon model expectations, in which resonances lead to large polarizations. However, the polarization transfer Cx does not vanish above 1 GeV, inconsistent with hadron helicity conservation. Thus, we show that the scaling behavior observed in the d(γ,p)ncross sections is not a result of perturbative QCD. These data should provide important tests of new nonperturbative calculations in the intermediate energy regime.
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| 9. |
- Aguilar, J. A., et al.
(författare)
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In situ, broadband measurement of the radio frequency attenuation length at Summit Station, Greenland
- 2022
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Ingår i: Journal of Glaciology. - : Cambridge University Press. - 0022-1430 .- 1727-5652. ; 68:272, s. 1234-1242
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Tidskriftsartikel (refereegranskat)abstract
- Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 10(17) electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length L-alpha. We find an approximately linear dependence of L-alpha on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: < L-alpha > = ((1154 +/- 121) - (0.81 +/- 0.14) (v/MHz)) m for frequencies v is an element of [145 - 3501 MHz.
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| 10. |
- Dutta, D, et al.
(författare)
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Nuclear transparency with the gamma n ->pi(-)p process in He-4
- 2003
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 68:2: 021001
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the nuclear transparency of the fundamental process gamman-->pi(-)p in He-4. These measurements were performed at Jefferson Lab in the photon energy range of 1.6-4.5 GeV and at theta(cm)(pi)=70degrees and 90degrees. These measurements are the first of their kind in the study of nuclear transparency in photoreactions. They also provide a benchmark test of Glauber calculations based on traditional models of nuclear physics. The transparency results suggest deviations from the traditional nuclear physics picture. The momentum transfer dependence of the measured nuclear transparency is consistent with Glauber calculations that include the quantum chromodynamics phenomenon of color transparency.
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| 11. |
- Grossmann, Igor, et al.
(författare)
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Insights into the accuracy of social scientists' forecasts of societal change
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
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Tidskriftsartikel (refereegranskat)abstract
- How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
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| 12. |
- Jacobsson, Jesper, 1984-, et al.
(författare)
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An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles
- 2022
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Ingår i: Nature Energy. - : Springer Nature. - 2058-7546. ; 7:1, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences.
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| 13. |
- Schulte, EC, et al.
(författare)
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High energy angular distribution measurements of the exclusive deuteron photodisintegration reaction
- 2002
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Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813 .- 1089-490X. ; 66:4
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Tidskriftsartikel (refereegranskat)abstract
- The first complete measurements of the angular distributions of the two-body deuteron photodisintegration differential cross section at photon energies above 1.6 GeV were performed at the Thomas Jefferson National Accelerator Facility. The results show a persistent forward-backward asymmetry up to E-gamma=2.4 GeV, the highest-energy measured in this experiment. The Hard Rescattering and the Quark-Gluon string models are in fair agreement with the results.
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| 14. |
- Wijesooriya, K, et al.
(författare)
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Polarization measurements in neutral pion photoproduction
- 2002
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 66:3
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the recoil proton polarization for the H-1((γ) over right arrow,(p) over right arrow)pi(0) reaction for theta(c.m.)(pi) = 60degrees-135degrees and for photon energies up to 4.1 GeV. These are the first data in this reaction for polarization transfer with circularly polarized photons. Various theoretical models are compared with the results. No evidence for hadron helicity conservation is observed. Models that employ factorization are not favored. It appears from the strong angular dependence of the induced polarization at photon energies of 2.5 and 3.1 GeV that a relatively high spin resonance or background amplitude might exist in this energy region.
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| 15. |
- Zhu, LY, et al.
(författare)
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Cross-section measurement of charged-pion photoproduction from hydrogen and deuterium
- 2003
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Ingår i: Physical Review Letters. - 1079-7114. ; 91:2: 022003
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the differential cross section for the gamman-->pi(-)p and gammap-->pi(+)n reactions at theta(c.m.)=90degrees in the photon energy range from 1.1 to 5.5 GeV at Jefferson Lab (JLab). The data at E(gamma)greater than or similar to3.3 GeV exhibit a global scaling behavior for both pi(-) and pi(+) photoproduction, consistent with the constituent counting rule and the existing pi(+) photoproduction data. Possible oscillations around the scaling value are suggested by these new data. The data show enhancement in the scaled cross section at a center-of-mass energy near 2.2 GeV. The cross section ratio of exclusive pi(-) to pi(+) photoproduction at high energy is consistent with the prediction based on one-hard-gluon-exchange diagrams.
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| 16. |
- Zhu, L Y, et al.
(författare)
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Cross section measurements of charged pion photoproduction in hydrogen and deuterium from 1.1 to 5.5 GeV
- 2005
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 71:4
-
Tidskriftsartikel (refereegranskat)abstract
- The differential cross sections for the gamma n ->pi(-)p and the gamma p ->pi(+)n processes were measured at Jefferson Lab. The photon energies ranged from 1.1 to 5.5 GeV, corresponding to center-of-mass energies from 1.7 to 3.4 GeV. The pion center-of-mass angles varied from 50(degrees) to 110(degrees). The pi(-) and pi(+) photoproduction data both exhibit a global scaling behavior at high energies and high transverse momenta, consistent with the constituent counting rule prediction and the existing pi(+) data. The data suggest possible substructure of the scaling behavior, which might be oscillations around the scaling value. The data show an enhancement in the scaled cross section at center-of-mass energy near 2.2 GeV. The differential cross section ratios [d sigma/dt(gamma n ->pi(-)p)/d sigma/dt(gamma p ->pi(+)n)] at high energies and high transverse momenta can be described by calculations based on one-hard-gluon-exchange diagrams.
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| 17. |
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| 18. |
- Kelly, J. J., et al.
(författare)
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Recoil polarization measurements for neutral pion electroproduction at Q(2)=1(GeV/c)(2) near the Delta resonance
- 2007
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 75:2
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Tidskriftsartikel (refereegranskat)abstract
- We measured angular distributions of differential cross section, beam analyzing power, and recoil polarization for neutral pion electroproduction at Q(2)=1.0 (GeV/c)(2) in 10 bins of 1.17 <= W <= 1.35 GeV across the Delta resonance. A total of 16 independent response functions were extracted, of which 12 were observed for the first time. Comparisons with recent model calculations show that response functions governed by real parts of interference products are determined relatively well near the physical mass, W=M-Delta approximate to 1.232 GeV, but the variation among models is large for response functions governed by imaginary parts, and for both types of response functions, the variation increases rapidly with W > M-Delta. We performed a multipole analysis that adjusts suitable subsets of center dot(pi)<= 2 amplitudes with higher partial waves constrained by baseline models. This analysis provides both real and imaginary parts. The fitted multipole amplitudes are nearly model independent-there is very little sensitivity to the choice of baseline model or truncation scheme. By contrast, truncation errors in the traditional Legendre analysis of N ->Delta quadrupole ratios are not negligible. Parabolic fits to the W dependence around M-Delta for the multiple analysis gives values for Re(S1+/M1+)=(-6.61 +/- 0.18)% and Re(E1+/M1+)=(-2.87 +/- 0.19)% for the p pi(0) channel at W=1.232 GeV and Q(2)=1.0 (GeV/c)(2) that are distinctly larger than those from the Legendre analysis of the same data. Similarly, the multipole analysis gives Re(S0+/M1+)=(+7.1 +/- 0.8)% at W=1.232 GeV, consistent with recent models, while the traditional Legendre analysis gives the opposite sign because its truncation errors are quite severe.
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| 19. |
- Gayou, O, et al.
(författare)
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Measurement of G(Ep)/G(Mp) in (e)over-right-arrowp -> e(p)over-right-arrow to Q(2)=5.6 GeV2
- 2002
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Ingår i: Physical Review Letters. - 1079-7114. ; 88:9
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Tidskriftsartikel (refereegranskat)abstract
- The ratio of the electric and magnetic form factors of the proton G(Ep)/G(Mp), which is an image of its charge and magnetization distributions, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic (e) over right arrowp --> e (p) over right arrow reaction. The new data presented span the range 3.5 < Q(2) < 5.6 GeV2 and are well described by a linear Q(2) fit. Also, the ratio rootQ(2) F-2p/F-1p reaches a constant value above Q(2) = 2 GeV2.
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| 20. |
- Limbocker, Ryan, et al.
(författare)
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Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-β peptide (Aβ42) are key pathogenic agents in Alzheimer’s disease (AD). To investigate the relationship between Aβ42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aβ42-induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.
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| 21. |
- Schott, Ryan K., et al.
(författare)
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Diversity and Evolution of Frog Visual Opsins : Spectral Tuning and Adaptation to Distinct Light Environments
- 2024
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Ingår i: Molecular biology and evolution. - 0737-4038. ; 41:4
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Tidskriftsartikel (refereegranskat)abstract
- Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution.
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| 22. |
- Strauch, S, et al.
(författare)
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Polarization transfer in the He-4((e)over-right-arrow,e '(p)over-right-arrow)H-3 reaction up to Q(2)=2.6 (GeV/c)(2)
- 2003
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Ingår i: Physical Review Letters. - 1079-7114. ; 91:5: 052301
-
Tidskriftsartikel (refereegranskat)abstract
- We have measured the proton recoil polarization in the He-4((e) over right arrow ,e(')(p) over right arrow)H-4 reaction at Q(2)=0.5, 1.0, 1.6, and 2.6 (GeV/c)(2). The measured ratio of polarization transfer coefficients differs from a fully relativistic calculation, favoring the inclusion of a medium modification of the proton form factors predicted by a quark-meson coupling model. In addition, the measured induced polarizations agree reasonably well with the fully relativistic calculation indicating that the treatment of final-state interactions is under control.
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| 23. |
- Cohen, Samuel I.A., et al.
(författare)
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Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide
- 2018
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Ingår i: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 10:5, s. 523-531
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Tidskriftsartikel (refereegranskat)abstract
- Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer's disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.
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| 24. |
- Hampson, Grace, et al.
(författare)
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Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare
- 2019
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Ingår i: European Journal of Health Economics. - : Springer Verlag (Germany). - 1439-6637 .- 1618-7598 .- 1618-7601. ; 20:3, s. 427-438
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Tidskriftsartikel (refereegranskat)abstract
- Background: Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. Objectives: To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology—specifically economic evaluation methods—in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. Methods: An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. Results: Three key topics were identified and prioritised for discussion—uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. Conclusions: ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access.
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| 25. |
- Meisl, Georg, et al.
(författare)
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Uncovering the universality of self-replication in protein aggregation and its link to disease
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:32
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Tidskriftsartikel (refereegranskat)abstract
- Fibrillar protein aggregates are a hallmark of a range of human disorders, from prion diseases to dementias, but are also encountered in several functional contexts. Yet, the fundamental links between protein assembly mechanisms and their functional or pathological roles have remained elusive. Here, we analyze the aggregation kinetics of a large set of proteins that self-assemble by a nucleated-growth mechanism, from those associated with disease, over those whose aggregates fulfill functional roles in biology, to those that aggregate only under artificial conditions. We find that, essentially, all such systems, regardless of their biological role, are capable of self-replication. However, for aggregates that have evolved to fulfill a structural role, the rate of self-replication is too low to be significant on the biologically relevant time scale. By contrast, all disease-related proteins are able to self-replicate quickly compared to the time scale of the associated disease. Our findings establish the ubiquity of self-replication and point to its potential importance across aggregation-related disorders.
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