| 1. |
|
|
| 2. |
- De Angelis, A., et al.
(författare)
-
Science with e-ASTROGAM A space mission for MeV-GeV gamma-ray astrophysics
- 2018
-
Ingår i: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 19, s. 1-106
-
Tidskriftsartikel (refereegranskat)abstract
- e-ASTROGAM ('enhanced ASTROGAM') is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV - the lower energy limit can be pushed to energies as low as 150 keV for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and LISA.
|
|
| 3. |
- Ackermann, M., et al.
(författare)
-
Unresolved Gamma-Ray Sky through its Angular Power Spectrum
- 2018
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:24
-
Tidskriftsartikel (refereegranskat)abstract
- The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi-large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products. The analysis is designed to be robust against contamination from resolved sources and noise systematics. The sensitivity to subthreshold sources is greatly enhanced with respect to previous measurements. We find evidence (with similar to 3.7 sigma significance) that the scenario in which two classes of sources contribute to the UGRB signal is favored over a single class. A double power law with exponential cutoff can explain the anisotropy energy spectrum well, with photon indices of the two populations being 2.55 +/- 0.23 and 1.86 +/- 0.15.
|
|
| 4. |
- Jentschel, M., et al.
(författare)
-
EXILL - a high-efficiency, high-resolution setup for gamma-spectroscopy at an intense cold neutron beam facility
- 2017
-
Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- In the EXILL campaign a highly efficient array of high purity germanium (HPGe) detectors was operated at the cold neutron beam facility PF1B of the Institut Laue-Langevin (ILL) to carry out nuclear structure studies, via measurements of gamma-rays following neutron-induced capture and fission reactions. The setup consisted of a collimation system producing a pencil beam with a thermal capture equivalent flux of about 10(8) ns(-1)cm(2) at the target position and negligible neutron halo. The targetwas surrounded by an array of eight to ten anti-Compton shielded EXOGAMClover detectors, four to six anti-Compton shielded large coaxial GASP detectors and two standard Clover detectors. For a part of the campaign the array was combined with 16 LaBr3:(Ce) detectors from the FATIMA collaboration. The detectorswere arranged in an array of rhombicuboctahedron geometry, providing the possibility to carry out very precise angular correlation and directional-polarization correlation measurements. The triggerless acquisition system allowed a signal collection rate of up to 6 x 10(5) Hz. The data allowed to set multi-fold coincidences to obtain decay schemes and in combination with the FATIMA array of LaBr3:(Ce) detectors to analyze half-lives of excited levels in the pico-to microsecond range. Precise energy and efficiency calibrations of EXILL were performed using standard calibration sources of Ba-133, Co-60 and Eu-152 as well as data from the reactions Al-27(n, gamma)Al-28 and Cl-35(n,gamma)Cl-36 in the energy range from 30 keV up to 10MeV.
|
|
| 5. |
- Chishti, M.M.R., et al.
(författare)
-
Response of the FAst TIMing Array (FATIMA) for DESPEC at FAIR Phase-0
- 2023
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier B.V.. - 0168-9002 .- 1872-9576. ; 1056
-
Tidskriftsartikel (refereegranskat)abstract
- The Monte-Carlo simulated response for γ-ray detection of the FAst TIMing Array (FATIMA) for exploitation within the DEcay SPECtroscopy (DESPEC) experimental system at the FAIR Phase-0 facility at Darmstadt, Germany is presented. In this configuration, FATIMA consisted of 36 LaBr3(Ce) detectors surrounding the AIDA, position-sensitive charged-particle active stopper. The decay of the Iπ=8+ isomer-fed decay cascade in 96Pd, measured in the first DESPEC experiment at the FAIR-0 facility was used to validate the simulations. The experimental data yielded in-situ full-energy peak efficiency values for FATIMA of 11.2(11)%, 6.8(7)%, 3.8(4)% and 2.1(4)% at 106, 325, 684 and 1415 keV respectively, consistent with the values derived from the simulated response.
|
|
| 6. |
- Pasqualato, G., et al.
(författare)
-
Shape evolution in even-mass 98-104Zr isotopes via lifetime measurements using the γ γ-coincidence technique
- 2023
-
Ingår i: European Physical Journal A. - : Springer. - 1434-6001 .- 1434-601X. ; 59:11
-
Tidskriftsartikel (refereegranskat)abstract
- The Zirconium (Z = 40) isotopic chain has attracted interest for more than four decades. The abrupt lowering of the energy of the first 2(+) state and the increase in the transition strength B(E2; 2(1)(+) -> 0(1)(+) ) going from Zr-98 to Zr-100 has been the first example of "quantum phase transition" in nuclear shapes, which has few equivalents in the nuclear chart. Although a multitude of experiments have been performed to measure nuclear properties related to nuclear shapes and collectivity in the region, none of the measured lifetimes were obtained using the Recoil Distance Doppler Shift method in the gamma gamma-coincidence mode where a gate on the direct feeding transition of the state of interest allows a strict control of systematical errors. This work reports the results of lifetime measurements for the first yrast excited states in Zr98-104 carried out to extract reduced transition probabilities. The new lifetime values in gamma gamma-coincidence and gamma-single mode are compared with the results of former experiments. Recent predictions of the Interacting Boson Model with Configuration Mixing, the Symmetry Conserving Configuration Mixing model based on the Hartree-Fock- Bogoliubov approach and the Monte Carlo Shell Model are presented and compared with the experimental data.
|
|
| 7. |
- Heald, G., et al.
(författare)
-
Magnetism science with the square kilometre array
- 2020
-
Ingår i: Galaxies. - : MDPI AG. - 2075-4434. ; 8:8
-
Tidskriftsartikel (refereegranskat)abstract
- The Square Kilometre Array (SKA) will answer fundamental questions about the origin, evolution, properties, and influence of magnetic fields throughout the Universe. Magnetic fields can illuminate and influence phenomena as diverse as star formation, galactic dynamics, fast radio bursts, active galactic nuclei, large-scale structure, and dark matter annihilation. Preparations for the SKA are swiftly continuing worldwide, and the community is making tremendous observational progress in the field of cosmic magnetism using data from a powerful international suite of SKA pathfinder and precursor telescopes. In this contribution, we revisit community plans for magnetism research using the SKA, in light of these recent rapid developments. We focus in particular on the impact that new radio telescope instrumentation is generating, thus advancing our understanding of key SKA magnetism science areas, as well as the new techniques that are required for processing and interpreting the data. We discuss these recent developments in the context of the ultimate scientific goals for the SKA era.
|
|
| 8. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
|
|
| 9. |
- Weltman, A., et al.
(författare)
-
Fundamental physics with the Square Kilometre Array
- 2020
-
Ingår i: Publications Astronomical Society of Australia. - : CAMBRIDGE UNIV PRESS. - 1323-3580 .- 1448-6083. ; 37
-
Forskningsöversikt (refereegranskat)abstract
- The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
|
|
| 10. |
- Werner, V., et al.
(författare)
-
Evolution of collectivity near mid-shell from excited-state lifetime measurements in rare earth nuclei
- 2016
-
Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 93:3
-
Tidskriftsartikel (refereegranskat)abstract
- The B(E2) excitation strength of the first excited 2(+) state in even-even nuclei should directly correlate with the size of the valence space and maximize at mid-shell. A previously found saturation of B(E2) strengths in well-deformed rotors at mid-shell is tested through high-precision measurements of the lifetimes of the lowest-lying 2(+) states of the Hf-168 and W-174 rare earth isotopes. Measurements were performed using fast LaBr3 scintillation detectors. Combined with the recently remeasured B(E2; 2(1)(+) -> 0(1)(+)) values for Hf and W isotopes the new data remove discrepancies observed in the differentials of B(E2) values for these isotopes.
|
|
| 11. |
- Zamora, Juan Carlos, et al.
(författare)
-
Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
-
Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
-
Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
|
|
| 12. |
- Andreoni, Igor, et al.
(författare)
-
Target-of-opportunity Observations of Gravitational-wave Events with Vera C. Rubin Observatory
- 2022
-
Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:1
-
Tidskriftsartikel (refereegranskat)abstract
- The discovery of the electromagnetic counterpart to the binary neutron star (NS) merger GW170817 has opened the era of gravitational-wave multimessenger astronomy. Rapid identification of the optical/infrared kilonova enabled a precise localization of the source, which paved the way to deep multiwavelength follow-up and its myriad of related science results. Fully exploiting this new territory of exploration requires the acquisition of electromagnetic data from samples of NS mergers and other gravitational-wave sources. After GW170817, the frontier is now to map the diversity of kilonova properties and provide more stringent constraints on the Hubble constant, and enable new tests of fundamental physics. The Vera C. Rubin Observatory's Legacy Survey of Space and Time can play a key role in this field in the 2020s, when an improved network of gravitational-wave detectors is expected to reach a sensitivity that will enable the discovery of a high rate of merger events involving NSs (∼tens per year) out to distances of several hundred megaparsecs. We design comprehensive target-of-opportunity observing strategies for follow-up of gravitational-wave triggers that will make the Rubin Observatory the premier instrument for discovery and early characterization of NS and other compact-object mergers, and yet unknown classes of gravitational-wave events.
|
|
| 13. |
- Arridge, Christopher S., et al.
(författare)
-
Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
- 2012
-
Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
-
Tidskriftsartikel (refereegranskat)abstract
- The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
|
|
| 14. |
- Beeh, Kai M, et al.
(författare)
-
How Do Dual Long-acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?
- 2017
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 196:2, s. 139-149
-
Forskningsöversikt (refereegranskat)abstract
- Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease (COPD). Several studies have documented that long-acting bronchodilators (LABDs) can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroids (LABA/ICS) combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single LABDs or LABA/ICS in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. While preclinical studies suggest LABAs and LAMAs have anti-inflammatory effects, such effects have not been demonstrated yet in patients with COPD.
|
|
| 15. |
- Brown, Solomon, et al.
(författare)
-
CO(2)QUEST : Techno-economic assessment of CO2 quality effect on its storage and transport
- 2014
-
Ingår i: 12TH INTERNATIONAL CONFERENCE ON GREENHOUSE GAS CONTROL TECHNOLOGIES, GHGT-12. - : Elsevier BV. ; , s. 2622-2629
-
Konferensbidrag (refereegranskat)abstract
- Presented is an overview of the CO(2)QUEST project that addresses fundamentally important issues regarding the impact of typical impurities in the gas or dense phase CO2 stream captured from fossil fuel power plants on its safe and economic transportation and storage. Previous studies have mainly investigated the impact of CO2 stream impurities on each part of the carbon capture and storage (CCS) chain in isolation. This is a significant drawback given the different sensitivities of pipeline, wellbore materials and storage sites to the various impurities. The project brings together leading researchers and stakeholders, to address the impact of the typical impurities upon safe and economic CO2 transportation and storage. State-of-the-art mathematical models, backed by laboratory and industrial-scale experimentation, are implemented to perform a comprehensive techno-economic assessment of the impact of impurities upon the thermo-physical phenomena governing pipeline and storage-site integrities.
|
|
| 16. |
- Gilbert, Penney M., et al.
(författare)
-
A single cell bioengineering approach to elucidate mechanisms of adult stem cell self-renewal
- 2012
-
Ingår i: Integrative Biology. - : Oxford University Press (OUP). - 1757-9694 .- 1757-9708. ; 4:4, s. 360-367
-
Tidskriftsartikel (refereegranskat)abstract
- The goal of regenerative medicine is to restore form and function to damaged and aging tissues. Adult stem cells, present in tissues such as skeletal muscle, comprise a reservoir of cells with a remarkable capacity to proliferate and repair tissue damage. Muscle stem cells, known as satellite cells, reside in a quiescent state in an anatomically distinct compartment, or niche, ensheathed between the membrane of the myofiber and the basal lamina. Recently, procedures for isolating satellite cells were developed and experiments testing their function upon transplantation into muscles revealed an extraordinary potential to contribute to muscle fibers and access and replenish the satellite cell compartment. However, these properties are rapidly lost once satellite cells are plated in culture. Accordingly, elucidating the role of extrinsic factors in controlling muscle stem cell fate, in particular self-renewal, is critical. Through careful design of bioengineered culture platforms, analysis of specific proteins presented to stem cells is possible. Critical to the success of the approach is single cell analysis, as more rapidly proliferating progenitors may mask the behavior of stem cells that proliferate slowly. Bioengineering approaches provide a potent means of gaining insight into the role of extrinsic factors in the stem cell microenvironment on stem cell function and the mechanisms that control their diverse fates. Ultimately, the multidisciplinary approach presented here will lead to novel therapeutic strategies for degenerative diseases.
|
|
| 17. |
- Neumann, Alexander, et al.
(författare)
-
Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.
- 2023
-
Ingår i: Genome medicine. - 1756-994X. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n=205 controls, n=546 mild cognitive impairment, n=222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analysesof the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.
|
|
| 18. |
- Porter, Richard T. J., et al.
(författare)
-
Techno-economic assessment of CO2 quality effect on its storage and transport : CO(2)QUEST An overview of aims, objectives and main findings
- 2016
-
Ingår i: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836 .- 1878-0148. ; 54, s. 662-681
-
Tidskriftsartikel (refereegranskat)abstract
- This paper provides an overview of the aims, objectives and the main findings of the CO(2)QUEST FP7 collaborative project, funded by the European Commission and designed to address the fundamentally important and urgent issues regarding the impact of the typical impurities in CO2 streams captured from fossil fuel power plants and other CO2 intensive industries on their safe and economic pipeline transportation and storage. The main features and results recorded from some of the unique test facilities constructed as part of the project are presented. These include an extensively instrumented realistic-scale test pipeline for conducting pipeline rupture and dispersion tests in China, an injection test facility in France to study the mobility of trace metallic elements contained in a CO2 stream following injection near a shallow-water qualifier and fluid/rock interactions and well integrity experiments conducted using a fully instrumented deep-well CO2/impurities injection test facility in Israel. The above, along with the various unique mathematical models developed, provide the fundamentally important tools needed to define impurity tolerance levels, mixing protocols and control measures for pipeline networks and storage infrastructure, thus contributing to the development of relevant standards for the safe design and economic operation of CCS.
|
|
| 19. |
- Shi, Liu, et al.
(författare)
-
Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.
- 2020
-
Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 77:3, s. 1353-1368
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.
|
|
| 20. |
- Shi, Liu, et al.
(författare)
-
Replication study of plasma proteins relating to Alzheimer's pathology.
- 2021
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 17:9, s. 1452-1464
-
Tidskriftsartikel (refereegranskat)abstract
- This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis.Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively.Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis.Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
|
|
| 21. |
- Sytiuk, Anna, et al.
(författare)
-
Predicting the structure and functions of peatland microbial communities from Sphagnum phylogeny, anatomical and morphological traits and metabolites
- 2022
-
Ingår i: Journal of Ecology. - : John Wiley & Sons. - 0022-0477 .- 1365-2745. ; 110:1, s. 80-96
-
Tidskriftsartikel (refereegranskat)abstract
- Sphagnum mosses are keystone species in northern peatlands. Notably, they play an important role in peatland carbon (C) cycling by regulating the composition and activity of microbial communities. However, it remains unclear whether information on Sphagnum phylogeny and/or traits-based composition (i.e. anatomical and morphological traits and metabolites) can be used to predict the structure of microbial communities and their functioning. Here we evaluated whether Sphagnum phylogeny and traits predict additional variation in peatland microbial community composition and functioning beyond what would be predicted from environmental characteristics (i.e. climatic and edaphic conditions).We collected Sphagnum and microbial data from five European peatlands distributed along a latitudinal gradient from northern Sweden to southern France. These data allowed us to assess Sphagnum anatomical and morphological traits and metabolites at different sites along changing environmental conditions. Using structural equation modelling (SEM) and phylogenetic distance analyses, we investigated the role of Sphagnum traits in shaping microbial community composition and functioning along with environmental conditions.We show that microbial community composition and traits varied independently from both Sphagnum phylogeny and the latitudinal gradient. Specifically, the addition of Sphagnum traits to climatic and edaphic variables to the SEM allowed it to explain a larger proportion of the explained variance (R2). This observation was most apparent for the biomass of decomposers (+42%) and phototrophs (+19%), as well as for growth yield microbial traits (+10%). As such, that Sphagnum metabolites were important drivers for microbial community structure and traits, while Sphagnum anatomical and morphological traits were poor predictors.Synthesis. Our results highlight that Sphagnum metabolites are more likely to influence peatland microbial food web structure and functioning than Sphagnum anatomical and morphological traits. We provide further evidence that measurements of the plant metabolome, when combined with classical functional traits, improve our understanding of how the plants interact with their associated microbiomes.
|
|
| 22. |
- van Bodegraven, Eduard A., et al.
(författare)
-
Minimally invasive robot-assisted and laparoscopic distal pancreatectomy in a pan-European registry a retrospective cohort study
- 2024
-
Ingår i: International Journal of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 1743-9191 .- 1743-9159. ; 110:6, s. 3554-3561
-
Tidskriftsartikel (refereegranskat)abstract
- Background: International guidelines recommend monitoring the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. Patients and methods: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and high-risk groups. Results: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% (P<0.001). RDP was associated with fewer grade 2 intraoperative events compared with LDP (9.6% vs. 16.8%, P<0.001), with longer operating time (238 vs. 201 min, P<0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P=0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P=0.344). Three high-risk groups were identified; BMI greater than 25 kg/m(2), previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. Conclusion: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with fewer conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences.
|
|
| 23. |
- Zeichner, Sarah S., et al.
(författare)
-
Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium
- 2023
-
Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 382:6677, s. 1411-1415
-
Tidskriftsartikel (refereegranskat)abstract
- Polycyclic aromatic hydrocarbons (PAHs) contain less than or similar to 20% of the carbon in the interstellar medium. They are potentially produced in circumstellar environments (at temperatures greater than or similar to 1000 kelvin), by (similar to 10 kelvin) interstellar clouds, or by processing of carbon-rich dust grains. We report isotopic properties of PAHs extracted from samples of the asteroid Ryugu and the meteorite Murchison. The doubly-C-13 substituted compositions (Delta 2x(13)C values) of the PAHs naphthalene, fluoranthene, and pyrene are 9 to 51 parts per thousand higher than values expected for a stochastic distribution of isotopes. The Delta 2x(13)C values are higher than expected if the PAHs formed in a circumstellar environment, but consistent with formation in the interstellar medium. By contrast, the PAHs phenanthrene and anthracene in Ryugu samples have Delta 2x(13)C values consistent with formation by higher-temperature reactions.
|
|
| 24. |
- Boudier, Anne, et al.
(författare)
-
Data-driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later
- 2019
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 74:5, s. 953-963
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundResearch based on cluster analyses led to the identification of particular phenotypes confirming phenotypic heterogeneity of asthma. The long-term clinical course of asthma phenotypes defined by clustering analysis remains unknown, although it is a key aspect to underpin their clinical relevance. We aimed to estimate risk of poor asthma events between asthma clusters identified 20years earlier. MethodsThe study relied on two cohorts of adults with asthma with 20-year follow-up, ECRHS (European Community Respiratory Health Survey) and EGEA (Epidemiological study on Genetics and Environment of Asthma). Regression models were used to compare asthma characteristics (current asthma, asthma exacerbations, asthma control, quality of life, and FEV1) at follow-up and the course of FEV(1)between sevencluster-based asthma phenotypes identified20years earlier. ResultsThe analysis included 1325 adults with ever asthma. For each asthma characteristic assessed at follow-up, the risk for adverse outcomes differed significantly between the seven asthma clusters identified at baseline. As compared with the mildest asthma phenotype, ORs (95% CI) for asthma exacerbations varied from 0.9 (0.4 to 2.0) to 4.0 (2.0 to 7.8) and the regression estimates (95% CI) for FEV1% predicted varied from 0.6 (-3.5 to 4.6) to -9.9 (-14.2 to -5.5) between clusters. Change in FEV1 over time did not differ significantly across clusters. ConclusionOur findings show that the long-term risk for poor asthma outcomes differed between comprehensive adult asthma phenotypes identified 20years earlier, and suggest a strong tracking of asthma activity and impaired lung function over time.
|
|
| 25. |
- Cerullo, Gabriella, et al.
(författare)
-
Directed evolution of the type C feruloyl esterase from Fusarium oxysporum FoFaeC and molecular docking analysis of its improved variants
- 2019
-
Ingår i: New Biotechnology. - : Elsevier. - 1871-6784 .- 1876-4347. ; 51, s. 14-20
-
Tidskriftsartikel (refereegranskat)abstract
- The need to develop competitive and eco-friendly processes in the cosmetic industry leads to the search for new enzymes with improved properties for industrial bioconversions in this sector. In the present study, a complete methodology to generate, express and screen diversity for the type C feruloyl esterase from Fusarium oxysporium FoFaeC was set up in a high-throughput fashion. A library of around 30,000 random mutants of FoFaeC was generated by error prone PCR of fofaec cDNA and expressed in Yarrowia lipolytica. Screening for enzymatic activity towards the substrates 5-bromo-4-chloroindol-3-yl and 4-nitrocatechol-1-yl ferulates allowed the selection of 96 enzyme variants endowed with improved enzymatic activity that were then characterized for thermo- and solvent- tolerance. The five best mutants in terms of higher activity, thermo- and solvent- tolerance were selected for analysis of substrate specificity. Variant L432I was shown to be able to hydrolyze all the tested substrates, except methyl sinapate, with higher activity than wild type FoFaeC towards methyl p-coumarate, methyl ferulate and methyl caffeate. Moreover, the E455D variant was found to maintain completely its hydrolytic activity after two hour incubation at 55 °C, whereas the L284Q/V405I variant showed both higher thermo- and solvent- tolerance than wild type FoFaeC. Small molecule docking simulations were applied to the five novel selected variants in order to examine the binding pattern of substrates used for enzyme characterization of wild type FoFaeC and the evolved variants.
|
|
