| 1. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 2. |
- Aad, G., et al.
(author)
-
- 2012
-
Journal article (peer-reviewed)
|
|
| 3. |
- Aad, G., et al.
(author)
-
- 2013
-
swepub:Mat__t (peer-reviewed)
|
|
| 4. |
- Aad, G., et al.
(author)
-
- 2012
-
swepub:Mat__t (peer-reviewed)
|
|
| 5. |
- Aad, G., et al.
(author)
-
- 2010
-
swepub:Mat__t
|
|
| 6. |
- Aad, G., et al.
(author)
-
- 2010
-
swepub:Mat__t
|
|
| 7. |
|
|
| 8. |
- Aad, G., et al.
(author)
-
- 2010
-
swepub:Mat__t
|
|
| 9. |
- Aad, G., et al.
(author)
-
- 2010
-
swepub:Mat__t
|
|
| 10. |
- Aad, G., et al.
(author)
-
- 2011
-
swepub:Mat__t
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Aad, G., et al.
(author)
-
Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
-
Journal article (peer-reviewed)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Obers, Niels A., et al.
(author)
-
Quantum gravity phenomenology at the dawn of the multi-messenger era—A review
- 2022
-
In: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410 .- 1873-2224. ; 125
-
Research review (peer-reviewed)abstract
- The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.
|
|
| 19. |
- Adamczewski-Musch, J., et al.
(author)
-
Production and electromagnetic decay of hyperons : a feasibility study with HADES as a phase-0 experiment at FAIR
- 2021
-
In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Journal article (peer-reviewed)abstract
- A feasibility study has been performed in order to investigate the performance of the HADES detector to measure the electromagnetic decays of the hyperon resonances Sigma(1385)(0), Lambda(1405) and Lambda(1520) as well as the production of double strange baryon systems Xi(-) and Lambda Lambda in p + p reactions at a beam kinetic energy of 4.5GeV. The existing HADES detector will be upgraded by a new Forward Detector, which extends the detector acceptance into a range of polar angles that plays a crucial role for these investigations. The analysis of each channel is preceded by a consideration of the production cross-sections. Afterwards the expected signal count rates using a target consisting of either liquid hydrogen or polyethylene are summarized.
|
|
| 20. |
- Tobias, Deirdre K, et al.
(author)
-
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
-
In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
-
Research review (peer-reviewed)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
|
|
| 21. |
- White, H, et al.
(author)
-
A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real time quantitative PCR.
- 2015
-
In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 29:2, s. 369-376
-
Journal article (peer-reviewed)abstract
- Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukemia, but there is substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 10(6), 1.08±0.11 × 10(5), 1.03±0.10 × 10(4), 1.02±0.09 × 10(3), 1.04±0.10 × 10(2) and 10.0±1.5 copies/μL. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise the numbers of measured transcripts of e14a2 BCR-ABL1 and three control genes; ABL1, BCR and GUSB. The set of 6 plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (http://irmm.jrc.ec.europa.eu; CRM code ERM-AD623a-f).Leukemia accepted article preview online, 18 July 2014; doi:10.1038/leu.2014.217.
|
|
| 22. |
- Pfeifer, H., et al.
(author)
-
Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph plus ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1
- 2019
-
In: Leukemia. - : NATURE PUBLISHING GROUP. - 0887-6924 .- 1476-5551. ; 33:8, s. 1910-1922
-
Journal article (peer-reviewed)abstract
- Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Standardised use of EAC primer/probe sets and of centrally prepared plasmid standards had the greatest impact on reducing interlaboratory variability. In QC1 the proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10(-3) and 36/67 (53%) and 53/67 (79%) at 10(-4)BCR-ABL1/ABL1. Standardized RNA extraction, cDNA synthesis and cycler platforms did not improve results further, whereas stringent application of technical criteria for assay quality and uniform criteria for data interpretation and reporting were essential. We provide detailed laboratory recommendations for the standardized MRD analysis in routine diagnostic settings and in multicenter clinical trials for Ph + ALL.
|
|
| 23. |
- Serra, J., et al.
(author)
-
European society of neurogastroenterology and motility guidelines on functional constipation in adults
- 2020
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:2
-
Journal article (peer-reviewed)abstract
- Introduction Chronic constipation is a common disorder with a reported prevalence ranging from 3% to 27% in the general population. Several management strategies, including diagnostic tests, empiric treatments, and specific treatments, have been developed. Our aim was to develop European guidelines for the clinical management of constipation. Design After a thorough review of the literature by experts in relevant fields, including gastroenterologists, surgeons, general practitioners, radiologists, and experts in gastrointestinal motility testing from various European countries, a Delphi consensus process was used to produce statements and practical algorithms for the management of chronic constipation. Key Results Seventy-three final statements were agreed upon after the Delphi process. The level of evidence for most statements was low or very low. A high level of evidence was agreed only for anorectal manometry as a comprehensive evaluation of anorectal function and for treatment with osmotic laxatives, especially polyethylene glycol, the prokinetic drug prucalopride, secretagogues, such as linaclotide and lubiprostone and PAMORAs for the treatment of opioid-induced constipation. However, the level of agreement between the authors was good for most statements (80% or more of the authors). The greatest disagreement was related to the surgical management of constipation. Conclusions and Inferences European guidelines on chronic constipation, with recommendations and algorithms, were developed by experts. Despite the high level of agreement between the different experts, the level of scientific evidence for most recommendations was low, highlighting the need for future research to increase the evidence and improve treatment outcomes in these patients.
|
|
| 24. |
- Jahnke, T., et al.
(author)
-
Inner-Shell-Ionization-Induced Femtosecond Structural Dynamics of Water Molecules Imaged at an X-Ray Free-Electron Laser
- 2021
-
In: Physical Review X. - : American Physical Society. - 2160-3308. ; 11:4
-
Journal article (peer-reviewed)abstract
- The ultrafast structural dynamics of water following inner-shell ionization is a crucial issue in high-energy radiation chemistry. We have exposed isolated water molecules to a short x-ray pulse from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we can image dissociation dynamics of individual molecules in unprecedented detail. We reveal significant molecular structural dynamics in H2O2+, such as asymmetric deformation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. We thus reconstruct several snapshots of structural dynamics at different time intervals, which highlight dynamical patterns that are relevant as initiating steps of subsequent radiation-damage processes.
|
|
| 25. |
|
|
| 26. |
- Okhuijsen-Pfeifer, C, et al.
(author)
-
Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- 2022
-
In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 145-
-
Journal article (peer-reviewed)abstract
- Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
|
|
| 27. |
- Wiedensohler, A., et al.
(author)
-
Mobility particle size spectrometers: harmonization of technical standards and data structure to facilitate high quality long-term observations of atmospheric particle number size distributions
- 2012
-
In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 5:3, s. 657-685
-
Journal article (peer-reviewed)abstract
- Mobility particle size spectrometers often referred to as DMPS (Differential Mobility Particle Sizers) or SMPS (Scanning Mobility Particle Sizers) have found a wide range of applications in atmospheric aerosol research. However, comparability of measurements conducted world-wide is hampered by lack of generally accepted technical standards and guidelines with respect to the instrumental set-up, measurement mode, data evaluation as well as quality control. Technical standards were developed for a minimum requirement of mobility size spectrometry to perform long-term atmospheric aerosol measurements. Technical recommendations include continuous monitoring of flow rates, temperature, pressure, and relative humidity for the sheath and sample air in the differential mobility analyzer. We compared commercial and custom-made inversion routines to calculate the particle number size distributions from the measured electrical mobility distribution. All inversion routines are comparable within few per cent uncertainty for a given set of raw data. Furthermore, this work summarizes the results from several instrument intercomparison workshops conducted within the European infrastructure project EUSAAR (European Supersites for Atmospheric Aerosol Research) and ACTRIS (Aerosols, Clouds, and Trace gases Research InfraStructure Network) to determine present uncertainties especially of custom-built mobility particle size spectrometers. Under controlled laboratory conditions, the particle number size distributions from 20 to 200 nm determined by mobility particle size spectrometers of different design are within an uncertainty range of around +/- 10% after correcting internal particle losses, while below and above this size range the discrepancies increased. For particles larger than 200 nm, the uncertainty range increased to 30%, which could not be explained. The network reference mobility spectrometers with identical design agreed within +/- 4% in the peak particle number concentration when all settings were done carefully. The consistency of these reference instruments to the total particle number concentration was demonstrated to be less than 5%. Additionally, a new data structure for particle number size distributions was introduced to store and disseminate the data at EMEP (European Monitoring and Evaluation Program). This structure contains three levels: raw data, processed data, and final particle size distributions. Importantly, we recommend reporting raw measurements including all relevant instrument parameters as well as a complete documentation on all data transformation and correction steps. These technical and data structure standards aim to enhance the quality of long-term size distribution measurements, their comparability between different networks and sites, and their transparency and traceability back to raw data.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Micke, Patrick, et al.
(author)
-
The Heidelberg compact electron beam ion traps
- 2018
-
In: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 89:6
-
Journal article (peer-reviewed)abstract
- Electron beam ion traps (EBITs) are ideal tools for both production and study of highly charged ions (HCIs). In order to reduce their construction, maintenance, and operation costs, we have developed a novel, compact, room-temperature design, the Heidelberg Compact EBIT (HC-EBIT). Four already commissioned devices operate at the strongest fields (up to 0.86 T) reported for such EBITs using permanent magnets, run electron beam currents up to 80 mA, and energies up to 10 keV. They demonstrate HCI production, trapping, and extraction of pulsed Ar16+ bunches and continuous 100 pA ion beams of highly charged Xe up to charge state 29+, already with a 4 mA, 2 keV electron beam. Moreover, HC-EBITs offer large solid-angle ports and thus high photon count rates, e.g., in x-ray spectroscopy of dielectronic recombination in HCIs up to Fe24+, achieving an electron-energy resolving power of E/ΔE > 1500 at 5 keV. Besides traditional on-axis electron guns, we have also implemented a novel off-axis gun for laser, synchrotron, and free-electron laser applications, offering clear optical access along the trap axis. We report on its first operation at a synchrotron radiation facility demonstrating the resonant photoexcitation of highly charged oxygen.
|
|
| 32. |
- Augustin, S., et al.
(author)
-
Signatures of autoionization in the angular electron distribution in two-photon double ionization of Ar
- 2018
-
In: Physical Review A. - 2469-9926. ; 98:3
-
Journal article (peer-reviewed)abstract
- A kinematically complete experiment on two-photon double ionization of Ar by free-electron laser radiation with a photon energy of 27.93 eV was performed. The electron energy spectra show that double ionization is dominated by the sequential process. Comparison of the electron angular distributions to our data for single ionization and to theory confirms that even in the sequential process the electrons from both ionization steps are correlated with each other through polarization of the intermediate Ar+ state. Furthermore, a very important role of autoionization in both ionization steps is found.
|
|
| 33. |
|
|
| 34. |
- Gnad, T., et al.
(author)
-
Adenosine activates brown adipose tissue and recruits beige adipocytes via A(2A) receptors
- 2014
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 516:7531
-
Journal article (peer-reviewed)abstract
- Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies(1-5). Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of beta-adrenergic receptors(1-5). Because BAT therapies based on cold exposureor beta-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat(6-8). However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A(2A) receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A(2A) receptors in mice causes adecrease in BAT-dependent thermogenesis, whereas treatment with A(2A) agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A(2A) receptors or injection of lentiviral vectors expressing the A(2A) receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A(2A) agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A(2A) signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.
|
|
| 35. |
- Li, Shunyi, et al.
(author)
-
Intrinsic energy band alignment of functional oxides
- 2014
-
In: Physica Status Solidi - Rapid Research Letetrs. - : Wiley. - 1862-6254 .- 1862-6270. ; 8:6, s. 571-576
-
Journal article (peer-reviewed)abstract
- The energy band alignment at interfaces between different materials is a key factor, which determines the function of electronic devices. While the energy band alignment of conventional semiconductors is quite well understood, systematic experimental studies on oxides are still missing. This work presents an extensive study on the intrinsic energy band alignment of a wide range of functional oxides using photoelectron spectroscopy with in-situ sample preparation. The studied materials have particular technological importance in diverse fields as solar cells, piezotronics, multiferroics, photoelectrochemistry and oxide electronics. Particular efforts have been made to verify the validity of transitivity, in order to confirm the intrinsic nature of the obtained band alignment and to understand the underlying principles. Valence band offsets up to 1.6 eV are observed. The large variation of valence band maximum energy can be explained by the different orbital contributions to the density of states in the valence band. The framework provided by this work enables the general understanding and prediction of energy band alignment at oxide interfaces, and furthermore the tailoring of energy level matching for charge transfer in functional oxides. (C) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
|
|
| 36. |
- Berrah, N., et al.
(author)
-
Femtosecond-resolved observation of the fragmentation of buckminsterfullerene following X-ray multiphoton ionization
- 2019
-
In: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 15, s. 1279-1283
-
Journal article (peer-reviewed)abstract
- X-ray free-electron lasers have, over the past decade, opened up the possibility of understanding the ultrafast response of matter to intense X-ray pulses. In earlier research on atoms and small molecules, new aspects of this response were uncovered, such as rapid sequences of inner-shell photoionization and Auger ionization. Here, we studied a larger molecule, buckminsterfullerene (C60), exposed to 640eV X-rays, and examined the role of chemical effects, such as chemical bonds and charge transfer, on the fragmentation following multiple ionization of the molecule. To provide time resolution, we performed femtosecond-resolved X-ray pump/X-ray probe measurements, which were accompanied by advanced simulations. The simulations and experiment reveal that despite substantial ionization induced by the ultrashort (20fs) X-ray pump pulse, the fragmentation of C60 is considerably delayed. This work uncovers the persistence of the molecular structure of C60, which hinders fragmentation over a timescale of hundreds of femtoseconds. Furthermore, we demonstrate that a substantial fraction of the ejected fragments are neutral carbon atoms. These findings provide insights into X-ray free-electron laser-induced radiation damage in large molecules, including biomolecules.
|
|
| 37. |
- Cui, H, et al.
(author)
-
Inactivation of H19, an imprinted and putative tumor repressor gene, is a preneoplastic event during Wilms' tumorigenesis
- 1997
-
In: Cancer Research. ; 57:20, s. 4469-4473
-
Journal article (peer-reviewed)abstract
- Genetic evidence shows that the parent of origin-dependent expression patterns of the Igf2 and H19 genes is coordinated in mouse, such that H19 controls the activity of Igf2 in cis. Equally compelling evidence for a similar situation in humans is absent, although the frequently observed activation of the maternal IGF2 allele (ie., loss of imprinting) in Wilms' tumors has been attributed to the silencing of the maternal H19 locus. We show here that loss of H19 activity is generally a preneoplastic event, which may be linked with an overgrowth lesion that has been proposed to be permissive for tumor formation. Although our results document one instance in which a postneoplastic loss of H19 activity correlates with loss of IGF2 imprinting at the cellular level, it appears that inactivation of H19 is more generally independent of loss of imprinting of IGF2, at least in our specimens. Our results imply that inactivation of H19 correlates with blastema overgrowth and can be independent of a regulatory role with respect to IGF2 imprinting status in cis.
|
|
| 38. |
- Huang, H., et al.
(author)
-
Extracellular domain shedding of the ALK receptor mediates neuroblastoma cell migration
- 2021
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 36:2
-
Journal article (peer-reviewed)abstract
- Although activating mutations of the anaplastic lymphoma kinase (ALK) membrane receptor occur in similar to 10% of neuroblastoma (NB) tumors, the role of the wild-type (WT) receptor, which is aberrantly expressed in most non-mutated cases, is unclear. Both WT and mutant proteins undergo extracellular domain (ECD) cleavage. Here, we map the cleavage site to Asn654-Leu655 and demonstrate that cleavage inhibition of WT ALK significantly impedes NB cell migration with subsequent prolongation of survival in mouse models. Cleavage inhibition results in the downregulation of an epithelial-to-mesenchymal transition (EMT) gene signature, with decreased nuclear localization and occupancy of beta-catenin at EMT gene promoters. We further show that cleavage is mediated by matrix metalloproteinase 9, whose genetic and pharmacologic inactivation inhibits cleavage and decreases NB cell migration. Together, our results indicate a pivotal role forWTALK ECD cleavage in NB pathogenesis, which may be harnessed for therapeutic benefit.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Ohlsson, R, et al.
(author)
-
Random monoallelic expression of the imprinted IGF2 and H19 genes in the absence of discriminative parental marks
- 1999
-
In: Dev Genes and Evolution. ; 209, s. 113-
-
Journal article (peer-reviewed)abstract
- PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated embryonic blood vessels and reduced numbers of both pericytes and trophoblasts. These changes are seen from embryonic day (E) 13.5, which coincides with the upregulation of PDGFB mRNA levels in normal placentas. By E17, modifications in shape, size, and number of the fetal blood vessels in the mutant placentas cause an abnormal ratio of the surface areas between the fetal and the maternal blood vessels in the labyrinthine layer. Our data suggest that PDGFB acts locally to contribute to the development of the labyrinthine layer of the fetal placenta and the formation of a proper nutrient-waste exchange system during fetal development. We point out that the roles of PDGFB/Rbeta signaling in the placenta may be analogous to those in the developing kidney, by controlling pericytes in the labyrinthine layer and mesangial cells in the kidney.
|
|
| 43. |
|
|
| 44. |
- Arnqvist, Anna, et al.
(author)
-
The Crl protein activates cryptic genes for curli formation and fibronectin binding in Escherichia coli HB101.
- 1992
-
In: Molecular Microbiology. - 0950-382X .- 1365-2958. ; 6:17, s. 2443-52
-
Journal article (peer-reviewed)abstract
- Curli are thin, coiled, temperature-regulated fibres on fibronectin-binding Escherichia coli. The subunit protein of curli was highly homologous at its amino terminus to SEF-17, the subunit protein of thin, aggregative fimbriae of Salmonella enteritidis 27655 strain 3b, suggesting that these fibres form a novel class of surface organelles on enterobacteria. E. coli HB101 is non-curliated and unable to bind soluble, iodinated fibronectin. The phenotypically cryptic curlin subunit gene, csgA, in HB101 is transcriptionally activated by expressing the cytoplasmic Crl on a multicopy plasmid. Transcriptional activation of csgA by Crl was observed after growth at 26 degrees C but not at 37 degrees C, even though crl transcription was not thermoregulated. A deletion of the 39 carboxy-terminal residues abolished Crl activity, whereas a deletion of 10 residues at the C-terminus did not, implying that a region between residue 93 and 122 in the 132-amino-acid-residue large Crl protein is required for activating curli expression in E. coli HB101. crl is a normal housekeeping gene in E. coli and it is suggested that its gene product may either be a DNA-binding protein affecting chromatin structure as has been suggested for histone-like protein H1 or interact with specific regulatory protein(s) controlling transcription of genes required for curli formation and fibronectin binding.
|
|
| 45. |
- Casanueva, Felipe F., et al.
(author)
-
Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement
- 2017
-
In: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20, s. 489-498
-
Research review (peer-reviewed)abstract
- © 2017, The Author(s). Introduction: With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods: To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results: After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions: Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Ertel, D., et al.
(author)
-
Ultrastable, high-repetition-rate attosecond beamline for time-resolved XUV-IR coincidence spectroscopy
- 2023
-
In: Review of Scientific Instruments. - 0034-6748. ; 94:7
-
Journal article (peer-reviewed)abstract
- The implementation of attosecond photoelectron-photoion coincidence spectroscopy for the investigation of atomic and molecular dynamics calls for a high-repetition-rate driving source combined with experimental setups characterized by excellent stability for data acquisition over time intervals ranging from a few hours up to a few days. This requirement is crucial for the investigation of processes characterized by low cross sections and for the characterization of fully differential photoelectron(s) and photoion(s) angular and energy distributions. We demonstrate that the implementation of industrial-grade lasers, combined with a careful design of the delay line implemented in the pump-probe setup, allows one to reach ultrastable experimental conditions leading to an error in the estimation of the time delays of only 12 as over an acquisition time of 6.5 h. This result opens up new possibilities for the investigation of attosecond dynamics in simple quantum systems.
|
|
| 49. |
- Guillemin, R., et al.
(author)
-
Isotope effects in dynamics of water isotopologues induced by core ionization at an x-ray free-electron laser
- 2023
-
In: STRUCTURAL DYNAMICS-US. - 2329-7778. ; 10:5
-
Journal article (peer-reviewed)abstract
- Dynamical response of water exposed to x-rays is of utmost importance in a wealth of science areas. We exposed isolated water isotopologues to short x-ray pulses from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we identify significant structural dynamics with characteristic isotope effects in H2O2+, D2O2+, and HDO2+, such as asymmetric bond elongation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. A method to disentangle the sequences of events taking place upon the consecutive absorption of two x-ray photons is described. The obtained deep look into structural properties and dynamics of dissociating water isotopologues provides essential insights into the underlying mechanisms.
|
|
| 50. |
|
|
