| 1. |
- Capel, Pierre, et al.
(författare)
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Effective field theory analysis of the Coulomb breakup of the one-neutron halo nucleus 19 C
- 2023
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Ingår i: European Physical Journal A. - 1434-601X .- 1434-6001. ; 59:11
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Tidskriftsartikel (refereegranskat)abstract
- We analyse the Coulomb breakup of 19 C measured at 67A MeV at RIKEN. We use the Coulomb-Corrected Eikonal (CCE) approximation to model the reaction and describe the one-neutron halo nucleus 19 C within Halo Effective Field Theory (Halo EFT). At leading order we obtain a fair reproduction of the measured cross section as a function of energy and angle. The description is insensitive to the choice of optical potential, as long as it accurately represents the size of 18 C. It is also insensitive to the interior of the 19 C wave function. Comparison between theory and experiment thus enables us to infer asymptotic properties of the ground state of 19 C: these data put constraints on the one-neutron separation energy of this nucleus and, for a given binding energy, can be used to extract an asymptotic normalisation coefficient (ANC). These results are confirmed by CCE calculations employing next-to-leading order Halo EFT descriptions of 19 C: at this order the results for the Coulomb breakup cross section are completely insensitive to the choice of the regulator. Accordingly, this reaction can be used to constrain the one-neutron separation energy and ANC of 19 C.
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| 2. |
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| 3. |
- Svensson, Pierre, et al.
(författare)
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Las viktig i kampen mot sextrakasserier
- 2018
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Ingår i: Göteborgs-Posten, 2018-04-06.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Var tredje kvinna har utsatts för sexuella trakasserier på jobbet och många lämnar sin anställning. Därför är det allvarligt att lagen om anställningsskydd nu ifrågasätts från flera håll. Ett försvagat anställningsskydd skulle vara förödande i arbetet mot sexuella trakasserier på arbetsplatsen, skriver Pierre Svensson och Camilla Lundgren från Unionen, tillsammans med Eva-Maria Svensson och Ninni Carlsson från Göteborgs universitet
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| 4. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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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.
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| 5. |
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| 6. |
- Hasselgren, Jon, et al.
(författare)
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HMS: A Predictive Text Entry Method using Bigrams
- 2003
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Ingår i: Proceedings of the Workshop on Language Modeling for Text Entry Methods. ; , s. 43-49
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Konferensbidrag (refereegranskat)abstract
- Due to the emergence of SMS messages, the significance of effective text entry on limited-size keyboards has increased. In this paper, we describe and discuss a new method to enter text more efficiently using a mobile telephone keyboard. This method, which we called HMS, predicts words from a sequence of keystrokes using a dictionary and a function combining bigram frequencies and word length. We implemented the HMS text entry method on a software-simulated mobile telephone keyboard and we compared it to a widely available commercial system. We trained the language model on a corpus of Swedish news and we evaluated the method. Although the training corpus does not reflect the language used in SMS messages, the results show a decrease by 7 to 13 percent in the number of keystrokes needed to enter a text. These figures are very encouraging even though the implementation can be optimized in several ways. The HMS text entry method can easily be transferred to other languages.
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| 7. |
- Lopez-Varela, Elisa, et al.
(författare)
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Drug concentration at the site of disease in children with pulmonary tuberculosis
- 2022
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 77:6, s. 1710-1719
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Tidskriftsartikel (refereegranskat)abstract
- Background Current TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB. Objectives To determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB. Methods We quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions. Results Isoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions. Conclusions Despite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.
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| 8. |
- Lopman, Ben, et al.
(författare)
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Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant
- 2004
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 363:9410, s. 682-688
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Tidskriftsartikel (refereegranskat)abstract
- Background Highly publicised outbreaks of norovirus gastroenteritis in hospitals in the UK and Ireland and cruise ships in the USA sparked speculation about whether this reported activity was unusual. Methods We analysed data collected through a collaborative research and surveillance network of viral gastroenteritis in ten European countries (England and Wales were analysed as one region). We compiled data on total number of outbreaks by month, and compared genetic sequences from the isolated viruses. Data were compared with historic data from a systematic retrospective review of surveillance systems and with a central database of viral sequences. Findings Three regions (England and Wales, Germany, and the Netherlands) had sustained epidemiological and viral characterisation data from 1995 to 2002. In all three, we noted a striking increase in norovirus outbreaks in 2002 that coincided with the detection and emergence of a new predominant norovirus variant of genogroup II4, which had a consistent mutation in the polymerase gene. Eight of nine regions had an annual peak in 2002 and the new genogroup II4 variant was detected in nine countries. Also, the detection of the new variant preceded an atypical spring and summer peak of outbreaks in three countries. Interpretation Our data from ten European countries show a striking increase and unusual seasonal pattern of norovirus gastroenteritis in 2002 that occurred concurrently with the emergence of a novel genetic variant. In addition to showing the added value of an international network for viral gastroenteritis outbreaks, these observations raise questions about the biological properties of the variant and the mechanisms for its rapid dissemination.
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| 9. |
- Pierre, Mathieu, 1983, et al.
(författare)
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Resonant and off-resonant microwave signal manipulation in coupled superconducting resonators
- 2019
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 99:9
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Tidskriftsartikel (refereegranskat)abstract
- We present an experimental demonstration as well as a theoretical model of an integrated circuit designed for the manipulation of a microwave field down to the single-photon level. The device is made of a superconducting resonator coupled to a transmission line via a second frequency-tunable resonator. The tunable resonator can be used as a tunable coupler between the fixed resonator and the transmission line. Moreover, the manipulation of the microwave field between the two resonators is possible. In particular, we demonstrate the swapping of the field from one resonator to the other by pulsing the frequency detuning between the two resonators. The behavior of the system, which determines how the device can be operated, is analyzed as a function of one key parameter of the system, the damping ratio of the coupled resonators. We show a good agreement between experiments and simulations, realized by solving a set of coupled differential equations.
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| 10. |
- Pierre, Mathieu, 1983, et al.
(författare)
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Storage and on-demand release of microwaves using superconducting resonators with tunable coupling
- 2014
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 104:23, s. Art. Nr. 232604-
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Tidskriftsartikel (refereegranskat)abstract
- We present a system which allows to tune the coupling between a superconducting resonator and a transmission line. This storage resonator is addressed through a second, coupling resonator, which is frequency-tunable and controlled by a magnetic flux applied to a superconducting quantum interference device. We experimentally demonstrate that the lifetime of the storage resonator can be tuned by more than three orders of magnitude. A field can be stored for 18 mu s when the coupling resonator is tuned off resonance and it can be released in 14 ns when the coupling resonator is tuned on resonance. The device allows capture, storage, and on-demand release of microwaves at a tunable rate.
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| 11. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.1, Requirement analysis and design approaches for 5G air interface
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This document describes the problem space for the METIS research conducted in the radio link context. Firstly, a requirement analysis for the air interface design is conducted based on the test case descriptions presented in METIS deliverable D1.1. It follows an introduction of the research topics being pursued in the radio link research together with an illustration of how these topics are addressing the derived requirements. Moreover, it is shown which of thoserequirements address the needs of the METIS horizontal topics. To facilitate the achievement of these three objectives, a framework of General Requirements is introduced, which will be used throughout the project to assess and evaluate developed radio link solutions and to allow for measuring against the overall system performance goals.
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| 12. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.2 Novel radio link concepts and state of the art analysis
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This document provides a detailed overview of the Radio Link concepts being developed in METIS as well as a detailed analysis of the related state of the art. For each of the research topics identified for the radio link research covering flexible air interface, new waveforms,modulation and coding techniques as well as multiple access, medium access control and enablers for radio resource management, a detailed description of the aspects to be investigated will be given, going beyond the limits imposed by the systems operated today and their planned evolutions. The state of the art analysis, which is conducted for each of the research topics separately, covers current standards, their future evolutions as well as latest academic research. Elaborating on how the approaches followed in the radio link research may advance this state of the art carves a promising track towards innovative solutions addressing the challenges of future wireless communication.
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| 13. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.3 Components of a new air interface - building blocks and performance
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This document provides intermediate results of the concepts being developed in the radio link research of METIS. For each of the technology components (TeC) within the technology component clusters (TeCC), covering flexible air interface, new waveforms, modulation and coding techniques as well as multiple access, medium access control and enablers for radio resource management, key findings and conclusions collected so far are summarized in section 2. Continuative descriptions and research outcomes are given in the annex and referred publications.The results presented here will be extended in the further progress of the project, and they will be used in the next phase of the project to develop and refine the overall METIS system concept instantiated by the horizontal topics. The suitability of the single technology components for the overall system design being able to meet the wide range of requirements for 5G will then be evaluated.
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| 14. |
- Popovski, Petar, et al.
(författare)
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EU FP7 INFSO-ICT-317669 METIS, D2.4 Proposed solutions for new radio access
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This deliverable represents the final report on the METIS radio link research. It provides a comprehensive and self-contained summary of all investigated technology components (TeCs), including evaluation results and conclusions on their potential for 5G. The METIS radio link research covers three main areas, which are considered key aspects for developing a self-contained air interface design for 5G: 1) Flexible air interface, 2) Waveforms, coding & modulation and transceiver design and 3) Multiple access, Medium Access Control (MAC) and Radio Resource Management (RRM). TeCs with similar research context and objectives have been grouped into clusters, whereof five have been selected as the most promising for 5G systems: From research area 1, TeC clusters providing key enablers for an air interface for ultra-dense networks (UDN) and for moving networks; from research area 2, multi-carrier transmission schemes with filtering; and from research area 3, novel access schemes for massive machine access as well as for non-orthogonal access.
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| 15. |
- Robinson, Jonathan, 1986, et al.
(författare)
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An atlas of human metabolism
- 2020
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 13:624
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models (GEMs) are valuable tools to study metabolism and provide a scaffold for the integrative analysis of omics data. Researchers have developed increasingly comprehensive human GEMs, but the disconnect among different model sources and versions impedes further progress. We therefore integrated and extensively curated the most recent human metabolic models to construct a consensus GEM, Human1. We demonstrated the versatility of Human1 through the generation and analysis of cell- and tissue-specific models using transcriptomic, proteomic, and kinetic data. We also present an accompanying web portal, Metabolic Atlas (https://www.metabolicatlas.org/), which facilitates further exploration and visualization of Human1 content. Human1 was created using a version-controlled, open-source model development framework to enable community-driven curation and refinement. This framework allows Human1 to be an evolving shared resource for future studies of human health and disease.
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| 16. |
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| 17. |
- Saux, Patrick, et al.
(författare)
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Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study.
- 2023
-
Ingår i: The Lancet. Digital health. - 2589-7500. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery.In this multinational retrospective observational study we enrolled adult participants (aged ≥18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year follow-up after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band. Patients with a previous history of bariatric surgery or large delays between scheduled and actual visits were excluded. The training cohort comprised patients from two centres in France (ABOS and BAREVAL). The primary outcome was BMI at 5 years. A model was developed using least absolute shrinkage and selection operator to select variables and the classification and regression trees algorithm to build interpretable regression trees. The performances of the model were assessed through the median absolute deviation (MAD) and root mean squared error (RMSE) of BMI.10231 patients from 12 centres in ten countries were included in the analysis, corresponding to 30602 patient-years. Among participants in all 12 cohorts, 7701 (75·3%) were female, 2530 (24·7%) were male. Among 434 baseline attributes available in the training cohort, seven variables were selected: height, weight, intervention type, age, diabetes status, diabetes duration, and smoking status. At 5 years, across external testing cohorts the overall mean MAD BMI was 2·8 kg/m2 (95% CI 2·6-3·0) and mean RMSE BMI was 4·7 kg/m2 (4·4-5·0), and the mean difference between predicted and observed BMI was -0·3 kg/m2 (SD 4·7). This model is incorporated in an easy to use and interpretable web-based prediction tool to help inform clinical decision before surgery.We developed a machine learning-based model, which is internationally validated, for predicting individual 5-year weight loss trajectories after three common bariatric interventions.SOPHIA Innovative Medicines Initiative 2 Joint Undertaking, supported by the EU's Horizon 2020 research and innovation programme, the European Federation of Pharmaceutical Industries and Associations, Type 1 Diabetes Exchange, and the Juvenile Diabetes Research Foundation and Obesity Action Coalition; Métropole Européenne de Lille; Agence Nationale de la Recherche; Institut national de recherche en sciences et technologies du numérique through the Artificial Intelligence chair Apprenf; Université de Lille Nord Europe's I-SITE EXPAND as part of the Bandits For Health project; Laboratoire d'excellence European Genomic Institute for Diabetes; Soutien aux Travaux Interdisciplinaires, Multi-établissements et Exploratoires programme by Conseil Régional Hauts-de-France (volet partenarial phase 2, project PERSO-SURG).
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| 18. |
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| 19. |
- Svensson, Elin, et al.
(författare)
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Hybrid raytrace modelling of an underwater acoustics communication channel
- 2004
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Ingår i: Proceedings of the Seventh European Conference on Underwater Acoustics. ; , s. 1211--1216
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Konferensbidrag (refereegranskat)abstract
- A hybrid method is described for modelling sound propagation in range-dependent shallow water environments. The method combines ray tracing in a range-dependent water column with local full-field modelling of interactions with a seabed composed of multiple range-dependent layers of fluid or solid materials. The method is assessed by simulations of the Yellow Shark 94 experiments in the Mediterranean, using environmental parameters available from previous acoustic full-field inversions of the experimental acoustic data, and from an oceanographic survey with a towed-oscillating CTD profiler. Results from applying the method to simulation of transmission and decoding of communication signals in the shallow-water waveguide are presented.
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| 20. |
- Svensson, Elin, et al.
(författare)
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Time variability of an underwater acoustic channel
- 2003
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Ingår i: Proceedings of the Tenth International Congress on Sound and Vibration. ; , s. 2633--2641
-
Konferensbidrag (refereegranskat)abstract
- Underwater acoustic communication systems deal with the problem of fading multipath propagation as well as Doppler shifts. Knowledge of the channel impulse response considerably simplifies the extraction of information from a transmitted signal. Supposed that the impulse response is known at one time instant, the bit-error rate is here studied using that impulse response for the equalisation at later instants, to get a picture of the time variability of the channel. The study is performed by computer simulations with different modulation schemes using channel impulse responses determined from measurements in the Mediterranean during Yellow Shark 94.
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| 21. |
- Svensson, Ida-Maria, 1988, et al.
(författare)
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Microwave photon generation in a doubly tunable superconducting resonator
- 2018
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 969:1
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Konferensbidrag (refereegranskat)abstract
- We have created a doubly tunable resonator, with the intention to simulate relativistic motion of the resonator boundaries in real space. Our device is a superconducting coplanar-waveguide microwave resonator, with fundamental resonant frequency ω 1 / (2 π ) ~ 5 GHz. Both of its ends are terminated to ground via dc-SQUIDs, which serve as magnetic-flux-controlled inductances. Applying a flux to either SQUID allows the tuning of ω 1 / (2 π ) by approximately 700 MHz. Using two separate on-chip magnetic-flux lines, we modulate the SQUIDs with two tones of equal frequency, close to 2 ω 1 . We observe photon generation, at ω 1 , above a certain pump amplitude threshold. By varying the relative phase of the two pumps we are able to control this threshold, in good agreement with a theoretical model. At the same time, some of our observations deviate from the theoretical predictions, which we attribute to parasitic couplings resulting in current driving of the SQUIDs
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| 22. |
- Svensson, Johan, 1964, et al.
(författare)
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Growth hormone (GH) replacement therapy in GH deficient adults: predictors of one-year metabolic and clinical response.
- 2007
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 17:1, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study investigated whether baseline status could predict the responsiveness to one-year growth hormone (GH) replacement therapy in adult GH deficient (GHD) patients. DESIGN: A total of 380 European patients with adult onset GHD due to non-functioning pituitary adenoma that had been enrolled in Pfizer International Metabolic Database (KIMS), and that had completed one year of GH replacement therapy within KIMS, were studied. RESULTS: The mean initial dose of GH was 0.22 (SEM 0.01) mg/day and after one year, the mean dose was 0.36 (0.01) mg/day. The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.75 (0.08) at baseline to 0.47 (0.05) after one year. Quality of life (QoL)-Assessment of GHD in Adults (QoL-AGHDA), waist circumference, waist:hip ratio, and serum lipid pattern improved. Women received a higher dose of GH than men after one year, and demonstrated similar treatment response. In multiple stepwise forward regression analyses, the one-year changes in QoL-AGHDA score, waist:hip ratio, and serum low density lipoprotein-cholesterol (LDL-C) level correlated inversely with the baseline values of the same variable. In addition, the change after one year in QoL-AGHDA score correlated inversely with duration of hypopituitarism and baseline serum high density lipoprotein-cholesterol (HDL-C) level, and the change in waist:hip ratio correlated inversely, although more weakly, with baseline serum HDL-C level and UK citizenship and positively with baseline waist circumference and the initial GH dose. The change in serum LDL-C level additionally correlated inversely with the mean GH dose and duration of hypopituitarism and positively with UK citizenship. CONCLUSIONS: Baseline status could, with moderate strength, predict the responsiveness in the same variable whereas it could not, or only weakly, predict the response in other variables. Therefore, when the decision to start GH replacement is undertaken, as many outcome variables as possible should be evaluated in order to adequately evaluate the likelihood of clinical benefit. Finally, women have a similar response to GH replacement as men when individualised GH dosing schedules are employed and should therefore be selected for GH therapy to a similar extent.
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| 23. |
- Teumer, A., et al.
(författare)
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Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits
- 2016
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 15:5, s. 811-824
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Tidskriftsartikel (refereegranskat)abstract
- The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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| 24. |
- Wang, Hao, 1975, et al.
(författare)
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Genome-scale metabolic network reconstruction of model animals as a platform for translational research
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:30
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.
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| 25. |
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