| 41. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 42. |
- Bull, Philip, et al.
(författare)
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Beyond ΛCDM : Problems, solutions, and the road ahead
- 2016
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Ingår i: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 12, s. 56-99
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Tidskriftsartikel (refereegranskat)abstract
- Despite its continued observational successes, there is a persistent (and growing) interest in extending cosmology beyond the standard model, Lambda CDM. This is motivated by a range of apparently serious theoretical issues, involving such questions as the cosmological constant problem, the particle nature of dark matter, the validity of general relativity on large scales, the existence of anomalies in the CMB and on small scales, and the predictivity and testability of the inflationary paradigm. In this paper, we summarize the current status of Lambda CDM as a physical theory, and review investigations into possible alternatives along a number of different lines, with a particular focus on highlighting the most promising directions. While the fundamental problems are proving reluctant to yield, the study of alternative cosmologies has led to considerable progress, with much more to come if hopes about forthcoming high-precision observations and new theoretical ideas are fulfilled.
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| 43. |
- Gerhards, R, et al.
(författare)
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Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS
- 2020
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 8:1, s. 207-
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune disorders of the central nervous system (CNS) comprise a broad spectrum of clinical entities. The stratification of patients based on the recognized autoantigen is of great importance for therapy optimization and for concepts of pathogenicity, but for most of these patients, the actual target of their autoimmune response is unknown. Here we investigated oligodendrocyte myelin glycoprotein (OMGP) as autoimmune target, because OMGP is expressed specifically in the CNS and there on oligodendrocytes and neurons. Using a stringent cell-based assay, we detected autoantibodies to OMGP in serum of 8/352 patients with multiple sclerosis, 1/28 children with acute disseminated encephalomyelitis and unexpectedly, also in one patient with psychosis, but in none of 114 healthy controls. Since OMGP is GPI-anchored, we validated its recognition also in GPI-anchored form. The autoantibodies to OMGP were largely IgG1 with a contribution of IgG4, indicating cognate T cell help. We found high levels of soluble OMGP in human spinal fluid, presumably due to shedding of the GPI-linked OMGP. Analyzing the pathogenic relevance of autoimmunity to OMGP in an animal model, we found that OMGP-specific T cells induce a novel type of experimental autoimmune encephalomyelitis dominated by meningitis above the cortical convexities. This unusual localization may be directed by intrathecal uptake and presentation of OMGP by meningeal phagocytes. Together, OMGP-directed autoimmunity provides a new element of heterogeneity, helping to improve the stratification of patients for diagnostic and therapeutic purposes.
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| 44. |
- Iacobelli, M., et al.
(författare)
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Studying Galactic interstellar turbulence through fluctuations in synchrotron emission: First LOFAR Galactic foreground detection
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 558, s. 721-
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The characteristic outer scale of turbulence (i.e. the scale at which the dominant source of turbulence injects energy to the interstellar medium) and the ratio of the random to ordered components of the magnetic field are key parameters to characterise magnetic turbulence in the interstellar gas, which affects the propagation of cosmic rays within the Galaxy. We provide new constraints to those two parameters. Methods. We use the LOw Frequency ARray (LOFAR) to image the diffuse continuum emission in the Fan region at (l,b) ∼ (137.0, +7.0) at 80′′ × 70′′ resolution in the range [146, 174] MHz. We detect multi-scale fluctuations in the Galactic synchrotron emission and compute their power spectrum. Applying theoretical estimates and derivations from the literature for the first time, we derive the outer scale of turbulence and the ratio of random to ordered magnetic field from the characteristics of these fluctuations. Results. We obtain the deepest image of the Fan region to date and find diffuse continuum emission within the primary beam. The power spectrum displays a power law behaviour for scales between 100 and 8 arcmin with a slope α =-1.84 ± 0.19. We find an upper limit of ∼20 pc for the outer scale of the magnetic interstellar turbulence toward the Fan region, which is in agreement with previous estimates in literature. We also find a variation of the ratio of random to ordered field as a function of Galactic coordinates, supporting different turbulent regimes. Conclusions. We present the first LOFAR detection and imaging of the Galactic diffuse synchrotron emission around 160 MHz from the highly polarized Fan region. The power spectrum of the foreground synchrotron fluctuations is approximately a power law with a slope α ≈-1.84 up to angular multipoles of ≤1300, corresponding to an angular scale of ∼8 arcmin. We use power spectra fluctuations from LOFAR as well as earlier GMRT and WSRT observations to constrain the outer scale of turbulence (Lout) of the Galactic synchrotron foreground, finding a range of plausible values of 10-20 pc. Then, we use this information to deduce lower limits of the ratio of ordered to random magnetic field strength. These are found to be 0.3, 0.3, and 0.5 for the LOFAR, WSRT and GMRT fields considered respectively. Both these constraints are in agreement with previous estimates. © 2013 ESO.
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| 45. |
- Jouhten, P., et al.
(författare)
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Predictive evolution of metabolic phenotypes using model-designed environments
- 2022
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive evolution under controlled laboratory conditions has been highly effective in selecting organisms with beneficial phenotypes such as stress tolerance. The evolution route is particularly attractive when the organisms are either difficult to engineer or the genetic basis of the phenotype is complex. However, many desired traits, like metabolite secretion, have been inaccessible to adaptive selection due to their trade-off with cell growth. Here, we utilize genome-scale metabolic models to design nutrient environments for selecting lineages with enhanced metabolite secretion. To overcome the growth-secretion trade-off, we identify environments wherein growth becomes correlated with a secondary trait termed tacking trait. The latter is selected to be coupled with the desired trait in the application environment where the trait manifestation is required. Thus, adaptive evolution in the model-designed selection environment and subsequent return to the application environment is predicted to enhance the desired trait. We experimentally validate this strategy by evolving Saccharomyces cerevisiae for increased secretion of aroma compounds, and confirm the predicted flux-rerouting using genomic, transcriptomic, and proteomic analyses. Overall, model-designed selection environments open new opportunities for predictive evolution.
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| 46. |
- Matalonga, L, et al.
(författare)
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Solving patients with rare diseases through programmatic reanalysis of genome-phenome data
- 2021
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 29:9, s. 1337-1347
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Tidskriftsartikel (refereegranskat)abstract
- Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP’s Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics.
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| 47. |
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| 48. |
- Prusakov, Pavel, et al.
(författare)
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A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study
- 2021
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 32
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Tidskriftsartikel (refereegranskat)abstract
- Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received >= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02).Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.
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| 49. |
- Yagoubov, P., et al.
(författare)
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Wideband 67-116 GHz receiver development for ALMA Band 2
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 634
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Atacama Large Millimeter/submillimeter Array (ALMA) has been in operation since 2011, but it has not yet been populated with the full suite of its planned frequency bands. In particular, ALMA Band 2 (67-90 GHz) is the final band in the original ALMA band definition to be approved for production. Aims. We aim to produce a wideband, tuneable, sideband-separating receiver with 28 GHz of instantaneous bandwidth per polarisation operating in the sky frequency range of 67-116 GHz. Our design anticipates new ALMA requirements following the recommendations of the 2030 ALMA Development Roadmap. Methods. The cryogenic cartridge is designed to be compatible with the ALMA Band 2 cartridge slot, where the coldest components - the feedhorns, orthomode transducers, and cryogenic low noise amplifiers - operate at a temperature of 15 K. We use multiple simulation methods and tools to optimise our designs for both the passive optics and the active components. The cryogenic cartridge is interfaced with a room-temperature (warm) cartridge hosting the local oscillator and the downconverter module. This warm cartridge is largely based on GaAs semiconductor technology and is optimised to match the cryogenic receiver bandwidth with the required instantaneous local oscillator frequency tuning range. Results. Our collaboration has resulted in the design, fabrication, and testing of multiple technical solutions for each of the receiver components, producing a state-of-the-art receiver covering the full ALMA Band 2 and 3 atmospheric window. The receiver is suitable for deployment on ALMA in the coming years and it is capable of dual-polarisation, sideband-separating observations in intermediate frequency bands spanning 4-18 GHz for a total of 28 GHz on-sky bandwidth per polarisation channel. Conclusions. We conclude that the 67-116 GHz wideband implementation for ALMA Band 2 is now feasible and that this receiver provides a compelling instrumental upgrade for ALMA that will enhance observational capabilities and scientific reach.
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