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- Ghara, Raghunath, et al.
(author)
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Constraining the intergalactic medium at z approximate to 9.1 using LOFAR Epoch of Reionization observations
- 2020
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 493:4, s. 4728-4747
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Journal article (peer-reviewed)abstract
- We derive constraints on the thermal and ionization states of the intergalactic medium (IGM) at redshift approximate to 9.1 using new upper limits on the 21-cm power spectrum measured by the LOFAR radio telescope and a prior on the ionized fraction at that redshift estimated from recent cosmic microwave background (CMB) observations. We have used results from the reionization simulation code GRIZZLY and a Bayesian inference framework to constrain the parameters which describe the physical state of the IGM. We find that, if the gas heating remains negligible, an IGM with ionized fraction greater than or similar to 0.13 and a distribution of the ionized regions with a characteristic size greater than or similar to 8 h(-1) comoving megaparsec (Mpc) and a full width at half-maximum (FWHM) greater than or similar to 16 h(-1) Mpc is ruled out. For an IGM with a uniform spin temperature T-S greater than or similar to 3 K, no constraints on the ionized component can be computed. If the large-scale fluctuations of the signal are driven by spin temperature fluctuations, an IGM with a volume fraction less than or similar to 0.34 of heated regions with a temperature larger than CMB, average gas temperature 7-160 K, and a distribution of the heated regions with characteristic size 3.5-70 h(-1) Mpc and FWHM of less than or similar to 110 h(-1) Mpc is ruled out. These constraints are within the 95 per cent credible intervals. With more stringent future upper limits from LOFAR at multiple redshifts, the constraints will become tighter and will exclude an increasingly large region of the parameter space.
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| 2. |
- Mertens, F. G., et al.
(author)
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Improved upper limits on the 21 cm signal power spectrum of neutral hydrogen at z approximate to 9.1 from LOFAR
- 2020
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 493:2, s. 1662-1685
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Journal article (peer-reviewed)abstract
- A new upper limit on the 21 cm signal power spectrum at a redshift of z approximate to 9.1 is presented, based on 141 h of data obtained with the Low-Frequency Array (LOFAR). The analysis includes significant improvements in spectrally smooth gain-calibration, Gaussian Process Regression (GPR) foreground mitigation and optimally weighted power spectrum inference. Previously seen 'excess power' due to spectral structure in the gain solutions has markedly reduced but some excess power still remains with a spectral correlation distinct from thermal noise. This excess has a spectral coherence scale of 0.25-0.45 MHz and is partially correlated between nights, especially in the foreground wedge region. The correlation is stronger between nights covering similar local sidereal times. A best 2-sigma upper limit of Delta(2)(21) < (73)(2) mK(2) at k = 0.075 h cMpc(-1) is found, an improvement by a factor approximate to 8 in power compared to the previously reported upper limit. The remaining excess power could be due to residual foreground emission from sources or diffuse emission far away from the phase centre, polarization leakage, chromatic calibration errors, ionosphere, or low-level radiofrequency interference. We discuss future improvements to the signal processing chain that can further reduce or even eliminate these causes of excess power.
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- Ruiz, N. Herrera, et al.
(author)
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Lofar deep fields: Probing a broader population of polarized radio galaxies in elais-n1
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 648
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Journal article (peer-reviewed)abstract
- We present deep polarimetric observations of the European Large Area ISO Survey-North 1 (ELAIS-N1) field using the Low Frequency Array (LOFAR) at 114.9-177.4 MHz. The ELAIS-N1 field is part of the LOFAR Two-metre Sky Survey deep fields data release I. For six eight-hour observing epochs, we align the polarization angles and stack the 20″-resolution Stokes Q, U-parameter data cubes. This produces a 16 deg2 image with 1σQU sensitivity of 26 μJy beam-1 in the central area. In this paper, we demonstrate the feasibility of the stacking technique, and we generate a catalog of polarized sources in ELAIS-N1 and their associated Faraday rotation measures (RMs). While in a single-epoch observation we detect three polarized sources, this number increases by a factor of about three when we consider the stacked data, with a total of ten sources. This yields a surface density of polarized sources of one per 1.6 deg2. The Stokes I images of three of the ten detected polarized sources have morphologies resembling those of FR I radio galaxies. This represents a greater fraction of this type of source than previously found, which suggests that more sensitive observations may help with their detection.
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- Eyjolfsdottir, H, et al.
(author)
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Fast Alpha Activity in EEG of Patients With Alzheimer's Disease Is Paralleled by Changes in Cognition and Cholinergic Markers During Encapsulated Cell Biodelivery of Nerve Growth Factor
- 2022
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In: Frontiers in aging neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14, s. 756687-
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Journal article (peer-reviewed)abstract
- Basal forebrain cholinergic neurons are dependent on nerve growth factor (NGF) for growth and survival and these cells are among the first to degenerate in Alzheimer’s disease (AD). Targeted delivery of NGF has been suggested as a potential therapy for AD. This hypothesis was tested in a clinical trial with encapsulated cell biodelivery of NGF (NGF-ECB) in AD patients. Three of six patients showed improved biomarkers for cognition by the end of the study. Here, we report on the effects of targeted delivery of NGF on human resting EEG.Materials and methodsNGF-ECB implants were implanted bilaterally in the basal forebrain of six AD patients for 12 months. EEG recordings and quantitative analysis were performed at baseline, 3 and 12 months of NGF delivery, and analyzed for correlation with changes in Mini-mental state examination (MMSE) and levels of the cholinergic marker choline acetyltransferase (ChAT) in cerebrospinal fluid (CSF).ResultsWe found significant correlations between the topographic variance of EEG spectral power at the three study points (baseline, 3 and 12 months) and changes in MMSE and CSF ChAT. This possible effect of NGF was identified in a narrow window of alpha frequency 10–11.5 Hz, where a stabilization in MMSE score during treatment was related to an increase in EEG alpha power. A similar relation was observed between the alpha power and ChAT. More theta power at 6.5 Hz was on the contrary associated with a decrease in CSF ChAT during the trial period.ConclusionIn this exploratory study, there was a positive correlative pattern between physiological high-frequency alpha activity and stabilization in MMSE and increase in CSF ChAT in AD patients receiving targeted delivery of NGF to the cholinergic basal forebrain.
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| 15. |
- Jiang, R. C., et al.
(author)
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Increased CSF-decorin predicts brain pathological changes driven by Alzheimer's A beta amyloidosis
- 2022
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In: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 10:1
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) biomarkers play an important role in diagnosing Alzheimer's disease (AD) which is characterized by amyloid-beta (A beta) amyloidosis. Here, we used two App knock-in mouse models, App(NL-F/NL-F) and App(NL-G-F/NL-G-F), exhibiting AD-like A beta pathology to analyze how the brain pathologies translate to CSF proteomes by label-free mass spectrometry (MS). This identified several extracellular matrix (ECM) proteins as significantly altered in App knock-in mice. Next, we compared mouse CSF proteomes with previously reported human CSF MS results acquired from patients across the AD spectrum. Intriguingly, the ECM protein decorin was similarly and significantly increased in both App(NL-F/NL-F) and App(NL-G-F/NL-G-F) mice, strikingly already at three months of age in the App(NL-F/NL-F) mice and preclinical AD subjects having abnormal CSF-A beta 42 but normal cognition. Notably, in this group of subjects, CSF-decorin levels positively correlated with CSF-A beta 42 levels indicating that the change in CSF-decorin is associated with early A beta amyloidosis. Importantly, receiver operating characteristic analysis revealed that CSF-decorin can predict a specific AD subtype having innate immune activation and potential choroid plexus dysfunction in the brain. Consistently, in App(NL-F/NL-F) mice, increased CSF-decorin correlated with both AP plaque load and with decorin levels in choroid plexus. In addition, a low concentration of human A beta 42 induces decorin secretion from mouse primary neurons. Interestingly, we finally identify decorin to activate neuronal autophagy through enhancing lysosomal function. Altogether, the increased CSF-decorin levels occurring at an early stage of A beta amyloidosis in the brain may reflect pathological changes in choroid plexus, present in a subtype of AD subjects.
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- Koopmans, Léon V. E., et al.
(author)
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Peering into the dark (ages) with low-frequency space interferometers : Using the 21-cm signal of neutral hydrogen from the infant universe to probe fundamental (Astro)physics
- 2021
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51, s. 1641-1676
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Journal article (peer-reviewed)abstract
- The Dark Ages and Cosmic Dawn are largely unexplored windows on the infant Universe (z ~ 200–10). Observations of the redshifted 21-cm line of neutral hydrogen can provide valuable new insight into fundamental physics and astrophysics during these eras that no other probe can provide, and drives the design of many future ground-based instruments such as the Square Kilometre Array (SKA) and the Hydrogen Epoch of Reionization Array (HERA). We review progress in the field of high-redshift 21-cm Cosmology, in particular focussing on what questions can be addressed by probing the Dark Ages at z > 30. We conclude that only a space- or lunar-based radio telescope, shielded from the Earth’s radio-frequency interference (RFI) signals and its ionosphere, enable the 21-cm signal from the Dark Ages to be detected. We suggest a generic mission design concept, CoDEX, that will enable this in the coming decades.
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| 20. |
- Logroscino, G, et al.
(author)
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Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries
- 2023
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 80:3, s. 279-286
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Journal article (peer-reviewed)abstract
- Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches.ObjectiveTo assess the incidence of FTLD across Europe.Design, Setting, and ParticipantsThe Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021.Main Outcomes and MeasuresRandom-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity.ResultsBased on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057.Conclusions and RelevanceThe findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.
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| 25. |
- Smailovic, U., et al.
(author)
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Synaptic Molecular and Neurophysiological Markers Are Independent Predictors of Progression in Alzheimer's Disease
- 2021
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 83:1, s. 355-366
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Journal article (peer-reviewed)abstract
- Background: Cerebrospinal fluid (CSF) neurogranin and quantitative electroencephalography (qEEG) are potential molecular and functional markers of synaptic pathology in Alzheimer's disease (AD). Synaptic markers have emerged as candidate prognostic indicators of AD since synaptic degeneration was shown to be an early event and the best correlate of cognitive deficits in patients along the disease continuum. Objective: The present study investigated the association between CSF neurogranin and qEEG measures as well as their potential to predict clinical deterioration in mild cognitive impairment (MCI) patients. Methods: Patients diagnosed with MCI (n = 99) underwent CSF conventional AD biomarkers and neurogranin analysis and resting-state EEG recordings. The study population was further stratified into stable (n = 41) and progressive MCI (n = 31), based on the progression to AD dementia during two years follow-up. qEEG analysis included computation of global field power and global field synchronization in four conventional frequency bands. Results: CSF neurogranin levels were associated with theta power and synchronization in the progressive MCI group. CSF neurogranin and qEEG measures were significant predictors of progression to AD dementia, independent of baseline amyloid status in MCI patients. A combination of CSF neurogranin with global EEG power in theta and global EEG synchronization in beta band exhibited the highest classification accuracy as compared to either of these markers alone. Conclusion: qEEG and CSF neurogranin are independent predictors of progression to AD dementia in MCI patients. Molecular and neurophysiological synaptic markers may have additive value in a multimodal diagnostic and prognostic approach to dementia.
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| 26. |
- Wallace, Megan A., et al.
(author)
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The discovery, distribution, and diversity of DNA viruses associated with Drosophila melanogaster in Europe
- 2021
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In: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 7:1
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Journal article (peer-reviewed)abstract
- Drosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here, we report fourteen DNA viruses detected in a metagenomic analysis of 6668 pool-sequenced Drosophila, sampled from forty-seven European locations between 2014 and 2016. These include three new nudiviruses, a new and divergent entomopoxvirus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of galbut virus, a double-stranded RNA partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a bidnavirus, may be composed of up to twelve segments and thus represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2 per cent or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D.melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses.
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