Search

PURPOSE: Systematic reviews evaluating and comparing the measurement properties of outcome measurement instruments (OMIs) play an important role in OMI selection. Earlier overviews of review quality (2007, 2014) evidenced substantial concerns with regards to alignment to scientific standards. This overview aimed to investigate whether the quality of recent systematic reviews of OMIs lives up to the current scientific standards.METHODS: One hundred systematic reviews of OMIs published from June 1, 2021 onwards were randomly selected through a systematic literature search performed on March 17, 2022 in MEDLINE and EMBASE. The quality of systematic reviews was appraised by two independent reviewers. An updated data extraction form was informed by the earlier studies, and results were compared to these earlier studies' findings.RESULTS: A quarter of the reviews had an unclear research question or aim, and in 22% of the reviews the search strategy did not match the aim. Half of the reviews had an incomprehensive search strategy, because relevant search terms were not included. In 63% of the reviews (compared to 41% in 2014 and 30% in 2007) a risk of bias assessment was conducted. In 73% of the reviews (some) measurement properties were evaluated (58% in 2014 and 55% in 2007). In 60% of the reviews the data were (partly) synthesized (42% in 2014 and 7% in 2007); evaluation of measurement properties and data syntheses was not conducted separately for subscales in the majority. Certainty assessments of the quality of the total body of evidence were conducted in only 33% of reviews (not assessed in 2014 and 2007). The majority (58%) did not make any recommendations on which OMI (not) to use.CONCLUSION: Despite clear improvements in risk of bias assessments, measurement property evaluation and data synthesis, specifying the research question, conducting the search strategy and performing a certainty assessment remain poor. To ensure that systematic rev

In sweet pepper (Capsicum annuum L.), the fruit yield is often negatively affected by fruit abortion. Here we investigated whether fruit abortion is affected by the blue:red light ratio (B:R) and the possible underlying physiological mechanisms related to carbohydrates and hormones. Sweet pepper plants were grown at B:R of 1:10, 1:3, 1:1 or 9:1 with a total photosynthetic photon flux density of 200 µmol m−2 s−1, resulting in a phytochrome photostationary state (PSS) of 0.88, 0.88, 0.86 and 0.72, respectively. For fruit set observations, each plant was allowed to retain 12 flowers on 4 main stems. Sweet pepper plants grown at the highest B:R (9:1) showed a low fruit set (around 3 fruits per plant), whereas the other three treatments resulted in higher fruit set (6–7 fruits per plant). This response matched with the changes in PSS, suggesting the B:R effect on fruit set might be controlled by phytochrome signaling, which requires further investigation. Plant shoot biomass and leaf area were reduced at B:R of 1:1 and 9:1. The reduced fruit set was associated with a drop in starch content and sucrose synthases activity; and a low auxin, high salicylic acid and high cis-Zeatin type levels in flowers. Flowers in the low fruit set treatment also failed to reduce the abscisic acid and ethylene levels after anthesis. We concluded that both the reduced starch content and the hormonal changes in flowers play a role in triggering fruit abortion at the high B:R of 9:1.

Far-red radiation affects many plant processes, including reproductive organ abortion. Our research aimed to determine the role of apical dominance in far-red light-induced flower and fruit abortion in sweet pepper (Capsicum annuum L.). We conducted several climate room experiments where plants were grown under white- or red-rich LED light, with or without additional far-red light. Additional far-red light enhanced apical dominance: it increased auxin levels in the apices of dominant shoots, and caused a greater difference in internode length and apical auxin levels between dominant and subordinate shoots. Additional far-red light stimulated fruit abortion in intact plants but not in decapitated plants, suggesting a crucial role of shoot apices in this effect. However, reducing basipetal auxin transport in the stems with N-1-naphthylphthalamic acid did not influence far-red light-stimulated fruit abortion, although auxin levels in the stem were largely reduced. Applying the synthetic auxin 1-naphthaleneacetic acid on decapitated apices did not influence fruit abortion. However, applying the auxin biosynthesis inhibitor yucasin to shoot apices reduced fruit abortion regardless of the light conditions, accompanied by slight shoot growth retardation. These findings suggest that the basipetal auxin stream does not mediate far-red light-stimulated fruit abortion. Far-red light-stimulated fruit abortion was associated with reduced sucrose accumulation and lower invertase activities in flowers. We suggest that under additional far-red light conditions, increased auxin levels in shoot apices promote fruit abortion probably through enhanced competition for assimilates between apices and flowers, which limits assimilate import into flowers.

Contains fulltext : 305092.pdf (Publisher’s version ) (Closed access), OBJECTIVE: To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA). DESIGN: Secondary analysis of a randomised placebo-controlled trial. SETTING: Dutch and Belgian neonatal intensive care units. PATIENTS: Infants born <30 weeks' gestational age (GA), ventilator-dependent in the second week of postnatal life. INTERVENTION: Infants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). MAIN OUTCOME MEASURES: The composite of death or neurodevelopmental impairment (NDI) at 2 years' CA and its components. Candidate effect modifiers (GA, small for GA, respiratory index, sex, multiple births, risk of moderate/severe bronchopulmonary dysplasia or death) were analysed using regression models with interaction terms and subpopulation treatment effect pattern plots. RESULTS: The composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn). For this outcome, treatment effect heterogeneity was seen across GA subgroups (<27 weeks: hydrocortisone (n=141) vs placebo (n=156), 54.6% vs 66.2%; OR 0.61 (95% CI 0.38 to 0.98); ≥27 weeks: hydrocortisone (n=30) vs placebo (n=31), 66.7% vs 45.2%; OR 2.43 (95% CI 0.86 to 6.85); p=0.02 for interaction). This effect was also found for the component death (<27 weeks: 20.1% vs 32.1%; OR 0.53 (95% CI 0.32 to 0.90); ≥27 weeks: 28.1% vs 16.1%; OR 2.04 (95% CI 0.60 to 6.95); p=0.049 for interaction) but not for the component NDI. No differential treatment effects were observed across other subgroups. CONCLUSION: This secondary analysis suggests that in infants <27 weeks' GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by its component death. There was insufficient evidence for other selected candidate effect modifiers.

Context. The occultation of a radio source by the plasma tail of a comet can be used to probe structure and dynamics in the tail. Such occultations are rare, and the occurrence of scintillation, due to small-scale density variations in the tail, remains somewhat controversial. Aims. A detailed observation taken with the Low-Frequency Array (LOFAR) of a serendipitous occultation of the compact radio source 3C196 by the plasma tail of comet C/2020 F3 (Neowise) is presented. 3C196 tracked almost perpendicularly behind the tail, providing a unique profile cut only a short distance downstream from the cometary nucleus itself. Methods. Interplanetary scintillation (IPS) is observed as the rapid variation of the intensity received of a compact radio source due to density variations in the solar wind. IPS in the signal received from 3C196 was observed for five hours, covering the full transit behind the plasma tail of comet C/2020 F3 (Neowise) on 16 July 2020, and allowing an assessment of the solar wind in which the comet and its tail are embedded. Results. The results reveal a sudden and strong enhancement in scintillation which is unequivocally attributable to the plasma tail. The strongest scintillation is associated with the tail boundaries, weaker scintillation is seen within the tail, and previously-unreported periodic variations in scintillation are noted, possibly associated with individual filaments of plasma. Furthermore, contributions from the solar wind and comet tail are separated to measure a sharp decrease in the velocity of material within the tail, suggesting a steep velocity shear resulting in strong turbulence along the tail boundary.

OBJECTIVES: Clear outcome reporting in clinical trials facilitates accurate interpretation and application of findings and improves evidence-informed decision-making. Standardized core outcomes for reporting neonatal trials have been developed, but little is known about how primary outcomes are reported in neonatal trials. Our aim was to identify strengths and weaknesses of primary outcome reporting in recent neonatal trials. METHODS: Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed. RESULTS: Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity. CONCLUSIONS: Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.

BACKGROUND AND OBJECTIVES: There is variability in the selection and reporting of outcomes in neonatal trials with key information frequently omitted. This can impact applicability of trial findings to clinicians, families, and caregivers, and impair evidence synthesis. The Neonatal Core Outcomes Set describes outcomes agreed as clinically important that should be assessed in all neonatal trials, and Consolidated Standards of Reporting Trials (CONSORT)-Outcomes 2022 is a new, harmonized, evidence-based reporting guideline for trial outcomes. We reviewed published trials using CONSORT-Outcomes 2022 guidance to identify exemplars of neonatal core outcome reporting to strengthen description of outcomes in future trial publications. METHODS: Neonatal trials including >100 participants per arm published between 2015 to 2020 with a primary outcome included in the Neonatal Core Outcome Set were identified. Primary outcome reporting was reviewed using CONSORT 2010 and CONSORT-Outcomes 2022 guidelines by assessors recruited from Cochrane Neonatal. Examples of clear and complete outcome reporting were identified with verbatim text extracted from trial reports. RESULTS: Thirty-six trials were reviewed by 39 assessors. Examples of good reporting for CONSORT 2010 and CONSORT-Outcomes 2022 criteria were identified and subdivided into 3 outcome categories: "survival," "short-term neonatal complications," and "long-term developmental outcomes" depending on the core outcomes to which they relate. These examples are presented to strengthen future research reporting. CONCLUSIONS: We have identified examples of good trial outcome reporting. These illustrate how important neonatal outcomes should be reported to meet the CONSORT 2010 and CONSORT-Outcomes 2022 guidelines. Emulating these examples will improve the transmission of information relating to outcomes and reduce associated research waste.

2,4-dichlorophenoxyacetic acid (2,4-D) is a synthetic analogue of the plant hormone auxin that is commonly used in many in vitro plant regeneration systems, such as somatic embryogenesis (SE). Its effectiveness in inducing SE, compared to the natural auxin indole-3-acetic acid (IAA), has been attributed to the stress triggered by this compound rather than its auxinic activity. However, this hypothesis has never been thoroughly tested. Here we used a library of forty 2,4-D analogues to test the structure–activity relationship with respect to the capacity to induce SE and auxinic activity in Arabidopsis thaliana. Four analogues induced SE as effectively as 2,4-D and 13 analogues induced SE but were less effective. Based on root growth inhibition and auxin response reporter expression, the 2,4-D analogues were classified into different groups, ranging from very active to not active auxin analogues. A halogen at the 4-position of the aromatic ring was important for auxinic activity, whereas a halogen at the 3-position resulted in reduced activity. Moreover, a small substitution at the carboxylate chain was tolerated, as was extending the carboxylate chain with an even number of carbons. The auxinic activity of most 2,4-D analogues was consistent with their simulated TIR1-Aux/IAA coreceptor binding characteristics. A strong correlation was observed between SE induction efficiency and auxinic activity, which is in line with our observation that 2,4-D-induced SE and stress both require TIR1/AFB auxin co-receptor function. Our data indicate that the stress-related effects triggered by 2,4-D and considered important for SE induction are downstream of auxin signalling.

OBJECTIVE: Registry-based randomized controlled trials (RRCTs) are increasingly used, promising to address challenges associated with traditional RCTs. We identified strengths and limitations reported in planned and completed RRCTs to inform future RRCTs. STUDY DESIGN AND SETTING: We conducted an environmental scan of literature discussing conceptual or methodological strengths and limitations of using registries for trial design and conduct (n=12), followed by an analysis of RRCT protocols (n=13) and reports (n=77) identified from a scoping review. Using framework analysis, we developed and refined a conceptual framework of RRCT-specific strengths and limitations. We mapped and interpreted strengths and limitations discussed by authors of RRCT articles using framework codes and quantified the frequencies at which these were mentioned. RESULTS: Our conceptual framework identified six main RRCT strengths and four main RRCT limitations. Considering implications for RRCT conduct and design, we formulated ten recommendations for registry designers, administrators, and trialists planning future RRCTs. CONCLUSION: Consideration and application of empirically underpinned recommendations for future registry design and trial conduct may help trialists utilize registries and RRCTs to their full potential., Funding agencies:Canadian Institutes of Health Research (CIHR) MYG-171684Canada Research Chairs

We present a new method, called "forced-spectrum fitting", for physically-based spectral modelling of radio sources during deconvolution. This improves upon current common deconvolution fitting methods, which often produce inaccurate spectra. Our method uses any pre-existing spectral index map to assign spectral indices to each model component cleaned during the multi-frequency deconvolution of WSClean, where the pre-determined spectrum is fitted. The component magnitude is evaluated by performing a modified weighted linear least-squares fit. We test this method on a simulated LOFAR-HBA observation of the 3C196 QSO and a real LOFAR-HBA observation of the 4C+55.16 FRI galaxy. We compare the results from the forced-spectrum fitting with traditional joined-channel deconvolution using polynomial fitting. Because no prior spectral information was available for 4C+55.16, we demonstrate a method for extracting spectral indices in the observed frequency band using "clustering". The models generated by the forced-spectrum fitting are used to improve the calibration of the datasets. The final residuals are comparable to existing multi-frequency deconvolution methods, but the output model agrees with the provided spectral index map, embedding correct spectral information. While forced-spectrum fitting does not solve the determination of the spectral information itself, it enables the construction of accurate multi-frequency models that can be used for wide-band calibration and subtraction., Comment: 17 pages, 9 figures, 5 tables. Accepted for publication in MNRAS

We present a new image of a 26.5 square degree region in the Bo\"otes constellation obtained at 1.4 GHz using the Aperture Tile in Focus (Apertif) system on the Westerbork Synthesis Radio Telescope. We use a newly developed processing pipeline which includes direction-dependent self-calibration which provides a significant improvement of the quality of the images compared to those released as part of the Apertif first data release. For the Bo\"otes region, we mosaic 187 Apertif images and extract a source catalog. The mosaic image has an angular resolution of 27${\times}$11.5 arcseconds and a median background noise of 40 ${\mu}$Jy/beam. The catalog has 8994 sources and is complete down to the 0.3 mJy level. We combine the Apertif image with LOFAR images of the Bo\"otes field at 54 and 150 MHz to study spectral properties of the sources. We find a spectral flattening towards low flux density sources. Using the spectral index limits from Apertif non-detections we derive that up to 9 percent of the sources have ultra-steep spectra with a slope steeper than -1.2. Steepening of the spectral index with increasing redshift is also seen in the data showing a different dependency for the low-frequency spectral index and the high frequency one. This can be explained by a population of sources having concave radio spectra with a turnover frequency around the LOFAR band. Additionally, we discuss cases of individual extended sources with an interesting resolved spectral structure. With the improved pipeline, we aim to continue processing data from the Apertif wide-area surveys and release the improved 1.4 GHz images of several famous fields., Comment: 13 pages, 9 figures; to be published in A&A

We present the largest low frequency (120~MHz) arcminute resolution image of the radio synchrotron background (RSB) to date, and its corresponding angular power spectrum of anisotropies (APS) with angular scales ranging from $3^\circ$ to $0.3^\prime$. We show that the RSB around the North Celestial Pole has a significant excess anisotropy power at all scales over a model of unclustered point sources based on source counts of known source classes. This anisotropy excess, which does not seem attributable to the diffuse Galactic emission, could be linked to the surface brightness excess of the RSB. To better understand the information contained within the measured APS, we model the RSB varying the brightness distribution, size, and angular clustering of potential sources. We show that the observed APS could be produced by a population of faint clustered point sources only if the clustering is extreme and the size of the Gaussian clusters is $\lesssim 1'$. We also show that the observed APS could be produced by a population of faint diffuse sources with sizes $\lesssim 1'$, and this is supported by features present in our image. Both of these cases would also cause an associated surface brightness excess. These classes of sources are in a parameter space not well probed by even the deepest radio surveys to date., Comment: 13 pages, 14 figures. Accepted for publication in MNRAS

Radio spectroscopy provides a unique inspection perspective for solar and space weather research, which can reveal the plasma and energetic electron information in the solar corona and inner heliosphere. However, Radio-Frequency Interference (RFI) from human activities affects sensitive radio telescopes, and significantly affects the quality of observation. Thus, RFI detection and mitigation for the observations is necessary to obtain high quality, science-ready data. The flagging of RFI is particularly challenging for the solar and space weather observations at low frequency, because the solar radio bursts can be brighter than the RFI, and may show similar temporal behavior. In this work, we investigate RFI flagging methods for solar and space weather observations, including a strategy for AOFlagger, and a novel method that makes use of a morphology convolution. These algorithms can effectively flag RFI while preserving solar radio bursts.

The Low Frequency Array (LOFAR) is the only existing radio interferometer able to observe at ultra-low frequencies (<100 MHz) with high resolution (<15") and high sensitivity (<1 mJy/beam). To exploit these capabilities, the LOFAR Surveys Key Science Project is using the LOFAR Low Band Antenna (LBA) to carry out a sensitive wide-area survey at 41-66 MHz named the LOFAR LBA Sky Survey (LoLSS). LoLSS is covering the whole northern sky above declination 24 deg with a resolution of 15" and a sensitivity of 1-2 mJy/beam (1 sigma) depending on declination, field properties, and observing conditions. Here we present the first data release. An automated pipeline was used to reduce the 95 fields included in this data release. The data reduction procedures developed for this project have general application and are currently being used to process LOFAR LBA interferometric observations. Compared to the preliminary release, direction-dependent errors have been corrected for during the calibration process. This results in a typical sensitivity of 1.55 mJy/beam at the target resolution of 15". The first data release of the LOFAR LBA Sky Survey covers 650 sqdeg in the HETDEX spring field. The resultant data products released to the community include mosaic images (I and V Stokes) of the region, and a catalogue of 42463 detected sources and related Gaussian components used to describe sources' morphologies. Separate catalogues for 6 in-band frequencies are also released. The first data release of LoLSS shows that, despite the influences of the ionosphere, LOFAR can conduct large-scale surveys in the frequency window 42-66 MHz with unprecedentedly high sensitivity and resolution. The data can be used to derive unique information on the low-frequency spectral properties of many thousands of sources with a wide range of applications in extragalactic and galactic astronomy., Comment: 20 pages, 22 figures, images and catalogues available at https://www.lofar-surveys.org/lolss.html

Context. Apertif is a multi-beam receiver system for the Westerbork Synthesis Radio Telescope that operates at 1.1-1.5 GHz, which overlaps with various radio services, resulting in contamination of astronomical signals with radio-frequency interference (RFI).Aims. We analyse approaches to mitigate Apertif interference and design an automated detection procedure for its imaging mode. Using this approach, we present long-term RFI detection results of over 300 Apertif observations.Methods. Our approach is based on the AOFlagger detection approach. We introduce several new features, including ways to deal with ranges of invalid data (e.g. caused by shadowing) in both the SumThreshold and scale-invariant rank operator steps; pre-calibration bandpass calibration; auto-correlation flagging; and HI flagging avoidance. These methods have been implemented in a new framework that uses the Lua language for scripting, which is new in AOFlagger version 3.Results. Our approach removes RFI fully automatically, and it is robust and effective enough for further calibration and (continuum) imaging of these data. The analysis of 304 observations shows an average of 11.1% of lost data due to RFI with a large spread. We observe 14.6% RFI in auto-correlations. Computationally, AOFlagger achieves a throughput of 370 MB/s on a single computing node. Compared to published machine learning results, the method is one to two orders of magnitude faster.

Aim: Necrotizing enterocolitis (NEC) is the most lethal disease of the gastrointestinal tract of preterm infants. New and existing management strategies need clinical evaluation. Large heterogeneity exists in the selection, measurement, and reporting of outcome measures in NEC intervention studies. This hampers meta-analyses and the development of evidence-based management guidelines. We aim to develop a Core Outcome Set (COS) for NEC that includes the most relevant outcomes for patients and physicians, from moment of diagnosis into adulthood. This COS is designed for use in NEC treatment trials, in infants with confirmed NEC. Methods: This study is designed according to COS-STAD (Core Outcome Set-STAndards for Development) recommendations and the COMET (Core Outcome Measures in Effectiveness Trials) Initiative Handbook. We obtained a waiver from the Ethics Review Board and prospectively registered this study with COMET (Study 1920). We will approach 125 clinicians and/or researchers from low-middle and high-income countries based on their scientific output (using SCIVAL, a bibliometric tool). Patients and parents will be approached through local patient organisations. Participants will be separated into three panels, to assess differences in priorities between former patients and parents (1. lay panel), clinicians and researchers involved in the neonatal period (2. neonatal panel) and after the neonatal period (3. post-neonatal panel). They will be presented with outcomes currently used in NEC research, identified through a systematic review, in a Delphi process. Eligible outcome domains are also identified from the patients and parents’ perspectives. Using a consensus process, including three online Delphi rounds and a final face-to-face consensus meeting, the COS will be finalised and include outcomes deemed essential to all stakeholders: health care professionals, parents and patients’ representatives. The final COS will be reported in accordance with the COS

The synergy between drought-responsive traits across different organs is crucial in the whole-plant mechanism influencing drought resilience. These organ interactions, however, are poorly understood, limiting our understanding of drought response strategies at the whole-plant level. Therefore, we need more integrative studies, especially on herbaceous species that represent many important food crops but remain underexplored in their drought response. We investigated inflorescence stems and rosette leaves of six Arabidopsis thaliana genotypes with contrasting drought tolerance, and combined anatomical observations with hydraulic measurements and gene expression studies to assess differences in drought response. The soc1ful double mutant was the most drought-tolerant genotype based on its synergistic combination of low stomatal conductance, largest stomatal safety margin, more stable leaf water potential during non-watering, reduced transcript levels of drought stress marker genes, and reduced loss of chlorophyll content in leaves, in combination with stems showing the highest embolism resistance, most pronounced lignification, and thickest intervessel pit membranes. In contrast, the most sensitive Cvi ecotype shows the opposite extreme of the same set of traits. The remaining four genotypes show variations in this drought syndrome. Our results reveal that anatomical, ecophysiological, and molecular adaptations across organs are intertwined, and multiple (differentially combined) strategies can be applied to acquire a certain level of drought tolerance.

Context. Apertif is a multi-beam receiver system for the Westerbork Synthesis Radio Telescope that operates at 1.1–1.5 GHz, which overlaps with various radio services, resulting in contamination of astronomical signals with radio-frequency interference (RFI). Aims. We analyse approaches to mitigate Apertif interference and design an automated detection procedure for its imaging mode. Using this approach, we present long-term RFI detection results of over 300 Apertif observations. Methods. Our approach is based on the AOFlagger detection approach. We introduce several new features, including ways to deal with ranges of invalid data (e.g. caused by shadowing) in both the SumThreshold and scale-invariant rank operator steps; pre-calibration bandpass calibration; auto-correlation flagging; and HI flagging avoidance. These methods have been implemented in a new framework that uses the Lua language for scripting, which is new in AOFlagger version 3. Results. Our approach removes RFI fully automatically, and it is robust and effective enough for further calibration and (continuum) imaging of these data. The analysis of 304 observations shows an average of 11.1% of lost data due to RFI with a large spread. We observe 14.6% RFI in auto-correlations. Computationally, AOFlagger achieves a throughput of 370 MB/s on a single computing node. Compared to published machine learning results, the method is one to two orders of magnitude faster. © The Authors 2023.

Context. Apertif is a multi-beam receiver system for the Westerbork Synthesis Radio Telescope that operates at 1.1-1.5 GHz, which overlaps with various radio services, resulting in contamination of astronomical signals with radio-frequency interference (RFI). Aims. We analyze approaches to mitigate Apertif interference and design an automated detection procedure for its imaging mode. Using this approach, we present long-term RFI detection results of over 300 Apertif observations. Methods. Our approach is based on the AOFlagger detection approach. We introduce several new features, including ways to deal with ranges of invalid data (e.g. caused by shadowing) in both the SumThreshold and scale-invariant rank operator steps; pre-calibration bandpass calibration; auto-correlation flagging; and HI flagging avoidance. These methods are implemented in a new framework that uses the Lua language for scripting, which is new in AOFlagger version 3. Results. Our approach removes RFI fully automatically, and is robust and effective enough for further calibration and (continuum) imaging of these data. Analysis of 304 observations show an average of 11.1% of lost data due to RFI with a large spread. We observe 14.6% RFI in auto-correlations. Computationally, AOFlagger achieves a throughput of 370 MB/s on a single computing node. Compared to published machine learning results, the method is one to two orders of magnitude faster., Comment: 15 pages, 10 figures. Accepted for publication in A&A

Somatic embryogenesis (SE), or embryo development from in vitro cultured vegetative explants, can be induced in Arabidopsis by the synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D) or by overexpression of specific transcription factors, such as AT-HOOK MOTIF NUCLEAR LOCALIZED 15 (AHL15). Here, we explored the role of endogenous auxin [indole-3-acetic acid (IAA)] during 2,4-D and AHL15-induced SE. Using the pWOX2:NLS-YFP reporter, we identified three distinct developmental stages for 2,4-D and AHL15-induced SE in Arabidopsis, with these being (i) acquisition of embryo identity; (ii) formation of pro-embryos; and (iii) somatic embryo patterning and development. The acquisition of embryo identity coincided with enhanced expression of the indole-3-pyruvic acid auxin biosynthesis YUCCA genes, resulting in an enhanced pDR5:GFP-reported auxin response in the embryo-forming tissues. Chemical inhibition of the indole-3-pyruvic acid pathway did not affect the acquisition of embryo identity, but significantly reduced or completely inhibited the formation of pro-embryos. Co-application of IAA with auxin biosynthesis inhibitors in the AHL15-induced SE system rescued differentiated somatic embryo formation, confirming that increased IAA levels are important during the last two stages of SE. Our analyses also showed that polar auxin transport, with AUXIN/LIKE-AUX influx and PIN-FORMED1 efflux carriers as important drivers, is required for the transition of embryonic cells to proembryos and, later, for correct cell fate specification and differentiation. Taken together, our results indicate that endogenous IAA biosynthesis and its polar transport are not required for the acquisition of embryo identity, but rather to maintain embryonic cell identity and for the formation of multicellular proembryos and their development into histodifferentiated embryos.

The origin of the radio synchrotron background (RSB) is currently unknown. Its understanding might have profound implications in fundamental physics or might reveal a new class of radio emitters. In this work, we consider the scenario in which the RSB is due to extragalactic radio sources and measure the angular cross-correlation of LOFAR images of the diffuse radio sky with matter tracers at different redshifts, provided by galaxy catalogs and CMB lensing. We compare these measured cross-correlations to those expected for models of RSB sources. We find that low-redshift populations of discrete sources are excluded by the data, while higher redshift explanations are compatible with available observations. We also conclude that at least 20\% of the RSB surface brightness level must originate from populations tracing the large-scale distribution of matter in the universe, indicating that at least this fraction of the RSB is of extragalactic origin. Future measurements of the correlation between the RSB and tracers of high-redshift sources will be crucial to constraining the source population of the RSB., Comment: 12 pages, 8 figures. Version accepted for publication in MNRAS

The redshifted 21-cm signal from neutral hydrogen is a direct probe of the physics of the early universe and has been an important science driver of many present and upcoming radio interferometers. In this study, we use a single night of observations with the New Extension in Nan\c{c}ay Upgrading LOFAR (NenuFAR) to place upper limits on the 21-cm power spectrum from the Cosmic Dawn at a redshift of $z$ = 20.3. NenuFAR is a new low-frequency radio interferometer, operating in the 10-85 MHz frequency range, currently under construction at the Nan\c{c}ay Radio Observatory in France. It is a phased array instrument with a very dense uv-coverage at short baselines, making it one of the most sensitive instruments for 21-cm cosmology analyses at these frequencies. Our analysis adopts the foreground subtraction approach, in which sky sources are modeled and subtracted through calibration, and residual foregrounds are subsequently removed using Gaussian process regression (GPR). The final power spectra are constructed from the gridded residual data cubes in the uv-plane. Signal injection tests are performed at each step of the analysis pipeline, and the relevant pipeline settings are optimized to ensure minimal signal loss, and any signal suppression is accounted for through a bias correction on our final upper limits. We obtain a best 2$\sigma$ upper limit of $2.4\times 10^7$ $\text{mK}^{2}$ at $z$ = 20.3 and $k$ = 0.041 $h\,\text{cMpc}^{-1}$. We see a strong excess power in the data, making our upper limits two orders of magnitude higher than the thermal noise limit. We investigate the origin and nature of this excess power and discuss further improvements in the analysis pipeline, which can potentially mitigate it and consequently allow us to reach the thermal noise sensitivity when multiple nights of observations are processed in the future., Comment: 27 pages, 21 figures, and 6 tables; accepted for publication in Astronomy and Astrophysics (A&A)

Measurement of the redshifted 21-cm signal of neutral hydrogen from the Cosmic Dawn (CD) and Epoch of Reionisation (EoR) promises to unveil a wealth of information about the astrophysical processes during the first billion years of evolution of the universe. The AARTFAAC Cosmic Explorer (ACE) utilises the AARTFAAC wide-field imager of LOFAR to measure the power spectrum of the intensity fluctuations of the redshifted 21-cm signal from the CD at z~18. The RFI from various sources contaminates the observed data and it is crucial to exclude the RFI-affected data in the analysis for reliable detection. In this work, we investigate the impact of non-ground-based transient RFI using cross-power spectra and cross-coherence metrics to assess the correlation of RFI over time and investigate the level of impact of transient RFI on the ACE 21-cm power spectrum estimation. We detected moving sky-based transient RFI sources that cross the field of view within a few minutes and appear to be mainly from aeroplane communication beacons at the location of the LOFAR core in the 72-75 MHz band, by inspecting filtered images. This transient RFI is mostly uncorrelated over time and is only expected to dominate over the thermal noise for an extremely deep integration time of 3000 hours or more with a hypothetical instrument that is sky temperature dominated at 75 MHz. We find no visible correlation over different k-modes in Fourier space in the presence of noise for realistic thermal noise scenarios. We conclude that the sky-based transient RFI from aeroplanes, satellites and meteorites at present does not pose a significant concern for the ACE analyses at the current level of sensitivity and after integrating over the available 500 hours of observed data. However, it is crucial to mitigate or filter such transient RFI for more sensitive experiments aiming for significantly deeper integration., Comment: 13 pages, 9 figures, and 3 tables; accepted for publication in Astronomy and Astrophysics (A&A)

AE3200 - Design Synthesis Exercise, Aerospace Engineering

In this data release from the LOFAR Two-metre Sky Survey (LoTSS) we present 120-168MHz images covering 27% of the northern sky. Our coverage is split into two regions centred at approximately 12h45m +44$^\circ$30' and 1h00m +28$^\circ$00' and spanning 4178 and 1457 square degrees respectively. The images were derived from 3,451hrs (7.6PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4,396,228 radio sources is derived from our total intensity (Stokes I) maps, where the majority of these have never been detected at radio wavelengths before. At 6" resolution, our full bandwidth Stokes I continuum maps with a central frequency of 144MHz have: a median rms sensitivity of 83$\mu$Jy/beam; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2"; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8mJy/beam. By creating three 16MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of +/-0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes V) 20" resolution 120-168MHz continuum images have a median rms sensitivity of 95$\mu$Jy/beam, and we estimate a Stokes I to Stokes V leakage of 0.056%. Our linear polarisation (Stokes Q and Stokes U) image cubes consist of 480 x 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8mJy/beam at 4' and 2.2mJy/beam at 20"; we estimate the Stokes I to Stokes Q/U leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes I, Q, U and V images in addition to the calibrated uv-data., Comment: 23 figures, 1 table and 29 pages. The catalogues, images and uv-data associated with this data release are publicly available via https://lofar-surveys.org

The detection of the 21 cm signal of neutral hydrogen from the Epoch of Reionization (EoR) is challenging due to bright foreground sources, radio frequency interference (RFI), the ionosphere, and instrumental effects. Even after correcting for these effects in the calibration step and applying foreground removal techniques, the remaining residuals in the observed 21 cm power spectra are still above the thermal noise, which is referred to as the "excess variance." We study potential causes of this excess variance based on 13 nights of data obtained with the Low-Frequency Array (LOFAR). We focused on the impact of gain errors, the sky model, and ionospheric effects on the excess variance by correlating the relevant parameters such as the gain variance over time or frequency, local sidereal time (LST), diffractive scale, and phase structure-function slope with the level of excess variance. Our analysis shows that excess variance has an LST dependence, which is related to the power from the sky. And the simulated Stokes I power spectra from bright sources and the excess variance show a similar progression over LST with the minimum power appearing at LST bin 6h to 9h. This LST dependence is also present in sky images of the residual Stokes I of the observations. In very-wide sky images, we demonstrate that the extra power comes exactly from the direction of bright and distant sources Cassiopeia A and Cygnus A with the array beam patterns. These results suggest that the level of excess variance in the 21 cm signal power spectra is related to sky effects and, hence, it depends on LST. In particular, very bright and distant sources such as Cassiopeia A and Cygnus A can dominate the effect. This is in line with earlier studies and offers a path forward toward a solution since the correlation between the sky-related effects and the excess variance is non-negligible., Comment: 29 pages, 14 figures, accepted for publication in A&A

High quality low-frequency radio surveys have the promise of advancing our understanding of many important topics in astrophysics, including the life cycle of active galactic nuclei (AGN), particle acceleration processes in jets, the history of star formation, and exoplanet magnetospheres. Currently leading low-frequency surveys reach an angular resolution of a few arcseconds. However, this resolution is not yet sufficient to study the more compact and distant sources in detail. Sub-arcsecond resolution is therefore the next milestone in advancing these fields. The biggest challenge at low radio frequencies is the ionosphere. If not adequately corrected for, ionospheric seeing blurs the images to arcsecond or even arcminute scales. Additionally, the required image size to map the degree-scale field of view of low-frequency radio telescopes at this resolution is far greater than what typical soft- and hardware is currently capable of handling. Here we present for the first time (to the best of our knowledge) widefield sub-arcsecond imaging at low radio frequencies. We derive ionospheric corrections in a few dozen individual directions and apply those during imaging efficiently using a recently developed imaging algorithm (arXiv:1407.1943, arXiv:1909.07226). We demonstrate our method by applying it to an eight hour observation of the International LOw Frequency ARray (LOFAR) Telescope (ILT) (arXiv:1305.3550). Doing so we have made a sensitive $7.4\ \mathrm{deg}^2$ $144\ \mathrm{MHz}$ map at a resolution of $0.3''$ reaching $25\ \mu\mathrm{Jy\ beam}^{-1}$ near the phase centre. The estimated $250,000$ core hours used to produce this image, fit comfortably in the budget of available computing facilities. This result will enable future mapping of the entire northern low-frequency sky at sub-arcsecond resolution., Comment: 19 pages, 4 figures; This preprint has not undergone peer review or any post-submission improvements or corrections. The Version of Record of this article is published in Nature Astronomy, and is available online at https://doi.org/10.1038/s41550-021-01573-z

Entrepreneurs have certain personality traits that are evaluated by venture capitalists (VCs) when making their investment decision, which have been studied in literature. However, personality traits in ecopreneurs, or sustainable entrepreneurs, that may impact the investment decision of a sustainable venture capitalist (SVC) are not known to have been studied, and therefore warrant research opportunities. New innovations are becoming increasingly important to help solve some of the world’s pressing environmental issues, and therefore, there is a need to better understand how ecopreneurs can financially sustain their new ventures. This study aims to understand how the ecopreneur’s personality traits impact the SVC’s investment decision, by doing a qualitative study through semi-structured interviews of SVCs located in Scandinavia. A personality trait model used for traditional entrepreneurs was used as a framework for this study and applied in the ecopreneurial context and thus, a deductive approach was taken. The personality traits in the model include risk aversion, ability to perform a continuous and intense effort, desire to earn money, honesty and integrity, attention to detail, favorable to suggestions and critics, and long-term vision, and were proposed to be an enabler or disabler in the SVC’s investment decision. Through five interviews with SVCs, it was found that honesty and integrity was the most important trait in the SVCs decision to invest in the ecopreneur. The desire to earn money was found to have both enabling and disabling aspects. Long-term vision emerged from the research as important, specific to ecopreneurs and their vision of making a positive global environmental impact, but should include short-term goals to achieve that long-term vision. Furthermore, the research allowed for new insights to come to light, wherein two personality traits were adjusted to better suit the context of the ecopreneur, and two additional traits were added to the

Context. The detection of the 21 cm signal of neutral hydrogen from the Epoch of Reionization (EoR) is challenging due to bright foreground sources, radio frequency interference (RFI), and the ionosphere as well as instrumental effects. Even after correcting for these effects in the calibration step and applying foreground removal techniques, the remaining residuals in the observed 21 cm power spectra are still above the thermal noise, which is referred to as the “excess variance.” Aims. We study a number of potential causes of this excess variance based on 13 nights of data obtained with the Low-Frequency Array (LOFAR). Methods. We focused on the impact of gain errors, the sky model, and ionospheric effects on the excess variance by correlating the relevant parameters such as the gain variance over time or frequency, local sidereal time (LST), diffractive scale, and phase structure–function slope with the level of excess variance. Results. Our analysis shows that the excess variance, at the current level, is neither strongly correlated with gain variance nor the ionospheric parameters. Rather, excess variance has an LST dependence, which is related to the power from the sky. Furthermore, the simulated Stokes I power spectra from bright sources and the excess variance show a similar progression over LST with the minimum power appearing at LST bin 6h to 9h. This LST dependence is also present in sky images of the residual Stokes I of the observations. In very-wide sky images based on one night of observation after direction-dependent calibration, we demonstrate that the extra power comes exactly from the direction of bright and distant sources Cassiopeia A and Cygnus A with the array beam patterns. Conclusions. These results suggest that the level of excess variance in the 21 cm signal power spectra is related to sky effects and, hence, it depends on LST. In particular, very bright and distant sources such as Cassiopeia A and Cygnus A can dominate the effect. This is

Many acute and chronic diseases affect the distal lung alveoli. Alveolar epithelial cell (AEC) lines are needed to better model these diseases. We used de-identified human remnant transplant lungs to develop a method to establish AEC lines. The lines grow well in 2-dimensional (2D) culture as epithelial monolayers expressing lung progenitor markers. In 3-dimensional (3D) culture with fibroblasts, Matrigel, and specific media conditions, the cells form alveolar-like organoids expressing mature AEC markers including aquaporin 5 (AQP5), G-protein-coupled receptor class C group 5 member A (GPRC5A), and surface marker HTII280. Single-cell RNA sequencing of an AEC line in 2D versus 3D culture revealed increased cellular heterogeneity and induction of cytokine and lipoprotein signaling in 3D organoids. Our approach yields lung progenitor lines that retain the ability to differentiate along the alveolar cell lineage despite long-term expansion and provides a valuable system to model and study the distal lung in vitro.

Purpose: Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual’s limb. In the early stage of experimental NEC, RIC decreased intestinal injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy. Methods: RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention. Results: We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility. Conclusions: The newly established NEC consortium has generated novel data on NEC dia

Taurine is an amino sulfonic acid that is implicated in numerous physiological functions, including the regulation of oxidative stress, which plays an important role in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), together with other pathophysiological processes. The recent finding of decreased serum taurine levels in SARS-CoV-2-infected patients, in tandem with its potential modulatory role in COVID-19 due to its antiviral, antioxidant, anti-inflammatory, and vascular-related effects, provides a rationale for considering taurine as a beneficial supplement in patients suffering from COVID-19. Here, we reviewed the potential disease-modifying effects of taurine and combined these with the current knowledge on COVID-19 to clarify the potential role of taurine in this respiratory disease.

Welke lessen over droogte, mitigatie en adaptatie kunnen Nederlandse waterschappen trekken uit ervaringen, wetenschappelijke artikelen en droogteplannen uit landen met veel langdurige droogte? Hoogheemraadschap de Stichtse Rijnlanden liet hierover een verkenning doen ter aanvulling op de Blue Deal, een programma van Dutch Water Authorities met zeventien langdurige partnerschappen in vijftien landen.

Context. The occultation of a radio source by the plasma tail of a comet can be used to probe structure and dynamics in the tail. Such occultations are rare, and the occurrence of scintillation, due to small-scale density variations in the tail, remains somewhat controversial. Aims. A detailed observation taken with the Low-Frequency Array (LOFAR) of a serendipitous occultation of the compact radio source 3C196 by the plasma tail of comet C/2020 F3 (Neowise) is presented. 3C196 tracked almost perpendicularly behind the tail, providing a unique profile cut only a short distance downstream from the cometary nucleus itself. Methods. Interplanetary scintillation (IPS) is observed as the rapid variation of the intensity received of a compact radio source due to density variations in the solar wind. IPS in the signal received from 3C196 was observed for five hours, covering the full transit behind the plasma tail of comet C/2020 F3 (Neowise) on 16 July 2020, and allowing an assessment of the solar wind in which the comet and its tail are embedded. Results. The results reveal a sudden and strong enhancement in scintillation which is unequivocally attributable to the plasma tail. The strongest scintillation is associated with the tail boundaries, weaker scintillation is seen within the tail, and previously-unreported periodic variations in scintillation are noted, possibly associated with individual filaments of plasma. Furthermore, contributions from the solar wind and comet tail are separated to measure a sharp decrease in the velocity of material within the tail, suggesting a steep velocity shear resulting in strong turbulence along the tail boundary, Comment: Accepted for publication in Astronomy and Astrophysics, 8 pages, 9 figures

Detecting the 21-cm signal from the Epoch of Reionisation (EoR) is challenging due to the strong astrophysical foregrounds, ionospheric effects, radio frequency interference and instrumental effects. Understanding and calibrating these effects are crucial for the detection. In this work, we introduce a newly developed direction-dependent (DD) calibration algorithm DDECAL and compare its performance with an existing algorithm, SAGECAL, in the context of the LOFAR-EoR 21-cm power spectrum experiment. In our data set, the North Celestial Pole (NCP) and its flanking fields were observed simultaneously. We analyse the NCP and one of its flanking fields. The NCP field is calibrated by the standard pipeline, using SAGECAL with an extensive sky model and 122 directions, and the flanking field is calibrated by DDECAL and SAGECAL with a simpler sky model and 22 directions. Additionally, two strategies are used for subtracting Cassiopeia A and Cygnus A. The results show that DDECAL performs better at subtracting sources in the primary beam region due to the application of a beam model, while SAGECAL performs better at subtracting Cassiopeia A and Cygnus A. This indicates that including a beam model during DD calibration significantly improves the performance. The benefit is obvious in the primary beam region. We also compare the 21-cm power spectra on two different fields. The results show that the flanking field produces better upper limits compared to the NCP in this particular observation. Despite the minor differences between DDECAL and SAGECAL due to the beam application, we find that the two algorithms yield comparable 21-cm power spectra on the LOFAR-EoR data after foreground removal. Hence, the current LOFAR-EoR 21-cm power spectrum limits are not likely to depend on the DD calibration method., Comment: 28 pages, 14 figures, accepted for publication in A&A

(Abridged) Apertif is a phased-array feed system for WSRT, providing forty instantaneous beams over 300 MHz of bandwidth. A dedicated survey program started on 1 July 2019, with the last observations taken on 28 February 2022. We describe the release of data products from the first year of survey operations, through 30 June 2020. We focus on defining quality control metrics for the processed data products. The Apertif imaging pipeline, Apercal, automatically produces non-primary beam corrected continuum images, polarization images and cubes, and uncleaned spectral line and dirty beam cubes for each beam of an Apertif imaging observation. For this release, processed data products are considered on a beam-by-beam basis within an observation. We validate the continuum images by using metrics that identify deviations from Gaussian noise in the residual images. If the continuum image passes validation, we release all processed data products for a given beam. We apply further validation to the polarization and line data products. We release all raw observational data from the first year of survey observations, for a total of 221 observations of 160 independent target fields, covering approximately one thousand square degrees of sky. Images and cubes are released on a per beam basis, and 3374 beams are released. The median noise in the continuum images is 41.4 uJy/bm, with a slightly lower median noise of 36.9 uJy/bm in the Stokes V polarization image. The median angular resolution is 11.6"/sin(Dec). The median noise for all line cubes, with a spectral resolution of 36.6 kHz, is 1.6 mJy/bm, corresponding to a 3-sigma HI column density sensitivity of 1.8 x 10^20 atoms cm^-2 over 20 km/s (for a median angular resolution of 24" x 15"). We also provide primary beam images for each individual Apertif compound beam. The data are made accessible using a Virtual Observatory interface., Comment: Accepted for publication in A&A, updated Figure 1

The first data release of Apertif survey contains 3074 radio continuum images covering a thousand square degrees of the sky. The observations were performed during August 2019 to July 2020. The continuum images were produced at a central frequency 1355 MHz with the bandwidth of $\sim$150 MHz and angular resolution reaching 10". In this work we introduce and apply a new method to obtain a primary beam model using a machine learning approach, Gaussian process regression. The primary beam models obtained with this method are published along with the data products for the first Apertif data release. We apply the method to the continuum images, mosaic them and extract the source catalog. The catalog contains 249672 radio sources many of which are detected for the first time at these frequencies. We cross-match the coordinates with the NVSS, LOFAR/DR1/value-added and LOFAR/DR2 catalogs resulting in 44523, 22825 and 152824 common sources respectively. The first sample provides a unique opportunity to detect long term transient sources which have significantly changed their flux density for the last 25 years. The second and the third ones combined together provide information about spectral properties of the sources as well as the redshift estimates., Comment: 12 pages, 9 figures; accepted for publication in A&A

Relatively little information is available about the Universe at ultra-low radio frequencies (ULF; i.e., below 50 MHz), although the ULF spectral window contains a wealth of unique diagnostics for studying galactic and extragalactic phenomena. Subarcsecond resolution imaging at these frequencies is extremely difficult, due to the long baselines (>1000 km) required and large ionospheric perturbations. We have conducted a pilot project to investigate the ULF performance and potential of the International LOFAR Telescope (ILT), a trans-European interferometric array with baselines up to ~2000 km and observing frequencies down to 10 MHz. We have successfully produced images with subarcsecond resolution for six radio sources at frequencies down to 30 MHz. This resolution is more than an order of magnitude better than pre-ILT observations at similar frequencies. The six targets that we imaged (3C 196, 3C 225, 3C 273, 3C 295, 3C 298, and 3C 380) are bright radio sources with compact structures. By comparing our data of 3C 196 and 3C 273 with observations at higher frequencies, we investigate their spatially resolved radio spectral properties. Our success shows that at frequencies down to 30 MHz, subarcsecond imaging with the ILT is possible. Further analysis is needed to determine the feasibility of observations of fainter sources or sources with less compact emission. © ESO 2022.

The detection of the 21 cm signal of neutral hydrogen from the Epoch of Reionization (EoR) is challenging due to bright foreground sources, radio frequency interference (RFI), the ionosphere, and instrumental effects. Even after correcting for these effects in the calibration step and applying foreground removal techniques, the remaining residuals in the observed 21 cm power spectra are still above the thermal noise, which is referred to as the "excess variance." We study potential causes of this excess variance based on 13 nights of data obtained with the Low-Frequency Array (LOFAR). We focused on the impact of gain errors, the sky model, and ionospheric effects on the excess variance by correlating the relevant parameters such as the gain variance over time or frequency, local sidereal time (LST), diffractive scale, and phase structure-function slope with the level of excess variance. Our analysis shows that excess variance has an LST dependence, which is related to the power from the sky. And the simulated Stokes I power spectra from bright sources and the excess variance show a similar progression over LST with the minimum power appearing at LST bin 6h to 9h. This LST dependence is also present in sky images of the residual Stokes I of the observations. In very-wide sky images, we demonstrate that the extra power comes exactly from the direction of bright and distant sources Cassiopeia A and Cygnus A with the array beam patterns. These results suggest that the level of excess variance in the 21 cm signal power spectra is related to sky effects and, hence, it depends on LST. In particular, very bright and distant sources such as Cassiopeia A and Cygnus A can dominate the effect. This is in line with earlier studies and offers a path forward toward a solution since the correlation between the sky-related effects and the excess variance is non-negligible., Comment: 29 pages, 14 figures, accepted for publication in A&A

In this data release from the LOFAR Two-metre Sky Survey (LoTSS) we present 120-168MHz images covering 27% of the northern sky. Our coverage is split into two regions centred at approximately 12h45m +44$^\circ$30' and 1h00m +28$^\circ$00' and spanning 4178 and 1457 square degrees respectively. The images were derived from 3,451hrs (7.6PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4,396,228 radio sources is derived from our total intensity (Stokes I) maps, where the majority of these have never been detected at radio wavelengths before. At 6" resolution, our full bandwidth Stokes I continuum maps with a central frequency of 144MHz have: a median rms sensitivity of 83$\mu$Jy/beam; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2"; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8mJy/beam. By creating three 16MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of +/-0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes V) 20" resolution 120-168MHz continuum images have a median rms sensitivity of 95$\mu$Jy/beam, and we estimate a Stokes I to Stokes V leakage of 0.056%. Our linear polarisation (Stokes Q and Stokes U) image cubes consist of 480 x 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8mJy/beam at 4' and 2.2mJy/beam at 20"; we estimate the Stokes I to Stokes Q/U leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes I, Q, U and V images in addition to the calibrated uv-data., Comment: 23 figures, 1 table and 29 pages. The catalogues, images and uv-data associated with this data release are publicly available via https://lofar-surveys.org

High quality low-frequency radio surveys have the promise of advancing our understanding of many important topics in astrophysics, including the life cycle of active galactic nuclei (AGN), particle acceleration processes in jets, the history of star formation, and exoplanet magnetospheres. Currently leading low-frequency surveys reach an angular resolution of a few arcseconds. However, this resolution is not yet sufficient to study the more compact and distant sources in detail. Sub-arcsecond resolution is therefore the next milestone in advancing these fields. The biggest challenge at low radio frequencies is the ionosphere. If not adequately corrected for, ionospheric seeing blurs the images to arcsecond or even arcminute scales. Additionally, the required image size to map the degree-scale field of view of low-frequency radio telescopes at this resolution is far greater than what typical soft- and hardware is currently capable of handling. Here we present for the first time (to the best of our knowledge) widefield sub-arcsecond imaging at low radio frequencies. We derive ionospheric corrections in a few dozen individual directions and apply those during imaging efficiently using a recently developed imaging algorithm (arXiv:1407.1943, arXiv:1909.07226). We demonstrate our method by applying it to an eight hour observation of the International LOw Frequency ARray (LOFAR) Telescope (ILT) (arXiv:1305.3550). Doing so we have made a sensitive $7.4\ \mathrm{deg}^2$ $144\ \mathrm{MHz}$ map at a resolution of $0.3''$ reaching $25\ \mu\mathrm{Jy\ beam}^{-1}$ near the phase centre. The estimated $250,000$ core hours used to produce this image, fit comfortably in the budget of available computing facilities. This result will enable future mapping of the entire northern low-frequency sky at sub-arcsecond resolution., Comment: 19 pages, 4 figures; This preprint has not undergone peer review or any post-submission improvements or corrections. The Version of Record of this article is published in Nature Astronomy, and is available online at https://doi.org/10.1038/s41550-021-01573-z

Der adoptive Transfer von T-Zell-Rezeptor (TZR) modifizierten T-Zellen gegen krebsspezifische Antigene ist ein vielversprechender Ansatz in der Immuntherapie. Geeignete Zielmoleküle für diese Therapie sollten wichtig für das Überleben von Krebszellen sein und zudem in ausreichenden Mengen auf der Zelloberfläche exprimiert werden, um von T-Zellen erkannt zu werden. Die Identifizierung dieser Zielmoleküle ist jedoch eine Herausforderung und erfordert eine intensive Charakterisierung, um eine ausreichende Prozessierung und Präsentation auf den Tumorzellen zu validieren. Ziel dieser Arbeit war, HLA-A2-spezifische Neoepitope als Zielmoleküle für adoptive T-Zell-Therapie zu validieren. Dafür wurden erfolgreich Immunantworten in einem humanen transgenen Mausmodell nach Peptidimmunisierung induziert und TZRs mit hoher Affinität isoliert. Trotz einer hohen funktionellen Avidität von H3.3K27M-spezifischen T-Zellen wurde keine Erkennung von Tumorzellen erreicht. Zweitens wurden TZR-transduzierte T-Zellen gegen die häufige Melanommutation Rac1P29S isoliert, welche zytotoxisch gegen Melanomzelllinien waren. Letztlich wurde beobachtetet, dass TZRs mit hoher Affinität gegen gespleißte Kras und Rac2 Epitope, welche durch Proteasom-katalysiertes Peptidspleißen erzeugt wurden, keine Immunantwort gegen endogen exprimierte Mutationen hervorrufen konnten. Daraus lässt sich schließen, dass gespleißte Epitope wahrscheinlich seltener vorkommen als zuvor angenommen und daher möglicherweise irrelevant für die adoptive T-Zelltherapie sind. Diese Daten deuten darauf hin, dass die Auswahl von Zielmolekülen für die adoptive T-Zell-Therapie mit Hilfe reverser Immunologie auf der Grundlage von Bindungsalgorithmen und der Häufigkeit von Mutationen allein nicht ausreicht. Daher sind vor der Isolierung und Charakterisierung von TZRs zusätzliche Strategien wie z.B. die Analyse des MHC-Immunopeptidoms erforderlich, um die Auswahl geeigneter Zielmoleküle für die T-Zelltherapie zu verbessern., Adoptive transfer of T cell receptor (TCR)-engineered T cells against tumour-specific neoantigens is a promising approach in cancer immunotherapy. Ideally, targeted antigens are crucial for cancer cell survival and are generated in sufficient amounts to be recognised by T cells. However, the identification of ideal targets remains challenging and requires intensive characterisation to validate sufficient antigen processing and presentation by the tumour cells. This thesis focused on the validation of HLA-A2 binding neoepitopes carrying the recurrent cancer mutations H3.3K27M, Rac1P29S, Rac2P29L or KrasG12V as targets for adoptive T cell therapy. After peptide immunisation, immune responses in a human transgenic mouse model were elicited and high-affinity TCRs successfully isolated. Although H3.3K27M-specific T cells showed high functional avidity, no recognition of cells endogenously expressing mutant H3.3 was achieved. Furthermore, a mechanism to target the common melanoma mutation Rac1P29S with a TCR raised against a heterologous mutation with higher peptide-MHC affinity was described. TCR-transduced T cells induced cytotoxicity against Rac1P29S expressing melanoma cell lines. Lastly, high-affinity TCRs specific for mutant Kras and Rac2 spliced epitopes generated by proteasome-catalysed peptide splicing were successfully isolated, however, TCR-transduced T cells did not induce an immune response against endogenously expressed mutant transgenes. The results indicate that spliced epitopes are probably less abundant than previously estimated and therefore may play a minor role in the generation of targets for adoptive T cell therapy. These data suggest that target selection using a reverse immunology approach based on binding algorithms and frequency of mutations alone is not sufficient. Thus, additional strategies to improve the selection of suitable targets such as the analysis of the MHC immunopeptidome are required prior to TCR isolation and characterisation.

Entrepreneurs have certain personality traits that are evaluated by venture capitalists (VCs) when making their investment decision, which have been studied in literature. However, personality traits in ecopreneurs, or sustainable entrepreneurs, that may impact the investment decision of a sustainable venture capitalist (SVC) are not known to have been studied, and therefore warrant research opportunities. New innovations are becoming increasingly important to help solve some of the world’s pressing environmental issues, and therefore, there is a need to better understand how ecopreneurs can financially sustain their new ventures. This study aims to understand how the ecopreneur’s personality traits impact the SVC’s investment decision, by doing a qualitative study through semi-structured interviews of SVCs located in Scandinavia. A personality trait model used for traditional entrepreneurs was used as a framework for this study and applied in the ecopreneurial context and thus, a deductive approach was taken. The personality traits in the model include risk aversion, ability to perform a continuous and intense effort, desire to earn money, honesty and integrity, attention to detail, favorable to suggestions and critics, and long-term vision, and were proposed to be an enabler or disabler in the SVC’s investment decision. Through five interviews with SVCs, it was found that honesty and integrity was the most important trait in the SVCs decision to invest in the ecopreneur. The desire to earn money was found to have both enabling and disabling aspects. Long-term vision emerged from the research as important, specific to ecopreneurs and their vision of making a positive global environmental impact, but should include short-term goals to achieve that long-term vision. Furthermore, the research allowed for new insights to come to light, wherein two personality traits were adjusted to better suit the context of the ecopreneur, and two additional traits were added to the