| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Ackley, K., et al.
(author)
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Observational constraints on the optical and near-infrared emission from the neutron star-black hole binary merger candidate S190814bv
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
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Journal article (peer-reviewed)abstract
- Context. Gravitational wave (GW) astronomy has rapidly reached maturity, becoming a fundamental observing window for modern astrophysics. The coalescences of a few tens of black hole (BH) binaries have been detected, while the number of events possibly including a neutron star (NS) is still limited to a few. On 2019 August 14, the LIGO and Virgo interferometers detected a high-significance event labelled S190814bv. A preliminary analysis of the GW data suggests that the event was likely due to the merger of a compact binary system formed by a BH and a NS.Aims. In this paper, we present our extensive search campaign aimed at uncovering the potential optical and near infrared electromagnetic counterpart of S190814bv. We found no convincing electromagnetic counterpart in our data. We therefore use our non-detection to place limits on the properties of the putative outflows that could have been produced by the binary during and after the merger.Methods. Thanks to the three-detector observation of S190814bv, and given the characteristics of the signal, the LIGO and Virgo Collaborations delivered a relatively narrow localisation in low latency - a 50% (90%) credible area of 5 deg(2) (23 deg(2)) - despite the relatively large distance of 26752 Mpc. ElectromagNetic counterparts of GRAvitational wave sources at the VEry Large Telescope collaboration members carried out an intensive multi-epoch, multi-instrument observational campaign to identify the possible optical and near infrared counterpart of the event. In addition, the ATLAS, GOTO, GRAWITA-VST, Pan-STARRS, and VINROUGE projects also carried out a search on this event. In this paper, we describe the combined observational campaign of these groups.Results. Our observations allow us to place limits on the presence of any counterpart and discuss the implications for the kilonova (KN), which was possibly generated by this NS-BH merger, and for the strategy of future searches. The typical depth of our wide-field observations, which cover most of the projected sky localisation probability (up to 99.8%, depending on the night and filter considered), is r similar to 22 (resp. K similar to 21) in the optical (resp. near infrared). We reach deeper limits in a subset of our galaxy-targeted observations, which cover a total similar to 50% of the galaxy-mass-weighted localisation probability. Altogether, our observations allow us to exclude a KN with large ejecta mass M greater than or similar to 0.1 M-circle dot to a high (> 90%) confidence, and we can exclude much smaller masses in a sub-sample of our observations. This disfavours the tidal disruption of the neutron star during the merger.Conclusions. Despite the sensitive instruments involved in the campaign, given the distance of S190814bv, we could not reach sufficiently deep limits to constrain a KN comparable in luminosity to AT 2017gfo on a large fraction of the localisation probability. This suggests that future (likely common) events at a few hundred megaparsecs will be detected only by large facilities with both a high sensitivity and large field of view. Galaxy-targeted observations can reach the needed depth over a relevant portion of the localisation probability with a smaller investment of resources, but the number of galaxies to be targeted in order to get a fairly complete coverage is large, even in the case of a localisation as good as that of this event.
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| 4. |
- Dyer, A. H., et al.
(author)
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Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
- 2020
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In: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
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Journal article (peer-reviewed)abstract
- Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 5. |
- Jersin, R. A., et al.
(author)
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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
- 2021
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
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Journal article (peer-reviewed)abstract
- Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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| 6. |
- Kapun, Martin, et al.
(author)
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Drosophila Evolution over Space and Time (DEST) : A New Population Genomics Resource
- 2021
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:12, s. 5782-5805
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Journal article (peer-reviewed)abstract
- Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.
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| 8. |
- Baldwin, Lydia, et al.
(author)
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Development of a dual-flow tissue perfusion device for modeling the gastrointestinal tract-brain axis
- 2023
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In: Biomicrofluidics. - 1932-1058. ; 17:5
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Journal article (peer-reviewed)abstract
- Despite the large number of microfluidic devices that have been described over the past decade for the study of tissues and organs, few have become widely adopted. There are many reasons for this lack of adoption, primarily that devices are constructed for a single purpose or because they are highly complex and require relatively expensive investment in facilities and training. Here, we describe a microphysiological system (MPS) that is simple to use and provides fluid channels above and below cells, or tissue biopsies, maintained on a disposable, poly(methyl methacrylate), carrier held between polycarbonate outer plates. All other fittings are standard Luer sizes for ease of adoption. The carrier can be coated with cells on both sides to generate membrane barriers, and the devices can be established in series to allow medium to flow from one cell layer to another. Furthermore, the carrier containing cells can be easily removed after treatment on the device and the cells can be visualized or recovered for additional off-chip analysis. A 0.4 mu m membrane with cell monolayers proved most effective in maintaining separate fluid flows, allowing apical and basal surfaces to be perfused independently. A panel of different cell lines (Caco-2, HT29-MTX-E12, SH-SY5Y, and HUVEC) were successfully maintained in the MPS for up to 7 days, either alone or on devices connected in series. The presence of tight junctions and mucin was expressed as expected by Caco-2 and HT-29-MTX-E12, with Concanavalin A showing uniform staining. Addition of Annexin V and PI showed viability of these cells to be >80% at 7 days. Bacterial extracellular vesicles (BEVs) produced by Bacteroides thetaiotaomicron and labeled with 1,1 '-dioctadecyl-3,3,3 ',3 '-tetramethylindocarbo-cyanine perchlorate (DiD) were used as a model component of the human colonic microbiota and were visualized translocating from an apical surface containing Caco-2 cells to differentiated SH-SY5Y neuronal cells cultured on the basal surface of connected devices. The newly described MPS can be easily adapted, by changing the carrier to maintain spheroids, pieces, or slices of biopsy tissue and joined in series to study a variety of cell and tissue processes. The cell layers can be made more complex through the addition of multiple cell types and/or different patterning of extracellular matrix and the ability to culture cells adjacent to one another to allow study of cell:cell transfer, e.g., passive or active drug transfer, virus or bacterial entry or BEV uptake and transfer.
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| 9. |
- Lehman, Joel, et al.
(author)
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The Surprising Creativity of Digital Evolution: A Collection of Anecdotes from the Evolutionary Computation and Artificial Life Research Communities
- 2020
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In: Artificial Life. - : MIT Press - Journals. - 1530-9185 .- 1064-5462. ; 26:2, s. 274-306
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Journal article (peer-reviewed)abstract
- Evolution provides a creative fount of complex and subtle adaptations that often surprise the scientists who discover them. However, the creativity of evolution is not limited to the natural world: Artificial organisms evolving in computational environments have also elicited surprise and wonder from the researchers studying them. The process of evolution is an algorithmic process that transcends the substrate in which it occurs. Indeed, many researchers in the field of digital evolution can provide examples of how their evolving algorithms and organisms have creatively subverted their expectations or intentions, exposed unrecognized bugs in their code, produced unexpectedly adaptations, or engaged in behaviors and outcomes, uncannily convergent with ones found in nature. Such stories routinely reveal surprise and creativity by evolution in these digital worlds, but they rarely fit into the standard scientific narrative. Instead they are often treated as mere obstacles to be overcome, rather than results that warrant study in their own right. Bugs are fixed, experiments are refocused, and one-off surprises are collapsed into a single data point. The stories themselves are traded among researchers through oral tradition, but that mode of information transmission is inefficient and prone to error and outright loss. Moreover, the fact that these stories tend to be shared only among practitioners means that many natural scientists do not realize how interesting and lifelike digital organisms are and how natural their evolution can be. To our knowledge, no collection of such anecdotes has been published before. This article is the crowd-sourced product of researchers in the fields of artificial life and evolutionary computation who have provided first-hand accounts of such cases. It thus serves as a written, fact-checked collection of scientifically important and even entertaining stories. In doing so we also present here substantial evidence that the existence and importance of evolutionary surprises extends beyond the natural world, and may indeed be a universal property of all complex evolving systems.
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| 10. |
- Pereira, Laura, et al.
(author)
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Transformative spaces in the making : key lessons from nine cases in the Global South
- 2020
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In: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 15:1, s. 161-178
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Journal article (peer-reviewed)abstract
- Creating a just and sustainable planet will require not only small changes, but also systemic transformations in how humans relate to the planet and to each other, i.e., social-ecological transformations. We suggest there is a need for collaborative environments where experimentation with new configurations of social-ecological systems can occur, and we refer to these as transformative spaces. In this paper, we seek a better understanding of how to design and enable the creation of transformative spaces in a development context. We analyse nine case studies from a previous special issue on Designing Transformative Spaces that aimed to collect examples of cutting-edge action-oriented research on transformations from the Global South. The analysis showed five design phases as being essential: Problem Definition Phase; Operationalisation Phase; Tactical Phase; Outcome Phase; and Reflection Phase. From this synthesis, we distilled five key messages that should be considered when designing research, including: (a) there are ethical dilemmas associated with creating a transformative space in a system; (b) it is important to assess the readiness of the system for change before engaging in it; (c) there is a need to balance between 'safe' and 'safe-enough' spaces for transformation; (d) convening a transformative space requires an assemblage of diverse methodological frameworks and tools; and (e) transformative spaces can act as a starting point for institutionalising transformative change. Many researchers are now engaging in transdisciplinary transformations research, and are finding themselves at the knowledge-action interface contributing to transformative space-making. We hope that by analysing experiences from across different geographies we can contribute towards better understanding of how to navigate the processes needed for the urgent global transformations that are being called for to create a more equitable and sustainable planet Earth.
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