| 1. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 2. |
- Barausse, Enrico, et al.
(författare)
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Prospects for fundamental physics with LISA
- 2020
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Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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| 3. |
- Wollenberg, Andreas, et al.
(författare)
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European Task Force on Atopic Dermatitis (ETFAD) statement on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-infection and atopic dermatitis
- 2020
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Ingår i: Journal of the European Academy of Dermatology and Venereology : JEADV. - : Wiley. - 1468-3083 .- 0926-9959. ; 34:6, s. 241-242
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Tidskriftsartikel (refereegranskat)abstract
- Atopic dermatitis (AD) is a complex disease with elevated risk of respiratory comorbidities.1,2 Severely affected patients are often treated with immune-modulating systemic drugs.3,4 On March 11th 2020, the World Health Organization declared the 2019 novel coronavirus severe acute respiratory syndrome (SARS-Cov-2) epidemic to be a pandemic. The number of cases worldwide is increasing exponentially and poses a major health threat, especially for those who are elderly, immuno-compromised, or have comorbidities. This also applies to AD patients on systemic immune-modulating treatment. In these days of uncertainty, reallocation of medical resources, curfew, hoarding, and shutdown of normal social life, patients, caregivers and doctors ask questions regarding the continuation of systemic immune-modulating treatment of AD patients. The ETFAD decided to address some of these questions here.
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| 4. |
- Amendola, L., et al.
(författare)
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Cosmology and fundamental physics with the Euclid satellite
- 2018
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Ingår i: Living Reviews in Relativity. - : Springer. - 1433-8351 .- 2367-3613. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015–2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid’s Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.
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| 5. |
- Bauer, Michael, et al.
(författare)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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| 6. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 7. |
- Bowlin, Melissa, et al.
(författare)
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Grand Challenges in Migration Biology
- 2010
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Ingår i: Integrative and Comparative Biology. - : Oxford University Press (OUP). - 1540-7063 .- 1557-7023. ; 50:3, s. 261-279
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Konferensbidrag (refereegranskat)abstract
- Billions of animals migrate each year. To successfully reach their destination, migrants must have evolved an appropriate genetic program and suitable developmental, morphological, physiological, biomechanical, behavioral, and life-history traits. Moreover, they must interact successfully with biotic and abiotic factors in their environment. Migration therefore provides an excellent model system in which to address several of the "grand challenges" in organismal biology. Previous research on migration, however, has often focused on a single aspect of the phenomenon, largely due to methodological, geographical, or financial constraints. Integrative migration biology asks 'big questions' such as how, when, where, and why animals migrate, which can be answered by examining the process from multiple ecological and evolutionary perspectives, incorporating multifaceted knowledge from various other scientific disciplines, and using new technologies and modeling approaches, all within the context of an annual cycle. Adopting an integrative research strategy will provide a better understanding of the interactions between biological levels of organization, of what role migrants play in disease transmission, and of how to conserve migrants and the habitats upon which they depend.
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| 8. |
- Dillon, Joseph S., et al.
(författare)
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Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl : Analyses of Phase III Studies in Carcinoid Syndrome
- 2021
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Ingår i: Journal of Gastrointestinal Cancer. - : Springer Science and Business Media LLC. - 1941-6628 .- 1941-6636. ; 52:1, s. 212-221
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTelotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods.MethodsFirst occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial.ResultsIn TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3–4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2–3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6–11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7–11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR.ConclusionThe time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency.
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| 9. |
- Gamboa, G., et al.
(författare)
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Mg/Ca ratios in coralline algae record northwest Atlantic temperature variations and North Atlantic Oscillation relationships
- 2010
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Ingår i: Journal of Geophysical Research-Oceans. - 0148-0227. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- [1] Climate variability in the North Atlantic has been linked in part to the North Atlantic Oscillation (NAO). The NAO influences marine ecosystems in the northwestern Atlantic and transport variability of the cold Labrador Current. Understanding historic patterns of NAO variability requires long-term and high-resolution climate records that are not available from instrumental data. Here we present the first century-scale proxy record of sea surface temperature (SST) variability from the Newfoundland shelf, a region from which other annual-resolution shallow marine proxies are unavailable. The 116 year record was obtained from three sites along the eastern Newfoundland shelf using laser ablation inductively coupled mass spectrometry-determined Mg/Ca ratios in the crustose coralline alga Clathromorphum compactum. The alga is characterized by a high Mg-calcite skeleton exhibiting annual growth increments and a century-scale lifespan. Results indicate positive correlations between interannual variations in Mg/Ca ratios and both station-based and gridded instrumental SST. In addition, the record shows high spatial correlations to SST across the Newfoundland shelf and the Gulf of St. Lawrence. Before 1950 the Mg/Ca proxy record reveals significant departures from gridded temperature records. While the Newfoundland shelf is generally considered a region of negative correlations to the NAO, the algal time series as well as a recent modeling study suggest a variable negative relationship with the NAO which is strongest after similar to 1960 and before the mid-1930s.
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| 10. |
- Halfar, J., et al.
(författare)
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Coralline algal growth-increment widths archive North Atlantic climate variability
- 2011
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Ingår i: Palaeogeography Palaeoclimatology Palaeoecology. - 0031-0182. ; 302:1-2, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Over the past decade coralline algae have increasingly been used as archives of paleoclimate information. Encrusting coralline algae, which deposit annual growth increments in a high Mg-calcite skeleton, are amongst the longest-lived shallow marine organisms. In fact, a live-collected plant has recently been shown to have lived for at least 850 years based on radiometric dating. While a number of investigations have successfully used geochemical information of coralline algal skeletons to reconstruct sea surface temperatures, less attention has been paid to employ growth increment widths as a temperature proxy. Here we explore the relationship between growth and environmental parameters in Clathromorphum compactum collected in the subarctic Northwestern Atlantic. Results indicate that growth-increment widths of individual plants are poorly correlated with instrumental sea surface temperatures (SST). However, an averaged record of multiple growth increment-width time series from a regional network of C. compactum specimens up to 800 km apart reveals strong correlations with annual instrumental SST since 1950. Hence, similar to methods applied in dendrochronology, averaging of multiple sclerochronological records of coralline algae provides accurate climate information. A 115-year growth-increment width master chronology created from modern-collected and museum specimens is highly correlated to multidecadal variability seen in North Atlantic sea surface temperatures. Positive changes in algal growth anomalies record the well-documented regime shift and warming in the northwestern Atlantic during the 1990s. Large positive changes in algal growth anomalies were also present in the 1920s and 1930s, indicating that the impact of a concurrent large-scale regime shift throughout the North Atlantic was more strongly felt in the subarctic Northwestern Atlantic than previously thought, and may have even exceeded the 1990s event with respect to the magnitude of the warming. (C) 2010 Elsevier B.V. All rights reserved.
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