| 1. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 3. |
- Wedemeyer, S., et al.
(författare)
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Solar Science with the Atacama Large Millimeter/Submillimeter Array-A New View of Our Sun
- 2016
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 200:1-4, s. 1-73
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Forskningsöversikt (refereegranskat)abstract
- The Atacama Large Millimeter/submillimeter Array (ALMA) is a new powerful tool for observing the Sun at high spatial, temporal, and spectral resolution. These capabilities can address a broad range of fundamental scientific questions in solar physics. The radiation observed by ALMA originates mostly from the chromosphere-a complex and dynamic region between the photosphere and corona, which plays a crucial role in the transport of energy and matter and, ultimately, the heating of the outer layers of the solar atmosphere. Based on first solar test observations, strategies for regular solar campaigns are currently being developed. State-of-the-art numerical simulations of the solar atmosphere and modeling of instrumental effects can help constrain and optimize future observing modes for ALMA. Here we present a short technical description of ALMA and an overview of past efforts and future possibilities for solar observations at submillimeter and millimeter wavelengths. In addition, selected numerical simulations and observations at other wavelengths demonstrate ALMA's scientific potential for studying the Sun for a large range of science cases.
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| 4. |
- Wedemeyer, S., et al.
(författare)
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SSALMON - The Solar Simulations for the Atacama Large Millimeter Observatory Network
- 2015
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Ingår i: Advances in Space Research. - : Elsevier BV. - 1879-1948 .- 0273-1177. ; 56:12, s. 2679-2692
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Tidskriftsartikel (refereegranskat)abstract
- The Solar Simulations for the Atacama Large Millimeter Observatory Network (SSALMON) was initiated in 2014 in connection with two ALMA development studies. The Atacama Large Millimeter/submillimeter Array (ALMA) is a powerful new tool, which can also observe the Sun at high spatial, temporal, and spectral resolution. The international SSALMONetwork aims at co-ordinating the further development of solar observing modes for ALMA and at promoting scientific opportunities for solar physics with particular focus on numerical simulations, which can provide important constraints for the observing modes and can aid the interpretation of future observations. The radiation detected by ALMA originates mostly in the solar chromosphere - a complex and dynamic layer between the photosphere and corona, which plays an important role in the transport of energy and matter and the heating of the outer layers of the solar atmosphere. Potential targets include active regions, prominences, quiet Sun regions, flares. Here, we give a brief overview over the network and potential science cases for future solar observations with ALMA.
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| 5. |
- Cook, A, et al.
(författare)
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Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study
- 2023
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Ingår i: Medical mycology. - : Oxford University Press (OUP). - 1460-2709 .- 1369-3786. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018–February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28–34), and median birth weight was 1270 gr (interquartile range [IQR]: 990–1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.
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