| 1. |
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| 2. |
- 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. |
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| 4. |
- Silventoinen, K., et al.
(författare)
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The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
- 2019
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
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Tidskriftsartikel (refereegranskat)abstract
- The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
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| 5. |
- D'Orazi, V., et al.
(författare)
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Mapping of shadows cast on a protoplanetary disk by a close binary system
- 2019
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 3:2, s. 167-172
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Tidskriftsartikel (refereegranskat)abstract
- For a comprehensive understanding of planetary formation and evolution, we need to investigate the environment in which planets form: circumstellar disks. Here we present high-contrast imaging observations of V4046 Sagittarii, a 20-Myr-old close binary known to host a circumbinary disk. We have discovered the presence of rotating shadows in the disk, caused by mutual occultations of the central binary. Shadow-like features are often observed in disks(1,2), but those found thus far have not been due to eclipsing phenomena. We have used the phase difference due to light travel time to measure the flaring of the disk and the geometrical distance of the system. We calculate a distance that is in very good agreement with the value obtained from the Gaia mission's Data Release 2 (DR2), and flaring angles of alpha = (6.2 +/- 0.6)degrees and alpha = (8.5 +/- 1.0)degrees for the inner and outer disk rings, respectively. Our technique opens up a path to explore other binary systems, providing an independent estimate of distance and the flaring angle, a crucial parameter for disk modelling.
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| 6. |
- Choi, J. H., et al.
(författare)
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Influence of Biogenic Organics on the Chemical Composition of Arctic Aerosols
- 2019
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 33:10, s. 1238-1250
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Tidskriftsartikel (refereegranskat)abstract
- We use an ultrahigh-resolution 15-T Fourier transform ion cyclotron resonance mass spectrometer to elucidate the compositional changes in Arctic organic aerosols collected at Ny-angstrom lesund, Svalbard, in May 2015. The Fourier transform ion cyclotron resonance mass spectrometer analysis of airborne organic matter provided information on the molecular compositions of aerosol particles collected during the Arctic spring period. The air mass transport history, combined with satellite-derived geographical information and chlorophyll concentration data, revealed that the molecular compositions of organic aerosols drastically differed depending on the origin of the potential source region. The protein and lignin compound populations contributed more than 70% of the total intensity of assigned molecules when the air masses mainly passed over the ocean region. Interestingly, the intensity of microbe-derived organics (protein and carbohydrate compounds) was positively correlated with the air mass exposure to phytoplankton biomass proxied as chlorophyll. Furthermore, the intensities of lignin and unsaturated hydrocarbon compounds, typically derived from terrestrial vegetation, increased with an increase in the advection time of the air mass over the ocean domain. These results suggest that the accumulation of dissolved biogenic organics in the Arctic Ocean possibly derived from both phytoplankton and terrestrial vegetation could significantly influence the chemical properties of Arctic organic aerosols during a productive spring period. The interpretation of molecular changes in organic aerosols using an ultrahigh-resolution mass spectrometer could provide deep insight for understanding organic aerosols in the atmosphere over the Arctic and the relationship of organic aerosols with biogeochemical processes in terms of aerosol formation and environmental changes.
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| 7. |
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| 8. |
- Kondratyuk, Sergey Y., et al.
(författare)
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New and noteworthy lichen-forming and lichenicolous fungi 9
- 2019
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Ingår i: Acta Botanica Hungarica. - : Akademiai Kiado Zrt.. - 1588-2578 .- 0236-6495. ; 61:3-4, s. 325-367
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Tidskriftsartikel (refereegranskat)abstract
- The new for science genus Loekoeslaszloa S. Y. Kondr. et J.-S. Hur, confirmed by three gene phylogeny of the subfamily Teloschistoideae of the Teloschistaceae based on nrITS, nrLSU and mtSSU sequences, and ten new to science species from Eastern Asia, i.e. from South Korea: Bacidina loekoesiana S. Y. Kondr. et J.-S. Hur, Fauriea jejuensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Gyalecta ulleungdoensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Loekoeslaszloa huriana S. Y. Kondr., Orientophila dodongana S. Y. Kondr., L. Lőkös et J.-S. Hur, O. imjadoensis S. Y. Kondr., L. Lőkös et J.-S. Hur, O. incheonensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Oxneriopsis taehaensis S. Y. Kondr., L. Lőkös et J.-S. Hur, Yoshimuria ivanpisutiana S. Y. Kondr., L. Lőkös et J.-S. Hur and Y. seokpoensis S. Y. Kondr., L. Lőkös et J.-S. Hur are described, illustrated and compared with closely related taxa. Molecular data for the recently described species Flavoplaca laszloana are for the first time provided. Position of Tassiloa magellanica in the subfamily Teloschistoideae as well as Yoshimuria stipitata in the Ikaerioideae ad int. is for the first time illustrated. An identification key to Fauriea species (including six species, i.e.: F. chujaensis, F. jejuensis, F. orientochinensis, F. patwolseleyae, F. tabidella and F. yonaguniensis), a key to Orientophila species of the Eastern Asian region (of the Orientophila loekoesii and the O. diffluens groups), and a key to Yoshimuria and Loekoeslaszloa species of the Eastern Asian region (including four species, i.e.: Y. galbina, Y. ivanpisutiana, Y. seokpoensis, and Y. spodoplaca, as well as Loekoeslaszloa geumohdoensis and L. huriana) are presented. Seven new combinations, i.e. Fauriea patwolseleyae (basionym: Caloplaca patwolseleyae S. Y. Kondr., U. Jayalal et J.-S. Hur),Fauriea tabidella (basionym: Lecanora tabidella Nyl.), Loekoeslaszloa geumohdoensis (basionym: Mikhtomia geumohdoensis S. Y. Kondr., D. Liu et Hur), Niesslia coarctatae (basionym: Stigmidium coarctatae S. Y. Kondr., L. Lőkös et J.-S. Hur), Opeltia epiphyta (basionym: Caloplaca epiphyta Lynge), Tassiloa magellanica (basionym: Caloplaca magellanica Søchting et Sancho) and Yoshimuria stipitata (basionym: Caloplaca stipitata Wetmore) are proposed. Yoshimuria galbina and Lecanora ussuriensis are for the first time recorded from Japan.
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| 9. |
- Kondratyuk, Sergey Y., et al.
(författare)
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Three new genera of the Ramalinaceae (lichen-forming Ascomycota) and the phenomenon of presence of ‘extraneous mycobiont DNA’ in lichen associations
- 2019
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Ingår i: Acta Botanica Hungarica. - : Akademiai Kiado Zrt.. - 1588-2578 .- 0236-6495. ; 61:3-4, s. 275-323
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Tidskriftsartikel (refereegranskat)abstract
- Three new genera Coppinsidea, Vandenboomia and Wolseleyidea are described and the genera Ivanpisutia, Lecaniella and Myrionora are resurrected on the basis of a phylogenetic analysisof multi-locus sequence data of the Ramalinaceae including the nuclear protein-codingmarker rpb2, the internal transcribed spacer and a fragment of the small mitochondrialsubunit. The genus Hertelidea was positioned within the Ramalina clade of the phylogenetic tree of the Ramalinaceae. Bacidia sipmanii, Phyllopsora chlorophaea, P. castaneocincta and Ramalina subbreviuscula were recorded from South Korea for the first time here confirming by molecular data, too.Forty-eight new combinations are proposed: Bacidia alnetorum (basionym: Biatoraalnetorum S. Ekman et Tønsberg), Biatora amazonica (basionym: Phyllopsora amazonica Kistenich et Timdal), Biatora cuyabensis (basionym: Lecidea cuyabensis Malme), Biatora halei (basionym: Pannaria halei Tuck.), Biatora kalbii (basionym: Phyllopsora kalbii Brako), Biatora subhispidula (basionym: Psoroma subhispidulum Nyl.), Coppinsidea alba (basionym: Catillaria alba Coppins et Vězda), Coppinsidea aphana (basionym: Lecidea aphana Nyl.), Coppinsidea croatica (basionym: Catillaria croatica Zahlbr.), Coppinsidea fuscoviridis (basionym: Bilimbia fuscoviridis Anzi), Coppinsidea pallens (basionym: Bilimbia pallens Kullh.), Coppinsidea ropalosporoides(basionym: Gyalidea ropalosporoides S. Y. Kondr., L. Lőkös et J.-S. Hur), Coppinsidea scotinodes (basionym: Lecidea scotinodes Nyl.), Coppinsidea sphaerella (basionym: Lecidea sphaerella Hedl.), Ivanpisutia hypophaea (basionym: Biatora hypophaea Printzen et Tønsberg), Ivanpisutia ocelliformis (basionym: Lecidea ocelliformis Nyl.), Lecaniella belgica (basionym: Lecania belgica van den Boom et Reese Naesb.), Lecaniella cyrtellina (basionym: Lecanora cyrtellina Nyl.), Lecaniella dubitans (basionym: Lecidea dubitans Nyl.), Lecaniella erysibe (basionym: Lichenerysibe Ach.), Lecaniella hutchinsiae (basionym: Lecanora hutchinsiae Nyl.), Lecaniella naegelii(basionym: Biatora naegelii Hepp), Lecaniella prasinoides (basionym: Lecania prasinoides Elenkin), Lecaniella sylvestris (basionym: Biatora sylvestris Arnold), Lecaniella tenera (basionym: Scoliciosporum tenerum Lönnr.), Mycobilimbia albohyalina (basionym: Lecidea anomala f. albohyalina Nyl.), Mycobilimbia cinchonarum (basionym: Triclinum cinchonarum Fée), Mycobilimbia concinna (basionym: Phyllopsora concinna Kistenich et Timdal), Mycobilimbia ramea (basionym:Bacidina ramea S. Ekman), Mycobilimbia siamensis (basionym: Phyllopsora siamensisKistenich et Timdal), Myrionora australis (basionym: Biatora australis Rodr. Flakus et Printzen), Myrionora ementiens (basionym: Lecidea ementiens Nyl.), Myrionora flavopunctata (basionym: Lecanora flavopunctata Tønsberg), Myrionora globulosa (basionym: Lecidea globulosa Flörke), Myrionora hemipolia (basionym: Lecidea arceutina f. hemipolia Nyl.), Myrionora lignimollis (basionym: Biatora ligni-mollis T. Sprib. et Printzen), Myrionora malcolmii (basionym: Phyllopsora malcolmii Vězda et Kalb), Myrionora vacciniicola (basionym: Lecidea vacciniicola Tønsberg), Phyllopsora agonimioides (basionym: Coenogonium agonimioides J. P. Halda, S.-O. Oh et J.-S. Hur), Phyllopsora sunchonensis (basionym: Agonimia sunchonensis S. Y. Kondr. etJ.-S. Hur), Vandenboomia chlorotiza (basionym: Lecidea chlorotiza Nyl.), Vandenboomia falcata (basionym: Lecania falcata van den Boom, M. Brand, Coppins, Magain et Sérus.), Wolseleyidea africana (basionym: Phyllopsora africana Timdal et Krog), Wolseleyidea byssiseda (basionym: Lecidea byssiseda Nyl. ex Hue), Wolseleyidea canoumbrina (basionym: Lecidea canoumbrina Vain.), Wolseleyidea furfurella (basionym: Phyllopsora furfurella Kistenich et Timdal), Wolseleyidea ochroxantha (basionym: Lecidea ochroxantha Nyl.), and Wolseleyidea swinscowii (basionym: Phyllopsora swinscowii Timdal et Krog). The combination Biatora longispora (Degel.)Lendemer et Printzen is validated here. The new names Biatora vezdana for Lecaniafurfuracea Vĕzda and Coppinsidea vainioana for Lecidea sphaeroidiza Vain. are proposed. The phenomenon of presence of ‘extraneous mycobiont DNA’ in lichen association, i.e. DNA, belonging neither to mycobiont nor photobiont or to endophytic fungi is for the first time illustrated. So the presence of nrITS and mtSSU sequences of crustose lichen Coppinsidea ropalosporoides in thalli of crustose Verrucaria margacea and foliose Kashiwadia orientalis, as well as nrITS of Phyllopsora sp. KoLRI in Agonimia pacifica and Biatora longispora, or nrITS and mtSSU of Biatora longispora in thalli of Agonimia pacifica, Oxneriopsis oxneri and Pyxine limbulata, Ivanpisutia oxneri in thalli of Rinodina xanthophaea, etc. is documented. Scarce cases of presence of ‘extraneous mycobiont DNA’ in representatives of the Teloschistaceae, Physciaceae known from literature data are discussed, too.
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| 10. |
- López-Fauqued, M., et al.
(författare)
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Safety profile of the adjuvanted recombinant zoster vaccine : Pooled analysis of two large randomised phase 3 trials
- 2019
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Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 37:18, s. 2482-2493
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. © 2019 GlaxoSmithKline Biologicals SA
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