| 1. |
- Dalin, P., et al.
(författare)
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Studies of noctilucent clouds from the stratosphere during the SONC balloon-borne experiment in 2021
- 2022
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Ingår i: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 240
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Tidskriftsartikel (refereegranskat)abstract
- On the night 16–17 August 2021, a balloon-borne experiment called Stratospheric Observations of Noctilucent Clouds (SONC) was successfully performed. A big scientific balloon, having onboard three automated cameras for studies of noctilucent clouds (NLC), was launched to 32.7 km altitude from Esrange (northern Sweden). All three NLC cameras and electronics were completely operational in the stratosphere for more than 10 h at low temperatures of about −30 °C. Two wide angle cameras registered an extended NLC field of about 1700 km long in the twilight sky sector from the north-west to the north-east of Esrange. NLC were of a moderate brightness and were located at high latitudes between 68° and 71°N. The NLC field was located in a cold area (138–142 K) below the frost point temperature (145–148 K) in the mesopause region that was confirmed by Aura/MLS satellite and Esrange lidar measurements. The balloon-borne NLC measurements were accompanied by ground-based lidar and radar measurements. The latter have registered Polar Mesosphere Summer Echoes (PMSE) in the same volume of the summer mesopause along with NLC observed from the stratosphere that has been performed for the first time above northern Scandinavia. We describe the technique and method of the NLC observation from the stratosphere as well as present the first scientific results of the SONC experiment.
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| 2. |
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| 3. |
- Li, Dalin, et al.
(författare)
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A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition
- 2016
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Ingår i: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 151:4, s. 724-732
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).Methods: Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing.Results: We identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24 × 10(-16)) and overweight individuals (P = 6.73 × 10(-16)).Conclusions: Our results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.
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| 4. |
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| 5. |
- Barabash, Victoria, et al.
(författare)
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Electron density profiles in the quiet lower ionosphere based on the results of modeling and experimental data
- 2012
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Ingår i: Annales Geophysicae. - : European Geosciences Union (EGU). - 0992-7689 .- 1432-0576. ; 30:9, s. 1345-1360
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Tidskriftsartikel (refereegranskat)abstract
- The theoretical PGI (Polar Geophysical Institute) model for the quiet lower ionosphere has been applied for computing the ionization rate and electron density profiles in the summer and winter D-region at solar zenith angles less than 80° and larger than 99° under steady state conditions. In order to minimize possible errors in estimation of ionization rates provided by solar electromagnetic radiation and to obtain the most exact values of electron density, each wavelength range of the solar spectrum has been divided into several intervals and the relations between the solar radiation intensity at these wavelengths and the solar activity index F10.7 have been incorporated into the model. Influence of minor neutral species (NO, H2O, O, O3) concentrations on the electron number density at different altitudes of the sunlit quiet D-region has been examined. The results demonstrate that at altitudes above 70 km, the modeled electron density is most sensitive to variations of nitric oxide concentration. Changes of water vapor concentration in the whole altitude range of the mesosphere influence the electron density only in the narrow height interval 73–85 km. The effect of the change of atomic oxygen and ozone concentration is the least significant and takes place only below 70 km. Model responses to changes of the solar zenith angle, solar activity (low–high) and season (summer–winter) have been considered. Modeled electron density profiles have been evaluated by comparison with experimental profiles available from the rocket measurements for the same conditions. It is demonstrated that the theoretical model for the quiet lower ionosphere is quite effective in describing variations in ionization rate, electron number density and effective recombination coefficient as functions of solar zenith angle, solar activity and season. The model may be used for solving inverse tasks, in particular, for estimations of nitric oxide concentration in the mesosphere.
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| 6. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 7. |
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| 8. |
- Dalin, Martin, 1982, et al.
(författare)
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Androgen Receptor Signaling in Salivary Gland Cancer
- 2017
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Salivary gland cancers comprise a small subset of human malignancies, and are classified into multiple subtypes that exhibit diverse histology, molecular biology and clinical presentation. Local disease is potentially curable with surgery, which may be combined with adjuvant radiotherapy. However, metastatic or unresectable tumors rarely respond to chemotherapy and carry a poorer prognosis. Recent molecular studies have shown evidence of androgen receptor signaling in several types of salivary gland cancer, mainly salivary duct carcinoma. Successful treatment with anti-androgen therapy in other androgen receptor-positive malignancies such as prostate and breast cancer has inspired researchers to investigate this treatment in salivary gland cancer as well. In this review, we describe the prevalence, biology, and therapeutic implications of androgen receptor signaling in salivary gland cancer.
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| 9. |
- Dherbecourt, J. B., et al.
(författare)
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Design and pre-development of an airborne multi-species differential absorption Lidar system for water vapor and HDO isotope, carbon dioxide, and methane observation
- 2021
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE-Intl Soc Optical Eng.
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Konferensbidrag (refereegranskat)abstract
- We report on the current design and preliminary developments of the airborne Lidar Emitter and Multi-species greenhouse gases Observation iNstrument (LEMON), which is aiming at probing H2O and its isotope HDO at 1982 nm, CO2 at 2051 nm, and potentially CH4 at 2290 nm, with the Differential Absorption Lidar method (DIAL). The infrared emitter is based on the combination of two Nested Cavity OPOs (NesCOPOs) with a single optical parametric amplifier (OPA) line for high-energy pulse generation. This configuration is enabled by the use of high-aperture periodically poled KTP crystals (PPKTP), which provide efficient amplification in the spectral range of interest around 2 μm with slight temperature adjustments. The parametric stages are pumped with a Nd:YAG laser providing 200 mJ nanosecond double pulses at 75 Hz. According to parametric conversion simulations supported by current laboratory experiments, output energies in the 40 - 50 mJ range are expected in the extracted signal beam whilst maintaining a good beam quality (M2 < 2). The ruler for all the optical frequencies involved in the system is planned to be provided by a GPS referenced frequency comb with large mode spacing (1 GHz) against which the emitter output pulses can be heterodyned. The frequency precision measurement is expected to be better than 200 kHz for the optical frequencies of interest. The presentation will give an overview of the key elements of design and of preliminary experimental characterizations of sub-systems building blocks.
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| 10. |
- Dherbecourt, J. B., et al.
(författare)
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Lidar Emitter and Multi-species greenhouse gases Observation iNstrument (LEMON) : advances on a multi-species differential absorption Lidar system
- 2022
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Ingår i: 73rd International Astronautical Congress, IAC 2022. - : International Astronautical Federation, IAF.
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Konferensbidrag (refereegranskat)abstract
- In the frame of LEMON project (Lidar Emitter and Multi-species greenhouse gases Observation iNstrument - European Union's Horizon 2020 research and innovation program, GA n°821868), we are developing a multi-species differential absorption Lidar (DIAL). The goal is to benefit from innovative technological developments in terms of optical emitter, spectral reference, to be able to address H2O and its isotope HDO at 1982 nm, CO2 at 2051 nm, and potentially CH4 at 2290 nm, for future ground-based range-resolved DIAL sensing, and with the prospect of future airborne integrated-path DIAL (IPDA). The infrared emitter is based on the combination of two specific, patented, no-seeder Nested Cavity OPOs (NesCOPOs) coupled to a single optical parametric amplifier (OPA) line for high energy pulses generation. Specific developments are also pursued on the frequency reference for the emitter, which is planned to be provided by a GPS referenced frequency comb against which the emitter output pulses can be heterodyned. Besides the instrument design, specific tests experiments have been carried out, covering a wide panel of activities: radiation testing of some critical components to assess the potential of some key components for future space applications, emitter and frequency reference testing, preliminary DIAL tests with laboratory test-beds and comparison with specific in-situ calibration instruments as well as additional innovative techniques evaluation for the emitter. The final instrument design was carried out and the sub-units are now being built.
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| 11. |
- Lossow, Stefan, et al.
(författare)
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Middle atmospheric water vapour and dynamics in the vicinity of the polar vortex during the Hygrosonde-2 campaign
- 2009
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Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 9, s. 4407-4417
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Tidskriftsartikel (refereegranskat)abstract
- The Hygrosonde-2 campaign took place on 16 December 2001 at Esrange/Sweden (68° N, 21° E) with the aim to investigate the small scale distribution of water vapour in the middle atmosphere in the vicinity of the Arctic polar vortex. In situ balloon and rocket-borne measurements of water vapour were performed by means of OH fluorescence hygrometry. The combined measurements yielded a high resolution water vapour profile up to an altitude of 75 km. Using the characteristic of water vapour being a dynamical tracer it was possible to directly relate the water vapour data to the location of the polar vortex edge, which separates air masses of different character inside and outside the polar vortex. The measurements probed extra-vortex air in the altitude range between 45 km and 60 km and vortex air elsewhere. Transitions between vortex and extra-vortex usually coincided with wind shears caused by gravity waves which advect air masses with different water vapour volume mixing ratios. From the combination of the results from the Hygrosonde-2 campaign and the first flight of the optical hygrometer in 1994 (Hygrosonde-1) a clear picture of the characteristic water vapour distribution inside and outside the polar vortex can be drawn. Systematic differences in the water vapour concentration between the inside and outside of the polar vortex can be observed all the way up into the mesosphere. It is also evident that in situ measurements with high spatial resolution are needed to fully account for the small-scale exchange processes in the polar winter middle atmosphere.
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| 12. |
- Mann, I., et al.
(författare)
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First wind shear observation in PMSE with the tristatic EISCAT VHF radar
- 2016
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing Ltd. - 2169-9380 .- 2169-9402. ; 121:11, s. 11,271-11,281
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Tidskriftsartikel (refereegranskat)abstract
- The Polar Summer Mesosphere has the lowest temperatures that occur in the entire Earth system. Water ice particles below the optically observable size range participate there in the formation of strong radar echoes (Polar Mesospheric Summer Echoes, PMSE). To study PMSE we carried out observations with the European Incoherent Scatter (EISCAT) VHF and EISCAT UHF radar simultaneously from a site near Tromsø (69.58°N, 19.2272°E) and observed VHF backscattering also with the EISCAT receivers in Kiruna (67.86°N, 20.44°E) and Sodankylä (67.36°N, 26.63°E). This is one of the first tristatic measurements with EISCAT VHF, and we therefore describe the observations and geometry in detail. We present observations made on 26 June 2013 from 7:00 to 13:00 h UT where we found similar PMSE patterns with all three VHF receivers and found signs of wind shear in PMSE. The observations suggest that the PMSE contains sublayers that move in different directions horizontally, and this points to Kelvin-Helmholtz instability possibly playing a role in PMSE formation. We find no signs of PMSE in the UHF data. The electron densities that we derive from observed incoherent scatter at UHF are at PMSE altitudes close to the noise level but possibly indicate reduced electron densities directly above the PMSE.
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| 13. |
- Rivas, Manuel A., et al.
(författare)
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A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
- 2016
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Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
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| 14. |
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| 15. |
- Sjögren, Anna-Karin, 1980, et al.
(författare)
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GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer
- 2007
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Ingår i: J Clin Invest. - 0021-9738. ; 117:5, s. 1294-304
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Tidskriftsartikel (refereegranskat)abstract
- Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a host of other diseases. Although several GGTase-I inhibitors (GGTIs) have been synthesized, they have very different properties, and the effects of GGTIs and GGTase-I deficiency are unclear. One concern is that inhibiting GGTase-I might lead to severe toxicity. In this study, we determined the effects of GGTase-I deficiency on cell viability and K-RAS-induced cancer development in mice. Inactivating the gene for the critical beta subunit of GGTase-I eliminated GGTase-I activity, disrupted the actin cytoskeleton, reduced cell migration, and blocked the proliferation of fibroblasts expressing oncogenic K-RAS. Moreover, the absence of GGTase-I activity reduced lung tumor formation, eliminated myeloproliferative phenotypes, and increased survival of mice in which expression of oncogenic K-RAS was switched on in lung cells and myeloid cells. Interestingly, several cell types remained viable in the absence of GGTase-I, and myelopoiesis appeared to function normally. These findings suggest that inhibiting GGTase-I may be a useful strategy to treat K-RAS-induced malignancies.
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| 16. |
- Ström, Lena, et al.
(författare)
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Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility
- 2021
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Ingår i: BMC Veterinary Research. - : BioMed Central (BMC). - 1746-6148. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment.Results Atropine sulfate (1mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and topically (manually as eye drops and through a subpalpebral lavage system) to six horses to document atropine disposition. Blood-samples were collected regularly and plasma was analyzed for atropine using UHPLC-MS/MS. Atropine plasma concentration was below lower limit of quantification (0.05 mu g/L) within five hours, after both topical and IV administration. Atropine data were analyzed by means of population compartmental modeling and pharmacokinetic parameters estimated. The typical value was 1.7L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9L/h?kg. The bioavailability after administration of an ophthalmic preparation as an eye drop or topical infusion were 69 and 68%, respectively. The terminal half-life was short (0.8h). In part II, topical ophthalmic atropine sulfate and control treatment was administered to four horses in two dosing regimens to assess the effect on gastro-intestinal motility. Borborygmi-frequency monitored by auscultation was used for estimation of gut motility. A statistically significant decrease in intestinal motility was observed after administration of 1mg topical ophthalmic atropine sulfate every three hours compared to control, but not after administration every six hours. Clinical signs of colic were not observed under any of the treatment protocols.Conclusions Taking the plasma exposure after topical administration into consideration, data and simulations indicate that eye drops administrated at a one and three hour interval will lead to atropine accumulation in plasma over 24h but that a six hour interval allows total washout of atropine between two topical administrations. If constant corneal and conjunctival atropine exposure is required, a topical constant rate infusion at 5 mu g/kg/24h offers a safe alternative.
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| 17. |
- Watts, Nick, et al.
(författare)
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The 2020 report of The Lancet Countdown on health and climate change : responding to converging crises
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10269, s. 129-170
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Forskningsöversikt (refereegranskat)abstract
- The Lancet Countdown is an international collaboration established to provide an independent, global monitoring system dedicated to tracking the emerging health profile of the changing climate.The 2020 report presents 43 indicators across five sections: climate change impacts, exposures, and vulnerabilities; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. This report represents the findings and consensus of the 35 leading academic institutions and UN agencies that make up The Lancet Countdown, and draws on the expertise of climate scientists, geographers, engineers, experts in energy, food, and transport, economists, social, and political scientists, data scientists, public health professionals, and doctors.
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| 18. |
- Yang, W., et al.
(författare)
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Immunogenic neoantigens derived from gene fusions stimulate T cell responses
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:5
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Tidskriftsartikel (refereegranskat)abstract
- Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. We identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. Using whole-genome sequencing and RNA sequencing, we identified a novel gene fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic T cell response. In a cohort of head and neck tumors with low mutation burden, minimal immune infiltration and prevalent gene fusions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses. Finally, analyzing additional datasets of fusion-positive cancers, including checkpoint-inhibitor-treated tumors, we found evidence of immune surveillance resulting in negative selective pressure against gene fusion-derived neoantigens. These findings highlight an important class of tumor-specific antigens and have implications for targeting gene fusion events in cancers that would otherwise be less poised for response to immunotherapy, including cancers with low mutational load and minimal immune infiltration.
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