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- 2019
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Tidskriftsartikel (refereegranskat)
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- Khatri, B., et al.
(författare)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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- Eshmvminov, D., et al.
(författare)
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FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review
- 2023
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Ingår i: Annals of Surgical Oncology. - 1068-9265. ; 30:7, s. 4417-4428
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Forskningsöversikt (refereegranskat)abstract
- BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
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| 8. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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- Berthelsen, A., et al.
(författare)
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Recording marine airgun shots at offsets between 300 and 700 km
- 1991
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 18:4, s. 645-648
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates that - under favorable conditions - by using multichannel recording and subsequent stacking of adjacent records marine airgun shots have been detected at offset distances up to 700 km, the maximum offset at which the authors attempted to record data.^Besides a powerful airgun array, a low noise environment at the recording site and the elimination of static shifts are the prerequisites to obtain refracted and reflected arrivals from the crust and upper mantle at such large offsets.^Primary arrivals detected at offsets between 400 and 700 km image the upper mantle from 70 to about 120 km depth.^Stacking of neighboring shots and/or receivers successfully increases the signal-to-noise ratio, if the traces have been corrected for offset differences, which requires knowledge of the apparent phase velocities.^The data presented here were collected in autumn 1989 during the BABEL Project on the Baltic Shield.
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- Cirino, Glauber, et al.
(författare)
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Observations of Manaus urban plume evolution and interaction with biogenic emissions in GoAmazon 2014/5
- 2018
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 191, s. 513-524
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Tidskriftsartikel (refereegranskat)abstract
- As part of the Observations and Modeling of the Green Ocean Amazon (GoAmazon 2014/5) Experiment, detailed aerosol and trace gas measurements were conducted near Manaus, a metropolis located in the central Amazon Basin. Measurements of aerosol particles and trace gases were done downwind Manaus at the sites T2 (Tiwa Hotel) and T3 (Manacapuru), at a distance of 8 and 70 km from Manaus, respectively. Based on in-plume measurements closer to Manaus (site T2), the chemical signatures of city emissions were used to improve the interpretation of pollutant levels at the T3 site. We derived chemical and physical properties for the city's atmospheric emission ensemble, taking into account only air masses impacted by the Manaus plume at both sites, during the wet and dry season Intensive Operating Periods (IOPs). At T2, average concentrations of aerosol number (CN), CO and SO2 were 5500 cm(-3) (between 10 and 490 nm), 145 ppb and 0.60 ppb, respectively, with a typical ratio ACN/ACO of 60-130 particles cm(-3) ppb(-1). The aerosol scattering (at RH < 60%) and absorption at 637 nm at T2 ranged from 10 to 50 M m(-1) and 5-10 M m(-1), respectively, leading to a mean single scattering albedo (SSA) of 0.70. In addition to identifying periods dominated by Manaus emissions at both T2 and T3, the plume transport between the two sampling sites was studied using back trajectory calculations. Results show that the presence of the Manaus plume at site T3 was important mainly during the daytime and at the end of the afternoons. During time periods directly impacted by Manaus emissions, an average aerosol number concentration of 3200 cm(-3) was measured at T3. Analysis of plume evolution between T2 and T3 indicates a transport time of 4-5 h. Changes of submicron organic and sulfate aerosols ratios relative to CO (Delta OA/Delta CO and Delta SO4/Delta CO, respectively) indicate significant production of secondary organic aerosol (SOA), corresponding to a 40% mass increase in OA and a 30% in SO4 mass concentration. Similarly, during air mass arrival at T3 the SSA increased to 0.83 from 0.70 at T2, mainly associated with an increase in organic aerosol concentration. Aerosol particle size distributions show a strong decrease in the Aitken nuclei mode (10-100 nm) during the transport from T2 to T3, in particular above 30 nm, as a result of efficient coagulation processes into larger particles. A decrease of 30% in the particle number concentration and an increase of about 50 nm in geometric mean diameter were observed from T2 to T3 sites. The study of the evolution of aerosol properties downwind of the city of Manaus improves our understanding of how coupling of anthropogenic and biogenic sources may be impacting the sensitive Amazonian atmosphere.
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- Hobbs, R. W., et al.
(författare)
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Integrated seismic studies of the Baltic shield using data in the Gulf of Bothnia region
- 1993
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Ingår i: Geophysical Journal International. - 0956-540X .- 1365-246X. ; 112:3, s. 305-324
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Tidskriftsartikel (refereegranskat)abstract
- In the autumn of 1989 a co-operative experiment involving 12 research institutions in northwestern Europe collected 2268 km of deep seismic reflection profiles in the Gulf of Bothnia and the Baltic Sea. the 121 litre airgun array used for this profiling was also recorded by 62 muiticomponent land stations to provide coincident refraction surveys, fan-spreads, and 3-D seismic coverage of much of the Gulf of Bothnia. We thus have potentially both high-resolution impedance contrast images as well as more regional 3-D velocity models in both P- and S-waves. In the Bothnian Bay a south-dipping, non-reflective zone coincides with the conductive Archaean-Proterozoic boundary onshore in Finland. Between the Bothnian Bay and Bothnian Sea observed reflectivity geometries and velocity models at Moho depths suggest structures inherited from a 1.9Ga subduction zone; the upper crust here appears to have anomalously low velocity. Within the Bothnian Sea, reflectivity varies considerably beneath the metasedimentary/granitoid rocks of the Central Svecofennian Province (CSP) and the surrounding metavolcanic-arc rocks. Numerous dipping reflectors appear throughout the metavolcanic crust, whereas the CSP has little reflectivity. Wide-angle reflections indicate that the metasedimentary crust of the Bothnian Basin is 10 km thicker than the neighbouring Svecofennian subprovinces. Near the Åland archipelago Rapakivi granite plutons exhibit bright reflections, a contrast to the usual non-reflective plutons elsewhere in western Europe. Additional dipping reflections deep in the crust of this area may support models of rifting and crustal thinning during emplacement of the 1.70-1.54 Ga Rapakivi granites. Coeval gabbroic/anorthositic magmatism may explain the high reflectivity and high velocity of these plutons. the c. 1.25 Ga mafic sills and feeder dykes of the Central Scandinavian Dolerite Group also produce clear reflections on both near- and far-offset seismic sections. Continued modelling will produce better velocity models of the crust and better constrained contour maps of crustal thickness in this part of the Baltic shield.
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| 18. |
- Ignatowicz, Monika, 1983-, et al.
(författare)
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Cesium and ammonium salts as low temperature secondary fluids
- 2019
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Ingår i: Refrigeration Science and Technology. - : International Institute of Refrigeration. - 9782362150357 ; , s. 2568-2575
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Konferensbidrag (refereegranskat)abstract
- Potassium formate and potassium acetate, as well as their blends are known as environmentally friendly secondary fluids with good thermophysical properties. The aim of this work was to investigate properties of cesium formate, cesium acetate and ammonium acetate solutions. Results showed that various alkali metal ions such as potassium, sodium, cesium or ammonium are affecting the freezing point, thermal conductivity, viscosity and specific heat capacity in different ways. Among examined salts, ammonium formate showed the best performance by giving the highest specific heat capacity and highest thermal conductivity and the lowest dynamic viscosity compared to potassium formate and other salts. Cesium formate solutions had the lowest viscosity among all tested salts. This study shows that both cesium formate and sodium formate could be used as different additives to enhance different properties of potassium formate and potassium acetate secondary based fluids.
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- Ryman, N., et al.
(författare)
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Power for detecting genetic divergence: differences between statistical methods and marker loci
- 2006
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Ingår i: Molecular Ecology. - 0962-1083. ; 15:8, s. 2031-2045
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Tidskriftsartikel (refereegranskat)abstract
- Information on statistical power is critical when planning investigations and evaluating empirical data, but actual power estimates are rarely presented in population genetic studies. We used computer simulations to assess and evaluate power when testing for genetic differentiation at multiple loci through combining test statistics or P values obtained by four different statistical approaches, viz. Pearson's chi-square, the log-likelihood ratio G-test, Fisher's exact test, and an F-ST-based permutation test. Factors considered in the comparisons include the number of samples, their size, and the number and type of genetic marker loci. It is shown that power for detecting divergence may be substantial for frequently used sample sizes and sets of markers, also at quite low levels of differentiation. The choice of statistical method may be critical, though. For multi-allelic loci such as microsatellites, combining exact P values using Fisher's method is robust and generally provides a high resolving power. In contrast, for few-allele loci (e.g. allozymes and single nucleotide polymorphisms) and when making pairwise sample comparisons, this approach may yield a remarkably low power. In such situations chi-square typically represents a better alternative. The G-test without Williams's correction frequently tends to provide an unduly high proportion of false significances, and results from this test should be interpreted with great care. Our results are not confined to population genetic analyses but applicable to contingency testing in general.
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| 23. |
- Torres-Sangiao, E, et al.
(författare)
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Quantification of Adaptive Immune Responses Against Protein-Binding Interfaces in the Streptococcal M1 Protein
- 2024
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Ingår i: Molecular & Cellular Proteomics. - : Elsevier. - 1535-9476 .- 1535-9484. ; 23:5
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial or viral antigens can contain subdominant protein regions that elicit weak antibody responses upon vaccination or infection although there is accumulating evidence that antibody responses against subdominant regions can enhance the protective immune response. One proposed mechanism for subdominant protein regions is the binding of host proteins that prevent antibody production against epitopes hidden within the protein binding interfaces. Here, we used affinity purification combined with quantitative mass spectrometry (AP-MS) to examine the level of competition between antigen-specific antibodies and host-pathogen protein interaction networks using the M1 protein from Streptococcus pyogenes as a model system. As most humans have circulating antibodies against the M1 protein, we first used AP-MS to show that the M1 protein interspecies protein network formed with human plasma proteins is largely conserved in naïve mice. Immunizing mice with the M1 protein generated a time-dependent increase of anti-M1 antibodies. AP-MS analysis comparing the composition of the M1-plasma protein network from naïve and immunized mice showed significant enrichment of 292 IgG peptides associated with 56 IgG chains in the immune mice. Despite the significant increase of bound IgGs, the levels of interacting plasma proteins were not significantly reduced in the immune mice. The results indicate that the antigen-specific polyclonal IgG against the M1 protein primarily targets epitopes outside the other plasma protein binding interfaces. In conclusion, this study demonstrates that AP-MS is a promising strategy to determine the relationship between antigen-specific antibodies and host-pathogen interaction networks that could be used to define subdominant protein regions of relevance for vaccine development.
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