| 1. |
- Erni, W., et al.
(författare)
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Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
- 2013
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
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Tidskriftsartikel (refereegranskat)abstract
- This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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| 2. |
- Meech, K. J., et al.
(författare)
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EPOXI: Comet 103P/Hartley 2 Observations from a Worldwide Campaign
- 2011
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Ingår i: Astrophysical Journal Letters. - London : IOP. - 2041-8213 .- 2041-8205. ; 734:L1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4?hr. Starting in 2010 August the period changed from 16.6?hr to near 19?hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
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| 3. |
- Berthomier, M., et al.
(författare)
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Alfven : magnetosphere-ionosphere connection explorers
- 2012
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Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
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Tidskriftsartikel (refereegranskat)abstract
- The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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| 4. |
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| 5. |
- Savage, C., et al.
(författare)
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Turning the tables : When the student teaches the professional - A case description of an innovative teaching approach as told by the students
- 2011
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Ingår i: Nurse Education Today. - : Elsevier BV. - 0260-6917 .- 1532-2793. ; 31:8, s. 803-808
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Tidskriftsartikel (refereegranskat)abstract
- Background: Is it possible to increase the value, meaningfulness, and relevance of a course experience by integrating it with the healthcare context? Students and teachers from a course on organization, learning and leadership sought to explore this possibility through a collaborative effort with nurses from an affiliated teaching hospital. Methods: Working as teachers, students created continuing nursing education (CNE) courses using the Adaptive Reflection process. The students and teachers then researched the experience in terms of: 1) content analysis of student self-reflections (discussion notes and logbooks) on the learning process, 2) a student self-assessed outcome achievement survey, and 3) perceived relevance of the CNE courses by the clinical nurse educators. Results: Thirteen nursing students created three CNE courses together with sixteen nurses. Each course consisted of multiple 20-minute long web-based modules with automatic formative feedback. In the process, students exceeded course outcome-levels, journeyed from chaos to confidence and experienced new ways of viewing the group and their own capabilities. Conclusions: The innovative design of the course moved the focus from student-centered learning to learning by contributing to health care. Working in a real world context, the content of the students' efforts and the skills they developed not only met course requirements, but were also aligned with the needs of the wards. This contribution was valued by the students and the RNs which enhanced students' feelings of self-confidence. Further research lies in testing the model in other contexts.
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| 6. |
- Bestas, Burcu, et al.
(författare)
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Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model
- 2014
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:9, s. 4067-4081
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Tidskriftsartikel (refereegranskat)abstract
- X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.
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| 7. |
- Brenning, Nils, et al.
(författare)
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Spokes and charged particle transport in HiPIMS magnetrons
- 2013
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 46:8, s. 084005-
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Tidskriftsartikel (refereegranskat)abstract
- Two separate scientific communities are shown to have studied one common phenomenon, azimuthally rotating dense plasma structures, also called spokes, in pulsed-power E x B discharges, starting from quite different approaches. The first body of work is motivated by fundamental plasma science and concerns a phenomenon called the critical ionization velocity, CIV, while the other body of work is motivated by the applied plasma science of high power impulse magnetron sputtering (HiPIMS). Here we make use of this situation by applying experimental observations, and theoretical analysis, from the CIV literature to HiPIMS discharges. For a practical example, we take data from observed spokes in HiPIMS discharges and focus on their role in charged particle transport, and in electron energization. We also touch upon the closely related questions of how they channel the cross-B discharge current, how they maintain their internal potential structure and how they influence the energy spectrum of the ions? New particle-in-cell Monte Carlo collisional simulations that shed light on the azimuthal drift and expansion of the spokes are also presented.
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| 8. |
- Geahlen, J. H., et al.
(författare)
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Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3
- 2013
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 45:15, s. 667-683
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Tidskriftsartikel (refereegranskat)abstract
- In a screen for genes expressed specifically in gastric mucous neck cells, we identified GKN3, the recently discovered third member of the gastrokine family. We present confirmatory mouse data and novel porcine data showing that mouse GKN3 expression is confined to mucous cells of the corpus neck and antrum base and is prominently expressed in metaplastic lesions. GKN3 was proposed originally to be expressed in some human populations and a pseudogene in others. To investigate that hypothesis, we studied human GKN3 evolution in the context of its paralogous genomic neighbors, GKN1 and GKN2. Haplotype analysis revealed that GKN3 mimics GKN2 in patterns of exonic SNP allocation, whereas GKN1 appeared to be more stringently selected. GKN3 showed signatures of both directional selection and population based selective sweeps in humans. One such selective sweep includes SNP rs10187256, originally identified as an ancestral tryptophan to premature STOP codon mutation. The derived (nonancestral) allele went to fixation in Asia. We show that another SNP, rs75578132, identified 5 bp downstream of rs10187256, exhibits a second selective sweep in almost all Europeans, some Latinos, and some Africans, possibly resulting from a reintroduction of European genes during African colonization. Finally, we identify a mutation that would destroy the splice donor site in the putative exon3-intron3 boundary, which occurs in all human genomes examined to date. Our results highlight a stomach-specific human genetic locus, which has undergone various selective sweeps across European, Asian, and African populations and thus reflects geographic and ethnic patterns in genome evolution.
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| 9. |
- Harton, G L, et al.
(författare)
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ESHRE PGD Consortium/Embryology Special Interest Group--best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS).
- 2011
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 26:1, s. 41-6
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Tidskriftsartikel (refereegranskat)abstract
- In 2005, the European Society for Human Reproduction and Embryology (ESHRE) Preimplantation Genetic Diagnosis (PGD) Consortium published a set of Guidelines for Best Practice to give information, support and guidance to potential, existing and fledgling PGD programmes (Thornhill AR, De Die-Smulders CE, Geraedts JP, Harper JC, Harton GL, Lavery SA, Moutou C, Robinson MD, Schmutzler AG, Scriven PN et al. ESHRE PGD Consortium best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Hum Reprod 2005;20:35-48.). The subsequent years have seen the introduction of a number of new technologies as well as the evolution of current techniques. Additionally, in light of ESHRE's recent advice on how practice guidelines should be written and formulated, the Consortium believed it was timely to revise and update the PGD guidelines. Rather than one document that covers all of PGD as in the original publication, these guidelines are separated into four new documents that apply to different aspects of a PGD programme; Organization of a PGD centre, fluorescence in situ hybridization-based testing, amplification-based testing and polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS). Here we have updated the sections that pertain to embryology (including cryopreservation) and biopsy of embryos prior to PGD or PGS. Topics covered in this guideline include uses of embryo biopsy, laboratory issues relating to biopsy, timing of biopsy, biopsy procedure and cryopreserving biopsied embryos.
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| 10. |
- Lammer, H., et al.
(författare)
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Geophysical and Atmospheric Evolution of Habitable Planets
- 2010
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Ingår i: Astrobiology. - : Mary Ann Liebert Inc. - 1531-1074 .- 1557-8070. ; 10:1, s. 45-68
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of Earth-like habitable planets is a complex process that depends on the geodynamical and geophysical environments. In particular, it is necessary that plate tectonics remain active over billions of years. These geophysically active environments are strongly coupled to a planet's host star parameters, such as mass, luminosity and activity, orbit location of the habitable zone, and the planet's initial water inventory. Depending on the host star's radiation and particle flux evolution, the composition in the thermosphere, and the availability of an active magnetic dynamo, the atmospheres of Earth-like planets within their habitable zones are differently affected due to thermal and nonthermal escape processes. For some planets, strong atmospheric escape could even effect the stability of the atmosphere.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Sampo, M., et al.
(författare)
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A web-based prognostic tool for extremity and trunk wall soft tissue sarcomas and its external validation
- 2012
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 106:6, s. 1076-1082
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We developed a web-based, prognostic tool for extremity and trunk wall soft tissue sarcoma to predict 10-year sarcoma-specific survival. External validation was performed. METHODS: Patients referred during 1987-2002 to Helsinki University Central Hospital are included. External validation was obtained from the Lund University Hospital register. Cox proportional hazards models were fitted with the Helsinki data. The previously described model (SIN) includes size, necrosis, and vascular invasion. The extended model (SAM) includes the SIN factors and in addition depth, location, grade, and size on a continuous scale. Models were statistically compared according to accuracy (area under the ROC curve = AUC) of 10-year sarcoma-specific survival prediction. RESULTS: The AUC of the SAM model in 10-year survival prediction in the Helsinki patient series was 0.81 as compared with 0.74 for the SIN model (P = 0.0007). The corresponding AUCs in the external validation series were 0.77 for the SAM model and 0.73 for the SIN model (P = 0.03). A web-based calculator for the SAM model is available at http://www.prognomics.org/sam. CONCLUSION: Addition of grade, depth, and location as well as tumour size on a continuous scale significantly improved the accuracy of the prognostic model when compared with a model that includes only size, necrosis, and vascular invasion. British Journal of Cancer (2012) 106, 1076-1082. doi:10.1038/bjc.2012.48 www.bjcancer.com Published online 21 February 2012 (C) 2012 Cancer Research UK
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| 15. |
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| 16. |
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| 17. |
- Braem, Marieke G. M., et al.
(författare)
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Coffee and tea consumption and the risk of ovarian cancer : a prospective cohort study and updated meta-analysis
- 2012
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Ingår i: American Journal of Clinical Nutrition. - Bethesda : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 95:5, s. 1172-1181
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. Design: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. Results: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% Cl: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer. Am J Clin Nutr 2012;95:1172-81.
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| 18. |
- Englund, Mikael C. O., 1971, et al.
(författare)
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The establishment of 20 different human embryonic stem cell lines and subclones; a report on derivation, culture, characterisation and banking.
- 2010
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Ingår i: In vitro cellular & developmental biology. Animal. - : Springer Science and Business Media LLC. - 1543-706X .- 1071-2690. ; 46:3-4, s. 217-30
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Tidskriftsartikel (refereegranskat)abstract
- This report summarises our efforts in deriving, characterising and banking of 20 different human embryonic stem cell lines. We have derived a large number of human embryonic stem cell lines between 2001 and 2005. One of these cell lines was established under totally xeno-free culture conditions. In addition, several subclones have been established, including a karyoptypical normal clone from a trisomic mother line. A master cell banking system has been utilised in concert with an extensive characterisation programme, ensuring a supply of high quality pluripotent stem cells for further research and development. In this report we also present the first data on a proprietary novel antibody, hES-Cellect, that exhibits high specificity for undifferentiated hES cells. In addition to the traditional manual dissection approach of propagating hES cells, we here also report on the successful approaches of feeder-free cultures as well as single cell cultures based on enzymatic digestion. All culture systems used as reported here have maintained the hES cells in a karyotypical normal and pluripotent state. These systems also have the advantage of being the principal springboards for further scale up of cultures for industrial or clinical applications that would require vastly more cells that can be produced by mechanical means.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Larsson, Britt-Marie, et al.
(författare)
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Limited airway effects in mild asthmatics after exposure to air pollution in a road tunnel
- 2010
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 104:12, s. 1912-1918
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Tidskriftsartikel (refereegranskat)abstract
- Ambient air pollution is a contributing factor to respiratory morbidity and mortality and asthmatics are a particularly vulnerable population. The aim of the study was to investigate whether acute exposure to traffic related air pollution in a road tunnel would increase bronchial responsiveness in mild asthmatics, and if this would be accompanied by increased measures of inflammatory markers in the airways assessed by nasal lavage (NAL) and induced sputum. Fourteen mild asthmatics (7 treated with inhaled corticosteroids) were exposed for 2 h in a road tunnel and a control environment, respectively, separated by at least 3 weeks. Symptoms and peak expiratory flow (PEF) were recorded. Seven hours following exposure sessions, subjects underwent measurements of fraction of exhaled nitric oxide (FENO), spirometry, and a bronchial provocation test. NAL, induced sputum and blood samples were collected. The median PM(2.5) and PM(10) levels during the exposure occasions in the road tunnel were 80 (range 41-93) μg/m(3) and 183 (72-213) μg/m(3) respectively. Irritative symptoms from the airways increased and PEF decreased after road tunnel exposure. Increased levels of IL-10, IL-12 and TNF-α were observed in NAL fluid from subjects without ongoing inhaled corticosteroid treatment. Forced expiratory volume in 1 s (FEV(1)) and the degree of bronchial responsiveness in asthmatics did not change significantly after tunnel exposure. We conclude that asthmatics exhibit increased symptoms, decreased PEF and signs of inflammatory response in the upper airways, after a 2 h road tunnel exposure. Our findings may further emphasize asthmatics as a vulnerable group to common air pollutants.
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| 24. |
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| 25. |
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| 26. |
- Lehto, Taavi, et al.
(författare)
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A Peptide-based Vector for Efficient Gene Transfer In Vitro and In Vivo
- 2011
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 19:8, s. 1457-1467
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Tidskriftsartikel (refereegranskat)abstract
- Finding suitable nonviral delivery vehicles for nucleic acid-based therapeutics is a landmark goal in gene therapy. Cell-penetrating peptides (CPPs) are one class of delivery vectors that has been exploited for this purpose. However, since CPPs use endocytosis to enter cells, a large fraction of peptides remain trapped in endosomes. We have previously reported that stearylation of amphipathic CPPs, such as transportan 10 (TP10), dramatically increases transfection of oligonucleotides in vitro partially by promoting endosomal escape. Therefore, we aimed to evaluate whether stearyl-TP10 could be used for the delivery of plasmids as well. Our results demonstrate that stearyl-TP10 forms stable nanoparticles with plasmids that efficiently enter different cell-types in a ubiquitous manner, including primary cells, resulting in significantly higher gene expression levels than when using stearyl-Arg9 or unmodified CPPs. In fact, the transfection efficacy of stearyl-TP10 almost reached the levels of Lipofectamine 2000 (LF2000), however, without any of the observed lipofection-associated toxicities. Most importantly, stearyl-TP10/plasmid nanoparticles are nonimmunogenic, mediate efficient gene delivery in vivo, when administrated intramuscularly (i.m.) or intradermally (i.d.) without any associated toxicity in mice.
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| 27. |
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| 28. |
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| 29. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Diagnosis and management of adult coeliac disease : guidelines from the British Society of Gastroenterology
- 2014
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 63:8, s. 1210-1228
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Tidskriftsartikel (refereegranskat)abstract
- A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
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| 30. |
- Ludvigsson, Jonas F., et al.
(författare)
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The Oslo definitions for coeliac disease and related terms
- 2013
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 62:1, s. 43-52
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Tidskriftsartikel (refereegranskat)abstract
- Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to 'CD', the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as 'a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Classical CD was defined as 'CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.' 'Gluten-related disorders' is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.
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| 31. |
- Lundin, Anna, et al.
(författare)
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Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus
- 2014
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Ingår i: Plos Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.
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| 32. |
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| 33. |
- Lundin, Fredrik, et al.
(författare)
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Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification
- 2011
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group. - 0022-3050 .- 1468-330X. ; 82:7, s. 772-778
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). Subjects and methods 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. 1 H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. Results INPH patients had lower NAA (p = 0.02) and lower tNA (p = 0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myoinositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Conclusion Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.
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| 34. |
- MacKay, Craig, et al.
(författare)
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Identification of KIAA1018/FAN1, a DNA Repair Nuclease Recruited to DNA Damage by Monoubiquitinated FANCD2
- 2010
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 142:1, s. 65-76
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Tidskriftsartikel (refereegranskat)abstract
- DNA interstrand crosslinks (ICLs) are highly toxic because they block the progression of replisomes. The Fanconi Anemia (FA) proteins, encoded by genes that are mutated in FA, are important for repair of ICLs. The FA core complex catalyzes the monoubiquitination of FANCD2, and this event is essential for several steps of ICL repair. However, how monoubiquitination of FANCD2 promotes ICL repair at the molecular level is unknown. Here, we describe a highly conserved protein, KIAA1018/MTMR15/FAN1, that interacts with, and is recruited to sites of DNA damage by, the monoubiquitinated form of FANCD2. FAN1 exhibits endonuclease activity toward 50 flaps and has 5' exonuclease activity, and these activities are mediated by an ancient VRR_nuc domain. Depletion of FAN1 from human cells causes hypersensitivity to ICLs, defects in ICL repair, and genome instability. These data at least partly explain how ubiquitination of FANCD2 promotes DNA repair.
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| 35. |
- Makonyi, Karoly, et al.
(författare)
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Evaluating vacuum phototriodes designed for the PANDA electromagnetic calorimeter
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576 .- 0167-5087. ; 763, s. 36-43
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Tidskriftsartikel (refereegranskat)abstract
- In this work properties of a vacuum phototriode (VPT) and preamplifier unit designed for the electromagnetic calorimeter of the PANDA experiment being built at FAIR are investigated. With the use of lead tungstate and lanthanium bromide scintillators the VPT properties are studied at low photon energies, from tens of key in the lanthanium bromide measurements and between 10 MeV and 60 MeV in the lead tungstate measurements. At these energies the noise of the VPT unit can be expected to influence its performance significantly. It is shown that the noise contribution to the measured energy resolution, under optimal conditions, is consistent with a fluctuation of (one standard deviation) approximately 200 electrons at the VPT anode. For a lead tungstate crystal this is equivalent to a noise of 1.2 MeV. For lanthanium bromide this makes it possible to use VPTs for gamma ray spectroscopy above a few hundreds of keV without noticeable effects on the energy resolution compared to measurements with a standard photomultiplier.
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| 36. |
- Merritt, Melissa A., et al.
(författare)
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Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 38:5, s. 528-537
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Tidskriftsartikel (refereegranskat)abstract
- There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n = 1095) and borderline (n = 96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR = 1.22, 95% CI = 1.02-1.48, P-trend = 0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development.
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| 37. |
- Minea, T. M., et al.
(författare)
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Kinetics of plasma species and their ionization in short-HiPIMS by particle modeling
- 2014
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Ingår i: Surface & Coatings Technology. - : Elsevier BV. - 0257-8972 .- 1879-3347. ; 255, s. 52-61
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Tidskriftsartikel (refereegranskat)abstract
- The ionization efficiency of High Power Impulse Magnetron Sputtering (HiPIMS) discharges is the key parameter leading to (i) gas ion production and consequently controlling the sputtering effectiveness and (ii) sputtered vapor ionization, self-consistently linked to self-sputtering and thin film properties. To study the HiPIMS discharge time dependent two dimensional Particle in Cell (2D PIC) modelling coupled with Monte Carlo treatment of the plasma kinetics is discussed in terms of numerical scheme and stability criteria. The first microscopic results are presented for very short pulses (similar to 5 mu s) using superimposed DC pre-ionization. During this modeled HiPIMS short-pulse the plasma density increases at least two orders of magnitude driven by the pulse voltage, which also continues for a short time in the afterglow. During the pulse voltage plateau, the plasma potential shows a linear dependency going away from the target with two slopes over two space regions. First region is very narrow (<0.5 mm), corresponding to the cathode sheath in front of the race-track, while the second region, much larger, corresponds to the pre-sheath or Ionization Region (IR). Modeling results show an increasing electric field in the sheath with the voltage rise of the pulse, while it stays almost constant in the IR, corresponding to about 150 Vcm(-1), in agreement with reported probe measurements. The local electron energy distribution functions in the IR and further out in the Diffusion Region (DR) are very different. IR electrons are much more energetic compared to the ones found in the DR, which have an important low energy population as a result of the ionization processes. The transport of sputtered metal vapor from the target is simulated by 3D Monte Carlo (MC) modeling, in the intermediary pressure range - between ballistic and diffusive. Using the self-consistent output of plasma density maps from PLC with MC transport of sputtered vapor including their possible ionization when they cross the HiPIMS dense plasma, it is possible to estimate the metal ionization fraction, found here slightly lower than in previous reported works.
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| 38. |
- Muhammad, Junaid, et al.
(författare)
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Two-domain formation during the epitaxial growth of GaN (0001) on c-plane Al2O3 (0001) by high power impulse magnetron sputtering
- 2011
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Ingår i: Journal of Applied Physics. - : American Institute of Physics (AIP). - 0021-8979 .- 1089-7550. ; 110:12, s. 123519-
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Tidskriftsartikel (refereegranskat)abstract
- We study the effect of high power pulses in reactive magnetron sputter epitaxy on the structural properties of GaN (0001) thin films grown directly on Al2O3 (0001) substrates. The epilayers are grown by sputtering from a liquid Ga target, using a high power impulse magnetron sputtering power supply in a mixed N2/Ar discharge. X-ray diffraction, micro-Raman, micro-photoluminescence, and transmission electron microscopy investigations show the formation of two distinct types of domains. One almost fully relaxed domain exhibits superior structural and optical properties as evidenced by rocking curves with a full width at half maximum of 885 arc sec and a low temperature band edge luminescence at 3.47 eV with the full width at half maximum of 10 meV. The other domain exhibits a 14 times higher isotropic strain component, which is due to the higher densities of the point and extended defects, resulting from the ion bombardment during growth. Voids form at the domain boundaries. Mechanisms for the formation of differently strained domains, along with voids during the epitaxial growth of GaN are discussed.
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| 39. |
- Myers, L. S., et al.
(författare)
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Compton scattering from C-12 using tagged photons in the energy range 65-115 MeV
- 2014
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 89:3
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Tidskriftsartikel (refereegranskat)abstract
- Elastic scattering of photons from C-12 has been investigated using quasimonoenergetic tagged photons with energies in the range 65-115 MeV at laboratory angles of 60 degrees, 120 degrees, and 150 degrees. at the Tagged-Photon Facility at the MAX IV Laboratory in Lund, Sweden. A phenomenological model was employed to provide an estimate of the sensitivity of the C-12(gamma,gamma)C-12 cross section to the bound- nucleon polarizabilities.
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| 40. |
- Myers, L S, et al.
(författare)
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Measurement of compton scattering from the deuteron and an improved extraction of the neutron electromagnetic polarizabilities.
- 2014
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Ingår i: Physical Review Letters. - 1079-7114. ; 113:26
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Tidskriftsartikel (refereegranskat)abstract
- The electromagnetic polarizabilities of the nucleon are fundamental properties that describe its response to external electric and magnetic fields. They can be extracted from Compton-scattering data-and have been, with good accuracy, in the case of the proton. In contradistinction, information for the neutron requires the use of Compton scattering from nuclear targets. Here, we report a new measurement of elastic photon scattering from deuterium using quasimonoenergetic tagged photons at the MAX IV Laboratory in Lund, Sweden. These first new data in more than a decade effectively double the world data set. Their energy range overlaps with previous experiments and extends it by 20 MeV to higher energies. An analysis using chiral effective field theory with dynamical Δ(1232) degrees of freedom shows the data are consistent with and within the world data set. After demonstrating that the fit is consistent with the Baldin sum rule, extracting values for the isoscalar nucleon polarizabilities, and combining them with a recent result for the proton, we obtain the neutron polarizabilities as α_{n}=[11.55±1.25(stat)±0.2(BSR)±0.8(th)]×10^{-4} fm^{3} and β_{n}=[3.65∓1.25(stat)±0.2(BSR)∓0.8(th)]×10^{-4} fm^{3}, with χ^{2}=45.2 for 44 degrees of freedom.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Ose, Jennifer, et al.
(författare)
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Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:2, s. 399-410
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Tidskriftsartikel (refereegranskat)abstract
- The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75 [0.61-0.93], p(het)0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What's new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research.
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| 46. |
- Russnes, HG, et al.
(författare)
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Genomic architecture characterizes tumor progression paths and fate in breast cancer patients
- 2010
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Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 2:38, s. 38ra47-
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Tidskriftsartikel (refereegranskat)abstract
- This study demonstrates the relation among structural genomic alterations, molecular subtype, and clinical behavior and shows that an objective score of genomic complexity can provide independent prognostic information in breast cancer.
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| 47. |
- Santangelo, G., et al.
(författare)
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First spectrally-resolved H-2 observations towards HH 54 Low H2O abundance in shocks
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 569, s. Art. no. L8-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Herschel observations suggest that the H2O distribution in outflows from low-mass stars resembles the H-2 emission. It is still unclear which of the different excitation components that characterise the mid-and near-IR H-2 distribution is associated with H2O. Aims. The aim is to spectrally resolve the different excitation components observed in the H-2 emission. This will allow us to identify the H-2 counterpart associated with H2O and finally derive directly an H2O abundance estimate with respect to H-2. Methods. We present new high spectral resolution observations of H-2 0-0 S(4), 0-0 S(9), and 1-0 S(1) towards HH 54, a bright nearby shock region in the southern sky. In addition, new Herschel/HIFI H2O (2(12)-1(01)) observations at 1670 GHz are presented. Results. Our observations show for the first time a clear separation in velocity of the different H-2 lines: the 0-0 S(4) line at the lowest excitation peaks at -7 kms(-1), while the more excited 0-0 S(9) and 1-0 S(1) lines peak at -15 km s(-1). H2O and high-J CO appear to be associated with the H-2 0-0 S(4) emission, which traces a gas component with a temperature of 700-1000 K. The H2O abundance with respect to H-2 0-0 S(4) is estimated to be X(H2O)
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| 48. |
- Sassi, Atfa, et al.
(författare)
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Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels
- 2014
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 133:5, s. 1410-U681
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. Objective: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. Methods: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. Results: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p. Glu340del and p. Leu83Ser). A third homozygous mutation (p. Asp502Tyr) and the p. Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. Conclusion: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.
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| 49. |
- Skoog, Emma C, 1983, et al.
(författare)
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Human Gastric Mucins Differently Regulate Helicobacter pylori Proliferation, Gene Expression and Interactions with Host Cells. : Effects of gastric mucins on Helicobacter pylori
- 2012
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Ingår i: PLoS One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA) appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host.
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| 50. |
- Stenler, S., et al.
(författare)
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Micro-minicircle gene therapy : Implications of size on fermentation, complexation, shearing resistance, and expression
- 2014
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Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier BV. - 2162-2531. ; 3, s. e140-
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Tidskriftsartikel (refereegranskat)abstract
- The minicircle (MC), composed of eukaryotic sequences only, is an interesting approach to increase the safety and efficiency of plasmid-based vectors for gene therapy. In this paper, we investigate micro-MC (miMC) vectors encoding small regulatory RNA. We use a construct encoding a splice-correcting U7 small nuclear RNA, which results in a vector of 650 base pairs (bp), as compared to a conventional 3600 bp plasmid carrying the same expression cassette. Furthermore, we construct miMCs of varying sizes carrying different number of these cassettes. This allows us to evaluate how size influences production, supercoiling, stability and efficiency of the vector. We characterize coiling morphology by atomic force microscopy and measure the resistance to shearing forces caused by an injector device, the Biojector. We compare the behavior of miMCs and plasmids in vitro using lipofection and electroporation, as well as in vivo in mice. We here show that when the size of the miMC is reduced, the formation of dimers and trimers increases. There seems to be a lower size limit for efficient expression. We demonstrate that miMCs are more robust than plasmids when exposed to shearing forces, and that they show extended expression in vivo.
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