| 1. |
- Governa, Valeria, et al.
(author)
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Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:9
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Journal article (peer-reviewed)abstract
- Therapeutic strategies directed at the tumor surfaceome (TS), including checkpoint inhibitor blocking antibodies, antibody drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cells, provide a new armament to fight cancer. However, a remaining bottleneck is the lack of strategies to comprehensively interrogate patient tumors for potential TS targets. Here, we have developed a platform (tumor surfaceome mapping [TS-MAP]) integrated with a newly curated TS classifier (SURFME) that allows profiling of primary 3D cultures and intact patient glioma tumors with preserved tissue architecture. Moreover, TS-MAP specifically identifies proteins capable of endocytosis as tractable targets for ADCs and other modalities requiring toxic payload internalization. In high-grade gliomas that remain among the most aggressive forms of cancer, we show that cellular spatial organization (2D vs. 3D) fundamentally transforms the surfaceome and endocytome (e.g., integrins, proteoglycans, semaphorins, and cancer stem cell markers) with general implications for target screening approaches, as exemplified by an ADC targeting EGFR. The TS-MAP platform was further applied to profile the surfaceome and endocytome landscape in a cohort of freshly resected gliomas. We found a highly diverse TS repertoire between patient tumors, not directly associated with grade and histology, which highlights the need for individualized approaches. Our data provide additional layers of understanding fundamental to the future development of immunotherapy strategies, as well as procedures for proteomics-based target identification and selection. The TS-MAP platform should be widely applicable in efforts aiming at a better understanding of how to harness the TS for personalized immunotherapy.
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| 2. |
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| 3. |
- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 4. |
- Andersson Varga, Pernilla, 1961, et al.
(author)
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Att försöka få grepp om genrepedagogik(en) – exemplet Läslyftet
- 2022
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In: SMDI 15 Språk och litteratur – en omöjlig eller skön förening? Lunds universitet, 23–24 november 2022..
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Conference paper (other academic/artistic)abstract
- I den svenska skolkontexten framställs genrepedagogik som inflytelserik och ofta använd (Bergh Nestlog, Danielsson & Krog 2018, Borsgård 2021, Hansson 2013, Kinderberg 2021, Liberg, Wiksten Folkeryd & af Geijerstam 2012, Nygård Larsson 2015, Walldén 2019). Dock är den inhemska forskningen om vad som förstås som genrepedagogisk undervisning eller hur den iscensätts relativt begränsad. Ännu mindre vet vi om i vilken utsträckning pedagogiken förekommer i svensk skola. I detta paper undersöks hur Sydneyskolans genrepedagogik uppfattas och rekontextualiseras (Bernstein 2000) i den statliga fortbildningssatsningen Läslyftet vars syfte är att stärka lärares kompetens att undervisa språk- och kunskapsutvecklande i alla ämnen och på alla stadier i svensk skola. I analysen av materialet används verktyg som hämtas från de teorier som Sydneyskolans genrepedagogik vilar på – systemisk funktionell lingvistik (Halliday 2004), genreteori (Martin 1992) och Vygotskijs sociokulturella teorier (Vygotskij 1986). Flertalet av de Läslyftsartiklar som presenterar genrepedagogiken reducerar den till arbete enligt cirkelmodellen, där pedagogiken beskrivs som ett arbetssätt uppdelat i tre eller fyra faser, närmast jämförbara de faser som skrivprocessen (Flower & Hayes 1980) inrymmer. I den mån genrepedagogiken förankras teoretisk, gäller det främst stöttning, men vad som ska stöttas förblir ofta oklart. Språkvetenskapliga teorier tas enbart upp i ett fåtal artiklar, och genrepedagogikens potential att stärka elevernas kritiska förhållningssätt till text förbigås. Den preliminära slutsatsen av studien är att rekontextualiseringen av genrepedagogiken inom Läslyftet är förenklad och ibland också förvanskad, vilket gör att den potential som inryms i Sydneyskolans ursprungliga version av genrepedagogik inte kommer i bruk.
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| 5. |
- Andersson Varga, Pernilla, 1961, et al.
(author)
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Att försöka få grepp om genrepedagogik(en) i den svenska skolkontexen.
- 2022
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In: Skriv! Les! Nordisk forskerkonferanse om lesing, skriving, og literacy. NTNU Trondheim, 10-11 maj, 2022..
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Conference paper (other academic/artistic)abstract
- I den svenska skolkontexten framställs genrepedagogik(en) som inflytelserik och ofta använd (Bergh Nestlog, Danielsson & Krog 2018, Borsgård 2021, Hansson 2013, Kinderberg 2021, Liberg, Wiksten Folkeryd & af Geijerstam 2012, Nygård Larsson 2015, Walldén 2019). Dock är den inhemska forskningen om vad som förstås som genrepedagogisk undervisning eller hur den iscensätts relativt begränsad. Ännu mindre vet vi om i vilken utsträckning pedagogiken förekommer i svensk skola. I detta paper undersöks hur Sydneyskolans genrepedagogik uppfattas och rekontextualiseras (Bernstein 2000) på olika nivåer i det svenska utbildningssystemet.
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| 6. |
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| 7. |
- Andersson Varga, Pernilla, 1961, et al.
(author)
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Getting to grips with genre pedagogy - Mapping and analysing the recontextualisation of Sydney school genre pedagogy in the Swedish educational context
- 2023
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In: Linguistics and Education. - 0898-5898. ; 78
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Journal article (peer-reviewed)abstract
- In Sweden, genre pedagogy is repeatedly put forward as influential. However, there is little research on how it is understood and applied in practice. This article is an attempt to get to grips with how genre pedagogy has been recontextualised in the Swedish school context. This is done by discourse analyses of curriculum and syllabuses, a professional development programme on literacy and teacher guides claiming to draw on genre pedagogy. We conclude that the recontextualisation of genre pedagogy is a simplification, primarily focusing on the pedagogical know-how through a student-centred application of the Teaching and Learning Cycle, while knowledge about language and the underlying ideology aiming at redistributing educational capital is downplayed or absent.
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| 9. |
- Bott, Lukas Thomas, et al.
(author)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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In: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Conference paper (peer-reviewed)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 10. |
- Campbell, Richard A., et al.
(author)
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Direct Impact of Nonequilibrium Aggregates on the Structure and Morphology of Pdadmac/SDS Layers at the Air/Water Interface
- 2014
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:29, s. 8664-8674
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Journal article (peer-reviewed)abstract
- We discuss different nonequilibrium mechanisms by which bulk aggregates directly modify, and can even control, the interfacial structure and morphology of an oppositely charged polyelectrolyte/surfactant (P/S) mixture. Samples are categorized at the air/water interface with respect to the dynamic changes in the bulk phase behavior, the bulk composition, and the sample history using complementary surface-sensitive techniques. First, we show that bulk aggregates can spontaneously interact with the adsorption layer and are retained in it and that this process occurs most readily for positively charged aggregates with an expanded structure. In this case, key nonequilibrium issues of aggregate dissociation and spreading of surface-active material at the interface have a marked influence on the macroscopic interfacial properties. In a second distinct mechanism, aggregates inherently become trapped at the interface during its creation and lateral flocculation occurs. This irreversible process is most pronounced for aggregates with the lowest charge. A third mechanism involves the deposition of aggregates at interfaces due to their transport under gravity. The specificity of this process at an interface depends on its location and is mediated by density effects in the bulk. The prevalence of each mechanism critically depends on a number of different factors, which are outlined systematically here for the first time. This study highlights the sheer complexity by which aggregates can directly impact the interfacial properties of a P/S mixture. Our findings offer scope for understanding seemingly mysterious irreproducible effects which can compromise the performance of formulations in wide-ranging applications from foams to emulsions and lubricants.
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