| 1. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 2. |
- Isaksson, Björn, et al.
(författare)
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Hepatic encephalopathy verified by psychometric testing and EEG in cirrhotic patients : Effects of mesocaval interposition shunt or sclerotherapy
- 2005
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Ingår i: HPB. - : Elsevier BV. - 1365-182X .- 1477-2574. ; 7:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- Background. The aim of this randomised prospective study was to evaluate hepatic encephalopathy after mesocaval interposition shunt operation and after repeated endoscopic sclerotherapy. Methods. Forty-five patients with bleeding oesophageal varices due to liver cirrhosis were randomised to the two treatment groups, 24 to the shunt group and 21 to the sclerotherapy group. The patients were evaluated preoperatively regarding blood tests, hepatic encephalopathy as measured by electroencephalogram with spectral analysis and by a battery of psychometric tests. The direction of portal flow in the shunt group was investigated by shunt phlebography and ultrasonography with Doppler. During follow-up the same investigations were performed twice at median 6.7 and 14.7 months after operation. Results. No statistically significant difference was found during follow-up regarding blood tests and electroencephalography with spectral analysis. Although the preoperative psychometric tests showed that the shunt group performed significantly better than the sclerotherapy group, the first follow-up showed that the shunt group performed statistically worse than the sclerotherapy group in seven of the tests: Synonyms (measuring verbal ability), Block Design Test (measuring visuo-spatial ability), Memory for Design Test, Error Score (measuring memory function), Revised Visual Retention Test, correct answers and the same test error answers (measuring visuo-spatial memory, ability and immediate memory), Digit Symbol Test (measuring perceptual ability) and Trial Making Test B (measuring cognitive motor abilities). Conclusions. Patients treated by mesocaval interposition shunt showed a progressive general reduction in psychometric performance compared with patients treated with repeated sclerotherapy, in whom a general intellectual improvement was observed. This finding corresponds to the reverse direction of the preoperative portal flow to a hepatofugal pattern at first follow-up and at 12 months among two-thirds of the patients. © 2005 Taylor & Francis Group Ltd.
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| 3. |
- Amin, Tamer, et al.
(författare)
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Arrow of time : Metaphorical construals of entropy and the second law of thermodynamics
- 2012
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Ingår i: Science Education. - : John Wiley & Sons. - 0036-8326 .- 1098-237X. ; 5:96, s. 818-848
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Tidskriftsartikel (refereegranskat)abstract
- Various features of scientific discourse have been characterized in the science education literature, and challenges students face in appropriating these features have been explored. Using the framework of conceptual metaphor, this paper sought to identify explicit and implicit metaphors in pedagogical texts dealing with the concept of entropy and the second law of thermodynamics, an abstract and challenging domain for learners. Three university-level textbooks were analyzed from a conceptual metaphor perspective, and a range of explicit and implicit metaphors were identified. Explicit metaphors identified include entropy as disorder, thermodynamics processes as movements along a path, and energetic exchange as financial transactions among others. Implicit metaphors include application and elaboration of the generic Location Event Structure metaphor, application of the Object Event Structure metaphor, and others. The similarities and differences between explicit and implicit metaphors found in the textbooks are also described. Two key pedagogical implications are discussed: that the selection of explicit instructional metaphors can be guided by consistency with implicit metaphors; and that the range of implicit metaphors found in pedagogical texts implies that a multiple instructional metaphor strategy is warranted. The depth of the phenomenon of conceptual metaphor and its implications for future research are also discussed
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| 4. |
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| 5. |
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| 6. |
- Andersson, Henrik, et al.
(författare)
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Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
- 2010
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Ingår i: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
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| 7. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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In vitro assessment of platelet concentrates with multiple electrode aggregometry.
- 2015
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 26:2, s. 132-137
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Storage impairs platelet function. It was hypothesized that multiple electrode aggregometry in vitro could be used to follow aggregability in platelet concentrates over time and that the results predict the efficacy of platelet transfusion in an ex vivo transfusion model. In vitro platelet aggregability was assessed in apheresis and pooled buffy coat platelet concentrates (BCs) (n = 13 each) using multiple electrode aggregometry with different agonists 1, 3, 5 and 7 days after preparation. In the ex vivo transfusion model, whole blood samples from nine healthy volunteers were collected every second day. The samples were supplemented with stored platelets (+146 × 10(9) × l(-1)) from the same unit 1, 3, 5 and 7 days after preparation. Platelet aggregability was assessed in the concentrate and in the whole blood samples before and after platelet supplementation. There was a continuous reduction in in vitro platelet aggregability over time in both apheresis and pooled BCs. The same pattern was observed after ex vivo addition of apheresis and pooled BCs to whole blood samples. The best correlation between in vitro aggregability and changes in aggregation after addition was achieved with collagen as agonist (r = 0.67, p
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| 8. |
- Austeng, Dordi, et al.
(författare)
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Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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| 9. |
- Axelsson, Feyza, 1989-
(författare)
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Study guidance practices in science with Turkish speaking recently arrived pupils : A study focusing on scaffolding and meaning making
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Recently arrived pupils are part of the school population at schools in Sweden as well as in other European countries. In Sweden these pupils might receive study guidance support in their first language in various school subjects including science. My dissertation aims to provide insights into Swedish study guidance practices for recently arrived pupils, with a focus on science study guidance, by investigating interactions between recently arrived Turkish-speaking pupils (grades 3–9) and their tutors. My theoretical framework draws on an approach to interactions from sociocultural theory: in particular, the theoretical concepts of meaning-making and scaffolding. The data are based on observations of interactions between the pupils and their tutor from 14 study guidance sessions in seven Swedish cities. The multimodal analysis method is used to analyze video recordings of interactions. I found three different ways that tutors used scaffolding to assist their pupils’ meaning-making of science content: translations, reformulations, and questions and answers. Science content was translated, reformulated, and investigated through questions and answers through interactions in Turkish and Swedish. The tutors used Turkish and Swedish as well as other multimodal resources in study guidance interactions as a way to increase the opportunities for pupils to make meaning around various phenomena and concepts in science. The pupils showed evidence of their meaning-making by, for example, associating the science content with their personal experiences in their homeland, by recalling previous knowledge, or by joining in scientific discussions using their first language. However, not every attempt at scaffolding using translations, reformulations, and questions and answers led to successful acquisition of the desired science content. In some cases, the pupils’ opportunities to gain access to more advanced scientific discussions about scientific texts in Swedish were limited, because the discussion between pupil and tutor addressed a simplified scientific content. In some other cases, tutors made incorrect translations, reformulations and questions and answers in respect of the scientific content, something that could make the pupil’s meaning-making about science challenging.
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| 10. |
- Cilingir, Feyza, 1989-, et al.
(författare)
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Meaning-making Processes in Science within a Swedish Context : The Case of Newly-arrived Turkish Pupils in Sweden
- 2020
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Ingår i: ESERA Virtual Doctoral Network 2020. - Oxford. ; , s. 141-152
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Recently, educational institutions, especially in Europe, have received a growing number of newly-arrived pupils (Eurydice, 2019), which has attracted researchers to assess the educational attainment of these pupils. This research project hence aims to investigate meaning-making processes in the subject of Science where the learning process of newlyarrived Turkish pupils is scaffolded by their study-guidance teachers during studyguidance sessions. To outline the theoretical perspective of the research, Vygotsky’s sociocultural theory on meaning-making and scaffolding is adopted. Data was collected through the observation of newly-arrived Turkish pupils and their study guidanceteachers during the study-guidance sessions. A piece of dialogue between a studyguidance teacher and a newly-arrived pupil has been presented to indicate the challenges which arise during scaffolded interactions.
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