| 1. |
|
|
| 2. |
- George, Julie, et al.
(författare)
-
Comprehensive genomic profiles of small cell lung cancer
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
-
Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
|
|
| 3. |
- Hesselkilde, Eva Zander, et al.
(författare)
-
Longitudinal study of electrical, functional and structural remodelling in an equine model of atrial fibrillation
- 2019
-
Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model. Method: Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups. Results: AFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed. Conclusion: Horses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.
|
|
| 4. |
|
|
| 5. |
- Boustedt, Jonas, 1965-, et al.
(författare)
-
Students' perceptions of the differences between formal and informal learning
- 2011
-
Ingår i: ICER '11 Proceedings of the seventh international workshop on Computing education research. - New York, USA : Association for Computing Machinery (ACM). - 9781450308298 ; , s. 61-68
-
Konferensbidrag (refereegranskat)abstract
- Research has shown that most learning in the workplace takes place outside of formal training and, given the swiftly changing nature of the field, computer science graduates more than most workers, need to be able to learn computing topics outside of organized classes.In this paper we discuss students' perceptions of the difference between formal and informal learning of computing topics, based on three datasets: essays collected from a technical writing course at a single university; the results of a brainstorming exercise conducted in the same course; and semi-structured interviews conducted at six institutions in three countries.The students report strengths and weaknesses in informal learning. On the one hand, they are motivated, can choose their level of learning, can be more flexible about how they learn, and often retain the material better. On the other hand, they perceive that they may miss important aspects of a topic, learn in an ad hoc way, and have difficulty assessing their learning.
|
|
| 6. |
- Carstensen, Helena, et al.
(författare)
-
Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation
- 2019
-
Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1045-3873 .- 1540-8167. ; 30:4, s. 596-606
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses. Methods and Results: Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. Atrial fibrillatory activity was extracted from surface ECGs using spatiotemporal QRST cancellation. The mean atrial fibrillatory rate before drug infusion was 297 ± 27 fpm. Dofetilide reduced the atrial fibrillatory rate following the infusion of low doses (0.89 µg/kg, P < 0.05) and within 5 minutes preceding cardioversion (P < 0.05). Cardioversion with ranolazine was preceded by a reduction in the atrial fibrillatory rate in the last minute (P < 0.05). The combination of drugs reduced the atrial fibrillatory rate in a similar manner to dofetilide used alone. A trend toward a lower atrial fibrillatory rate before drug infusion was found among horses cardioverting on low doses of the drugs. Conclusion: The atrial fibrillatory rate derived from surface ECGs showed a difference in the mode of action on AF between dofetilide and ranolazine. Dofetilide reduced the atrial fibrillatory rate, whereas ranolazine displayed a cardioverting mechanism that was distinct from a slowing of the fibrillatory process.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Ericson, Thomas, et al.
(författare)
-
Meteor Burst Communication without feedback
- 1995
-
Ingår i: IEEE Transactions on Communications. - : IEEE. - 0090-6778 .- 1558-0857. ; 43:234, s. 851-857
-
Tidskriftsartikel (refereegranskat)abstract
- Traditional meteor burst communication (MBC) systems are duplex (or half-duplex) systems. These systems provide the transmitter with feedback information for the detection of usable meteor trails. To achieve this feedback, a high power transmitter is required also at receive-only sites. In this paper, however, we discuss the application of channel coding to construct a true broadcast-type MBC system that allows for the simultaneous reception of messages at several receiving sites. Furthermore, MBC-systems without feedback allow for simple low power receivers that are impossible to to detect. Suitable codes, system performance and implementation complexity aspects are considered. Simulations with actual field trial data show that these systems are feasible and provide reliable, low-cost transmission of broadcast data.
|
|
| 10. |
- Fang, Jun, et al.
(författare)
-
Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
|
|
