| 61. |
- Chung, Hyun-Kyung, et al.
(författare)
-
Notes on critical assessment of theoretical calculations of atomic structure and transition probabilities
- 2013
-
Ingår i: Atoms. - : MDPI. - 2218-2004. ; 1:3, s. 14-15
-
Tidskriftsartikel (refereegranskat)abstract
- Atomic structure and transition probabilities are fundamental physical data required in many fields of science and technology. Atomic physics codes are freely available to other community users to generate atomic data for their interest, but the quality of these data is rarely verified. This special issue addresses estimation of uncertainties in atomic structure and transition probability calculations, and discusses methods and strategies to assess and ensure the quality of theoretical atomic data.
|
|
| 62. |
- Dahl, Christina, et al.
(författare)
-
Mutual Exclusivity Analysis of Genetic and Epigenetic Drivers in Melanoma Identifies a Link Between p14(ARF) and RAR beta Signaling
- 2013
-
Ingår i: Molecular Cancer Research. - 1557-3125. ; 11:10, s. 1166-1178
-
Tidskriftsartikel (refereegranskat)abstract
- Melanoma genomes contain thousands of alterations including: mutations, copy number alterations, structural aberrations, and methylation changes. The bulk of this variation is stochastic and functionally neutral, with only a small minority representing "drivers" that contribute to the genesis and maintenance of tumors. Drivers are often directly or inversely correlated across tumors, reflecting the molecular and regulatory signaling pathways in which they operate. Here, a profile of genetic and epigenetic drivers in 110 human melanoma cell lines was generated and searched for non-random distribution patterns. Statistically significant mutual exclusivity was revealed among components of each of the p16(INK4A)-CDK4-RB, RAS-RAF-MEK-ERK and PI3K-AKT signaling pathways. In addition, an inverse correlation was observed between promoter hypermethylation of retinoic acid receptor beta (RARB) and CDKN2A alterations affecting p14(ARF) (P < 0.0001), suggesting a functional link between RAR beta signaling and the melanoma-suppressive activities of p14(ARF). Mechanistically, all-trans retinoic acid (ATRA) treatment increased the expression of p14(ARF) in primary human melanocytes and the steady-state levels of p14(ARF) in these cells were shown to be regulated via RAR beta. Furthermore, the ability of ATRA to induce senescence is reduced in p14(ARF)-depleted melanocytes, and we provide proof-of-concept that ATRA can induce irreversible growth arrest in melanoma cells with an intact RARb-p14(ARF) signaling axis, independent of p16(INK4A) and p53 status. Implications: These data highlight the power of mutual exclusivity analysis of cancer drivers to unravel molecular pathways and establish a previously unrecognized cross-talk between RAR beta and p14(ARF) with potential implications for melanoma treatment.
|
|
| 63. |
- Davidson, Per, et al.
(författare)
-
A daytime nap does not increase pattern separation ability
- 2019
-
Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 42:1, s. 42-42
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction A large body of studies has showed that the ability to learn new information is impaired when we are sleep deprived. Pattern separation (PS), the ability to form distinct memories for events that are highly similar and share overlapping features, has also previously been found to be impaired by sleep deprivation. In the present study, we examined if a daytime nap would increase PS performance. Methods 108 young healthy participants came to the lab in the morning and completed the Mnemonic Similarity Task (MST). This task starts with an encoding phase where participants view images of common everyday objects and are asked to classify them as indoor or outdoor objects. During a subsequent memory test, participants view three different kinds of objects; ‘old’ objects that were also present during the encoding phase, ‘new’ objects that have not been seen before, and ‘lure’ objects that are similar to, but not exactly the same as, objects viewed during encoding. The task of the participants during the re-test is to say if the objects presented are ‘old’, ‘new’ or ‘similar’. This test gives two different outcome measures: General Recognition (GR) - the ability to separate old objects from new ones, and PS - the ability to separate similar objects from old ones. After this task, participants were randomly allocated to either a sleep or a wake group. The sleep group had a two-hour nap opportunity and the wake group spent an equal amount of time resting. After this delay interval, participants completed the MST for a second time with a new set of images. Results Results revealed no support for sleep in increasing either GR or PS ability. Within the sleep group, there were no correlations between changes in PS ability and time spent in any sleep stage. Conclusion Previous studies that have found a role of sleep for PS ability has done so using larger manipulation of sleep. Based on the present study however, just a short daytime nap does not seem to have any effect on PS ability.
|
|
| 64. |
|
|
| 65. |
- Davidson, Per, et al.
(författare)
-
A more generalized fear response after a daytime nap
- 2018
-
Ingår i: Neurobiology of Learning and Memory. - : Elsevier BV. - 1074-7427 .- 1095-9564. ; 151, s. 18-27
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine how a daytime nap affected the consolidation of fear learning. Participants first underwent fear conditioning during which they were exposed to a large and a small circle. One of these was repeatedly paired with an electric shock (making it the CS+), whereas the other circle was never paired with the shock (the CS−). After a delay interval containing either a nap or wake, participants again viewed the CS+ and the CS− intermixed with eight novel circles that varied in size between the two stimuli seen before, as well as a blue triangle that served as a novel stimulus without prior fear relevance. We examined both fear retention (the difference between the CS+ and the CS−) and fear generalization (responses to the novel stimuli based on their similarity to the original CS+). Contrary to previous studies, results from the participants who acquired a differentiated fear response during the acquisition phase revealed that the wake group showed significantly larger skin conductance responses to the CS+ compared to the CS−, whereas no such difference was present in the sleep group. These results were not driven by differences in explicit memory or by differences in general reactivity. Analyzing responses to the novel stimuli revealed a tendency towards a more generalized response in the sleep group, with no differences between the CS+ and any other stimulus, whereas the wake group showed increased responses to the stimuli depending on their similarity to the original CS+. This effect was however only present when controlling for baseline differences in worry.
|
|
| 66. |
|
|
| 67. |
- Davidson, Per, et al.
(författare)
-
No effect of sleep on the generalization of fear learning
- 2014
-
Ingår i: Journal of Sleep Research. - : Wiley-Blackwell Publishing Ltd. - 1365-2869 .- 0962-1105. ; 23
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Sleep has been shown to be involved both in emotion regulation and in the active processing of information. We combined these two concepts and tested if sleep affected the generalization of fear learning. Methods: In a fear conditioning paradigm, participants were shown images of a small and a big circle where one of them was paired with an aversive sound, making it the CS+. Fear was measured with skin conductance responses. Participants were then randomly divided into a sleep or a wake group. The sleep group took a 2 h nap while the wake group rested for 2 h. Participants were then exposed to the two circles seen before, combined with 8 novel circles that gradually varied in size from the small one to the big one. We looked at how many circle sizes away from the CS+ that participants still exhibited a fear response, and if this differed between the sleep and the wake group. Results: We found no effect of sleep on the slope of the generalization across the different circles. There was a main effect of circle size, F(1,25) = 10.42, P = 0.01, but no main effect of sleep/wake, F (1,25) = 0.40, P = 0.54, and no interaction between sleep/wake X circle size, F(1,25) = 0.62, P = 0.44. Conclusions: The fear conditioning manipulation worked, with a gradual increase of fear depending on the stimuli’s similarity to the CS+. However, there was no effect of sleep or wake, which could possibly be explained by that just a 2 h nap not being a sufficient sleep manipulation to detect any differences.
|
|
| 68. |
- Davidson, Per, et al.
(författare)
-
Sleep and the generalization of fear learning
- 2016
-
Ingår i: Journal of Sleep Research. - : Wiley-Blackwell Publishing Ltd. - 0962-1105 .- 1365-2869. ; 25:1, s. 88-95
-
Tidskriftsartikel (refereegranskat)abstract
- Fear conditioning is an important survival mechanism, as is the ability to generalize learned fear responses to stimuli that are similar to the original conditioned stimulus. Overgeneralization of fear learning, prominent in many anxiety disorders, is however highly maladaptive. Because sleep is involved in the consolidation of fear learning, and in active processing of information, the present study explored the effect of sleep on generalization of fear learning. Participants watched a random sequence of pictures of a small and a big circle, one of them coupled with an aversive sound. Then, after a delay period containing either a nap or wake, generalization was examined as participants watched the two circles again, together with eight novel circles that gradually varied in size between the former two. Results showed that the fear response increased as a function of similarity to the conditioned response. However, there was no difference in the degree of generalization between the sleep and the wake group.
|
|
| 69. |
|
|
| 70. |
- Donia, Marco, et al.
(författare)
-
Acquired immune resistance follows complete tumor regression without loss of target antigens or IFNγ signaling
- 2017
-
Ingår i: Cancer Research. - 0008-5472. ; 77:17, s. 4562-4566
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8þ T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I–related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted.
|
|
