| 1. |
|
|
| 2. |
|
|
| 3. |
- Baptista, Marisa A. P., et al.
(författare)
-
Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8(+) T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFN gamma-producing CD8(+) T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8(+) T cells at the expense of CD4(+) T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8(+) T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells.
|
|
| 4. |
- Jenkins, Andrew J., et al.
(författare)
-
The Ehrenfest method with fully quantum nuclear motion (Qu-Eh) : Application to charge migration in radical cations
- 2018
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 149:9
-
Tidskriftsartikel (refereegranskat)abstract
- An algorithm is described for quantum dynamics where an Ehrenfest potential is combined with fully quantum nuclear motion (Quantum-Ehrenfest, Qu-Eh). The method is related to the single-set variational multi-configuration Gaussian approach (vMCG) but has the advantage that only a single quantum chemistry computation is required at each time step since there is only a single time-dependent potential surface. Also shown is the close relationship to the “exact factorization method.” The quantum Ehrenfest method is compared with vMCG for study of electron dynamics in a modified bismethylene-adamantane cation system. Illustrative examples of electron-nuclear dynamics are presented for a distorted allene system and for HCCI+ where one has a degenerate Π system.
|
|
| 5. |
- Schuette, Moritz, et al.
(författare)
-
Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
|
|
| 6. |
- Spinlove, K. E., et al.
(författare)
-
Using quantum dynamics simulations to follow the competition between charge migration and charge transfer in polyatomic molecules
- 2017
-
Ingår i: Chemical Physics. - : ELSEVIER SCIENCE BV. - 0301-0104 .- 1873-4421. ; 482, s. 52-63
-
Tidskriftsartikel (refereegranskat)abstract
- Recent work, particularly by Cederbaum and co-workers, has identified the phenomenon of charge migration, whereby charge flow occurs over a static molecular framework after the creation of an electronic wavepacket. In a real molecule, this charge migration competes with charge transfer, whereby the nuclear motion also results in the re-distribution of charge. To study this competition, quantum dynamics simulations need to be performed. To break the exponential scaling of standard grid-based algorithms, approximate methods need to be developed that are efficient yet able to follow the coupled electronic-nuclear motion of these systems. Using a simple model Hamiltonian based on the ionisation of the allene molecule, the performance of different methods based on Gaussian Wavepackets is demonstrated.
|
|
| 7. |
|
|
| 8. |
- Mansouri, Kamel, et al.
(författare)
-
CERAPP : Collaborative Estrogen Receptor Activity Prediction Project
- 2016
-
Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:7, s. 1023-1033
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. OBJECTIVES: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. METHODS: CERAPP combined multiple models developed in collaboration with 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were evaluated on a set of 7,522 chemicals curated from the literature. To overcome the limitations of single models, a consensus was built by weighting models on scores based on their evaluated accuracies. RESULTS: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing.CONCLUSION: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches. This concept will be applied in future projects related to other end points.
|
|
| 9. |
- Stjerna, Marie-Louise, et al.
(författare)
-
Risk as a relational phenomenon : a cross-cultural analysis of parents’ understandings of child food allergy and risk management
- 2017
-
Ingår i: Health, Risk and Society. - : Routledge. - 1369-8575 .- 1469-8331. ; 19:7-8, s. 351-368
-
Tidskriftsartikel (refereegranskat)abstract
- Western culture can be seen as permeated by risk-consciousness. In particular, parents are under scrutiny in their roles as risk managers. In this article, we address parental experiences of children more at risk than other children, children with food allergy, and the management of allergy risk in everyday life. Drawing on a notion of risk as ‘situated’ in local everyday life, we argue that a further exploration of parental understandings of child food allergy risk would benefit from an analysis of studies across different local contexts. In this article, we draw on a secondary qualitative cross-cultural analysis of interview data from several studies of parents in Sweden and Scotland through 2006–2010, which focused on parents’ understandings of the nature of food allergy and the children’s management of the allergy risk. We found some common themes in the different data sets. First, parents depicted food allergy as life-threatening, a ‘death risk’ lurking in the background, more or less constantly present in different everyday situations, amounting to an existential condition in parenting. Second, they talked about food allergy risk as a relational phenomenon, meaning that the risk emerged in the encounter between the young person’s individual competence to manage allergy risk and the understandings of allergy risk in others – thus depending on contexts and interaction between several actors. Finally, the analysis showed that unpredictability and risk in constant flux are the prominent aspects of living with food allergy. We also discussed the ways risk and trust are related, as well as how the involvement of others can be seen as both a risk and a safeguard.
|
|
| 10. |
- Wu, Guorong, et al.
(författare)
-
Excited state non-adiabatic dynamics of N-methylpyrrole : A time-resolved photoelectron spectroscopy and quantum dynamics study
- 2016
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 144:1
-
Tidskriftsartikel (refereegranskat)abstract
- The dynamics of N-methylpyrrole following excitation at wavelengths in the range 241.5-217.0 nm were studied using a combination of time-resolved photoelectron spectroscopy (TRPES), ab initio quantum dynamics calculations using the multi-layer multi-configurational time-dependent Hartree method, as well as high-level photoionization cross section calculations. Excitation at 241.5 and 236.2 nm results in population of the A(2)(pi sigma*) state, in agreement with previous studies. Excitation at 217.0 nm prepares the previously neglected B-1(pi 3p(y)) Rydberg state, followed by prompt internal conversion to the A(2)(pi sigma*) state. In contrast with the photoinduced dynamics of pyrrole, the lifetime of the wavepacket in the A(2)(pi sigma*) state was found to vary with excitation wavelength, decreasing by one order of magnitude upon tuning from 241.5 nm to 236.2 nm and by more than three orders of magnitude when excited at 217.0 nm. The order of magnitude difference in lifetimes measured at the longer excitation wavelengths is attributed to vibrational excitation in the A(2)(pi sigma*) state, facilitating wavepacket motion around the potential barrier in the N-CH3 dissociation coordinate.
|
|
