| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Lee, EF, et al.
(author)
-
BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival
- 2019
-
In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 10:5, s. 342-
-
Journal article (peer-reviewed)abstract
- Malignant melanoma is one of the most difficult cancers to treat due to its resistance to chemotherapy. Despite recent successes with BRAF inhibitors and immune checkpoint inhibitors, many patients do not respond or become resistant to these drugs. Hence, alternative treatments are still required. Due to the importance of the BCL-2-regulated apoptosis pathway in cancer development and drug resistance, it is of interest to establish which proteins are most important for melanoma cell survival, though the outcomes of previous studies have been conflicting. To conclusively address this question, we tested a panel of established and early passage patient-derived cell lines against several BH3-mimetic drugs designed to target individual or subsets of pro-survival BCL-2 proteins, alone and in combination, in both 2D and 3D cell cultures. None of the drugs demonstrated significant activity as single agents, though combinations targeting MCL-1 plus BCL-XL, and to a lesser extent BCL-2, showed considerable synergistic killing activity that was elicited via both BAX and BAK. Genetic deletion of BFL-1 in cell lines that express it at relatively high levels only had minor impact on BH3-mimetic drug sensitivity, suggesting it is not a critical pro-survival protein in melanoma. Combinations of MCL-1 inhibitors with BRAF inhibitors also caused only minimal additional melanoma cell killing over each drug alone, whilst combinations with the proteasome inhibitor bortezomib was more effective in multiple cell lines. Our data show for the first time that therapies targeting specific combinations of BCL-2 pro-survival proteins, namely MCL-1 plus BCL-XL and MCL-1 plus BCL-2, could have significant benefit for the treatment of melanoma.
|
|
| 7. |
|
|
| 8. |
- Andersson, M., et al.
(author)
-
Coupling of lattice boltzmann and volume of fluid approaches to study the droplet behavior at the gas diffusion layer/gas channel interface
- 2018. - 13
-
In: ECS Transactions. - : The Electrochemical Society. - 1938-6737 .- 1938-5862. - 9781607688600 ; 86, s. 329-336
-
Conference paper (peer-reviewed)abstract
- A typical polymer electrolyte fuel cell (PEFC) flow field consists of micro/minichannels. The continues removal of liquid water from the cathode channels is a critical topic, as water droplets forming in the channels may block the transport of gaseous oxygen to the active sites, which not only gives an uneven current distribution and substantial loss of performance, but also, increases degradation rates and unstable operation. Water generated by the electrochemical reactions condenses, depending on temperature mainly, into liquid form, potentially flooding various part of the PEFC. The aim of this work is to obtain an increased understanding of the droplet behavior at the gas diffusion layer (GDL) interface with the gas channels in PEFCs by the coupling of Lattice Boltzmann (LB) and Volume of Fluid (VOF) approaches. A multiscale environment is established with input parameters in the VOF model being extracted from in-house LB calculations. It is clear that the contact angle as well as the size of the liquid droplet vary with positions at the GDL surface, depending on the stochastic GDL geometry. A VOF model describing one straight channel with one gas inlet, one liquid inlet (at the GDL surface) and one two-phase outlet is employed.
|
|
| 9. |
|
|
| 10. |
- Zhang, Shidong, et al.
(author)
-
Simple and complex polymer electrolyte fuel cell stack models : A comparison
- 2018. - 13
-
In: ECS Transactions. - : The Electrochemical Society. - 1938-6737 .- 1938-5862. - 9781607685395 ; 86, s. 287-300
-
Conference paper (peer-reviewed)abstract
- In this paper, two distinct polymer electrolyte fuel cell stack models are constructed: a detailed numerical model (DNM) employing a fine-scale computational mesh and a coarse-mesh approach based on a distributed resistance analogy (DRA) where diffusion terms in the transport equations are replaced by rate terms. Both methods are applied to a 5-cell, high-temperature polymer electrolyte fuel cell stack with an active area of 200 cm2 per cell. The polarization curve and local current density distributions from both the DRA and DNM are compared with experimental data, finding good agreement. Temperature, pressure, Nernst potential, and species distributions are also exhibited. The DNM displays details of fine-scale local extrema not captured by the DRA; however, the latter requires orders of magnitude less computer processor power and memory for execution. Both methods provide much finer-scale results than present experimental techniques.
|
|
