| 1. |
- Keller, Magdalena, et al.
(författare)
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Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth
- 2023
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : BioMed Central (BMC). - 1756-9966. ; 42
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intrinsic or acquired resistance to HER2-targeted therapy is often a problem when small molecule tyrosine kinase inhibitors or antibodies are used to treat patients with HER2 positive breast cancer. Therefore, the identification of new targets and therapies for this patient group is warranted. Activated choline metabolism, characterized by elevated levels of choline-containing compounds, has been previously reported in breast cancer. The glycerophosphodiesterase EDI3 (GPCPD1), which hydrolyses glycerophosphocholine to choline and glycerol-3-phosphate, directly influences choline and phospholipid metabolism, and has been linked to cancer-relevant phenotypes in vitro. While the importance of choline metabolism has been addressed in breast cancer, the role of EDI3 in this cancer type has not been explored.Methods: EDI3 mRNA and protein expression in human breast cancer tissue were investigated using publicly-available Affymetrix gene expression microarray datasets (n = 540) and with immunohistochemistry on a tissue microarray (n = 265), respectively. A panel of breast cancer cell lines of different molecular subtypes were used to investigate expression and activity of EDI3 in vitro. To determine whether EDI3 expression is regulated by HER2 signalling, the effect of pharmacological inhibition and siRNA silencing of HER2, as well as the influence of inhibiting key components of signalling cascades downstream of HER2 were studied. Finally, the influence of silencing and pharmacologically inhibiting EDI3 on viability was investigated in vitro and on tumour growth in vivo.Results: In the present study, we show that EDI3 expression is highest in ER-HER2 + human breast tumours, and both expression and activity were also highest in ER-HER2 + breast cancer cell lines. Silencing HER2 using siRNA, as well as inhibiting HER2 signalling with lapatinib decreased EDI3 expression. Pathways downstream of PI3K/Akt/mTOR and GSK3 beta, and transcription factors, including HIF1 alpha, CREB and STAT3 were identified as relevant in regulating EDI3 expression. Silencing EDI3 preferentially decreased cell viability in the ER-HER2 + cells. Furthermore, silencing or pharmacologically inhibiting EDI3 using dipyridamole in ER-HER2 + cells resistant to HER2-targeted therapy decreased cell viability in vitro and tumour growth in vivo.Conclusions: Our results indicate that EDI3 may be a potential novel therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2 + breast cancer that should be further explored.
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| 2. |
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| 3. |
- Aalbers, Jelle, et al.
(författare)
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Solar neutrino detection sensitivity in DARWIN via electron scattering
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:12
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Tidskriftsartikel (refereegranskat)abstract
- We detail the sensitivity of the proposed liquid xenon DARWIN observatory to solar neutrinos via elastic electron scattering. We find that DARWIN will have the potential to measure the fluxes of five solar neutrino components: pp, 7Be, 13N, 15O and pep. The precision of the 13N, 15O and pep components is hindered by the double-beta decay of 136Xe and, thus, would benefit from a depleted target. A high-statistics observation of pp neutrinos would allow us to infer the values of the electroweak mixing angle, sin2 theta w, and the electron-type neutrino survival probability, Pee, in the electron recoil energy region from a few keV up to 200 keV for the first time, with relative precision of 5% and 4%, respectively, with 10 live years of data and a 30 tonne fiducial volume. An observation of pp and 7Be neutrinos would constrain the neutrino-inferred solar luminosity down to 0.2%. A combination of all flux measurements would distinguish between the high- (GS98) and low-metallicity (AGS09) solar models with 2.1-2.5 sigma significance, independent of external measurements from other experiments or a measurement of 8B neutrinos through coherent elastic neutrino-nucleus scattering in DARWIN. Finally, we demonstrate that with a depleted target DARWIN may be sensitive to the neutrino capture process of 131Xe.
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| 4. |
- Avdic, Kenan, et al.
(författare)
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Pipelined parallel sorting on the Intel SCC
- 2011
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Ingår i: Fourth Swedish Workshop on Multi-Core Computing MCC-2011. - Linköping : Linköping University. ; , s. 96-101
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The Single-Chip Cloud Computer (SCC) is an experimental processor created by Intel Labs. It comprises 48 Intel-IA32 cores linked by an on-chip high performance mesh network, as well as four DDR3 memory controllers to access an off-chip main memory. We investigate the adaptation of sorting onto SCC as an algorithm engineering problem. We argue that a combination of pipelined mergesort and sample sort will fit best to SCC's architecture. We also provide a mapping based on integer linear programming to address load balancing and latency considerations. We describe a prototype implementation of our proposai together with preliminary runtime measurements, that indicate the usefulness of this approach. As mergesort can be considered as a representative of the class of streaming applications, the techniques deveioped here should also apply to the other problems in this class, such as many applications for parallel embedded systems, i.e. MPSoC.
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| 5. |
- Brenner, Jürgen, et al.
(författare)
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Executing PRAM Programs on GPUs
- 2012
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Ingår i: Procedia Computer Science. - : Elsevier. - 1877-0509. ; 9, s. 1799-1806
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Tidskriftsartikel (refereegranskat)abstract
- We present a framework to transform PRAM programs from the PRAM programming language Fork to CUDA C, so that they can be compiled and executed on a Graphics Processor (GPU). This allows to explore parallel algorithmics on a scale beyond toy problems, to which the previous, sequential PRAM simulator restricted practical use. We explain the design decisions and evaluate a prototype implementation consisting of a runtime library and a set of rules to transform simple Fork programs which we for now apply by hand. The resulting CUDA code is almost 100 times faster than the previous simulator for compiled Fork programs and allows to handle larger data sizes. Compared to a sequential program for the same problem, the GPU code might be faster or slower, depending on the Fork program structure, i.e. on the overhead incurred. We also give an outlook how future GPUs might notably reduce the overhead.
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| 6. |
- Cichowski, Patrick, et al.
(författare)
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Energy-efficient Mapping of Task Collections onto Manycore Processors
- 2013
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Ingår i: Proceedings of MULTIPROG'13 workshop at HiPEAC'13.
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Konferensbidrag (refereegranskat)abstract
- Streaming applications consist of a number of tasks that all run concurrently, and that process data at certain rates. On manycore processors, the tasks of the streaming application must be mapped onto the cores. While load balancing of such applications has been considered, especially in the MPSoC community, we investigate energy-efficient mapping of such task collections onto manycore processors. We first derive rules that guide the mapping process and show that as long as dynamic power consumption dominates static power consumption, the latter can be ignored and the problem reduces to load balancing. When however, as expected in the coming years, static power consumption will be a notable fraction of total power consumption, then an energy-efficient mapping must take it into account, e.g. by temporary shutdown of cores or by restricting the number of cores. We validate our findings with synthetic and real-world applications on the Intel SCC manycore processor.
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| 7. |
- Cichowski, Patrick, et al.
(författare)
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Modelling Power Consumption of the Intel SCC
- 2012
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Ingår i: Proceedings of the 6th Many-core Applications Research Community (MARC) Symposium. - : HAL Archives Ouvertes. - 9782725700168
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Konferensbidrag (refereegranskat)abstract
- The Intel SCC manycore processor supports energy-efficient computing by dynamic voltage and frequency scaling of cores on a fine-grained level. In order to enable the use of that feature in application-level energy optimizations, we report on experiments to measure power consumption in different situations. We process those measurements by a least-squares error analysis to derive the parameters of popular models for power consumption which are used on an algorithmic level. Thus, we provide a link between the worlds of hardware and high-level algorithmics.
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| 8. |
- Ernstsson, August, 1992-, et al.
(författare)
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A Deterministic Portable Parallel Pseudo-Random Number Generator for Pattern-Based Programming of Heterogeneous Parallel Systems
- 2022
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Ingår i: International journal of parallel programming. - : Springer / Plenum. - 0885-7458 .- 1573-7640. ; 50, s. 319-340
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Tidskriftsartikel (refereegranskat)abstract
- SkePU is a pattern-based high-level programming model for transparent program execution on heterogeneous parallel computing systems. A key feature of SkePU is that, in general, the selection of the execution platform for a skeleton-based function call need not be determined statically. On single-node systems, SkePU can select among CPU, multithreaded CPU, single or multi-GPU execution. Many scientific applications use pseudo-random number generators (PRNGs) as part of the computation. In the interest of correctness and debugging, deterministic parallel execution is a desirable property, which however requires a deterministically parallelized pseudo-random number generator. We present the API and implementation of a deterministic, portable parallel PRNG extension to SkePU that is scalable by design and exhibits the same behavior regardless where and with how many resources it is executed. We evaluate it with four probabilistic applications and show that the PRNG enables scalability on both multi-core CPU and GPU resources, and hence supports the universal portability of SkePU code even in the presence of PRNG calls, while source code complexity is reduced.
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| 9. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
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