| 1. |
- Cao, Danfeng, et al.
(författare)
-
Tunable electroactive biomimetic bone-like surfaces for bone marrow-on-chips
- 2023
-
Ingår i: 2023 IEEE BIOSENSORS CONFERENCE, BIOSENSORS. - : IEEE. - 9798350346046 - 9798350346114
-
Konferensbidrag (refereegranskat)abstract
- Electro-stimulation is an effective way to manipulate the presentation of bio-factors at the materials interface. This study aimed to develop electrochemically-modified trabecular bone-like surfaces for manipulation of mesenchymal and hematopoietic cells. The electroactive surface was based on the conducting polymer polypyrrole for dynamic control of the presentation and mineralisation of chondrocyte-derived plasma membrane nanofragments (PMNFs) covalently immobilized on the surface. Electrochemical redox switching resulted in the PMNF-based formation of bone minerals with different morphologies, which further demonstrated to have distinct effects on the survival of mouse bone marrow-derived mesenchymal and hematopoietic cell populations cultured on the surface. This tunable electroactive surface could be a valuable tool for dynamically sensing and/or controlling stem cell functions in more suitable biomimetic microenvironments housing a stem cell niche.
|
|
| 2. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
-
Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
-
Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
|
|
| 3. |
- Hultin, Hanna
(författare)
-
Generative models of limit order books
- 2021
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis generative models in machine learning are developed with the overall aim to improve methods for algorithmic trading on high-frequency electronic exchanges based on limit order books. The thesis consists of two papers.In the first paper a new generative model for the dynamic evolution of a limit order book, based on recurrent neural networks, is developed. The model captures the full dynamics of the limit order book by decomposing the probability of each transition of the limit order book into a product of conditional probabilities of order type, price level, order size, and time delay. Each such conditional probability is modeled by a recurrent neural network. In addition several evaluation metrics for generative models related to order execution are introduced. The generative model is successfully trained to fit both synthetic data generated by a Markov model and real data from the Nasdaq Stockholm exchange.The second paper explores reinforcement learning methods to find optimal policies for trading execution in Markovian models. A number of different approaches are implemented and compared, including a baseline time-weighted average price (TWAP) strategy, tabular Q-learning, and deep Q-learning based on predefined features as well as with the entire limit order book as input. The results indicate that it is preferable to use deep Q-learning with the entire limit order book as input to design efficient execution policies. In order to improve the understanding of the decisions taken by the agent, the learned action-value function for the deep Q-learning with predefined features is visualized as a function of selected features.
|
|
| 4. |
- Khalilian, Maryam, et al.
(författare)
-
Dislocation-Free and Atomically Flat GaN Hexagonal Microprisms for Device Applications
- 2020
-
Ingår i: Small. - : Wiley-VCH Verlag. - 1613-6810 .- 1613-6829. ; 16:30
-
Tidskriftsartikel (refereegranskat)abstract
- III-nitrides are considered the material of choice for light-emitting diodes (LEDs) and lasers in the visible to ultraviolet spectral range. The development is hampered by lattice and thermal mismatch between the nitride layers and the growth substrate leading to high dislocation densities. In order to overcome the issue, efforts have gone into selected area growth of nanowires (NWs), using their small footprint in the substrate to grow virtually dislocation-free material. Their geometry is defined by six tall side-facets and a pointed tip which limits the design of optoelectronic devices. Growth of dislocation-free and atomically smooth 3D hexagonal GaN micro-prisms with a flat, micrometer-sized top-surface is presented. These self-forming structures are suitable for optical devices such as low-loss optical cavities for high-efficiency LEDs. The structures are made by annealing GaN NWs with a thick radial shell, reforming them into hexagonal flat-top prisms with six equivalents either m- or s-facets depending on the initial heights of the top pyramid and m-facets of the NWs. This shape is kinetically controlled and the reformation can be explained with a phenomenological model based on Wulff construction that have been developed. It is expected that the results will inspire further research into micron-sized III-nitride-based devices. © 2020 The Authors.
|
|
| 5. |
- Rörby, Emma, et al.
(författare)
-
Multiplexed single-cell mass cytometry reveals distinct inhibitory effects on intracellular phosphoproteins by midostaurin in combination with chemotherapy in AML cells
- 2021
-
Ingår i: Experimental Hematology & Oncology. - : BMC. - 2162-3619. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundFms-related tyrosine kinase 3 (FLT3) receptor serves as a prognostic marker and therapeutic target in acute myeloid leukemia (AML). Approximately one-third of AML patients carry mutation in FLT3, associated with unfavourable prognosis and high relapse rate. The multitargeted kinase inhibitor midostaurin (PKC412) in combination with standard chemotherapy (daunorubicin and cytarabine) was recently shown to increase overall survival of AML patients. For that reason, PKC412 has been approved for treatment of AML patients with FLT3-mutation. PKC412 synergizes with standard chemotherapy, but the mechanism involved is not fully understood and the risk of relapse is still highly problematic.MethodsBy utilizing the unique nature of mass cytometry for single cell multiparameter analysis, we have explored the proteomic effect and intracellular signaling response in individual leukemic cells with internal tandem duplication of FLT3 (FLT3-ITD) after midostaurin treatment in combination with daunorubicin or cytarabine.ResultsWe have identified a synergistic inhibition of intracellular signaling proteins after PKC412 treatment in combination with daunorubicin. In contrast, cytarabine antagonized phosphorylation inhibition of PKC412. Moreover, we found elevated levels of FLT3 surface expression after cytarabine treatment. Interestingly, the surface localization of FLT3 receptor increased in vivo on the blast cell population of two AML patients during day 3 of induction therapy (daunorubicin; once/day from day 1-3 and cytarabine; twice/day from day 1-7). We found FLT3 receptor expression to correlate with intracellular cytarabine (AraC) response. AML cell line cultured with AraC with or without PKC412 had an antagonizing phosphorylation inhibition of pAKT (p=0.042 and 0.0261, respectively) and pERK1/2 (0.0134 and 0.0096, respectively) in FLT3(high) compared to FLT3(low) expressing cell populations.ConclusionsOur study provides insights into how conventional chemotherapy affects protein phosphorylation of vital signaling proteins in human leukemia cells. The results presented here support further investigation of novel strategies to treat FLT3-mutated AML patients with PKC412 in combination with chemotherapy agents and the potential development of novel treatment strategies.
|
|
