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- Blid, Jan, et al.
(författare)
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Lewis Acid Mediated [2,3]-Sigmatropic Rearrangement of Allylic alpha-Amino Amides
- 2004
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 69:9, s. 3043-3049
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Tidskriftsartikel (refereegranskat)abstract
- Boron trifluoride and BBr3 mediated [2,3]-sigmatropic rearrangements of allylic alpha-amino amides have been developed affording secondary amines in good yields. (E)-Crotyl and (E)-cinnamyl alpha-amino amides 2b and 2c exhibit excellent syn-diastereoselectivity upon rearrangement with either Lewis acid. The allylic amine 2a forms upon treatment with BF3 or BBr3 a five-membered heterocylic complex in which a single halide anion has been displaced by the carbonyl oxygen atom. The structures of the Lewis acid-amine complexes were elucidated using NMR spectroscopy. A plausible reaction mechanism, based on DFT calculations, is presented. Thus, BF3- or BBr3-complexed allylic amines 2 are shown to preferentially proceed, after deprotonation, via an endo transition state.
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| 4. |
- Sarha, Dhifaf, et al.
(författare)
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161533 TriKE stimulates NK-cell function to overcome myeloid-derived suppressor cells in MDS
- 2018
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Ingår i: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 2:12, s. 1459-1469
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Tidskriftsartikel (refereegranskat)abstract
- Myelodysplastic syndrome (MDS) is a clonal heterogeneous stem cell disorder driven by multiple genetic and epigenetic alterations resulting in ineffective hematopoiesis. MDS has a high frequency of immune suppressors, including myeloid-derived suppressor cells (MDSCs), that collectively result in a poor immune response. MDSCs in MDS patients express CD155 that ligates the T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and delivers an inhibitory signal to natural killer (NK) cells. To mediate a productive immune response against MDS, negative regulatory checkpoints, like TIGIT, expressed on MDS NK cells must be overcome. NK cells can be directed to lyse MDS cells by bispecific killer engagers (BiKEs) that ligate CD16 on NK cells and CD33 on MDS cells. However, such CD16 x CD33 (1633) BiKEs do not induce the proliferative response in MDS NK cells needed to sustain their function. Here, we show that the addition of an NK stimulatory cytokine, interleukin-15 (IL-15), into the BiKE platform leads to productive IL-15 signaling without TIGIT upregulation on NK cells from MDS patients. Lower TIGIT expression allowed NK cells to resist MDSC inhibition. When compared with 1633 BiKE, 161533 trispecific killer engager (TriKE)-treated NK cells demonstrated superior killing kinetics associated with increased STAT5 phosphorylation. Furthermore, 161533 TriKE-treated MDS NK cells had higher proliferation and enhanced NK-cell function than 1633 BiKE-treated cells without the IL-15 linker. Collectively, our data demonstrate novel characteristics of the 161533 TriKE that support its application as an immunotherapeutic agent for MDS patients.
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| 5. |
- Schmid, Peter J., et al.
(författare)
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Analysis of Fluid Systems : Stability, Receptivity, Sensitivity
- 2014
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Ingår i: Applied Mechanics Review. - : ASME International. - 0003-6900 .- 1088-8535 .- 2379-0407. ; 66:2, s. 024803-
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Forskningsöversikt (refereegranskat)abstract
- This article presents techniques for the analysis of fluid systems. It adopts an optimization-based point of view, formulating common concepts such as stability and receptivity in terms of a cost functional to be optimized subject to constraints given by the governing equations. This approach differs significantly from eigenvalue-based methods that cover the time-asymptotic limit for stability problems or the resonant limit for receptivity problems. Formal substitution of the solution operator for linear time-invariant systems results in the matrix exponential norm and the resolvent norm as measures to assess the optimal response to initial conditions or external harmonic forcing. The optimization-based approach can be extended by introducing adjoint variables that enforce governing equations and constraints. This step allows the analysis of far more general fluid systems, such as time-varying and nonlinear flows, and the investigation of wavemaker regions, structural sensitivities, and passive control strategies.
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| 6. |
- Wang, Fei, et al.
(författare)
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Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-beta, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia.
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| 8. |
- Yajnanarayana, Vijaya, et al.
(författare)
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Optimal Scheduling for Interference Mitigation by Range Information
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This paper describes several algorithms for generating an optimal schedule for multiple access on a shared channel by utilizing range information in a fully connected network. We also provide detailed analysis for the proposed algorithms in terms of their complexity, convergence, and effect of non-idealities in the network. The performance of the proposed schemes are compared with non-aided methods to quantify the benefits of using the range information in the communication. We argue that the proposed techniques yield significant benefits as the number of nodes in the network increases. We provide simulation results in support of the claim. The proposed methods indicate that the throughput can be increased on average by 3-10 times for typical network configurations.
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