164 research outputs found
Neural network optimal control for nonlinear system based on zero-sum differential game
summary:In this paper, for a class of the complex nonlinear system control problems, based on the two-person zero-sum game theory, combined with the idea of approximate dynamic programming(ADP), the constrained optimization control problem is solved for the nonlinear systems with unknown system functions and unknown time-varying disturbances. In order to obtain the approximate optimal solution of the zero-sum game, the multilayer neural network is used to fit the evaluation network, the execution network and the disturbance network of ADP respectively. The Lyapunov stability theory is used to prove the uniform convergence, and the system control output converges to the neighborhood of the target reference value. Finally, the simulation example verifies the effectiveness of the algorithm
14-3-3σ regulation of and interaction with YAP1 in acquired gemcitabine resistance via promoting ribonucleotide reductase expression
Gemcitabine is an important anticancer therapeutics approved for treatment of several human cancers including locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Its clinical effectiveness, however, is hindered by existence of intrinsic and development of acquired resistances. Previously, it was found that 14-3-3σ expression associates with poor clinical outcome of PDAC patients. It was also found that 14-3-3σ expression is up-regulated in gemcitabine resistant PDAC cells and contributes to the acquired gemcitabine resistance. In this study, we investigated the molecular mechanism of 14-3-3σ function in gemcitabine resistance and found that 14-3-3σ up-regulates YAP1 expression and then binds to YAP1 to inhibit gemcitabine-induced caspase 8 activation and apoptosis. 14-3-3σ association with YAP1 up-regulates the expression of ribonucleotide reductase M1 and M2, which may mediate 14-3-3σ/YAP1 function in the acquired gemcitabine resistance. These findings suggest a possible role of YAP1 signaling in gemcitabine resistance
Reversible epigenetic regulation of 14-3-3σ expression in acquired gemcitabine resistance by uhrf1 and DNA methyltransferase 1
Although gemcitabine is the most commonly used drug for treating pancreatic cancers, acquired gemcitabine resistance in a substantial number of patients appears to hinder its effectiveness in successful treatment of this dreadful disease. To understand acquired gemcitabine resistance, we generated a gemcitabine-resistant pancreatic cancer cell line using stepwise selection and found that, in addition to the known mechanisms of upregulated expression of ribonucleotide reductase, 14-3-3σ expression is dramatically upregulated, and that 14-3-3σ overexpression contributes to the acquired resistance to gemcitabine and cross-resistance to cytarabine. We also found that the increased 14-3-3σ expression in the gemcitabine-resistant cells is due to demethylation of the 14-3-3σ gene during gemcitabine selection, which could be partially reversed with removal of the gemcitabine selection pressure. Most importantly, the reversible methylation/demethylation of the 14-3-3σ gene appears to be carried out by DNA methyltransferase 1 under regulation by Uhrf1. These findings suggest that the epigenetic regulation of gene expression may play an important role in gemcitabine resistance, and that epigenetic modification is reversible in response to gemcitabine treatment
Improved Decoding of Staircase Codes: The Soft-aided Bit-marking (SABM) Algorithm
Staircase codes (SCCs) are typically decoded using iterative bounded-distance
decoding (BDD) and hard decisions. In this paper, a novel decoding algorithm is
proposed, which partially uses soft information from the channel. The proposed
algorithm is based on marking certain number of highly reliable and highly
unreliable bits. These marked bits are used to improve the
miscorrection-detection capability of the SCC decoder and the error-correcting
capability of BDD. For SCCs with -error-correcting
Bose-Chaudhuri-Hocquenghem component codes, our algorithm improves upon
standard SCC decoding by up to ~dB at a bit-error rate (BER) of
. The proposed algorithm is shown to achieve almost half of the gain
achievable by an idealized decoder with this structure. A complexity analysis
based on the number of additional calls to the component BDD decoder shows that
the relative complexity increase is only around at a BER of .
This additional complexity is shown to decrease as the channel quality
improves. Our algorithm is also extended (with minor modifications) to product
codes. The simulation results show that in this case, the algorithm offers
gains of up to ~dB at a BER of .Comment: 10 pages, 12 figure
Determinants of price fluctuations in the electricity market: a study with PCA and NARDL models
In the modern electricity markets, negative prices and spike prices coexist as a pair of opposite economic phenomena. This study investigates how these extreme prices play as the determinants to drive price fluctuations in the electricity market. We construct a two-stage analysis including a principal component analysis (PCA) and a nonlinear autoregressive distributed lags model (NARDL). We apply this analytical method to the wholesale Pennsylvania, New Jersey and Maryland (PJM) electricity market. We find that according to PCA, in the individual transmission lines, spike prices are determinants with largest explanatory power to the variation of prices, while according to NARDL, from the standpoint of the overall market, negative prices have a larger potential effect on both the real-time market and the forward market. These results are valuable and contributive to managers and operators in the electricity markets for policy decision making
An Innovative Approach for Gob-Side Entry Retaining With Thick and Hard Roof: A Case Study
An innovative roadway layout in a Chinese colliery based on gob-side entry retaining (GER) with thick and hard roof (THR) was introduced. Suspended roof is left with a large area in GER with THR, which leads to large area roof weighting (LARW). LARW for GER with THR and mechanism of shallow-hole blasting to force roof caving in GER were expounded. Key parameters of shallow-hole blasting to force roof caving are proposed. LS-DYNA3D was used to validate the rationality of those key parameters, and UDEC was used to discuss and validate shallow-hole blasting to force roof-caving effect by contrast to the model without blasting and the model with shallow-hole blasting. Moreover, shallow-hole blasting technology to force roof caving for GER with THR was carried out in the Chinese colliery as a case study. Field test indicates that shallow-hole blasting technology effectively controls ground deformation of GER with THR and prevents LARW
PointMatch: A Consistency Training Framework for Weakly Supervised Semantic Segmentation of 3D Point Clouds
Semantic segmentation of point cloud usually relies on dense annotation that
is exhausting and costly, so it attracts wide attention to investigate
solutions for the weakly supervised scheme with only sparse points annotated.
Existing works start from the given labels and propagate them to highly-related
but unlabeled points, with the guidance of data, e.g. intra-point relation.
However, it suffers from (i) the inefficient exploitation of data information,
and (ii) the strong reliance on labels thus is easily suppressed when given
much fewer annotations. Therefore, we propose a novel framework, PointMatch,
that stands on both data and label, by applying consistency regularization to
sufficiently probe information from data itself and leveraging weak labels as
assistance at the same time. By doing so, meaningful information can be learned
from both data and label for better representation learning, which also enables
the model more robust to the extent of label sparsity. Simple yet effective,
the proposed PointMatch achieves the state-of-the-art performance under various
weakly-supervised schemes on both ScanNet-v2 and S3DIS datasets, especially on
the settings with extremely sparse labels, e.g. surpassing SQN by 21.2% and
17.2% on the 0.01% and 0.1% setting of ScanNet-v2, respectively.Comment: 8 pages, 3 figure
14-3-3σ Contributes to Radioresistance by Regulating DNA Repair and Cell Cycle via PARP1 and CHK2
14-3-3σ has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3σ contributes to these resistances via inhibiting apoptosis and arresting cells in G2–M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3σ causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2–M phase following DNA-damaging treatments. We showed that 14-3-3σ contributed to ionizing radiation (IR) resistance by arresting cancer cells in G2–M phase following IR and by increasing non-homologous end joining (NHEJ) repair of the IR-induced DNA double strand breaks (DSB). The increased NHEJ repair activity was due to 14-3-3σ–mediated upregulation of PARP1 expression that promoted the recruitment of DNA-PKcs to the DNA damage sites for repair of DSBs. On the other hand, the increased G2–M arrest following IR was due to 14-3-3σ–induced Chk2 expression.
Implications: These findings reveal an important molecular basis of 14-3-3σ function in cancer cell resistance to chemo/radiation therapy and in poor prognosis of human cancers
A Novel Two Mode-Acting Inhibitor of ABCG2-Mediated Multidrug Transport and Resistance in Cancer Chemotherapy
Multidrug resistance (MDR) is a major problem in successful treatment of cancers. Human ABCG2, a member of the ATP-binding cassette transporter superfamily, plays a key role in MDR and an important role in protecting cancer stem cells. Knockout of ABCG2 had no apparent adverse effect on the mice. Thus, ABCG2 is an ideal target for development of chemo-sensitizing agents for better treatment of drug resistant cancers and helping eradicate cancer stem cells.Using rational screening of representatives from a chemical compound library, we found a novel inhibitor of ABCG2, PZ-39 (N-(4-chlorophenyl)-2-[(6-{[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]amino}-1,3-benzothiazol-2-yl)sulfanyl]acetamide), that has two modes of actions by inhibiting ABCG2 activity and by accelerating its lysosome-dependent degradation. PZ-39 has no effect on ABCB1 and ABCC1-mediated drug efflux, resistance, and their expression, indicating that it may be specific to ABCG2. Analyses of its analogue compounds showed that the pharmacophore of PZ-39 is benzothiazole linked to a triazine ring backbone.Unlike any previously known ABCG2 transporter inhibitors, PZ-39 has a novel two-mode action by inhibiting ABCG2 activity, an acute effect, and by accelerating lysosome-dependent degradation, a chronic effect. PZ-39 is potentially a valuable probe for structure-function studies of ABCG2 and a lead compound for developing therapeutics targeting ABCG2-mediated MDR in combinational cancer chemotherapy
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Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation.
Ischemic injury to white matter tracts is increasingly recognized to play a key role in age-related cognitive decline, vascular dementia, and Alzheimer's disease. Knowledge of the effects of ischemic axonal injury on cortical neurons is limited yet critical to identifying molecular pathways that link neurodegeneration and ischemia. Using a mouse model of subcortical white matter ischemic injury coupled with retrograde neuronal tracing, we employed magnetic affinity cell sorting with fluorescence-activated cell sorting to capture layer-specific cortical neurons and performed RNA-sequencing. With this approach, we identified a role for microtubule reorganization within stroke-injured neurons acting through the regulation of tau. We find that subcortical stroke-injured Layer 5 cortical neurons up-regulate the microtubule affinity-regulating kinase, Mark4, in response to axonal injury. Stroke-induced up-regulation of Mark4 is associated with selective remodeling of the apical dendrite after stroke and the phosphorylation of tau in vivo. In a cell-based tau biosensor assay, Mark4 promotes the aggregation of human tau in vitro. Increased expression of Mark4 after ischemic axonal injury in deep layer cortical neurons provides new evidence for synergism between axonal and neurodegenerative pathologies by priming of tau phosphorylation and aggregation
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