RAS mutations are among the most prevalent oncogenic drivers in cancers. RAS proteins propagate signals only when associated with cellular membranes as a consequence of lipid modifications that ...impact their trafficking. Here, we discovered that RAB27B, a RAB family small GTPase, controlled NRAS palmitoylation and trafficking to the plasma membrane, a localization required for activation. Our proteomic studies revealed RAB27B upregulation in CBL- or JAK2-mutated myeloid malignancies, and its expression correlated with poor prognosis in acute myeloid leukemias (AMLs). RAB27B depletion inhibited the growth of CBL-deficient or NRAS-mutant cell lines. Strikingly, Rab27b deficiency in mice abrogated mutant but not WT NRAS-mediated progenitor cell growth, ERK signaling, and NRAS palmitoylation. Further, Rab27b deficiency significantly reduced myelomonocytic leukemia development in vivo. Mechanistically, RAB27B interacted with ZDHHC9, a palmitoyl acyltransferase that modifies NRAS. By regulating palmitoylation, RAB27B controlled c-RAF/MEK/ERK signaling and affected leukemia development. Importantly, RAB27B depletion in primary human AMLs inhibited oncogenic NRAS signaling and leukemic growth. We further revealed a significant correlation between RAB27B expression and sensitivity to MEK inhibitors in AMLs. Thus, our studies presented a link between RAB proteins and fundamental aspects of RAS posttranslational modification and trafficking, highlighting future therapeutic strategies for RAS-driven cancers.
We investigated how human proislet peptide (HIP) regulates differentiation of human fetus-derived pancreatic progenitor cells (HFPPCs) and explored the potential link between HIP signaling and the ...menin pathway, which is key to regulating pancreatic islet differentiation. The data show that HIP promoted expression of proislet transcription factors (TFs), including PDX-1, MAFA, and NKX6.1, as well as other maturation markers of β-cells, such as insulin, GLUT2, KIR6.2, SUR1, and VDCC. Moreover, HIP increased insulin content and promoted the ability of HFPPCs to normalize blood glucose in diabetic mice. HIP inhibited the TF FOXO1 by increasing AKT-mediated phosphorylation. HIP-induced repression of FOXO1 suppressed menin expression, leading to reducing menin binding to the promoter of the three key proislet TFs, decreasing recruitment of H3K9 methyltransferase SUV39H1, and thus reducing repressive H3K9me3 at the promoter. These coordinated actions lead to increased expression of the proislet TFs, resulting in induction of HFPPC differentiation. Consistently, constitutive activation of FOXO1 blocks HIP-induced transcription of these TFs. Together, these studies unravel the crucial role of the HIP/AKT/FOXO/menin axis in epigenetically controlling expression of proislet TFs, regulating the differentiation of HFPPCs, and normalizing blood glucose in diabetic mice.
Abstract
In order to solve the problem of the traditional Canny edge detection algorithm, due to the inaccurate selection of the threshold value, the recognition rate is low in the fish edge ...detection process. This paper proposes an adaptive Canny edge detection algorithm. The image enhancement is carried out by using automatic color scale, and the optimal recognition of underwater fish target is completed. The experimental results show that the improved algorithm and edge contour are more complete, which proves the effectiveness of the fish density recognition method.
Oxidation of petroleum-based byproduct dicyclopentadiene derived diformyltricyclodecanes (DFTD) to dicarboxyltriclodecanesacids (DCTDA) was conducted under catalyst-free and ultra-low temperature ...conditions with O2 as oxidant. In the perspective of industry process, oxygen pressure and contents, solvent and raw material initial concentrations were screened to evaluate their influence on DCTDA generation. Results indicate that DFTD oxidation can occur rather easily under no-catalyst and ultra-low temperature conditions with O2 as oxidant. Oxygen content and pressure had positive effect on DCTDA production, γ-valerolactone (GVL) behaved best on DFTD generation in dynamics, while methanol could be used as a protective solvent to preserve DFTD. Besides, the existence of water in solvent was not beneficial to DCTDA production because of poor DFTD compatibility with water. The mechanisms of O2 and solvent influence on DCTDA generation were discussed. Meanwhile, the oxidation route of DFTD–Intermediate–DCTDA was proposed. The present work exhibits the valued potential of DFTD, which will have a positive effect on high added value of petroleum based by-products.
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Structural thermal deformation is an important factor that affects the performance of MEMS devices. The mismatch of thermal expansion coefficient (CTE) between different materials is a major source. ...For single center supported MEMS devices, expansion difference between device and the substrate leads to the out of plane thermal deformation of the structure, resulting in the performance deterioration. This paper presents a thermal deformation suppression chip (TDSC) for single center supporting MEMS devices. It is fabricated by the MEMS process and consists of an upper plate and a lower plate. The materials of the upper and lower plates are the same as those of the device substrate and structure respectively. The principle of TDSC to suppress thermal deformation is material symmetry design. Single center anchor is adapted to connect the upper and lower plates. Besides, the center anchor can also isolate the packaging stress generated between TDSC and package shell. In this paper, center supported quadruple mass gyroscope (CSQMG) is used to verify the effect of TDSC. Finite element simulation shows that the thermal deformation suppression effect is determined by radius of TDSC anchor, and the deformation can be suppressed to 0. The conclusion is confirmed by White light interference experiment. In addition, the experiment results also show that the TDSC effectively reduce the thermal out-of-plane deformation after packaging, which is even better than that of the gyroscope without any packaging. It is further proved that TDSC can also significantly improve the temperature performance of the CSQMG. Moreover, the TDSC has simple process steps, small chip area, low cost, and is suitable for various MEMS devices with single center anchor.
High-precision microelectromechanical system (MEMS) gyroscopes are significant in many applications. Bias instability (BI) is an important parameter that indicates the performance of a MEMS gyroscope ...and is affected by the 1/
noise of the MEMS resonator and readout circuit. Since the bandgap reference (BGR) is an important block in the readout circuit, reducing its 1/
noise is key to improving a gyroscope's BI. In a traditional BGR, the error amplifier is applied to provide a virtual short-circuit point, but it introduces the main low-frequency noise sources. This paper proposes an ultralow 1/
noise BGR by removing the error amplifier and applying an optimized circuit topology. In addition, a simplified but accurate noise model of the proposed BGR is obtained to optimize the BGR's output noise performance. To verify this design, the proposed BGR has been implemented in a 180 nm CMOS process with a chip area of 545 × 423 μm. The experimental results show that the BGR's output integrated noise from 0.1 to 10 Hz is 0.82 μV and the thermal noise is 35 nV/√Hz. Furthermore, bias stability tests of the MEMS gyroscope fabricated in our laboratory with the proposed BGR and some commercial BGRs are carried out. Statistical results show that reducing the BGR's 1/f noise can nearly linearly improve the gyroscope's BI.
In order to have a better evaluation process to determine the experts weight in the evaluation process, this paper proposes a new expert weight calculation method. First of all to establish electric ...propulsion simulation evaluation system, use AHP method to calculate the initial weight principle of index. Then use the D-S to fuse the experts evaluation information, combined with the weight vector, structure of the expert weight objective function, and through the genetic algorithm to solve the expert weight size. According to the expert weight vector, calculate the final weight vector. Not only can it greatly make use of the experts information and analyze the similarity of information effectively but also it calculates the weight of each expert objectively. At the same time the evaluation subjective factors have been reduced by the adoption of this new method.
Ship information system: overview and research trends Liu, Sheng; Xing, Bowen; Li, Bing ...
International journal of naval architecture and ocean engineering,
September 2014, 2014-9-1, 2014-09-00, 2014-09-01, 2014-09, Letnik:
6, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Ship Information Systems (SISs) have been one of the main research focuses in ship design and become a multidisciplinary area. With these growing research trends, it is important to consolidate the ...latest knowledge and information to keep up with the research needs. In this paper, the SIS and its different forms are introduced and discussed. The beginning of this paper discusses the history and evolution of SIS. The next part of this paper focuses on different fields and research areas such as networking technology, information fusion, information decision, message display, ship control in real-time SISs. A Semi-Physical Simulation Platform (SPSIM) designed for SIS research and its running effect through a new Fuzzy-PID fusion algorithm are introduced in this paper then. A brief literature survey and possible future direction concerning each topic is included.
In the past few years, pre-trained language models (PTLMs) have brought significant improvements to target sentiment classification (TSC). Existing PTLM-based models can be categorized into two ...groups: 1) fine-tuning-based models that adopt PTLM as the context encoder; 2) prompting-based models that transfer the classification task to the text/word generation task. Despite the improvements achieved by these models, we argue that they have their respective limitations. For fine-tuning-based models, they cannot make the best use of the PTLMs’ strong language modeling ability because the pre-train task and downstream fine-tuning task are not consistent. For prompting-based models, although they can sufficiently leverage the language modeling ability, it is hard to explicitly model the target-context interactions, which are widely realized as a crucial point of this task. In this paper, we present a new perspective of leveraging PTLM for TSC: simultaneously leveraging the merits of both language modeling and explicit target-context interactions via contextual target attributes. Specifically, we design the domain- and target-constrained cloze test, which can leverage the PTLMs’ strong language modeling ability to generate the given target’s attributes pertaining to the review context. The attributes contain the background and property information of the target, which can help to enrich the semantics of the review context and the target. To exploit the attributes for tackling TSC, we first construct a heterogeneous information graph by treating the attributes as nodes and combining them with (1) the syntax graph automatically produced by the off-the-shelf dependency parser and (2) the semantics graph of the review context, which is derived from the self-attention mechanism. Then we propose a heterogeneous information gated graph convolutional network to model the interactions among the attribute information, the syntactic information, and the contextual information. The experimental results on three benchmark datasets demonstrate the superiority of our model, which achieves new state-of-the-art performance.
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