A deep neural network-based smart error measurement method for fiscal accounting data.

The error measurement of fiscal accounting data can effectively slow down the change of financial assets. Based on deep neural network theory, we constructed an error measurement model for fiscal and tax accounting data, and we analyzed the relevant theories of fiscal and tax performance evaluation. By establishing a batch evaluation index of finance and tax accounting, the model can monitor the changing trend of the error of urban finance and tax benchmark data scientifically and accurately, as well as solve the problem of high cost and delay in predicting the error of finance and tax benchmark data. In the simulation process, based on the panel data of credit unions, the entropy method and a deep neural network were used to measure the fiscal and tax performance of regional credit unions. In the example application, the model, combined with MATLAB programming, calculated the contribution rate of regional higher fiscal and tax accounting input to economic growth. The data show that the contribution rates of some fiscal and tax accounting input, commodity and service expenditure, other capital expenditure and capital construction expenditure to regional economic growth are 0.0060, 0.0924, 0.1696 and -0.0822, respectively. The results show that the proposed method can effectively map the relationships between variables.

Regional Lymph Node Metastasis and Axillary Surgery of Microinvasive Breast Cancer: A Population-Based Study.

Microinvasive breast cancer (MBC for short) is a rare entity with the decision of axillary surgery under debate in clinical practice. We aimed to unravel the lymph node metastasis (LNM) rate, axillary surgery, and prognosis of MBC based on 11,692 patients derived from the Surveillance Epidemiology and End Results (SEER) database between 2003 and 2015. In this retrospective study, 19.5% (2276/11,692) of patients received axillary lymph node dissection (ALND), 80.5% (9416/11,692) received non-ALND. In the total cohort, 10-year breast cancer-specific survival (BCSS) was 96.3%, and the LNM rate was 6.4% (754/11,692). Multivariate analyses showed that LNM had the strongest predictive weight (N3, HR 14.200, 95% CI 7.933−25.417; N2, HR 12.945, 95% CI 7.725−21.694; N1, HR 3.05, 95% CI 2.246−4.140, all p < 0.001). Kaplan−Meier analyses showed that ALND did not confer a survival benefit on 10-year BCS in patients with N0 (94.7% vs. 97.1%, p < 0.001) and in patients with 1−2 positive nodes (92.1% vs. 89.5%, p = 0.355), respectively, when compared to non-ALND. Our study demonstrated that the vast majority of MBC have a low LNM rate and excellent prognosis; patients with LNM showed poor prognosis. Assessment of lymph node status is necessary, and non-ALND surgery is required and sufficient for MBC with 0−2 positive nodes.

Heterogeneous irradiated-pristine polyethylene nanofiber junction as a high-performance solid-state thermal diode.

In this work, we demonstrate two types of heterogeneous irradiated-pristine polyethylene nanofiber junctions, 'heavily-irradiated-pristine' (HI-P) and 'lightly-irradiated-pristine' (LI-P) junctions, as high-performance solid-state thermal diodes. The HI-P junction rectifies heat flux in a single direction, while the LI-P junction shows dual-directional rectification under different working temperatures. We accurately model the phase transition of polyethylene nanofibers with a finite temperature range rather than a step function. The finite-temperature-range model suggests that the rectification factor increases with temperature bias and there is a minimum threshold of temperature bias for notable rectification. Besides, the finite-temperature-range model shows better prediction for the heat flow data from experiments, while the step function model tends to overestimate the rectification performance around the optimal length fraction of irradiation. Although both the models show that an optimal rectification occurs when the interface temperatures in the forward and the reverse biases are equal, the optimized rectification factor is determined by the temperature bias and the temperature range of phase transition. This work elucidates the influence of both the temperature bias and the temperature range of phase transition on thermal rectification performance, which could incredibly benefit the evaluation and design of thermal diodes.

Effects of fluidity and charge density on the morphology of a bicellar mixture - A SANS study.

The spontaneously formed structures of physiologically relevant lipid model membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) and 1,2-hexanoyl-sn-glycero-3-phosphocholine have been evaluated in depth using small angle neutron scattering. Although a common molar ratio of long- to short- chain phospholipids (~4) as reported in many bicellar mixtures was used, discoidal bicelles were not found as the major phase throughout the range of lipid concentration and temperature studied, indicating that the required condition for the formation of bicelle is the immiscibility between the long- and short- chain lipids, which were in the gel and Lα phases, respectively, in previous reports. In this study, all lipids are in the Lα phase. The characterization outcome suggests that the spontaneous structures tie strongly with the physical parameters of the system such as melting transition temperature of the long-chain lipid, total lipid concentration and charge density of the system. Multilamellar vesicles, unilamellar vesicles, ribbons and perforated lamellae can be obtained based on the analysis of the small angle neutron scattering results, leading to the construction of structural diagrams. This report provides the important map to choose suitable lipid systems for the structural study of membrane-associated proteins, design of theranostic nanocarriers or other related research fields.

Early prediction of the differentiation potential during the formation of human iPSC-derived embryoid bodies.

Induced pluripotent stem cells (iPSCs) show huge variations in their differentiation potential, even in the same condition. However, methods for predicting these differentiation tendencies, especially in the early stage of differentiation, are still scarce. This study aimed to establish a simple and practical system to predict the differentiation tendency of iPSC lines using embryoid bodies (EBs) with identified parameters in the early stage. We compared four human iPSC lines in terms of the morphology and maintenance of EBs and their gene expression levels of specific markers for three germ-layers. Furthermore, the differentiation potentials of these iPSC lines into melanocytes, which are ectoderm-derived cells, were also compared and correlated with the above parameters. The results showed that iPSC lines forming regular, smooth, and not cystic EBs, which could be maintained in culture for a relatively longer time, also expressed higher levels of ectoderm-specific markers and lower levels of mesoderm/endoderm markers. Additionally, these iPSC lines showed greater potential in melanocyte differentiation using EB-based protocol, and the induced melanocytes expressed melanocytic markers and presented characteristics that were similar to those of normal human melanocytes. By contrast, iPSC lines that formed cystic EBs with bright or dark cavities and expressed relatively lower levels of ectoderm-specific markers failed in the melanocyte differentiation. Collectively, the differentiation tendency of human iPSC lines may be predicted by specific parameters in the EB stage. The formation and maintenance of optimal EBs and the expression of germ layer-specific markers are particularly important and practical for the prediction assay in the early stage.

MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma.

Melanoma can be stratified into unique subtypes based on distinct pathologies. The acral/mucosal melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene receptor tyrosine kinase C-KIT, which drives tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has proven challenging, prompting us to investigate the downstream effectors of the C-KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins. Moreover, we developed an MNK1/2 inhibitor (SEL201), and found that SEL201-treated KIT-mutant melanoma cells had lower oncogenicity and reduced metastatic ability. Clinically, tumors from melanoma patients harboring KIT mutations displayed a marked increase in MNK1 and phospho-eIF4E. Thus, our studies indicate that blocking MNK1/2 exerts potent antimelanoma effects and support blocking MNK1/2 as a potential strategy to treat patients positive for KIT mutations.

mTORC1 and CK2 coordinate ternary and eIF4F complex assembly.

Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2ß phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling. Accordingly, eIF2ß mediates the effect of mTORC1 on protein synthesis and proliferation. In addition, we demonstrate a formerly undocumented role for CK2 in regulation of translation initiation, whereby CK2 stimulates phosphorylation of eIF2ß and simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway. These findings imply a previously unrecognized mode of translation regulation, whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell proliferation.

nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs.

The diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5' TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5' TOP motif but that 5' UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5' UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5' UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5' UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5' UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5' UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells.

Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes.

G-quadruplexes (G4) are extremely stable secondary structures forming stacks of guanine tetrads. DNA G4 structures have been extensively studied, however, less is known about G4 motifs in mRNAs, especially in their coding sequences. Herein, we show that Aven stimulates the mRNA translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine methylation-dependent manner. The Aven RGG/RG motif bound G4 structures within the coding regions of the MLL1 and MLL4 mRNAs increasing their polysomal association and translation, resulting in the induction of transcription of leukemic genes. The DHX36 RNA helicase associated with the Aven complex and was required for optimal translation of G4 mRNAs. Depletion of Aven led to a decrease in synthesis of MLL1 and MLL4 proteins resulting in reduced proliferation of leukemic cells. These findings identify an Aven-centered complex that stimulates the translation of G4 harboring mRNAs, thereby promoting survival of leukemic cells.