How do Internet applications affect process innovation in Chinese manufacturing companies?

This study distinguishes between two dimensions of firm process innovation, namely, quantity and quality, and uses data from the World Bank’s China Manufacturing Firm Survey to analyse the differential impact of Internet applications on the quantity and quality of process innovation and their mechanisms of action. Internet applications have a significant facilitating effect on the quantity and quality of process innovation. However, from the perspective of the average marginal effect, the facilitating effect of Internet applications on the quantity of process innovation is greater than that on the quality of process innovation. Further analysing firm size, industry, ownership, and regional heterogeneity shows that in terms of the quantity of process innovation, Internet applications have a greater impact on small- and medium-sized firms, labourintensive firms, non-state-owned firms, and eastern firms. As for the quality of process innovation, Internet applications have a stronger promoting effect on large firms, technology-intensive firms, and state-owned firms. The mechanism test reveals that open innovation and informatisation capability play a mediating role in the influence of a firm’s Internet applications on process innovation. This study provides micro-empirical evidence for firms’ Internet applications to promote process innovation and policy insights into China’s manufacturing transformation and upgrading

TreeCSS: An Efficient Framework for Vertical Federated Learning

Vertical federated learning (VFL) considers the case that the features of data samples are partitioned over different participants. VFL consists of two main steps, i.e., identify the common data samples for all participants (alignment) and train model using the aligned data samples (training). However, when there are many participants and data samples, both alignment and training become slow. As such, we propose TreeCSS as an efficient VFL framework that accelerates the two main steps. In particular, for sample alignment, we design an efficient multi-party private set intersection (MPSI) protocol called Tree-MPSI, which adopts a tree-based structure and a data-volume-aware scheduling strategy to parallelize alignment among the participants. As model training time scales with the number of data samples, we conduct coreset selection (CSS) to choose some representative data samples for training. Our CCS method adopts a clustering-based scheme for security and generality, which first clusters the features locally on each participant and then merges the local clustering results to select representative samples. In addition, we weight the samples according to their distances to the centroids to reflect their importance to model training. We evaluate the effectiveness and efficiency of our TreeCSS framework on various datasets and models. The results show that compared with vanilla VFL, TreeCSS accelerates training by up to 2.93x and achieves comparable model accuracy.Comment: 16 pages, 7 figure

Reconstruction of one-dimensional chaotic maps from sequences of probability density functions

In many practical situations, it is impossible to measure the individual trajectories generated by an unknown chaotic system, but we can observe the evolution of probability density functions generated by such a system. The paper proposes for the first time a matrix-based approach to solve the generalized inverse Frobenius–Perron problem, that is, to reconstruct an unknown one-dimensional chaotic transformation, based on a temporal sequence of probability density functions generated by the transformation. Numerical examples are used to demonstrate the applicability of the proposed approach and evaluate its robustness with respect to constantly applied stochastic perturbations

Measuring charge distribution of molecular cations by atomic Coulomb probe microscope

Imaging the charge distributions and structures of molecules and clusters will promote the understanding of the dynamics of the quantum system. Here, we report a method by using an Ar atom as a tip to probe the charge distributions of benzene (Bz) cations in gas phase. Remarkably, the measured charge distributions of Bz cation (QH =0.204,QC=-0.037)and dication (QH =0.248,QC=0.0853)agree well with the calculated Mulliken distributions,and the structures of Bz dimer is reconstructed by using the measured charge distributions. The structures of two Bz dimer isomers (T-shaped and PD isomers) can be resolved from the measured inter-molecular potential V(R) between two Bz ions, and the structures of Bz dimer agree well with the theoretical predictions.Comment: 7 pages, 3 Figure

Mediator Kinase Inhibitors Suppress Triple-Negative Breast Cancer Growth and Extend Tumor Suppression by mTOR and AKT Inhibitors

Triple-negative breast cancers (TNBC) are treated primarily by chemotherapy and lack clinically validated therapeutic targets. In particular, inhibitors of the PI3K/AKT/mTOR pathway, abnormally activated in many breast cancers, failed to achieve clinical efficacy in TNBC due to the development of adaptive drug resistance, which is largely driven by the transcriptomic plasticity of TNBC. Expression of CDK8/19 Mediator kinases that control transcriptional reprogramming correlates with relapse-free survival and treatment failure in breast cancer patients, including TNBC. We now investigated how CDK8/19 inhibitors affect the growth of TNBC tumors and their response to mTOR and AKT inhibitors. In contrast to the effects of most anticancer drugs, all the tested human TNBC models (including patient-derived xenografts) responded to CDK8/19 inhibitors in vivo even when they did not respond in vitro. Furthermore, CDK8/19 inhibition extended the host survival of established lung metastases in a murine TNBC model, where the primary tumors were not significantly affected. CDK8/19 inhibitors synergized with an mTORC1 inhibitor everolimus and a pan-AKT inhibitor capivasertib in vitro and strongly potentiated these drugs in long-term in vivo studies. Transcriptomic analysis of tumors that responded or became adapted to everolimus revealed that drug adaptation in vivo was associated with major transcriptional changes in both tumor and stromal cells. Combining everolimus with a CDK8/19 inhibitor counteracted many of these changes and induced combination-specific effects on the expression of multiple genes that affect tumor growth. These results warrant the exploration of CDK8/19 Mediator kinase inhibitors as a new type of drugs for TNBC therapy

CDK8 and CDK19: Positive Regulators of Signal-Induced Transcription and Negative Regulators of Mediator Complex Proteins

We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module associated with transcriptional Mediator complex and implicated in development and diseases. This analysis was performed using genetic modifications of CDK8 and CDK19, selective CDK8/19 small molecule kinase inhibitors and a potent CDK8/19 PROTAC degrader. CDK8/19 inhibition in cells exposed to serum or to agonists of NFκB or protein kinase C (PKC) reduced the induction of signal-responsive genes, indicating a pleiotropic role of Mediator kinases in signal-induced transcriptional reprogramming. CDK8/19 inhibition under basal conditions initially downregulated a small group of genes, most of which were inducible by serum or PKC stimulation. Prolonged CDK8/19 inhibition or mutagenesis upregulated a larger gene set, along with a post-transcriptional increase in the proteins comprising the core Mediator complex and its kinase module. Regulation of both RNA and protein expression required CDK8/19 kinase activities but both enzymes protected their binding partner cyclin C from proteolytic degradation in a kinase-independent manner. Analysis of isogenic cell populations expressing CDK8, CDK19 or their kinase-inactive mutants revealed that CDK8 and CDK19 have the same qualitative effects on protein phosphorylation and gene expression at the RNA and protein levels, whereas differential effects of CDK8 versus CDK19 knockouts were attributable to quantitative differences in their expression and activity rather than different functions

Mediator Kinase Inhibitors for Breast Cancer Therapy

Breast cancers (BrCa) that overexpress oncogenic tyrosine kinase receptor HER2 are treated with HER2-targeting antibodies (such as trastuzumab) or small-molecule kinase inhibitors (such as lapatinib). However, most patients with metastatic HER2+ BrCa have intrinsic resistance and nearly all eventually become resistant to HER2-targeting therapy. Resistance to HER2-targeting drugs frequently involves transcriptional reprogramming associated with constitutive activation of different signaling pathways. We have investigated the role of CDK8/19 Mediator kinase, a regulator of transcriptional reprogramming, in the response of HER2+ BrCa to HER2-targeting drugs. Selective CDK8/19 inhibitors (senexin B and SNX631) showed synergistic interactions with lapatinib and trastuzumab in a panel of HER2+ BrCa cell lines, overcoming and preventing resistance to HER2-targeting drugs. The synergistic effects were mediated in part through the PI3K/AKT/mTOR pathway and reduced by PI3K inhibition. Combination of HER2- and CDK8/19-targeting agents inhibited STAT1 and STAT3 phosphorylation at S727 and upregulated tumor suppressor BTG2. The growth of xenograft tumors formed by lapatinib-sensitive or resistant HER2+ breast cancer cells was partially inhibited by SNX631 alone and strongly suppressed by the combination of SNX631 and lapatinib, overcoming lapatinib resistance. These effects were associated with decreased tumor cell proliferation and altered recruitment of stromal components to the xenograft tumors. Triple negative breast cancer (TNBC) is the most aggressive subtype of all breast cancers, however, unlike other subtypes, which have relatively more treatment options, current treatments for TNBC are restricted and this scarcity of viable options is the key contributor to poorer prognosis. Despite early response, almost all the targeted drugs tested in TNBC eventually fail due to the development of resistance. Here we analyzed the effect of CDK8/19 inhibition on the outcome of treatment with mTORC1 inhibitor everolimus (RAD001), an approved drug for several cancers with mutations of PTEN or PI3KCA. In vivo treatment with everolimus in a TNBC xenograft model achieved remarkable tumor growth inhibition but all the tumors eventually developed resistance. However, the addition of a CDK8/19 inhibitor prevented the emergence of everolimus resistance in all the tumors. RNA-Seq analysis demonstrated that this effect was due to the prevention of transcriptional reprogramming associated with everolimus resistance in tumor cells. In summary, targeting CDK8/19 has exhibited potential clinical benefits, either as a single agent or in combination with lapatinib or everolimus, for HER2- positive and triple-negative breast cancers

Insight into Differential Responses of Upland and Paddy Rice to Drought Stress by Comparative Expression Profiling Analysis

Abstract: In this study, the drought responses of two genotypes, IRAT109 and Zhenshan 97 (ZS97), representing upland and paddy rice, respectively, were systematically compared at the morphological, physiological and transcriptional levels. IRAT109 has better performance in traits related to drought avoidance, such as leaf rolling, root volumes, the ratio of leaf water loss and relative conductivity. At the transcriptional level, more genes were induced by drought in IRAT109 at the early drought stage, but more genes had dynamic expression patterns in ZS97 at different drought degrees. Under drought conditions, more genes related to reproductive development and establishment of localization were repressed in IRAT109, but more genes involved in degradation of cellular components were induced in ZS97. By checking the expression patterns of 36 drought-responsive genes (located in 14 quantitative trail loci [QTL] intervals) in ZS97, IRAT109 and near isogenic lines (NILs) of the QTL intervals, we found that more than half of these genes had their expression patterns or expression levels changed in the NILs when compared to that in ZS97 or IRAT109. Our results may provide valuable information for dissecting the genetic bases of traits related to drought resistance, as well as fo