How does experience change firms' foreign investment decisions to non-market events?

We examine how experience with two types of non-market risks (e.g., natural disasters and armed conflicts) changes foreign direct investment (FDI) decisions. Extending research on organizational learning and FDI, we hypothesize that the greater the experience with recent, frequent and high-intensity risk, the more likely that experience can moderate the relationship between non-market risks and firm international expansion. Given a sample of 625 Fortune Global 500 firms and their investments in 117 countries between 1999 and 2008, we find that experience with recent, frequent, and high-intensity risk can change a firm?s FDI decision from risk avoidance to risk management

PRESSURE-IMPULSE DIAGRAM OF MULTI-LAYERED ALUMINUM FOAM PANELS UNDER BLAST PRESSURE

Anti-terror engineering has increasing demand in construction industry, but basis of design (BOD) is normally not clear for designers. Hardening of structures has limitations when design loads are not defined. Sacrificial foam claddings are one of the most efficient methods to protect blast pressure. Aluminum foam can have designed yield strength according to relative density and mitigate the blast pressure below a target transmitted pressure. In this paper, multi-layered aluminum foam panels were proposed to enhance the pressure mitigation by increasing effective range of blast pressure. Through explicit finite element analyses, the performance of blast pressure mitigation by the multi-layered foams was evaluated. Pressure-impulse diagrams for the foam panels were developed from extensive analyses. Combination of low and high strength foams showed better applicability in wider range of blast pressure

A New Paradigm Unifying the Concepts in Particle Abrasion and Breakage

This study introduces a new paradigm that unifies abrasion and breakage concepts, allowing for a holistic understanding of the comminution process. The significance of this paradigm lies in its ability to present both abrasion and breakage in a single big picture because both processes can co-occur under loading as particles are subjected to friction as well as collision. A comprehensive descriptive framework is employed to this end, which operates in a log-transformed surface-area-to-volume ratio ($A/V$) and volume ($V$) space. This space facilitates a holistic characterization of the four-dimensional particle geometry features, i.e., volume ($V$), surface area ($A$), size ($D$), and shape (${\beta}$). Consequently, this approach enables to systematically relate the co-occurring abrasion and breakage process to co-evolving particle shape and size. Transformative concepts including the breakage line, sphere line, and average shape-conserving line are introduced to describe the limit states and a special comminution process. This approach also uncovers a self-similar nature in evolving particle geometry during comminution, which will be a significant discovery for the granular materials research community given the most fundamental properties observed in natural phenomena.Comment: 10 pages, 5 figures; No difference from arXiv:2306.04635v1 except the first page stam

Functional roles of heterogeneous nuclear ribonucleoprotein K in post-transcriptional gene regulation

Since it is widely accepted that the accumulation of genetic alterations is the main cause of cancer, understanding how cancer-associated genes are regulated is crucial to the development of cancertherapies. As one of important RNA-binding proteins (RBPs), heterogeneous nuclearribonucleoprotein K (hnRNPK), is known to regulate the expression of target genes involved in various pathways, such as transcription, splicing, and translation. HnRNPK is also closely associated with cancer progression, including the acquisition of metastatic potential. At the post-transcriptional level, gene expression is determined by competitive or cooperative interactions betweentrans-acting factors including RBPs and non-coding RNAs (ncRNAs) which are capable of binding to cis-elements in target genes. In this review, we discuss the roles of hnRNPK in post-transcriptional gene regulation. The regulation of cancer-associated genes (oncogenes and tumor suppressors) via crosstalk between hnRNPK and ncRNAs such as microRNAs and long ncRNAs is described in detail. This review highlights how hnRNPK may be a promising targetforthe development of cancertherapeutics

IRF8 Governs Expression of Genes Involved in Innate and Adaptive Immunity in Human and Mouse Germinal Center B Cells

IRF8 (Interferon Regulatory Factor 8) is a transcription factor expressed throughout B cell differentiation except for mature plasma cells. Previous studies showed it is part of the transcriptional network governing B cell specification and commitment in the bone marrow, regulates the distribution of mature B cells into the splenic follicular and marginal zone compartments, and is expressed at highest levels in germinal center (GC) B cells. Here, we investigated the transcriptional programs and signaling pathways affected by IRF8 in human and mouse GC B cells as defined by ChIP-chip analyses and transcriptional profiling. We show that IRF8 binds a large number of genes by targeting two distinct motifs, half of which are also targeted by PU.1. Over 70% of the binding sites localized to proximal and distal promoter regions with ∼25% being intragenic. There was significant enrichment among targeted genes for those involved in innate and adaptive immunity with over 30% previously defined as interferon stimulated genes. We also showed that IRF8 target genes contributes to multiple aspects of the biology of mature B cells including critical components of the molecular crosstalk among GC B cells, T follicular helper cells, and follicular dendritic cells

Significance of EpCAM and TROP2 expression in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The tumor-associated calcium signal transducer (<it>TACSTD</it>) genes, originally designated epithelial cell adhesion molecule (EpCAM) and TROP2, represent true oncogenes. Little is known about EpCAM and TROP2 gene expression in non-small cell lung carcinoma (NSCLC). This study evaluated EpCAM and TROP2 protein expression and clinicopathologic significance in cases of NSCLC.</p> <p>Methods</p> <p>Tissue microarray blocks acquired from 164 cases of NSCLC, including 100 cases of adenocarcinoma (AdC) and 64 of squamous cell carcinoma (SCC), were examined by immunohistochemical staining for EpCAM, and TROP2. The results were correlated with clinicopathologic data.</p> <p>Results</p> <p>EpCAM and TROP2 were significantly overexpressed in SCC than in AdC (<it>P </it>< 0.01). In AdC, EpCAM overexpression was closely related to sex, histologic grade, pathologic T stage, pathologic N stage, and TNM stage, and TROP2 overexpression was only related to histologic grade (<it>P </it>< 0.05, respectively). In SCC, correlations were evident between EpCAM overexpression and TNM stage (<it>P </it>= 0.01), and between TROP2 overexpression and pathologic T stage (<it>P </it>= 0.02). EpCAM overexpression showed no significance with overall survival in AdC and SCC patients. However, TROP2 overexpression in AdC had a positive influence on overall survival (<it>P </it>= 0.02) and disease-free survival (<it>P </it>= 0.03). In particular, AdC patients with stage II or III showed better overall survival (<it>P </it>= 0.05) and disease-free survival (<it>P </it>= 0.04).</p> <p>Conclusions</p> <p>While EpCAM and TROP2 show weak and non-complete membranous staining in normal bronchial epithelium and pneumocyte, their complete membranous expression in carcinoma suggests their role in carcinogenesis. EpCAM and TROP2 were more frequently overexpressed in SCC. EpCAM overexpression had no prognostic value in this study, but TROP2 overexpression showed better survival in AdC patients and might be a better prognostic marker in advanced stage AdC.</p

Nitric oxide directly activates calcium-activated potassium channels from rat brain reconstituted into planar lipid bilayer

AbstractUsing the planar lipid bilayer technique, we tested whether NO directly activates calcium-activated potassium (Maxi-K) channels isolated from rat brain. We used streptozotocin (STZ) as NO donor, and the NO release was controlled with light. In the presence of 100–800 μM STZ, the Maxi-K channel activity increased up to 3-fold within several tens of seconds after the light was on, and reversed to the control level several minutes after shutting off the light. Similar activation was observed with other NO donors such as S-nitroso-N-acetylpenicillamine and sodium nitroprusside. The degree of activity increase was dependent upon the initial open probability (Pinit). When the Pinit was lower, the activity increase was greater. These results demonstrate that NO can directly affect the Maxi-K channel activity, and suggest that the Maxi-K channel might be one of the physiological targets of NO in brain

The Transcription Factor NRF2 Has Epigenetic Regulatory Functions Modulating HDACs, DNMTs, and miRNA Biogenesis

The epigenetic regulation of gene expression is a complex and tightly regulated process that defines cellular identity and is associated with health and disease processes. Oxidative stress is capable of inducing epigenetic modifications. The transcription factor NRF2 (nuclear factor erythroid-derived 2-like 2) is a master regulator of cellular homeostasis, regulating genes bearing antioxidant response elements (AREs) in their promoters. Here, we report the identification of ARE sequences in the promoter regions of genes encoding several epigenetic regulatory factors, such as histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and proteins involved in microRNA biogenesis. In this research, we study this possibility by integrating bioinformatic, genetic, pharmacological, and molecular approaches. We found ARE sequences in the promoter regions of genes encoding several HDACs, DNMTs, and proteins involved in miRNA biogenesis. We confirmed that NRF2 regulates the production of these genes by studying NRF2-deficient cells and cells treated with dimethyl fumarate (DMF), an inducer of the NRF2 signaling pathway. In addition, we found that NRF2 could be involved in the target RNA-dependent microRNA degradation (TDMD) of miR-155-5p through its interaction with Nfe2l2 mRNA. Our data indicate that NRF2 has an epigenetic regulatory function, complementing its traditional function and expanding the regulatory dimensions that should be considered when developing NRF2-centered therapeutic strategiesThis work was supported MINECO (SAF2016-76520-R to I.L-B., PID2019-105600RB-I00 to I.L-B) and ISCiii CIBERNED (CB06/05/0089 to I.L.-B.