R&D offshoring and technology learning in emerging economies: Firm-level evidence from the ICT industry

This paper studies the impact of the R&D offshoring of multinational enterprises on the firms in host emerging economies. We develop a two-stage non-cooperative game to analyze the strategic interaction between multinational and host country enterprises engaged in R&D investment. An empirical analysis of 12,309 manufacturing firms in the ICT industry in China shows that R&D offshoring has a positive effect on the intensity of the R&D of host country firms. However, the magnitude of the impact depends on both the technological and geographical distance between the multinational and host country firms. The policy implications of these findings are that the governments of host country should be cautious about allowing advanced multinational R&D investment in under-developed sectors, but they should encourage such investment in developed sectors; and that local governments should be involved in R&D policy making because the positive impact of multinational R&D offshoring diminishes as the geographical distance between the multinational and host country firms increases.Research and Development, Offshoring, Spillovers, Emerging Economies

Rescue of auditory function by a single Administration of AAV-TMPRSS3 Gene Therapy in Aged Mice of Human Recessive Deafness DFNB8

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3 injection in Tmprss3A306T/A306T mice of an average age of 18.5 months leads to sustained rescue of the auditory function to a level similar to wild-type mice. AAV2-hTMPRSS3 delivery rescues the hair cells and the spiral ganglions neurons. This study demonstrates successful gene therapy in an aged mouse model of human genetic deafness. It lays the foundation to develop AAV2-hTMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation

Genome-wide CRISPR/Cas9 screening for drug resistance in tumors

Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) screening is a simple screening method for locating loci under specific conditions, and it has been utilized in tumor drug resistance research for finding potential drug resistance-associated genes. This screening strategy has significant implications for further treatment of malignancies with acquired drug resistance. In recent years, studies involving genome-wide CRISPR/Cas9 screening have gradually increased. Here we review the recent application of genome-wide CRISPR/Cas9 screening for drug resistance, involving mitogen-activated protein kinase (MAPK) pathway inhibitors, poly (ADP-ribose) polymerase inhibitors (PARPi), alkylating agents, mitotic inhibitors, antimetabolites, immune checkpoint inhibitors (ICIs), and cyclin-dependent kinase inhibitors (CDKI). We summarize drug resistance pathways such as the KEAP1/Nrf2 pathway MAPK pathway, and NF-κB pathway. Also, we analyze the limitations and conditions for the application of genome-wide CRISPR/Cas9 screening techniques

Growth Mechanism of Siliceous Cement in Tight Sandstone and Its Influence on Reservoir Physical Properties

To investigate the effect of siliceous cementation on the densification of sandstone and the forming process of tight sandstone, based on cathodoluminescence, scanning electron microscopy and thin section analysis, the growth mechanism and characteristics of quartz particles in tight sandstone formations are explored. Meanwhile, combined with conventional core analysis and X-ray diffraction experiments, the factors affecting the crystallization of quartz particles, including the chlorite content, grain size and clay mineral, are analyzed, respectively. The entire siliceous cementation is divided into two processes. The first part is the process in which the weathered and rounded particles in the formation are restored to the hexagonal dipyramid crystal by siliceous cementation. The second part is the process of coaxial growth that the hexagonal dipyramid crystal continues to increase with the form of micro-quartz film. As siliceous cements continue to increase, the petrological characteristics of sandstones are constantly changing. The tight sandstone developed in the study area is composed of lithic sandstone and quartz lithic sandstone. Based on the analysis results, 2D and 3D evolution models are established for densification of two different lithic sandstones. When the content of siliceous cement in the study area is less than 17%, the porosity of tight sandstone increases with the increase of cement. When the content of cement is more than 17%, the porosity of tight sandstone is negatively correlated with the content of cement. When the cement content is greater than 10%, the reservoir permeability is negatively correlated with it. Furthermore, the particle size mainly affects the permeability of reservoir, and the particle size is negatively correlated with the permeability of tight sandstone. The most high-quality tight sandstone reservoir in the study area is in the first cementation stage when siliceous cements are distributed in porphyritic texture with the content of 10⁻15% and a grain size of 0.2⁻0.3 mm. In addition, the relatively high-quality reservoir is the one developing clay mineral film with a content of cementation about 5⁻12%