Technology capacity, product position and firm’s competitiveness: an empirical analysis

Using firm-level data from a 2009 survey conducted in Suzhou City, Jiangsu Province, China, this paper examines impacts of technology capacity and value-chain position on firm’s product competitiveness. Both technology capacity and product competitiveness are self-assessed relative to other firms and products in the same industry. The position of value-chain is measured relative to if a firm is an original brand manufacturer or not. Our empirical results show that competitiveness rises with firm’s technology capacity and its position in the global value chain. This finding is consistent with the theoretical prediction. The paper also investigates determinants of technology capacity and value-chain position, including firm’s size, R&D spending, location dummies, education level of technical and management personnel, wages of technical and management personnel, and enterprise ownership. Bootstrapping, Probit, and linear probability regression models are employed.Technology Capacity; Original Brand Manufacturer; Competitiveness; Global Value Chain; Bootstrapping

The effects of inductive electric field on the spatial and temporal evolution of the inner magnetospheric ring current

Charged particles are observed to be injected into the inner magnetosphere from the plasma sheet and energized up to high energies over a short distance and time, during both geomagnetic storms and substorms. Numerous studies suggest that it is the short-duration and high-speed plasma flows, which are closely associated with the global effects of magnetic reconnection and inductive effects, rather than the slow and steady convection that control the earthward transport of plasma and magnetic flux from the magnetotail, especially during geomagnetic activities. In order to include the effect of the inductive electric field produced by the temporal change of magnetic field on the dynamics of ring current, we implemented both theoretical and numerical modifications to an inner magnetosphere kinetic model---Hot Electron-Ion Drift Integrator. New drift terms associated with the inductive electric field are incorporated into the calculation of bounce-averaged coefficients for the distribution function, and their numerical implementations and the associated effects on total drift and energization rate are discussed. Numerical simulations show that the local particle drifts are significantly altered by the presence of inductive electric fields, in addition to the changing magnetic gradient-curvature drift due to the distortion of the magnetic field, and at certain locations, the inductive drift dominates both the potential and the magnetic gradient-curvature drift. The presence of a self-consistent inductive electric field alters the overall particle trajectories, energization, and pitch angle, resulting in significant changes in the topology and the strength of the ring current

Regulation of Interleukin-10 Receptor Ubiquitination and Stability by Beta-TrCP-Containing Ubiquitin E3 Ligase

Interleukin-10 (IL-10) initiates potent anti-inflammatory effects via activating its cell surface receptor, composed of IL-10R1 and IL-10R2 subunits. The level of IL-10R1 is a major determinant of the cells' responsiveness to IL-10. Here, via a series of biochemical analyses using 293T cells reconstituted with IL-10R1, we identify the latter as a novel substrate of βTrCP-containing ubiquitin E3 ligase. Within the intracellular tail of IL-10R1, a canonical (318DpSGFGpS) and a slightly deviated (369DpSGICLQEP) βTrCP recognition motif can additively recruit βTrCP in a phosphorylation-dependent manner. βTrCP recruitment leads to ubiquitination, endocytosis and degradation of IL-10R1, subsequently reducing the cellular responsiveness to IL-10. Our study uncovers a novel negative regulatory mechanism that may potentially affect IL-10 function in target cells under physiological or pathological conditions

Technology capacity, product position and firm’s competitiveness: an empirical analysis

Using firm-level data from a 2009 survey conducted in Suzhou City, Jiangsu Province, China, this paper examines impacts of technology capacity and value-chain position on firm’s product competitiveness. Both technology capacity and product competitiveness are self-assessed relative to other firms and products in the same industry. The position of value-chain is measured relative to if a firm is an original brand manufacturer or not. Our empirical results show that competitiveness rises with firm’s technology capacity and its position in the global value chain. This finding is consistent with the theoretical prediction. The paper also investigates determinants of technology capacity and value-chain position, including firm’s size, R&D spending, location dummies, education level of technical and management personnel, wages of technical and management personnel, and enterprise ownership. Bootstrapping, Probit, and linear probability regression models are employed

Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis

Ligand-induced endocytosis and lysosomal degradation of cognate receptors regulate the extent of cell signaling. Along with linear endocytic motifs that recruit the adaptin protein complex 2 (AP2)–clathrin molecules, monoubiquitination of receptors has emerged as a major endocytic signal. By investigating ubiquitin-dependent lysosomal degradation of the interferon (IFN)-α/β receptor 1 (IFNAR1) subunit of the type I IFN receptor, we reveal that IFNAR1 is polyubiquitinated via both Lys48- and Lys63-linked chains. The SCFβTrcp (Skp1–Cullin1–F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro. Although either polyubiquitin linkage suffices for postinternalization sorting, both types of chains are necessary but not sufficient for robust IFNAR1 turnover and internalization. These processes also depend on the proximity of ubiquitin-acceptor lysines to a linear endocytic motif and on its integrity. Furthermore, ubiquitination of IFNAR1 promotes its interaction with the AP2 adaptin complex that is required for the robust internalization of IFNAR1, implicating cooperation between site-specific ubiquitination and the linear endocytic motif in regulating this process

Pathogen Recognition Receptor Signaling Accelerates Phosphorylation-Dependent Degradation of IFNAR1

An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays a central role in host's defenses. Activation of these cells through the stimulation of the pathogen-recognition receptors induces the production of a number of cytokines including Type I interferons (IFNs) that mediate the diverse mechanisms of innate immunity. Type I IFNs interact with the Type I IFN receptor, composed of IFNAR1 and IFNAR2 chains, to mount the host defense responses. However, at the same time, Type I IFNs elicit potent anti-proliferative and pro-apoptotic effects that could be detrimental for IFN-producing cells. Here, we report that the activation of p38 kinase in response to pathogen-recognition receptors stimulation results in a series of phosphorylation events within the IFNAR1 chain of the Type I IFN receptor. This phosphorylation promotes IFNAR1 ubiquitination and accelerates the proteolytic turnover of this receptor leading to an attenuation of Type I IFN signaling and the protection of activated dendritic cells from the cytotoxic effects of autocrine or paracrine Type I IFN. In this paper we discuss a potential role of this mechanism in regulating the processes of innate immunity

Regulation of lung elastin gene expression and fibroblast migration by elastase-released growth factors

Thesis (Ph.D.)--Boston UniversityPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [email protected]. Thank you.Degradation of elastin within alveolar walls is an important event in the development of pulmonary emphysema. Elastases release growth factors from extracellular matrices and interstitial cell surfaces, which can regulate the repair process. Brief treatment of matrix-laden rat pulmonary fibroblast cultures with porcine pancreatic elastase results in the release of soluble heparin-binding epidermal growth factor-like growth factor (HB-EGF) together with previously identified fibroblast growth factor-2 (FGF-2). In matrix-laden pulmonary fibroblasts, HB-EGF and two other EGF family ligands, i.e. EGF and transforming growth factor a, significantly down-regulate elastin mRNA via activation of the EGF receptor. HB-EGF treatment initiates a signaling pathway involving extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation and subsequent nuclear accumulation of Fra-1, which leads to inhibition of elastin gene transcription. Co-addition of HB-EGF and FGF-2 results in an additive inhibitory effect on elastin mRNA levels. The increased effect of HB-EGF and FGF-2 on elastin mRNA is associated with their additive actions on ERK1/2 activation, c-fos mRNA induction and Fra-1 nuclear accumulation. Further, HB-EGF induces FGF-2 mRNA and protein, suggesting a potential role of endogenous FGF-2 in mediating HB-EGF-dependent responses. Cell migration represents an important component of injury/repair. A chemotactic activity for pulmonary fibroblasts was identified within the elastase-released products. Characterization of this activity indicates that elastase-released FGF-2 is a major chemotactic component of the elastase digest. Furthermore, our data strongly suggest that the elastase digest contains another component(s) that potentiates the chemotactic activity of FGF-2. Collectively, the present study supports a model in which elastase-released growth factors and other components act in concert to regulate elastin gene expression and cell migration in injury/repair situations.2031-01-0

IL-6/ERK signaling pathway participates in type I IFN-programmed, unconventional M2-like macrophage polarization

Abstract Type I interferons (IFN-Is) have been harnessed for cancer therapies due to their immunostimulatory functions. However, certain tumor-tolerating activities by IFN-Is also exist, and may potentially thwart their therapeutic effects. In this respect, our previous studies have demonstrated a monocyte-orchestrated, IFN-I-to-IL-4 cytokine axis, which can subsequently drive M2-skewed pro-tumoral polarization of macrophages. Whether other IFN-dependent signals may also contribute to such an unconventional circumstance of M2-like macrophage skewing remain unexplored. Herein, we first unveil IL-6 as another ligand that participates in IFN-dependent induction of a typical M2 marker (ARG1) in transitional monocytes. Indeed, IL-6 significantly promotes IL-4-dependent induction of a major group of prominent M2 markers in mouse bone marrow-derived macrophages (BMDMs) and human peripheral blood-derived macrophages, while it alone does not engage marked increases of these markers. Such a pattern of regulation is confirmed globally by RNAseq analyses in BMDMs, which in turn suggests an association of IL-6-amplified subset of M2 genes with the ERK1/2 signaling pathway. Interestingly, pharmacological experiments establish the role of SHP2-ERK cascade in mediating IL-6’s enhancement effect on these M2 targets. Similar approaches also validate the involvement of IL-6/ERK signaling in promoting the IFN-dependent, unconventional M2-skewing phenotype in transitional monocytes. Furthermore, an inhibitor of ERK signaling cooperates with an IFN-I inducer to enable a greater antitumor effect, which correlates with suppression of treatment-elicited ARG1. The present work establishes a role of IL-6/ERK signaling in promoting M2-like macrophage polarization, and suggests this axis as a potential therapeutic target for combination with IFN-I-based cancer treatments

A New Mechanism for Early-Time Plasmaspheric Refilling: The Role of Charge Exchange Reactions in the Transport of Energy and Mass Throughout the Ring Current—Plasmasphere System

Cold H+ produced via charge exchange reactions between ring current ions and exospheric neutral hydrogen constitutes an additional source of cold plasma that further contributes to the plasmasphere and affects the plasma dynamics in the Earth’s magnetosphere system; however, its production and associated effects on the plasmasphere dynamics have not been fully assessed and quantified. In this study, we perform numerical simulations mimicking an idealized three-phase geomagnetic storm to investigate the role of heavy ion composition in the ring current (O+ vs. N+) and exospheric neutral hydrogen density in the production of cold H+ via charge exchange reactions. It is found that ring current heavy ions produce more than 50% of the total cold H+ via charge exchange reactions, and energetic N+ is more efficient in producing cold H+ via charge exchange reactions than O+. Furthermore, the density structure of the cold H+ is highly dependent on the mass of the parent ion; that is, cold H+ deriving from charge exchange reactions involving energetic O+ with neutral hydrogen, populates the lower L-shells, while cold H+ deriving from charge exchange reactions involving energetic N+ with neutral hydrogen populates the higher L-shells. In addition, the density of cold H+ produced via charge exchange reactions involving N+ can be peak at values up to one order of magnitude larger than the local plasmaspheric density, suggesting that solely considering the supply of cold plasma from the ionosphere to the plasmasphere can lead to a significant underestimation of plasmasphere density.Key PointsRing current heavy ions are responsible for the production of over 50% of the cold H+ population following a geomagnetic stormThe density of H+ produced via charge exchange reactions can be as high as ∼10 times the local plasmaspheric densityCold H+ production is limited by the abundance of heavy ions from the plasma sheet source; the exospheric structure does not play a rolePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175109/1/jgra57440_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175109/2/jgra57440.pd