International Licensing and R&D Subsidy

R&D rivalry and optimal R&D policies are investigated in an asymmetric four-stage game that involves international licensing. It is found that a government’s R&D policy crucially depends on its domestic firm’s bargaining power over the licensing gain. When the firm’s bargaining power is greater than one half, the government subsidizes its home firm’s R&D investment, while imposes a tax if the firm’s bargaining power is less than one half. Additionally, this result does not depend on the status of the firm (the licensor or the licensee). Finally, the effects of two different licensing contracts (fixedfee v.s. royalty per unit) on governments’ optimal R&D policies are investigated. ZUSAMMENFASSUNG - (Internationale Lizenzierungen und F&E Beihilfen) Der Beitrag beschäftigt sich mit Innovationswettbewerb und der Rolle von nationaler Politik im Falle von internationalen Lizenzierungspraktiken. In einem mehrstufigen Spiel werden die Anreizmechanismen untersucht. Es stellt sich heraus, daß die Verhandlungsstärke der nationalen Unternehmen im Lizenzierungsmarkt eine wichtige Rolle spielen. So erfolgt aus nationaler Sicht eine Subvention (Besteuerung) von F&EInvestitionen immer dann, wenn die Verhandlungsmacht groß (klein) ist. Darüber hinaus untersucht der Beitrag die Konsequenzen unterschiedlicher Lizenzierungspraktiken auf die optimale nationale F&E-Politik.International Licensing; R&D Subsidy; R&D Investment

International licensing and R&D subsidy

"R&D rivalry and optimal R&D policies are investigated in an asymmetric four-stage game that involves international licensing. It is found that a government's R&D policy crucially depends on its domestic firm's bargaining power over the licensing gain. When the firm's bargaining power is greater than one half, the government subsidizes its home firm's R&D investment, while imposes a tax if the firm's bargaining power is less than one half. Additionally, this result does not depend on the status of the firm (the licensor or the licensee). Finally, the effects of two different licensing contracts (fixed-fee v.s. royalty per unit) on governments' optimal R&D policies are investigated." (author's abstract)"Der Beitrag beschäftigt sich mit Innovationswettbewerb und der Rolle von nationaler Politik im Falle von internationalen Lizenzierungspraktiken. In einem mehrstufigen Spiel werden die Anreizmechanismen untersucht. Es stellt sich heraus, dass die Verhandlungsstärke der nationalen Unternehmen im Lizenzierungsmarkt eine wichtige Rolle spielen. So erfolgt aus nationaler Sicht eine Subvention (Besteuerung) von F&E-Investitionen immer dann, wenn die Verhandlungsmacht groß (klein) ist. Darüber hinaus untersucht der Beitrag die Konsequenzen unterschiedlicher Lizenzierungspraktiken auf die optimale nationale F&E-Politik." (Autorenreferat

Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: A study protocol for a longitudinal prospective cohort study

Introduction Immune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes. Methods and analysis Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. In total, 2720 participants routinely examined by carotid ultrasound will be divided into different groups according to plaque phenotype characteristics. Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke. Ethics and dissemination The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). Findings of this study will be submitted for publication in peer-reviewed journals. Trial registration number ChiCTR2100048740

Elongation of long-chain fatty acids in rabbitfish Siganus canaliculatus: Cloning, functional characterisation and tissue distribution of Elovl5- and Elovl4-like elongases

Elongases of very long-chain fatty acids (Elovl) catalyse the rate-limiting step of the elongation pathway that results in net 2 C elongation of pre-existing fatty acyl chains. As the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) is particularly relevant in fish, Elovl involved in the pathway have been investigated in various studies. Here we report the molecular cloning, functional characterisation and tissue distribution of two distinct elovl-like cDNAs isolated from the herbivorous marine teleost Siganus canaliculatus. Unlike the carnivorous marine fish previously investigated, we hypothesise that the rabbitfish has an enhanced LC-PUFA biosynthetic capability as previously anticipated in a former study on fatty acyl desaturases (Fad). The results of the present study showed that rabbitfish expresses at least two elovl cDNAs, which have high homology in sequence and function to Elovl5 and Elovl4 elongases that have been investigated previously in other fish species. Furthermore, the results confirm that the activities of the Elovl5 and Elovl4 enzymes enable rabbitfish to perform all the elongation reactions required for the biosynthesis of the physiologically essential C20-22 LC-PUFA including eicosapentaenoic (20:5n-3), arachidonic (20:4n-6) and docosahexaenoic (22:6n-3, DHA) acids, as well as the less common very long-chain fatty acids (greater than C24). Rabbitfish is thus the first marine teleost in which genes encoding Fad and Elovl enzymes, with all the activities required for the production of DHA from C18 PUFA, have been characterised. Highlights Rabbitfish possess at least two fatty acid elongases. The elongases were functionally characterised as Elovl5 and Elovl4 types.  The elongases possess all the activities necessary for the biosynthesis of DHA.  Elovl4 is capable of synthesising very long-chain fatty acids up to C36 in length.  Rabbitfish represent a marine fish not dependent upon dietary EPA and DH

Drag reduction mechanism of Paramisgurnus dabryanus loach with self-lubricating and flexible micro-morphology

Underwater machinery withstands great resistance in the water, which can result in consumption of a large amount of power. Inspired by the character that loach could move quickly in mud, the drag reduction mechanism of Paramisgurnus dabryanus loach is discussed in this paper. Subjected to the compression and scraping of water and sediments, a loach could not only secrete a lubricating mucus film, but also importantly, retain its mucus well from losing rapidly through its surface micro structure. In addition, it has been found that flexible deformations can maximize the drag reduction rate. This self-adaptation characteristic can keep the drag reduction rate always at high level in wider range of speeds. Therefore, even though the part of surface of underwater machinery cannot secrete mucus, it should be designed by imitating the bionic micro-morphology to absorb and store fluid, and eventually form a self-lubrication film to reduce the resistance. In the present study, the Paramisgurnus dabryanus loach is taken as the bionic prototype to learn how to avoid or slow down the mucus loss through its body surface. This combination of the flexible and micro morphology method provides a potential reference for drag reduction of underwater machinery

Monitoring Enzyme Reaction and Screening of Inhibitors of Acetylcholinesterase by Quantitative Matrix-Assisted Laser Desorption/Ionization Fourier Transform Mass Spectrometry

A matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS)–based assay was developed for kinetic measurements and inhibitor screening of acetylcholinesterase. Here, FTMS coupled to MALDI was applied to quantitative analysis of choline using the ratio of choline/acetylcholine without the use of additional internal standard, which simplified the experiment. The Michaelis constant (Km) of acetylcholinesterase (AChE) was determined to be 73.9 μmol L−1 by this approach. For Huperzine A, the linear mixed inhibition of AChE reflected the presence of competitive and noncompetitive components. The half maximal inhibitory concentration (IC50) value of galantamine obtained for AChE was 2.39 μmol L−1. Inhibitory potentials of Rhizoma Coptidis extracts were identified with the present method. In light of the results the referred extracts as a whole showed inhibitory action against AChE. The use of high-resolution FTMS largely eliminated the interference with the determination of ACh and Ch, produced by the low-mass compounds of chemical libraries for inhibitor screening. The excellent correlation with the reported kinetic parameters confirms that the MS-based assay is both accurate and precise for determining kinetic constants and for identifying enzyme inhibitors. The obvious advantages were demonstrated for quantitative analysis and also high-throughput characterization. This study offers a perspective into the utility of MALDI-FTMS as an alternate quantitative tool for inhibitor screening of AChE

Assessing Predictive Discrimination Performance of Biomarkers in the Presence of Treatment-induced Dependent Censoring

In medical studies, some therapeutic decisions could lead to dependent censoring for the survival outcome of interest. This is exemplified by a study of paediatric acute liver failure, where death was subject to dependent censoring due to liver transplantation. Existing methods for assessing the predictive performance of biomarkers often pose the independent censoring assumption and are thus not applicable. In this work, we propose to tackle the dependence between the failure event and dependent censoring event using auxiliary information in multiple longitudinal risk factors. We propose estimators of sensitivity, specificity and area under curve, to discern the predictive power of biomarkers for the failure event by removing the disturbance of dependent censoring. Point estimation and inferential procedures were developed by adopting the joint modelling framework. The proposed methods performed satisfactorily in extensive simulation studies. We applied them to examine the predictive value of various biomarkers and risk scores for mortality in the motivating example

Investigating long-chain polyunsaturated fatty acid biosynthesis in teleost fish: Functional characterization of fatty acyl desaturase (Fads2) and Elovl5 elongase in the catadromous species, Japanese eel Anguilla japonica

The capacity for endogenous production of LC-PUFA from PUFA in euryhaline or diadromous fish is largely unknown other than for Atlantic salmon (Salmo salar), an anadromous species, which displays a freshwater pattern. The aim of the present study was to characterize the enzymes of the LC-PUFA pathway in Japanese eel (Anguilla japonica), the most important catadromous species currently being farmed. cDNAs of two key genes were cloned and functional assays showed they encoded a desaturase (Fads2) with D6 and D8 activity and an elongase (Elovl5) with activity towards C18 and C20 PUFA, with activities similar to marine fish and an D6/D8 activity ratio similar to Atlantic salmon. Furthermore, tissue distribution of the mRNA showed a clear marine pattern with highest expression in brain and eye. Phylogenetic analysis placed the eel cDNAs in line with classical taxonomy. The data suggest that diadromous species display a pattern of LC-PUFA biosynthesis capacity that likely reflects the environmental and nutritional influence of their early life stages rather than those of adult fish. Future studies aim to establish the full range of PUFA desaturases and elongases in Japanese eel and to provide further insight to the importance and relevance of LC-PUFA biosynthesis in fish species and the influence of diadromy

The miR-33 gene is identified in a marine teleost: a potential role in regulation of LC-PUFA biosynthesis in Siganus canaliculatus

As the first marine teleost demonstrated to have the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18PUFA precursors, rabbitfishSiganus canaliculatusprovides a good model for studying the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. Here the potential roles of miR-33 in such regulation were investigated. The miR-33 gene was identified within intron 16 of the gene encoding sterol regulatory element-binding protein 1 (Srebp1), an activator of LC-PUFA biosynthesis. Expression of miR-33 in rabbitfish tissues correlated with that ofsrebp1, while its expression in liver was highly responsive to ambient salinities and PUFA components, factors affecting LC-PUFA biosynthesis. Srebp1 activation promoted the expression of Δ4 and Δ6 Δ5 fatty acyl desaturases (Fad), key enzymes for LC-PUFA biosynthesis, accompanied by elevated miR-33 abundance in rabbitfish hepatocytes. miR-33 overexpression induced the expression of the twofad, but suppressed that of insulin-induced gene 1 (insig1), which encodes a repressor blocking Srebp proteolytic activation and has targeting sites of miR-33. These results indicated that miR-33, cooperating with Srebp1, may be involved in regulation of LC-PUFA biosynthesis by facilitatingfadexpression, probably through targetinginsig1. To our knowledge, this is the first report of the participation of miR-33 in LC-PUFA biosynthesis in vertebrates