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Background Survivors of invasive group B Streptococcus (iGBS) disease, notably meningitis, are at increased risk of neurodevelopmental impairment. However, the limited studies to date have a median follow-up to 18 months and have mainly focused on moderate or severe neurodevelopmental impairment, with no previous studies on emotional-behavioral problems among iGBS survivors. Methods In this multicountry, matched cohort study, we included children aged 18 months to 17 years with infant iGBS sepsis and meningitis from health demographic surveillance systems, or hospital records in Argentina, India, Kenya, Mozambique, and South Africa. Children without an iGBS history were matched to iGBS survivors for sex and age. Our primary outcomes were emotional-behavioral problems and psychopathological conditions as measured with the Child Behavior Checklist (CBCL). The CBCL was completed by the child’s primary caregiver. Results Between October 2019 and April 2021, 573 children (mean age, 7.18 years) were assessed, including 156 iGBS survivors and 417 non-iGBS comparison children. On average, we observed more total problems and more anxiety, attention, and conduct problems for school-aged iGBS survivors compared with the non-iGBS group. No differences were found in the proportion of clinically significant psychopathological conditions defined by the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Conclusions Our findings suggested that school-aged iGBS survivors experienced increased mild emotional behavioral problems that may affect children and families. At-risk neonates including iGBS survivors need long-term follow-up with integrated emotional-behavioral assessments and appropriate care. Scale-up will require simplified assessments that are free and culturally adapted.

This paper analyses how China’s investments in Germany have developed over time and the potential impact of the COVID-19 pandemic in this regard, based on four different datasets, including our own survey in mid-2020. Our analysis shows that Germany is currently one of the most attractive investment destinations for Chinese investors. Chinese state-owned enterprises have played an important role as investors in Germany — particularly in large-scale projects. The COVID-19 pandemic has had some negative but rather temporary effects on Chinese investments in Germany. Germany is expected to stay attractive to Chinese investors who seek to gain access to advanced technologies and know-how in the future.

Long-non-coding RNAs (lncRNAs) are defined as RNA sequences which are >200 nt with no coding capacity. These lncRNAs participate in various biological mechanisms, and are widely abundant in a diversity of species. There is well-documented evidence that lncRNAs can interact with genomic DNAs by forming triple helices (triplexes). Previously, several computational methods have been designed based on the Hoogsteen base-pair rule to find theoretical RNA–DNA:DNA triplexes. While powerful, these methods suffer from a high false-positive rate between the predicted triplexes and the biological experiments. To address this issue, we first collected the experimental data of genomic RNA-DNA triplexes from antisense oligonucleotide (ASO)-mediated capture assays and used Triplexator, the most widely used tool for lncRNA–DNA interaction, to reveal the intrinsic information on true triplex binding potential. Based on the analysis, we proposed six computational attributes as filters to improve the in-silico triplex prediction by removing most false positives. Further, we have built a new database, TRIPBASE, as the first comprehensive collection of genome-wide triplex predictions of human lncRNAs. In TRIPBASE, the user interface allows scientists to apply customized filtering criteria to access the potential triplexes of human lncRNAs in the cis-regulatory regions of the human genome. TRIPBASE can be accessed at https://tripbase.iis.sinica.edu.tw/.

This paper analyzes the development of spatial concentration of various innovation activities in China from 2000 to 2015 by using a generalized Theil index based on a balanced provincial dataset. It tracks concentration development back to the developing heterogeneity within and between regions in general and the mega‐economic zones in particular. Results show that innovation activities tend to be distributed unequally across provinces in China, with more pronounced unequal distribution of innovation outcomes than innovation inputs. Over the research period, the innovation activities considered became more and more equally distributed across provinces. The between‐region inequality of innovation activities has, however, not yet significantly improved, despite the implementation of Chinese regional policies to encourage more equal regional development. Instead, more equal distribution of innovation activities within mega‐economic zones is observed.

The international system for the governance of foreign investments is highly fragmented consisting mainly of bilateral agreements. With the adoption of nine guiding principles for global investment policy‐making in 2016, some observers argue that the G20 can actually serve as a launchpad for negotiations of a multilateral investment agreement. This paper provides empirical evidence on the question of whether the contents of international investment agreements (IIAs) have gradually converged to facilitate the multilateralisation of investment rules. We find that IIAs negotiated among non‐G20 countries are more similar to each other than those concluded by G20 countries in general and even more so since 2000 in particular. This result calls into question the premise that the G20 can serve as the most suitable forum to initiate multilateral negotiations on multilateral investment rules. Instead, an extended analysis using different country grouping criteria suggests that the Member States of the European Union may be a more suitable alternative in this regard. Here, the EU can jointly take a leading role in facilitating related negotiations on multilateral investment rules.

Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

With the expansion of the higher education system in China since the late 1990s, questions on the distribution of higher education opportunities and resources have attracted increasing attention from academics, policymakers, and the general public. While there have been an increasing studies on the development of higher education opportunity equality in China, quantitative, systematic research on the distribution of higher education resources across China is still rather limited. This paper aims at filling this gap. It provides quantitative and comprehensive evidence on the development of the distribution of higher education resources across Chinese provinces. The analysis is based on a provincial panel dataset and uses a generalized Theil index to measure inequality. Results show that higher education resources have been far from equally provided in relation to the size of provincial student populations in China. The unequal distribution has become even more pronounced over the past decade. In other words, even if high school students have an increasingly equal access to higher education in China (Bickenbach & Liu, 2013b), the increasingly unequal distribution of higher education resources makes it difficult for university students to equally benefit from higher education.

It is open to question whether the intensified worldwide competition for FDI has reduced its traditionally strong concentration in a few large and relatively advanced host countries. We calculate and decompose Theil indices to track changes in absolute and relative concentration of FDI during the period 1970-2013. We find that both absolute and relative concentration decreased when excluding offshore financial centers from the overall sample. In addition to the narrowing gap between OECD and non-OECD countries, the concentration across non-OECD countries declined for both the absolute and relative measures. This is also true for major subgroups of non-OECD countries. Finally, recent developments indicate that low-income countries are no longer at the losing end of the competition for FDI.

Since the early 2000s, the growth rate of real wages in Taiwan has been very low, even negative for high-skilled workers. This paper sheds light on the potential causes of this puzzling development through a comparison of Taiwan's performance with that of South Korea. In many dimensions, most notably wages and labour productivity, both economies developed quite similarly between 1995 and 2001–02, but diverged thereafter. We relate the development of wages and labour productivity in the two economies to sectoral structural change and to sectoral differences in labour productivity growth, skills upgrading, and foreign trade.

BackgroundThe regulatory roles of long intergenic noncoding RNAs (lincRNAs) in humans have been revealed through the use of advanced sequencing technology. Recently, three possible scenarios of lincRNA origin have been proposed: de novo origination from intergenic regions, duplication from long noncoding RNA, and pseudogenization from protein. The first two scenarios are largely studied and supported, yet few studies focused on the evolution from pseudo genized protein-coding sequence to lincRNA. Due to the non-mutually exclusive nature that these three scenarios have, accompanied by the need of systematic investigation of lincRNA origination, we conduct a comparative genomics study to investigate the evolution of human lincRNAs.ResultsCombining with syntenic analysis and stringent Blastn e-value cutoff, we found that the majority of lincRNAs are aligned to the intergenic regions of other species. Interestingly, 193 human lincRNAs could have protein-coding orthologs in at least two of nine vertebrates. Transposable elements in these conserved regions in human genome are much less than expectation. Moreover, 19% of these lincRNAs have overlaps with or are close to pseudogenes in the human genome.ConclusionsWe suggest that a notable portion of lincRNAs could be derived from pseudogenized protein-coding genes. Furthermore, based on our computational analysis, we hypothesize that a subset of these lincRNAs could have potential to regulate their paralogs by functioning as competing endogenous RNAs. Our results provide evolutionary evidence of the relationship between human lincRNAs and protein-coding genes.

The Blastn e-value distributions of shuffled sequences and 193 lincRNAs (see Methods). (PDF 5Â kb)

The estrogen pathway has long been implicated as a tumor protector in female hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Our previous study identified that estrogen receptor alpha (ERα) protein is downregulated in 60% of female HCC cases, via a miR-18a elevation mediated suppression of ERα translation. This study aims to delineate the mechanism underlying the upregulation of miR-18a in female HCC. The analysis of 77 female HCC specimens revealed that miR-18a levels were associated with pre-miR-18a rather than pri-miR-18a levels, suggesting an enhanced processing of pri- to pre-miR-18a. Among a panel of factors involved in microRNA processing, p53 was identified as a novel regulator for miR-18a maturation process. Knockdown of p53 by si-RNA decreased the level of miR-18a, whereas overexpression of either wild-type or mutant p53 increased its level. The association between the elevation of miR-18a and the accumulation of p53, mainly caused by somatic mutations, was confirmed in the clinical specimens of HBV-related female HCC. By analyzing the association with clinicopathological features, activation of this p53/miR-18a pathway mainly occurs in younger or noncirrhosis female HCC patients and associated with a trend of worse overall survival. Therefore, this study demonstrated a novel function of elevated/mutant p53 in regulating the amount of ERα protein through its promoting the biogenesis of miR-18a, which could lead to decrease the tumor-protective function of the estrogen pathway in female hepatocarcinogenesis.

This study investigates industrial innovation and innovation patterns in China with a comparison to the Asian Newly Industrialized Economies (NIEs). It estimates knowledge production functions based on an original firm-level dataset. Estimation results suggest that even though firms in China carry out various innovation activities at the same time, the innovation pattern found among their counterparts in the Asian NIEs is still relevant for contemporary China. In particular, sourcing knowledge and technologies from their OEM customers still plays a crucial role for Chinese firms' process innovation. In contrast, firms cannot rely on this knowledge source for realizing more sophisticated, knowledge-intensive innovation outcomes, such as product innovation and patenting, for which their own R&D engagement is more significant.

Over the past decade the scale of higher education in China has expanded substantially. Regional development policies attempted to make use of the scale expansion as a tool to reduce the inequality of higher education among different regions with different development levels through providing the poor regions preferential treatment and support in this regard. This paper analyses a provincial dataset (1997-2008), aiming to provide comprehensive quantitative evidence for the development of inequality of higher education opportunities across provinces in China over the period of the scale expansion, taking different sizes and economic development levels of provinces into account. Results show that the regional inequality of higher education relative to provinces’ different population sizes clearly decreased over the research period. Accompanying the reduction in overall inequality across provinces, the inequality between the poor and the rich regions actually increased over the same period. However, the increase was realised in favour of the poor region. The empirical results are consistent with the policy orientation of reforming the higher education system and of promoting regional development in China over the past decade

This paper describes the Chinese economic and institutional reform process as a gradual transition of an informal, relation-based governance system into a more formal and rule-based governance system. The consequences of macro-level institutional reforms on the importance of personal relationships for the firm-level governance of business operations are discussed. Theoretical considerations suggest that in a transition economy such as China companies’ incentives to reduce the reliance on personal relationships should depend on firm characteristics such as the age, size and the internationalization of the firm. We confront these suppositions with empirical data obtained from a company survey performed among 222 companies in the electronics industry operating in the Pearl River Delta, China. From this we obtain some, though often weak, evidence in favor of the suppositions.

Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated. By examining the expression of 22 HCC-related miRNAs between precancerous and cancerous liver tissues, we found miR-216a and miR-224 were significantly up-regulated, starting from the precancerous stage. Furthermore, the elevation of miR-216a was mainly identified in male patients. To study this gender difference, we demonstrated that pri-miR-216a is activated transcriptionally by the androgen pathway in a ligand-dependent manner and is further enhanced by the hepatitis B virus X protein. The transcription initiation site for pri-miR-216a was delineated, and one putative androgen-responsive element site was identified within its promoter region. Mutation of this site abolished the elevation of pri-miR-216a by the androgen pathway. One target of miR-216a was shown to be the tumor suppressor in lung cancer-1 gene (TSLC1) messenger RNA (mRNA) through the three target sites at its 3′ untranslated region. Finally, the androgen receptor level increased in male liver tissues during hepatocarcinogenesis, starting from the precancerous stage, with a concomitant elevation of miR-216a but a decrease of TSLC1. Conclusion: The current study discovered the up-regulation of miRNA-216a by the androgen pathway and a subsequent suppression of TSLC1 as a new mechanism for the androgen pathway in early hepatocarcinogenesis. (HEPATOLOGY 2012)

Background Antiviral therapy by nucleoside/nucleotide analogues (NAs) effectively reduces HBV replication in chronic hepatitis B (CHB) patients. Because long-term NA treatments will eventually select for drug- resistant mutants, early detection of mutants and frequent monitoring of viral loads is crucial for successful NA therapy. Because no efficient test for one-tube quantification and qualification of various HBV-resistant mutants exists, we propose to use high-resolution melting (HRM) analysis in combination with real-time PCR to achieve this unmet need. Methods We developed a single amplicon for detecting HBV mutants resistant to lamivudine (LMV), adefovir (ADV) and entecavir (ETV), which are commonly used for CHB treatment. Our design consists of two steps: real-time PCR for viral quantification, and hybridization probe HRM analysis for detection of specific drug-resistant mutants. Results Assay quantification was accurate ( R=0.98) for viral loads from 103 to 109 copies/ml. HRM analysis produced distinct melting temperatures that clearly distinguished the mutants, rtM204V/I (LMV), rtA181V and rtN236T (ADV), and rtT184G and rtM250V (ETV), from their respective wild types. The assay detected mutants at only 10–25% of the HBV population. The clinical applicability of this assay was tested in a pilot study with serial samples from patients receiving LMV treatment. Conclusions Flexibility, speed and cost-efficiency are additional benefits unique to our assay. The clinical sample results further support the feasibility of applying our design to frequent and long-term monitoring of CHB patients receiving NA treatments in the clinical setting.

This article investigates the role of personal relationships for doing business in the Greater Pearl River Delta, China (GPRD). First, it discusses the interplay of formal and informal (relationship-based) institutions based on institutional economics. Second, it describes the institutional environment for doing business in China, and in the GPRD in particular. Third, it uses data obtained from a survey among executives of Hong Kong electronics SMEs with business operations in the Pearl River Delta (PRD) to gain insights into their perceptions of the importance and the motives of using personal relationships for business in PRD in general, and on the impact of personal relationships on location and partner decisions for companies' production as well as innovation activities, in particular. The results confirm the importance of personal relationships for doing business in the GPRD and suggest that companies rely on personal relationships for business not only for cultural reasons but also to cope with defi...

Background & Aims Men have a higher incidence of hepatocellular carcinoma (HCC) than women, which is believed to partly be because of protective effects of estrogen. We sought to determine whether there were differences in levels of microRNA (miRNA) molecules between male and female HCC samples. Methods The expression profiles of a panel of candidate miRNAs were compared between male and female HCC tissues using the TaqMan miRNA assay. A luciferase reporter assay was used to identify mRNA targets recognized by specific miRNAs. The levels of pri- and pre-miRNA for each specific miRNA were assayed by quantitative reverse-transcription polymerase chain reaction to delineate the step deregulated in the biogenesis process. Finally, a colorimetric assay was used to determine the effect of specific miRNAs on hepatoma cell proliferation. Results The miR-18a miRNA increased specifically in samples from female HCC patients (female/male ratio, 4.58; P = .0023). The gene ESR1, which encodes the estrogen receptor-α (ERα), was identified as a target of miR-18a. miR-18a can repress ERα translation by binding to its mRNA at the 3′ untranslated region. Increased levels of miR-18a in female HCC tissues correlated with reduced ERα expression; the level of pre-miR-18a changed in concordance with that of mature miR-18a in these tissues. Overexpression of miR-18a decreased ERα levels but stimulated the proliferation of hepatoma cells. Conclusions This study provides a novel miRNA-mediated regulatory mechanism for controlling ERα expression in hepatocytes. miR-18a prevents translation of ERα, potentially blocking the protective effects of estrogen and promoting the development of HCC in women.

This paper investigates the role of regional credit systems for Chinese regional innovation, using data for the period 2000–2008. Both the effects of credit depth and government intervention are investigated. Results show that regional credit depth has a significantly positive effect on regional innovation performance. Credit depth has more marked impacts on major innovations (i.e., invention patents) than on less complicated innovations (i.e., utility model and external design patents). Additionally, our results do not suggest a reduction in the efficiency of regional innovation from increased government intervention via state-owned commercial banks.

Technology transfer (TT) is not mandatory for Clean Development Mechanism (CDM) projects, yet proponents of CDM argue that TT in CDM can bring new technologies to developing countries and thus not only reduce emissions but also foster development. We review the quantitative literature on determinants of TT in CDM and estimate determinants for CDM projects in China. China is by far the largest host country of CDM projects and it is therefore crucial to understand the factors that drive TT there. To gain better interpretation, we focus on heterogeneity within a single country and results can thus be linked to specific policies of the country. Our probit estimations confirm previous international cross-country studies, indicating that larger projects and more advanced technologies are more likely to involve TT. In addition, we find evidence that agglomeration effects are more pronounced at the province level rather than larger regions. We also find a positive effect of foreign direct investment (FDI) on TT, ...

Genetic tractability and easy manipulation make Caenorhabditis elegans a good model to study host–pathogen interactions. Dozens of different bacterial species can pathogenically infect C. elegans under laboratory conditions, and all of these microbes are extracellular pathogens to nematodes. Viruses, on the other hand, are obligate intracellular parasites, and yet no viral infections have been reported for C. elegans . We established a procedure allowing vaccinia virus to enter and subsequently replicate in C. elegans . Virus replication was significantly enhanced in ced-3 , ced-4 , ced-9(gf) , and egl-1(lf) mutants, demonstrating that the core programmed cell death (PCD) genes ced-3 , ced-4 , ced-9 , and egl-1 control vaccinia virus replication in C. elegans. The ability of ced-3 and ced-4 alleles to restrict virus replication is correlated with their cell-killing activities. Moreover, the increase in vaccinia virus replication levels in the PCD-defective mutants was not likely to be caused by the extra live cells, as neither the inhibition of PCD by icd-1 overexpression nor the presence of extra cells after extra cell divisions in cul-1 or lin-23 mutants had any significant effect on vaccinia virus replication. Therefore, the core PCD genes possess a unique function in controlling vaccinia virus replication in C. elegans .

The estrogen pathway has long been implicated as a tumor protector in female hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Our previous study identified that estrogen receptor alpha (ERα) protein is downregulated in 60% of female HCC cases, via a miR-18a elevation mediated suppression of ERα translation. This study aims to delineate the mechanism underlying the upregulation of miR-18a in female HCC. The analysis of 77 female HCC specimens revealed that miR-18a levels were associated with pre-miR-18a rather than pri-miR-18a levels, suggesting an enhanced processing of pri- to pre-miR-18a. Among a panel of factors involved in microRNA processing, p53 was identified as a novel regulator for miR-18a maturation process. Knockdown of p53 by si-RNA decreased the level of miR-18a, whereas overexpression of either wild-type or mutant p53 increased its level. The association between the elevation of miR-18a and the accumulation of p53, mainly caused by somatic mutations, was confirmed in the clinical specimens of HBV-related female HCC. By analyzing the association with clinicopathological features, activation of this p53/miR-18a pathway mainly occurs in younger or noncirrhosis female HCC patients and associated with a trend of worse overall survival. Therefore, this study demonstrated a novel function of elevated/mutant p53 in regulating the amount of ERα protein through its promoting the biogenesis of miR-18a, which could lead to decrease the tumor-protective function of the estrogen pathway in female hepatocarcinogenesis.

We analyze the concentration of foreign direct investment (FDI) in India at the district level, based on project-specific location choices since the reform program in the early 1990s. The decomposition property of the Theil index allows us to trace changes over time in the overall concentration of FDI to changes in concentration between and within subgroups of districts. We also differentiate between major types and sources of FDI. We find that FDI concentrated in a persistently decreasing number of districts. Concentration across those districts that received at least one FDI project within a given time interval also increased, but this increase leveled off in the more recent past. These trends hold for essentially all types and sources of FDI, while the average level of concentration varies considerably between these types and sources.

This chapter analyses an original firm-level dataset collected by our own Hong Kong (HK) Company Survey 2007 to investigate agility patterns applied by HK companies in the Pearl River Delta (PRD) in organising relations to their producers in the PRD and their customers. It also investigates the role of informality proxied by personal relationships for companies in the PRD in governing their production as well as their innovation activities, which have gained greatly in importance in the PRD in the new century. Our findings suggest that different agility patterns can be identified that are applied by companies to organise their relations to their producers and customers. Moreover, the findings show that companies generally tend to vertically integrate their production or innovation activities rather than carrying out such activities under a cooperative governance structure. With regard to cooperative governance structures, there is evidence of a complementary relationship between the importance of informality proxied by personal relationships and the importance of cooperative governance structures both for production and for innovation.

This paper investigates whether proximity to universities matters for corporate patenting in Chinese provinces. The investigation is based on estimating regional knowledge production functions using a Chinese provincial data set for the years from 2000 to 2008. Geographic proximity of companies to universities is taken as a key element to measure firms’ accessibility to university research. In addition, quality-adjusted accessibility measures are considered in extended models to take into account quality difference in university research. The results suggest the existence of spatial academic effects on corporate patenting activities in China as found in the previous literature for Western economies. In China, however, these effects are especially strong for realising technologically less demanding non-invention corporate patents than for invention corporate patents. Moreover, companies’ geographic proximity to universities dominates over university research quality difference for determining the relevance of universities as knowledge sources for companies. Extended models are estimated for robustness checks which ascertain the main results.

This paper describes the Chinese economic and institutional reform process as a gradual transition of an informal, relation-based governance system into a more formal and rule-based governance system. The consequences of macro-level institutional reforms on the importance of personal relationships for the firm-level governance of business operations are discussed. Theoretical considerations based on the New Institutional Economics suggest that, in a transition economy such as China, companies’ incentives to reduce the reliance on personal relationships should depend on firm characteristics such as the age, size and the internationalization of the firm. We confront these suppositions with empirical data obtained from a company survey performed among 222 (electronics industry) companies operating in the PRD, China. From this we obtain some, though often weak, evidence in favor of the suppositions

The hepatitis B virus (HBV) is a widespread human pathogen and chronic HBV infection is a major risk factor for hepatocellular carcinoma (HCC). The role of microRNA (miRNA) in the replication and pathogenesis was reviewed. So far none of HBV-encoded miRNA has been identified. Cellular miRNAs have shown able to regulate HBV at the transcription level either by targeting to cellular transcriptions factors required for HBV gene expression, or by a directly binding to HBV transcripts. We also summarized the changed patterns of cellular miRNAs from hepatitis B progressing to cirrhosis and then liver cancer. The changing of a few of miRNAs, such as miR-122 or miR-21, were reproduced and worthy of further research by a deep sequencing and functional validation. These HBV-specific miRNAs should potentially become biomarkers for HBV infection and HBV-positive HCC diagnosis. The understanding of miRNA biology paved the way for applying miRNAs-based RNAi against HBV replication with minimal toxicities. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation.

This paper investigates the role of regional financial development, in addition to FDI, for regional innovation in China, using a more recent provincial dataset and more sophisticated panel data estimation techniques than previous studies. Two aspects of regional financial system development are considered: its financial depth and government intervention in the financial system. Estimation results show that the financial depth of a region has a significantly positive effect on regional innovation (patenting) performance. This positive effect is found to be higher for minor innovations such as external design patents than for more complicated innovations such as utility model patents and invention patents. Surprisingly, estimation results do not show that government financial system intervention reduces allocative efficiency of resources which would otherwise impede regional innovation performance

This paper investigates whether knowledge transferred from different sources matter differently for carrying out different innovation outcomes, using a firm-level dataset collected in the Pearl River Delta (PRD) in China. It also investigates whether companies in the PRD in China tend to innovate in a similar way as companies in the Asian Newly Industrialised Economies (NIEs) did decades ago. Our estimation results suggest that companies in the PRD, as companies in the Asian NIEs, strongly rely on sourcing from their OEM customers but not on own R&D activities to implement innovative processes to increase production efficiency. In contrast, they engage in own R&D activities in order to develop innovative products, to realise higher innovation sales and to create new knowledge qualified for patenting. In addition to own R&D activities, they rely on sourcing knowledge from different sets of sources to support them to carry out the last three types of innovation outcomes

This paper analyses academia-industry linkages of the Hong Kong (HK) electronics small- and medium-sized enterprises (SMEs) and investigates the role of active innovation policies in this regard. It uses data collected from a questionnaire survey in HK, focusing on three main academia-industry linkages: academic institutions as training bases, as innovation sources and as innovation partners for companies. Our analysis results show that HK companies tend to rely on hiring highly-qualified labour trained by academic institutions to gain access to advanced academic knowledge. In contrast, they do not yet perceive academic institutions as important sources or partners for their innovation activities; however, their willingness to do so seems to be positively affected by the active innovation policies on site

It is widely feared that outward FDI gradually hollows out domestic manufacturing and displaces local workers. We address this concern by drawing on exceptionally informative firm-specific data on Taiwanese multinationals in manufacturing. In particular, we assess whether repercussions at home depend on the size, location and type of outward FDI. We control for firm heterogeneity and estimate ordered probit models with the firms’ own assessment of domestic production and employment effects as dependent variables. We find that the probability of negative effects increases slightly with the size of FDI. The effects of locating in China differ from those of locating in advanced countries not only in size but also in sign. In contrast to vertical and export-platform FDI, employment effects of horizontal FDI tend to be positive. The quantitative impact is typically small, however

Since 1997 the Hong Kong (HK) government has markedly changed its role from being a mere institution provider to being an active innovation promoter. As such, it has actively implemented innovation policies that focus especially on creating new funding opportunities and establishing several R&D centres to facilitate information flow and innovation cooperation between universities and industries. One of the industries in which it has been especially active is the electronics industry. Thus this study looks at the electronics industry to examine, using data collected from a questionnaire survey on the HK electronics SMEs, whether these policies have positively affected innovation intensity in HK. The survey findings indicate that there has been an increase in innovation activities in HK, but also that neither the R&D centres nor the universities have played important roles as innovation sources or innovation partners for the HK electronics SMEs. Rather, the main way through which universities and R&D centres support the HK electronics SMEs’ innovation activities seems to be the provision of a highly-qualified labour-force transmitting academic knowledge to companies

Background Tumors expressing a transforming growth factor-beta type I receptor (TβRI) mutant with sequence deletions in a nine-alanine (9A) stretch of the signal peptide are reported to be highly associated with disease progression. Expression of this mutant could interfere with endogenous TGFβ signaling in the cell. However, little is known about the importance of the remaining part of the signal peptide on the cellular function of TβRI. Results We cloned and identified four new in-frame deletion variants of TβRI, designated DM1 to DM4, in pleural effusion-derived tumor cells. Intriguingly, DM1 and DM2, with a small region truncated in the putative signal peptide of TβRI, had a serious defect in their protein expression compared with that of the wild-type receptor. Using serial deletion mutagenesis, we characterized a region encoded by nucleotides 16–51 as a key element controlling TβRI protein expression. Consistently, both DM1 and DM2 have this peptide deleted. Experiments using cycloheximde and MG132 further confirmed its indispensable role for the protein stability of TβRI. In contrast, truncation of the 9A-stretch itself or a region downstream to the stretch barely affected TβRI expression. However, variants lacking a region C-terminal to the stretch completely lost their capability to conduct TGFβ-induced transcriptional activation. Intriguingly, expression of DM3 in a cell sensitive to TGFβ made it significantly refractory to TGFβ-mediated growth inhibition. The effect of DM3 was to ablate the apoptotic event induced by TGFβ. Conclusion We identified four new transcript variants of TβRI in malignant effusion tumor cells and characterized two key elements controlling its protein stability and transcriptional activation. Expression of one of variants bestowed cancer cells with a growth advantage in the presence of TGFβ. These results highlight the potential roles of some naturally occurring TβRI variants on the promotion of tumor malignancy.

Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and other serotypes of coxsackie A viruses have raised serious public health concerns in the Asia-Pacific region. These concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. In this report, we present a platform for the large-scale production of a vaccine based on the inactivated EV71(E59-B4) virus. The viruses were produced in Vero cells in a 200 L bioreactor with serum-free medium, and the viral titer reached 10(7) TCID50/mL 10 days after infection when using an MOI of 10(-4). The EV71 virus particles were harvested and purified by sucrose density gradient centrifugation. Fractions containing viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to characterize the morphologies of the viral particles. To evaluate the cross-protective efficacy of the EV71 vaccine, the pooled antigens were combined with squalene-based adjuvant (AddaVAX) or aluminum phosphate (AlPO4) and tested in human SCARB2 transgenic (Tg) mice. The Tg mice immunized with either the AddaVAX- or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the subgenotype C2 and C4 viruses, and surviving animals did not show any degree of neurological paralysis symptoms or muscle damage. Vaccine treatments significantly reduced virus antigen presented in the central nervous system of Tg mice and alleviated the virus-associated inflammatory response. These results strongly suggest that this preparation results in an efficacious vaccine and that the microcarrier/bioreactor platform offers a superior alternative to the previously described roller-bottle system.

A growing list of microRNAs (miRNAs) show aberrant expression patterns in hepatocellular carcinoma (HCC), but the regulatory mechanisms largely remain unclear. RNA editing catalyzed by members of the adenosine deaminase acting on the RNA (ADAR) family could target the miRNA precursors and affect the biogenesis process. Therefore, we investigate whether RNA editing could be one mechanism contributing to the deregulation of specific miRNAs in HCC. By overexpression of individual ADARs in hepatoma cells, RNA editing on the precursors of 16 miRNAs frequently deregulated in HCC was screened by a sensitive high-resolution melting platform. The results identified RNA precursors of miR-214 and miR-122 as potential targets edited by ADAR2. A subset of HCC showing elevated ADAR2 verified the major editings identified in ARAR2 overexpressed hepatoma cells, either with A-to-I or U-to-C changes. The unusual U-to-C editing at specific residues was demonstrated as being attributed to the A-to-I editing on the RNA transcripts complementary to the pri-miRNAs. The editing event caused a decrease of the RNA transcript complementary to pri-miR-214, which led to the decrease of pri-miR-214 and miR-214 and resulted in the increased protein level of its novel target gene Rab15. In conclusion, the current study discovered ADAR2-mediated editing of the complementary antisense transcripts as a novel mechanism for regulating the biogenesis of specific miRNAs during hepatocarcinogenesis.