Responses to globalization in East Asia and Latin America: the activity locations of multinational manufacturers in the Asia-Pacific

Working Paper no. 3Arguably, no region in the world has benefited more from the globalization of the world economy over the last thirty years than East Asia. At the same time, the prevailing wisdom has been that they have not benefited from globalization to the same extent. The present paper shows that the differences in economic performance between East Asia and Latin America can be attributed in part to differences in their linkages with the global economy. It goes on to show that different corporate activities can represent different types of foreign investment. Data from a survey of manufacturing multinationals active in the Asia-Pacific region shows that the determinants of foreign investment differ by activity. This indicates that nations interested in attracting different corporate activities might wish to adopt different policy mixes. The results indicate that investments in infrastructure and managerial capabilities can contribute to an economy’s ability to attract a broad range of corporate activities. Results on tariffs and capital controls do not support the Washington consensus that greater openness will lead to greater investment. Instead, the results support the revisionist view that protection and a relatively active government have contributed to the attraction of foreign direct investment and the development of the Asian economies.published_or_final_versionThe Annual Conference of the Strategic Management Society, Paris, France, 22-25 September 2002. In LAEBA Proceedings, 2002, p. 1-3

Subsidiary types, activities, and location: an empirical investigation

Paper selected to be included in the AIB Best Paper Proceedings: Ref no. AIB2008-0668Session 2.4.4 - Competitive: Track 4 Subsudiary Evolution and StrategyConference Theme: Knowledge, Development and Exchange in International Business NetworksThe present paper extends the literature on the functions of foreign subsidiaries in the strategies of multinational companies in two ways: (a) by using a series of activities to induce subsidiary roles and (b) by investigating the firm-specific and location-specific determinants of subsidiary roles. Cluster analysis of responses of multinational subsidiary managers in the Asia-Pacific support a four-fold subsidiary typology. Categorical modeling on the resulting subsidiary types showed that several firm-specific and location-specific variables such as firm size, nationality, host market size and the level of host market openness have an impact on subsidiary mandate.published_or_final_versionThe 50th Annual Meeting of the Academy of International Business (AIB 2008), Milan, Italy, 30 June-2 July 2008. In Proceedings of the 50th Annual Meeting of AIB, 2008, p. 17

Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma.

DICER1 is a critical gene in the biogenesis of mature microRNAs, short non-coding RNAs that derive from either -3p or -5p precursor microRNA strands. Germline mutations of DICER1 are associated with a range of human malignancies, including pleuropulmonary blastoma (PPB). Additional somatic 'hotspot' mutations in the microRNA processing ribonuclease IIIb (RNase IIIb) domain of DICER1 are reported in cancer, and which affect microRNA biogenesis, resulting in a -3p mature microRNA strand bias. Here, in a germline (exon11 c.1806_1810insATTGA) DICER1-mutated PPB, we first confirmed the presence of an additional somatic RNase IIIb hotspot mutation (exon25 c.5425G>A [p.G1809R]) by conventional sequencing. Second, we investigated serum levels of mature microRNAs at the time of PPB diagnosis, and compared the findings with serum results from a comprehensive range of pediatric cancer patients and controls (n=52). We identified a panel of 45 microRNAs that were present at elevated levels in the serum at the time of PPB diagnosis, with a significant majority noted be derived from the -3p strand (P=0.013). In addition, we identified a subset of 10 serum microRNAs (namely miR-125a-3p, miR-125b-2-3p, miR-380-5p, miR-125b-1-3p, let-7f-2-3p, let-7a-3p, let-7b-3p, miR-708-3p, miR-138-1-3p and miR-532-3p) that were most abundant in the PPB case. Serum levels of two representative microRNAs, miR-125a-3p and miR-125b-2-3p, were not elevated in DICER1 germline-mutated relatives. In the PPB case, serum levels of miR-125a-3p and miR-125b-2-3p increased before chemotherapy, and then showed an early reduction following treatment. These microRNAs may offer future utility as serum biomarkers for screening patients with known germline DICER1 mutations for early detection of PPB, and for potential disease-monitoring in cases with confirmed PPB.We would like to thank the following for providing financial support: SPARKS (NC, MJM), Medical Research Council Fellowship (MJM), TD Bank/LDI scholarship (LdK), Alex’s Lemonade Stand Foundation (WDF), Cancer Research UK (NC) and European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 310018 (MT).This is the final published version. It first appeared at http://www.nature.com/oncsis/journal/v3/n2/full/oncsis20141a.html

An Evaluation of Prediction Equations for the 6 Minute Walk Test in Healthy European Adults Aged 50-85 Years

This study compared actual 6 minute walk test (6MWT) performance with predicted 6MWT using previously validated equations and then determined whether allometric modelling offers a sounder alternative to estimating 6MWT in adults aged 50-80 years.We compared actual 6MWT performance against predicted 6MWT in 125 adults aged 50-85 years (62 male, 63 female). In a second sample of 246 adults aged 50-85 years (74 male, 172 female), a new prediction equation for 6MWT performance was developed using allometric modelling. This equation was then cross validated using the same sample that the other prediction equations were compared with.Significant relationships were evident between 6MWT actual and 6MWT predicted using all of the commonly available prediction equations (all P<0.05 or better) with the exception of the Alameri et al prediction equation (P>0.05). A series of paired t-tests indicated significant differences between 6MWT actual and 6MWT predicted for all available prediction equations (all P<0.05 or better) with the exception of the Iwama et al equation (P = .540). The Iwama et al equation also had similar bias (79.8m) and a coefficient of variation of over 15%. Using sample 2, a log-linear model significantly predicted 6MWT from the log of body mass and height and age (P = 0.001, adjusted R2 = .526), predicting 52.6% of the variance in actual 6MWT. When this allometric equation was applied to the original sample, the relationship between 6MWT actual and 6MWT predicted was in excess of values reported for the other previously validated prediction equations (r = .706, P = 0.001). There was a significant difference between actual 6MWT and 6MWT predicted using this new equation (P = 0.001) but the bias, standard deviation of differences and coefficient of variation were all less than for the other equations.Where actual assessment of the 6MWT is not possible, the allometrically derived equation presented in the current study, offers a viable alternative which has been cross validated and has the least SD of differences and smallest coefficient of variation compared to any of the previously validated equations for the 6MWT

On the early and developed stages of surface condensation: competition mechanism between interfacial and condensate bulk thermal resistances

Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged.Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged.Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged.We use molecular dynamics simulation to investigate the early and developed stages of surface condensation. We find that the liquid-vapor and solid-liquid interfacial thermal resistances depend on the properties of solid and fluid, which are time-independent, while the condensate bulk thermal resistance depends on the condensate thickness, which is time-dependent. There exists intrinsic competition between the interfacial and condensate bulk thermal resistances in timeline and the resultant total thermal resistance determines the condensation intensity for a given vapor-solid temperature difference. We reveal the competition mechanism that the interfacial thermal resistance dominates at the onset of condensation and holds afterwards while the condensate bulk thermal resistance gradually takes over with condensate thickness growing. The weaker the solid-liquid bonding, the later the takeover occurs. This competition mechanism suggests that only when the condensate bulk thermal resistance is reduced after it takes over the domination can the condensation be effectively intensified. We propose a unified theoretical model for the thermal resistance analysis by making dropwise condensation equivalent to filmwise condensation. We further find that near a critical point (contact angle being ca. 153°) the bulk thermal resistance has the least opportunity to take over the domination while away from it the probability increases.Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

Lack of correlation between predicted and actual off-target effects of short-interfering RNAs targeting the human papillomavirus type 16 E7 oncogene.

BACKGROUND: When designing therapeutic short-interfering RNAs (siRNAs), off-target effects (OTEs) are usually predicted by computational quantification of messenger RNAs (mRNAs) that contain matches to the siRNA seed sequence in their 3' UTRs. It is assumed that the higher the number of predicted transcriptional OTEs, the greater the size of the actual OTE signature and the more detrimental the phenotypic consequences in target-negative cells. METHODS: We tested this general assumption by investigating the OTEs of potential therapeutic siRNAs targeting the human papillomavirus (HPV) type-16 E7 oncogene. We studied HPV-negative squamous epithelial cells, from normal cervix (NCx) and skin (HaCaT), which would be vulnerable to 'bystander' OTEs following transfection in vivo. RESULTS: We observed no correlation between the number of computationally predicted OTEs and the actual number of seed-dependent OTEs (P=0.76). On average only 20.5% of actual transcriptional OTEs were seed-dependent (i.e., predicted). The unpredicted OTEs included stimulation of innate immune pathways, as well as indirect (downstream) effects of other OTEs, which affected important cancer-associated pathways. Although most significant OTEs observed were seen in both NCx and HaCaT cells, only 0-5.9% of differentially expressed genes overlapped between the two cell types. CONCLUSION: These data do not support the assumption that actual OTEs correlate well with predicted OTEs

Significant variation in transformation frequency in Streptococcus pneumoniae

The naturally transformable bacterium Streptococcus pneumoniae is able to take up extracellular DNA and incorporate it into its genome. Maintaining natural transformation within a species requires that the benefits of transformation outweigh its costs. Although much is known about the distribution of natural transformation among bacterial species, little is known about the degree to which transformation frequencies vary within species. Here we find that there is significant variation in transformation frequency between strains of Streptococcus pneumoniae isolated from asymptomatic carriage, and that this variation is not concordant with isolate genetic relatedness. Polymorphism in the signalling system regulating competence is also not causally related to differences in transformation frequency, although this polymorphism does influence the degree of genetic admixture experienced by bacterial strains. These data suggest that bacteria can evolve new transformation frequencies over short evolutionary timescales. This facility may permit cells to balance the potential costs and benefits of transformation by regulating transformation frequency in response to environmental conditions

The six-minute walk test in community dwelling elderly: influence of health status.

BACKGROUND: The 6 minutes walk test (6MWT) is a useful assessment instrument for the exercise capacity of elderly persons. The impact of the health status on the 6MWT-distance in elderly, however, remains unclear, reducing its value in clinical settings. The objective of this study was to investigate to what extent the 6MWT-distance in community dwelling elderly is determined by health conditions. METHODS: One hundred and fifty-six community dwelling elderly people (53 male, 103 female) were assessed for health status and performed the 6MWT. After clinical evaluation, electrocardiography and laboratory examination participants were categorized into a stratified six-level classification system according to their health status, going from A (completely healthy) to D (signs of active disease at the moment of examination). RESULTS: The mean 6MWT-distance was 603 m (SD = 178). The 6MWT-distance decreased significantly with increasing age (ANOVA p = 0.0001) and with worsening health status (ANCOVA, corrected for age p < 0.001). A multiple linear regression model with health status, age and gender as independent variables explained 31% of the 6MWT-distance variability. Anthropometrical measures (stature, weight and BMI) did not significantly improve the prediction model. A significant relationship between 6MWT-distance and stature was only present in category A (completely healthy). CONCLUSIONS: Significant differences in 6MWT-distance are observed according to health status in community-dwelling elderly persons. The proposed health categorizing system for elderly people is able to distinguish persons with lower physical exercise capacity and can be useful when advising physical trainers for seniors

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics