The Latin American Contribution to Center-Periphery Perspectives: History and Prospect

In this essay I will trace the formulation of the Latin American contribution to Center-Periphery analysis, its diffusion, crisis, reformulation, and decline. I further consider how Center-Periphery perspectives may be reincorporated into (standard) neoclassical economics.

Rational design of expression vectors for high quality biologics

Commercial proteins (e.g. antibodies, enzymes, vaccine components) for applications from biopharmaceuticals to commodity chemicals require low-cost manufacturing of high-quality products. The engineering of recombinant hosts to achieve large quantities of high-quality heterologous proteins is crucial to both minimizing costs and maximizing safety and efficacy (in the case of biopharmaceuticals). High-quality proteins are properly folded and full-length (intact), with native N-, and C-, termini and bear no significant proteolysis or other degradation (oxidation, deamidation, etc…). As most expression hosts rely on recombinant DNA technology for production of the heterologous protein, the transgene cassette provides an early, and inexpensive, opportunity for optimization of quality and protein titer. Commonly, transgene cassettes include a promoter, a heterologous gene of interest, and terminator for expression of the heterologous gene. A targeting sequence for guided recombination and selective marker for isolation of positive clones are also key elements. In engineering the transgene cassette, factors such as the promoter for heterologous gene expression, target site for transgene integration, sequence for translation initiation, and mRNA codon-optimization of the gene of interest are critical design points for a given protein-expressing strain. Here, we demonstrate an approach to transgene cassette optimization in the methylotrophic yeast, Pichia pastoris, informed by functional genomics. Omics-based techniques such as RNA-Seq, ATAC-Seq and ribosomal foot-printing afford greater upfront understanding for subsequent optimized strain engineering on a product-by-product basis. These types of data are cheap and easy to acquire for yeast and can indicate host- or sequence-derived bottlenecks in transgene transcription, translation and expression. Linking these data to product quality attributes can enlighten the design of the expression vector for fast in silico optimization of wide-ranging factors such as gene dosage balance, translation efficiency, and balanced cell kinetics enabling high-quality protein production. Collectively, we show that these tools can enable fast vector design for new heterologous protein-producing strains, including those expressing recombinant vaccines, and robust optimization when engineering higher productivity cell lines

Correlates of day school/adult learners and students academic performance: implication for counselling in Nigeria

The purpose of the study was to identify those challenges that hinder the day schools students/adult learners the opportunity to learn information, master new skills and improve old ones. The academic performance of day school secondary students’ grades and adult learners in Nigeria were influenced by factors such as, socioeconomic status, the quality of the home environment, parental involvement,societal aspirations and the school factor continue to influence the course of school achievement. To this, the writer critically looked at the challenges before the school and society and discuss how the values and expectation of the government, school/home can programme its activities for the projection and effective teaching and learning conditions for academic growth. On this, possible counselling implications were made to help improve the academic performance of day secondary school students and adult learners in Nigeria

A reversal in the historical role of tariffs in economic growth? The cases of Brazil and Portugal

Este artigo discute o papel comparativo do protecionismo sobre o crescimento econômico brasileiro e português no período 1860-1950 no contexto das aproximações teóricas disponíveis da Economia Internacional. Embora o papel das tarifas tenha sido longamente discutido na historiografia dos dois países, este artigo fornece o primeiro exercício que usa a metodologia baseada na aproximação macroeconométrica para sucessões cronológicas de longa duração. Dada a conclusão de Clemens e Williamson de que o enquadramento mundial conta, testamos para os dois países a sua pretensão do tariff reversal paradox. As experiências brasileira e portuguesa confirmam que a proteção esteve correlacionada com o crescimento no período anterior à Primeira Guerra Mundial, e não é provável que comércio mais livre tivesse aumentado o crescimento econômico português, contrariamente à tese estabelecida. A Primeira Guerra Mundial, contudo, foi um momento decisivo para o Brasil. Ao fazer-se este estudo, usaram-se os melhores dados disponíveis, partindo-se ocasionalmente dos usados por Clemens e Williamson. As nossas conclusões prevalecem com dados alternativos.This paper discusses the comparative role of protectionism on Brazilian and Portuguese economic growth for the period 1860-1950 in the context of the available theoretical approaches from international economics. Although the role of tariffs has long been debated in the historiography of both countries, this paper provides the first exercise that uses a methodology based on a macro-econometric approach for long-run time-series. Given Clemens' and Williamson's conclusion that the world environment matters, we test their claim for two countries on the tariff reversal paradox. The Brazilian and the Portuguese experiences confirm that protection was correlated with growth in the period before World War I, and it is unlikely that freer trade would have increased Portuguese growth, contrary to the established thesis. The First World War, however, was a turning point for Brazil. In carrying out this study, we have used the best data available to us, occasionally departing from those used by Clemens and Williamson. Our conclusions hold for alternative data sets

Molecular quality engineering for low cost vaccine production

Vaccines based on recombinant proteins provide a compelling case for low cost products with broad global accessibility. Protein immunogens are typically derived directly from native sequences found in bacterial or viral pathogens, and may not be well-suited for efficient expression in recombinant hosts. Native immunogens may also suffer from numerous challenges during expression that impact their quality or efficient production, including truncation, aggregation and poor stability. These challenges can lead to inefficiencies in manufacturing of subunit protein vaccines. Typically, recombinant vaccine manufacturing processes are complex, serial batch operations requiring extensive quality testing throughout to ensure product integrity. In response to the Gates Foundation’s Grand Challenge for Innovations in Vaccine Manufacturing for Global Markets, we are co-developing the ULTRA program for flexible, low cost vaccine products. This program aims to develop platform processes for production of recombinant vaccines. We believe that molecular design of the antigens provides a critical handle in improving antigen quality, manufacturability, and product stability, all of which could enable potent, low-cost vaccines. Addressing potential manufacturing challenges early on in product development should enable simple integrated processes for antigen production while minimizing costs associated with quality testing. To this end, we are demonstrating our platform approach with a recombinant trivalent subunit vaccine for rotavirus currently in clinical development. We chose to express the three VP8 subunits in Pichia pastoris to take advantage of the high titers of secreted proteins and minimal process-related contaminants typically experienced with this organism—critical features when developing simple intensified processes to meet our cost targets of $0.15/dose. Initial expression results showed the rotavirus antigens were poorly expressed and suffered from N-terminal truncation and aggregation—all of which were also observed in a previously developed E. coli-based process. We have deployed a two-pronged approach toward improving the manufacturability of these antigens. First, we used a functional genomics approach to identify bottlenecks experienced during cellular expression of the antigens. RNA-sequencing is a mature, inexpensive and acccessible technique for yeast that can indicate host- or sequence-derived bottlenecks in antigen transcription, translation and expression. Second, we made direct sequence changes to the antigens to mitigate specific quality challenges, such as aggregation. Iterations of this approach have enabled robust titers of rotavirus antigens with improved quality. This framework for incorporation of molecular engineering early in development provides a useful model for improving target product profiles that include manufacturability for low-costs, while maintaining immunogenicity