Quantifying the impact of technical barriers to trade : a framework for analysis

There has been increasing use of technical regulations as instruments of commercial policy in the context of multilateral, regional, and global trade. These nontariff barriers are of special concern to developing countries, which may bear additional costs in meeting mandatory standards. Many industrial and developing countries express frustration with regulations that vary across their export markets, require duplicative conformity procedures, and are continually revised to exclude imports. The authors provide a comprehensive overview of the policy debate and methodological issues surrounding product standards and technical barriers to trade. They begin with a review of the policy context driving demand for empirical analysis of standards in trade, then provide an analytical overview of the role of standards and their relationship to trade. They then review methodological approaches that have been used to analyze standards and theirimpact on trade. Their main interest lies in advancing techniques that are practical and may be fruitfully extended to the empirical analysis of regulations and trade. They discuss concrete steps that could be taken to move forward a practical, policy-relevant program of empirical research. Such steps would include: a) administering firm-level surveys in developing countries; b) devising methods for assessing how much standards restrict trade; and c) establishing econometric approaches that could be applied to survey and microeconomic data, to improve understanding of the role of standards in exports.Environmental Economics&Policies,Economic Theory&Research,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Trade and Services,Trade and Regional Integration

The cost of compliance with product standards for firms in developing countries: an econometric study

Standards and technical regulations exist to protect consumer safety or to achieve other goals, such as ensuring the interoperability of telecommunications systems, for example. Standards and technical regulations can, however, raise substantially both start-up and production costs for firms. Maskus, Otsuki, and Wilson develop econometric models to provide the first estimates of the incremental production costs for firms in developing nations in conforming to standards imposed by major importing countries. They use firm-level data generated from 16 developing countries in the World Bank Technical Barriers to Trade (TBT) Survey Database. Their findings indicate that standards do increase short-run production costs by requiring additional inputs of labor and capital. A 1 percent increase in investment to meet compliance costs in importing countries raises variable production costs by between 0.06 and 0.13 percent, a statistically significant increase. The authors also find that the fixed costs of compliance are nontrivial-approximately $425,000 per firm, or about 4.7 percent of value added on average. The results may be interpreted as one indication of the extent to which standards and technical regulations might constitute barriers to trade. While the relative impact on costs of compliance is relatively small, these costs can be decisive factors driving export success for companies. In this context, there is scope for considering that the costs associated with more limited exports to countries with import regulations may not conform to World Trade Organization rules encouraging harmonization of regulations to international standards, for example. Policy solutions then might be sought by identifying the extent to which subsidies or public support programs are needed to offset the cost disadvantage that arises from nonharmonized technical regulations.Environmental Economics&Policies,Economic Theory&Research,Health Economics&Finance,Administrative&Regulatory Law,Science Education

From crystal to structure with CCP4

An introduction to the 2017 CCP4 Study Weekend Special Issue

From crystal to structure with CCP4

An introduction to the proceedings of the CCP4 study weekend is given

Sialic Acid Mutarotation Is Catalyzed by the Escherichia coli β-Propeller Protein YjhT

The acquisition of host-derived sialic acid is an important virulence factor for some bacterial pathogens, but in vivo this sugar acid is sequestered in sialoconjugates as the {alpha}-anomer. In solution, however, sialic acid is present mainly as the β-anomer, formed by a slow spontaneous mutarotation. We studied the Escherichia coli protein YjhT as a member of a family of uncharacterized proteins present in many sialic acid-utilizing pathogens. This protein is able to accelerate the equilibration of the {alpha}- and β-anomers of the sialic acid N-acetylneuraminic acid, thus describing a novel sialic acid mutarotase activity. The structure of this periplasmic protein, solved to 1.5Å resolution, reveals a dimeric 6-bladed unclosed β-propeller, the first of a bacterial Kelch domain protein. Mutagenesis of conserved residues in YjhT demonstrated an important role for Glu-209 and Arg-215 in mutarotase activity. We also present data suggesting that the ability to utilize {alpha}-N-acetylneuraminic acid released from complex sialoconjugates in vivo provides a physiological advantage to bacteria containing YjhT

The structure of Rph, an exoribonuclease from Bacillus anthracis, at 1.7 angstrom resolution

Maturation of tRNA precursors into functional tRNA molecules requires trimming of the primary transcript at both the 5' and 3' ends. Cleavage of nucleotides from the 3' stem of tRNA precursors, releasing nucleotide diphosphates, is accomplished in Bacillus by a phosphate-dependent exoribonuclease, Rph. The crystal structure of this enzyme from B. anthracis has been solved by molecular replacement to a resolution of 1.7 angstrom and refined to an R factor of 19.3%. There is one molecule in the asymmetric unit; the crystal packing reveals the assembly of the protein into a hexamer arranged as a trimer of dimers. The structure shows two sulfate ions bound in the active-site pocket, probably mimicking the phosphate substrate and the phosphate of the 3'-terminal nucleotide of the tRNA precursor. Three other bound sulfate ions point to likely RNA-binding sites

Carbohydrate structure: : the rocky road to automation

With the introduction of intuitive graphical software, structural biologists who are not experts in crystallography are now able to build complete protein or nucleic acid models rapidly. In contrast, carbohydrates are in a wholly different situation: scant automation exists, with manual building attempts being sometimes toppled by incorrect dictionaries or refinement problems. Sugars are the most stereochemically complex family of biomolecules and, as pyranose rings, have clear conformational preferences. Despite this, all refinement programs may produce high-energy conformations at medium to low resolution, without any support from the electron density. This problem renders the affected structures unusable in glyco-chemical terms. Bringing structural glycobiology up to ‘protein standards’ will require a total overhaul of the methodology. Time is of the essence, as the community is steadily increasing the production rate of glycoproteins, and electron cryo-microscopy has just started to image them in precisely that resolution range where crystallographic methods falter most

An endogenous inhibitor of angiogenesis downregulated by hypoxia in human aortic valve stenosis promotes disease pathogenesis

Acknowledgements The authors would like to acknowledge the NHS Grampian Biorepository for their support and assistance with all immunohistochemistry. Sources of funding This work was generously funded by the British Heart Foundation, UK (FS/17/28/32807) and Grampian NHS Endowments.Peer reviewedPublisher PD

Dual Requirement for Yeast hnRNP Nab2p in mRNA poly(A) Tail Length Control and Nuclear Export

Recent studies of mRNA export factors have provided additional evidence for a mechanistic link between mRNA 3′‐end formation and nuclear export. Here, we identify Nab2p as a nuclear poly(A)‐binding protein required for both poly(A) tail length control and nuclear export of mRNA. Loss of NAB2 expression leads to hyperadenylation and nuclear accumulation of poly(A)+ RNA but, in contrast to mRNA export mutants, these defects can be uncoupled in a nab2 mutant strain. Previous studies have implicated the cytoplasmic poly(A) tail‐binding protein Pab1p in poly(A) tail length control during polyadenylation. Although cells are viable in the absence of NAB2 expression when PAB1 is overexpressed, Pab1p fails to resolve the nab2Δ hyperadenylation defect even when Pab1p is tagged with a nuclear localization sequence and targeted to the nucleus. These results indicate that Nab2p is essential for poly(A) tail length control in vivo, and we demonstrate that Nab2p activates polyadenylation, while inhibiting hyperadenylation, in the absence of Pab1p in vitro. We propose that Nab2p provides an important link between the termination of mRNA polyadenylation and nuclear export