115 research outputs found
Structural Interdependence among Colombian Departments
This paper advances on the analysis of the structural interdependence among Colombian departments. The results show that Bogotá has a large influence in the other regional economies through its purchasing power. Additionally, it can be observed a centerperiphery pattern in the spatial concentration of the effects of the hypothetical extraction of any territory. From a policy point of view, the main findings reaffirm the role played by Bogotá in the polarization process observed in the regional economies in Colombia in the last years. Any policy action oriented to reduce these regional disparities should take into account that, given the structural interdependence among Colombian departments, new investment in the lagged regions would flow through Bogotá and the major regional economies.Input-output; extraction method; Colombia Classification JEL: R12; R15.
The role of regions in global value chains: an analysis for the European Union
While considerable attention has been directed to the national-level impacts of global value chains, far less attention has been focused on the way in which global production fragmentation has affected regional economies. Using some measures derived from a multiregional, multisectoral input–output model, this paper analyzes the position and share of EU regions in Global Value Chains (GVC). The spatial determinants of these two dimensions are explored using spatial econometric methods to capture the influence of neighboring regions on these outcomes. Empirically, the focus is on a set of NUTS2 European regions for the most recent year (2010) of the EUREGIO database. Our results confirm the hypothesis of spatial dependence between regions conditioning the engagement and position GVCs, suggesting that global production processes are influenced by regional and local factors. In particular, spatial spillover effects play a significant role conditioned by both geographical proximity and similarity of production structures. The results show that sharing certain characteristics, some of them associated to their degree of proximity and the neighbouring situation of regions condition their specialization, participation and positioning in GVC, generating some important insights informative for the formulation of regional development policies
Structural interdependence among colombian departments
This paper advances on the analysis of the structural interdependence among Colombian departments. The results show that Bogotá has a large influence in the other regional economies through its purchasing power. Additionally, it can be observed a center-
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Isoxazole-Derived Amino Acids are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation into Histone H4 Peptides and Histone H3.
A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3.Pfizer Neusentis for studentship suppor
Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.
BACKGROUND
Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development.
METHOD
The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut.
RESULTS
A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity.
CONCLUSIONS
Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting
Econometric estimation of Armington import elasticities for a regional CGE model of the Illinois economy
One of the main concerns associated with the development and use of regional CGE models is the determination of key parameter values, particularly substitution and other price elasticities. A common problem is the lack of appropriate regional data for econometric estimation. Consequently, it is important to identify key parameters that are likely to be important in determining quantitative results and then to prioritize these for estimation where appropriate data are available. In this paper, the focus is on the estimation of the regional trade (import) substitution parameters, which tend to be important in analysis for regional economies (given their openness to trade). Here, commodity import elasticities for the Illinois economy are estimated and tested in a single region CGE model of the Illinois economy. In our econometric estimation, we apply a model that takes account of market size and distance in estimating the substitutability between commodities produced in Illinois and other US states
Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers
The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products
The discovery of I-BRD9, a selective cell active chemical probe for bromodomain containing protein 9 inhibition
Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain “reader” modules. Inhibitors of the bromodomain and extra terminal domain (BET) family of bromodomains have shown profound anticancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition
Issues of ideology in English language education worldwide: an overview
The relatively limited consideration of ideology in mainstream theory and research of teaching the English language to speakers of other languages has arguably prevented the problematization of many taken-for-granted perceptions and practices of the field. In this article I attempt to bring part of this marginalized body of scholarship on issues of ideology in the area of English language teaching (ELT) to highlight its potential insights for the field. The article sets out from a view of ideology as the most fundamental beliefs in any social practice, which may provide a less-formidable conception of the term and lessen the divergence among the minority of ELT researchers and professionals that do concern themselves with ideology. Then, after a brief sketch of the notion of ideology of language (education), I present an overview of aspects of this marginal but vibrant stream of thought on issues of ideology in ELT worldwide. Overall, the discussion is aimed to act as a call for the further understanding and embracement of sociopolitically-sensitive and ideologically-informed approaches to ELT theory, research, and practice
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