Characterisation of Antibody Interactions with the G Protein of Vesicular Stomatitis Virus Indiana Strain and Other Vesiculovirus G Proteins

Vesicular stomatitis virus Indiana strain G protein (VSVind.G) is the most commonly used envelope glycoprotein to pseudotype lentiviral vectors (LV) for experimental and clinical applications. Recently, G proteins derived from other vesiculoviruses (VesG), for example Cocal virus, have been proposed as alternative LV envelopes with possible advantages compared to VSVind.G. Well-characterised antibodies that recognise VesG will be useful for vesiculovirus research, development of G protein-containing advanced therapy medicinal products (ATMPs), and deployment of VSVind-based vaccine vectors. Here we show that one commercially available monoclonal antibody, 8G5F11, binds to and neutralises G proteins from three strains of VSV as well as Cocal, and Maraba viruses, whereas the other commercially available monoclonal anti-VSVind.G antibody, IE9F9, binds to and neutralises only VSVind.G. Using a combination of G protein chimeras and site-directed mutations, we mapped the binding epitopes of IE9F9 and 8G5F11 on VSVind.G. IE9F9 binds close to the receptor binding site and competes with soluble low-density lipoprotein receptor (LDLR) for binding to VSVind.G, explaining its mechanism of neutralisation. In contrast, 8G5F11 binds close to a region known to undergo conformational changes when the G protein moves to its post-fusion structure, and we propose that 8G5F11 cross-neutralises VesGs by inhibiting this.IMPORTANCE VSVind.G is currently regarded as the gold-standard envelope to pseudotype lentiviral vectors. However, recently other G proteins derived from vesiculoviruses have been proposed as alternative envelopes. Here, we investigated two commercially available anti-VSVind.G monoclonal antibodies for their ability to cross-react with other vesiculovirus G proteins, and identified the epitopes they recognise, and explored their neutralisation activity. We have identified 8G5F11, for the first time, as a cross-neutralising antibody against several vesiculovirus G proteins. Furthermore, we elucidated the two different neutralisation mechanisms employed by these two monoclonal antibodies. Understanding how cross-neutralising antibodies interact with other G proteins may be of interest in the context of host-pathogen interaction and co-evolution as well as providing the opportunity to modify the G proteins and improve G protein-containing medicinal products and vaccine vectors

Análisis del impacto de las publicaciones sobre PYMES en revistas latinoamericanas. Parte 1: Primera Parte

oai:ojs.rmlconsultores.com:article/1From a search of the literature related to Small and Medium sized Enterprises (SMEs) in the Network of Scientific Journals from Latin America and the Caribbean, Spain and Portugal (REDALYC) were determined 149 articles related to the topic in 8 countries and international organizations referenced in that network. The most important journals for the subject and also from the analysis of the keywords presented in the abstract, the relevant thematics for the publications about SMEs were found. Utilizing Perish (Harzing, 2007) the literature on SMEs referenced in Google Scholar and h indicator was determined. Of the 1000 articles founded 215 had an h index > = 1 indicator and 75% of the articles referenced even they appear in Google Scholar, have not a real impact (h = 0). The methodology allows to recommend a simple form that can be incorporated in the Academic Master Programs for determining for a thesis topic, those articles published an indexed in scientific journals and with a real impact for the topic.Se determinaron a partir de una búsqueda de las publicaciones relacionadas con la Pequeña y Mediana Empresa (PYMES) en la Red de Revistas Cientí­ficas de América Latina y el Caribe, España y Portugal (REDALYC), 149 artí­culos relacionados con el tema en revistas de 8 paí­ses y de Organismos Internacionales referenciados en la misma.  Se determinó igualmente las revistas más importantes para el tema en cuestión y a partir del análisis de las palabras claves presentadas en el resumen, las sub temáticas que más se analizan en cuanto a PYMES para las revista indexadas en la red mencionada. Se empleó la herramienta Perish (Harzing, 2007) para el análisis de las publicaciones sobre la temática PYMES referenciadas en el Google Académico y su indicador h. De los 1000 artí­culos encontrados 215 tienen un indicador h >= 1 y el 75 % de los artí­culos aunque aparezcan referenciados en el Google Académico, no han tenido un impacto real (h=0). La metodologí­a empleada permite recomendar una forma simple que puede incorporarse en los Programas Académicos de Maestrí­a y que permite determinar para un tema de Tesis, aquellos artí­culos publicados en revistas indexadas y con mayor impacto para la misma.Se determinaron a partir de una búsqueda de las publicaciones relacionadas con la Pequeña y Mediana Empresa (PYMES) en la Red de Revistas Cientí­ficas de América Latina y el Caribe, España y Portugal (REDALYC), 149 artí­culos relacionados con el tema en revistas de 8 paí­ses y de Organismos Internacionales referenciados en la misma.  Se determinó igualmente las revistas más importantes para el tema en cuestión y a partir del análisis de las palabras claves presentadas en el resumen, las sub temáticas que más se analizan en cuanto a PYMES para las revista indexadas en la red mencionada. Se empleó la herramienta Perish (Harzing, 2007) para el análisis de las publicaciones sobre la temática PYMES referenciadas en el Google Académico y su indicador h. De los 1000 artí­culos encontrados 215 tienen un indicador h >= 1 y el 75 % de los artí­culos aunque aparezcan referenciados en el Google Académico, no han tenido un impacto real (h=0). La metodologí­a empleada permite recomendar una forma simple que puede incorporarse en los Programas Académicos de Maestrí­a y que permite determinar para un tema de Tesis, aquellos artí­culos publicados en revistas indexadas y con mayor impacto para la misma

Genetic diversity, population structure, and genetic correlation with climatic variation in chickpea (Cicer arietinum) landraces from Pakistan

Chickpea (Cicer arietinum L.) production in arid regions, such as those predominant in Pakistan, faces immense challenges of drought and heat stress. Addressing these challenges is made more difficult by the lack of genetic and phenotypic characterization of available cultivated varieties and breeding materials. Genotyping-by-sequencing offers a rapid and cost-effective means to identify genome-wide nucleotide variation in crop germplasm. When combined with extended crop phenotypes deduced from climatic variation at sites of collection, the data can predict which portions of genetic variation might have roles in climate resilience. Here we use 8113 single nucleotide polymorphism markers to determine genetic variation and compare population structure within a previously uncharacterized collection of 77 landraces and 5 elite cultivars, currently grown in situ on farms throughout the chickpea growing regions of Pakistan. The compiled landraces span a striking aridity gradient into the Thal Desert of the Punjab. Despite low levels of variation across the collection and limited genetic structure, we found some differentiation between accessions from arid, semiarid, irrigated, and coastal areas. In a subset of 232 markers, we found evidence of differentiation along gradients of elevation and isothermality. Our results highlight the utility of exploring large germplasm collections for nucleotide variation associated with environmental extremes, and the use of such data to nominate germplasm accessions with the potential to improve crop drought tolerance and other environmental traits

The Developing Laminar Flow and Pressure Drop in the Entrance Region of Annular Ducts

BRIEF NOTES the most frequently used assumption is that of uniform flow at inlet, which simulates the actual condition of well-rounded entrance. This assumption was adopted in the present analysis and thus, at x = 0, the axial velocity and pressure are uniform with values u 0 and p 0 , respectively. Following the procedure suggested in TT/32, 2.03 for ex = TT/16, 1.92 for a = ir/8, and 1.86 for a = 7r/4) seem to conform with the asymptotic value of 1.82 obtained in The most commonly used parameters for presenting the pressure results are the product of the friction factor and Reynolds number fRe, and the pressure defect K. In the present analysis, the friction factor was defined as: f=(D h /2)(-dp/dx)/(pu 2 b ), and hence The pressure defect is normally defined as: , which reduces to the following nondimensional form: Results based on equations Acknowledgments The authors gratefully acknowledge the support provided for this research by the Natural Sciences and Engineering Research Council of Canada. References 1 Shah, R. K., and London, A. L., Laminar Flow Forced Convection in Duels, Academic Press, 1978. 2 Wendt, R. L., and Wiginton, C. L., "Incompressible Laminar Entrance Flow in a Circular Sector Duct," JOURNAL OF APPLIED MECHANICS, Vol. 98, 1976, pp.357-359. 3 Munis, A A., "Analysis of Laminar Fluid Flow in the Entrance Region of Circular Sector Ducts," M.Sc. Thesis, University of-Manitoba, 1981. 4 Sparrow, E. M., Lin, S. H., and Lundgren, T. S., "Flow Development in the Hydrodynamic Entrance Region of Tubes and Ducts," Physics of Fluids, Vol. 7, 1964, pp. 338-347. 5 Sparrow, E. M., and Lin, S. H., "The Developing Laminar Flow and Pressure Drop in the Entrance Region of Annular Ducts," Journal of Bask Engineering, Vol. 86,1964, pp. 827-834. 6 Fleming, D. P., and Sparrow, E. M., "Flow in the Hydrodynamic Entrance Region of Ducts of Arbitrary Cross-Section," ASME Journal of Heat Transfer, Vol. 91,1969, pp. 345-354. Numerical Results The resulting values of Le are listed i

Expression of Ghrelin and GHSR-1a in Long Term Diabetic Rat's Kidney

The aim of this work was to study the relative ghrelin and growth hormone secretagogue receptor (GHS-R)1a gene expression in the kidney of long-term diabetic rats. Forty male Wistar albino rats were divided into four groups: C- control group, DI- one month diabetic rats group, DII- two months diabetic rats group, and DIII- three months diabetic rats group. Diabetes was induced by streptozotocin STZ (40mg/kg i.p). The rats were decapitated under ketamine anesthesia and their kidney tissues were removed. Tissue GHS-R mRNA levels, ghrelin expression, and histopathological damage scores were compared. Dilatation in the distal tubules, epithelial desquamation into the lumen of the tubules and transparent tubules showing glycogen vacuolation were observed in all the diabetic groups. Ghrelin immunoreactivity was significantly higher in group DI compared to group C, whereas in groups DII and DIII, ghrelin immunoreactivity was similar with group C. GHSR-1a mRNA level in group DIII was significantly lower than in group C. As a result, ghrelin immunoreactivity increased at the beginning of diabetes; however, with increase in the duration of diabetes ghrelin immunoreactivity approached to the control values. The expression of GHSR-1a mRNA decreased with increase in diabetes duration. It seemed that down-regulation of GHSR-1a contributed to the renal damage induced by long-term diabetes

A study of recent advances in cache memories

Registers within a processor, cache within, on, or outside the processor, and virtual memory on the disk drive builds memory hierarchy in modern computer systems. The principle of locality of reference makes this memory hierarchy work efficiently. In recent years, cache organizations and designs have witnessed several advances that have not only improved their performance such as hit rates, speed, latency, energy consumption, etc. but various new designs and organizations for chip multi-processors such as multilevel caches, Non-Uniform Cache Access (NUCA), hybrid caches, etc. have also emerged. This paper presents a study of current competing processors in terms of various factors determining performance and throughput of cache organization and design. To evaluate their performance and viability, it reviews recent cache trends that include hybrid cache memory, non-uniform cache architecture, energy efficient replacement algorithms, cache memory programming, software defined caches and emerging techniques for making cache reliable against soft errors. It discusses the pros and cons of emerging cache architectures and designs

Characterization of Bonded Zone and Evaluation of Cracking in Vacuum Brazed Zircaloy-4 and Stainless Steel-316L Joint

Brazing of two dissimilar structural materials; Zircaloy-4 and SS-316L was performed at 900°C under high vacuum conditions. The metallic glass ribbons (Zr55Cu30Al10Ni2Fe3-at.%) of 30 μm thickness, were used as an interlayer. The bonded region was characterized by scanning electron microscope (SEM), energy dispersive spectroscope (EDS) and microhardness testing. The metallurgical bond formation was due to compositional changes in the molten interlayer and later on its subsequent solidification. Assessment of the bonded zone (BZ) revealed three distinct regions (Region-I, Region-II and Region-III). Diffusion transformation was observed in Region-I and Region-III which were interface with base alloys SS-316L and Zircaloy-4 respectively. However, Region-II at the middle of the BZ was composed of isothermally and athermally solidified portions. The highest values of Microhardness were observed in Region-III which was due to the presence of hard phases. Moreover, a crack parallel to BZ was observed in Region-III and was attributed to differential contraction of base alloys during cooling. Maximum shear stress acting on the BZ was calculated and correlated to the brittle phase cracking

Characterization of antibody interactions with the G protein of vesicular stomatitis virus Indiana strain and other vesiculovirus G proteins

Vesicular stomatitis virus Indiana strain G protein (VSVind.G) is the most commonly used envelope glycoprotein to pseudotype lentiviral vectors (LV) for experimental and clinical applications. Recently, G proteins derived from other vesiculoviruses (VesG), for example, Cocal virus, have been proposed as alternative LV envelopes with possible advantages over VSVind.G. Well-characterized antibodies that recognize VesG will be useful for vesiculovirus research, development of G protein-containing advanced therapy medicinal products (ATMPs), and deployment of VSVind-based vaccine vectors. Here, we show that one commercially available monoclonal antibody, 8G5F11, binds to and neutralizes G proteins from three strains of VSV, as well as Cocal and Maraba viruses, whereas the other commercially available monoclonal anti-VSVind.G antibody, IE9F9, binds to and neutralizes only VSVind.G. Using a combination of G protein chimeras and site-directed mutations, we mapped the binding epitopes of IE9F9 and 8G5F11 on VSVind.G. IE9F9 binds close to the receptor binding site and competes with soluble low-density lipoprotein receptor (LDLR) for binding to VSVind.G, explaining its mechanism of neutralization. In contrast, 8G5F11 binds close to a region known to undergo conformational changes when the G protein moves to its postfusion structure, and we propose that 8G5F11 cross-neutralizes VesGs by inhibiting this