43,892 research outputs found
Fragments of bacterial endoglycosidase S and immunoglobulin G reveal subdomains of each that contribute to deglycosylation
No full textEndoglycosidase S (EndoS) is a glycoside-hydrolase secreted by the bacterium Streptococcus pyogenes. EndoS preferentially hydrolyzes the N-linked glycans from the Fc region of IgG during infection. This hydrolysis impedes Fc functionality and contributes to the immune evasion strategy of S. pyogenes. Here, we investigate the mechanism of human serum IgG deactivation by EndoS. We expressed fragments of IgG1 and demonstrated that EndoS was catalytically active against all of them including the isolated CH2 domain of the Fc domain. Similarly, we sought to investigate which domains within EndoS could contribute to activity. Bioinformatics analysis of the domain organization of EndoS confirmed the previous predictions of a chitinase domain and leucine-rich repeat but also revealed a putative carbohydrate binding module (CBM) followed by a C-terminal region. Using expressed fragments of EndoS, circular dichroism of the isolated CBM, and a CBM-C-terminal region fusion revealed folded domains dominated by β sheet and α helical structure, respectively. Nuclear magnetic resonance analysis of the CBM with monosaccharides was suggestive of carbohydrate binding functionality. Functional analysis of truncations of EndoS revealed that, whereas the C-terminal of EndoS is dispensable for activity, its deletion impedes the hydrolysis of IgG glycans
1.07 – Structure and biosynthesis of glycoprotein carbohydrates
No full textIn eukaryotes, the majority of cell surface and secreted proteins are covalently modified with carbohydrates. This type of posttranslational modification, glycosylation, is inherently complex exhibiting extensive chemical and conformational heterogeneity. Despite this complexity, there are common structural and biosynthetic principles. Here, we present an introduction to the different hierarchies of carbohydrate structure from stereochemistry of monosaccharides and their linkages to the structural diversity of complex mammalian glycosylation. These structures are discussed in the context of the glycan biosynthetic pathways, with an emphasis on N-linked glycosylation, and we outline the nomenclature with which these complex structures can be described. We describe the biosynthesis and crystal structures of antibodies and their glycans to illustrate the conformational properties of glycoprotein carbohydrates and how therapeutic antibodies are being developed by modulating these glycans.</p
Modeling of modulus graded axisymmetric adhesive joints
No full textThis study presents a refined theoretical framework for the stress analysis of modulus graded axisymmetric adhesive joints which takes into account the radial stresses in the bonded assembly. This semi-analytical is based on a variational method which minimizes the complementary energy of the bonded system. The joint consists of similar or dissimilar polar anisotropic composite adherends or metallic adherends and a functionally modulus graded bondline (FMGB) adhesive. The elastic modulus of the adhesive is functionally graded along the bondlength by assuming smooth modulus profiles which reflect the behavior of practically producible graded bondline. The stress distribution predicted by this refined model is compared with that of MMB model which also accounts for in the bonded system to estimate reduction in shear and peel stress peaks in the bondline. The axisymmetric stress analysis reveals that the peel and shear stress peaks in the FMGB are much smaller and the stress distribution is more uniform along its length than those of mono-modulus bondline (MMB) adhesive joints under the same axial tensile load. A systematic parametric study has been conducted by selectively perturbing the material and geometrical properties of the joint in order to study their influence onstress distribution in the bondline. Furthermore, the results suggest that the peel and shear strengths can be optimized by spatially controlling the modulus of theadhesive
Design and flight test of a civil unmanned aerial vehicle for maritime patrol: the use of 3D-printed structural components
No full textThis paper describes the design of the “Spotter” unmanned aerial vehicle, developed by the University of Southampton as part of the 2SEAS-3i European Interreg project. Spotter is a twin engine, 4m wing span, fixed-wing aircraft which has been designed to perform long-endurance, all-weather patrol missions in coastal and maritime environments. Reliability and safety have been among the strongest design drivers of this project; Spotter is able to survive the failure of one engine and of any single control surface. A modular approach has been adopted for the payload unit in order to allow the users to rapidly interchange the sensors required to perform different missions.One of the most innovative aspects of Spotter is the extensive use of the Selective Laser Sintering (SLS) technology (also known as 3D printing) for many of the components of its airframe. By eliminating tooling and manual labour, the 3D printing technology allows the designer to produce complex and high-performance structures at a relatively low cost and within hours of the completion of the design. Spotter and a sub-20kg version, codenamed 2SEAS-20, have undergone an extensive flight test campaign, totalling hundreds of autonomous flights (including autonomous take-off and landings) and many flight hours. This has provided the opportunity to test the reliability and robustness of the system and to gain a deeper insight into the opportunities and problems presented by the use of 3D printed structures for large airframe components
On axisymmetric adhesive joints with graded interface stiffness
No full textAn improved analytical model is presented for the stress analysis of interface stiffness graded axisymmetric adhesive joints. The governing integro-differential equation of the problem is obtained through a variational method which minimizes the complementary energy of the bonded assembly. The joint is composed of similar or dissimilar polar anisotropic and/or isotropic adherends and a functionally modulus graded bondline (FMGB) adhesive. The elastic modulus of the adhesive is functionally graded along the bondlength by assuming smooth modulus profiles which reflect the behavior of practically producible graded bondline. Influence of non-zero radial stresses in the bonded system on shear and normal stresses is evaluated. The stress distribution predicted by this refined model is compared with that of mono-modulus bondline (MMB) model for the same axial tensile load in order to estimate reduction in shear and normal stress peaks in the bondline and the adherends. A systematic parametric study indicates that an optimum joint strength can be achieved by employing a stiffness graded bondline with an appropriate combination of geometrical and material properties of the adherends. This model can also be applied to examine the effects of loss of interface stiffness due to an existing defect and/or damage in the bondlin
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
Mapping customer needs to engineering characteristics: an aerospace perspective for conceptual design
No full textDesigning complex engineering systems, such as an aircraft or an aero-engine, is immensely challenging. Formal Systems Engineering (SE) practices are widely used in the aerospace industry throughout the overall design process to minimise the overall design effort, corrective re-work, and ultimately overall development and manufacturing costs. Incorporating the needs and requirements from customers and other stakeholders into the conceptual and early design process is vital for the success and viability of any development programme. This paper presents a formal methodology, the Value-Driven Design (VDD) methodology that has been developed for collaborative and iterative use in the Extended Enterprise (EE) within the aerospace industry, and that has been applied using the Concept Design Analysis (CODA) method to map captured Customer Needs (CNs) into Engineering Characteristics (ECs) and to model an overall ‘design merit’ metric to be used in design assessments, sensitivity analyses, and engineering design optimisation studies. Two different case studies with increasing complexity are presented to elucidate the application areas of the CODA method in the context of the VDD methodology for the EE within the aerospace secto
Rapid development of bespoke sensorcraft: a proposed design loop
No full textThe ability to quickly fabricate sensorcraft, or other small unmanned aircraft, via additive manufacturing techniques opens a range of new possibilities for the design and optimization of these vehicles. In this paper we propose a design loop that makes use of surrogate modeling and additive manufacturing to reduce the design and optimization time of scientific sensorcraft. Additive manufacturing reduces the time and effort required to fabricate a complete aircraft, allowing design iterations to be quickly manufactured and flight tested. Co-Kriging surrogate models allow data collected from test flights to correct Kriging models trained with numerically simulated data. The resulting model provides physically accurate and computationally cheap aircraft performance predictions. A global optimizer is used to search this model to find an optimal design for a bespoke aircraft. This paper presents the design loop and the progress made in implementing this design loop. Results are shown from Kriging models trained using numerically simulated data. Progress towards extracting aerodynamic data from flight testing small unmanned aircraft is also documented
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Travelling wave ion mobility and negative ion fragmentation for the structural determination of N-linked glycans
No full textTravelling wave ion mobility was investigated for its ability to separate N-glycans from other compounds and for resolution of isomers. Charged glycans, exemplified by sialylated complex N-glycans released from bovine fetuin and ionised by electrospray, could be separated from residual glycopeptides allowing the minor, more highly sialylated compounds to be detected where their ions were obscured by ions from other compounds in different charge states. This technique was also found to be excellent for extracting the N-glycan profiles from contaminated samples. Structural identification of the glycans was performed by negative ion CID fragmentation, a method that provides a wealth of structurally diagnostic ions. However, fragment ions can also appear in the glycan profiles where they can be mistaken for glycan molecular ions. Fragments and molecular ions were frequently shown to have different drift time profiles, allowing them to be differentiated. Some separation of isomers was found but only for the smallest compounds. Differentiation from conformers was achieved by plotting drift time profiles of the fragments; these profiles matched those of the precursor ions where conformers were present. The techniques were applied to investigations of N-glycans released from the fungus Piptoporus betulinus where the technique was used to separate different carbohydrate types present in biological extracts
Providing value to a business using a lightweight design system to support knowledge reuse by designers
No full textThis paper describes an alternative approach to knowledge based systems in engineering than traditional geometry or explicit knowledge focused systems. Past systems have supported product optimisation rather than creative solutions and provide little benefit to businesses for bespoke and low volume products or products which do not benefit from optimisation. The approach here addresses this by supporting the creativity of designers through codified tacit knowledge and encouraging knowledge reuse for bespoke product development, in particular for small to medium sized enterprises. The implementation and evaluation of the approach is described within a company producing bespoke fixtures and tooling in shorter than average lead times. The active support of knowledge management in the company is intended to add value to the business by further reducing the lead times of the designs and creating a positive impact to business processes. The evaluation demonstrates a viable alternative framework to the traditional management of knowledge in engineering, which could be implemented by other small to medium enterprises
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