Discriminating antigen and non-antigen using proteome dissimilarity III:tumour and parasite antigens

Computational genome analysis enables systematic identification of potential immunogenic proteins within a pathogen. Immunogenicity is a system property that arises through the interaction of host and pathogen as mediated through the medium of a immunogenic protein. The overt dissimilarity of pathogenic proteins when compared to the host proteome is conjectured by some to be the determining principal of immunogenicity. Previously, we explored this idea in the context of Bacterial, Viral, and Fungal antigen. In this paper, we broaden and extend our analysis to include complex antigens of eukaryotic origin, arising from tumours and from parasite pathogens. For both types of antigen, known antigenic and non-antigenic protein sequences were compared to human and mouse proteomes. In contrast to our previous results, both visual inspection and statistical evaluation indicate a much wider range of homologues and a significant level of discrimination; but, as before, we could not determine a viable threshold capable of properly separating non-antigen from antigen. In concert with our previous work, we conclude that global proteome dissimilarity is not a useful metric for immunogenicity for presently available antigens arising from Bacteria, viruses, fungi, parasites, and tumours. While we see some signal for certain antigen types, using dissimilarity is not a useful approach to identifying antigenic molecules within pathogen genomes.

Discriminating antigen and non-antigen using proteome dissimilarity II:viral and fungal antigens

Immunogenicity arises via many synergistic mechanisms, yet the overall dissimilarity of pathogenic proteins versus the host proteome has been proposed as a key arbiter. We have previously explored this concept in relation to Bacterial antigens; here we extend our analysis to antigens of viral and fungal origin. Sets of known viral and fungal antigenic and non-antigenic protein sequences were compared to human and mouse proteomes. Both antigenic and non-antigenic sequences lacked human or mouse homologues. Observed distributions were compared using the non-parametric Mann-Whitney test. The statistical null hypothesis was accepted, indicating that antigen and non-antigens did not differ significantly. Likewise, we could not determine a threshold able meaningfully to separate non-antigen from antigen. We conclude that viral and fungal antigens cannot be predicted from pathogen genomes based solely on their dissimilarity to mammalian genomes.

Discriminating behaviors through value added premium online grocery offering

Despite many interest in e-grocery, little has changed, over the years, in the offering that is often geared only towards low value staple products. Yet, from an e-supermarket perspective, the number of sourcing stores is increasing regularly providing an illusion of service improvement. This situation, we argue is leading e-grocery providers to forego profits as consumers need to look both at the competition online and offline to satisfy their overall regular grocery needs. Expansion of e-grocery operations could be better achieved, we argue, by serving diverse and premium priced products (e.g. organic, limited production, regional items; special occasions items and products related to health e.g. allergies, diabetes) and utilizing more efficiently modern logistic techniques. A framework is offered presenting a model including the delivery of premium products from various suppliers and providing an integrated service solution to e-grocery customers that complete traditional supermarket ranges, creating potential high value added products niches. In this context, the objective was to understand the consumer discrimination factors (ie: range of product, delivery timing, location, service quality) leading to intentions towards purchasing more items from e-grocery retailers. Data are derived from a survey of 356 respondents in Turkey’s three biggest metropolitan areas. The relationship between consumer attitudes and demographic characteristics are also analyzed. Factor and SEM analyses are used to discriminate within the sample (n=356, no of items=150). Results, future research and policy implications are discussed.

Current capacity limits and activities within the EU project MODE-GAP to overcome them

In this presentation we will discuss the implications of the so called Nonlinear Shannon Limit. We will compare technologies including new fibres for long haul transmission and techniques to expand the capacity of existing standard single mode fibres.

Discriminating contact in lumen with a moving flexible digit using fibre Bragg grating sensing elements

Minimal access procedures in surgery offer benefits of reduced patient recovery time and less pain, yet for the surgeon the task is more complex, as both tactile and visual perception of the working site is reduced. In this paper, experimental evidence of the performance of a novel sensing system embedded in an actuated flexible digit element is presented. The digit represents a steerable tip element of devices such as endoscopes and laparoscopes. This solution is able to discriminate types of contact and tissue interaction, and to feed back this information with the shape of the flexible digit. As an alternative to this information, force level, force distribution, and other quantifiable descriptors can also be evaluated. These can be used to aid perception in processes such as navigation and investigation of tissues through palpation. The solution is pragmatic, and by virtue of its efficient mechanical construction and a polymer construction, it offers opportunities for a disposable element with suitability for magnetic resonance imaging (MRI) and other scanning environments. By using only four photonics sensing elements, full perception of tissue contact and the shape of the actuated digit can be described in the feedback of this information. The distributive sensory method applied to the sensory signals relies on the coupled values of the sensory data transients of the four deployed sensing elements to discriminate tissue interaction directly in near real time.

Local delivery of the KCa3.1 blocker, TRAM-34, prevents acute angioplasty-induced coronary smooth muscle phenotypic modulation and limits stenosis

Objective-We previously demonstrated that upregulation of intermediate-conductance Ca2+ -activated K+ channels (KCa 3.1) is necessary for mitogen-induced phenotypic modulation in isolated porcine coronary smooth muscle cells (SMCs). The objective of the present study was to determine the role of KCa3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis. Methods and Results-Balloon angioplasty was performed on coronary arteries of swine using either noncoated or balloons coated with the specific KCa3.1 blocker TRAM-34. Expression of KCa3.1, c-jun, c-fos, repressor element-1 silencing transcription factor (REST), smooth muscle myosin heavy chain (SMMHC), and myocardin was measured using qRT-PCR in isolated medial cells 2 hours and 2 days postangioplasty. KCa3.1, c-jun, and c-fos mRNA levels were increased 2 hours postangioplasty, whereas REST expression decreased. SMMHC expression was unchanged at 2 hours, but decreased 2 days postangioplasty. Use of TRAM-34 coated balloons prevented KCa3.1 upregulation and REST downregulation at 2 hours, SMMHC and myocardin downregulation at 2 days, and attenuated subsequent restenosis 14 and 28 days postangioplasty. Immunohistochemical analysis demonstrated corresponding changes at the protein level. Conclusion-Blockade of KCa3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis. © 2008 American Heart Association, Inc.

Direct measurement of coherency limits for strain relaxation in heteroepitaxial core/shell nanowires

The growth of heteroepitaxially strained semiconductors at the nanoscale enables tailoring of material properties for enhanced device performance. For core/shell nanowires (NWs), theoretical predictions of the coherency limits and the implications they carry remain uncertain without proper identification of the mechanisms by which strains relax. We present here for the Ge/Si core/shell NW system the first experimental measurement of critical shell thickness for strain relaxation in a semiconductor NW heterostructure and the identification of the relaxation mechanisms. Axial and tangential strain relief is initiated by the formation of periodic a/2 〈110〉 perfect dislocations via nucleation and glide on {111} slip-planes. Glide of dislocation segments is directly confirmed by real-time in situ transmission electron microscope observations and by dislocation dynamics simulations. Further shell growth leads to roughening and grain formation which provides additional strain relief. As a consequence of core/shell strain sharing in NWs, a 16 nm radius Ge NW with a 3 nm Si shell is shown to accommodate 3% coherent strain at equilibrium, a factor of 3 increase over the 1 nm equilibrium critical thickness for planar Si/Ge heteroepitaxial growth. © 2012 American Chemical Society.

A predictor of membrane class:discriminating α-helical and β-barrel membrane proteins from non-membranous proteins

Accurate protein structure prediction remains an active objective of research in bioinformatics. Membrane proteins comprise approximately 20% of most genomes. They are, however, poorly tractable targets of experimental structure determination. Their analysis using bioinformatics thus makes an important contribution to their on-going study. Using a method based on Bayesian Networks, which provides a flexible and powerful framework for statistical inference, we have addressed the alignment-free discrimination of membrane from non-membrane proteins. The method successfully identifies prokaryotic and eukaryotic α-helical membrane proteins at 94.4% accuracy, β-barrel proteins at 72.4% accuracy, and distinguishes assorted non-membranous proteins with 85.9% accuracy. The method here is an important potential advance in the computational analysis of membrane protein structure. It represents a useful tool for the characterisation of membrane proteins with a wide variety of potential applications.

Discriminating contact in lumen with a moving flexible digit using fibre Bragg grating sensing elements

Minimal access procedures in surgery offer benefits of reduced patient recovery time and less pain, yet for the surgeon the task is more complex, as both tactile and visual perception of the working site is reduced. In this paper, experimental evidence of the performance of a novel sensing system embedded in an actuated flexible digit element is presented. The digit represents a steerable tip element of devices such as endoscopes and laparoscopes. This solution is able to discriminate types of contact and tissue interaction, and to feed back this information with the shape of the flexible digit. As an alternative to this information, force level, force distribution, and other quantifiable descriptors can also be evaluated. These can be used to aid perception in processes such as navigation and investigation of tissues through palpation. The solution is pragmatic, and by virtue of its efficient mechanical construction and a polymer construction, it offers opportunities for a disposable element with suitability for magnetic resonance imaging (MRI) and other scanning environments. By using only four photonics sensing elements, full perception of tissue contact and the shape of the actuated digit can be described in the feedback of this information. The distributive sensory method applied to the sensory signals relies on the coupled values of the sensory data transients of the four deployed sensing elements to discriminate tissue interaction directly in near real time.

Translating Nietzsche, mediating literature: Alexander Tille and the limits of Anglo-German intercultural transfer

Dr. Alexander Tille (1866–1912) was one of the key-figures in Anglo-German intercultural transfer towards the end of the 19th century. As a lecturer in German at Glasgow University he was the first to translate and edit Nietzsche’s work into English. Writers such as W. B. Yeats were influenced by Nietzsche and used Tille’s translations. Tille’s social Darwinist reading of the philosopher’s oeuvre, however, had a narrowing impact on the reception of Nietzsche in the Anglo-Saxon world for decades. Through numerous publications Tille disseminated knowledge about British authors (e.g., Robert Louis Stevenson, William Wordsworth) in Germany and about German authors (e.g., Johann Wolfgang von Goethe) in Britain. His role as mediator also extended into areas such as history, religion, and industry. During the Boer war, however, Tille’s outspoken pro-German nationalism brought him in conflict with his British host society. After being physically attacked by his students he returned to Germany and published a highly anglophobic monograph. Tille personifies the paradox of Anglo-German relations in the pre-war years, which deteriorated despite an increase in intercultural transfer and knowledge about the respective Other.

Reshoring:opportunities and limits for manufacturing in the UK - the case of the auto sector

In recent years, offshoring and outsourcing have transformed fundamentally nationally based auto sectors into global networks of design, production and distribution across the global value chains coordinated by the major automotive Original Equipment Manufacturers (OEMs). As manufacturing activities tended to be shifted to low-labour cost locations in Asia, Africa and Latin America, high-end design, R&D, product development have stayed anchored mostly to high-cost and high knowledge-intensive home economy locations (perhaps with the except of some design and styling activities which are often located in major end markets around the world. However, very recently the weaknesses of and risks inherent in such global value chains (GVCs) have been exposed, triggering attempts to rethink their nature and also raising possibilities to reshore some manufacturing activities to home countries. A combination of a more competitive exchange rate (despite the very recent appreciation of sterling), increased transport costs, rising wages in key areas of China, and a greater awareness of supply chain resilience have all contributed to a perceived change in some business fundamentals. The potential for some supply chain relocalisation also links in with the servitisation of manufacturing including the auto sector and shift to a hybrid model where manufacturing and services are increasingly intertwined. However, there are limits as to how far this can go and these raise some important questions and issues over the possible role for industrial policy.

Manufacturing reshoring and its limits:the UK automotive case

This paper explores the meaning of reshoring and its drivers in the case of UK manufacturing and in particular its automotive sector. Drawing on interviews, policy reviews and a range of recent surveys, the paper finds that while reshoring is a discernable trend in UK manufacturing, it is less pronounced than many have claimed and that – in the UK case at least - there are severe limits as to how far this reshoring trend can go, particularly in relation to the availability of skills and finance in the supply chain. This is in turn raises questions over the stance of British policy and whether more could be done, with comparisons made to US experience.

Suboptimal Nonparametric Hypotheses Discriminating from Small Dependent Observations

2000 Mathematics Subject Classification: 62L10.

Capacity limits of systems employing multiple optical phase conjugators

We extend the theory of parametric noise amplification to the case of transmission systems employing multiple optical phase conjugators, demonstrating that the excess noise due to this process may be reduced in direct proportion to the number of phase conjugation devices employed. We further identify that the optimum noise suppression is achieved for an odd number of phase conjugators, and that the noise may be further suppressed by up to 3dB by partial digital back propagation (or fractional spans at the ends of the links).