When Clusters become Networks

Policy makers spend large amounts of public resources on the foundation of science parks and other forms of geographically clustered business activities, in order to stimulate regional innovation. Underlying the relation between clusters and innovation is the assumption that co-located firms engaged in innovative activities benefit from knowledge that diffuses locally. In order to access this knowledge, firms are often required to form more- or less formal relations with co-located firms. Empirical evidence shows however that besides some success cases like Silicon Valley and the Emilia- Romagna region where firms collaborate intensively, many regional clusters are mere co-locations of firms. To enhance our understanding of why some clusters become networks of strategic collaboration and others don’t, we study link formation within European biopharmaceutical clusters. More specifically we look at the effect of cluster characteristics such as number of start-up firms, established firms or academic institutions, or the nature of the collaborations on the probability of local link formation

Come Close and Co-create: Proximities in Pharmaceutical Innovation Networks

In studying firm behavior, economists tend to have an under-socialized view of the firm, while sociologists tend to have an over-socialized view of the firm. Socialization in this respect refers to the extent to which a firm is embedded in- and affected by its relational environment. On the one extreme, economists building on transaction costs economics assume the market to be an anonymous environment where firms can behave opportunistically without reper

Developing credit risk score using SAS programming

Объектом исследования являются данные о кредитоспособности заемщиков. Предмет исследования: модель кредитного риска и системный интерфейс (GUI). Цель проекта - разработать систему на основе модели кредитного риска с использованием программирования SAS, чтобы помочь банку в принятии решений, контролировать риск и выбирать более хороших заемщиков и удалять плохих заемщиков из банка.The object of the study is data on the creditworthiness of borrowers. The subject of the research the credit risk model and make a system interface (GUI). The objective of the project is to develop the system from credit risk model by using SAS programming to help the bank in decision-making, control the risk and choose more good borrowers and delete bad borrowers from the bank. In the research project, to learn how to develop credit scoring using SAS programming and create program calculate credit risk score using Python . As a result of the study, it is show that to improves the accuracy of the assessment of creditworthiness by using logistic regression (selection variables method, evaluation dataset). The conclusion is the program calculator is made

Обнаружение бронхолегочных сегментов на основе интеграции методов локализации сущностей и семантической сегментации

В работе обсуждаются аспекты анализа интеллектуальных инструментов, пакетов и новых методов для автоматического обнаружения и распознавания патологий. Целью работы является обеспечение надежной процедуры сегментации изображений и обнаружения патологий для упрощения работы радиолога. В исследовании обсуждаются программные интерфейсы и тестирование предлагаемых решений для анализа КТ-изображений.Analysis of medical instruments, packages and images for automatic detection and recognition of pathologies. Providing image segmentation and pathology detection to simplify the work of a radiologist. Also providing a user friendly interface and testing it to analyse output results

Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.This work was supported by a PhD studentship funded by QMUL and awarded to D.C.S. and a Leverhulme Trust grant (RPG- 2013-351) awarded to M.R.E. Sequencing of the A. rubens neural transcriptome was funded by an EPSRC grant (EP/J501360/1

Radical Innovation and Network Evolution

This paper examines how a radical technological innovation affects alliance formation of firms and subsequent network structures. We use longitudinal data of interfirm R&D collaborations in the biopharmaceutical industry in which a new technological regime is established. Our findings suggest that it requires radical technological change for firms to leave their embedded path of existing alliances and form new alliances with new partners. While new partners are mostly found through the firms’ existing network, we provide some insight into distant link formation with unknown partners, which contributes to our understanding of how ‘small-worlds’ might emerg

The evolution of neuropeptide signalling: insights from echinoderms

This work was supported by Leverhulme Trust grant RGP-2013-351 and BBSRC grant BB/M001644/1 (awarded to M.R.E.). Dean Semmens has a BSc in Molecular and Cellular Biology (University of Bath, 2011), a PhD in Neurobiology (Queen Mary University of London, 2015) and is a Leverhulme Trust-funded Postdoctoral Fellow. Maurice Elphick studied at Royal Holloway University of London (BSc Biology, 1988; PhD Neurobiology, 1991) and became Professor of Physiology and Neuroscience at Queen Mary University of London in 2004

Transcriptomic analysis of crustacean neuropeptide signaling during the moult cycle in the green shore crab, Carcinus maenas

Abstract Background Ecdysis is an innate behaviour programme by which all arthropods moult their exoskeletons. The complex suite of interacting neuropeptides that orchestrate ecdysis is well studied in insects, but details of the crustacean ecdysis cassette are fragmented and our understanding of this process is comparatively crude, preventing a meaningful evolutionary comparison. To begin to address this issue we identified transcripts coding for neuropeptides and their putative receptors in the central nervous system (CNS) and Y-organs (YO) within the crab, Carcinus maenas, and mapped their expression profiles across accurately defined stages of the moult cycle using RNA-sequencing. We also studied gene expression within the epidermally-derived YO, the only defined role for which is the synthesis of ecdysteroid moulting hormones, to elucidate peptides and G protein-coupled receptors (GPCRs) that might have a function in ecdysis. Results Transcriptome mining of the CNS transcriptome yielded neuropeptide transcripts representing 47 neuropeptide families and 66 putative GPCRs. Neuropeptide transcripts that were differentially expressed across the moult cycle included carcikinin, crustacean hyperglycemic hormone-2, and crustacean cardioactive peptide, whilst a single putative neuropeptide receptor, proctolin R1, was differentially expressed. Carcikinin mRNA in particular exhibited dramatic increases in expression pre-moult, suggesting a role in ecdysis regulation. Crustacean hyperglycemic hormone-2 mRNA expression was elevated post- and pre-moult whilst that for crustacean cardioactive peptide, which regulates insect ecdysis and plays a role in stereotyped motor activity during crustacean ecdysis, was elevated in pre-moult. In the YO, several putative neuropeptide receptor transcripts were differentially expressed across the moult cycle, as was the mRNA for the neuropeptide, neuroparsin-1. Whilst differential gene expression of putative neuropeptide receptors was expected, the discovery and differential expression of neuropeptide transcripts was surprising. Analysis of GPCR transcript expression between YO and epidermis revealed 11 to be upregulated in the YO and thus are now candidates for peptide control of ecdysis. Conclusions The data presented represent a comprehensive survey of the deduced C. maenas neuropeptidome and putative GPCRs. Importantly, we have described the differential expression profiles of these transcripts across accurately staged moult cycles in tissues key to the ecdysis programme. This study provides important avenues for the future exploration of functionality of receptor-ligand pairs in crustaceans

Untersuchungen zur Struktur und Funktion der Glutathionsynthetase bei der Spalthefe Schizosaccharomyces pombe

In the literature the enzyme glutathione synthetase of the fission yeast S. pombe had been described - in contrast to the homodimeric enzymes of other eucaryotic organisms - as a heterotetramer composed of two „large” 33 kDa and two „small” 26 kDa subunits. The „large” subunit had been assigned to the 3' region of the GSH2 gene. The sequences of the 56 kDa protein encoded by the full length S. pombe GSH2 open reading frame and glutathione synthetases from other eukaryotes show high levels of homology over the whole alignment. Based on this alignment and on the x-ray coordinates of the human enzyme, a structural model of the fission yeast glutathione synthetase was produced. According to this model, the structure of the fission yeast protein is very similar to its human ortholog. The amino acid residues essential for binding of the substrates and cofactors are highly conserved between the two enzymes. The only striking difference involves a 15 amino acid segment (residues 204 - 218), which only exists in the fission yeast protein. The S. pombe GSH2 gene was cloned, and a histidine-tag was attached to the C-terminus of the protein. The protein was expressed in S. pombe and purified by two-step affinity chromatography. The recovered enzyme occurred in two different forms: a homodimeric protein consisting of two identical 56 kDa subunits and a heterotetrameric protein composed of two „small” 24 kDa and two „large” 32 kDa subfragments. Both variants showed glutathione synthetase activity. Both the homodimer and the heterotetramer are encoded by the GSH2 gene. The 56 kDa subunit corresponds to the complete GSH2 open reading frame. By MALDI-TOF-MS and peptide mapping, the „small” subfragment was assigned to the 5' area of the open reading frame. The 24 kDa and the 32 kDa proteins are produced following proteolytic cleavage of the 56 kDa protein. The 24 kDa protein represents the N-terminal, the 32 kDa protein the C-terminal subfragment. Protease inhibition experiments showed that the protease responsible for cleaving belongs to the metalloproteases class. The cleavage site is localized between the amino acid residues alanine and serine at positions 217 and 218, as determined by N-terminal sequencing and MALDI-TOF-MS. Site-directed mutagenesis was performed to obtain a stable homodimer: The region around the cleavage site - the amino acid residues 204 - 218 - which only occur in the fission yeast protein, were deleted. The protein was enzymatically active in vivo and in vitro. The regions of the subfragments of glutathione synthetase were subcloned and co-expressed in S. pombe as independent proteins. A heterotetrameric protein, composed of two 24 kDa and 32 kDa subfragments each, was isolated. The protein was functional in vivo and in vitro, which means that the subfragments assemble correctly within the cell. Moreover, a permuted version of the fission yeast glutathione synthetase was created by interchanging the positions of the two subfragments within the protein. The permutation yielded a catalytically active protein. The presence of the additional 15 amino acid residues in the fission yeast protein may trace back to a permutation event during the evolution of glutathione synthetase. The presence of an exon boundary in the respective region of the human gene might indicate the mechanism by which the insert was eliminated during the evolution of metazoans. In a crystallization screen of the S. pombe glutathione synthetase several conditions were identified under which the protein formed glassy aggregates, similar to very small crystals. In order to get bigger monocrystals, suitable for x-ray structure analysis, the conditions will have to be further optimized. As a result, the extraordinary subunit structure of the fission yeast glutathione synthetase was clarified by this work. The theory of a permutation event during the evolution of the enzyme was reproduced experimentally. Furthermore, the homologous expression of several variants of glutathione synthetase showed that S. pombe can serve as a model organism to provide insight into the mechanisms of protein processing and folding within the cell