Phylogenetic inference using cytochrome c oxidase subunit I (COI) in the poultry red mite, Dermanyssus gallinae in the United Kingdom relative to a European framework

The poultry red mite (Dermanyssus gallinae), an obligatory blood feeding ectoparasite, is primarily associated with laying hens where it is estimated to cause losses of ~€231 million per annum to European farmers. Moderate to high infestation levels result in negative impacts on hen welfare, including increased cannibalism, irritation, feather pecking, restlessness, anaemia and mortality. Acaricides are currently the prevailing method of population control for D. gallinae, although resistance against some classes of acaricide has been widely reported. The development of resistance highlights a growing need for research into alternative control methods, including the development of a suitable and effective vaccine. Understanding the genetic structure of D. gallinae populations can support improved management of acaricide resistance and sustainability of future vaccines, but limited data are currently available. The aim of this study was to characterise D. gallinae isolates from Europe, targeting the cytochrome c oxidase subunit 1 (COI) gene to gain an insight into population structure and genetic diversity of currently circulating mites. Dermanyssus gallinae isolates were collected from Albania, Belgium, Croatia, Czech Republic, Denmark, France, Greece, Italy, the Netherlands, Portugal, Romania, Slovenia, Turkey and the United Kingdom. Genomic DNA was extracted from individual adult D. gallinae mites and a 681bp fragment of the COI gene was amplified and sequenced. Phylogenetic analyses of 195 COI sequences confirmed the presence of multiple lineages across Europe with 76 distinct haplotypes split across three main haplogroups and six sub-haplogroups. Importantly there is considerable inter- and intra-country variation across Europe, which could result from the movement of poultry or transfer of contaminated equipment and/or materials and husbandry practices

Hadronic Parity Violation and Inelastic Electron-Deuteron Scattering

We compute contributions to the parity-violating (PV) inelastic electron-deuteron scattering asymmetry arising from hadronic PV. While hadronic PV effects can be relatively important in PV threshold electro- disintegration, we find that they are highly suppressed at quasielastic kinematics. The interpretation of the PV quasielastic asymmetry is, thus, largely unaffected by hadronic PV.Comment: 27 pages, 13 figures, uses REVTeX and BibTe

Proteomics uncover EPHA2 as a potential novel therapeutic target in colorectal cancer cell lines with acquired cetuximab resistance.

BACKGROUND: In metastatic colorectal cancer (mCRC), acquired resistance against anti-EGFR targeted monoclonal antibodies, such as cetuximab (CET), was shown to be frequently caused by activating alterations in the RAS genes KRAS or NRAS. To this day, no efficient follow-up treatment option has emerged to treat mCRC in such a setting of resistance. METHODS: To uncover potential targets for second-line targeted therapies, we used mass-spectrometric proteomics to shed light on kinome reprogramming in an established cellular model of acquired, KRAS-associated CET resistance. RESULTS: This CET resistance was reflected by significant changes in the kinome, most of them individual to each cell line. Interestingly, all investigated resistant cell lines displayed upregulation of the Ephrin type-A receptor 2 (EPHA2), a well-known driver of traits of progression. Expectedly resistant cell lines displayed increased migration (p < 0.01) that was significantly reduced by targeting the EPHA2 signalling axis using RNA interference (RNAi) (p < 0.001), ephrin-A1 stimulation (p < 0.001), dasatinib (p < 0.01), or anti-EPHA2 antibody treatment (p < 0.001), identifying it as an actionable target in mCRC with acquired CET resistance. CONCLUSION: These results highlight EPHA2 and its role in mCRC with KRAS-gene mutated acquired CET resistance and support its use as a potential actionable target for the development of future precision medicine therapies

Enhancing modeling and change support for process families through change patterns

The increasing adoption of process-aware information systems (PAISs), together with the variability of business processes (BPs), has resulted in large collections of related process model variants (i.e., process families). To effectively deal with process families, several proposals (e.g., C-EPC, Provop) exist that extend BP modeling languages with variability-specific constructs. While fostering reuse and reducing modeling efforts, respective constructs imply additional complexity and demand proper support for process designers when creating and modifying process families. Recently, generic and language independent adaptation patterns were successfully introduced for creating and evolving single BP models. However, they are not sufficient to cope with the specific needs for modeling and evolving process families. This paper suggests a complementary set of generic and language-independent change patterns specifically tailored to the needs of process families. When used in combination with existing adaptation patterns, change patterns for process families will enable the modeling and evolution of process families at a high-level of abstraction. Further, they will serve as reference for implementing tools or comparing proposals managing process families. © 2013 Springer-Verlag.This work has been developed with the support of MICINN under the Project EVERYWARE TIN2010-18011.Ayora Esteras, C.; Torres Bosch, MV.; Weber, B.; Reichert, M.; Pelechano Ferragud, V. (2013). Enhancing modeling and change support for process families through change patterns. En Enterprise, Business-Process and Information Systems Modeling, BPMDS 2013. Springer Verlag. 246-260. https://doi.org/10.1007/978-3-642-38484-4_18S246260van der Aalst, W.M.P., ter Hofstede, A.H.M., Barros, B.: Workflow Patterns. Distributed and Parallel Databases 14(1), 5–51 (2003)Aghakasiri, Z., Mirian-Hosseinabadi, S.H.: Workflow change patterns: Opportunities for extension and reuse. In: Proc. SERA 2009, pp. 265–275 (2009)Ayora, C., Torres, V., Reichert, M., Weber, B., Pelechano, V.: Towards run-time flexibility for process families: Open issues and research challenges. In: La Rosa, M., Soffer, P. (eds.) BPM 2012 Workshops. LNBIP, vol. 132, pp. 477–488. Springer, Heidelberg (2013)Ayora, C., Torres, V., Weber, B., Reichert, M., Pelechano, V.: Change patterns for process families. Technical Report, PROS-TR-2012-06, http://www.pros.upv.es/technicalreports/PROS-TR-2012-06.pdfDadam, P., Reichert, M.: The ADEPT project: a decade of research and development for robust and flexible process support. Com. Sci. - R&D 23, 81–97 (2009)Dijkman, R., La Rosa, M., Reijers, H.A.: Managing large collections of business process models - Current techniques and challenges. Comp. in Ind. 63(2), 91–97 (2012)Döhring, M., Zimmermann, B., Karg, L.: Flexible workflows at design- and runtime using BPMN2 adaptation patterns. In: Abramowicz, W. (ed.) BIS 2011. LNBIP, vol. 87, pp. 25–36. Springer, Heidelberg (2011)Gottschalk, F.: Configurable process models. Ph.D. thesis, Eindhoven University of Technology, The Netherlands (2009)Grambow, G., Oberhauser, R., Reichert, M.: Contextual injection of quality measures into software engineering processes. Intl. J. Adv. in Software 4, 76–99 (2011)Gschwind, T., Koehler, J., Wong, J.: Applying patterns during business process modeling. In: Dumas, M., Reichert, M., Shan, M.-C. (eds.) BPM 2008. LNCS, vol. 5240, pp. 4–19. Springer, Heidelberg (2008)Günther, C.W., Rinderle, S., Reichert, M., van der Aalst, W.M.P.: Change mining in adaptive process management systems. In: Meersman, R., Tari, Z. (eds.) OTM 2006. LNCS, vol. 4275, pp. 309–326. Springer, Heidelberg (2006)Hallerbach, A., Bauer, T., Reichert, M.: Context-based configuration of process variants. In: Proc. TCoB 2008, pp. 31–40 (2008)Hallerbach, A., Bauer, T., Reichert, M.: Capturing variability in business process models: the Provop approach. J. of Software Maintenance 22(6-7), 519–546 (2010)Kitchenham, B., Charters, S.: Guidelines for performing Systematic Literature Reviews in Software Engineering, Technical Report EBSE/EPIC–2007–01 (2007)Kulkarni, V., Barat, S., Roychoudhury, S.: Towards business application product lines. In: France, R.B., Kazmeier, J., Breu, R., Atkinson, C. (eds.) MODELS 2012. LNCS, vol. 7590, pp. 285–301. Springer, Heidelberg (2012)Küster, J.M., Gerth, C., Förster, A., Engels, G.: Detecting and resolving process model differences in the absence of a change log. In: Dumas, M., Reichert, M., Shan, M.-C. (eds.) BPM 2008. LNCS, vol. 5240, pp. 244–260. Springer, Heidelberg (2008)Küster, J.M., Gerth, C., Engels, G.: Dynamic computation of change operations in version management of business process models. In: Kühne, T., Selic, B., Gervais, M.-P., Terrier, F. (eds.) ECMFA 2010. LNCS, vol. 6138, pp. 201–216. Springer, Heidelberg (2010)Lanz, A., Weber, B., Reichert, M.: Time patterns for process-aware information systems. Requirements Engineering, 1–29 (2012)La Rosa, M., van der Aalst, W.M.P., Dumas, M., ter Hofstede, A.H.M.: Questionnaire-based variability modeling for system configuration. Software and System Modeling 8(2), 251–274 (2009)Lerner, B.S., Christov, S., Osterweil, L.J., Bendraou, R., Kannengiesser, U., Wise, A.: Exception Handling Patterns for Process Modeling. IEEE Transactions on Software Engineering 36(2), 162–183 (2010)Li, C., Reichert, M., Wombacher, A.: Mining business process variants: Challenges, scenarios, algorithms. Data Knowledge & Engineering 70(5), 409–434 (2011)Marrella, A., Mecella, M., Russo, A.: Featuring automatic adaptivity through workflow enactment and planning. In: Proc. CollaborateCom 2011, pp. 372–381 (2011)Müller, D., Herbst, J., Hammori, M., Reichert, M.: IT support for release management processes in the automotive industry. In: Dustdar, S., Fiadeiro, J.L., Sheth, A.P. (eds.) BPM 2006. LNCS, vol. 4102, pp. 368–377. Springer, Heidelberg (2006)Reichert, M., Weber, B.: Enabling flexibility in process-aware information systems: challenges, methods, technologies. Springer (2012)Reinhartz-Berger, I., Soffer, P., Sturm, A.: Organizational reference models: supporting an adequate design of local business processes. IBPIM 4(2), 134–149 (2009)Rosemann, M., van der Aalst, W.M.P.: A configurable reference modeling language. Information Systems 32(1), 1–23 (2007)Russell, N., ter Hofstede, A.H.M., Edmond, D., van der Aalst, W.M.P.: Workflow data patterns. Technical Report FIT-TR-2004-01, Queensland Univ. of Technology (2004)Russell, N., ter Hofstede, A.H.M., Edmond, D., van der Aalst, W.M.P.: Workflow resource patterns. Technical Report WP 127, Eindhoven Univ. of Technology (2004)Russell, N., van der Aalst, W.M.P., ter Hofstede, A.H.M.: Workflow Exception Patterns. In: Martinez, F.H., Pohl, K. (eds.) CAiSE 2006. 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Cell- and Tissue-Specific Transcriptome Analyses of Medicago truncatula Root Nodules

Legumes have the unique ability to host nitrogen-fixing Rhizobium bacteria as symbiosomes inside root nodule cells. To get insight into this key process, which forms the heart of the endosymbiosis, we isolated specific cells/tissues at different stages of symbiosome formation from nodules of the model legume Medicago truncatula using laser-capture microdissection. Next, we determined their associated expression profiles using Affymetrix Medicago GeneChips. Cells were collected from the nodule infection zone divided into a distal (where symbiosome formation and division occur) and proximal region (where symbiosomes are mainly differentiating), as well as infected cells from the fixation zone containing mature nitrogen fixing symbiosomes. As non-infected cells/tissue we included nodule meristem cells and uninfected cells from the fixation zone. Here, we present a comprehensive gene expression map of an indeterminate Medicago nodule and selected genes that show specific enriched expression in the different cells or tissues. Validation of the obtained expression profiles, by comparison to published gene expression profiles and experimental verification, indicates that the data can be used as digital “in situ”. This digital “in situ” offers a genome-wide insight into genes specifically associated with subsequent stages of symbiosome and nodule cell development, and can serve to guide future functional studies

A Model Driven Approach to the Analysis of Timeliness Properties

Abstract. The need for a design language that is rigorous but accessible and intuitive is often at odds with the formal and mathematical nature of languages used for analysis. UML and Petri Nets are a good example of this dichotomy. UML is a widely accepted modelling language capable of modelling the structural and behavioural aspects of a system. However UML lacks the mathematical foundation that is required for rigorous analysis. Petri Nets on the other hand have a strong mathematical base that is well suited for analysis of a system but lacks the appeal and ease-of-use of UML. Design in UML languages such as Sequence Diagrams and analysis in Petri Nets require on one hand some expertise in potentially two incompatible systems and their tools, and on the other a seamless transition from one system to the other. One way of addressing this impediment is to focus the software development mainly on the design language system and to facilitate the transition to the formal analysis by means of a combination of automation and tool support. The aim of this paper is to present a transformation system, which takes UML Sequence Diagrams augmented with time constraints and generates semantically equivalent Petri Nets that preserve the timing requirements. A case study on a small network is used in order to illustrate the proposed approach and in particular the design, the transformation and the analysis processes.

Voltammetric determination of indomenthyl

Cytokines are important mediators coordinating inflammation and wound healing in response to tissue damage and infection. Therefore, immobilization of cytokines on the surface of biomaterials is a promising approach to improve biocompatibility. Soluble cytokines signal through receptors on the cell surface leading to cell differentiation, proliferation, or other effector functions. Random immobilization of cytokines on surfaces will result in a large fraction of inactive protein due to impaired cytokine-receptor interaction. We developed a strategy that combined (i) directed covalent coupling of cytokines, (ii) quantification of coupling efficiency through fluorescence detection, and (iii) a reliable protease cleavage assay to control orientation of coupling. For this purpose, fusion proteins of the SNAP-tag followed by an enterokinase recognition site, yellow fluorescent protein (YFP), and the cytokine of interest being either interleukin-6 (IL-6) or oncostatin M (OSM) were generated. The SNAP-tag is a derivative of O6-alkylguanine-DNA alkyltransferase that couples itself covalently to benzylguanine. Bioactivities of the SNAP-YFP-cytokines were shown to be comparable with the nontagged cytokines. Efficient coupling of SNAP-YFP-cytokines to benzylguanine-modified beads was demonstrated by flow cytometry. The fact that enterokinase treatment released most of the fluorescence from the beads is indicative for directed coupling and only marginal adsorptive binding. Cellular responses to SNAP-YFP-cytokine beads were analyzed in cellular lysates and by confocal microscopy indicating that the directionally immobilized cytokines are fully signaling competent with respect to the activation of ERK and STAT3. The strategy presented here is generally applicable for the directed covalent immobilization of fluorescently labeled proteins including the convenient and reliable control of coupling efficiency and orientation