Strategic Management of Integrated Public Transport and its Value in the Air Bus Service Context

While there is a well-developed body of academic literature on how to procure ground transport services and how to integrate those services, there is virtually no literature on how to do this in the context of air services (in combination with ground services). This paper aims to substantially contribute to the area of strategic management of integrated transport based on the concept of mobility as a service including revenue management, marketing operations management and also policy making. All these areas relate to improving efficiency, acceptability and profitability of air services to regional and remote areas (but also air services more generally) that can benefit significantly from any form of integration (integrated fares, timetables, customer information, marketing etc.). We show that customer-centric public transport integration with aviation as the highest priority can create competitive advantage of the air bus transport value chain as particularly in the regional aviation context the total trip travel experience is of high importance given the potential competition from private car travel, except for island air services. The public ground transport experience will therefore not only impact on the perceived flight product quality but also on other products along the aviation value chain. In terms of the demand analysis and travel choice literature, we reveal that integrated planning and management efforts such as joint timetabling and joint pricing are most likely to have an impact on competitive advantage, demand (passenger numbers plus yields, measured in the customers’ willingness to pay) and hence the profitability of regional air services. We use stated choice experiments for flights from Sydney to regional NSW, Australia to establish the willingness to pay for integrated add-ons to scheduled regional air services

Collaboration as a service (CaaS) to fully integrate public transportation – lessons from long distance travel to reimagine Mobility as a Service

Integrated mobility aims to improve multimodal integration to make public transport an attractive alternative to private transport. This paper critically reviews extant literature and current public transport governance frameworks of both macro and micro transport operators. Our aim is to extent the concept of Mobility-as-a-Service (MaaS), a proposed coordination mechanism for public transport that in our view is yet to prove its commercial viability and general acceptance. Drawing from the airline experience, we propose that smart ticketing systems, providing Software-as-a-Service (SaaS) can be extended with governance and operational processes that enhance their ability to facilitate Collaboration-as-a-Service (CaaS) to offer a reimagined MaaS 2.0 = CaaS + SaaS. Rather than using the traditional MaaS broker, CaaS incorporates operators more fully and utilises their commercial self-interest to deliver commercially viable and attractive integrated public transport solutions to consumers. This would also facilitate more collaboration of private sector operators into public transport with potentially new opportunities for taxi/rideshare/bikeshare operators and cross geographical transport providers (i.e. transnational multimodal operating companies) to integrate

Air safety & security: Traveller perceptions post the Malaysian Air disasters

Air transport is of substantial importance to economies, societies and freedom as it connects businesses and individuals with the world. However, two recent Malaysia Airlines incidents have resulted in even more security measures at airports and have anecdotally changed the security and safety perceptions of the traveling (or no longer traveling) public. Our study investigates for the first time attitudes towards air travel, safety and security and determines empirically if travellers are willing to experience even more invasive security measures in light of these tragedies. Our results suggest that there is a latent demand for air services despite the recent of the Malaysian Airline tragedies. Out of our proposed measures the presence of visible uniformed police creates the greatest feeling of security and it is seen as important to better communicate what security operations do and why it is effective in threat minimisation. We find willingness to pay for avoiding additional incidents both in terms of money and time but respondents are also willing to pay more to speed up the security process. Our results also suggest there is no desire to accept security processes that invade privacy considerably more what is currently practiced. We conclude that with respect to air travel the magnitude of trade-of between personal freedoms for improved security is limited. Travellers appear willing to accept risks, or perceive them as isolated and limited to airlines with inferior safety records and/or destinations with inferior security records

Louis Reichardt: The long climb to science's summits

From the highest mountains to biology's own Everest—the brain—Reichardt tackles the biggest challenges of climbing and biology

A poxvirus pseudokinase represses viral DNA replication via a pathway antagonized by its paralog kinase

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that mutations correlating with a loss of function of the vaccinia B12 pseudokinase provide a striking fitness enhancement to this virus. In support of predictions that reductive evolution is a driver of poxvirus adaptation, this is clear experimental evidence that gene loss can be of significant benefit. Next, we present multiple lines of evidence demonstrating that expression of full length B12 leads to a fitness reduction in viruses with a defect in B1, but has no apparent impact on wild-type virus or other mutant poxviruses. From these data we infer that B12 possesses a potent inhibitory activity that can be masked by the presence of the B1 kinase. Further investigation of B12 attributes revealed that it primarily localizes to the nucleus, a characteristic only rarely found among poxviral proteins. Surprisingly, BAF phosphorylation is reduced under conditions in which B12 is present in infected cells without B1, indicating that B12 may function in part by enhancing antiviral activity of BAF. Together, our studies of B1 and B12 present novel evidence that a paralogous kinase-pseudokinase pair can exhibit a unique epistatic relationship in a virus, perhaps serving to enhance B1 conservation during poxvirus evolution and to orchestrate yet-to-be-discovered nuclear events during infection

Reforming Test Standards to Expand Student Opportunities

A poster presented by Riley Ground, Katie Lester, Ali Owen, Matthew Maines, Noah Thacker and Rico Walker for the class Design of Everyday Things.https://scholarworks.moreheadstate.edu/gsp_projects_2019/1014/thumbnail.jp

Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors

[EN] Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length FN to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) in these hydrogels to enhance angiogenesis and bone regeneration, respectively. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.This study was supported by the UK Regenerative Medicine Platform (MRC grant MR/L022710/1), the UK Engineering and Physical Sciences Research Council (EPSRC EP/P001114/1) and a programme grant from the Sir Bobby Charlton Foundation. mu CT work was supported by the European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013) (grant agreement No. [615030]). S.T. acknowledges support from the University of Glasgow through their internal scholarship funding program. We thank the support of David Adams (Anatomy lab, University of Glasgow) and the Biological Services and Veterinary Research Facility (University of Glasagow) for their assistance.Trujillo-Muñoz, S.; González-García, C.; Rico Tortosa, PM.; Reid, A.; Windmill, J.; Dalby, MJ.; Salmerón Sánchez, M. (2020). Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors. Biomaterials. 252:1-15. https://doi.org/10.1016/j.biomaterials.2020.120104S115252Jarad, M., Kuczynski, E. A., Morrison, J., Viloria-Petit, A. M., & Coomber, B. L. (2017). Release of endothelial cell associated VEGFR2 during TGF-β modulated angiogenesis in vitro. BMC Cell Biology, 18(1). doi:10.1186/s12860-017-0127-ySpence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K., … Wells, J. M. (2010). Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature, 470(7332), 105-109. doi:10.1038/nature09691Yang, S.-J., Son, J. 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M., Tortelli, F., Mochizuki, M., Traub, S., Ben-David, D., Kuhn, G. A., … Hubbell, J. A. (2011). Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing. Science Translational Medicine, 3(100). doi:10.1126/scitranslmed.3002614Wijelath, E. S., Rahman, S., Namekata, M., Murray, J., Nishimura, T., Mostafavi-Pour, Z., … Sobel, M. (2006). Heparin-II Domain of Fibronectin Is a Vascular Endothelial Growth Factor-Binding Domain. Circulation Research, 99(8), 853-860. doi:10.1161/01.res.0000246849.17887.66Wijelath, E. S., Rahman, S., Murray, J., Patel, Y., Savidge, G., & Sobel, M. (2004). Fibronectin promotes VEGF-induced CD34+ cell differentiation into endothelial cells. Journal of Vascular Surgery, 39(3), 655-660. doi:10.1016/j.jvs.2003.10.042Wijelath, E. S., Murray, J., Rahman, S., Patel, Y., Ishida, A., Strand, K., … Sobel, M. (2002). 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Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor α4β1. Cell, 60(1), 53-61. doi:10.1016/0092-8674(90)90715-qWayner, E. A., Garcia-Pardo, A., Humphries, M. J., McDonald, J. A., & Carter, W. G. (1989). Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. Journal of Cell Biology, 109(3), 1321-1330. doi:10.1083/jcb.109.3.1321Hielscher, A., Ellis, K., Qiu, C., Porterfield, J., & Gerecht, S. (2016). Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis. PLOS ONE, 11(1), e0147600. doi:10.1371/journal.pone.0147600Zhou, X., Rowe, R. G., Hiraoka, N., George, J. P., Wirtz, D., Mosher, D. F., … Weiss, S. J. (2008). Fibronectin fibrillogenesis regulates three-dimensional neovessel formation. Genes & Development, 22(9), 1231-1243. doi:10.1101/gad.1643308Pankov, R., & Yamada, K. M. (2002). Fibronectin at a glance. 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Annals of Biomedical Engineering, 43(3), 489-500. doi:10.1007/s10439-015-1297-4Myeroff, C., & Archdeacon, M. (2011). Autogenous Bone Graft: Donor Sites and Techniques. Journal of Bone and Joint Surgery, 93(23), 2227-2236. doi:10.2106/jbjs.j.01513Dimitriou, R., Mataliotakis, G. I., Angoules, A. G., Kanakaris, N. K., & Giannoudis, P. V. (2011). Complications following autologous bone graft harvesting from the iliac crest and using the RIA: A systematic review. Injury, 42, S3-S15. doi:10.1016/j.injury.2011.06.015Curry, A. S., Pensa, N. W., Barlow, A. M., & Bellis, S. L. (2016). Taking cues from the extracellular matrix to design bone-mimetic regenerative scaffolds. Matrix Biology, 52-54, 397-412. doi:10.1016/j.matbio.2016.02.011Wang, L., Fan, H., Zhang, Z.-Y., Lou, A.-J., Pei, G.-X., Jiang, S., … Jin, D. (2010). Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells. Biomaterials, 31(36), 9452-9461. doi:10.1016/j.biomaterials.2010.08.036Almany, L., & Seliktar, D. (2005). Biosynthetic hydrogel scaffolds made from fibrinogen and polyethylene glycol for 3D cell cultures. Biomaterials, 26(15), 2467-2477. doi:10.1016/j.biomaterials.2004.06.047Nakatsu, M. N., Sainson, R. C. A., Aoto, J. N., Taylor, K. L., Aitkenhead, M., Pérez-del-Pulgar, S., … Hughes, C. C. W. (2003). Angiogenic sprouting and capillary lumen formation modeled by human umbilical vein endothelial cells (HUVEC) in fibrin gels: the role of fibroblasts and Angiopoietin-1☆. Microvascular Research, 66(2), 102-112. doi:10.1016/s0026-2862(03)00045-1Li, S., Nih, L. R., Bachman, H., Fei, P., Li, Y., Nam, E., … Segura, T. (2017). Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability. Nature Materials, 16(9), 953-961. doi:10.1038/nmat4954Phelps, E. A., Enemchukwu, N. O., Fiore, V. F., Sy, J. C., Murthy, N., Sulchek, T. A., … García, A. J. (2011). Maleimide Cross-Linked Bioactive PEG Hydrogel Exhibits Improved Reaction Kinetics and Cross-Linking for Cell Encapsulation and In Situ Delivery. Advanced Materials, 24(1), 64-70. doi:10.1002/adma.201103574Phelps, E. A., Templeman, K. L., Thulé, P. M., & García, A. J. (2013). Engineered VEGF-releasing PEG–MAL hydrogel for pancreatic islet vascularization. Drug Delivery and Translational Research, 5(2), 125-136. doi:10.1007/s13346-013-0142-2Zhang, C., Ramanathan, A., & Karuri, N. W. (2014). Proteolytically stabilizing fibronectin without compromising cell and gelatin binding activity. Biotechnology Progress, 31(1), 277-288. doi:10.1002/btpr.2018Zhang, C., Desai, R., Perez-Luna, V., & Karuri, N. (2014). PEGylation of lysine residues improves the proteolytic stability of fibronectin while retaining biological activity. Biotechnology Journal, 9(8), 1033-1043. doi:10.1002/biot.201400115Francisco, A. T., Hwang, P. Y., Jeong, C. G., Jing, L., Chen, J., & Setton, L. A. (2014). Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for intervertebral disc regeneration. Acta Biomaterialia, 10(3), 1102-1111. doi:10.1016/j.actbio.2013.11.013Seidlits, S. K., Drinnan, C. T., Petersen, R. R., Shear, J. B., Suggs, L. J., & Schmidt, C. E. (2011). Fibronectin–hyaluronic acid composite hydrogels for three-dimensional endothelial cell culture. Acta Biomaterialia, 7(6), 2401-2409. doi:10.1016/j.actbio.2011.03.024Lutolf, M. P., & Hubbell, J. A. (2003). Synthesis and Physicochemical Characterization of End-Linked Poly(ethylene glycol)-co-peptide Hydrogels Formed by Michael-Type Addition. Biomacromolecules, 4(3), 713-722. doi:10.1021/bm025744eCambria, E., Renggli, K., Ahrens, C. C., Cook, C. D., Kroll, C., Krueger, A. T., … Griffith, L. G. (2015). Covalent Modification of Synthetic Hydrogels with Bioactive Proteins via Sortase-Mediated Ligation. Biomacromolecules, 16(8), 2316-2326. doi:10.1021/acs.biomac.5b00549Leslie-Barbick, J. E., Moon, J. J., & West, J. L. (2009). Covalently-Immobilized Vascular Endothelial Growth Factor Promotes Endothelial Cell Tubulogenesis in Poly(ethylene glycol) Diacrylate Hydrogels. Journal of Biomaterials Science, Polymer Edition, 20(12), 1763-1779. doi:10.1163/156856208x386381Ferrara, N., Gerber, H.-P., & LeCouter, J. (2003). The biology of VEGF and its receptors. Nature Medicine, 9(6), 669-676. doi:10.1038/nm0603-669Phelps, E. A., & García, A. J. (2010). Engineering more than a cell: vascularization strategies in tissue engineering. Current Opinion in Biotechnology, 21(5), 704-709. doi:10.1016/j.copbio.2010.06.005Ferrara, N., & Kerbel, R. S. (2005). Angiogenesis as a therapeutic target. Nature, 438(7070), 967-974. doi:10.1038/nature04483Semenza, G. L. (2007). Vasculogenesis, angiogenesis, and arteriogenesis: Mechanisms of blood vessel formation and remodeling. Journal of Cellular Biochemistry, 102(4), 840-847. doi:10.1002/jcb.21523Ribatti, D. (2016). The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model. Mechanisms of Development, 141, 70-77. doi:10.1016/j.mod.2016.05.003Shekaran, A., García, J. R., Clark, A. Y., Kavanaugh, T. E., Lin, A. S., Guldberg, R. E., & García, A. J. (2014). Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle. Biomaterials, 35(21), 5453-5461. doi:10.1016/j.biomaterials.2014.03.055Cruz-Acuña, R., Quirós, M., Farkas, A. E., Dedhia, P. H., Huang, S., Siuda, D., … García, A. J. (2017). Synthetic hydrogels for human intestinal organoid generation and colonic wound repair. Nature Cell Biology, 19(11), 1326-1335. doi:10.1038/ncb3632Cruz-Acuña, R., Quirós, M., Huang, S., Siuda, D., Spence, J. R., Nusrat, A., & García, A. J. (2018). PEG-4MAL hydrogels for human organoid generation, culture, and in vivo delivery. Nature Protocols, 13(9), 2102-2119. doi:10.1038/s41596-018-0036-3Baker, A. E. G., Bahlmann, L. C., Tam, R. Y., Liu, J. C., Ganesh, A. N., Mitrousis, N., … Shoichet, M. S. (2019). 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The effect of SDF-1α on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model. Journal of Biomedical Materials Research Part A, 104(9), 2126-2134. doi:10.1002/jbm.a.3574

The Vaccinia Virus (VACV) B1 and Cellular VRK2 Kinases Promote VACV Replication Factory Formation through Phosphorylation-Dependent Inhibition of VACV B12

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and viral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a common pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vaccinia virus protein B12, which otherwise impedes an early event in the viral lifecycle. Herein, we characterize the B1/VRK2 signaling axis to better understand their shared functions. First, we demonstrate that vaccinia virus uniquely requires VRK2 for viral replication in the absence of B1, unlike other DNA viruses. Employing loss-of-function analysis, we demonstrate that vaccinia virus’s dependence on VRK2 is only observed in the presence of B12, suggesting that B1 and VRK2 share a pathway controlling B12. Moreover, we substantiate a B1/VRK2/B12 signaling axis by examining coprecipitation of B12 by B1 and VRK2. Employing execution point analysis, we reveal that virus replication proceeds normally through early protein translation and uncoating but stalls at replication factory formation in the presence of B12 activity. Finally, structure/function analyses of B1 and VRK2 demonstrate that enzymatic activity is essential for B1 or VRK2 to inhibit B12. Together, these data provide novel insights into B1/VRK signaling coregulation and support a model in which these enzymes modulate B12 in a phosphorylation-dependent manner

Quantitative and Temporal Definition of the Mla Transcriptional Regulon During Barley–Powdery Mildew Interactions

Barley Mildew resistance locus a (Mla) is a major determinant of immunity to the powdery mildew pathogen, Blumeria graminis f. sp. hordei. Alleles of Mla encode cytoplasmic- and membrane-localized coiled-coil, nucleotide binding site, leucine-rich repeat proteins that mediate resistance when complementary avirulence effectors (AVRa) are present in the pathogen. Presence of an appropriate AVRa protein triggers nuclear relocalization of MLA, in which MLA binds repressing host transcription factors. Timecourse expression profiles of plants harboring Mla1, Mla6, and Mla12 wild-type alleles versus paired loss-of-function mutants were compared to discover conserved transcriptional targets of MLA and downstream signaling cascades. Pathogen-dependent gene expression was equivalent or stronger in susceptible plants at 20 h after inoculation (HAI) and was attenuated at later timepoints, whereas resistant plants exhibited a time-dependent strengthening of the transcriptional response, increasing in both fold change and the number of genes differentially expressed. Deregulation at 20 HAI implicated 16 HAI as a crucial point in determining the future trajectory of this interaction and was interrogated by quantitative analysis. In total, 28 potential transcriptional targets of the MLA regulon were identified. These candidate targets possess a diverse set of predicted functions, suggesting that multiple pathways are required to mediate the hypersensitive reaction