URRUC - Urban-rural Connectivity in Non-metropolitan Regions. Annex II: Conceptualisation and Methodology

Annex II contains a methodological overview of the URRUC project

Urban-rural Connectivity in Non-metropolitan Regions (URRUC)

Annex I focuses on contextualising non-metropolitan regions, including an in-depth focus on literature and European projects related to urban-rural connectivity in these areas

URRUC - Urban-rural Connectivity in Non-metropolitan Regions. Final report

Urban-rural linkages and interactions are of vital importance for the future development of the non-metropolitan regions and to achieve the Europe 2020 goals of smart, sustainable and inclusive growth actively supported by the current European Structural and Investment Funds and a number of EU policy initiatives. In particular, the new Cohesion Policy Regulation (2014-2020) puts a strong emphasis on the role of urban-rural interactions for achieving better coordination of structural funds as well as new tools fostering integrated strategies which can allow for EU Member States to make territorial investments in a more flexible and targeted way. The European Commission is currently working with the Member States, industry and public authorities to roll-out the “Intelligent Transport Systems” (ITS) initiative, which is considered “vital to increase safety and tackle Europe's growing emission and congestion problems”, but also for creating new services and jobs as well as supporting growth in the transport sector. This type of innovative demand-response transport management system provides an ideal solution for rural and low-population metropolitan areas as it allows for tailor-made services giving rural residents possibilities to move with the same freedom as residents in cities and towns. This has proven to be a cost-effective type of transport system offering wider territorial coverage The four stakeholders involved in this targeted analysis have identified a potential opportunity to improving transport policy and systems related to urban-rural connectivity in non-metropolitan areas by engaging in knowledge transfer processes and activities based on networks of exchange. This process will help identify good practices and generate recommendations for policy makers and stakeholders in the stakeholder regions and countries as well as in territories across the EU faced with similar challenges, particularly coastal locations with nearby isolated communities and hinterlands. The territorial evidence that will be produced within this activity will be particularly useful with regards to developing policies for non-metropolitan regions that suffer from limitations of connectivity, poor accessibility to services and unbalanced development by identifying good practices to improve the internal connectivity and sustainability of transport systems, supporting synergies and cross-sectoral dialogue, and advancing public transport planning

URRUC - Urban-Rural Connectivity in Non-Metropolitan Regions. Annex VIII: Policy Guidelines and Recommendations

Annex VIII contains a methodological overview of the policy development approach as well as the creation of European policy recommendations

Survey of Tyrosine Kinase Signaling Reveals ROS Kinase Fusions in Human Cholangiocarcinoma

Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23) of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted

Survey of Activated FLT3 Signaling in Leukemia

Activating mutations of FMS-like tyrosine kinase-3 (FLT3) are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3) and B cell acute lymphoblastic leukemia (normal and amplification of FLT3) cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC), we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr) that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia

EEG/ERP as a pragmatic method to expand the reach of infant-toddler neuroimaging in HBCD: Promises and challenges

Though electrophysiological measures (EEG and ERP) offer complementary information to MRI and a variety of advantages for studying infants and young children, these measures have not yet been included in large cohort studies of neurodevelopment. This review summarizes the types of EEG and ERP measures that could be used in the HEALthy Brain and Cognitive Development (HBCD) study, and the promises and challenges in doing so. First, we provide brief overview of the use of EEG/ERP for studying the developing brain and discuss exemplar findings, using resting or baseline EEG measures as well as the ERP mismatch negativity (MMN) as exemplars. We then discuss the promises of EEG/ERP such as feasibility, while balancing challenges such as ensuring good signal quality in diverse children with different hair types. We then describe an ongoing multi-site EEG data harmonization from our groups. We discuss the process of alignment and provide preliminary usability data for both resting state EEG data and auditory ERP MMN in diverse samples including over 300 infants and toddlers. Finally, we provide recommendations and considerations for the HBCD study and other studies of neurodevelopment