Mobile transitions : exploring synergies for urban sustainability research

Urban sustainability approaches focusing on a wide range of topics such as infrastructure and mobility, green construction and neighbourhood planning, or urban nature and green amenities have attracted scholarly interest for over three decades. Recent debates on the role of cities in climate change mitigation have triggered new attempts to conceptually and methodologically grasp the cross-sectorial and cross-level interplay of enrolled actors. Within these debates, urban and economic geographers have increasingly adopted co-evolutionary approaches such as the social studies of technology (SST or ‘transition studies’). Their plea for more spatial sensitivity of the transition approach has led to promising proposals to adapt geographic perspectives to case studies on urban sustainability. This paper advocates engagement with recent work in urban studies, specifically policy mobility, to explore conceptual and methodological synergies. It emphasises four strengths of an integrated approach: (1) a broadened understanding of innovations that emphasises not only processes of knowledge generation but also of knowledge transfer through (2) processes of learning, adaptation and mutation, (3) a relational understanding of the origin and dissemination of innovations focused on the complex nature of cities and (4) the importance of individual actors as agents of change and analytical scale that highlights social processes of innovation. The notion of urban assemblages further allows the operationalisation of both the relational embeddedness of local policies as well as their cross-sectoral actor constellations

ABC TRANSPORTERS IN GLIOBLASTOMA: ANTICANCER DRUG TRANSPORT AND TRANSPORTER REGULATION AT THE BLOOD-BRAIN BARRIER

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier have been unsuccessful in clinical trials. Therefore, novel therapeutic strategies are needed to overcome the blood-brain barrier for improved glioblastoma treatment. Here, I address this need in 3 independent aims: Elucidate the involvement and cooperation of ABC transporters in anticancer drug transport at the blood-brain barrier Establish and characterize human glioblastoma models Evaluate the impact of dual PI3K/Akt inhibition on brain uptake of anticancer drugs Aim 1: While Abcb1/Abcg2 inhibition improved survival in mouse glioblastoma models, clinical trials had to be terminated due to a lack of efficacy, sparking a discussion that other ABC transporters might be involved in this process. To discern how multiple ABC transporters cooperate in restricting anticancer drug uptake at the blood-brain barrier, I evaluated the effect of several efflux transporters at the blood-brain barrier on the brain level of anticancer drugs using transporter inhibitors or knockout mice. The results from this study suggest that Abcc4 works in concert with Abcb1/Abcg2 in restricting brain access of the tested anticancer drugs in mice. Further experiments are necessary to confirm this cooperation at the human blood-brain barrier. In part, these findings might provide one possible explanation why therapeutic strategies that solely focus on ABCB1/ABCG2 failed to improve treatment outcomes for glioblastoma patients. Aim 2: Successful treatment of glioblastoma requires reliable preclinical animal models to evaluate novel approaches and assess their potential therapeutic benefit. While many different glioblastoma models exist, most are not well characterized and only recapitulate a subset of glioblastoma characteristics. Here, I describe and compare two human glioblastoma models, U87-luc2 and U251-FLuc. While both models behave similarly in vitro, they have different in vivo tumor characteristics, such as invasiveness and blood-brain barrier disruption. Together, the two glioblastoma models recapitulate the tumor characteristics of a majority of patients. Aim 3: Direct transporter inhibition is unsuccessful in improving glioblastoma patient survival due to the low efficacy of inhibitors and adverse effects associated with combination treatment. However, efflux transporter regulation could open a “window-in-time” to allow anticancer drug uptake into the brain. Here, I tested a novel molecular switch approach to overcome Abcb1/Abcg2-mediated efflux at the blood-brain barrier. My data indicate that PI3K/Akt could serve as a molecular switch to transiently turn off Abcb1/Abcg2 at the blood-brain barrier and increase brain levels of anticancer drugs

Diffusion and bulk flow in phloem loading - a theoretical analysis of the polymer trap mechanism in plants

Plants create sugar in the mesophyll cells of their leaves by photosynthesis. This sugar, mostly sucrose, has to be loaded via the bundle sheath into the phloem vascular system (the sieve elements), where it is distributed to growing parts of the plant. We analyze the feasibility of a particular loading mechanism, active symplasmic loading, also called the polymer trap mechanism, where sucrose is transformed into heavier sugars, such as raffinose and stachyose, in the intermediary-type companion cells bordering the sieve elements in the minor veins of the phloem. Keeping the heavier sugars from diffusing back requires that the plasmodesmata connecting the bundle sheath with the intermediary cell act as extremely precise filters, which are able to distinguish between molecules that differ by less than 20% in size. In our modeling, we take into account the coupled water and sugar movement across the relevant interfaces, without explicitly considering the chemical reactions transforming the sucrose into the heavier sugars. Based on the available data for plasmodesmata geometry, sugar concentrations and flux rates, we conclude that this mechanism can in principle function. We find that the water flow through the plasmodesmata, which has not been quantified before, contributes only 10-20% to the sucrose flux into the intermediary cells, while the main part is transported by diffusion. On the other hand, the subsequent sugar translocation into the sieve elements would very likely be carried predominantly by bulk water flow through the plasmodesmata. Thus, in contrast to apoplasmic loaders, all the necessary water for phloem translocation would be supplied in this way with no need for additional water uptake across the plasma membranes of the phloem.Comment: 29 pages with 5 figure

Wie die nordischen Götter und Helden bis heute fortleben : ein Blick in die Edda-Sammlung des Instituts für Skandinavistik

Edda – diesen Namen tragen zwei isländische Werke aus dem 13. Jahrhundert. Gemeinsam überliefern sie, das eine in Liedern, das andere in Prosa, den größten erhaltenen Schatz an nordischer Mythologie und Heldensage. Gern für »germanisch« gehalten sind diese Stoffe seit dem 18. Jahrhundert weit über Island hinaus bekannt. Das spiegelt sich auch in den mehr als 1200 Objekten der Frankfurter Edda-Sammlung, die zeigen, wie die Mythen buchstäblich in jeden Winkel der Kultur vordringen können

Towards Model Checking Reconfigurable Petri Nets using Maude

This paper introduces an approach to model checking of reconfigurable Petri nets. The main task is to flatten the two levels of dynamic behavior that reconfigurable nets provide, the firing of transitions on the one hand and the transformation of the nets on the other hand. We show how to translate a reconfigurable net into  Maude modules. Maude's LTL model-checker is then used to verify properties of these modules

Positioning Vancouver through urban sustainability strategies? The Greenest City 2020 Action Plan

© 2017 Elsevier Ltd Cities around the world have launched greening initiatives to reduce their carbon footprint and to become more sustainable. At the same time, they have also sought to use these initiatives to position themselves as climate change leaders and green champions. This paper focuses on the City of Vancouver's Greenest City 2020 Action Plan as urban policy strategy to reduce carbon emissions. Based on interviews with actors and experts involved in the development and implementation of the plan, the paper evaluates the role green leadership aspirations play in shaping urban climate change policy and how policy makers and stakeholders use policy to position the city and its greening initiatives locally and globally. In particular, it analyzes the role of competitive positioning and green leadership in sustainability initiatives and change within and beyond urban boundaries. While leadership suggests increased buy-in of residents and those involved in the implementation of the strategy and multiplication effects through learning within the region and between (peer) cities, it can also pose challenges as the interest in meeting leadership claims can impede more radical change through specific targets and implementation strategies and challenge other sustainability objectives

Functional anatomy of the colonic bioreactor : impact of antibiotics and Saccharomyces boulardii on bacterial composition in human fecal cylinders

Sections of fecal cylinders were analyzed using fluorescence in situ hybridization targeting 180 bacterial groups. Samples were collected from three groups of women (N = 20 each) treated for bacterial vaginosis with ciprofloxacin + metronidazole. Group A only received the combined antibiotic regimen, whereas the A/Sb group received concomitant Saccharomyces boulardii CNCM I-745 treatment, and the A.Sb group received S. boulardii prophylaxis following the 14-day antibiotic course. The number of stool cylinders analyzed was 188 out of 228 in group A, 170 out of 228 in group A/Sb, and 172 out of 216 in group Ash. The colonic biomass was organized into a separate mucus layer with no bacteria, a 10-30 mu m broad unstirred transitional layer enriched with bacteria, and a patchy fermentative area that mixed digestive leftovers with bacteria. The antibiotics suppressed bacteria mainly in the fermentative area, whereas abundant bacterial clades retreated to the transitional mucus and survived. As a result, the total concentration of bacteria decreased only by one order. These effects were lasting, since the overall recovery of the microbial mass, bacterial diversity and concentrations were still below pre-antibiotic values 4 months after the end of antibiotic treatment. Sb-prophylaxis markedly reduced antibiotic effects and improved the recovery rates. Since the colon is a sophisticated bioreactor, the study indicated that the spatial anatomy of its biomass was crucial for its function

Expert Views on Effectiveness, Feasibility, and Implementation of Biosecurity Measures for Mitigating Tier 1 Disease Risks in the U.S. Swine, Beef Cattle, and Dairy Industries

Understanding disease transmission routes and implications for biosecurity is critical to mitigating livestock disease outbreaks and maintaining efficient and profitable production. The goal of biosecurity is to eliminate pathogen exposure and minimize endemic pathogen impact, particularly important for foreign animal diseases that threaten U.S. animal health and the economy. We elicit swine, beef cattle, and dairy expert views on the effectiveness, feasibility, and implementation of both biosecurity measures targeting disease transmission routes and specific biosecurity measures. Biosecurity targeting direct animal-to-animal contact, semen, people, and vehicles and other fomites was identified as the most effective and feasible for the swine, beef cattle, and dairy industries. Efforts targeting airborne and arthropod transmission were ranked low for effectiveness and feasibility across all three industries. The swine industry had higher estimated implementation of biosecurity against most disease transmission routes. All-in and all-out production had the highest estimated implementation in the swine industry. In the beef cattle industry, performing daily observations by producer/employees had the highest estimated implementation. Reduced environmental viral load through pathogen reduction had the lowest estimated implementation in the swine and beef cattle industries. In the dairy industry, monitoring production records for health status changes had the highest estimated implementation, and line of separation in place for all employees entering premises had the lowest. Swine experts considered separation line for all animals entering/leaving premises and reduced environmental viral load through pathogen reduction the most and least effective and feasible, respectively. Stabilization and monitoring for affected premises and daily observations by producer/employees were identified as most effective and feasible by beef cattle and dairy experts, respectively. All-in and all-out production was rated least effective and feasible by both beef cattle and dairy experts

Urban energy transitions through innovations in green building

Recent debates on climate change have increasingly focused on cities as a strategic spatial scale to implementss climate change mitigation and adaptation strategies. Within this context, green building and the way the built environment interfaces with urban structures and services have become significant levers of action for cities to reduce greenhouse gas emissions and become climate change leaders (Bulkeley et al., 2011). Approximately 30% to 40% of final energy consumption is linked to buildings and, as a consequence, the building sector has been identified as one of the most relevant sectors to reduce CObuilding is largely associated with technological innovations, building design and the way elements are embedded within the overall urban fabric, a shift towards green building in cities largely depends on modes of sustainable governance. Relevant dimensions include support of and for green policies and incentives, institutional support through resource centres, think tanks, certification bodies, and training, aspects of inclusivity both in the planning process as well as the later use of (and access to) buildings and to a considerable extent on lived sustainability (i.e. the ways individuals interact with and use buildings). This latter dimension of possibly changing user behaviour and consumer lifestyles seems to be absent from most of the energy scenario studies, as Samadi et al. (2016) revealed in their assessment of a series of internationally influential studies and policy programmes. Like other scholars (e.g. Sachs, 1999; Princen, 2003; Schneidewind & Zahrnt, 2014), they plead for a stronger conceptualization of sufficiency oriented policy approaches and differentiate persuasive instruments (e.g. through education and communication) from incentive based (price/tax policies) and more coercive approaches (limits, bans)