bluuebunny/crossref_metadata_2025_split huggingface dataset:
An interdisciplinary and catchment approach to enhancing urban flood resilience: a Melbourne case
Authors: Rogers B. C. , Bertram N. , Gersonius B. , Gunn A. , Löwe R. , Murphy C. , Pasman R. , Radhakrishnan M. , Urich C. , Wong T. H. F. , Arnbjerg-Nielsen K. 
Published: February 2020

This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture.
This article is part of the theme issue ‘Urban flood resilience’.
Evaluating the effectiveness of catchment-scale approaches in mitigating urban surface water flooding
Authors: Ferguson Charlie , Fenner Richard 
Published: February 2020

The argument for natural flood management in the UK has strengthened in recent years with increasing awareness of the potential benefits gained from upstream interventions (especially improvements in water quality, public amenities and biodiversity). This study aims to develop an understanding of another potential benefit—interventions promoting free discharge at downstream urban drainage outfalls by moderating water levels in receiving watercourses. A novel, coupled model (linking dynamic TOPMODEL, HEC-RAS and Infoworks ICM) is calibrated for the Asker catchment in Dorset, England. This predominantly rural watershed drains to the town of Bridport, frequently submerging a surface drainage outfall in a nearby housing estate. Two forms of upstream, catchment-scale intervention (hillslope tree planting and in-channel large woody debris) are modelled to understand their impacts on the functioning of the drainage network during both the calibration period and a range of design storms. The results indicate that interventions have the greatest positive impact during frequent events. For example, during a storm with a 10% annual exceedance probability (AEP), upstream NFM could reduce outfall inundation by up to 3.75 h and remove any surcharging of flow within the drainage system in Bridport. In more severe storms, the results suggest interventions could slightly prolong the time the outfall was submerged. However, by slowing the wider catchment's response during the 3.3% AEP storm, upstream interventions allow more water to escape the urban drainage system and reduce the maximum surface flooding extent within the housing estate by 35%.This article is part of the theme issue ‘Urban flood resilience’.
Methodology and application of flood footprint accounting in a hypothetical multiple two-flood event
Authors: Zeng Zhao , Guan Dabo 
Published: February 2020

Multiple natural disasters are becoming ever more frequent around the world, with both climate change and rapid urbanization increasing the risk of such disasters in human society. Comprehensive analysis of the economic impact of multiple disasters on the industrial and economic system has become an urgent and essential part of urban recovery and sustainable development. However, there is a lack of studies that focus on assessing the indirect economic impacts resulting from such multiple events, and thereafter providing a common quantitative approach within their assessment. With the concept of flood footprint and input–output theory, this study proposes a more externally oriented methodology (flood footprint model) for indirect flood footprint (IFF) accounting and offers various extensive sensitivity analyses based on a hypothetical two-flood event. Based on the two-flood case, we conclude that the total flood footprint of a multi-flood within a given region is larger than the sum of individual flood footprints and this is the same for the IFF due to the combination effect, while the flood footprint is highly constrained by factors such as occurrence time and physical damage caused by the ensuing disaster.This article is part of the theme issue ‘Urban flood resilience'.
Managing flooding: from a problem to an opportunity
Authors: Ashley Richard , Gersonius Berry , Horton Bruce 
Published: February 2020

The paper argues that the concept and practice of sustainability have proved too difficult to achieve within traditional water management, and there is a lack of political will to move towards truly sustainable water services. Instead, compromised concepts, including resistance, resilience, ecosystem services, natural capital and adaptation are defining approaches; each of which may contribute partially to sustainability. Pressures due to the changing climate, ecological degradation, human demands, urbanization and deteriorating assets are challenging sustainability and compelling changes to water management. Water is now seen less as a problem to be managed than as an opportunity, as wherever situated, water brings many opportunities to contribute to anthropogenic needs. New ideas are helping to frame the way in which water management is being approached: (i) waste is no longer waste, but a potential resource within a circular economy; (ii) the interconnectedness of infrastructure systems and services and circularity of the water cycle mean there is a need to integrate approaches; (iii) nature-based systems should be preferenced for water infrastructure. These issues and ideas are considered here, together with examples of schemes showing that managing flooding can lead to wider benefits, and potential longer-term sustainability.
This article is part of the theme issue ‘Urban flood resilience’.
Drivers of future urban flood risk
Authors: O'Donnell Emily C. , Thorne Colin R. 
Published: February 2020

Managing urban flood risk is a key global challenge of the twenty-first century. Drivers of future UK flood risk were identified and assessed by the Flood Foresight project in 2002–2004 and 2008; envisaging flood risk during the 2050s and 2080s under a range of scenarios for climate change and socio-economic development. This paper qualitatively reassesses and updates these drivers, using empirical evidence and advances in flood risk science, technology and practice gained since 2008. Of the original drivers, five have strengthened, three have weakened and 14 remain within their 2008 uncertainty bands. Rainfall, as impacted by climate change, is the leading source driver of future urban flood risk. Intra-urban asset deterioration, leading to increases in a range of consequential flood risks, is the primary pathway driver. Social impacts (risk to life and health, and the intangible impacts of flooding on communities) and continued capital investment in buildings and contents (leading to greater losses when newer buildings of higher economic worth are inundated) have strengthened as receptor drivers of urban flood risk. Further, we propose two new drivers: loss of floodable urban spaces and indirect economic impacts, which we suggest may have significant impacts on future urban flood risk.
This article is part of the theme issue ‘Urban flood resilience’.
Flood resilience, amenity and biodiversity benefits of an historic urban pond
Authors: Krivtsov Vladimir , Birkinshaw Steve , Arthur Scott , Knott David , Monfries Ruth , Wilson Kirsty , Christie Derek , Chamberlain David , Brownless Peter , Kelly David , Buckman Jim , Forbes Heather , Monteiro Yamina 
Published: February 2020

The main pond within the historic Royal Botanic Garden Edinburgh is an important component of urban blue-green infrastructure. This paper reports on flood resilience provided by the pond (simulated using the CityCAT hydrodynamic model), its water residence times (obtained using the Shetran hydrological model), and the ecology and biodiversity (vascular plants, bryophytes, aquatic invertebrates, phyto- and zooplankton, birds) of the pond and the adjacent area. The results show that the pond improves the flood resilience with at least a 27% reduction in the peak discharge during a 1 h, one in 100-year event. The area represents a biodiversity hot spot with a range of native taxa occurring among introduced plant species. The plankton community is dominated by diatoms, reflecting elevated levels of turbulence and a relatively short residence time, with an average value of 10 days. Analysis of macroinvertebrate community indicates a potential for water quality improvement. The results are discussed in relation to multiple societal benefits related to flood resilience, recreation, education, water quality, amenity and biodiversity value. The conclusions may prove particularly valuable for introducing practical measures in the water catchment, preventing waterlogging of the soil and ensuring an uninterrupted supply of public services.
This article is part of the theme issue ‘Urban flood resilience'.
Branched-chain amino acid catabolism depends on GRXS15 through mitochondrial lipoyl cofactor homeostasis
Authors: Moseler Anna , Kruse Inga , Maclean Andrew E. , Pedroletti Luca , Wagner Stephan , Wehler Regina , Fischer-Schrader Katrin , Poschet Gernot , Wirtz Markus , Dörmann Peter , Hildebrandt Tatjana M. , Hell Rüdiger , Schwarzländer Markus , Balk Janneke , Meyer Andreas J. 
Published: February 2020

AbstractIron-sulfur (Fe-S) clusters are ubiquitous cofactors in all life and are used in a wide array of diverse biological processes, including electron transfer chains and several metabolic pathways. Biosynthesis machineries for Fe-S clusters exist in plastids, the cytosol and mitochondria. A single monothiol glutaredoxin (GRX) has been shown to be involved in Fe-S cluster assembly in mitochondria of yeast and mammals. In plants, the role of the mitochondrial homologue GRXS15 has only partially been characterized. Arabidopsisgrxs15null mutants are not viable, but mutants complemented with the variantGRXS15 K83Adevelop with a dwarf phenotype. In an in-depth metabolic analysis, we show that most Fe-S cluster-dependent processes are not affected, including biotin biosynthesis, molybdenum cofactor biosynthesis and the electron transport chain. Instead, we observed an increase in most TCA cycle intermediates and amino acids, especially pyruvate, 2-oxoglutarate, glycine and branched-chain amino acids (BCAAs). The most pronounced accumulation occurred in branched-chain α-keto acids (BCKAs), the first degradation products resulting from deamination of BCAAs. In wild-type plants, pyruvate, 2-oxoglutarate, glycine and BCKAs are all metabolized through decarboxylation by four mitochondrial lipoyl cofactor-dependent dehydrogenase complexes. Because these enzyme complexes are very abundant and the biosynthesis of the lipoyl cofactor depends on continuous Fe-S cluster supply to lipoyl synthase, this could explain why lipoyl cofactor-dependent processes are most sensitive to restricted Fe-S supply inGRXS15 K83Amutants.One-sentence summaryDeficiency in GRXS15 restricts protein lipoylation and causes metabolic defects in lipoyl cofactor-dependent dehydrogenase complexes, with branched-chain amino acid catabolism as dominant bottleneck.
The Safety of a Therapeutic Product Composed of a Combination of Stem Cell Released Molecules from Adipose Mesenchymal Stem Cells and Fibroblasts
Authors: Maguire Greg , Friedman Peter 
Published: February 2020

AbstractStem cell transplants have demonstrated life-saving capabilities for some blood diseases, and the molecules and exosomes released from stem cells are currently in therapeutic development for a number of diseases and conditions, including neurodegenerative diseases, heart conditions, glaucoma, hearing loss, and skin diseases. Stem cell science is a relatively new science, and therapeutic development using stem cells, even approved stem cell therapies for blood diseases, is in need of a better understanding of mechanisms of action and acute and long-term safety profiles. Here we performed a number of safety tests for a stem cell-based therapeutic comprised of the stem cell released molecules from a combination of adipose derived mesenchymal stem cells and fibroblasts that have demonstrated efficacy in a number of conditions. Using in vitro, in vivo, and skin sensitivity studies in humans, the stem cell therapeutic comprised of stem cell released molecules was shown to have an excellent safety profile when tested for toxicity, mutagenicity, tumorigenesis, ocular toxicity, inflammation, and irritation.
Cross-Protection Against Zika Virus Infection Conferred by a Live Attenuated Japanese Encephalitis SA14-14-2 Vaccine
Authors: Wang Ran , Zhen Zida , Turtle Lance , Hou Baohua , Li Yueqi , Gao Na , Fan Dongying , Chen Hui , An Jing 
Published: February 2020

AbstractZika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection, but did mediate antibody dependent enhancementin vitro, though this did not have an adverse impact on survival. This study suggests that SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue into developing a novel bivalent vaccine against both ZIKV and JEV.ImportanceJapanese encephalitis is a controllable disease in many countries in Asia, especially in China, where many people have Japanese encephalitis virus (JEV) immunity due to extensive JEV vaccination campaigns or natural exposure. Live-attenuated SA14-14-2 strain is a safe and effective vaccine recommended by the World Health Organization and has been vaccinated more than 600 million doses since 1989. As the prevalence of Zika virus (ZIKV) and rising risk in above regions, the cross-reactive immune response between these two antigenically closely related flaviviruses, JEV and ZIKV, should also be fully recognized, which is presumed to be based on those ambiguous cross-reactive immunity between dengue virus and ZIKV. In this study, we found that JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice, which is mainly due to cellular immunity rather than neutralizing antibody response. However, specific protective components or cooperation between components warrant to be explored in subsequent experiments. In conclusion, this study can provide important evidence for those who live in JEV-endemic areas and are at risk for ZIKV infection.
DGAT-onco: A powerful method to detect oncogenes by integrating differential mutational analysis and functional impacts of somatic mutations
Authors: Zhang Haoyang , Wei Junkang , Liu Zifeng , Liu Xun , Chong Yutian , Lu Yutong , Zhao Huiying , Yang Yuedong 
Published: February 2020

AbstractMotivationOncogenes are genes whose malfunctions play critical roles in cancer development, and their discovery is a major aim of cancer mechanisms study. By counting the mutation frequency, oncogenes have been identified with frequent mutations, while it is believed that many more oncogenes could be discovered by differential mutational profile analysis. However, it is common that current methods only utilize mutations in the cancer population, which have an obvious bias in background mutation modelling.MethodsTo predict oncogenes efficiently, we developed a method, DGAT-onco that analyzed the frequency distribution and functional impacts of mutations in both cancer and natural population. Our method can capture the mutational difference of two population, and provide a comprehensive view of genomics basis underlying cancer development. DGAT-onco was constructed by germline mutations from the 1000 Genomes project and somatic mutations of 33 cancer types from the Cancer Genome Atlas (TCGA) dataset. Its reliability was verified on an independent test set including 19 cancers from other sources.ResultsWe demonstrated that our method is more effective than alternative methods in oncogenes discovering. Using this approach achieves higher classification performance in oncogene discovery than 6 alternative methods, and 22.8% significant genes identified by our method were verified as oncogenes by the Cancer Gene Census (CGC).AvailabilityDGAT-onco is available athttps://github.com/zhanghaoyang0/DGAT-onco.Contactyangyd25@mail.sysu.edu.cnorzhaohy8@mail.sysu.edu.cn
NovelKras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden
Authors: Salehi-Rad Ramin , Li Rui , Tran Linh M. , Lim Raymond J. , Abascal Jensen , Momcilovic Milica , Park Stacy J. , Ong Stephanie L. , Huang Zi Ling , Paul Manash , Shackelford David B. , Krysan Kostyantyn , Liu Bin , Dubinett Steven M. 
Published: February 2020

AbstractDespite recent advances in lung cancer immunotherapy, a major obstacle to the progress in the field is the lack of preclinical models that recapitulate the genetic and immunologic complexity of human disease. Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor the common oncogenic mutations of the disease, but these models possess low tumor mutational burden (TMB), which limits their utility in immunotherapy studies. Here, we establish novelKras-mutant murine models of NSCLC bearing common genetic alterations associated with the disease and increased TMB, byin vitroexposure of cell lines derived from GEMMs of NSCLC [KrasG12D(K),KrasG12DTp53−/−(KP),KrasG12DTp53+/−Lkb1−/−(KPL)] to the alkylating agentN-methyl-N-nitrosourea (MNU). Increased TMB was associated with enhanced anti-tumor T cell responses and improved anti-PD-1 efficacy in syngeneic models, across all genetic backgrounds. However, anti-PD-1 efficacy was comparatively modest in the KPL cell lines with increased TMB, which possessed a distinct immunosuppressed tumor microenvironment (TME) primarily composed of granulocytic myeloid-derived suppressor cells (G-MDSCs). This phenotype is consistent with findings in human NSCLC where LKB1 loss is a driver of primary resistance to PD-1 blockade. In summary, these novelKras-mutant murine NSCLC models bearing common co-occurring mutations with increased TMB possess clinically relevant TMEs and recapitulate the genetic complexity and therapeutic vulnerabilities of human NSCLC. We anticipate that these immunogenic models will facilitate the development of novel immunotherapies in NSCLC.
A Test of Memory: The Fish, The Mouse, The Fly And The Human
Authors: Cleal Madeleine , Fontana Barbara D , Ranson Daniel C , McBride Sebastian D , Swinny Jerome D , Redhead Edward S , Parker Matthew O 
Published: February 2020

AbstractSimple mazes have provided numerous tasks for assessing working memory. The discrete nature of choices in the T-maze has provided a robust protocol with sensitivity to cognitive deficits, whilst the continuous Y-maze reduces manual handling and pre-trial training. We have combined these attributes to develop a new behavioural task for assessing working memory, the Free-movement pattern (FMP) Y-maze. Using sequentially recorded left and right turns we demonstrate that zebrafish and mice use a single dominant strategy predominantly consisting of alternations between left and right choices trial-to-trial. We further tested this protocol withDrosophilaand discovered an alternative invertebrate search strategy. Finally, a virtual human FMP Y-maze confirmed a common strategy among all tested vertebrate species, validating the translational power of the task for human research. The FMP Y-maze combines robust investigation of working memory and high translational power, generating a simple task with far-reaching impact.
Exposure to auditory feedback delay while speaking induces perceptual habituation but does not mitigate the disruptive effect of delay on speech auditory-motor learning
Authors: Shiller Douglas M. , Mitsuya Takashi , Max Ludo 
Published: February 2020

ABSTRACTPerceiving the sensory consequences of our actions with a delay alters the interpretation of these afferent signals and impacts motor learning. For reaching movements, delayed visual feedback of hand position reduces the rate and extent of visuomotor adaptation, but substantial adaptation still occurs. Moreover, the detrimental effect of visual feedback delay on reach motor learning—selectively affecting its implicit component—can be mitigated by prior habituation to the delay. Auditory-motor learning for speech has been reported to be more sensitive to feedback delay, and it remains unknown whether habituation to auditory delay reduces its negative impact on learning. We investigated whether 30 minutes of exposure to auditory delay during speaking (a) affects the subjective perception of delay, and (b) mitigates its disruptive effect on speech auditory-motor learning. During a speech adaptation task with real-time perturbation of vowel spectral properties, participants heard this frequency-shifted feedback with no delay, 75 ms delay, or 115 ms delay. In the delay groups, 50% of participants had been exposed to the delay throughout a preceding 30-minute block of speaking whereas the remaining participants completed this block without delay. Although habituation minimized awareness of the delay, no improvement in adaptation to the spectral perturbation was observed. Thus, short-term habituation to auditory feedback delays is not effective in reducing the negative impact of delay on speech auditory-motor adaptation. Combined with previous findings, the strong negative effect of delay and the absence of an influence of delay awareness suggest the involvement of predominantly implicit learning mechanisms in speech.HIGHLIGHTSSpeech auditory-motor adaptation to a spectral perturbation was reduced by ~50% when feedback was delayed by 75 or 115 ms.Thirty minutes of prior delay exposure without perturbation effectively reduced participants’ awareness of the delay.However, habituation was ineffective in remediating the detrimental effect of delay on speech auditory-motor adaptation.The dissociation of delay awareness and adaptation suggests that speech auditory-motor learning is mostly implicit.