EspZ of enteropathogenic and enterohemorrhagic Escherichia coli regulates type III secretion system protein translocation

UNLABELLED: Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms that regulate the intracellular effector concentration. We present evidence that the effector EspZ controls T3SS effector translocation from enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Consistently, an EPEC espZ mutant is highly cytotoxic. Following ectopic expression, we found that EspZ inhibited the formation of actin pedestals as it blocked the translocation of Tir, as well as other effectors, including Map and EspF. Moreover, during infection EspZ inhibited effector translocation following superinfection. Importantly, while EspZ of EHEC O157:H7 had a universal "translocation stop" activity, EspZ of EPEC inhibited effector translocation from typical EPEC strains but not from EHEC O157:H7 or its progenitor, atypical EPEC O55:H7. We found that the N and C termini of EspZ, which contains two transmembrane domains, face the cytosolic leaflet of the plasma membrane at the site of bacterial attachment, while the extracellular loop of EspZ is responsible for its strain-specific activity. These results show that EPEC and EHEC acquired a sophisticated mechanism to regulate the effector translocation.

IMPORTANCE: Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are important diarrheal pathogens responsible for significant morbidity and mortality in developing countries and the developed world, respectively. The virulence strategy of EPEC and EHEC revolves around a conserved type III secretion system (T3SS), which translocates bacterial proteins known as effectors directly into host cells. Previous studies have shown that when cells are infected in two waves with EPEC, the first wave inhibits effector translocation by the second wave in a T3SS-dependent manner, although the factor involved was not known. Importantly, we identified EspZ as the effector responsible for blocking protein translocation following a secondary EPEC infection. Interestingly, we found that while EspZ of EHEC can block protein translocation from both EPEC and EHEC strains, EPEC EspZ cannot block translocation from EHEC. These studies show that EPEC and EHEC employ a novel infection strategy to regulate T3SS translocation.

Using UAV acquired photography and structure from motion techniques for studying glacier landforms: application to the glacial flutes at Isfallsglaciären

Glacier and ice sheet retreat exposes freshly deglaciated terrain which often contains small-scale fragile geomorphological features which could provide insight into subglacial or submarginal processes. Subaerial exposure results in potentially rapid landscape modification or even disappearance of the minor–relief landforms as wind, weather, water and vegetation impacts on the newly exposed surface. Ongoing retreat of many ice masses means there is a growing opportunity to obtain high resolution geospatial data from glacier forelands to aid in the understanding of recent subglacial and submarginal processes. Here we used an unmanned aerial vehicle to capture close-range aerial photography of the foreland of Isfallsglaciären, a small polythermal glacier situated in Swedish Lapland. An orthophoto and a digital elevation model with ~2 cm horizontal resolution were created from this photography using structure from motion software. These geospatial data was used to create a geomorphological map of the foreland, documenting moraines, fans, channels and flutes. The unprecedented resolution of the data enabled us to derive morphological metrics (length, width and relief) of the smallest flutes, which is not possible with other data products normally used for glacial landform metrics mapping. The map and flute metrics compare well with previous studies, highlighting the potential of this technique for rapidly documenting glacier foreland geomorphology at an unprecedented scale and resolution. The vast majority of flutes were found to have an associated stoss-side boulder, with the remainder having a likely explanation for boulder absence (burial or erosion). Furthermore, the size of this boulder was found to strongly correlate with the width and relief of the lee-side flute. This is consistent with the lee-side cavity infill model of flute formation. Whether this model is applicable to all flutes, or multiple mechanisms are required, awaits further study.

Money, (Co)Production and Power in Digital

This article discusses the contribution of critical political economy approaches to digital journalism studies and argues that these offer important correctives to celebratory perspectives. The first part offers a review and critique of influential claims arising from self-styled new studies of convergence culture, media and creative industries. The second part discusses the contribution of critical political economy in examining digital journalism and responding to celebrant claims. The final part reflects on problems of restrictive normativity and other limitations within media political economy perspectives and considers ways in which challenges might be addressed by more synthesising approaches. The paper proposes developing radical pluralist, media systems and comparative analysis, and advocates drawing on strengths in both political economy and culturalist traditions to map and evaluate practices across all sectors of digital journalism.

Australian Capital Territory July to December 2015

Effect of nitric oxide donors on blood pressure and pulse pressure in acute and subacute stroke

High blood pressure (BP), pulse pressure (PP), and rate pressure product (RPP) areeach associated independently with a poor outcome in acute ischemic stroke. Whereas nitric oxide (NO) donors, such as glyceryl trinitrate (GTN), lower blood pressure in acute ischemic stroke, their effect on other hemodynamic measures is not known. We performed a systematic review of the effects of NO donors on systemic hemodynamic measures in patients with acute/subacute stroke. Randomized controlled trials were identified from searches of the Cochrane Library, Pubmed, and Embase. Information on hemodynamic measures, including systolic BP (SBP), diastolic BP (DBP), and heart rate, were assessed, and hemodynamic derivatives of these were calculated: PP (PP SBP DBP), mean arterial pressure (MAP DBP PP/3), mid blood pressure (MBP (SBP DBP)/2), pulse pressure index (PPI PP/MAP), and RPP (RPP SBP HR). The effect of treatment on hemodynamic measures was calculated as the weighted mean difference (WMD) between treated and control groups with adjustment for baseline. Results: Three trials involving 145 patients were identified; 93 patients received the NO donor, GTN, and 52 control. As compared with placebo, GTN significantly reduced SBP (WMD -9.80 mmHg, p< 0.001), DBP (WMD -4.43 mmHg, p<0.001), MAP (WMD -6.41 mmHg, p< 0.001), MBP (WMD -7.33 mmHg,p<0.001), PP (WMD -6.11 mmHg, p<0.001 ) and PPI (WMD -0.03, p=0.04 ). 3 GTN increased HR (WMD +3.87 bpm, p<0.001) and non-significantly lowered RPP (WMD -323 mmHg.bpm, p=0.14). Conclusion: The NO donor GTN reduces BP, PP and other derivatives in acute and subacute stroke whilst increasing heart rate.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Delaware Water Gap National Recreation Area, New Jersey and Pennsylvania /

Scale ca. 1:130,000.

Delaware Water Gap National Recreational Area, New Jersey and Pennsylvania /

Panel title.

INVESTIGATIONS INTO MECHANISMS UNDERLYING EXTREME WAVE FORMATIONS AND COMPUTATIONALLY INTENSIVE SIMULATIONS

Various mechanisms have been proposed to explain extreme waves or rogue waves in an oceanic environment including directional focusing, dispersive focusing, wave-current interaction, and nonlinear modulational instability. The Benjamin-Feir instability (nonlinear modulational instability), however, is considered to be one of the primary mechanisms for rogue-wave occurrence. The nonlinear Schrodinger equation is a well-established approximate model based on the same assumptions as required for the derivation of the Benjamin-Feir theory. Solutions of the nonlinear Schrodinger equation, including new rogue-wave type solutions are presented in the author's dissertation work. The solutions are obtained by using a predictive eigenvalue map based predictor-corrector procedure developed by the author. Features of the predictive map are explored and the influences of certain parameter variations are investigated. The solutions are rescaled to match the length scales of waves generated in a wave tank. Based on the information provided by the map and the details of physical scaling, a framework is developed that can serve as a basis for experimental investigations into a variety of extreme waves as well localizations in wave fields. To derive further fundamental insights into the complexity of extreme wave conditions, Smoothed Particle Hydrodynamics (SPH) simulations are carried out on an advanced Graphic Processing Unit (GPU) based parallel computational platform. Free surface gravity wave simulations have successfully characterized water-wave dispersion in the SPH model while demonstrating extreme energy focusing and wave growth in both linear and nonlinear regimes. A virtual wave tank is simulated wherein wave motions can be excited from either side. Focusing of several wave trains and isolated waves has been simulated. With properly chosen parameters, dispersion effects are observed causing a chirped wave train to focus and exhibit growth. By using the insights derived from the study of the nonlinear Schrodinger equation, modulational instability or self-focusing has been induced in a numerical wave tank and studied through several numerical simulations. Due to the inherent dissipative nature of SPH models, simulating persistent progressive waves can be problematic. This issue has been addressed and an observation-based solution has been provided. The efficacy of SPH in modeling wave focusing can be critical to further our understanding and predicting extreme wave phenomena through simulations. A deeper understanding of the mechanisms underlying extreme energy localization phenomena can help facilitate energy harnessing and serve as a basis to predict and mitigate the impact of energy focusing.

A cidade e o rio: origem e evolução da frente ribeirinha de Lisboa

Em Lisboa, ao longo dos séculos, o homem foi conquistando as águas do Tejo. Hoje, após os diversos aterros, a frente ribeirinha da cidade é uma consolidada faixa de terreno, rematada por muros que, contra a «ondulação» do Tejo, definem uma expandida área que acolhe uma intensa actividade portuária. Foi nesta faixa junto do rio que se desenrolou parte importante da história de Lisboa, desde as ocupações romana e muçulmana, e também muito particularmente aquando do período dos Descobrimentos, da reconstrução pombalina pós-terramoto e do surto industrial do século XIX. Alguns destes momentos históricos encontram-se reflectidos nas inúmeras plantas, cartas e mapas disponíveis neste estudo, desde a Planta da Cidade de Lisboa : 1650, de João Nunes Tinoco, até ao Plano de Melhoramentos do Porto de Lisboa, de 1946. É com base nessas plantas, mas também em cartas manuscritas, relatos de época, gravuras e fotografias antigas – documentos em grande parte inéditos –, que este trabalho de investigação propõe cartografar este território, realizando desenhos originais que possibilitam um novo olhar sobre o seu processo de crescimento e consolidação. Assim, este estudo concilia todos estes elementos, constituindo uma análise completa que se debruça sobre a evolução da frente ribeirinha de Lisboa e que permite descobrir inúmeros aspectos até aqui desconhecidos, ajudando a responder à pergunta que hoje se coloca: perante o cenário que o porto actual atravessa, como melhor poderá Lisboa recuperar a relação com o rio?; THE CITY AND THE RIVER: ORIGIN AND EVOLUTION OF LISBON'S RIVERFRONT ABSTRACT: In Lisbon, over the centuries, man was conquering the waters of the Tagus. Today, after the various landfills, the city's riverfront is a consolidated strip of land, finished by walls that, against the "ripple" of the Tagus, define an expanded area that hosts an intense port activity. It was in this band along the river that unfolded important part of the history of Lisbon, from the Roman and Muslim occupations, and also very particularly during the period of the Discoveries, the post-earthquake reconstruction, and the industrial boom of the nineteenth century. Some of these historical moments are reflected in many plans, charts and maps available in this study, since the plan designated Planta da Cidade de Lisboa : 1650, made by João Nunes Tinoco, to the plan called Plano de Melhoramentos do Porto de Lisboa, drawn in the year of 1946. Based on these plans, but also in handwritten letters, time reports, antique prints and photographs – documents that are mostly unpublished – this research work proposes map this territory, performing original drawings that provide a new look at their growth process and consolidation. Thereby, this study combines all these elements, providing a complete analysis which focuses on the evolution of the Lisbon riverfront and that allows you to discover many aspects unknown until now, helping to answer the question that now arises: according to the present scenario that the harbour is going through, how can Lisbon recover the relationship with the river?

Population structure and growth of the hermit crab Pagurus brevidacylus (Anomura : Paguridae) from the northern coast of São Paulo, Brazil

The hermit crab Paguras brevidactylus (Crustacea: Anomura: Paguridea) from the infralittoral area of Anchieta Island, Ubatuba, was characterized by population Structure (size, sex ratio, reproduction and recruitment) and growth. Animals were collected monthly during 1999 by SCUBA diving. A total of 1525 individuals was collected (633 males and 892 females), 695 of them were ovigerous females. Overall sex ratio was 0.7:1 in favour of females. The crabs showed a unimodal distribution with males significantly larger than females. Ovigerous females were collected during all months and in high percentages from 1.0 mm of shield length, demonstrating intense and Continuous reproduction. The longevity was approximately 24 months for males and 18 for females, which showed larger growth rate and reached sexual maturity earlier (two months) than males. The low number of males in this Population may be due to the longer life span. Moreover, the sexual dimorphism favours males during the intra- and interspecific fights by shell, food, reproduction and territory. Females demonstrated a short life cycle and intense reproduction.

Location analysis of city sections: socio-demographic segmentation and restaurant potentiality estimation : a case study of Lisbon

One of the objectives of this study is to perform classification of socio-demographic components for the level of city section in City of Lisbon. In order to accomplish suitable platform for the restaurant potentiality map, the socio-demographic components were selected to produce a map of spatial clusters in accordance to restaurant suitability. Consequently, the second objective is to obtain potentiality map in terms of underestimation and overestimation in number of restaurants. To the best of our knowledge there has not been found identical methodology for the estimation of restaurant potentiality. The results were achieved with combination of SOM (Self-Organized Map) which provides a segmentation map and GAM (Generalized Additive Model) with spatial component for restaurant potentiality. Final results indicate that the highest influence in restaurant potentiality is given to tourist sites, spatial autocorrelation in terms of neighboring restaurants (spatial component), and tax value, where lower importance is given to household with 1 or 2 members and employed population, respectively. In addition, an important conclusion is that the most attractive market sites have shown no change or moderate underestimation in terms of restaurants potentiality.

Geospatial Data Indexing Analysis and Visualization via Web Services with Autonomic Resource Management

With the exponential growth of the usage of web-based map services, the web GIS application has become more and more popular. Spatial data index, search, analysis, visualization and the resource management of such services are becoming increasingly important to deliver user-desired Quality of Service. First, spatial indexing is typically time-consuming and is not available to end-users. To address this, we introduce TerraFly sksOpen, an open-sourced an Online Indexing and Querying System for Big Geospatial Data. Integrated with the TerraFly Geospatial database [1-9], sksOpen is an efficient indexing and query engine for processing Top-k Spatial Boolean Queries. Further, we provide ergonomic visualization of query results on interactive maps to facilitate the user’s data analysis. Second, due to the highly complex and dynamic nature of GIS systems, it is quite challenging for the end users to quickly understand and analyze the spatial data, and to efficiently share their own data and analysis results with others. Built on the TerraFly Geo spatial database, TerraFly GeoCloud is an extra layer running upon the TerraFly map and can efficiently support many different visualization functions and spatial data analysis models. Furthermore, users can create unique URLs to visualize and share the analysis results. TerraFly GeoCloud also enables the MapQL technology to customize map visualization using SQL-like statements [10]. Third, map systems often serve dynamic web workloads and involve multiple CPU and I/O intensive tiers, which make it challenging to meet the response time targets of map requests while using the resources efficiently. Virtualization facilitates the deployment of web map services and improves their resource utilization through encapsulation and consolidation. Autonomic resource management allows resources to be automatically provisioned to a map service and its internal tiers on demand. v-TerraFly are techniques to predict the demand of map workloads online and optimize resource allocations, considering both response time and data freshness as the QoS target. The proposed v-TerraFly system is prototyped on TerraFly, a production web map service, and evaluated using real TerraFly workloads. The results show that v-TerraFly can accurately predict the workload demands: 18.91% more accurate; and efficiently allocate resources to meet the QoS target: improves the QoS by 26.19% and saves resource usages by 20.83% compared to traditional peak load-based resource allocation.

Greening the city: an ecosystem-based framework to support planning towards urban sustainability and resilience

Cities are small-scale complex socio-ecological systems, that host around 60% of world population. Ecosystem Services (ES) provided by urban ecosystems offer multiple benefits necessary to cope with present and future urban challenges. These ES include microclimate regulation, runoff control, as well as opportunities for mental and physical recreation, affecting citizen’s health and wellbeing. Creating a balance between urban development, land take containment, climate adaptation and availability of Urban Green Areas and their related benefits, can improve the quality of the lives of the inhabitants, the economic performance of the city and the social justice and cohesion aspects. This work starts analysing current literature around the topic of Ecosystem Services (ES), Green and Blue Infrastructure (GBI) and Nature-based Solutions (NBS) and their integration within current European and International sustainability policies. Then, the thesis focuses on the role of ES, GBI and NBS towards urban sustainability and resilience setting the basis to build the core methodological and conceptual approach of this work. The developed ES-based conceptual approach provides guidance on how to map and assess ES, to better inform policy making and to give the proper value to ES within urban context. The proposed interdisciplinary approach navigates the topic of mapping and assessing ES benefits in terms of regulatory services, with a focus on climate mitigation and adaptation, and cultural services, to enhance wellbeing and justice in urban areas. Last, this thesis proposes a trans-disciplinary and participatory approach to build resilience over time around all relevant urban ES. The two case studies that will be presented in this dissertation, the city of Bologna and the city of Barcelona, have been used to implement, tailor and test the proposed conceptual framework, raising valuable inputs for planning, policies and science.

Design, development and guidance of the Airborne’s quadrotor

The main goal of the Airborne project is to develop, at technology readiness level 8 (TRL8), a few selected robotic aerial technologies for quick localization of victims by avalanches by equipping drones with two forefront sensors used in SAR operations in case of avalanches, namely the ARVA and RECCO. This thesis focuses on the design, development, and guidance of the TRL8 quadrotor developed during the project. We present and describe the design method that allowed us to obtain an EMI shielded UAV capable of integrating both RECCO and ARVA sensors. Besides, is presented the avionics and power train design and building procedure in order to obtain a modular UAV frame that can be easily carried by rescuers and achieves all the performance benchmarks of the project. Additionally, in addition to the onboard algorithms, a multivariate regressive convolutional neural network whose goal is the localization of the ARVA signal is presented. On guidance, the automatic flight procedure is described, and the onboard waypoint generator algorithm is presented. The goal of this algorithm is the generation and execution of an automatic grid pattern without the need to know the map in advance and without the support of a control ground station (CGS). Moreover, we present an iterative trajectory planner that does not need pre-knowledge of the map and uses Bézier curves to address optimal, dynamically feasible, safe, and re-plannable trajectories. The goal is to develop a method that allows local and fast replannings in case of an obstacle pop up or if some waypoints change. This makes the novel planner suitable to be applied in SAR operations. The introduction of the final version of the quadrotor is supported by internal flight tests and field tests performed in real operative scenarios by the Club Alpino Italiano (CAI).