1,419 research outputs found
SUMO-binding motifs mediate the Rad60-dependent response to replicative stress and self-association
No full textIn fission yeast, the replication checkpoint is enforced by the kinase Cds1 ( human Chk2), which regulates both cell cycle progression and DNA repair factors to ensure that the genome is faithfully duplicated prior to mitosis. Cds1 contains a forkhead-associated domain that mediates its interaction with phosphorylated residues in target proteins. One target of Cds1 is the essential nuclear protein Rad60, which contains the unique structural feature of tandem SUMO homology domains at its C terminus. Hypomorphic mutants of Rad60 cause profound defects in DNA repair and replication stress tolerance. To explore the physiological significance of the Cds1-Rad60 interaction, we have examined the phosphorylation of Rad60 by Cds1 in vitro and the in vivo phosphorylation of Rad60 in response to replication blocks. We find that the N terminus but not the SUMO-like domain of Rad60 is phosphorylated in both conditions. Three important Rad60 phosphorylation sites were identified: Thr(72), Ser(32), and Ser(34). Rad(60) Thr(72) mediates the Cds1-Rad60 interaction and is required for the Cds1-dependent phosphorylation of Rad60 in response to replication arrest. Phosphorylation of Rad60 Ser32 and Ser34 in a putative SUMO-binding motif is critical for the survival of replication stress. In addition, mutation of Rad60 Ser32 and Ser34 to alanine is lethal in cells deleted for the RecQ DNA helicase Rqh1. Finally, we find that Rad60 self-associates via its C-terminal SUMO-like domain and putative SUMO-binding motifs
The influence of meteorology, urban topography and traffic on the variability in concentrations of a traffic-related pollutant in urban street canyons
No full textA comprehensive study into the spatial and temporal variations in concentrations of a traffic-related pollutant was undertaken in two urban street canyons located in York,
U. K. During the field experiment, investigations were carried out in order to determine the influence of meteorology, urban topography and traffic on the
measured concentrations of a traffic-related pollutant. The pollutant measured in this study was carbon monoxide (CO).
Results are presented from simultaneous and continuous measurements of the background (or reference) wind speed and direction, the in-canyon wind and turbulence fields, traffic characteristics and CO concentrations collected
over a period of one month. The background wind was found to influence the development of in-canyon wind flow features, which became mechanisms for pollutant dispersion.
Under certain background winds, evidence of across-canyon recirculating flows with horizontally- and vertically-aligned axes is presented. During these conditions,
turbulence and traffic-related pollutants are likely to have been transported in the across-canyon re-circulating flows. During background wind orientated perpendicular
to the street axis, the 15-minute mean concentrations of CO were a factor of 2 or 3 higher on the leeward (or upwind) side of the street canyons compared to the windward side. This was caused by the development of an across-canyon
recirculating flow with a horizontally-aligned axis. Down draughts were measured on the windward side of the canyon during these conditions, while updraughts were measured on the leeward side. The wind direction at street level opposed the direction of the above-roof flow, causing the transport of CO towards the leeward side of the street
canyon where concentrations increased.
Evidence Results are presented from simultaneous and continuous measurements of the background (or reference) wind speed and direction, the in-canyon wind and
turbulence fields, traffic characteristics and CO concentrations collected over a period of one month. The background wind was found to influence the development of incanyon wind flow features, which became mechanisms for pollutant dispersion. Under certain background winds, evidence of across-canyon re circulating flows with
horizontally- and vertically-aligned axes is presented. During these conditions, turbulence and traffic-related pollutants are likely to have been transported in the
across-canyon re circulating flows. During background wind orientated perpendicular to the street axis, the 15-minute mean concentrations of CO were a factor of 2 or 3
higher on the leeward (or upwind) side of the street canyons compared to the windward side. This was caused by the development of an across-canyon recirculatingf low with a horizontally-aligned axis. Downdraughts were measured on
the windward side of the canyon during these conditions, while updraughts were measured on the leeward side. The wind direction at street level opposed the direction of the above-roof flow, causing the transport of CO towards the leeward side of the street canyon where concentrations in creased. Evidence of counter-rotating comer vortices with vertically-aligned axes are also presented and are thought to have been caused by along-canyon converging flows
during certain background winds. However, across-canyon flow during these conditions also accounted for the higher concentrations of CO measured on the leeward side of the canyon, compared to the windward side. Background winds
orientated oblique to the street axis were found to produce across-canyon rearticulating flows. On the other hand, parallel background winds produced channel flows, which had a 'flushing' effect, causing some of the lowest concentrations of CO to be measured during these
conditions.
Traffic-produced turbulence was investigated in the street canyon during the field experiment. Comparisons were made between calculated and measured turbulence parameters. The results indicate that the parameterisation performs reasonably well, particularly during weak perpendicular background winds when traffic-produced turbulence effects are likely to have been most dominant.
The traffic was also investigated due to the implications of traffic characteristics on the variability in concentrations of CO. The influence of free-, unstable- and
congested-traffic flows on measured CO concentrations was determined. The highest mean concentrations were measured during congested traffic conditions, when the emission levels are likely to have been elevated due to stop-start driving events. The combined influence of the background wind and traffic characteristics was investigated. Results are presented which show that the highest mean CO
concentrations were measured during perpendicular background winds and during congested traffic conditions. The implications of using variable emission rates in a
computational fluid dynamics (CFD) dispersion model were investigated in a sensitivity study. Results are also presented from the flow model study, which was conducted to help in the interpretation of the field experiment data
Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway
No full textProstaglandin E(2) (PGE(2)) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE(2) and exogenous PGE(2), present at high concentration in seminal plasma
New approaches to investigating the function of mycelial networks
No full textFungi play a key role in ecosystem nutrient cycles by scavenging, concentrating, translocating and redistributing nitrogen. To quantify and predict fungal nitrogen redistribution, and assess the importance of the integrity of fungal networks in soil for ecosystem function, we need better understanding of the structures and processes involved. Until recently nitrogen translocation has been experimentally intractable owing to the lack of a suitable radioisotope tracer for nitrogen, and the impossibility of observing nitrogen translocation in real time under realistic conditions. We have developed an imaging method for recording the magnitude and direction of amino acid flow through the whole mycelial network as it captures, assimilates and channels its carbon and nitrogen resources, while growing in realistically heterogeneous soil microcosms. Computer analysis and modeling, based on these digitized video records, can reveal patterns in transport that suggest experimentally testable hypotheses. Experimental approaches that we are developing include genomics and stable isotope NMR to investigate where in the system nitrogen compounds are being acquired and stored, and where they are mobilized for transport or broken down. The results are elucidating the interplay between environment, metabolism, and the development and function of transport networks as mycelium forages in soil. The highly adapted and selected foraging networks of fungi may illuminate fundamental principles applicable to other supply networks
Evaluating complex interventions and health technologies using normalization process theory: development of a simplified approach and web-enabled toolkit
No full text<b>Background</b> Normalization Process Theory (NPT) can be used to explain implementation processes in health care relating to new technologies and complex interventions. This paper describes the processes by which we developed a simplified version of NPT for use by clinicians, managers, and policy makers, and which could be embedded in a web-enabled toolkit and on-line users manual.<p></p>
<b>Methods</b> Between 2006 and 2010 we undertook four tasks. (i) We presented NPT to potential and actual users in multiple workshops, seminars, and presentations. (ii) Using what we discovered from these meetings, we decided to create a simplified set of statements and explanations expressing core constructs of the theory (iii) We circulated these statements to a criterion sample of 60 researchers, clinicians and others, using SurveyMonkey to collect qualitative textual data about their criticisms of the statements. (iv) We then reconstructed the statements and explanations to meet users' criticisms, embedded them in a web-enabled toolkit, and beta tested this 'in the wild'.<p></p>
<b>Results</b> On-line data collection was effective: over a four week period 50/60 participants responded using SurveyMonkey (40/60) or direct phone and email contact (10/60). An additional nine responses were received from people who had been sent the SurveyMonkey form by other respondents. Beta testing of the web enabled toolkit produced 13 responses, from 327 visits to www.normalizationprocess.org. Qualitative analysis of both sets of responses showed a high level of support for the statements but also showed that some statements poorly expressed their underlying constructs or overlapped with others. These were rewritten to take account of users' criticisms and then embedded in a web-enabled toolkit. As a result we were able to translate the core constructs into a simplified set of statements that could be utilized by non-experts.<p></p>
<b>Conclusion</b> Normalization Process Theory has been developed through transparent procedures at each stage of its life. The theory has been shown to be sufficiently robust to merit formal testing. This project has provided a user friendly version of NPT that can be embedded in a web-enabled toolkit and used as a heuristic device to think through implementation and integration problems
Projective techniques: Are they a victim of clashing paradigms?
No full textThis paper reviews the concept and historical development of projective techniques. It considers why, given the importance of their psychoanalytical foundations to the underlying paradigms of management theory, they have been generally marginalised as a mainstream business and management research tool. Projective techniques are defined and their historical origins delineated. This is followed by an overview of projective ‘types’. Some of the general advantages and current issues associated with employing projective techniques are also presented. Thereafter a discussion of the reasons projective techniques have not been widely adopted by positivist academic management researchers is made. We put forward the central argument that since many of the challenges facing management research are due to the restrictions introduced by bounded rationality, projective techniques offer a possible alternative to traditional mixed methods.Projective Techniques; Management Research;
EIA approach and the 'five pillars' of school-based teacher development
No full textA figure showing the EIA approach to whole school teacher development, mapped onto EIA's 'five pillars' of teacher development.The five pillars were derived from findings in:Westbrook, J., Durrani, N., Brown, R., Orr, D., Pryor, J., Boddy, J., & Salvi, F. (2013). Pedagogy, curriculum, teaching practices and teacher education in developing countries: Final report. [Education Rigorous Literature Review]. EPPI-Centre, Social Science Research Unit, Institute of Education, University of London. https://eppi.ioe.ac.uk/cms/LinkClick.aspx?fileticket=E93CRI7ONwA=&tabid=3433andPower, T., Gater, R., Grant, C., & Winters, N. (2014). Educational Technology Topic Guide. Health and Education Advice and Resource Team (HEART), Department for International Development (DFID). http://www.heart-resources.org/topic/educational-technology/</p
Cooperating Agents for 3D Scientific Data Interpretation
No full textMany organizations collect vast quantities of three-dimensional (3-D) scientific data in volumetric form for a range of purposes, including resource exploration, market forecasting, and process modelling. Traditionally, these data have been interpreted by human experts with only minimal software assistance. However, such manual interpretation is a painstakingly slow and tedious process. Moreover, since interpretation involves subjective judgements and each interpreter has different scientific knowledge and experience, formulation of an effective interpretation often requires the cooperation of numerous such experts. Hence, there is a pressing need for a software system in which individual interpretations can be generated automatically and then refined through the use of cooperative reasoning and information sharing. To this end, a prototype system, SurfaceMapper, has been developed in which a community of cooperating software agents automatically locate and display interpretations in a volume of 3-D scientific data. The challenges and experiences in designing and building such a system are discussed. Particular emphasis is given to the agents' interactions and an empirical evaluation of the effectiveness of different cooperation strategies is presented
Complicated intra-abdominal infections in Europe: preliminary data from the first three months of the CIAO Study
No full textContains fulltext :
110654.pdf (Publisher’s version ) (Open Access)ABSTRACT: The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012).This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period.Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.912 patients with a mean age of 54.4 years (range 4-98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified.The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38 degrees C or less than 36 degrees C by the third post-operative day were statistically significant indicators of patient mortality
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