3,446 research outputs found
Agile methods for agile universities
We explore a term, Agile, that is being used in various workplace settings, including the management of universities. The term may have several related but slightly different meanings. Agile is often used in the context of facilitating more creative problem-solving and advocating for the adoption, design, tailoring and continual updating of more innovative organizational processes. We consider a particular set of meanings of the term from the world of software development. Agile methods were created to address certain problems with the software development process. Many of those problems have interesting analogues in the context of universities, so a reflection on agile methods may be a useful heuristic for generating ideas for enabling universities to be more creative
Deep-water channel-lobe transition zone dynamics: Processes and depositional architecture, an example from the Karoo Basin, South Africa
Submarine channel-lobe transition zones separate well-defined channels from well-defined lobes and form morphologically complicated areas, commonly located at breaks in slope. These areas play a vital role in the transfer of sediment through deep-water systems. Extensive outcrop exposures in the Karoo Basin, South Africa, permit investigation of the depositional architecture and evolution of entirely exhumed dip transects of a channel-lobe transition zone for the first time. Furthermore, the excellent paleogeographic constraint allows correlation to genetically related updip channel-levee systems and downdip lobe deposits over 40 km, with strike control over 20 km. Unlike the single time slice afforded by modern systems, the Karoo example uniquely allows study of the temporal shifting of the channel-lobe transition zone and transfer into the stratigraphic record.
Key lateral changes along the base of slope include the variation from an interfingering levee-lobe transition zone to a bypass-dominated channel-lobe transition zone over a width of 14 km. Key recognition criteria for channel-lobe transition zones in the ancient record include combinations of scours and megaflutes, composite erosional surfaces, mudstone clast/coarse-grained sediment lags, and remnants of depositional bed forms, such as sediment waves. Documented here in a single channel-lobe transition zone, these features are arranged in a zone of juxtaposed remnant erosional and depositional features. The zone reaches 6 km in length, formed by at least four stages of expansion/contraction or migration. Strike variations and changes in the dimensions of the channel-lobe transition zone through time are interpreted to be the result of physiographic changes and variations in flow dynamics across the base of slope. The dynamic nature of channel-lobe transition zones results in complicated and composite stratigraphy, with preservation potential generally low but increasing distally and laterally away from the mouth of the feeder channel system. Here, we present the first generic model to account for dynamic channel-lobe transition zone development, encompassing distinctive recognition criteria, fluctuations in the morphology and position of the zone, and the complex transfer into the sedimentary record
Phase 2 study of combination SPI-1620 with docetaxel as second-line advanced biliary tract cancer treatment
Sporadic paediatric diarrhoeal illness in urban and rural sites in Nyanza province, Kenya
Objective: Investigate differences in the infectious aetiology, health seeking behaviour, and provider practices with regard to diarrhoeal illness among children presenting to urban versus rural clinics in Western Kenya.Design: Laboratory-based, passive surveillance.Setting: The urban portion of the study was conducted at the paediatric outpatient clinic of Nyanza Provincial Hospital in Kisumu. The rural portion of the study was conducted at four outpatient clinics in the Asembo Bay community approximately 20 kilometers west of Kisumu.Subjects: Children aged less than five years presenting to medical facilities for the treatment of diarrhoea from October 2001-October 2003 at the urban site and May 1997-April 2003 for the rural sites.Results: Among the 1303 urban and 1247 rural specimens collected, 24% of specimens yielded a bacterial pathogen (24% urban, 25% rural). Campylobacter was the predominant bacterial pathogen (17% urban, 15% rural), followed by Shigella and nontyphoidal Salmonella (both 4% urban and 5% rural). In both communities, susceptibilities of these pathogens to the most commonly prescribed antibiotics was low
A Human Development Framework for CO2 Reductions
Although developing countries are called to participate in CO2 emission
reduction efforts to avoid dangerous climate change, the implications of
proposed reduction schemes in human development standards of developing
countries remain a matter of debate. We show the existence of a positive and
time-dependent correlation between the Human Development Index (HDI) and per
capita CO2 emissions from fossil fuel combustion. Employing this empirical
relation, extrapolating the HDI, and using three population scenarios, the
cumulative CO2 emissions necessary for developing countries to achieve
particular HDI thresholds are assessed following a Development As Usual
approach (DAU). If current demographic and development trends are maintained,
we estimate that by 2050 around 85% of the world's population will live in
countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2
emissions between 2000 and 2050 are estimated to be necessary for the
development of 104 developing countries in the year 2000. This value represents
between 20% to 30% of previously calculated CO2 budgets limiting global warming
to 2{\deg}C. These constraints and results are incorporated into a CO2
reduction framework involving four domains of climate action for individual
countries. The framework reserves a fair emission path for developing countries
to proceed with their development by indexing country-dependent reduction rates
proportional to the HDI in order to preserve the 2{\deg}C target after a
particular development threshold is reached. Under this approach, global
cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of
CO2. These values are within the uncertainty range of emissions to limit global
temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl
A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation.
BACKGROUND: The mammalian DNA-damage response (DDR) has evolved to protect genome stability and maximize cell survival following DNA-damage. One of the key regulators of the DDR is p53, itself tightly regulated by MDM2. Following double-strand DNA breaks (DSBs), mediators including ATM are recruited to the site of DNA-damage. Subsequent phosphorylation of p53 by ATM and ATM-induced CHK2 results in p53 stabilization, ultimately intensifying transcription of p53-responsive genes involved in DNA repair, cell-cycle checkpoint control and apoptosis.
METHODS: In the current study, we investigated the stabilization and activation of p53 and associated DDR proteins in response to treatment of human colorectal cancer cells (HCT116p53+/+) with the MDM2 antagonist, Nutlin-3.
RESULTS: Using immunoblotting, Nutlin-3 was observed to stabilize p53, and activate p53 target proteins. Unexpectedly, Nutlin-3 also mediated phosphorylation of p53 at key DNA-damage-specific serine residues (Ser15, 20 and 37). Furthermore, Nutlin-3 induced activation of CHK2 and ATM - proteins required for DNA-damage-dependent phosphorylation and activation of p53, and the phosphorylation of BRCA1 and H2AX - proteins known to be activated specifically in response to DNA damage. Indeed, using immunofluorescent labeling, Nutlin-3 was seen to induce formation of γH2AX foci, an early hallmark of the DDR. Moreover, Nutlin-3 induced phosphorylation of key DDR proteins, initiated cell cycle arrest and led to formation of γH2AX foci in cells lacking p53, whilst γH2AX foci were also noted in MDM2-deficient cells.
CONCLUSION: To our knowledge, this is the first solid evidence showing a secondary role for Nutlin-3 as a DDR triggering agent, independent of p53 status, and unrelated to its role as an MDM2 antagonist
Designing an information system for updating land records in Bangladesh: action design ethnographic research (ADER)
Open Access. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Information Systems (IS) has developed through adapting, generating and applying diverse methodologies, methods, and techniques from reference disciplines. Further, Action Design Research (ADR) has recently developed as a broad research method that focuses on designing and redesigning IT and IS in organizational contexts. This paper reflects on applying ADR in a complex organizational context in a developing country. It shows that ADR requires additional lens for designing IS in such a complex organizational context. Through conducting ADR, it is seen that an ethnographic framework has potential complementarities for understanding complex contexts thereby enhancing the ADR processes. This paper argues that conducting ADR with an ethnographic approach enhances design of IS and organizational contexts. Finally, this paper aims presents a broader methodological framework, Action Design Ethnographic Research (ADER), for designing artefacts as well as IS. This is illustrated through the case of a land records updating service in Bangladesh
Family composition and age at menarche: findings from the international Health Behaviour in School-Aged Children Study
This research was funded by The University of St Andrews and NHS Health Scotland.Background Early menarche has been associated with father absence, stepfather presence and adverse health consequences in later life. This article assesses the association of different family compositions with the age at menarche. Pathways are explored which may explain any association between family characteristics and pubertal timing. Methods Cross-sectional, international data on the age at menarche, family structure and covariates (age, psychosomatic complaints, media consumption, physical activity) were collected from the 2009–2010 Health Behaviour in School-aged Children (HBSC) survey. The sample focuses on 15-year old girls comprising 36,175 individuals across 40 countries in Europe and North America (N = 21,075 for age at menarche). The study examined the association of different family characteristics with age at menarche. Regression and path analyses were applied incorporating multilevel techniques to adjust for the nested nature of data within countries. Results Living with mother (Cohen’s d = .12), father (d = .08), brothers (d = .04) and sisters (d = .06) are independently associated with later age at menarche. Living in a foster home (d = −.16), with ‘someone else’ (d = −.11), stepmother (d = −.10) or stepfather (d = −.06) was associated with earlier menarche. Path models show that up to 89% of these effects can be explained through lifestyle and psychological variables. Conclusions Earlier menarche is reported amongst those with living conditions other than a family consisting of two biological parents. This can partly be explained by girls’ higher Body Mass Index in these families which is a biological determinant of early menarche. Lower physical activity and elevated psychosomatic complaints were also more often found in girls in these family environments.Publisher PDFPeer reviewe
SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1
BACKGROUND
We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown.
METHODS
A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer.
RESULTS
Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53.
CONCLUSION
Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity
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