421 research outputs found
Recommended from our members
Machine dependence and reproducibility for coupled climate simulations: the HadGEM3-GC3.1 CMIP Preindustrial simulation
When the same weather or climate simulation is run on different high-performance computing (HPC) platforms, model outputs may not be identical for a given initial condition. While the role of HPC platforms in delivering better climate projections is to some extent discussed in the literature, attention is mainly focused on scalability and performance rather than on the impact of machine-dependent processes on the numerical solution.
Here we investigate the behaviour of the Preindustrial (PI) simulation prepared by the UK Met Office for the forthcoming CMIP6 (Coupled Model Intercomparison Project Phase 6) under different computing environments.
Discrepancies between the means of key climate variables were analysed at different timescales, from decadal to centennial. We found that for the two simulations to be statistically indistinguishable, a 200-year averaging period must be used for the analysis of the results. Thus, constant-forcing climate simulations using the HadGEM3-GC3.1 model are reproducible on different HPC platforms provided that a sufficiently long duration of simulation is used.
In regions where El Niño–Southern Oscillation (ENSO) teleconnection patterns were detected, we found large sea surface temperature and sea ice concentration differences on centennial timescales. This indicates that a 100-year constant-forcing climate simulation may not be long enough to adequately capture the internal variability of the HadGEM3-GC3.1 model, despite this being the minimum simulation length recommended by CMIP6 protocols for many MIP (Model Intercomparison Project) experiments.
On the basis of our findings, we recommend a minimum simulation length of 200 years whenever possible
Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer
Three metabolite patterns have previously shown prospective inverse associations with
the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer
and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate
cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins
(Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern
2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524)
and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations
of 24 dietary and lifestyle variables with each pattern and the contributing individual
metabolites. Associations statistically significant after both correction for multiple testing (False
Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered
robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively
associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which
appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty
fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish
and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of
aggressive prostate cancer.Cancer Research UK C8221/A30904
C8221/A29017World Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDanish Cancer SocietyLigue Contre le Cancer (France)
Institut Gustave Roussy (France)
Mutuelle Generale de l'Education Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeGerman Cancer Research Center (DKFZ) (Germany)
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany)Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancro
Compagnia di San Paolo
Consiglio Nazionale delle Ricerche (CNR)Netherlands Government
Netherlands GovernmentWorld Cancer Research Fund International (WCRF)Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain)Junta de AndaluciaPrincipality of AsturiasRegional Government of Basque Country (Spain)
Regional Government of Murcia (Spain)
Regional Government of Navarra (Spain)
Catalan Institute of Oncology-ICO (Spain)Swedish Cancer Society
Swedish Research Council
County Council of Skane (Sweden)
County Council of Vasterbotten (Sweden)UK Research & Innovation (UKRI)
Medical Research Council UK (MRC) 1000143
MR/N003284/1
MC-UU_12015/1
MC_UU_00006/1
MR/M012190/
Internuclear gene silencing in Phytophthora infestans is established through chromatin remodelling
In the plant pathogen Phytophthora infestans, nuclear integration of inf1 transgenic DNA sequences results in internuclear gene silencing of inf1. Although silencing is regulated at the transcriptional level, it also affects transcription from other nuclei within heterokaryotic cells of the mycelium. Here we report experiments exploring the mechanism of internuclear gene silencing in P. infestans. The DNA methylation inhibitor 5-azacytidine induced reversion of the inf1-silenced state. Also, the histone deacetylase inhibitor trichostatin-A was able to reverse inf1 silencing. inf1-expression levels returned to the silenced state when the inhibitors were removed except in non-transgenic inf1-silenced strains that were generated via internuclear gene silencing, where inf1 expression was restored permanently. Therefore, inf1-transgenic sequences are required to maintain the silenced state. Prolonged culture of non-transgenic inf1-silenced strains resulted in gradual reactivation of inf1 gene expression. Nuclease digestion of inf1-silenced and non-silenced nuclei showed that inf1 sequences in silenced nuclei were less rapidly degraded than non-silenced inf1 sequences. Bisulfite sequencing of the endogenous inf1 locus did not result in detection of any cytosine methylation. Our findings suggest that the inf1-silenced state is based on chromatin remodelling
Recommended from our members
The effects of explicit versus parameterized convection on the MJO in a large-domain high-resolution tropical case study. Part II: Processes leading to differences in MJO development
High-resolution simulations over a large tropical domain (∼20◦S–20◦N and 42◦E–180◦E) using both explicit and parameterized convection are analyzed and compared during a 10-day case study of an active Madden-Julian Oscillation (MJO) event. In Part II, the moisture budgets and moist entropy budgets are analyzed. Vertical subgrid diabatic heating profiles and vertical velocity profiles are also compared; these are related to the horizontal and vertical advective components of the moist entropy budget which contribute to gross moist stability, GMS, and normalized GMS (NGMS). The 4-km model with explicit convection and good MJO performance has a vertical heating structure that increases with height in the lower troposphere in regions of strong convection (like observations), whereas the 12-km model with parameterized convection and a poor MJO does not show this relationship. The 4-km explicit convection model also has a more top-heavy heating profile for the troposphere as a whole near and to the west of the active MJO-related convection, unlike the 12-km parameterized convection model. The dependence of entropy advection components on moisture convergence is fairly weak in all models, and differences between models are not always related to MJO performance, making comparisons to previous work somewhat inconclusive. However, models with relatively good MJO strength and propagation have a slightly larger increase of the vertical advective component with increasing moisture convergence, and their NGMS vertical terms have more variability in time and longitude, with total NGMS that is comparatively larger to the west and smaller to the east
Cultural molding, shielding, and shoring at Oilco: the role of culture in the integration of routines
We explore how organizational culture shapes an organization’s integration and enactment of an external routine that is not a cultural fit. Attending to employees’ use of culture as a repertoire of strategies of action, we found that the use of familiar cultural strategies of action shaped the routine’s artifacts and expectations even before it was performed, a process we call cultural molding. Subsequently, employees drew differently on cultural strategies of action as they performed the routine, generating patterns of workarounds or hindered performances. In response to these patterns, they undertook additional cultural work to either shield their workarounds and protect them from scrutiny or shore up hindered performances. We contribute to the routine dynamics literature by highlighting the effortful cultural work involved in integrating coveted routines, furthering our understanding of routines as truces and the embeddedness of routines.Social Sciences and Humanities Research Council of Canada [Grant 430-2012-195
A molecular insight into algal-oomycete warfare : cDNA analysis of Ectocarpus siliculosus infected with the basal oomycete Eurychasma dicksonii
Peer reviewedPublisher PD
Family routines and next-generation engagement in family firms
By focusing on the impact of different types of family routines and how they change, this commentary builds on concepts regarding the influence of perceived parental support and psychological control on next-generation engagement in family firms. Drawing on the organizational routines literature and the family studies literature, I propose that attention to family routines, and how these routines change (or not) over time can reveal additional insights regarding next-generation engagement in the family business
Recommended from our members
UniFHy v0.1.1: a community modelling framework for the terrestrial water cycle in Python
The land surface, hydrological, and groundwater modelling communities all have expertise in simulating the hydrological processes at play in the terrestrial component of the Earth system. However, these communities, and the wider Earth system modelling community, have largely remained distinct with limited collaboration between disciplines, hindering progress in the representation of hydrological processes in the land component of Earth system models (ESMs). In order to address key societal questions regarding the future availability of water resources and the intensity of extreme events such as floods and droughts in a changing climate, these communities must come together and build on the strengths of one another to produce next-generation land system models that are able to adequately simulate the terrestrial water cycle under change. The development of a common modelling infrastructure can contribute to stimulating cross-fertilisation by structuring and standardising the interactions. This paper presents such an infrastructure, a land system framework, which targets an intermediate level of complexity and constrains interfaces between components (and communities) and, in doing so, aims to facilitate an easier pipeline between the development of (sub-)community models and their integration, both for standalone use and for use in ESMs. This paper first outlines the conceptual design and technical capabilities of the framework; thereafter, its usage and useful characteristics are demonstrated through case studies. The main innovations presented here are (1) the interfacing constraints themselves; (2) the implementation in Python (the Unified Framework for Hydrology, unifhy); and (3) the demonstration of standalone use cases using the framework. The existing framework does not yet meet all our goals, in particular, of directly supporting integration into larger ESMs, so we conclude with the remaining limitations of the current framework and necessary future developments.</p
Recommended from our members
Sustainable development for a better world: contributions of leadership, management, and organizations
[first paragraph] On September 25th 2015, all 193 member countries of the United Nations (UN) adopted a set of 17 Sustainable Development Goals (SDGs) designed to end poverty, protect the planet, and ensure prosperity for all as part of a new global “Agenda 2030” (United Nations, 2015). Building on the earlier UN Millennium Development Goals and seeking to complete what had been left undone, this new agenda for sustainable development laid out a bold ambition: “We are resolved to free the human race from the tyranny of poverty ... and to heal and secure our planet. We are determined to take the bold and transformative steps which are urgently needed to shift the world on to a sustainable and resilient path. As we embark on this collective journey, we pledge that no one will be left behind.
Recommended from our members
Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer.
OBJECTIVES: To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis. DESIGN: Multicentre prospective observational cohort study. SETTING AND PARTICIPANTS: Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected. OUTCOMES: Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival. RESULTS: Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC. CONCLUSIONS: Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers
- …