A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway

Cholesterol is one of the key constituents for maintaining the cellular membrane and thus the integrity of the cell itself. In contrast high levels of cholesterol in the blood are known to be a major risk factor in the development of cardiovascular disease. We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in an hepatocyte. The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main precursor of cholesterol synthesis. Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. Model stability analysis shows that the only positive steady-state of the system exhibits purely oscillatory, damped oscillatory or monotic behaviour under certain parameter conditions. In light of our findings we postulate how cholesterol homestasis is maintained within the cell and the advantages of our model formulation are discussed with respect to other models of genetic regulation within the literature.

Does the PMSP connectionist model of single word reading learn to read in the same way as a child?

The Plaut, McClelland, Seidenberg and Patterson (1996) connectionist model of reading was evaluated at two points early in its training against reading data collected from British children on two occasions during their first year of literacy instruction. First, the network’s non-word reading was poor relative to word reading when compared with the children. Second, the network made more non-lexical than lexical errors, the opposite pattern to the children. Three adaptations were made to the training of the network to bring it closer to the learning environment of a child: an incremental training regime was adopted; the network was trained on grapheme– phoneme correspondences; and a training corpus based on words found in children’s early reading materials was used. The modifications caused a sharp improvement in non-word reading, relative to word reading, resulting in a near perfect match to the children’s data on this measure. The modified network, however, continued to make predominantly non-lexical errors, although evidence from a small-scale implementation of the full triangle framework suggests that this limitation stems from the lack of a semantic pathway. Taken together, these results suggest that, when properly trained, connectionist models of word reading can offer insights into key aspects of reading development in children.

Impact of vegetation and preferential source areas on global dust aerosol: results from a model study

[1] We present a model of the dust cycle that successfully predicts dust emissions as determined by land surface properties, monthly vegetation and snow cover, and 6-hourly surface wind speeds for the years 1982–1993. The model takes account of the role of dry lake beds as preferential source areas for dust emission. The occurrence of these preferential sources is determined by a water routing and storage model. The dust source scheme also explicitly takes into account the role of vegetation type as well as monthly vegetation cover. Dust transport is computed using assimilated winds for the years 1987–1990. Deposition of dust occurs through dry and wet deposition, where subcloud scavenging is calculated using assimilated precipitation fields. Comparison of simulated patterns of atmospheric dust loading with the Total Ozone Mapping Spectrometer satellite absorbing aerosol index shows that the model produces realistic results from daily to interannual timescales. The magnitude of dust deposition agrees well with sediment flux data from marine sites. Emission of submicron dust from preferential source areas are required for the computation of a realistic dust optical thickness. Sensitivity studies show that Asian dust source strengths are particularly sensitive to the seasonality of vegetation cover.

The Met Office unified model global atmosphere 4.0 and JULES global land 4.0 configurations

We describe Global Atmosphere 4.0 (GA4.0) and Global Land 4.0 (GL4.0): configurations of the Met Office Unified Model and JULES (Joint UK Land Environment Simulator) community land surface model developed for use in global and regional climate research and weather prediction activities. GA4.0 and GL4.0 are based on the previous GA3.0 and GL3.0 configurations, with the inclusion of developments made by the Met Office and its collaborators during its annual development cycle. This paper provides a comprehensive technical and scientific description of GA4.0 and GL4.0 as well as details of how these differ from their predecessors. We also present the results of some initial evaluations of their performance. Overall, performance is comparable with that of GA3.0/GL3.0; the updated configurations include improvements to the science of several parametrisation schemes, however, and will form a baseline for further ongoing development.

Dust sources and deposition during the last glacial maximum and current climate: a comparison of model results with paleodata from ice cores and marine sediments

Mineral dust aerosols in the atmosphere have the potential to affect the global climate by influencing the radiative balance of the atmosphere and the supply of micronutrients to the ocean. Ice and marine sediment cores indicate that dust deposition from the atmosphere was at some locations 2–20 times greater during glacial periods, raising the possibility that mineral aerosols might have contributed to climate change on glacial-interglacial time scales. To address this question, we have used linked terrestrial biosphere, dust source, and atmospheric transport models to simulate the dust cycle in the atmosphere for current and last glacial maximum (LGM) climates. We obtain a 2.5-fold higher dust loading in the entire atmosphere and a twenty-fold higher loading in high latitudes, in LGM relative to present. Comparisons to a compilation of atmospheric dust deposition flux estimates for LGM and present in marine sediment and ice cores show that the simulated flux ratios are broadly in agreement with observations; differences suggest where further improvements in the simple dust model could be made. The simulated increase in high-latitude dustiness depends on the expansion of unvegetated areas, especially in the high latitudes and in central Asia, caused by a combination of increased aridity and low atmospheric [CO2]. The existence of these dust source areas at the LGM is supported by pollen data and loess distribution in the northern continents. These results point to a role for vegetation feedbacks, including climate effects and physiological effects of low [CO2], in modulating the atmospheric distribution of dust.

Type-1 error inflation in the traditional by-participant analysis to metamemory accuracy: a generalized mixed-effects model perspective

In order to examine metacognitive accuracy (i.e., the relationship between metacognitive judgment and memory performance), researchers often rely on by-participant analysis, where metacognitive accuracy (e.g., resolution, as measured by the gamma coefficient or signal detection measures) is computed for each participant and the computed values are entered into group-level statistical tests such as the t-test. In the current work, we argue that the by-participant analysis, regardless of the accuracy measurements used, would produce a substantial inflation of Type-1 error rates, when a random item effect is present. A mixed-effects model is proposed as a way to effectively address the issue, and our simulation studies examining Type-1 error rates indeed showed superior performance of mixed-effects model analysis as compared to the conventional by-participant analysis. We also present real data applications to illustrate further strengths of mixed-effects model analysis. Our findings imply that caution is needed when using the by-participant analysis, and recommend the mixed-effects model analysis.

Development of a food-exchange model to replace saturated fat with MUFAS and n-6 PUFAS in adults at moderate cardiovascular risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21-60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n-6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n-6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n-6 PUFA in the respective diets, with significant overall diet effects for the changes in SFA, MUFA, and n-6 PUFA between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFA, MUFA, and n-6 PUFA for each diet group, with significant overall diet effects for total SFA and MUFA between groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFA with MUFA or n-6 PUFA with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov as NCT01478958.

Importance of resolution and model configuration when downscaling extreme precipitation

Dynamical downscaling is frequently used to investigate the dynamical variables of extra-tropical cyclones, for example, precipitation, using very high-resolution models nested within coarser resolution models to understand the processes that lead to intense precipitation. It is also used in climate change studies, using long timeseries to investigate trends in precipitation, or to look at the small-scale dynamical processes for specific case studies. This study investigates some of the problems associated with dynamical downscaling and looks at the optimum configuration to obtain the distribution and intensity of a precipitation field to match observations. This study uses the Met Office Unified Model run in limited area mode with grid spacings of 12, 4 and 1.5 km, driven by boundary conditions provided by the ECMWF Operational Analysis to produce high-resolution simulations for the Summer of 2007 UK flooding events. The numerical weather prediction model is initiated at varying times before the peak precipitation is observed to test the importance of the initialisation and boundary conditions, and how long the simulation can be run for. The results are compared to raingauge data as verification and show that the model intensities are most similar to observations when the model is initialised 12 hours before the peak precipitation is observed. It was also shown that using non-gridded datasets makes verification more difficult, with the density of observations also affecting the intensities observed. It is concluded that the simulations are able to produce realistic precipitation intensities when driven by the coarser resolution data.

Organisational politics: reconciling leadership's rational-emotional paradox

Purpose – Effective leadership action requires managers to harness power that is intrinsically political. This paper aims to study and characterise the political nature of a manager's behaviour when taking leadership action. Design/methodology/approach – The methodological approach is qualitative and examines three organisations over a three-year period when these entities experienced a major product failure. The paper analyses the actual managerial behaviour of managers and provides insight into the factors that most strongly influence the effectiveness of managers when taking leadership action. Findings – Political behaviour when taking leadership action can be conceptualised in terms of rationality and emotionality. In so doing, it can be clarified how behaviour must be modified to ensure that leadership action is consistently effective. Research limitations/implications – A case study of three multinational engineering companies engaged in the design, development and manufacturing of turbomachinery provides the platform for the research. The concepts presented in the paper will require validating in other organisations of different demographic profiles. Practical implications – The concepts presented and the implications discussed provide insight into the political nature of managerial behaviour when taking leadership action. The paper highlights the practical steps individual managers can embrace to ensure that their behaviour is appropriate to context, even under the most traumatic situations. Thus, the paper provides managers with a model that facilitates effective leadership action. Originality/value – This paper provides insight into how managers behaved in circumstances that mattered to them. Through immersion in events at the time they took place, the authors captured situations in which managers were under real pressure and, in so doing, avoided the bias inherent when interviewing a manager about past events. As such, the paper concludes that the political behaviour in which managers engage when taking leadership action is rooted in the reality of the adversity that the most capable managers have both experienced and overcome. This detailed study reports behaviour in a situation where managers' business and future prospects were in jeopardy. This paper identifies why some managers were able to use the experience positively, helping them to adopt politically intrinsic behaviour to facilitate effective leadership action.

Rethinking the ontology of the shareholder model of the corporation

Purpose – The purpose of this paper is to examine the critical assumptions lying behind the Anglo American model of corporate governance. Design/methodology/approach – Literature review examining the concept of a nexus of contracts underpinning agency theory which, it is argued, act as the platform for neo-liberal corporate governance focusing on shareholder wealth creation. Findings – The paper highlights the unaddressed critical challenge of why eighteenth century ownership structures are readily adopted in the twenty-first century. Social implications – A re-examination of wealth creation and wealth redistribution. Originality/value – The paper is highly original due to the fact that few contributions have been made in the area of rethinking shareholder value.

Mechanisms for AMOC variability simulated by the NEMO model

We have investigated mechanisms for the Atlantic Meridional Overturning Circulation (AMOC) variability at 26.5° N (other than the Ekman component) that can be related to external forcings, in particular wind variability. Resolution dependence is studied using identical experiments with 1° and 1/4° NEMO model runs over 1960–2010. The analysis shows that much of the variability in the AMOC at 26° N can be related to the wind strength over the North Atlantic, through mechanisms lagged on different timescales. At ~ 1-year lag the January–June difference of mean sea level pressure between high and mid-latitudes in the North Atlantic explains 35–50% of the interannual AMOC variability (with negative correlation between wind strength and AMOC). At longer lead timescales ~ 4 years, strong (weak) winds over the northern North Atlantic (specifically linked to the NAO index) are followed by higher (lower) AMOC transport, but this mechanism only works in the 1/4° model. Analysis of the density correlations suggests an increase (decrease) in deep water formation in the North Atlantic subpolar gyre to be the cause. Therefore another 30% of the AMOC variability at 26° N can be related to density changes in the top 1000 m in the Labrador and Irminger seas occurring ~ 4 years earlier.