Long-term diffusion experiment at Mont Terri: first results from field and laboratory data

The diffusion of radionuclides is an important safety aspect for nuclear waste disposal in argillaceous host rocks. A long-term diffusion experiment, termed DI-A, is being carried out at the Mont Terri Rock Laboratory in the Opalinus Clay formation. The aim of this experiment is the understanding of the migration and sorption behaviour of cationic and anionic species in consolidated clays. This study reports on the experimental layout and the first results obtained from the DI-A experiment, which include the investigation of HTO, Na-22(+), Cs+, and I- migration during a period of 1 year by analysing these tracers in the water circulating in the borehole. In addition, results obtained from through-diffusion experiments on small-sized samples with HTO, I-, and Cl-36(-) are presented. The decrease of tracer concentrations in the borehole is fastest for Cs+, followed by Na-22(+), HTO, and finally I-. The chemical composition of the artificial pore water in the borehole shows very little variation with time, thus indicating almost no chemical disturbance around the borehole. Through-diffusion experiments in the laboratory that were performed parallel to the bedding plane with two different methods yielded effective diffusion coefficients for HTO of 4-5 X 10(-11) m(2) s(-1) and significantly lower ones for anions Cl- and I- (0.7-1.6 X 10(-11) m(2) s(-1)). The results indicate the importance of anion exclusion effects arising from the negatively charged clay surfaces. Furthermore, they demonstrate the anisotropic diffusion properties of the clay formation with significantly increased diffusion rates parallel to bedding relative to the perpendicular direction. The tracer data of the in situ experiment were successfully described with 2D diffusion models using diffusion and sorption parameters obtained from the above mentioned and other laboratory studies. The modelling results indicate that HTO and I- diffused with no retardation. The retardation of Na+ and Cs+ could be described by empirical sorption expressions from previously derived batch sorption (Cs+) or diffusion (Na+) experiments. Overall, the obtained results demonstrate the feasibility of the technical concept to study the diffusion of nonsorbing and sorbing tracers in consolidated clays. (C) 2004 Elsevier B.V. All rights reserved.

A reconstruction of radiocarbon production and total solar irradiance from the Holocene ¹⁴C and CO₂ records: implications of data and model uncertainties

Radiocarbon production, solar activity, total solar irradiance (TSI) and solar-induced climate change are reconstructed for the Holocene (10 to 0 kyr BP), and TSI is predicted for the next centuries. The IntCal09/SHCal04 radiocarbon and ice core CO2 records, reconstructions of the geomagnetic dipole, and instrumental data of solar activity are applied in the Bern3D-LPJ, a fully featured Earth system model of intermediate complexity including a 3-D dynamic ocean, ocean sediments, and a dynamic vegetation model, and in formulations linking radiocarbon production, the solar modulation potential, and TSI. Uncertainties are assessed using Monte Carlo simulations and bounding scenarios. Transient climate simulations span the past 21 thousand years, thereby considering the time lags and uncertainties associated with the last glacial termination. Our carbon-cycle-based modern estimate of radiocarbon production of 1.7 atoms cm−2 s−1 is lower than previously reported for the cosmogenic nuclide production model by Masarik and Beer (2009) and is more in-line with Kovaltsov et al. (2012). In contrast to earlier studies, periods of high solar activity were quite common not only in recent millennia, but throughout the Holocene. Notable deviations compared to earlier reconstructions are also found on decadal to centennial timescales. We show that earlier Holocene reconstructions, not accounting for the interhemispheric gradients in radiocarbon, are biased low. Solar activity is during 28% of the time higher than the modern average (650 MeV), but the absolute values remain weakly constrained due to uncertainties in the normalisation of the solar modulation to instrumental data. A recently published solar activity–TSI relationship yields small changes in Holocene TSI of the order of 1 W m−2 with a Maunder Minimum irradiance reduction of 0.85 ± 0.16 W m−2. Related solar-induced variations in global mean surface air temperature are simulated to be within 0.1 K. Autoregressive modelling suggests a declining trend of solar activity in the 21st century towards average Holocene conditions.

MODELLING β2AR REGULATION

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models can be classified into three classes; (i) Six quantitative models of SABA-induced G protein coupled receptor kinase (GRK)-mediated β2AR regulation; (ii) Three phenomenological models of salmeterol (a LABA)-induced GRK-mediated β2AR regulation; and (iii) One semi-quantitative, unified model of SABA-induced GRK-, protein kinase A (PKA)-, and phosphodiesterase (PDE)-mediated regulation of β2AR signalling. The various models were constrained with all or some of the following experimental data; (i) GRK-mediated β2AR phosphorylation in response to various LABAs/SABAs; (ii) dephosphorylation of the GRK site on the β2AR; (iii) β2AR internalisation; (iv) β2AR recycling; (v) β2AR desensitisation; (vi) β2AR resensitisation; (vii) PKA-mediated β2AR phosphorylation in response to a SABA; and (viii) LABA/SABA induced cAMP profile ± PDE inhibitors. The models of GRK-mediated β2AR regulation show that plasma membrane dephosphorylation and recycling of the phosphorylated β2AR are required to reconcile with the measured dephosphorylation kinetics. We further used a consensus model to predict the consequences of rapid pulsatile agonist stimulation and found that although resensitisation was rapid, the β2AR system retained the memory of prior stimuli and desensitised much more rapidly and strongly in response to subsequent stimuli. This could explain tachyphylaxis of SABAs over repeated use in rescue therapy of asthma patients. The LABA models show that the long action of salmeterol can be explained due to decreased stability of the arrestin/β2AR/salmeterol complex. This could explain long action of β-agonists used in maintenance therapy of asthma patients. Our consensus model of PKA/PDE/GRK-mediated β2AR regulation is being used to identify the dominant β2AR desensitisation pathways under different therapeutic regimens in human airway cells. In summary our models represent a significant advance towards understanding agonist-specific β2AR regulation that will aid in a more rational use of the β2AR agonists in the treatment of asthma.

Inverse modelling of the 14C bomb pulse in stalagmites to constrain the dynamics of soil carbon cycling at selected European cave sites

The decomposition of soil organic matter (SOM) is temperature dependent, but its response to a future warmer climate remains equivocal. Enhanced rates of decomposition of SOM under increased global temperatures might cause higher CO2 emissions to the atmosphere, and could therefore constitute a strong positive feedback. The magnitude of this feedback however remains poorly understood, primarily because of the difficulty in quantifying the temperature sensitivity of stored, recalcitrant carbon that comprises the bulk (>90%) of SOM in most soils. In this study we investigated the effects of climatic conditions on soil carbon dynamics using the attenuation of the 14C ‘bomb’ pulse as recorded in selected modern European speleothems. These new data were combined with published results to further examine soil carbon dynamics, and to explore the sensitivity of labile and recalcitrant organic matter decomposition to different climatic conditions. Temporal changes in 14C activity inferred from each speleothem was modelled using a three pool soil carbon inverse model (applying a Monte Carlo method) to constrain soil carbon turnover rates at each site. Speleothems from sites that are characterised by semi-arid conditions, sparse vegetation, thin soil cover and high mean annual air temperatures (MAATs), exhibit weak attenuation of atmospheric 14C ‘bomb’ peak (a low damping effect, D in the range: 55–77%) and low modelled mean respired carbon ages (MRCA), indicating that decomposition is dominated by young, recently fixed soil carbon. By contrast, humid and high MAAT sites that are characterised by a thick soil cover and dense, well developed vegetation, display the highest damping effect (D = c. 90%), and the highest MRCA values (in the range from 350 ± 126 years to 571 ± 128 years). This suggests that carbon incorporated into these stalagmites originates predominantly from decomposition of old, recalcitrant organic matter. SOM turnover rates cannot be ascribed to a single climate variable, e.g. (MAAT) but instead reflect a complex interplay of climate (e.g. MAAT and moisture budget) and vegetation development.

Timing of bacterial carriage sampling in vaccine trials: A modelling study.

BACKGROUND Pathogenic bacteria are often asymptomatically carried in the nasopharynx. Bacterial carriage can be reduced by vaccination and has been used as an alternative endpoint to clinical disease in randomised controlled trials (RCTs). Vaccine efficacy (VE) is usually calculated as 1 minus a measure of effect. Estimates of vaccine efficacy from cross-sectional carriage data collected in RCTs are usually based on prevalence odds ratios (PORs) and prevalence ratios (PRs), but it is unclear when these should be measured. METHODS We developed dynamic compartmental transmission models simulating RCTs of a vaccine against a carried pathogen to investigate how VE can best be estimated from cross-sectional carriage data, at which time carriage should optimally be assessed, and to which factors this timing is most sensitive. In the models, vaccine could change carriage acquisition and clearance rates (leaky vaccine); values for these effects were explicitly defined (facq, 1/fdur). POR and PR were calculated from model outputs. Models differed in infection source: other participants or external sources unaffected by the trial. Simulations using multiple vaccine doses were compared to empirical data. RESULTS The combined VE against acquisition and duration calculated using POR (VEˆacq.dur, (1-POR)×100) best estimates the true VE (VEacq.dur, (1-facq×fdur)×100) for leaky vaccines in most scenarios. The mean duration of carriage was the most important factor determining the time until VEˆacq.dur first approximates VEacq.dur: if the mean duration of carriage is 1-1.5 months, up to 4 months are needed; if the mean duration is 2-3 months, up to 8 months are needed. Minor differences were seen between models with different infection sources. In RCTs with shorter intervals between vaccine doses it takes longer after the last dose until VEˆacq.dur approximates VEacq.dur. CONCLUSION The timing of sample collection should be considered when interpreting vaccine efficacy against bacterial carriage measured in RCTs.

Viral load versus CD4⁺ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: a cohort-based modelling study.

OBJECTIVES Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4⁺ to monitor ART. We assessed the benefit of replacing CD4⁺ by viral load monitoring. DESIGN A mathematical modelling study. METHODS A simulation model of HIV progression over 5 years in children on ART, parameterized by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4⁺ or 6- or 12-monthly viral load monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses, we varied the rate of virological failure, and assumed that the rate is higher with CD4⁺ than with viral load monitoring. RESULTS About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4⁺ monitoring, 12-monthly viral load monitoring reduced the 5-year risk of immunological failure from 1.6 to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4⁺ compared with 12% with viral load monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4⁺ than with viral load monitoring, up to 4.2% of children with CD4⁺ compared with 1.5% with viral load monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4⁺ monitoring and 6.0 months with viral load monitoring. Conclusion: Viral load monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART.

Modelling the system behaviour of wet snow avalanches using an expert system approach for risk management on high alpine traffic roads

The presented approach describes a model for a rule-based expert system calculating the temporal variability of the release of wet snow avalanches, using the assumption of avalanche triggering without the loading of new snow. The knowledge base of the model is created by using investigations on the system behaviour of wet snow avalanches in the Italian Ortles Alps, and is represented by a fuzzy logic rule-base. Input parameters of the expert system are numerical and linguistic variables, measurable meteorological and topographical factors and observable characteristics of the snow cover. Output of the inference method is the quantified release disposition for wet snow avalanches. Combining topographical parameters and the spatial interpolation of the calculated release disposition a hazard index map is dynamically generated. Furthermore, the spatial and temporal variability of damage potential on roads exposed to wet snow avalanches can be quantified, expressed by the number of persons at risk. The application of the rule base to the available data in the study area generated plausible results. The study demonstrates the potential for the application of expert systems and fuzzy logic in the field of natural hazard monitoring and risk management.

Untangling a Holocene pollen record with forest model simulations and independent climate data

Adaptation potential of forests to rapid climatic changes can be assessed from vegetation dynamics during past climatic changes as preserved in fossil pollen data. However, pollen data reflect the integrated effects of climate and biotic processes, such as establishment, survival, competition, and migration. To disentangle these processes, we compared an annually laminated late Würm and Holocene pollen record from the Central Swiss Plateau with simulations of a dynamic forest patch model. All input data used in the simulations were largely independent from pollen data; i.e. the presented analysis is non-circular. Temperature and precipitation scenarios were based on reconstructions from pollen-independent sources. The earliest arrival times of the species at the study site after the last glacial were inferred from pollen maps. We ran a series of simulations under different combinations of climate and immigration scenarios. In addition, the sensitivity of the simulated presence/absence of four major species to changes in the climate scenario was examined. The pattern of the pollen record could partly be explained by the used climate scenario, mostly by temperature. However, some features, in particular the absence of most species during the late Würm could only be simulated if the winter temperature anomalies of the used scenario were decreased considerably. Consequently, we had to assume in the simulations, that most species immigrated during or after the Younger Dryas (12 000 years BP), Abies and Fagus even later. Given the timing of tree species immigration, the vegetation was in equilibrium with climate during long periods, but responded with lags at the time-scale of centuries to millennia caused by a secondary succession after rapid climatic changes such as at the end of Younger Dryas, or immigration of dominant taxa. Climate influenced the tree taxa both directly and indirectly by changing inter-specific competition. We concluded, that also during the present fast climatic change, species migration might be an important process, particularly if geographic barriers, such as the Alps are in the migrational path.

Computational fluid dynamics modelling in cardiovascular medicine.

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges.

Lithology, biostratigraphy, and geochemistry of the Black Sea sediments, DSDP Leg 42 (pt. 2) data

The monograph presents results of deep-sea drilling in the Black Sea carried out in 1975. Detailed lithological, biostratigraphic and geochemical studies of Miocene-Holocene sediments have been carried out by specialists from institutes of the USSR Academy of Sciences, Moscow State University and other organizations. Drilling results are compared with geophysical data. Geological history of the Black Sea basin is considered as well.

Sedimentological and benthic foraminiferal data pertaining to ODP Holes 208-1262A and 208-1263C

Eocene Thermal Maximum 2 (ETM2) occurred ~1.8 Myr after the Paleocene Eocene Thermal Maximum (PETM) and, like the PETM, was characterized by a negative carbon isotope excursion coupled with warming. We combined benthic foraminiferal and sedimentological records for Southeast Atlantic Sites 1263 (1500 m paleodepth) and 1262 (3600 m paleodepth) to show that benthic foraminiferal diversity and accumulation rates declined more precipitously and severely at the shallower site during peak ETM2. The sites are in close proximity, so differences in surface productivity cannot have caused this differential effect. Instead, on the basis of an analysis of climate modelling experiments, we infer that changes in ocean circulation pattern across ETM2 may have resulted in more pronounced warming at intermediate depths (Site 1263). The effects of more pronounced warming include increased metabolic rates, leading to a decrease in effective food supply and increased deoxygenation, thus potentially explaining the more severe benthic impacts at Site 1263. In response to more severe benthic disturbance, bioturbation may have decreased at Site 1263 as compared to Site 1262, hence differentially affecting the bulk carbonate record. We use a sediment-enabled Earth system model to test whether a reduction in bioturbation and/or the likely reduced carbonate saturation of more poorly ventilated waters can explain the more extreme excursion in bulk d13C and sharper transition in wt% CaCO3 at Site 1263. We find that both enhanced acidification and reduced bioturbation during peak ELMO conditions are needed to account for the observed features. Our combined ecological and modelling analysis illustrates the potential role of ocean circulation changes in amplifying local environmental changes and driving temporary, but drastic, loss of benthic biodiversity and abundance.

Modelling of the TICS Catalyse : Realization of a project

An action of modelling of the Territorial Intelligence Community Systems or TICS began in 2009 at the end of the CaEnti project. It has several objectives: - Establish a set of documents understandable by computer specialists who are in charge of software developments, and by territorial intelligence specialists. - Lay the foundation of a vocabulary describing the main notions of TICS domain. - Ensure the evolution and sustainability of tools and systems, in a highly scalable research context. The definition of models representing the data manipulated by the tools of the suitcase Catalyse is not sufficient to describe in a complete way the TICS domain. We established a correspondence between this computer vocabulary and vocabulary related to the theme to allow communication between computer scientists and territorial intelligence specialists. Furthermore it is necessary to describe the roles of TICS. For that it is interesting to use other kinds of computing models. In this communication we present the modelling of TICS project with business process

Territorial Intelligence of Vulnerability Systems 2- Sustainable Modelling of Globalization Challenge

Globalization as progress of economic development has increased population socioeconomical vulnerability when unequal wealth distribution within economic development process constitutes the main rule, with widening the gap between rich and poors by environmental pricing. Econological vulnerability is therefore increasing too, as dangerous substance and techniques should produce polluted effluents and industrial or climatic risk increasing (Woloszyn, Quenault, Faburel, 2012). To illustrate and model this process, we propose to introduce an analogical induction-model to describe both vulnerability situations and associated resilience procedures. At this aim, we first develop a well-known late 80?s model of socio-economic crack-up, known as 'Silent Weapons for Quiet Wars', which presents economics as a social extension of natural energy systems. This last, also named 'E-model', is constituted by three passive components, potential energy, kinetic energy, and energy dissipation, thus allowing economical data to be treated as a thermodynamical system. To extend this model to social and ecological sustainability pillars, we propose to built an extended E(Economic)-S(Social)-O(Organic) model, based on the three previous components, as an open model considering feedbacks as evolution sources. An applicative illustration of this model will then be described, through this summer's american severe drought event analysis