The purpose of this study was to explore the subject of timescale estimating for rule-based systems. A model for estimating the timescale necessary to build rule-based systems was built and then tested in a controlled environment.

Compte tenu de la vulnérabilité de la population rurale de la région sahélienne aux aléas pluviométriques, et devant les ambitions de certains acteurs d’utiliser le levier de l’usage des terres pour contribuer à l’atténuation du changement climatique, il est important de comprendre les facteurs contribuant à la variabilité de la couverture végétale au Sahel.Une synthèse de la littérature expliquant l’évolution récente de la végétation au Sahel est donc d’abord présentée. Les études s’intéressant au paradigme qui souligne l’impact de l’usage des terres sur les précipitations en Afrique de l’Ouest évaluent principalement ces effets par le couplage de modèles dynamiques globaux de végétation – DGVM – avec des modèles de circulation générale. C’est à l’amélioration d’un tel DGVM, ORCHIDEE, développé à l’Institut Pierre Simon Laplace, que le reste du travail cherche à contribuer.Comme d’autres études ont montré qu’il était possible d’utiliser en première approximation les steppes pâturées et les jachères pour décrire le comportement global de la surface sahélienne, les écarts entre modèle et mesures sont caractérisés pour une jachère située à proximité de Wankama (Niger). Plus précisément, les forces et faiblesses de la paramétrisation et de la structure par défaut du modèle sont diagnostiqués, et l’importance de la réduction d’erreur permise par l’optimisation de certains des paramètres est donnée. En particulier, l’emploi d’une résolution aux différences finies de la diffusion de l’eau dans la colonne de sol est évalué, dans la mesure où cela permet de mieux simuler la réponse rapide du flux évaporatoire aux événements pluvieux que le schéma conceptuel utilisé par défaut dans ORCHIDEE.Le réalisme du modèle est également mesuré à l’échelle régionale, par la comparaison d’observations de NDVI GIMMS_3G à la couverture végétale simulée par le modèle en réponse à différents forçages climatiques . Si les modifications introduites au cours du travail ne permettent pas de mieux décrire les tendances de la végétation au cours des dernières décennies, tirer partie des leçons du présent travail pourra se révéler utile. Il en est de même des conclusions de l’étude de la transitivité des biais conditionnels du modèle réalisée avec Tao Wang et présentée en annexe B. / The evolution of the land-surface conditions is often assessed through the use of “dynamic global vegetation models”, as is shown in a review of the current understanding of the factors of variability and of the recent evolution of the vegetation cover in the Sahel. Such models are also coupled to atmospheric general circulation models to evaluate the land feedback on precipitation in monsoonal climates.Thus, the improvement of the skills of such surface models to simulate the radiative and turbulent fluxes between the land of surface and the atmosphere in the Sahel over a range of scales from hourly to multi-annual has a potential to have significant implications. This is especially true considering the vulnerability of the rural population of the region, which largely relies on rainfed agriculture and the interest on the evolution of the carbon stocks of ecosystems in the context of climate change. Such a work on the ORCHIDEE model is presented here. In complement to croplands, rangelands and fallows represent a large share of the sahelian landscapes and have intermediate characteristics between erosion glacis and acacia bushes. As such, their evolution (in terms of albedo, roughness length,…) may be used to study the Sahel ecosystem behaviour as a first approximation. Differences between model outputs and field observations are quantified for a fallow close to Wankama (Niger). More precisely, some of the drawbacks of the standard parametrisation and structure of the model are diagnosed, and the range of reduction of the model-observation mismatch that results from optimizing some of the parameters are given (plant phenology,…). In particular, the use of a finite difference resolution of the soil water diffusion is considered as it enables to better simulate the fast response of evaporative fluxes to rainfall than the conceptual scheme routinely used in ORCHIDEE. The benefits of the use of such a “physical” hydrological scheme on the different outputs of the surface scheme is evaluated.The realism of the model is also measured at the regional scale, through a comparison with GIMMS_3G NDVI time series over West Africa. If the modifications that have been introduced in the model don’t improve its ability to describe the vegetation cover trends over the last decades in the region, several lessons can be kept from the analysis that has been realised, especially from the work on the transitivity of state-dependant model biases that has been conducted with Tao Wang and which is presented in annex B.

Changes in external forcing having traditionally been the main area of interest in trying to understand paleo-depositional environments in sedimentary systems; however, autogenic variability has been rising in importance, while autogenic behavior has been thought of as a “noise” generator. Recently, autogenic variability has been rising in attention because decoupling allogenic signatures (externally driven) from the stratigraphic record requires robust understanding of autogenic variations (internally generated). This study aims to quantitatively measure autogenic processes under a range of flux conditions and to show that autogenic processes generate distinct signatures rather than random noise. We present data from a matrix of nine different tank experiments in order to systematically evaluate the effects of sediment flux and water discharge variations on the autogenic timescale of fluvial sediment storage and release processes and the implications of this data to the stratigraphic record. The sediment flux tow ater discharge ratio and the absolute values of these two discharges control the autogenic timescale. Variations in sediment supply yield two competing effects on the autogenic timescale. The primary sediment flux control causes a reduction in the autogenic timescale as an increase in sediment supply yields an increased rate of filling the “fluvial envelope” (the space between the maximum and minimum fluvial slopes obtained during storage and release events). In contrast, the secondary sediment flux control increases the size of the fluvial envelope and works against the primary sediment flux control. Increasing the water discharge increases the autogenic timescale by widening the fluvial envelope during the organization of the fluvial system and more importantly, diminishes the functionality of the secondary sediment control. A competition exists between these factors, causing a non-linear range of autogenic timescales for a given sediment flux to water discharge ratio. In the nine experiments here, as the ratio decreases, the secondary effects of variations in sediment supply are suppressed by the relatively high water discharge, and the timescale is more predictable using the primary sediment control. As the ratio increases, the secondary effects from sediment supply are enhanced by a poorly organized fluvial system, and the timescale converges to a narrow range. This suggests significant implications for autogenic sediment delivery and stratigraphic development in a wide range of discharge conditions in field cases. / text

Acetaminophen, known as paracetamol in the UK and Tylenol in the United States, is a widespread and commonly used painkiller all over the world. Taken in large enough doses, however, it can cause fatal liver damage. In the U.S., 56000 people are admitted to hospital each year due to acetaminophen overdose and its related effects, at great cost to healthcare services. In this thesis we present a number of different models of acetaminophen metabolism and toxicity. Previously, models of acetaminophen toxicity have been complex and due to this complexity, do not lend themselves well to more advanced mathematical analysis such as the perturbation analysis presented later in this thesis. We begin with a simple model of acetaminophen metabolism, studying a single liver cell and performing numerical and sensitivity analysis to further understand the most important mechanisms and pathways of the model. Through this we identify key parameters that affect the total toxicity in our model. We then proceed to perform singular perturbation analysis, studying the behaviour of the model over different timescales, finding a number of key timescales for the depletion and subsequent recovery of various cofactors as well as critical dose above which we see toxicity occurring. Later in the thesis, this model is used to model metabolism in a spheroid cell culture, examining the difference spatial effects have on metabolism across a 3D cell culture. We then present a more complex model, examining the difference the addition of an adaptive response to acetaminophen overdose from the Nrf2 signalling pathway, has on our results. We aim to reproduce an unexplained result in the experimental data of our colleagues, and so analyse the steady states of our model when subjected to an infused dose, rather than a bolus one. We identify another critical dose which leads to GSH depletion in the infused dose case and find that Nrf2 adaptation decreases toxicity and model sensitivity. This model is then used as part of a whole-body PBPK model, exploring the effects that the distribution of the drug across the bloodstream and different organs has. We explore the affects of that a delay in up-regulation from the Nrf2 pathway has on the model, and find that with rescaled parameters we can qualitatively reproduce the results of our collaborators. Finally, we present the results of in vitro work that we have undertaken, the aim of which was to find new parameters for the model in human hepatocytes, rather than from rodent models, and find a new value for a parameter in our model from human cell lines.

Contemporary cellular models of learning and memory are articulated around the idea that synapses undergo activity-dependent weight changes. However, conventional forms of Hebbian plasticity do not adequately address certain features inherent to behavioral learning. First, associative learning driven by delayed behavioral outcomes introduces a temporal credit assignment problem, whereby one must remember which action corresponds to which outcome. Yet, current models of associative synaptic plasticity, such as spike-timing-dependent plasticity, require near coincident activation of pre- and postsynaptic neurons (i.e., within ~ 10 ms), a time delay that is orders of magnitude smaller than that required for behavioral associations. For individual neurons to associate two cues, a biological mechanism capable of potentiating synaptic weights must be able to bind events that are separated in time. Theoretical work has suggested that a synaptic eligibility trace, a time-limited process that momentarily renders synapses eligible for weight updates via delayed instructive signals, can solve this problem. However, no material substrate of eligibility traces has been identified in the brain. Second, under certain conditions, neurons need to swiftly update their weights to reflect rapid learning. Current plasticity experiments require the repetition of multiple pairings to induce long-term synaptic plasticity. In this thesis, I addressed these problems using a combination of whole-cell recordings, two-photon uncaging, calcium imaging, and mechanistic modeling. I uncovered a form of synaptic plasticity known as behavioral timescale synaptic plasticity (BTSP) in layer 5 pyramidal neurons in the prefrontal cortex of mice. BTSP induced synaptic potentiation by pairing temporally separated pre- and postsynaptic events (0.5 s - 1 s), regardless of their order. The temporal window for BTSP induction offers a line of solution to the temporal credit assignment problem by highlighting the presence of a synaptic mechanism that expands the time for the induction of activity-dependent long-term synaptic plasticity, spanning hundreds of milliseconds. We further found that BTSP can be induced following a single pairing, enabling rapid weight updates required for one-shot learning. Using two-photon calcium imaging in apical oblique dendrites, I discovered a novel short-term and associative plasticity of calcium dynamics (STAPCD) that exhibited temporal characteristics mirroring the induction rules of BTSP. I identified a core set of molecular components crucial for both STAPCD and BTSP and developed a computational simulation that models the calcium dynamics as a latent memory trace of neural activity (i.e., eligibility traces). Together, we find that calcium handling by the endoplasmic reticulum enables synaptic weight updates upon receipt of delayed instructive signals, obeys rules of burst-dependent one-shot learning, and thus provides a mechanism that satisfies the requirements anticipated of eligibility traces. Collectively, these findings offer a neural mechanism for the binding of cellular events occurring in single shot and separated by behaviorally relevant temporal delays to induce potentiation at synapses, providing a cellular model of associative learning.

No description available.

Primärvårdens uppdrag innefattar behandling av psykisk ohälsa och för närvarande överstiger behandlingsbehovet vårdnivåns resurser. Integrerad beteendehälsa (IBH) är en organisationsmodell för primärvård som tidseffektivt tillgängliggör psykologisk behandling. Föreliggande pilotstudie ägde rum under perioden januari till april 2019 på vårdcentralen Centrum, som arbetade enligt modellen för IBH. Syftet för studien var att utvärdera effekterna av behandling med Brief Interventions (BI) respektive vägledd självhjälp avseende patienternas vardagliga funktionsnivå, livskvalitet och symtom. Mätningar genomfördes innan behandling påbörjades, efter fyra veckor samt efter åtta veckor. Vidare undersöktes processfaktorer, så som hur stor andel av patienterna som skulle kunna tillgodogöra sig behandling med självhjälp, samt huruvida införande av en sådan behandling skulle kunna vara motiverad i primärvårdsmiljö utifrån tidseffektivitetsperspektiv. Totalt randomiserades 41 patienter mellan behandling med BI respektive en utökad bedömning följt av behandling med vägledd självhjälp. De patienter som vid den utökade bedömningen inte befanns lämpliga för vägledd självhjälp fick behandling med BI. Sammantaget fullföljde 29 patienter behandling inom ramen för studien. Resultaten visade att både BI och självhjälp förbättrade patienternas vardagliga funktionsnivå, livskvalitet och symtomnivå, samt att det fanns få skillnader i behandlingsutfall mellan grupperna. Tidsåtgången för personalen var större för behandling med självhjälp jämfört med BI. Vidare forskning behövs för att utvärdera psykologisk behandling anpassad till primärvården. / A commitment of primary care is mental health treatment. At present the need for treatment exceeds accessible resources. Primary Care Behavioral Health (PCBH) is a model of organization of primary care with the aim to make access to mental treatment from a time-efficiency perspective. The present study was conducted between January and April 2019 at Vårdcentralen Centrum, a primary care unit organized in accordance with PCBH. The aim of the present study was to evaluate the effects of treatment with Brief Interventions (BI) and guided self-help regarding daily functioning, quality of life and aggregate level of symptoms. Self-assessments were filled out by the patients before treatment, at FU4 and at FU8. Furthermore, proportion of patients suitable for self-help treatment was examined, and whether introduction of such a treatment might be justified in the context of primary care on basis of time effectiveness approach. In overall, 41 patients were randomized to two conditions: BI treatment and, respectively, extended assessment with subsequent self-help treatment. Participants, not found suitable for self-help at the extended assessment, got treatment with BI. Within the study, 29 patients went through treatment. The results showed that groups treated with BI and self-help had improved significantly between before treatment and FU8 regarding daily functioning, quality of life and level of symptoms. There were in general little differences in improvement between the two groups. Furthermore, timescale for the group that got extended assessment and subsequent self-help treatment, was significantly larger than timescale for the group that got BI treatment. For future research, evaluation of short-term forms of mental treatment in primary care ought to be relevant.

<p>Sustained attention, the ability to direct and maintain attentional focus on tasks and stimuli, emerges during infancy and undergoes rapid development throughout early childhood. Abnormal patterns of sustained attention are implicated in several childhood psychological disorders. Improving our measurement of infant sustained attention may clarify how child psychopathology develops and inform targeted prevention and early intervention efforts. While several behavioral and psychophysiological measures index infant sustained attention, previous studies have employed these measures in isolation, focused on analyses at short timescales of milliseconds to a few seconds, and examined synchronous associations among these measures. Therefore, the associations and temporal relationships across multiple, concurrent behavioral and psychophysiological measures of infant sustained attention remain unclear, particularly at long timescales. The present study assessed sustained attention in 12-month-old infants using behavioral (looking), cardiac (heart rate), and neural (theta and alpha oscillations) measures to investigate two temporal aspects of infant sustained attention. First, we examined whether associations among infant sustained attention measures were similar or different across short (1-second) and long (10-second) timescales. Covariation analyses indicated largely similar association patterns among these measures across the two timescales. Second, we evaluated whether specific infant sustained attention measures temporally preceded other measures. Cross-correlation analyses broadly revealed that short-timescale measures exhibited asynchronous temporal relationships, such that looking behaviors preceded neural oscillations that in turn preceded cardiac responses. Our findings highlight the value of considering the temporal dimension when studying and measuring infant sustained attention. Additional multimodal research may yield greater insights into dynamic biobehavioral processes that underlie infant sustained attention and enhance clinical interventions aimed at promoting optimal outcomes for young children with abnormalities in sustained attention.</p>

Detta examensarbete undersöker tidsåtgången av två skilda planprocesser. Det ena projektet beläget i Sverige och det andra i Tyskland. Anledningen till att jämförelsen gjordes med Tyskland är på grund av deras paragraf 34. Paragrafen innebär att nybyggnation kan ske utanför ett detaljplanerat område inom tätort och har på senare tid varit omtalad i svensk media. Byggbolagen i Sverige anser idag att det är en omständlig process från projektidé till byggstart och begär en förändring i planprocessen för att kunna påskynda byggandet. Befolkningen växer i framför allt storstäderna och det byggs för få bostäder för att kunna tillgodose efterfrågan. En av de bidragande orsakerna till att det byggs för lite är en allt för långt utdragen planprocess. Undersökningen av planprocessen för de två projekt i denna rapport har utförts genom analys av deras respektive detaljplaner. Dessutom genomfördes intervjuer med Sveriges Byggindustrier(BI), Sveriges kommuner och landsting(SKL) och NCC för att erhålla deras bild av den svenska planprocessen. Resultatet visade att planprocessen var 1,9 år längre i Sverige och att det skiljde sig mellan de två projektens planförfaranden. Programskedet tog längst tid i Sverige och i Tyskland tog programskedet och samrådet lika lång tid. Undersökningen visade också att slutpriset för två likartade husprojekt i respektive land skiljde sig med cirka 51 % billigare pris för det tyska projektet. Till detta kan det påpekas att byggprisindex är lägre i Tyskland och de har en effektivare produktutveckling, som är ett led i en snabbare planprocess. Vid en kortare planprocess kan kapitalkostnaden minskas och ur kundens perspektiv innebär det att slutpriset kan sänkas. Det finns flera orsaker till varför bostadsbyggandet inte flyter på trots den rådande bostadsbristen. Ett är att det tar för lång tid i hanteringen kring dokumentation av handlingar i de olika skedena i planprocessen. Därutöver tar överklagandeprocessen en lång tid och ett förslag är att färre instanser skulle påskynda processen. Vidare rekommenderas tydligare riktlinjer i PBL, slopande av kommunala särkrav och att inte detaljplanera mer än nödvändigt. Det behövs en förändring av den svenska planprocessen för att påskynda bostadsbyggandet. Färre instanser under överklagandeprocessen, bättre riktlinjer i PBL och tydligare hantering i kommuner, införande av en mer enhetlig regeluppsättning över hela Sverige och att inte detaljplanera om det inte är nödvändigt. Dessa rekommendationer skulle förbättra den svenska planprocessen. / This thesis examines time and cost consumption under two different planning processes. One project located in Sweden and the other in Germany. The main reason why the comparison was done in relation to Germany is because of an article on paragraph 34.This paragraph has recently been in Swedish media and construction companies in Sweden are requesting a change in the planning process to make it easier and faster to build houses. The population is growing, especially in the larger cities and the buildings fail to meet the demands required by the city. The main reason being that they build far too few homes because of an inefficient planning process. The planning process for these two projects has been carried out through analysis of their planning documents. In addition, interviews were conducted with the Swedish Construction Organization, Sweden's municipalities and NCC to obtain their view on how the Swedish planning process works. The results showed that the planning process was 1.9 years longer in Sweden. The program period took the longest time in Sweden and in Germany the program period and the consultation period took equal time. The investigation revealed that the final price to the customer is about 51% less in Germany. Furthermore, the construction price index is lower in Germany and they have a more efficient product development. With a shorter planning process the cost of capital can be reduced and from the customer's perspective, this means that the final price can be lowered. There are many reasons as to why the buildings aren't meeting the demands despite the housing shortage. One of them is that it takes too long in the handling of documentations in the different stages of the planning process. In addition, the process of appeal takes a very long a time and one suggestion is that a fewer instances would hurry up the planning process. Further recommendations would be that the guidelines in the regulations should be clearer and easier to follow and not to plan in detail more than necessarily. The Swedish planning process needs to change to accelerate the housing construction. Fewer instances during the appeal process, better guidelines in PBL and clearer management in municipalities, create a more uniform set of rules across Sweden and no detailed plan if it is not necessary. These recommendations would improve the Swedish planning process.

This thesis is concerned with large-scale systems of Ordinary Differential Equations that model Biomolecular Reaction Networks (BRNs) in Systems and Synthetic Biology. It addresses the strategies of model reduction and decomposition used to overcome the challenges posed by the high dimension and stiffness typical of these models. A number of developments of these strategies are identified, and their implementation on various BRN models is demonstrated. The goal of model reduction is to construct a simplified ODE system to closely approximate a large-scale system. The error estimation problem seeks to quantify the approximation error; this is an example of the trajectory comparison problem. The first part of this thesis applies semi-definite programming (SDP) and dissipativity theory to this problem, producing a single a priori upper bound on the difference between two models in the presence of parameter uncertainty and for a range of initial conditions, for which exhaustive simulation is impractical. The second part of this thesis is concerned with the BRN decomposition problem of expressing a network as an interconnection of subnetworks. A novel framework, called layered decomposition, is introduced and compared with established modular techniques. Fundamental properties of layered decompositions are investigated, providing basic criteria for choosing an appropriate layered decomposition. Further aspects of the layering framework are considered: we illustrate the relationship between decomposition and scale separation by constructing singularly perturbed BRN models using layered decomposition; and we reveal the inter-layer signal propagation structure by decomposing the steady state response to parametric perturbations. Finally, we consider the large-scale SDP problem, where large scale SDP techniques fail to certify a system’s dissipativity. We describe the framework of Structured Storage Functions (SSF), defined where systems admit a cascaded decomposition, and demonstrate a significant resulting speed-up of large-scale dissipativity problems, with applications to the trajectory comparison technique discussed above.