Prediction of postprandial blood glucose under intra-patient variability and uncertainty and its use in the design of insulin dosing strategies for type 1 diabetic patients

In this thesis I propose a novel method to estimate the dose and injection-to-meal time for low-risk intensive insulin therapy. This dosage-aid system uses an optimization algorithm to determine the insulin dose and injection-to-meal time that minimizes the risk of postprandial hyper- and hypoglycaemia in type 1 diabetic patients. To this end, the algorithm applies a methodology that quantifies the risk of experiencing different grades of hypo- or hyperglycaemia in the postprandial state induced by insulin therapy according to an individual patient’s parameters. This methodology is based on modal interval analysis (MIA). Applying MIA, the postprandial glucose level is predicted with consideration of intra-patient variability and other sources of uncertainty. A worst-case approach is then used to calculate the risk index. In this way, a safer prediction of possible hyper- and hypoglycaemic episodes induced by the insulin therapy tested can be calculated in terms of these uncertainties.

Enhanced fault recovery methods for protected traffic services in GMPLS networks

Les noves tecnologies a la xarxa ens permeten transportar, cada cop més, grans volums d' informació i trànsit de xarxa amb diferents nivells de prioritat. En aquest escenari, on s'ofereix una millor qualitat de servei, les conseqüències d'una fallada en un enllaç o en un node esdevenen més importants. Multiprotocol Lavel Switching (MPLS), juntament amb l'extensió a MPLS generalitzat (GMPLS), proporcionen mecanismes ràpids de recuperació de fallada establint camins, Label Switch Path (LSPs), redundants per ser utilitzats com a camins alternatius. En cas de fallada podrem utilitzar aquests camins per redireccionar el trànsit. El principal objectiu d'aquesta tesi ha estat millorar alguns dels actuals mecanismes de recuperació de fallades MPLS/GMPLS, amb l'objectiu de suportar els requeriments de protecció dels serveis proporcionats per la nova Internet. Per tal de fer aquesta avaluació s'han tingut en compte alguns paràmetres de qualitat de protecció com els temps de recuperació de fallada, les pèrdues de paquets o el consum de recursos. En aquesta tesi presentem una completa revisió i comparació dels principals mètodes de recuperació de fallada basats en MPLS. Aquest anàlisi inclou els mètodes de protecció del camí (backups globals, backups inversos i protecció 1+1), els mètodes de protecció locals i els mètodes de protecció de segments. També s'ha tingut en compte l'extensió d'aquests mecanismes a les xarxes òptiques mitjançant el pla de control proporcionat per GMPLS. En una primera fase d'aquest treball, cada mètode de recuperació de fallades és analitzat sense tenir en compte restriccions de recursos o de topologia. Aquest anàlisi ens dóna una primera classificació dels millors mecanismes de protecció en termes de pèrdues de paquets i temps de recuperació. Aquest primer anàlisi no és aplicable a xarxes reals. Per tal de tenir en compte aquest nou escenari, en una segona fase, s'analitzen els algorismes d'encaminament on sí tindrem en compte aquestes limitacions i restriccions de la xarxa. Es presenten alguns dels principals algorismes d'encaminament amb qualitat de servei i alguna de les principals propostes d'encaminament per xarxes MPLS. La majoria dels actual algorismes d'encaminament no tenen en compte l'establiment de rutes alternatives o utilitzen els mateixos objectius per seleccionar els camins de treball i els de protecció. Per millorar el nivell de protecció introduïm i formalitzem dos nous conceptes: la Probabilitat de fallada de la xarxa i l'Impacte de fallada. Un anàlisi de la xarxa a nivell físic proporciona un primer element per avaluar el nivell de protecció en termes de fiabilitat i disponibilitat de la xarxa. Formalitzem l'impacte d'una fallada, quant a la degradació de la qualitat de servei (en termes de retard i pèrdues de paquets). Expliquem la nostra proposta per reduir la probabilitat de fallada i l'impacte de fallada. Per últim fem una nova definició i classificació dels serveis de xarxa segons els valors requerits de probabilitat de fallada i impacte. Un dels aspectes que destaquem dels resultats d'aquesta tesi és que els mecanismes de protecció global del camí maximitzen la fiabilitat de la xarxa, mentre que les tècniques de protecció local o de segments de xarxa minimitzen l'impacte de fallada. Per tant podem assolir mínim impacte i màxima fiabilitat aplicant protecció local a tota la xarxa, però no és una proposta escalable en termes de consum de recursos. Nosaltres proposem un mecanisme intermig, aplicant protecció de segments combinat amb el nostre model d'avaluació de la probabilitat de fallada. Resumint, aquesta tesi presenta diversos mecanismes per l'anàlisi del nivell de protecció de la xarxa. Els resultats dels models i mecanismes proposats milloren la fiabilitat i minimitzen l'impacte d'una fallada en la xarxa.

Reading hybrid texts : remarks on text/image transitions

The reading of printed materials implies the visual processing of information originated in two distinct semiotic systems. The rapid identification of redundancy, complementation or contradiction rhetoric strategies between the two information types may be crucial for an adequate interpretation of bimodal materials. Hybrid texts (verbal and visual) are particular instances of bimodal materials, where the redundant information is often neglected while the complementary and the contradictory ones are essential.Studies using the 504 ASL eye-tracking system while reading either additive or exhibiting captions (Baptista, 2009) revealed fixations on the verbal material and transitions between the written and the pictorial in a much higher number and duration than the initially foreseen as necessary to read the verbal text. We therefore hypothesized that confirmation strategies of the written information are taking place, by using information available in the other semiotic system.Such eye-gaze patterns obtained from denotative texts and pictures seem to contradict some of the scarce existing data on visual processing of texts and images, namely cartoons (Carroll, Young and Guertain, 1992), descriptive captions (Hegarty, 1992 a and b), and advertising images with descriptive and explanatory texts (cf. Rayner and Rotello, 2001, who refer to a previous reading of the whole text before looking at the image, or even Rayner, Miller and Rotello, 2008 who refer to an earlier and longer look at the picture) and seem to consolidate findings of Radach et al. (2003) on systematic transitions between text and image.By framing interest areas in the printed pictorial material of non redundant hybrid texts, we have identified the specific areas where transitions take place after fixations in the verbal text. The way those transitions are processed brings a new interest to further research.

Hoy empiezo a acordarme de Miguel Donoso Pareja: hiperconciencia de una memoria creativa (Crítica)

La autora lee la novela Hoy empiezo a acordarme, del ecuatoriano Miguel Donoso Pareja, desde la perspectiva de la ficción como un intento –vano–, por parte del narrador, de encontrarse a sí mismo, escritura-travesía hacia un yo que resulta ser siempre “otro”. El personaje pretendería transformar no exclusivamente su realidad, sino la ficción misma en un universo navegable para el lector, la escritura fragmentada en vehículo que no lo lleve a destino alguno, sino a su propio punto de partida. Más que construir una novela de perfección formal, el narrador pretendería involucrar al lector en su propio viaje-búsqueda. Donoso partiría de la escritura como presencia y ausencia, como verdad y mentira, para construir esta novela con historias fragmentadas que se alimentan tanto del recuerdo como del olvido, en un cabal ejercicio de hiperconciencia narrativa.

Morphological and molecular characteristics of a new species of Pasteuria parasitic on Meloidogyne ardenensis

A species of the hyper-parasitic bacterium Pasteuria was isolated from the root-knot nematode Meloidogyne ardenensis infecting the roots of ash (Fraxinus excelsior). It is morphologically different from some other Pasteuria pathogens of nematodes in that the spores lack a basal ring on the ventral side of the spore and have a unique clumping nature. Transmission electron microscopy (TEM) showed that the clumps of spores are not random aggregates but result from the disintegration of the suicide cells of the thalli. Sporulation within each vegetative mycelium was shown to be asynchronous. In addition to the novel morphological features 16S rRNA sequence analysis showed this to be a new species of Pasteuria which we have called P. hartismeri. Spores of P. hartismeri attach to juveniles of root-knot nematodes infecting a wide range of plants such as mint (Meloidogyne hapla), rye grass (unidentified Meloidogyne sp.) and potato (Meloidogyne fallax). (c) 2007 Elsevier Inc. All rights reserved.

Understanding biodiversity effects on prey in multi-enemy systems

Biodiversity-ecosystem functioning theory would predict that increasing natural enemy richness should enhance prey consumption rate due to functional complementarity of enemy species. However, several studies show that ecological interactions among natural enemies may result in complex effects of enemy diversity on prey consumption. Therefore, the challenge in understanding natural enemy diversity effects is to predict consumption rates of multiple enemies taking into account effects arising from patterns of prey use together with species interactions. Here, we show how complementary and redundant prey use patterns result in additive and saturating effects, respectively, and how ecological interactions such as phenotypic niche shifts, synergy and intraguild predation enlarge the range of outcomes to include null, synergistic and antagonistic effects. This study provides a simple theoretical framework that can be applied to experimental studies to infer the biological mechanisms underlying natural enemy diversity effects on prey.

Evidence of a possible role for Lys-gamma 3-MSH in the regulation of adipocyte function

Lys-gamma 3-MSH is a melanocortin peptide derived from the C-terminal of the 16 kDa fragment of POMC. The physiological role of Lys-gamma 3-MSH is unclear, although it has previously been shown that, although not directly steroidogenic, it can act to potentiate the steroidogenic response of adrenal cortical cells to ACTH. This synergistic effect appears to be correlated with an ability to increase the activity of hormone sensitive lipase (HSL) and therefore the rate of cholesterol ester hydrolysis. Ligand binding studies have suggested that high-affinity binding sites for Lys-gamma 3-MSH exist in the adrenal gland and a number of other rat tissues that express HSL, including adipose, skeletal muscle and testes. To investigate the hypothesis that Lys-gamma 3-MSH may play a wider role in cholesterol and lipid metabolism, we tested the effect of Lys-gamma 3-MSH on lipolysis, an HSL-mediated process, in 3T3-L1 adipocytes. In comparison with other melanocortin peptides, Lys-gamma 3-MSH was found to be a potent stimulator of lipolysis. It was also able to phosphorylate HSL at key serine residues and stimulate the hyper-phosphorylation of perilipin A. The receptor through which the lipolytic actions of Lys-gamma 3-MSH are being mediated is not clear. Attempts to characterise this receptor suggest that either the pharmacology of the melanocortin receptor 5 in 3T3-L1 adipocytes is different from that described when expressed in heterologous systems or the possibility that a further, as yet uncharacterised, receptor exists.

Analysis of void volumes in proteins and application to stability of the p53 tumour suppressor protein

We have developed a new method for the analysis of voids in proteins (defined as empty cavities not accessible to solvent). This method combines analysis of individual discrete voids with analysis of packing quality. While these are different aspects of the same effect, they have traditionally been analysed using different approaches. The method has been applied to the calculation of total void volume and maximum void size in a non-redundant set of protein domains and has been used to examine correlations between thermal stability and void size. The tumour-suppressor protein p53 has then been compared with the non-redundant data set to determine whether its low thermal stability results from poor packing. We found that p53 has average packing, but the detrimental effects of some previously unexplained mutations to p53 observed in cancer can be explained by the creation of unusually large voids. (C) 2004 Elsevier Ltd. All rights reserved.

Use of a novel Hill-climbing genetic algorithm in protein folding simulations

We have developed a novel Hill-climbing genetic algorithm (GA) for simulation of protein folding. The program (written in C) builds a set of Cartesian points to represent an unfolded polypeptide's backbone. The dihedral angles determining the chain's configuration are stored in an array of chromosome structures that is copied and then mutated. The fitness of the mutated chain's configuration is determined by its radius of gyration. A four-helix bundle was used to optimise simulation conditions, and the program was compared with other, larger, genetic algorithms on a variety of structures. The program ran 50% faster than other GA programs. Overall, tests on 100 non-redundant structures gave comparable results to other genetic algorithms, with the Hill-climbing program running from between 20 and 50% faster. Examples including crambin, cytochrome c, cytochrome B and hemerythrin gave good secondary structure fits with overall alpha carbon atom rms deviations of between 5 and 5.6 Angstrom with an optimised hydrophobic term in the fitness function. (C) 2003 Elsevier Ltd. All rights reserved.

Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis

Background: Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation. Objective: We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors. Methods: A keratinocyte proliferation assay was used to assess the effect of treatment with cannabinoids. Cell integrity and metabolic competence confirmed using lactate-dehydrogenase and adenosine tri-phosphate assays. To determine the involvement of the receptors, specific agonist and antagonist were used in conjunction with some phytocannabinoids. Western blot and RT-PCR analysis confirmed presence of CB1 and CB2 receptors. Results: The cannabinoids tested all inhibited keratinocyte proliferation in a concentration-dependent manner. The selective CB2 receptor agonists JWH015 and BML190 elicited only partial inhibition, the non-selective CB agonist HU210 produced a concentration-dependent response, the activity of theses agonists were not blocked by either C81 /C82 antagonists. Conclusion: The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process. Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis. (c) 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Controlling steering and judging heading: retinal flow, visual direction, and extraretinal information

The contribution of retinal flow (RF), extraretinal (ER), and egocentric visual direction (VD) information in locomotor control was explored. First, the recovery of heading from RF was examined when ER information was manipulated; results confirmed that ER signals affect heading judgments. Then the task was translated to steering curved paths, and the availability and veracity of VD were manipulated with either degraded or systematically biased RE Large steering errors resulted from selective manipulation of RF and VD, providing strong evidence for the combination of RF, ER, and VD. The relative weighting applied to RF and VD was estimated. A point-attractor model is proposed that combines redundant sources of information for robust locomotor control with flexible trajectory planning through active gaze.

Planning rigid body motions using elastic curves

This paper tackles the problem of computing smooth, optimal trajectories on the Euclidean group of motions SE(3). The problem is formulated as an optimal control problem where the cost function to be minimized is equal to the integral of the classical curvature squared. This problem is analogous to the elastic problem from differential geometry and thus the resulting rigid body motions will trace elastic curves. An application of the Maximum Principle to this optimal control problem shifts the emphasis to the language of symplectic geometry and to the associated Hamiltonian formalism. This results in a system of first order differential equations that yield coordinate free necessary conditions for optimality for these curves. From these necessary conditions we identify an integrable case and these particular set of curves are solved analytically. These analytic solutions provide interpolating curves between an initial given position and orientation and a desired position and orientation that would be useful in motion planning for systems such as robotic manipulators and autonomous-oriented vehicles.

Gene transcription in Daphnia magna: effects of acute exposure to a carbamate insecticide and an acetanilide herbicide.

Daphnia magna is a key invertebrate in the freshwater environment and is used widely as a model in ecotoxicological measurements and risk assessment. Understanding the genomic responses of D. magna to chemical challenges will be of value to regulatory authorities worldwide. Here we exposed D. magna to the insecticide methomyl and the herbicide propanil to compare phenotypic effects with changes in mRNA expression levels. Both pesticides are found in drainage ditches and surface water bodies standing adjacent to crops. Methomyl, a carbamate insecticide widely used in agriculture, inhibits acetylcholinesterase, a key enzyme in nerve transmission. Propanil, an acetanilide herbicide, is used to control grass and broad-leaf weeds. The phenotypic effects of single doses of each chemical were evaluated using a standard immobilisation assay. Immobilisation was linked to global mRNA expression levels using the previously estimated 48h-EC(1)s, followed by hybridization to a cDNA microarray with more than 13,000 redundant cDNA clones representing >5000 unique genes. Following exposure to methomyl and propanil, differential expression was found for 624 and 551 cDNAs, respectively (one-way ANOVA with Bonferroni correction, P