A dimensional analysis of the benzylic hydroxylase active site in mortierella isabellina

The spatial limits of the active site in the benzylic hydroxylase enzyme of the fungus Mortierella isabellina were investigated. Several molecular probes were used in incubation experiments to determine the acceptability of each compound by this enzyme. The yields of benzylic alcohols provided information on the acceptability of the particular compound into the active site, and the enantiomeric excess values provided information on the "fit" of acceptable substrates. Measurements of the molecular models were made using Cambridge Scientific Computing Inc. CSC Chem 3D Plus modeling program. i The dimensional limits of the aromatic binding pocket of the benzylic hydroxylase were tested using suitably substituted ethyl benzenes. Both the depth (para substituted substrates) and width (ortho and meta substituted substrates) of this region were investigated, with results demonstrating absolute spatial limits in both directions in the plane of the aromatic ring of 7.3 Angstroms for the depth and 7.1 Angstroms for the width. A minimum requirement for the height of this region has also been established at 6.2 Angstroms. The region containing the active oxygen species was also investigated, using a series of alkylphenylmethanes and fused ring systems in indan, 1,2,3,4-tetrahydronaphthalene and benzocycloheptene substrates. A maximum distance of 6.9 Angstroms (including the 1.5 Angstroms from the phenyl substituent to the active center of the heme prosthetic group of the enzyme) has been established extending directly in ii front of the aromatic binding pocket. The other dimensions in this region of the benzylic hydroxylase active site will require further investigation to establish maximum allowable values. An explanation of the stereochemical distributions in the obtained products has also been put forth that correlates well with the experimental observations.

Adult Participants’ Experiences of a Sport Program Implementing the Easy-Play Model: Implications for an Active Lifestyle

The Easy-Play Model is a useful framework for facilitating sport among a diverse group of participants of different ages and ability levels. The model’s focus on de-emphasizing competitiveness in an effort to establish an optimally competitive environment has facilitated positive play experiences. This study investigated the experiences of players who have been a part of a weekly soccer program implementing the Easy-Play Model. In-depth interviews of 8 participants provided insight concerning the benefits and weaknesses of the approach and the notable experiences of the players. Results provided data confirming the model’s effectiveness in facilitating positive social interactions, safe play experiences where injury is generally a negligible concern, and productive opportunities to be physically active through sport. This study of the Easy-Play Model sets the foundation for future research which should further add to our understanding of productive ways to engage people in physical activity through sport.

Active nuclear import and cytoplasmic retention of activation-induced deaminase

The enzyme activation-induced deaminase (AID) triggers antibody diversification in B cells by catalyzing deamination and consequently mutation of immunoglobulin genes. To minimize off-target deamination, AID is restrained by several regulatory mechanisms including nuclear exclusion, thought to be mediated exclusively by active nuclear export. Here we identify two other mechanisms involved in controlling AID subcellular localization. AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. We also identify in its C terminus a determinant for AID cytoplasmic retention, which hampers diffusion to the nucleus, competes with nuclear import and is crucial for maintaining the predominantly cytoplasmic localization of AID in steady-state conditions. Blocking nuclear import alters the balance between these processes in favor of cytoplasmic retention, resulting in reduced isotype class switching.

Models and algorithms for the capacitated location-routing problem

Le problème de localisation-routage avec capacités (PLRC) apparaît comme un problème clé dans la conception de réseaux de distribution de marchandises. Il généralisele problème de localisation avec capacités (PLC) ainsi que le problème de tournées de véhicules à multiples dépôts (PTVMD), le premier en ajoutant des décisions liées au routage et le deuxième en ajoutant des décisions liées à la localisation des dépôts. Dans cette thèse on dévelope des outils pour résoudre le PLRC à l’aide de la programmation mathématique. Dans le chapitre 3, on introduit trois nouveaux modèles pour le PLRC basés sur des flots de véhicules et des flots de commodités, et on montre comment ceux-ci dominent, en termes de la qualité de la borne inférieure, la formulation originale à deux indices [19]. Des nouvelles inégalités valides ont été dévelopées et ajoutées aux modèles, de même que des inégalités connues. De nouveaux algorithmes de séparation ont aussi été dévelopés qui dans la plupart de cas généralisent ceux trouvés dans la litterature. Les résultats numériques montrent que ces modèles de flot sont en fait utiles pour résoudre des instances de petite à moyenne taille. Dans le chapitre 4, on présente une nouvelle méthode de génération de colonnes basée sur une formulation de partition d’ensemble. Le sous-problème consiste en un problème de plus court chemin avec capacités (PCCC). En particulier, on utilise une relaxation de ce problème dans laquelle il est possible de produire des routes avec des cycles de longueur trois ou plus. Ceci est complété par des nouvelles coupes qui permettent de réduire encore davantage le saut d’intégralité en même temps que de défavoriser l’apparition de cycles dans les routes. Ces résultats suggèrent que cette méthode fournit la meilleure méthode exacte pour le PLRC. Dans le chapitre 5, on introduit une nouvelle méthode heuristique pour le PLRC. Premièrement, on démarre une méthode randomisée de type GRASP pour trouver un premier ensemble de solutions de bonne qualité. Les solutions de cet ensemble sont alors combinées de façon à les améliorer. Finalement, on démarre une méthode de type détruir et réparer basée sur la résolution d’un nouveau modèle de localisation et réaffectation qui généralise le problème de réaffectaction [48].

Theory and numerical integration of subsurface light transport

En synthèse d’images, reproduire les effets complexes de la lumière sur des matériaux transluminescents, tels que la cire, le marbre ou la peau, contribue grandement au réalisme d’une image. Malheureusement, ce réalisme supplémentaire est couteux en temps de calcul. Les modèles basés sur la théorie de la diffusion visent à réduire ce coût en simulant le comportement physique du transport de la lumière sous surfacique tout en imposant des contraintes de variation sur la lumière incidente et sortante. Une composante importante de ces modèles est leur application à évaluer hiérarchiquement l’intégrale numérique de l’illumination sur la surface d’un objet. Cette thèse révise en premier lieu la littérature actuelle sur la simulation réaliste de la transluminescence, avant d’investiguer plus en profondeur leur application et les extensions des modèles de diffusion en synthèse d’images. Ainsi, nous proposons et évaluons une nouvelle technique d’intégration numérique hiérarchique utilisant une nouvelle analyse fréquentielle de la lumière sortante et incidente pour adapter efficacement le taux d’échantillonnage pendant l’intégration. Nous appliquons cette théorie à plusieurs modèles qui correspondent à l’état de l’art en diffusion, octroyant une amélioration possible à leur efficacité et précision.

Simplification, approximation and deformation of large models

The high level of realism and interaction in many computer graphic applications requires techniques for processing complex geometric models. First, we present a method that provides an accurate low-resolution approximation from a multi-chart textured model that guarantees geometric fidelity and correct preservation of the appearance attributes. Then, we introduce a mesh structure called Compact Model that approximates dense triangular meshes while preserving sharp features, allowing adaptive reconstructions and supporting textured models. Next, we design a new space deformation technique called *Cages based on a multi-level system of cages that preserves the smoothness of the mesh between neighbouring cages and is extremely versatile, allowing the use of heterogeneous sets of coordinates and different levels of deformation. Finally, we propose a hybrid method that allows to apply any deformation technique on large models obtaining high quality results with a reduced memory footprint and a high performance.

L'evolució dels models de turisme litoral: el Regne Unit, la Costa brava i Cuba

La tesi es centra en una anàlisi prèvia de les implicacions de la teoria del cicle de vida aplicada a les destinacions turístiques pel geògraf canadenc Richard W. Butler (1982) i en un estudi del significat de l'aparició del postmodernisme i les seves repercussions en el turisme, a la vegada que es resegueix la història que ha fet possible l'aparició del turisme massificat de sol i platja. Tot això és la base teòrica imprescindible per poder estudiar empíricament les destinacions de Saltburn (Regne Unit), l'Estartit (Costa Brava) i Cayo Coco (Cuba), utilitzant el cicle de vida per escriure la seva història i veure les polítiques de desenvolupament i regeneració turística que s'han seguit i si aquestes es poden qualificar de postfordistes. La principal conclusió és que el concepte del cicle de vida es limita a ser una eina de diagnòstic a posteriori. El cicle de vida, com a instrument prescriptiu, no serveix. Es específic per a cada destinació, amb unes etapes i punts d'inflexió que només es poden establir en restrospectiva. El cicle de vida és una eina descriptiva molt útil per entendre l'evolució de les destinacions turístiques i els seus mercats, però vigilant de no caure en falses exploracions o perillosos determinismes.

Global models for concrete realities

This paper intends to analyze the evolution of the Ecomuseums from their early appearance in the seventies until the present, emphasizing the characteristics which make them unique and different from all the other museums. This analysis will be used to show the Japanese landscape on ecomuseums and how the ecomuseum evolution might be a reference at internatioal level.

Subseasonal extremes of precipitation and active-break cycles of the Indian summer monsoon in a climate-change scenario

Changes to the behaviour of subseasonal precipitation extremes and active-break cycles of the Indian summer monsoon are assessed in this study using pre-industrial and 2 × CO2 integrations of the Hadley Centre coupled model HadCM3, which is able to simulate the monsoon seasonal cycle reasonably. At 2 × CO2, mean summer rainfall increases slightly, especially over central and northern India. The mean intensity of daily precipitation during the monsoon is found to increase, consistent with fewer wet days, and there are increases to heavy rain events beyond changes in the mean alone. The chance of reaching particular thresholds of heavy rainfall is found to approximately double over northern India, increasing the likelihood of damaging floods on a seasonal basis. The local distribution of such projections is uncertain, however, given the large spread in mean monsoon rainfall change and associated extremes amongst even the most recent coupled climate models. The measured increase of the heaviest precipitation events over India is found to be broadly in line with the degree of atmospheric warming and associated increases in specific humidity, lending a degree of predictability to changes in rainfall extremes. Active-break cycles of the Indian summer monsoon, important particularly due to their effect on agricultural output, are shown to be reasonably represented in HadCM3, in particular with some degree of northward propagation. We note an intensification of both active and break events, particularly when measured against the annual cycle, although there is no suggestion of any change to the duration or likelihood of monsoon breaks. Copyright © 2009 Royal Meteorological Society

Modelling convective processes during the suppressed phase of the a Madden-Julian Oscillation: Comparing single-column models with cloud resolving models

The role of convective processes in moistening the atmosphere during suppressed periods of the suppressed phase of a Madden-Julian oscillation is investigated in cloud-resolving model (CRM) simulations, and the impact of moistening on the subsequent evolution of convection is assessed as part of a Global Energy and Water Cycle Experiment Cloud System Study (GCSS) intercomparison project. The ability of single-column model (SCM) versions of a number of state-of-the-art climate and numerical weather prediction models to capture these convective processes is also evaluated. During the suppressed periods, the CRMs are found to simulate a maximum moistening around 3 km, which is associated with a predominance of shallow convection. All SCMs produce adequate amounts of shallow convection during the suppressed periods, comparable to that seen in CRMs, but the relatively drier SCMs have higher precipitation rates than the relatively wetter SCMs and CRMs. The relatively drier SCMs dry, rather than moisten, the lower troposphere below the melting level. During the transition periods, convective processes act to moisten the atmosphere above the level at which mean advection changes from moistening to drying, despite an overall drying effect for the column. The SCMs capture some essence of this moistening at upper levels. A gradual transition from shallow to deep convection is simulated by the CRMs and the wetter SCMs during the transition periods, but the onset of deep convection is delayed in the drier SCMs. This results in lower precipitation rates for these SCMs during the active periods, although much better agreement exists between the models at this time.

Assembling spatially explicit landscape models of pollen and spore dispersal by wind for risk assessment

Models of windblown pollen or spore movement are required to predict gene flow from genetically modified (GM) crops and the spread of fungal diseases. We suggest a simple form for a function describing the distance moved by a pollen grain or fungal spore, for use in generic models of dispersal. The function has power-law behaviour over sub-continental distances. We show that air-borne dispersal of rapeseed pollen in two experiments was inconsistent with an exponential model, but was fitted by power-law models, implying a large contribution from distant fields to the catches observed. After allowance for this 'background' by applying Fourier transforms to deconvolve the mixture of distant and local sources, the data were best fit by power-laws with exponents between 1.5 and 2. We also demonstrate that for a simple model of area sources, the median dispersal distance is a function of field radius and that measurement from the source edge can be misleading. Using an inverse-square dispersal distribution deduced from the experimental data and the distribution of rapeseed fields deduced by remote sensing, we successfully predict observed rapeseed pollen density in the city centres of Derby and Leicester (UK).

Evaluation of data for atmospheric models: master equation/RRKM calculations on the combination reaction, BrO+NO2 -> BrONO2, a conundrum

Experimental data for the title reaction were modeled using master equation (ME)/RRKM methods based on the Multiwell suite of programs. The starting point for the exercise was the empirical fitting provided by the NASA (Sander, S. P.; Finlayson-Pitts, B. J.; Friedl, R. R.; Golden, D. M.; Huie, R. E.; Kolb, C. E.; Kurylo, M. J.; Molina, M. J.; Moortgat, G. K.; Orkin, V. L.; Ravishankara, A. R. Chemical Kinetics and Photochemical Data for Use in Atmospheric Studies, Evaluation Number 15; Jet Propulsion Laboratory: Pasadena, California, 2006)(1) and IUPAC (Atkinson, R.; Baulch, D. L.; Cox, R. A.: R. F. Hampson, J.; Kerr, J. A.; Rossi, M. J.; Troe, J. J. Phys. Chem. Ref. Data. 2000, 29, 167) 2 data evaluation panels, which represents the data in the experimental pressure ranges rather well. Despite the availability of quite reliable parameters for these calculations (molecular vibrational frequencies (Parthiban, S.; Lee, T. J. J. Chem. Phys. 2000, 113, 145)3 and a. value (Orlando, J. J.; Tyndall, G. S. J. Phys. Chem. 1996, 100,. 19398)4 of the bond dissociation energy, D-298(BrO-NO2) = 118 kJ mol(-1), corresponding to Delta H-0(circle) = 114.3 kJ mol(-1) at 0 K) and the use of RRKM/ME methods, fitting calculations to the reported data or the empirical equations was anything but straightforward. Using these molecular parameters resulted in a discrepancy between the calculations and the database of rate constants of a factor of ca. 4 at, or close to, the low-pressure limit. Agreement between calculation and experiment could be achieved in two ways, either by increasing Delta H-0(circle) to an unrealistically high value (149.3 kJ mol(-1)) or by increasing , the average energy transferred in a downward collision, to an unusually large value (> 5000 cm(-1)). The discrepancy could also be reduced by making all overall rotations fully active. The system was relatively insensitive to changing the moments of inertia in the transition state to increase the centrifugal effect. The possibility of involvement of BrOONO was tested and cannot account for the difficulties of fitting the data.

Using continuous ground-based radar and lidar measurements for evaluating the representation of clouds in four operational models

The ability of four operational weather forecast models [ECMWF, Action de Recherche Petite Echelle Grande Echelle model (ARPEGE), Regional Atmospheric Climate Model (RACMO), and Met Office] to generate a cloud at the right location and time (the cloud frequency of occurrence) is assessed in the present paper using a two-year time series of observations collected by profiling ground-based active remote sensors (cloud radar and lidar) located at three different sites in western Europe (Cabauw. Netherlands; Chilbolton, United Kingdom; and Palaiseau, France). Particular attention is given to potential biases that may arise from instrumentation differences (especially sensitivity) from one site to another and intermittent sampling. In a second step the statistical properties of the cloud variables involved in most advanced cloud schemes of numerical weather forecast models (ice water content and cloud fraction) are characterized and compared with their counterparts in the models. The two years of observations are first considered as a whole in order to evaluate the accuracy of the statistical representation of the cloud variables in each model. It is shown that all models tend to produce too many high-level clouds, with too-high cloud fraction and ice water content. The midlevel and low-level cloud occurrence is also generally overestimated, with too-low cloud fraction but a correct ice water content. The dataset is then divided into seasons to evaluate the potential of the models to generate different cloud situations in response to different large-scale forcings. Strong variations in cloud occurrence are found in the observations from one season to the same season the following year as well as in the seasonal cycle. Overall, the model biases observed using the whole dataset are still found at seasonal scale, but the models generally manage to well reproduce the observed seasonal variations in cloud occurrence. Overall, models do not generate the same cloud fraction distributions and these distributions do not agree with the observations. Another general conclusion is that the use of continuous ground-based radar and lidar observations is definitely a powerful tool for evaluating model cloud schemes and for a responsive assessment of the benefit achieved by changing or tuning a model cloud

Energetics of climate models: net energy balance and meridional enthalpy transport

We analyze the publicly released outputs of the simulations performed by climate models (CMs) in preindustrial (PI) and Special Report on Emissions Scenarios A1B (SRESA1B) conditions. In the PI simulations, most CMs feature biases of the order of 1 W m −2 for the net global and the net atmospheric, oceanic, and land energy balances. This does not result from transient effects but depends on the imperfect closure of the energy cycle in the fluid components and on inconsistencies over land. Thus, the planetary emission temperature is underestimated, which may explain the CMs' cold bias. In the PI scenario, CMs agree on the meridional atmospheric enthalpy transport's peak location (around 40°N/S), while discrepancies of ∼20% exist on the intensity. Disagreements on the oceanic transport peaks' location and intensity amount to ∼10° and ∼50%, respectively. In the SRESA1B runs, the atmospheric transport's peak shifts poleward, and its intensity increases up to ∼10% in both hemispheres. In most CMs, the Northern Hemispheric oceanic transport decreases, and the peaks shift equatorward in both hemispheres. The Bjerknes compensation mechanism is active both on climatological and interannual time scales. The total meridional transport peaks around 35° in both hemispheres and scenarios, whereas disagreements on the intensity reach ∼20%. With increased CO 2 concentration, the total transport increases up to ∼10%, thus contributing to polar amplification of global warming. Advances are needed for achieving a self-consistent representation of climate as a nonequilibrium thermodynamical system. This is crucial for improving the CMs' skill in representing past and future climate changes.

Monophosphothreonyl extracellular signal-regulated kinases 1 and 2 (ERK1/2) are formed endogenously in intact cardiac myocytes and are enzymically active

ERK1 and ERK2 (ERK1/2) are central to the regulation of cell division, growth and survival. They are activated by phosphorylation of the Thr- and the Tyr- residues in their Thr-Glu-Tyr activation loops. The dogma is that dually-phosphorylated ERK1/2 constitute the principal activities in intact cells. We previously showed that, in neonatal rat cardiac myocytes, endothelin-1 and phorbol 12-myristate 13-acetate (PMA) powerfully and rapidly (maximal at ~ 5 min) activate ERK1/2. Here, we show that dually-phosphorylated ERK1/2 rapidly (< 2 min) appear in the nucleus following stimulation with endothelin-1. We characterized the active ERK1/2 species in myocytes exposed to endothelin-1 or PMA using MonoQ FPLC. Unexpectedly, two peaks of ERK1 and two peaks of ERK2 activity were resolved using in vitro kinase assays. One of each of these represented the dually-phosphorylated species. The other two represented activities for ERK1 or ERK2 which were phosphorylated solely on the Thr- residue. Monophosphothreonyl ERK1/2 represented maximally ~ 30% of total ERK1/2 activity after stimulation with endothelin-1 or PMA, and their kcat values were estimated to be minimally ~ 30% of the dually-phosphorylated species. Appearance of monophosphothreonyl ERK1/2 was rapid but delayed in comparison with dually-phosphorylated ERK1/2. Of 10 agonists studied, endothelin-1 and PMA were most effective in terms of ERK1/2 activation and in stimulating the appearance of monophosphothreonyl and dually-phosphorylated ERK1/2. Thus, enzymically active monophosphothreonyl ERK1/2 are formed endogenously following activation of the ERK1/2 cascade and we suggest that monophosphothreonyl ERK1/2 arise by protein tyrosine phosphatase-mediated dephosphorylation of dually-phosphorylated ERK1/2.