Study of the impact of lithography techniques and the current fabrication processes on the design rules of tridimensional fabrication technologies

Working for the photolithography tool manufacturer leader sometimes gives me the impression of how complex and specific is the sector I am working on. This master thesis topic came with the goal of getting the overall picture of the state-of-the-art: stepping out and trying to get a helicopter view usually helps to understand where a process is in the productive chain, or what other firms and markets are doing to continue improvingUniversidad de sevilla.Máster Universitario en Microelectrónica: Diseño y Aplicaciones de Sistemas Micro/Nanométrico

Markov chain models of instantaneously coupled intracellular calcium channels

Localized calcium elevations known as calcium puffs or sparks are cellular signals arising from cooperative activity of clusters of inositol 1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RyRs) located at calcium release sites on the endoplasmic or sarcoplasmic reticulum membrane. When Markov chain models of these intracellular calcium-regulated calcium channels are coupled via a mathematical representation of the calcium microdomain, simulated calcium release sites may exhibit the phenomenon of stochastic calcium excitability where the IP3Rs or RyRs open and close in a concerted fashion. Although the biophysical theory relating the kinetics of single channels to the collective phenomena of puffs and sparks is only beginning to be developed, Markov chain models of coupled intracellular channels give insight into the dynamics of calcium puffs and sparks.;Interestingly, under some conditions simulated puffs and sparks can be observed even when the single channel model used does not include slow calcium inactivation or any long-lived closed state. In this case termination of the localized calcium elevation occurs when all of the intracellular channels at a release site simultaneously close through a process called stochastic attrition. This dissertation investigates the statistical properties of stochastic attrition viewed as an absorption time on a terminating Markov chain that represents a calcium release site composed of two-state channels that are activated by calcium. Assuming that the local calcium concentration experienced by a channel depends only on the number of open channels at the calcium release site, the probability distribution function for the time until stochastic attrition occurs is derived and an analytical formula for the expectation of this random variable is presented. Also explored is how the contribution of stochastic attrition to the termination of calcium puffs and sparks depends on the number of channels at a release site, the source amplitude of the channels, the background calcium concentration, channel kinetics, and the cooperativity of calcium binding.;This dissertation also studies whether single channel models with calcium inactivation are less sensitive to the details of release site ultrastructure than models that lack a slow calcium-inactivation process. Release site dynamics obtained from simulated calcium release sites composed of instantaneously coupled calcium-regulated calcium channels whose random spatial locations were chosen from a uniform distribution on a disc of specified radius are compared to simulations with channels arranged on hexagonal lattices. Analysis of puff/spark statistics confirms that puffs and sparks are less sensitive to the spatial organization of release sites when the single channel model includes a slow inactivation process. The validity of several different mean-field reductions that do not explicitly account for the details of release site ultrastructure is also investigated.;Calcium release site models are stochastic automata networks that involve many functional transitions, that is, the transition probabilities of each channel depend on the local calcium concentration and thus the state of the other channels. A Kronecker structured representation for calcium release site models is presented and benchmark stationary distribution calculations using both exact and approximate iterative numerical solution techniques that leverage this structure are performed. When it is possible to obtain an exact solution, response measures such as the number of channels in a particular state converge more quickly using the iterative numerical methods than occupation measures calculated via Monte Carlo simulation. When an exact solution is not feasible, iterative approximate methods based on the Power method may be used, with performance similar to Monte Carlo estimates

Solute energy based REMD:developments and applications to prion protein misfold predictions

Molecular dynamics (MD) simulations have increasingly contributed to the understanding of biomolecular processes, allowing for predictions of thermodynamic and structural properties. Unfortunately, the holy grail of protein structure prediction was soon found to be severely hampered by the very rugged free energy surface of proteins, with small relative free energies separating native, folded protein conformations from unfolded states. These multiple minima frequently trap present-day protein MD simulations permanently. In order to allow the simulation to escape minima and explore wider portions of conformational space, enhanced sampling techniques were developed. One of the most popular ones, replica exchange molecular dynamics (REMD), is based on multiple parallel MD simulations that are performed with replicas of a system at increasing temperatures T1, T2, etc. Periodic Monte Carlo exchange moves are attempted, aiming to allow conformations to exchange temperature ensembles with a probability that depends on their potential energy and temperature difference. Thus, conformations are simulated at all temperatures and escape local minima with the kinetic energy provided at higher temperatures, while Boltzmann distributions are generated at all temperatures. REMD has been successful in ab-initio folding of a variety of small peptides and proteins (up to 20-30 residues). However, with larger proteins, the overlap of potential energy distributions diminishes, since the potential energy and its fluctuation scale with fkBT, respectively with √fkBT, where f is the number of degrees of freedom of the system, kB Boltzmann's constant and T the temperature. Consequently, the related Monte Carlo exchange probability and number of exchanges in a simulation are also diminished. This is generally compensated by choosing smaller temperature intervals between replicas and thereby increasing the number of necessary replicas (as well as the computational cost of the simulation) to cover a given temperature range. An additional problem relates to explicit solvent simulations, in which solvent to solvent interactions account for the largest part of the total potential energy. Consequently, explicit solvent REMD simulations almost exclusively sample solvent degrees of freedom. These two limitations have lead to the development of REMD protocols for large explicit solvent systems that are based on exchange probabilities computed with subsystem (e.g. protein only) potential energy functions, allowing for a targeted sampling of protein degrees of freedom and a reduction of the computational effort. In this thesis, this approximation is tested by implementing its simplest variation that entirely neglects solvent-solvent interaction as a new REMD protocol termed REM Dpe (Chapter 2). Possible REMD limitations for large explicit solvent systems are tested (Chapter 3) with REM Dpe, which is further applied to perform a thorough and comparative investigation of prion (Chapter 4) and doppel (Chapter 5) protein misfolding. In Chapter 2, the practical validity of the REM Dpe approximation is assessed with simulations of the prion protein, a system that is too large (i.e. 103 residues) to allow for efficient simulations using traditional REMD over the necessary temperature range. A first validation consists in testing whether protein and total potential energy distributions are consistent with their analogs from straightforward reference MD simulations. Second, the overlap pattern of the total potential energy distributions are characterized at different temperatures and show that the exchanges in the REM Dpe simulations are performed according to a Boltzmann weight. Native structures are found to have the lowest protein and total potential energies, as compared to higher energies found for various unfolded structures. Although no obvious bias is detected in the three validations, the conformational landscapes of the REM Dpe simulation at low temperatures progressively shift to non-native regions of the free energy surface. In Chapter 3, this phenomenon is quantified, and its origin identified in insufficient low temperature residence times required for refolding native-like structures. REMD is based on the assumption that systems have to be decorrelated between exchange attempts. Increasing inter-exchange times accordingly would allow for decorrelation and sufficient low temperature residence times but is practically impossible to achieve for large protein simulations, highlighting a major limitation and possible source of bias for present-day REMD simulations. We have chosen the prion as a test case because of its link to transmissible spongiform encephalopathies. Diseases of this category are believed to be caused by a rare prion protein (PrP) misfold leading from the cellular, monomeric, soluble, α-helical PrPC isoform to a pathogenic, aggregated, insoluble, β-rich PrPSc isoform of unknown structure. Gaining experimental knowledge of the PrPSc structure has remained elusive, and aroused interest in predictions supplied by computer simulations. REMD provides a powerful tool allowing to explore a diversity of misfolds and select stable ones that accumulate at lower temperatures. In Chapter 4, we describe a PrP REM Dpe simulation in which rare new β-strands are formed and arrange into a multitude of different β-sheets, reproducing the α-helix → β-sheet conversion observed with circular dichroism spectra. The α-helical and β-sheet propensities along the sequence can thus be computed. We develop and apply the β contact map clustering (bcmc) protocol to identify the most frequent β-sheet pattern defining β-rich folds. 10 new β-rich folds are found and compared to recent experimental data characterizing PrPSc, providing atomistically detailed models for putative monomeric precursors of PrPSc or β-oligomeric conformations. In Chapter 5, an analogous simulation is performed with doppel, a structural homolog of prion (with an identical three α-helix, two β-strand fold) originating from the same gene family, but characterized by a different sequence (only 25% sequence homology), expression pattern and physiological function. Unrelated to amyloid neurodegenerative diseases, doppel supplies the perfect test system to investigate the misfolding of a non-amyloidogenic protein. Prion and doppel misfolding are compared in their monomeric form in the quest to identify prion-specific features that might reveal the mechanism of conversion to PrPSc. In agreement with experiments, we find a lower thermal stability for doppel. Surprisingly, we also observe β-rich forms for doppel. However, the β-rich folds of the two proteins are very different. Moreover, a major difference is found in the free energy barriers leading from the native structure to such conformations as well as to non-native conformations in general: These barriers are low for prion and can already be crossed at 300K, while for doppel they are at least 3 times higher. This difference suggests an intrinsic misfolding and β-enrichment propensity for the monomeric form of prion as compared to doppel

An ecological understanding

Tese de Doutoramento em Design apresentada na Faculdade de Arquitetura da Universidade de Lisboa para obtenção do grau de Doutor.Tese de Doutoramento financiada pela FCT (Foundation for Science and Techology).N/

Renewing Local Planning to Face Climate Change in the Tropics

This book aims to inspire decision makers and practitioners to change their approach to climate planning in the tropics through the application of modern technologies for characterizing local climate and tracking vulnerability and risk, and using decision-making tools. Drawing on 16 case studies conducted mainly in the Caribbean, Central America, Western and Eastern Africa, and South East Asia it is shown how successful integration of traditional and modern knowledge can enhance disaster risk reduction and adaptation to climate change in the tropics. The case studies encompass both rural and urban settings and cover different scales: rural communities, cities, and regions. In addition, the book looks to the future of planning by addressing topics of major importance, including residual risk integration in local development plans, damage insurance and the potential role of climate vulnerability reduction credits. In many regions of the tropics, climate planning is growing but has still very low quality. This book identifies the weaknesses and proposes effective solutions

Renewing Local Planning to Face Climate Change in the Tropics

climate vulnerability; urban resilience; climate change; adaptation; planning; environmental risk analysis; decision making; disaster risk reduction; tropical climate managemen

Mathematical surfaces models between art and reality

In this paper, I want to document the history of the mathematical surfaces models used for the didactics of pure and applied “High Mathematics” and as art pieces. These models were built between the second half of nineteenth century and the 1930s. I want here also to underline several important links that put in correspondence conception and construction of models with scholars, cultural institutes, specific views of research and didactical studies in mathematical sciences and with the world of the figurative arts furthermore. At the same time the singular beauty of form and colour which the models possessed, aroused the admiration of those entirely ignorant of their mathematical attraction

TWINLATIN: Twinning European and Latin-American river basins for research enabling sustainable water resources management. Combined Report D3.1 Hydrological modelling report and D3.2 Evaluation report

Water use has almost tripled over the past 50 years and in some regions the water demand already exceeds supply (Vorosmarty et al., 2000). The world is facing a “global water crisis”; in many countries, current levels of water use are unsustainable, with systems vulnerable to collapse from even small changes in water availability. The need for a scientifically-based assessment of the potential impacts on water resources of future changes, as a basis for society to adapt to such changes, is strong for most parts of the world. Although the focus of such assessments has tended to be climate change, socio-economic changes can have as significant an impact on water availability across the four main use sectors i.e. domestic, agricultural, industrial (including energy) and environmental. Withdrawal and consumption of water is expected to continue to grow substantially over the next 20-50 years (Cosgrove & Rijsberman, 2002), and consequent changes in availability may drastically affect society and economies. One of the most needed improvements in Latin American river basin management is a higher level of detail in hydrological modelling and erosion risk assessment, as a basis for identification and analysis of mitigation actions, as well as for analysis of global change scenarios. Flow measurements are too costly to be realised at more than a few locations, which means that modelled data are required for the rest of the basin. Hence, TWINLATIN Work Package 3 “Hydrological modelling and extremes” was formulated to provide methods and tools to be used by other WPs, in particular WP6 on “Pollution pressure and impact analysis” and WP8 on “Change effects and vulnerability assessment”. With an emphasis on high and low flows and their impacts, WP3 was originally called “Hydrological modelling, flooding, erosion, water scarcity and water abstraction”. However, at the TWINLATIN kick-off meeting it was agreed that some of these issues resided more appropriately in WP6 and WP8, and so WP3 was renamed to focus on hydrological modelling and hydrological extremes. The specific objectives of WP3 as set out in the Description of Work are

Immediation II

All “media-tion” stages and distributes real, embodied – that is, immediate, events. The concept of immediation entails that cultural, technical, aesthetic objects, subjects, and events can no longer be abstracted from the ways in which they contribute to and are changed by broader ecologies. Immediation I and II seek to engage the entwined questions of relation, event and ecology from outside already claimed territories, nomenclature and calls to action