Infrared linear dichroism spectroscopy on amyloid fibrils aligned by molecular combing

We report the use of molecular combing as an alignment method to obtain macroscopically oriented amyloid fibrils on planar surfaces. The aligned fibrils are studied by polarized infrared spectroscopy. This gives structural information that cannot be definitively obtained from standard infrared experiments on isotropic samples, for example, confirmation of the characteristic cross-beta amyloid core structure, the side-chain orientation from specific amino acids, and the arrangement of the strands within the fibrils, as we demonstrate here. We employed amyloid fibrils from hen egg white lysozyme (HEWL) and from a model octapeptide. Our results demonstrate molecular combing as a straightforward method to align amyloid fibrils, producing highly anisotropic infrared linear dichroism (IRLD) spectra.

Synthesis of Phthalocyanines-ALA Conjugates: Water-Soluble Compounds with Low Aggregation

Syntheses of two water-soluble phthalocyanines (Pc) containing 5-aminolevulinic acid (ALA) linked to the core structure are described. These compounds were prepared by using original functionalizations, and they present remarkable structural and photophysical features, indicating that they could be applied to photodynamic therapy (PDT).

Multi-resolução com fóvea móvel para redução e abstração de dados em tempo real

We propose a new approach to reduction and abstraction of visual information for robotics vision applications. Basically, we propose to use a multi-resolution representation in combination with a moving fovea for reducing the amount of information from an image. We introduce the mathematical formalization of the moving fovea approach and mapping functions that help to use this model. Two indexes (resolution and cost) are proposed that can be useful to choose the proposed model variables. With this new theoretical approach, it is possible to apply several filters, to calculate disparity and to obtain motion analysis in real time (less than 33ms to process an image pair at a notebook AMD Turion Dual Core 2GHz). As the main result, most of time, the moving fovea allows the robot not to perform physical motion of its robotics devices to keep a possible region of interest visible in both images. We validate the proposed model with experimental results

Using genetic algorithm to design protein sequence

In this work, genetic algorithms concepts along with a rotamer library for proteins side chains are used to optimize the tertiary structure of the hydrophobic core of Cytochrome b(562) starting from the known PDB structure of its backbone which is kept fixed while the side chains of the hydrophobic core are allowed to adopt the conformations present in the rotamer library. The atoms of the side chains forming the core interact via van der Waals energy. Besides the prediction of the native core structure, it is also suggested a set of different amino acid sequences for this core. Comparison between these new cores and the native are made in terms of their volumes, van der Waals energies values and the numbers of contacts made by the side chains forming the cores. This paper proves that genetic algorithms area efficient to design new sequence for the protein core. (C) 2007 Elsevier B.V. All rights reserved.

Solitons in Bose-Einstein condensates trapped in a double-well potential

We investigate, analytically and numerically, families of bright solitons in a system of two linearly coupled nonlinear Schrodinger/Gross-Pitaevskii equations, describing two Bose-Einstein condensates trapped in an asymmetric double-well potential, in particular, when the scattering lengths in the condensates have arbitrary magnitudes and opposite signs. The solitons are found to exist everywhere where they are permitted by the dispersion law. Using the Vakhitov-Kolokolov criterion and numerical methods, we show that, except for small regions in the parameter space, the solitons are stable to small perturbations. Some of them feature self-trapping of almost all the atoms in the condensate with no atomic interaction or weak repulsion is coupled to the self-attractive condensate. An unusual bifurcation is found, when the soliton bifurcates from the zero solution with vanishing amplitude and width simultaneously diverging but at a finite number of atoms in the soliton. By means of numerical simulations, it is found that, depending on values of the parameters and the initial perturbation, unstable solitons either give rise to breathers or completely break down into incoherent waves (radiation). A version of the model with the self-attraction in both components, which applies to the description of dual-core fibers in nonlinear optics, is considered too, and new results are obtained for this much studied system. (C) 2003 Elsevier B.V. All rights reserved.

High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses

Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al.

Influência do tratamento térmico sobre a tenacidade de um aço com AISI SAE 1045 com médio teor de carbono, avaliada por ensaios de impacto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização mecânica e microestrutural de um aço de baixo carbono

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparação in vivo da biocompatilidade de amostras com superfície porosa confeccionadas com diferentes ligas de titânio

Pós-graduação em Biopatologia Bucal - ICT

Comparação entre modelos de análise genômica utilizando dados simulados e dados reais em ovinos

Pós-graduação em Genética e Melhoramento Animal - FCAV

Large-scale Network Analysis on Distributed Architectures

Questa dissertazione esamina le sfide e i limiti che gli algoritmi di analisi di grafi incontrano in architetture distribuite costituite da personal computer. In particolare, analizza il comportamento dell'algoritmo del PageRank così come implementato in una popolare libreria C++ di analisi di grafi distribuiti, la Parallel Boost Graph Library (Parallel BGL). I risultati qui presentati mostrano che il modello di programmazione parallela Bulk Synchronous Parallel è inadatto all'implementazione efficiente del PageRank su cluster costituiti da personal computer. L'implementazione analizzata ha infatti evidenziato una scalabilità negativa, il tempo di esecuzione dell'algoritmo aumenta linearmente in funzione del numero di processori. Questi risultati sono stati ottenuti lanciando l'algoritmo del PageRank della Parallel BGL su un cluster di 43 PC dual-core con 2GB di RAM l'uno, usando diversi grafi scelti in modo da facilitare l'identificazione delle variabili che influenzano la scalabilità. Grafi rappresentanti modelli diversi hanno dato risultati differenti, mostrando che c'è una relazione tra il coefficiente di clustering e l'inclinazione della retta che rappresenta il tempo in funzione del numero di processori. Ad esempio, i grafi Erdős–Rényi, aventi un basso coefficiente di clustering, hanno rappresentato il caso peggiore nei test del PageRank, mentre i grafi Small-World, aventi un alto coefficiente di clustering, hanno rappresentato il caso migliore. Anche le dimensioni del grafo hanno mostrato un'influenza sul tempo di esecuzione particolarmente interessante. Infatti, si è mostrato che la relazione tra il numero di nodi e il numero di archi determina il tempo totale.

Algorithms for network design and routing problems

In this thesis we study three combinatorial optimization problems belonging to the classes of Network Design and Vehicle Routing problems that are strongly linked in the context of the design and management of transportation networks: the Non-Bifurcated Capacitated Network Design Problem (NBP), the Period Vehicle Routing Problem (PVRP) and the Pickup and Delivery Problem with Time Windows (PDPTW). These problems are NP-hard and contain as special cases some well known difficult problems such as the Traveling Salesman Problem and the Steiner Tree Problem. Moreover, they model the core structure of many practical problems arising in logistics and telecommunications. The NBP is the problem of designing the optimum network to satisfy a given set of traffic demands. Given a set of nodes, a set of potential links and a set of point-to-point demands called commodities, the objective is to select the links to install and dimension their capacities so that all the demands can be routed between their respective endpoints, and the sum of link fixed costs and commodity routing costs is minimized. The problem is called non- bifurcated because the solution network must allow each demand to follow a single path, i.e., the flow of each demand cannot be splitted. Although this is the case in many real applications, the NBP has received significantly less attention in the literature than other capacitated network design problems that allow bifurcation. We describe an exact algorithm for the NBP that is based on solving by an integer programming solver a formulation of the problem strengthened by simple valid inequalities and four new heuristic algorithms. One of these heuristics is an adaptive memory metaheuristic, based on partial enumeration, that could be applied to a wider class of structured combinatorial optimization problems. In the PVRP a fleet of vehicles of identical capacity must be used to service a set of customers over a planning period of several days. Each customer specifies a service frequency, a set of allowable day-combinations and a quantity of product that the customer must receive every time he is visited. For example, a customer may require to be visited twice during a 5-day period imposing that these visits take place on Monday-Thursday or Monday-Friday or Tuesday-Friday. The problem consists in simultaneously assigning a day- combination to each customer and in designing the vehicle routes for each day so that each customer is visited the required number of times, the number of routes on each day does not exceed the number of vehicles available, and the total cost of the routes over the period is minimized. We also consider a tactical variant of this problem, called Tactical Planning Vehicle Routing Problem, where customers require to be visited on a specific day of the period but a penalty cost, called service cost, can be paid to postpone the visit to a later day than that required. At our knowledge all the algorithms proposed in the literature for the PVRP are heuristics. In this thesis we present for the first time an exact algorithm for the PVRP that is based on different relaxations of a set partitioning-like formulation. The effectiveness of the proposed algorithm is tested on a set of instances from the literature and on a new set of instances. Finally, the PDPTW is to service a set of transportation requests using a fleet of identical vehicles of limited capacity located at a central depot. Each request specifies a pickup location and a delivery location and requires that a given quantity of load is transported from the pickup location to the delivery location. Moreover, each location can be visited only within an associated time window. Each vehicle can perform at most one route and the problem is to satisfy all the requests using the available vehicles so that each request is serviced by a single vehicle, the load on each vehicle does not exceed the capacity, and all locations are visited according to their time window. We formulate the PDPTW as a set partitioning-like problem with additional cuts and we propose an exact algorithm based on different relaxations of the mathematical formulation and a branch-and-cut-and-price algorithm. The new algorithm is tested on two classes of problems from the literature and compared with a recent branch-and-cut-and-price algorithm from the literature.

Solving the cooling flow problem through mechanical AGN feedback

A fundamental gap in the current understanding of collapsed structures in the universe concerns the thermodynamical evolution of the ordinary, baryonic component. Unopposed radiative cooling of plasma would lead to the cooling catastrophe, a massive inflow of condensing gas toward the centre of galaxies, groups and clusters. The last generation of multiwavelength observations has radically changed our view on baryons, suggesting that the heating linked to the active galactic nucleus (AGN) may be the balancing counterpart of cooling. In this Thesis, I investigate the engine of the heating regulated by the central black hole. I argue that the mechanical feedback, based on massive subrelativistic outflows, is the key to solving the cooling flow problem, i.e. dramatically quenching the cooling rates for several billion years without destroying the cool-core structure. Using an upgraded version of the parallel 3D hydrodynamic code FLASH, I show that anisotropic AGN outflows can further reproduce fundamental observed features, such as buoyant bubbles, cocoon shocks, sonic ripples, metals dredge-up, and subsonic turbulence. The latter is an essential ingredient to drive nonlinear thermal instabilities, which cause cold gas condensation, a residual of the quenched cooling flow and, later, fuel for the AGN feedback engine. The self-regulated outflows are systematically tested on the scales of massive clusters, groups and isolated elliptical galaxies: in lighter less bound objects the feedback needs to be gentler and less efficient, in order to avoid drastic overheating. In this Thesis, I describe in depth the complex hydrodynamics, involving the coupling of the feedback energy to that of the surrounding hot medium. Finally, I present the merits and flaws of all the proposed models, with a critical eye toward observational concordance.

Nanopartikelcharakterisierung: Untersuchung des Retentionsverhaltens in der AF-FFF und der bimodalen Größenverteilung sauer katalysierter Poly(organosiloxan)-Dispersionen

Polymere Hohlstrukturen eignen sich um eine große Anzahl an Gastmolekülen zu verkapseln und bieten somit interessante Anwendungsmöglichkeiten, z.B. im Bereich kontrollierter Transportsysteme. Solche wohl definierten Strukturen lassen sich mittels des Sol-Gel-Prozesses durch Hydrolyse und Kondensation von Dialkoxydialkyl- und Trialkoxyalkylsilanen in wässriger Dispersion in Gegenwart von Tensiden synthetisieren. Die Methode ermöglicht den Aufbau verschiedener Kern-Schale-Systeme, inklusive Hohlkugelarchitekturen, mit Durchmessern von 10-100 nm. Abhängig von den eingestellten Parametern wird dabei eine bimodale Größenverteilung der Partikel beobachtet. Die bimodalen Proben wurden mittels der circularen asymmetrischen Fluss Feld-Fluss Fraktionierung (CAFFFE) fraktioniert. NMR-Untersuchungen deuten darauf hin, dass die Ursache der bimodalen Verteilung in der Synthese der Kerndispersion zu liegen scheint. MALDI-TOF-MS und GC-Messungen zeigen, dass der Kern der größeren Partikel ausschließlich aus zyklischen Kondensationsprodukten besteht, während im Kernmaterial der kleineren Partikel zusätzlich noch lineare Polydimethylsiloxan-Ketten vorhanden sind. Unter der Annahme, dass PDMS als Ultrahydrophob wirkt, lässt sich die Ostwaldreifung als Ursache der Bimodalität ausmachen. Eine Erhöhung des PDMS-Anteils, der zur Stabilisierung gegen den Reifungsprozess notwendig ist, führt zu einer monomodalen Verteilung der erhaltenen Partikel.

Synthese von optisch aktiven 2-Vinyl-piperidinen - Schlüsselbausteine für die Clavepictin-Totalsynthese

Im Rahmen der vorliegenden Arbeit wurden eine Vielzahl optisch aktiver 1,2,6-trisubstituierte Piperidine stereoselekiv dargestellt. Bei der anschließenden Aza-Claisen-Umlagerunge wurden daraus chirale Azecinone (zyklische, ungesättigte, zehngliedrige Lactame) gebildet, die sich für die Totalsynthese u. a. von Clavepictin A eignen.rnrnDazu wurde zunächst über eine weitere zwitterionische Aza-Claisen-Umlagerung ein Dien aufgebaut, welches durch intramolekulare Grubbs-Metathese zum Piperidin geschlossen werden konnte. Daraus wurde ein Baikiain- sowie ein Pipecolinsäure-Derivat hergestellt.rnrnAuf einem weiteren Weg zu hochsubstituierten Piperidinen wurde eine von Katritzky et al. erarbeitete Synthese eines Bisaminals auf ihre Flexibilität bezüglich des Substitutionsmusters in 2- und 6-Position am Piperidinring durch eine Kaskade an Reduktionen und Grignard-Reaktionen zu stereoselektiv trisubstituierten 2-Vinyl-Piperidinen untersucht. rnrnDie anschließende zwitterionische Aza-Claisen-Umlagerung an diesen Vinyl-Piperidinen mit verschiedenen Säurefluoriden diente jeweils zur Überprüfung der Tauglichkeit der ausgewählten Reaktionswege zur Totalsynthese von Clavepictin. Durch Strukturbestimmung der gebildeten Azecinone mittels NOESY wurde der erwartete Chiralitätstransfer bei der Umlagerungsreaktion untersucht bzw. bestätigt.rnrnNebenbei wurde dabei ein Chinolizidin-Derivat gefunden, dessen Darstellung durch eine neuartige Dominoreaktion erklärt wurde und dessen Grundstruktur einen weiteren und ggf. kürzeren Syntheseweg zu Clavepictin A und seinen Derivaten zulassen sollte. rn