PROTEIN-TRIGGERED SUSTAINED DRUG RELEASE CONTROLLED BY APTAMERS BOUND TO OLIGOMER-CROSSLINKED ALGINATE

Sustained drug release systems provide many advantages over traditional delivery methods such as extending the time in which the drug is found to be within an effective concentration within the therapeutic window, which decreases the frequency of administration of the drug, and increases patient compliance. Research using polyacrylamide crosslinked by oligomers containing an aptamer sequence, has demonstrated a pulsatile release over 50 minutes triggered by a 2 mM target adenosine concentration. This thesis aims to build off this concept by designing a system that delivers in a sustained manner when triggered by micromolar target concentrations reflective of disease in vivo, using macromolecular targets. For example, the disease wet age related macular degeneration (wet AMD) is associated with increased concentrations of the protein vascular endothelial growth factor (VEGF-A) – a macromolecule. Patients with wet AMD would benefit from the implantation of devices or microspheres that release drugs in a sustained manner in response to local VEGF concentrations. In this thesis, we hypothesize that the protein lysozyme, used to demonstrate proof-of-concept, could trigger the increased release of drugs from oligomer-crosslinked alginate. The objectives are to (i) demonstrate sustained release from alginate, (ii) design oligomer crosslinked alginate that degrades in response to lysozyme, and then (iii) use these systems to control the release of FITC-dextran with and without lysozyme. A series of control experiments and analyses were used to optimize the crosslinking of alginate by annealed oligomers. The cumulative release of FITC-dextran (MW 20,000) from oligomer crosslinked alginate increased by 3.4 μg when lysozyme (3 μM) was introduced at 48 hours, as opposed to controls which released only 0.2 μg. FITC-loaded alginate microspheres coated by oligomer-crosslinked alginate released 15% more FITC-dextran over 120 hours when placed into 3 μM of lysozyme than without lysozyme. Controls of alginate crosslinked with PEG or control oligomers (without a lysozyme aptamer sequence) had no changes in release with lysozyme. The incorporation of a lysozyme aptamer onto oligomers used to crosslink alginate disks or alginate coatings on microspheres resulted in different diffusion and release of FITC-dextran into PBS with or without lysozyme. This approach could be adapted for the delivery of drugs to diseases with specific protein profiles such as wet AMD.

Shaken not stirred: creating exotic angular momentum states by shaking an optical lattice

We propose a method to create higher orbital states of ultracold atoms in the Mott regime of an optical lattice. This is done by periodically modulating the position of the trap minima (known as shaking) and controlling the interference term of the lasers creating the lattice. These methods are combined with techniques of shortcuts to adiabaticity. As an example of this, we show specifically how to create an anti-ferromagnetic type ordering of angular momentum states of atoms. The specific pulse sequences are designed using Lewis-Riesenfeld invariants and a fourlevel model for each well. The results are compared with numerical simulations of the full Schrodinger equation.

Query routing in cooperative semi-structured peer-to-peer information retrieval networks

Conventional web search engines are centralised in that a single entity crawls and indexes the documents selected for future retrieval, and the relevance models used to determine which documents are relevant to a given user query. As a result, these search engines suffer from several technical drawbacks such as handling scale, timeliness and reliability, in addition to ethical concerns such as commercial manipulation and information censorship. Alleviating the need to rely entirely on a single entity, Peer-to-Peer (P2P) Information Retrieval (IR) has been proposed as a solution, as it distributes the functional components of a web search engine – from crawling and indexing documents, to query processing – across the network of users (or, peers) who use the search engine. This strategy for constructing an IR system poses several efficiency and effectiveness challenges which have been identified in past work. Accordingly, this thesis makes several contributions towards advancing the state of the art in P2P-IR effectiveness by improving the query processing and relevance scoring aspects of a P2P web search. Federated search systems are a form of distributed information retrieval model that route the user’s information need, formulated as a query, to distributed resources and merge the retrieved result lists into a final list. P2P-IR networks are one form of federated search in routing queries and merging result among participating peers. The query is propagated through disseminated nodes to hit the peers that are most likely to contain relevant documents, then the retrieved result lists are merged at different points along the path from the relevant peers to the query initializer (or namely, customer). However, query routing in P2P-IR networks is considered as one of the major challenges and critical part in P2P-IR networks; as the relevant peers might be lost in low-quality peer selection while executing the query routing, and inevitably lead to less effective retrieval results. This motivates this thesis to study and propose query routing techniques to improve retrieval quality in such networks. Cluster-based semi-structured P2P-IR networks exploit the cluster hypothesis to organise the peers into similar semantic clusters where each such semantic cluster is managed by super-peers. In this thesis, I construct three semi-structured P2P-IR models and examine their retrieval effectiveness. I also leverage the cluster centroids at the super-peer level as content representations gathered from cooperative peers to propose a query routing approach called Inverted PeerCluster Index (IPI) that simulates the conventional inverted index of the centralised corpus to organise the statistics of peers’ terms. The results show a competitive retrieval quality in comparison to baseline approaches. Furthermore, I study the applicability of using the conventional Information Retrieval models as peer selection approaches where each peer can be considered as a big document of documents. The experimental evaluation shows comparative and significant results and explains that document retrieval methods are very effective for peer selection that brings back the analogy between documents and peers. Additionally, Learning to Rank (LtR) algorithms are exploited to build a learned classifier for peer ranking at the super-peer level. The experiments show significant results with state-of-the-art resource selection methods and competitive results to corresponding classification-based approaches. Finally, I propose reputation-based query routing approaches that exploit the idea of providing feedback on a specific item in the social community networks and manage it for future decision-making. The system monitors users’ behaviours when they click or download documents from the final ranked list as implicit feedback and mines the given information to build a reputation-based data structure. The data structure is used to score peers and then rank them for query routing. I conduct a set of experiments to cover various scenarios including noisy feedback information (i.e, providing positive feedback on non-relevant documents) to examine the robustness of reputation-based approaches. The empirical evaluation shows significant results in almost all measurement metrics with approximate improvement more than 56% compared to baseline approaches. Thus, based on the results, if one were to choose one technique, reputation-based approaches are clearly the natural choices which also can be deployed on any P2P network.

Ravines in Angola. Causes and restraint methods

The Earth we know today was not always so. Over millions of years have undergone significant ch an g e s brought about by numerous geological phenomena aimed at your balance, some internal order, creating new geological formations and other external order smoothing formations previously created. From t h e tectonic standpoint, Angola is located in a relatively stable area which gives it a certain p ri v i l e g e w h e n compared with some Asian countries or even Americans where quite often occur earthquakes and volcanic eruptions. However, the same cannot be said in relation to the occurrence of an external geodynamics phenomena, such as the ravines, which in recent years has taken shape in many provinces, especially due to anthropogenic activity, giving rise to geological hazards, increasing the risk of damage in buildings and others infrastructures, losses direct or indirect in economic activities and loss of human lives. We understand that the reducing of these risks starts, in particular, by their identification, for later take preventive measures. This work is the result of some research work carried out by the authors through erosion courses of s o i l and stabilization of soils subject to erosion phenomena, carried out by Engineering Laboratory of Angola (LEA). For the realization of this work, we resorted to cartographic data query, literature, listening to s o m e o f the provincial representatives and local residents, as well as the observation in lo co o f s o m e af f e ct ed areas. The results allow us to infer that the main provinces affected by ravine phenomenon are located in Central and Northern highlands, as well as in the eastern region, and more recently in Cuando-Cub an go province. Not ruling out, however, other regions, such as in Luanda and Cabinda [1]. Relatively the causes, we can say that the ravines in Angola are primarily due to the combination of three natural factors: climate, topography and type of soil [2]. When we add the anthropogenic activit y , namely the execution of construction works, the drainage system obstructio n, exploration of m i n e ral s, agriculture and fires, it is verified an increasing of the phenomenon, often requiring immedi at e act i o n . These interventions can be done through structural or engineering measures and by the stabilization measures on the degraded soil cover [3]. We present an example of stabilization measures throu g h t h e deployment of a local vegetation called Pennisetum purpureum. It is expected that the results may contribute to a better understanding of the causes of the ravine phenomenon in Angola and that the adopted stabilization method can be adapted in other affected provinces in order to prevent and making the contention of the ravines.

"Portuguese Observatory of Taeniasis and Cysticercosis": A "One Health" example for epidemiological surveillance of one neglected disease in a European country

Cysticercosis results from the ingestion Taenia solium eggs directly by faecal-oral route or contaminated food or water. Human tapeworm carriers who have become infected after ingesting pork meat contaminated with cysticerci release these eggs. Cysticercosis occurs after tapeworm eggs are ingested by an intermediate host (pig or human) and then hatch, migrate, and lodge in the host's tissues, where they develop onto larval cysticerci. When they lodged in the central nervous system of humans, results in the disease condition called Neurocysticercosis (NCC), with a heterogeneous manifestations depending of the locations of cysts, number, size and their stage of evolution (1). Consequently the prognostic ranges from asymptomatic to situations leading to death in 2% to 9.8%. of cases (7) In swine’s there are few studies, but recent works have proved that animals, for the same reasons, also have neurological abnormalities, expressed by seizures, stereotypic walk in circles, chewing motions with foamy salivation included tonic muscle contractions followed by a sudden diminution in all muscle tone leading to collapse (2). Conventional domestic wastewater treatment processes may not be totally effective in inactivating parasites eggs from Taenia solium, allowing some contamination of soils and agricultural products (11). In Portugal there are some evidence of aggregation of human cysticercosis cases in specific regions, bases in ecological design studies (6). There are few information about human tapeworm carriers and social and economic factors associated with them. Success in knowledge and consequently in lowering transmission is limited by the complex network of biological and social factors that maintain the spread. Effective control of mostly zoonosis require One Health approach, after a real knowledge and transparency in the information provided by the institutions responsible for both animal and human health, allowing sustained interventions targeted at the transmission cycle's crucial nodes. In general, the model used to control, reflects a rural reality, where pigs are raised freely, poor sanitation conditions and incipient sanitary inspection. In cysticercosis, pigs are obligate intermediate hosts and so considered as first targets for control and used as sentinels to monitor environmental T. solium contamination (3). Usually environmental contamination with Taenia spp. eggs is a key issue in most of studies with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans (5). Soil-related factors as well as socio-economic and behavioural factors are associated with the emergence of significant clustering human cysticercosis (4,5). However scarce studies has been produced in urban environmental and in developed countries with the finality to characterize the spatial pattern. There are still few data available regarding its prevalence and spatial distribution; Transmission patterns are likely to exhibit correlations as housing conditions, water supply, basic sanitation, schooling and birthplace of the individual or relatives, more than pigs rearing free, soil conditions (9). As a matter of fact, tapeworm carriers from endemic zones can auto-infect or transmit infection to other people or arrive already suffering NCC (as a result of travelling to or being a citizen from an endemic cysticercosis country) to a free cysticercosis country. Transmission is fecal-oral; this includes transmission through person-to-person contact, through autoinfection, or through contaminated food This has been happening in different continents as North America (5.4–18% been autochthonous), Europe and Australia (7). Recently, case reports of NCC have also emerged from Muslim countries. (10). Actually, different papers relate an epidemic situation in Spain and Portugal (7, 8). However the kind of study done does not authorize such conclusion. There are no evidence that infections were acquired in Portugal and there are not characterized the mode of transmission. Papers with these kind of information will be allow to have economic consequences resulted from artificial trade barriers with serious consequences for pig producers and pig meat trade. We need transparency in information’s that allow provide the basis to support the development and targeting of future effective control programmes (and prove we need that). So, to have a real picture of the disease, it is necessary integrate data from human, animal and environmental factors surrounding human and pig cases to characterize the pattern of the transmission. The design needs to be able to capture unexpected, and not common outcomes (routine data). We need to think “One Health” to get a genuine image of the situation.

Scene Mapping and Understanding by Robotic Vision

The first mechanical Automaton concept was found in a Chinese text written in the 3rd century BC, while Computer Vision was born in the late 1960s. Therefore, visual perception applied to machines (i.e. the Machine Vision) is a young and exciting alliance. When robots came in, the new field of Robotic Vision was born, and these terms began to be erroneously interchanged. In short, we can say that Machine Vision is an engineering domain, which concern the industrial use of Vision. The Robotic Vision, instead, is a research field that tries to incorporate robotics aspects in computer vision algorithms. Visual Servoing, for example, is one of the problems that cannot be solved by computer vision only. Accordingly, a large part of this work deals with boosting popular Computer Vision techniques by exploiting robotics: e.g. the use of kinematics to localize a vision sensor, mounted as the robot end-effector. The remainder of this work is dedicated to the counterparty, i.e. the use of computer vision to solve real robotic problems like grasping objects or navigate avoiding obstacles. Will be presented a brief survey about mapping data structures most widely used in robotics along with SkiMap, a novel sparse data structure created both for robotic mapping and as a general purpose 3D spatial index. Thus, several approaches to implement Object Detection and Manipulation, by exploiting the aforementioned mapping strategies, will be proposed, along with a completely new Machine Teaching facility in order to simply the training procedure of modern Deep Learning networks.

Shaping transverse beam distributions by means of adiabatic crossing of resonances

Non-linear effects are responsible for peculiar phenomena in charged particles dynamics in circular accelerators. Recently, they have been used to propose novel beam manipulations where one can modify the transverse beam distribution in a controlled way, to fulfil the constraints posed by new applications. One example is the resonant beam splitting used at CERN for the Multi-Turn Extraction (MTE), to transfer proton beams from PS to SPS. The theoretical description of these effects relies on the formulation of the particle's dynamics in terms of Hamiltonian systems and symplectic maps, and on the theory of adiabatic invariance and resonant separatrix crossing. Close to resonance, new stable regions and new separatrices appear in the phase space. As non-linear effects do not preserve the Courant-Snyder invariant, it is possible for a particle to cross a separatrix, changing the value of its adiabatic invariant. This process opens the path to new beam manipulations. This thesis deals with various possible effects that can be used to shape the transverse beam dynamics, using 2D and 4D models of particles' motion. We show the possibility of splitting a beam using a resonant external exciter, or combining its action with MTE-like tune modulation close to resonance. Non-linear effects can also be used to cool a beam acting on its transverse beam distribution. We discuss the case of an annular beam distribution, showing that emittance can be reduced modulating amplitude and frequency of a resonant oscillating dipole. We then consider 4D models where, close to resonance, motion in the two transverse planes is coupled. This is exploited to operate on the transverse emittances with a 2D resonance crossing. Depending on the resonance, the result is an emittance exchange between the two planes, or an emittance sharing. These phenomena are described and understood in terms of adiabatic invariance theory.

Biotechnological approaches to valorize alternative protein source, waste and by-products from food industries

The PhD research project was a striking example of the enhancement of milling by-product and alternative protein sources from house cricket (Acheta domesticus), conceived as sustainable and renewable sources, to produce innovative food products. During milling processing of wheat and rye, several by-products with high technological and functional potential, are produced. The use of selected microbial consortia, allowed to obtain a pre-fermented ingredient for use in the bakery. The pre-ferments obtained were characterized by a high technological, functional and nutritional value, also interesting from a nutraceutical point of view. Bakery products obtained by the addition of pre-fermented ingredients were characterized by a greater quantity of aromatic molecules and an increase in SCFA, antioxidant activity, total amino acids and total phenols resulting in positive effect on the functionality. Moreover, the industrial scaling-up of pre-ferment and innovative bakery goods production, developed in this research, underlined the technological applicability of pre-fermented ingredients on a large scale. Moreover, the identification of innovative protein sources, can address the request of new sustainable ingredients able to less impact on the environment and to satisfy the food global demand. To upscale the insect production and ensure food safety of insect-based products, biotechnological formulations based on Acheta domesticus powder were optimized. The use of Yarrowia lipolytica in the biotechnological transformation of cricket powder led to the achievement of a cricket-based food ingredient characterized by a reduced content of chitin and an increase of antimicrobial and health-promoting molecules. The innovative bakery products containing cricket-based hydrolysates from Y. lipolytica possessed specific sensory, qualitative and functional characteristics to the final product. Moreover, the combination of Y. lipolytica hydrolysis and baking showed promising results regarding a reduced allergenicity in cricket-based baked products. Thus, the hydrolysate of cricket powder may represent a versatile and promising ingredient in the production of innovative foods.

Thermodynamic Study Of The Micellization Of Zwitterionic Surfactants And Their Interaction With Polymers In Water By Isothermal Titration Calorimetry.

The micellization of a homologous series of zwitterionic surfactants, a group of sulfobetaines, was studied using isothermal titration calorimetry (ITC) in the temperature range from 15 to 65 °C. The increase in both temperature and the alkyl chain length leads to more negative values of ΔGmic(0) , favoring the micellization. The entropic term (ΔSmic(0)) is predominant at lower temperatures, and above ca. 55-65 °C, the enthalpic term (ΔHmic(0)) becomes prevalent, figuring a jointly driven process as the temperature increases. The interaction of these sulfobetaines with different polymers was also studied by ITC. Among the polymers studied, only two induced the formation of micellar aggregates at lower surfactant concentration: poly(acrylic acid), PAA, probably due to the formation of hydrogen bonds between the carboxylic group of the polymer and the sulfonate group of the surfactant, and poly(sodium 4-styrenesulfonate), PSS, probably due to the incorporation of the hydrophobic styrene group into the micelles. The prevalence of the hydrophobic and not the electrostatic contributions to the interaction between sulfobetaine and PSS was confirmed by an increased interaction enthalpy in the presence of electrolytes (NaCl) and by the observation of a significant temperature dependence, the latter consistent with the proposed removal of hydrophobic groups from water.

Neutralisation Of The Pharmacological Activities Of Bothrops Alternatus Venom By Anti-pla2 Iggs.

Basic phospholipases A2 (PLA2) are toxic and induce a wide spectrum of pharmacological effects, although the acidic enzyme types are not lethal or cause low lethality. Therefore, it is challenging to elucidate the mechanism of action of acidic phospholipases. This study used the acidic non-toxic Ba SpII RP4 PLA2 from Bothrops alternatus as an antigen to develop anti-PLA2 IgG antibodies in rabbits and used in vivo assays to examine the changes in crude venom when pre-incubated with these antibodies. Using Ouchterlony and western blot analyses on B. alternatus venom, we examined the specificity and sensitivity of phospholipase A2 recognition by the specific antibodies (anti-PLA2 IgG). Neutralisation assays using a non-toxic PLA2 antigen revealed unexpected results. The (indirect) haemolytic activity of whole venom was completely inhibited, and all catalytically active phospholipases A2 were blocked. Myotoxicity and lethality were reduced when the crude venom was pre-incubated with anti-PLA2 immunoglobulins. CK levels in the skeletal muscle were significantly reduced at 6 h, and the muscular damage was more significant at this time-point compared to 3 and 12 h. When four times the LD50 was used (224 μg), half the animals treated with the venom-anti PLA2 IgG mixture survived after 48 h. All assays performed with the specific antibodies revealed that Ba SpII RP4 PLA2 had a synergistic effect on whole-venom toxicity. IgG antibodies against the venom of the Argentinean species B. alternatus represent a valuable tool for elucidation of the roles of acidic PLA2 that appear to have purely digestive roles and for further studies on immunotherapy and snake envenoming in affected areas in Argentina and Brazil.

Changes In Chromatin Structure In Nih 3t3 Cells Induced By Valproic Acid And Trichostatin A.

Valproic acid (VPA) and trichostatin A (TSA) are known histone deacetylase inhibitors (HDACIs) with epigenetic activity that affect chromatin supra-organization, nuclear architecture, and cellular proliferation, particularly in tumor cells. In this study, chromatin remodeling with effects extending to heterochromatic areas was investigated by image analysis in non-transformed NIH 3T3 cells treated for different periods with different doses of VPA and TSA under conditions that indicated no loss of cell viability. Image analysis revealed chromatin decondensation that affected not only euchromatin but also heterochromatin, concomitant with a decreased activity of histone deacetylases and a general increase in histone H3 acetylation. Heterochromatin protein 1-α (HP1-α), identified immunocytochemically, was depleted from the pericentromeric heterochromatin following exposure to both HDACIs. Drastic changes affecting cell proliferation and micronucleation but not alteration in CCND2 expression and in ratios of Bcl-2/Bax expression and cell death occurred following a 48-h exposure of the NIH 3T3 cells particularly in response to higher doses of VPA. Our results demonstrated that even low doses of VPA (0.05 mM) and TSA (10 ng/ml) treatments for 1 h can affect chromatin structure, including that of the heterochromatin areas, in non-transformed cells. HP1-α depletion, probably related to histone demethylation at H3K9me3, in addition to the effect of VPA and TSA on histone H3 acetylation, is induced on NIH 3T3 cells. Despite these facts, alterations in cell proliferation and micronucleation, possibly depending on mitotic spindle defects, require a longer exposure to higher doses of VPA and TSA.

Yellowing And Bleaching Of Grey Hair Caused By Photo And Thermal Degradation.

Yellowing is an undesirable phenomenon that is common in people with white and grey hair. Because white hair has no melanin, the pigment responsible for hair colour, the effects of photodegradation are more visible in this type of hair. The origin of yellowing and its relation to photodegradation processes are not properly established, and many questions remain open in this field. In this work, the photodegradation of grey hair was investigated as a function of the wavelength of incident radiation, and its ultrastructure was determined, always comparing the results obtained for the white and black fibres present in grey hair with the results of white wool. The results presented herein indicate that the photobehaviour of grey hair irradiated with a mercury lamp or with solar radiation is dependent on the wavelength range of the incident radiation and on the initial shade of yellow in the sample. Two types of grey hair were used: (1) blended grey hair (more yellow) and (2) grey hair from a single-donor (less yellow). After exposure to a full-spectrum mercury lamp for 200 h, the blended white hair turned less yellow (the yellow-blue difference, Db(*) becomes negative, Db(*)=-6), whereas the white hair from the single-donor turned slightly yellower (Db(*)=2). In contrast, VIS+IR irradiation resulted in bleaching in both types of hair, whereas a thermal treatment (at 81 °C) caused yellowing of both types of hair, resulting in a Db(*)=3 for blended white hair and Db(*)=9 for single-donor hair. The identity of the yellow chromophores was investigated by UV-Vis spectroscopy. The results obtained with this technique were contradictory, however, and it was not possible to obtain a simple correlation between the sample shade of yellow and the absorption spectra. In addition, the results are discussed in terms of the morphology differences between the pigmented and non-pigmented parts of grey hair, the yellowing and bleaching effects of grey hair, and the occurrence of dark-follow reactions.

Metabolic Memory Of ß-cells Controls Insulin Secretion And Is Mediated By Camkii.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in calcium pulses as a form of metabolic memory, just as neurons store cognitive information. To test this hypothesis, we developed a novel paradigm of pulsed exposure of ß-cells to intervals of high glucose, followed by a 24-h consolidation period to eliminate any acute metabolic effects. Strikingly, ß-cells exposed to this high-glucose pulse paradigm exhibited significantly stronger insulin secretion. This metabolic memory was entirely dependent on CaMKII. Metabolic memory was reflected on the protein level by increased expression of proteins involved in glucose sensing and Ca(2+)-dependent vesicle secretion, and by elevated levels of the key ß-cell transcription factor MAFA. In summary, like neurons, human and mouse ß-cells are able to acquire and retrieve information.

Effect Of Simulated Microwave Disinfection On The Linear Dimensional Change, Hardness And Impact Strength Of Acrylic Resins Processed By Different Polymerizing Cycles.

This study investigated the effect of simulated microwave disinfection (SMD) on the linear dimensional changes, hardness and impact strength of acrylic resins under different polymerization cycles. Metal dies with referential points were embedded in flasks with dental stone. Samples of Classico and Vipi acrylic resins were made following the manufacturers' recommendations. The assessed polymerization cycles were: A-- water bath at 74ºC for 9 h; B-- water bath at 74ºC for 8 h and temperature increased to 100ºC for 1 h; C-- water bath at 74ºC for 2 h and temperature increased to 100ºC for 1 h;; and D-- water bath at 120ºC and pressure of 60 pounds. Linear dimensional distances in length and width were measured after SMD and water storage at 37ºC for 7 and 30 days using an optical microscope. SMD was carried out with the samples immersed in 150 mL of water in an oven (650 W for 3 min). A load of 25 gf for 10 sec was used in the hardness test. Charpy impact test was performed with 40 kpcm. Data were submitted to ANOVA and Tukey's test (5%). The Classico resin was dimensionally steady in length in the A and D cycles for all periods, while the Vipi resin was steady in the A, B and C cycles for all periods. The Classico resin was dimensionally steady in width in the C and D cycles for all periods, and the Vipi resin was steady in all cycles and periods. The hardness values for Classico resin were steady in all cycles and periods, while the Vipi resin was steady only in the C cycle for all periods. Impact strength values for Classico resin were steady in the A, C and D cycles for all periods, while Vipi resin was steady in all cycles and periods. SMD promoted different effects on the linear dimensional changes, hardness and impact strength of acrylic resins submitted to different polymerization cycles when after SMD and water storage were considered.

Iis--integrated Interactome System: A Web-based Platform For The Annotation, Analysis And Visualization Of Protein-metabolite-gene-drug Interactions By Integrating A Variety Of Data Sources And Tools.

High-throughput screening of physical, genetic and chemical-genetic interactions brings important perspectives in the Systems Biology field, as the analysis of these interactions provides new insights into protein/gene function, cellular metabolic variations and the validation of therapeutic targets and drug design. However, such analysis depends on a pipeline connecting different tools that can automatically integrate data from diverse sources and result in a more comprehensive dataset that can be properly interpreted. We describe here the Integrated Interactome System (IIS), an integrative platform with a web-based interface for the annotation, analysis and visualization of the interaction profiles of proteins/genes, metabolites and drugs of interest. IIS works in four connected modules: (i) Submission module, which receives raw data derived from Sanger sequencing (e.g. two-hybrid system); (ii) Search module, which enables the user to search for the processed reads to be assembled into contigs/singlets, or for lists of proteins/genes, metabolites and drugs of interest, and add them to the project; (iii) Annotation module, which assigns annotations from several databases for the contigs/singlets or lists of proteins/genes, generating tables with automatic annotation that can be manually curated; and (iv) Interactome module, which maps the contigs/singlets or the uploaded lists to entries in our integrated database, building networks that gather novel identified interactions, protein and metabolite expression/concentration levels, subcellular localization and computed topological metrics, GO biological processes and KEGG pathways enrichment. This module generates a XGMML file that can be imported into Cytoscape or be visualized directly on the web. We have developed IIS by the integration of diverse databases following the need of appropriate tools for a systematic analysis of physical, genetic and chemical-genetic interactions. IIS was validated with yeast two-hybrid, proteomics and metabolomics datasets, but it is also extendable to other datasets. IIS is freely available online at: http://www.lge.ibi.unicamp.br/lnbio/IIS/.