Chitosan-based magnetic nanoparticles for osteosarcoma theranostic

Cancer is a well-known disease with a significant impact in society not only due to its incidence, more evident in more developed countries, but also due to the expenses related to medical treat-ments. Cancer research is considered an increasingly logical science with great potential for the development of new treatment options. Advances in nanomedicine have resulted in rapid devel-opment of nanomaterials with considerable potential in cancer diagnostics and treatment. The combination of diagnosis and treatment in a single nano-platform is named theranostic. In this PhD thesis a theranostic system for osteosarcoma was proposed, composed by a magnetic core, a polymeric coating, and a chemotherapeutic drug. The presence of a specific targeting agent, in this case a monoclonal antibody, provides high specificity to the proposed theranostic system. For the core of the proposed theranostic system, stable aqueous suspensions of superparamagnetic iron oxide nanoparticles with an average diameter of 9 nm were produced. Chitosan-based poly-meric nanoparticles with a hydrodynamic diameter around 150 nm were successfully produced. Incorporation of iron oxide nanoparticles into the polymeric ones increased their hydrodynamic diameter to at least 250 nm. A monoclonal antibody specific for a transmembranar protein (car-bonic anhydrase IX) present in solid tumors was developed by hybridoma technology. Functional hybridomas producing the desired monoclonal antibodies were obtained. The proposed theranostic system functionality was evaluated in separated parts of its components. Uncoated and coated iron oxide nanoparticles with chitosan-based polymers generated heat under the application of an external alternating magnetic field. Uncoated iron oxide nanoparticles sta-bilized with oleic acid were able to enhance contrast in magnetic resonance imaging. Drug deliv-ery studies were conducted in chitosan-based polymeric nanoparticles without and with the in-corporation of iron oxide nanoparticles, demonstrating to be an effective drug delivery platform for doxorubicin. The theranostic system proposed in this PhD thesis is very promising for cancer theranostic, demonstrating to be applicable in solid tumors such as osteosarcoma.

Development and validation of gold nanoprobes for human SNP detection towards commercial application

Conventional molecular techniques for detection and characterization of relevant nucleic acid (i.e. DNA) sequences are, nowadays, cumbersome, expensive and with reduced portability. The main objective of this dissertation consisted in the optimization and validation of a fast and low-cost colorimetric nanodiagnostic methodology for the detection of single nucleotide polymorphisms (SNPs). This was done considering SNPs associated to obesity of commercial interest for STAB VIDA, and subsequent evaluation of other clinically relevant targets. Also, integration of this methodology into a microfluidic platform envisaging portability and application on points-of-care (POC) was achieved. To warrant success in pursuing these objectives, the experimental work was divided in four sections: i) genetic association of SNPs to obesity in the Portuguese population; ii) optimization and validation of the non-cross-linking approach for complete genotype characterization of these SNPs; iii) incorporation into a microfluidic platform; and iv) translation to other relevant commercial targets. FTO dbSNP rs#:9939609 carriers had higher body mass index (BMI), total body fat mass, waist perimeter and 2.5 times higher risk to obesity. AuNPs functionalized with thiolated oligonucleotides (Au-nanoprobes) were used via the non-cross-linking to validate a diagnostics approach against the gold standard technique - Sanger Sequencing - with high levels of sensitivity (87.50%) and specificity (91.67%). A proof-of-concept POC microfluidic device was assembled towards incorporation of the molecular detection strategy. In conclusion a successful framework was developed and validated for the detection of SNPs with commercial interest for STAB VIDA, towards future translation into a POC device.

Growth strategies in tourism entertainment industry - a pratical application-

In the past few years, prompted by the globalization and the quality and ease of travel, the world has witnessed a boom in the tourism sector. The forecast is that this tendency will continue in the upcoming years, representing a set of opportunities for companies operating in this business area. Boost Tourism operates in the tourism entertainment industry. Its revenues growth has been exponential so the founders decided that it was time to take it to new heights. This Work Project aims to study three alternative growth strategies and, based on a comprehensive analysis of the industry and the market, provide recommendations to outline the optimal expansion path.

A pictorial field guide for the rapid identification of sandflies (DIPTERA: PSYCHODIDAE), commonly encountered in Pará state, Brazil.

A pictorial field guide to the 30 species of sandfly most commonly encountered in Pará State is presented, based on the easily recognised external characters of the length of the 5th palpal segment, thoracic infuscation, abdominal colour and head and body size. In most cases this allows identification to the species. In others, especially with females, it gives an indication of the species, which may then be confirmed with data from more detailed taxanomix studies. This type of field guide helps in teaching, rapid sorting of flies prior to dissection and in acquainting visitors with the variety of species present in a given area.A rapid technique for the taxonomic sorting of unmounted, freshly killed female sandflies is required, prior to the dissection of large numbers of a particular species. Such a method is useful in areas where numerous species occur in studies on natural flagellate infections, age determination and for ecological studies. With the above points in mind a pictorial field guide has been designed that enables the identification of unmounted, unmacerated specimens of the 30 more commonly encountered species of phleboto-mine sandflies (***) in Pará State, North Brazil. It is based on the easily recognised external characters of the length of the 5th palpal segment, thoracic infuscation, ad-dominal colour and proboscis and body size.Taxonomy of male phlebotomine sandflies is based on the structure of the genitalia and, as most of this is external, a wholly external character key is readily made. Female taxonomy, however, is based on the internal character of the cibarium, pharynx and sperma thecae. In order to produce an external character key we therefore return to an unso phisticated "phlebotometry" (see Martins et al., 1978 p. 3 for review), using relative lengths of the proboscis, palpal segments and body, along with the degree of infuscation. Ihis idea is not new; indeed many sandfly specialists presently use external characters to separate certain species (H. Fraiha, R. P. Lane, P. D. Ready, D. G. Young and R. D. Ward personal communications 1983 & 1984).A key used to separate five anthropophillic sandflies by Biagi (1966), in Mexico, was based mainly on palpal segment length and infuscation. Floch and Abonnenc (1952) stressed the use of relative lengths of palpal segments in their keys to the sandflies of French Guiana, and four members of the shannoni group have been similarly separated according to the degree of infuscation by Morales et al. (1982). The use of thoracic infuscation as a reliable character seems to be gaining favour, having been used by young & Fairchild (1974) and Ready & Fraiha (1981). Indeed Chariotis 1974) showed the usefulness of thoracic infuscation to sepenate 7 anthropophillic species, during studies onvesicular stomatitis in Panama. Identification using external characters is essential for work on viral isolations from sandflies, where bulk samples of whole sandflies are used.Perhaps the major advantage of a simple visual guide is for teaching purposes. Technical staff in this lnstitute are able to identify most of the species they encounter without having to use the standard, more unwieldly (and in many cases unavailable) internal character keys, and the guides presented below have allowed rapid species sorting prior to the dissection of sandflies in our leismaniasis study areas (Ryan et at. ,1985).

Vehicle-to-anything application (v2anything app) for electric vehicles

This paper presents a mobile information system denominated as Vehicle-to-Anything Application (V2Anything App), and explains its conceptual aspects. This application is aimed at giving relevant information to Full Electric Vehicle (FEV) drivers, by supporting the integration of several sources of data in a mobile application, thus contributing to the deployment of the electric mobility process. The V2Anything App provides recommendations to the drivers about the FEV range autonomy, location of battery charging stations, information of the electricity market, and also a route planner taking into account public transportations and car or bike sharing systems. The main contributions of this application are related with the creation of an Information and Communication Technology (ICT) platform, recommender systems, data integration systems, driver profile, and personalized range prediction. Thus, it is possible to deliver relevant information to the FEV drivers related with the electric mobility process, electricity market, public transportation, and the FEV performance.

Application of wavelets to the study of political history

\The idea that social processes develop in a cyclical manner is somewhat like a `Lorelei'. Researchers are lured to it because of its theoretical promise, only to become entangled in (if not wrecked by) messy problems of empirical inference. The reasoning leading to hypotheses of some kind of cycle is often elegant enough, yet the data from repeated observations rarely display the supposed cyclical pattern. (...) In addition, various `schools' seem to exist which frequently arrive at di erent conclusions on the basis of the same data." (van der Eijk and Weber 1987:271). Much of the empirical controversies around these issues arise because of three distinct problems: the coexistence of cycles of di erent periodicities, the possibility of transient cycles and the existence of cycles without xed periodicity. In some cases, there are no reasons to expect any of these phenomena to be relevant. Seasonality caused by Christmas is one such example (Wen 2002). In such cases, researchers mostly rely on spectral analysis and Auto-Regressive Moving-Average (ARMA) models to estimate the periodicity of cycles.1 However, and this is particularly true in social sciences, sometimes there are good theoretical reasons to expect irregular cycles. In such cases, \the identi cation of periodic movement in something like the vote is a daunting task all by itself. When a pendulum swings with an irregular beat (frequency), and the extent of the swing (amplitude) is not constant, mathematical functions like sine-waves are of no use."(Lebo and Norpoth 2007:73) In the past, this di culty has led to two di erent approaches. On the one hand, some researchers dismissed these methods altogether, relying on informal alternatives that do not meet rigorous standards of statistical inference. Goldstein (1985 and 1988), studying the severity of Great power wars is one such example. On the other hand, there are authors who transfer the assumptions of spectral analysis (and ARMA models) into fundamental assumptions about the nature of social phenomena. This type of argument was produced by Beck (1991) who, in a reply to Goldstein (1988), claimed that only \ xed period models are meaningful models of cyclic phenomena".We argue that wavelet analysis|a mathematical framework developed in the mid-1980s (Grossman and Morlet 1984; Goupillaud et al. 1984) | is a very viable alternative to study cycles in political time-series. It has the advantage of staying close to the frequency domain approach of spectral analysis while addressing its main limitations. Its principal contribution comes from estimating the spectral characteristics of a time-series as a function of time, thus revealing how its di erent periodic components may change over time. The rest of article proceeds as follows. In the section \Time-frequency Analysis", we study in some detail the continuous wavelet transform and compare its time-frequency properties with the more standard tool for that purpose, the windowed Fourier transform. In the section \The British Political Pendulum", we apply wavelet analysis to essentially the same data analyzed by Lebo and Norpoth (2007) and Merrill, Grofman and Brunell (2011) and try to provide a more nuanced answer to the same question discussed by these authors: do British electoral politics exhibit cycles? Finally, in the last section, we present a concise list of future directions.