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Controlled drug delivery strategies: Advances on the synthesis and molecular dynamics of dendrimers, and optimization of liposomes preparation by Dual Asymmetric Centrifugation(2017-12-01)In early phase of drug development, New Chemical Entities (NCEs) are used as highly active drugs, with limited availability, and high cost. This study presents two alternatives of drug delivery systems, site-specific dendrimers and liposomes, with potential use as carriers of highly active drugs like pristimerin. Advances in the synthesis of site-specific dendrimers with bis-MPA as branching precursor and three key building blocks are reported, including compounds with folic acid (FA) to provide selectivity to folate receptors of cancer cells, pristimerin as cancer drug model, and fluorescein isothiocyanate (FITC) as fluorescent dye for future evaluation as cancer treatment. Five different dendrimer syntheses were reported, differing on their nucleus (bis-MPA or ethylene glycol) and the linker of folic acid (PEG 3350 and triethylene glycol TEG). Different purification techniques, such as normal-phase and reverse-phase column chromatography, size exclusion chromaography, dialysis and ultrafiltration, were probed according to their chemical characteristics and solubility. Characterization was carried out by FT-IR, MALDITOF-MS and/or NMR. Theoretical evidence generated in this work supports that FA-PEG750 and FA-PEG3350 dendrimers can be applied to selectively carry drugs and interact with cancer cell receptors (FR-α). Another drug delivery carrier and a viable alternative to the use of dendrimers is liposomes. Liposomes are the most mature drug carriers for passive and active targeting commercially available in oncology and other disease treatments. Dual Asymmetric Centrifugation (DAC) is a novel, fast, simple, and reproducible method for liposomal formulation screening, it facilitates liposomes preparation, and favors small diameters (<120 nm) in a small scale, with high drug encapsulation (EE). An optimization of DAC parameters (type and volume of buffer, beads size, centrifugation speed and time) was done to obtain liposomes of 70-80 nm with high encapsulation efficiency (71%). Also, dialysis was the best method for liposomes purification in comparison to Zeba-Spin and Micro-Spin size-exclusion columns, and can be applied to other drug delivery systems, like dendrimers. Over all, site-specific dendrimers demand a meticulous control on their structure during synthesis. Their preparation is time consuming and analytically complex. Meanwhile, theoretical evidence supports their potential to selectively carry drugs and interact with cancer cell receptors. Meanwhile, liposomes are a faster, easier and versatile alternative as drug delivery carriers of highly toxic drugs.
Sliding mode control for doubly fed induction machine(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2017-12-01)The objective of this thesis is to provide robust control methods for Doubly Fed Induction Generator (DFIG) mainly used for wind energy conversion systems (WECS). The controller deals with the power electronic stage needed to control the electric machine. Due to the high sensibility of this machine against disturbances the systems requires an accurate controller that allows to follow the stator power regulation despite the presence of disturbances. DFIG-based WECS are highly sensible to stator voltage perturbations because the stator is directly connected to the electric grid. The offered controller can regulate torque and reactive power even during low depth voltage dips by injecting negative sequence current without the necessity of sequence components separation of the rotor current. The proposed control system is based on Sliding-Mode Control (SMC), offering a fast-dynamic response and providing insensitivity to matched and bounded disturbance/uncertainties. The naturally discontinuous control signals of SMC can be used for direct switching of power electronic devices avoiding modulation and making the control system simple and robust. Furthermore, the controller does not depend on electric machine's parameters and it is decoupled by means of reference frame orientation. The switching frequency is analyzed using a frequency-domain method known as Tsypkin's locus, therefore it is possible to calculate a hysteresis width which will maintain the switching frequency inside safe operational range preventing to exceed the maximum switching frequency of semiconductor devices. The dynamic response of the control system under balanced and unbalanced voltage faults is enhanced by the application of demagnetizing current for fast natural flux clearance. The demagnetizing current is supplied using the original controller by modifying the torque and reactive power references. The operation of the controller and the ideas presented in this thesis have been verified through simulations made in National Instruments\textsuperscript LabVIEW and Matlab Simulink.
Nutraceutical properties of isolated starch, phytochemical compounds and bioactive peptides from pigmented chickpea cultivars influenced by cooking or germination process.(2017-12-14)Chickpea (Cicer arietinum L.) is the third most consumed pulse worldwide and a potential functional ingredient due to its nutritious composition and bioactive compounds. The aim of this investigation was to evaluate the potential of ten pigmented chickpea cultivars as ingredients in functional foods using cooking or germination to enhance bioactive compounds with health effect. The investigation was performed in five steps in order to evaluate the potential of ten chickpea cultivars differing in seed coat color (black, brown, green, red and cream). The first approach was to evaluate chickpea flours on the techno-functionality, chemical composition and nutritional properties related to starch and protein. The colored chickpeas flours showed higher content of bioactive compounds as total phenolics (TPC), β-glucans, resistant starch and higher protein digestibility corrected amino acid score (PDCAAS) compared with the commercial chickpea Blanco Sinaloa (cream seed coat). The limiting amino acids in chickpea flours were Trp, Thr and Met+Cys, whereas PDCAAS ranged from 0.59 to 0.82. Correlation analysis showed a possible interaction between TPC and starch which influenced thermal properties and starch digestion. The principal component analysis (PCA) showed several differences among the chemical compositions, starch digestions and seed protein qualities. Moreover, starch is the major component of chickpea seeds; therefore the wet-milled chickpea starches were studied on physicochemical, functional and in vitro starch digestion properties. The yield of chickpea starches ranged from 19.22 to 30.06%; total starch and amylose contents in the starches varied from 87.14 to 96.02% and 25.05 to 35.26%, respectively. Gelatinization properties (DSC, RVA) showed large differences among starches. The rapidly digestible (RDS), slowly digestible (SDS) and resistant (RS) gelatinized starch fractions varied from 56.34 to 59.15%, 33.22 to 35.43% and 6.42 to 9.22%, respectively. The predicted glycemic indexes (pGI) of native and gelatinized chickpea starches ranged from 65.52 to 66.10 and 74.39 to 75.74, respectively. A close correlation among the viscosity characteristics of isolated starches and the starch digestion fractions were found after PCA analysis. The starches properties were not dependent of the seed coat coloration of the cultivars. Overall, the results suggest that the starches of the array of chickpeas studied may hold a potential for the development of functional foods especially due to its functional properties, medium glycemic index, high SDS and RS contents. Additionally, the fate of phytochemicals during cooking and germination was evaluated. The 10 chickpea cultivars were soaked and cooked for the phytochemical evaluation. The compounds were identified by HPLC-IT-MS and quantified by HPLC-UV-ELSD. In Milán-Noris, A.K. 7 the raw chickpea seeds, eleven compounds were identified among cultivars; soyasaponin βg (m/z 1068) and biochanin A (m/z 285) were the principal compounds found. The thermal process caused significant (p≤0.05) reduction in flavonoids content but only minor lost of total saponins content. Besides, the effect of the germination process on phytochemicals of four chickpea cultivars (black, cream, green and red) was evaluated. Chickpea cultivars were germinated during five day at 24ºC. Eight isoflavonoids and soyasaponin βg were identified in germinated chickpea cultivars. However, genotype showed a significant effect on the profile and content of isoflavonoids during germination process. Phytochemical content increased significantly during germination process in all chickpea cultivars. Lastly, the anti-inflammatory effects of peptides and isoflavonoids associated to the unabsorbed digestion of protein concentrates from cooked or germinated (G.ICC5613 and Blanco Sinaloa) chickpea cultivars were investigated. The simulated gastrointestinal digestion released isoflavonoids and peptides (<10 kda=""><10kDa) in coocked and germinated samples whit adequate capacity to reduce nitric oxide production in induced- LPS macrophages. In both cultivars, the germinated samples showed higher reduction in nitric oxide by phenolics and peptides fraction. The digest from ferminated Blanco Sinaloa showed anti-inflammatory effects exerted by phenolics (IC50 : 0.22 mg/mL) and peptides (IC50: 1.92 mg protein/mL). The major phenolics were biochanin-A and formononetin. The further purification of the most active fraction produced peptides from legumin and vicilin. This is the first report of anti-inflammatory peptides from processed chickpea released by simulated gastrointestinal digestion. Overall, the results suggest that pigmented chickpea cultivars of this study showed a great potential as functional ingredients.
El texto literario como puesta en escena: seis obras de Mario Bellatin. Hacia la construcción de un modelo operativo del concepto de mise en scene.(2017-05-15)La presente disertación es un primer intento por identificar y abstraer los elementos que hacen del concepto de mise en scène un modelo semiótico operativo que pueda ser aplicado, como sugiere Mieke Bal, a cualquier práctica cultural de la vida cotidiana que involucre la subjetividad del espectador. El concepto de mise en scène proviene del teatro, y se refiere a la disposición de actores, atrezo y escenografía sobre el escenario de una producción teatral, o bien al entorno o escenario donde sucede algo. En su obra Travelling Concepts in the Humanities: a rough guide (2002), Mieke Bal propone interpretar la mise en scène no sólo como una práctica ligada a las artes escénicas, sino como un concepto teorético que pueda utilizarse como una herramienta para el análisis semiótico de prácticas culturales: As a concept, mise en scène provides an internal connection between narrative, still, visual imagery, and psychoanalysis, the latter of which is seen here as the theory par excellence of the formation of subjectivity but in need of a cultural basis beyond the individual. I will suggest that it can be useful –indeed, revealing- to speak of an aesthetic of mise en scène in enabling us to understand specific effects in a great variety of semiotic practices, ranking from everyday life to high art. (Bal, 109) El trabajo de Mieke Bal brinda ejemplos concretos provenientes de las artes visuales, la instalación e, incluso, los sueños, pero no hace una disección respecto a cuáles son los elementos, los pasos o el procedimiento que harían del concepto de mise en scène un modelo operativo para cualquier práctica semiótica