Delivery of nucleic acids for cancer gene therapy: overcoming extra- and intra-cellular barriers

The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective nonviral delivery systems can be applied successfully in oncology. Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration.

Structural and Electrical Investigation of C 60 –Graphene Vertical Heterostructures

Graphene, with its unique electronic and structural qualities, has become an important playground for studying adsorption and assembly of various materials including organic molecules. Moreover, organic/graphene vertical structures assembled by van der Waals interaction have potential for multifunctional device applications. Here, we investigate structural and electrical properties of vertical heterostructures composed of C60 thin film on graphene. The assembled film structure of C60 on graphene is investigated using transmission electron microscopy, which reveals a uniform morphology of C60 film on graphene with a grain size as large as 500 nm. The strong epitaxial relations between C60 crystal and graphene lattice directions are found, and van der Waals ab initio calculations support the observed phenomena. Moreover, using C60-graphene heterostructures, we fabricate vertical graphene transistors incorporating n-type organic semiconducting materials with an on/off ratio above 3 × 10(3). Our work demonstrates that graphene can serve as an excellent substrate for assembly of molecules, and attained organic/graphene heterostructures have great potential for electronics applications.

Radiopacity and Chemical resistance of Elastomer-Barium sulphate nanocomposites

The Human race of our century is in gluttonous search for novel engineering products which led to a skyrocketed progress in research and fabrication of filled polymers. Recently, a big window has been opened up for speciality polymers especially elastomers with promising properties. Among the many reasons why rubbers are widely used in the process industries, three are considered as important. Firstly, rubbers operate in a variety of environments and possess usable ranges of deformity and durability and can be exploited through suitable and more or less conventional equipment design principles. Secondly, rubber is an eminently suitable construction material for protection against corrosion in the chemical plant and equipment against various corrosive chemicals as, acids and alkalies and if property tailored, can shield ionising radiations as X-rays and gamma rays in medical industry, with minimum maintenance lower down time, negligible corrosion and a preferred choice for aggressive corroding and ionising environment. Thirdly, rubber can readily and hastily, and at a relatively lower cost, be converted into serviceable products, having intricate shapes and dimensions. In a century’s gap, large employment of flexible polymer materials in the different segments of industry has stimulated the development of new materials with special properties, which paved its way to the synthesis of various nanoscale materials. At nano scale, one makes an entry into a world where multidisciplinary sciences meet and utilises the previously unapproached infinitesimal length scale, having dimension which measure upto one billionth of a meter, to create novel properties. The nano fillers augment the elastomers properties in an astonishing fashion due to their multifunctional nature and unprecedented properties have been exhibited by these polymer-nanocomposites just to beat the shortcomings of traditional micro composites. The current research aims to investigate the possibility of using synthesised nano barium sulphate for fabricating elastomer-based nanocomposites and thereby imparting several properties to the rubber. In this thesis, nano materials, their synthesis, structure, properties and applications are studied. The properties of barium sulphate like chemical resistance and radiopacity have been utilized in the present study and is imparted to the elastomers by preparing composites.

Development of a Wireless MEMS Multifunction Sensor System and Field Demonstration of Embedded Sensors for Monitoring Concrete Pavements, TR-637, 2016

Pavements tend to deteriorate with time under repeated traffic and/or environmental loading. By detecting pavement distresses and damage early enough, it is possible for transportation agencies to develop more effective pavement maintenance and rehabilitation programs and thereby achieve significant cost and time savings. The structural health monitoring (SHM) concept can be considered as a systematic method for assessing the structural state of pavement infrastructure systems and documenting their condition. Over the past several years, this process has traditionally been accomplished through the use of wired sensors embedded in bridge and highway pavement. However, the use of wired sensors has limitations for long-term SHM and presents other associated cost and safety concerns. Recently, micro-electromechanical sensors and systems (MEMS) and nano-electromechanical systems (NEMS) have emerged as advanced/smart-sensing technologies with potential for cost-effective and long-term SHM. This two-pronged study evaluated the performance of commercial off-the-shelf (COTS) MEMS sensors embedded in concrete pavement (Final Report Volume I) and developed a wireless MEMS multifunctional sensor system for health monitoring of concrete pavement (Final Report Volume II).

Books for asset management in hospitals in Seville.

Hospitals from ancient Seville had an important heritage for survival of the institution and its patients. In order to keep this heritage, the officialdom settled down several control mechanisms that would serve to manage a profitable management of their income and rights. For this purpose, they developed devising instruments able to preserve their possessions and put them into operation. This article attempts to identify the defining elements of these books, called “protocolos de bienes” (protocols goods), indicating their characteristics and evolution from archaic models until the final form. This final form was reached late sixteenth and early seventeenth century, at which time devoted use main codex of hospitality. To do this, we used the documentary collec-tions of Seville, preserved in different archives of the city, from where they have taken several significant examples showing the changes that occurred in both its internal structure and its mate-rials manufacturing, underlining the participation of official, booksellers, illuminators and calligraphers. Similarly, it has high-lighted the multifaceted and multifunctional character of this ins-titutions that became also a corporate identity. The multiplicity of hospitals in Sevilla had different types and features of protocols, which were modificated according to the different needs of each institution.

#srynotfunny : Communicative functions of hashtags on Twitter

This study investigates various communicative functions served by hashtags in written communication on Twitter from a linguistic pragmatic perspective. A tweet containing a hashtag links to, and is integrated into, a timeline of other tweets containing the same hashtag. Thus, hashtags are by default categorizing or organizing; a user of Twitter may add the tag #food to their tweet to integrate it into a general conversation about this topic. However, this study demonstrates that hashtags are also used creatively to perform other communicative functions. In the data presented, hashtags are employed as complexly multifunctional linguistic devices for, among other things, structuring information, playing games, and engaging in reflexive meta-commentary. Notably, while pragmatic methodology is typically applied to speech, this study indicates that a traditional speech acts framework may be profitably applied to written communication in new media.

Molecular cloning and expression of leptin in gray and harbor seal blubber, bone marrow, and lung and its potential role in marine mammal respiratory physiology

Leptin is a multifunctional hormone, produced predominantly in adipocytes. It regulates energy balance through its impact on appetite and fat metabolism, and its concentration indicates the size of body fat reserves. Leptin also plays a vital role in stretch-induced surfactant production during alveolar development in the fetus. The structure, expression pattern, and role of leptin have not previously been explored in marine mammals. Phocid seals undergo cyclical changes in body composition as a result of prolonged fasting and intensive foraging bouts and experience rapid, dramatic, and repeated changes in lung volume during diving. Here, we report the tissue-specific expression pattern of leptin in these animals. This is the first demonstration of leptin expression in the lung tissue of a mature mammal, in addition to its expression in the blubber and bone marrow, in common with other animals. We propose a role for leptin in seal pulmonary surfactant production, in addition to its likely role in long-term energy balance. We identify substitutions in the phocine leptin sequence in regions normally highly conserved between widely distinct vertebrate groups, and, using a purified seal leptin antiserum, we confirm the presence of the leptin protein in gray seal lung and serum fractions. Finally, we report the substantial inadequacies of using heterologous antibodies to measure leptin in unextracted gray seal serum.

La enseñanza por competencias

La enseñanza por competencias, de manera semejante con el conjunto de actividades académicas que realizan los centros de educación superior, poseen una compleja estructura de atributos, tales como: conocimientos, actitudes, valores y habilidades. Bajo estas consideraciones, entendemos que los docentes de las universidades deberían de orientar entre otras, sus preocupaciones académicas, para impulsar el cambio de enfoque educativo que viabilice la construcción de puentes, para modificar favorablemente el desfase existente entre lo que demanda el sector productivo y la práctica cotidiana en los salones de clase de las universidades. Las universidades como entes responsables de la formación profesional de los(as) ciudadanos(as) de la sociedad, deben velar por coadyuvar a insertar al mercado laboral a sus graduados con una mentalidad flexible, dinámica, creativos, y con visión de futuros conocedores de las realidades de mercado, con una formación integral, plurifuncionales y versados en las herramientas tecnológicas de punta, con el propósito que sean competentes en sus labores específicas. Abstract Teaching through competencies as well as the academic activities carried out in universities, has complex structures as attributes such as: knowledge, values, and abilities. Based on this consideration, we understand that university professors should guide their academic interest towards a change on the teaching approach, allowing the building of bridges that can positively modify the existing gap between the demands of the productive sector on the current practice in the university classroom. The Universities are responsible for the professional education of the members of society and should watch over to help introduce graduates in the labor market. These graduates should characterized by a flexible, dynamic, and creative mind, capable of future projections, as acquainted with the characteristics of the real market, with a well rounded formation, multifunctional and versed in the leading technological tools; so they can be competent on their specific tasks.

Bioanalytical applications of microfluidic devices

The first part of the thesis describes a new patterning technique--microfluidic contact printing--that combines several of the desirable aspects of microcontact printing and microfluidic patterning and addresses some of their important limitations through the integration of a track-etched polycarbonate (PCTE) membrane. Using this technique, biomolecules (e.g., peptides, polysaccharides, and proteins) were printed in high fidelity on a receptor modified polyacrylamide hydrogel substrate. The patterns obtained can be controlled through modifications of channel design and secondary programming via selective membrane wetting. The protocols support the printing of multiple reagents without registration steps and fast recycle times. The second part describes a non-enzymatic, isothermal method to discriminate single nucleotide polymorphisms (SNPs). SNP discrimination using alkaline dehybridization has long been neglected because the pH range in which thermodynamic discrimination can be done is quite narrow. We found, however, that SNPs can be discriminated by the kinetic differences exhibited in the dehybridization of PM and MM DNA duplexes in an alkaline solution using fluorescence microscopy. We combined this method with multifunctional encoded hydrogel particle array (fabricated by stop-flow lithography) to achieve fast kinetics and high versatility. This approach may serve as an effective alternative to temperature-based method for analyzing unamplified genomic DNA in point-of-care diagnostic.

Interference lithography for optical devices and coatings

Interference lithography can create large-area, defect-free nanostructures with unique optical properties. In this thesis, interference lithography will be utilized to create photonic crystals for functional devices or coatings. For instance, typical lithographic processing techniques were used to create 1, 2 and 3 dimensional photonic crystals in SU8 photoresist. These structures were in-filled with birefringent liquid crystal to make active devices, and the orientation of the liquid crystal directors within the SU8 matrix was studied. Most of this thesis will be focused on utilizing polymerization induced phase separation as a single-step method for fabrication by interference lithography. For example, layered polymer/nanoparticle composites have been created through the one-step two-beam interference lithographic exposure of a dispersion of 25 and 50 nm silica particles within a photopolymerizable mixture at a wavelength of 532 nm. In the areas of constructive interference, the monomer begins to polymerize via a free-radical process and concurrently the nanoparticles move into the regions of destructive interference. The holographic exposure of the particles within the monomer resin offers a single-step method to anisotropically structure the nanoconstituents within a composite. A one-step holographic exposure was also used to fabricate self- healing coatings that use water from the environment to catalyze polymerization. Polymerization induced phase separation was used to sequester an isocyanate monomer within an acrylate matrix. Due to the periodic modulation of the index of refraction between the monomer and polymer, the coating can reflect a desired wavelength, allowing for tunable coloration. When the coating is scratched, polymerization of the liquid isocyanate is catalyzed by moisture in air; if the indices of the two polymers are matched, the coatings turn transparent after healing. Interference lithography offers a method of creating multifunctional self-healing coatings that readout when damage has occurred.

Synteza, modyfikacja powierzchni i charakterystyka fizykochemiczna wielofunkcyjnych nanomateriałów luminescencyjnych zawierających jony pierwiastków ziem rzadkich

Wydział Chemii: Zakład Ziem Rzadkich

Challenges for a shared European countryside of uncertain future. Towards a modern community based landscape perspective

This paper addresses current changes in the highly diverse European landscape, and the way these transitions are being treated in policy and landscape management in the fragmented, heterogeneous and dynamic context of today’s Europe. It appears that intersecting driving forces are increasing the complexity of European landscapes and causing polarising developments in agricultural land use, biodiversity conservation and cultural landscape management. On the one hand, multifunctional rural landscapes, especially in peri-urban regions, provide services and functions that serve the citizens in their demand for identity, support their sense of belonging and offer opportunities for recreation and involvement in practical landscape management. On the other hand, industrial agricultural production on increasingly large farms produces food, feed, fibre and energy to serve expanding international markets with rural live ability and accessibility as a minor issue. The intermediate areas of traditionally dominant small and family farms in Europe seem to be gradually declining in profitability. The paper discusses the potential of a governance approach that can cope with the requirement of optimising land-sharing conditions and community-based landscape development, while adapting to global market conditions.

Effects of supplemental osteopontin on intestinal development and serum antibody responses to rotavirus vaccination in piglets

Milk contains numerous bioactive substances including immunoglobulins, cytokines, growth factors and components that exert antibiotic and prebiotic activity (Field, 2005). Little is known about the biological effects of individual milk bioactives, despite the fact that natural milk improves intestinal development and immune system functions in neonates (Donovan et al., 1994; Field, 2005) relative to milk formula. Characterization of the biological effects of such components is important for optimal production of infant milk formulas to be used when mother’s milk is not available. Milk components with preliminary evidence of positive effects on the intestinal growth and mucosal immunity include osteopontin (OPN). Osteopontin is a phosphorylated acidic glycoprotein expressed by a number of different immune and non-immune cells and tissues (Sodek et al., 2000). It is also present in body fluids including blood, bile and milk (Sodek et al., 2000). Osteopontin is a multifunctional protein that is implicated in a wide number of biological processes including cell survival, bone remodeling, and immune modulatory functions (Sodek et al., 2000). Furthermore, Schack and colleagues (2009) demonstrated that the concentration of OPN in human milk is considerably higher than in bovine milk and infant formulas. Taken together, it is likely that OPN plays a role in the early development of gastrointestinal tract and mucosal immune responses in infants. Since the neonatal pig shares anatomical, physiological, immunological, and metabolic similarities with the human infants (Moughan, et al., 1992), they were selected as the animal model in our studies. Our first aim was to investigate the effects of OPN on piglet intestinal development. Newborn, colostrum-deprived piglets (n=27) were randomized to receive three treatments: formula with bovine OPN (OPN; 140 mg/L); formula alone (FF); or sow reared (SR) for 21 days. Body weight, intestinal weight and length, mucosal protein and DNA content, disaccharidase activity, villus morphology, and crypt cell proliferation were measured. Statistical significance was assigned at P<0.05. No significant effects of OPN were observed for body weight, intestinal weight and length. Mucosal protein content of SR piglets was lower than FF and OPN piglets in the duodenum, but higher than FF and OPN piglets in the ileum. No significant effects of diet in mucosal DNA content were detected for the three regions of the small intestine. Lactase and sucrase activities of SR piglets were higher than the two formula-fed groups in the duodenum, lower in the ileum. No significant effects of diet on lactase and sucrase activities were noted between two formula-fed groups in the duodenum and ileum. Jejunal lactase activity of FF piglets was higher than SR piglets, whereas no significant effect of diet was observed in jejunal sucrase activity among the three groups. Duodenal and ileal villus height and villus area of SR piglets were lower than two formula-fed groups, while OPN piglets did not differ from FF piglets. There was a significant effect of diet (P<0.0001) on jejunal crypt cell proliferation, with proliferation in OPN piglets being intermediate between that of FF and SR. In summary, supplemental OPN increased jejunal crypt cell proliferation, independent of evident morphological growth, and had a minor impact on disaccharidase activity in the small intestine of neonatal piglets. Rotavirus (RV) is the most common viral cause of severe gastroenteritis in infants and young children worldwide (Parashar et al., 2006). Maeno et al. (2009) reported that OPN knockout (OPN-KO) suckling mice were more susceptible to RV infection compared to wild-type (WT) suckling mice. To detect the role of OPN in intestinal immune responses of neonates, the goal of the second study was to evaluate whether supplemental OPN influenced the serum antibody responses to RV vaccination in neonatal piglets. Newborn, colostrum-deprived piglets were randomized into two dietary groups: formula with bovine OPN (OPN; 140 mg/L) and formula alone (FF) for 35 days. On d7, piglets in each dietary group were further randomized to receive rotavirus (RV) vaccination (Rotarix®) (FF+RV and OPN+RV) or remained non-vaccinated (FF+NV and OPN+NV). Booster vaccination was provided on d14. Blood samples were collected on d7, 14, 21, 28 and 35. RV-specific serum immunoglobulin (Ig) G, IgA, IgM and total serum IgG, IgA, IgM were measured by ELISA. Statistical significance was assigned at P<0.05, with trends reported as P<0.10. Body weight gain was unaffected by diet and/or vaccination. No significant effect of oral OPN supplementation was observed for RV-specific antibody responses and total Igs levels. After the combination of dietary groups, RV piglets had significantly higher RV-specific IgM concentrations compared to NV piglets. Although there were higher means of RV-specific IgG and RV-specific IgA concentrations in RV group than their counterparts in NV group, the difference did not reach statistical significance. RV-specific IgM reached a peak at d7 post booster vaccination (PBV), whereas the RV-specific IgG and IgA peaked later at PBV 14 or 21. Total Igs were unaffected by RV vaccination but were significantly increased over time, following similar pattern as RV-specific Igs. In summary, neonatal piglets generated weak antibody responses to RV vaccination. Supplemental OPN did not enhance RV-specific serum antibody responses and total serum Igs levels in neonatal piglets with or without RV vaccination. In conclusion, we observed normal developmental changes in the small intestine and serum Igs levels in neonatal piglets over time. Oral OPN supplementation showed minimal impacts on intestinal development and no effect on serum Igs levels. The role of supplemental OPN on the growth and development of infants is still inconclusive. Future studies should measure other physiological and immunological parameters by using different models of vaccination or infection.

Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: a high-sensitivity microfluidic tool

The poor heating efficiency of the most reported magnetic nanoparticles (MNPs), allied to the lack of comprehensive biocompatibility and haemodynamic studies, hampers the spread of multifunctional nanoparticles as the next generation of therapeutic bio-agents in medicine. The present work reports the synthesis and characterization, with special focus on biological/toxicological compatibility, of superparamagnetic nanoparticles with diameter around 18 nm, suitable for theranostic applications (i.e. simultaneous diagnosis and therapy of cancer). Envisioning more insights into the complex nanoparticle-red blood cells (RBCs) membrane interaction, the deformability of the human RBCs in contact with magnetic nanoparticles (MNPs) was assessed for the first time with a microfluidic extensional approach, and used as an indicator of haematological disorders in comparison with a conventional haematological test, i.e. the haemolysis analysis. Microfluidic results highlight the potential of this microfluidic tool over traditional haemolysis analysis, by detecting small increments in the rigidity of the blood cells, when traditional haemotoxicology analysis showed no significant alteration (haemolysis rates lower than 2 %). The detected rigidity has been predicted to be due to the wrapping of small MNPs by the bilayer membrane of the RBCs, which is directly related to MNPs size, shape and composition. The proposed microfluidic tool adds a new dimension into the field of nanomedicine, allowing to be applied as a highsensitivity technique capable of bringing a better understanding of the biological impact of nanoparticles developed for clinical applications.

Anteproyecto arquitectónico diseño de un conjunto de residencias universitarias

El presente trabajo de grado previo a la obtención del título de Arquitecto, presenta una propuesta de diseño de un conjunto de residencias universitarias, un servicio y equipamiento que la ciudad evidencia que ya lo necesita. El anteproyecto no sólo está dirigido a la edificación de vivienda para estudiantes sino como un espacio apto para actividades académicas, espacios destina¬dos a dar un lugar para descansar y a su vez para estudiar y prepararse para la próxima vida profesional que le tocará vivir. La edificación está resuelta en base a módulos habitacionales para uno, dos, tres o cuatro usuarios, y otro destinado a un usuario con capacidades diferentes. Los espacios son multifuncionales y versátiles, ayudando así a las diversas tareas que podrían desarrollar los usuarios en las distintas carreras profesionales. Además el proyecto prevé la ubicación de espacios y servicios complementa¬rios indispensables para facilidad de los usuarios: cajeros, salas de estudio, cafetería, gimnasio, etc. Finalmente el proyecto se localizó de tal manera que quedará a distancias equitativas de las princi¬pales universidades de Cuenca.