Modified gold nanostructures for biological applications

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de Lectura: 22-09-2022This thesis has been focused on the functionalization of nanostructures for their use in drug delivery projects or the development of sensors of nucleic acids. In this regard, several linkers for the functionalization of nanostructures have been prepared, which have been designed to contain different reactive moieties, such as dithiolane or maleimide. Moreover, these derivatives have been prepared with stimuli-responsive bonds to ease the release of the drugs or oligonucleotides. Also, a new protocol to quantify the loading of oligonucleotides on gold nanoparticles was developed. In this case, after some manipulations of the samples, the oligonucleotides were quantified from the supernatant by absorbance spectrum using a corresponding calibration curve. In this line, the procedure to modify AuNPs has been optimized, achieving excellent results in a very short time (1 hour). With modified AuNPs, some applications have been developed, such as a novel catalytic complex and ligand for CuAAC fluorogenic reactions. Using the catalytic complex approach the best results were obtained with a PolyG of 12 nts. On the other hand, using the nanoparticles as ligand, the best results were obtained with the PolyT of 12 nts. Also, nanostructures as gold and albumin-based nanoparticles have been functionalized with different drugs (SN38, AZD8055 or Doxorubicin) and used for the treatment of cancer with excellent results. Modified gold nanoparticles have also been used as biosensors of nucleic acids involved in diseases, such as cancer or SARS-CoV-2. For the detection of cancer, a nanostructure containing a molecular beacon-like oligonucleotide with several modifications has been used to develop a sensor for Uveal melanoma. In this case, a double stimuli system has been implemented to control better the specificity and intensity of the system. For SARS-CoV-2 detection, two approaches have been developed. One approach is based on a molecular beacon-like structure containing a cholesterol modification, which in the presence of the target sequence, the nanoparticles aggregate. The other approach exploits a CRISPR/CAS-based Colorimetric nucleic Acid Detection (CASCADE) system that, in the presence of the target sequence, Cas13 nuclease activity was activated, leading to the aggregation of the nanoparticle

Las motivaciones de los árbitros de fútbol

En el trabajo empírico que a continuación presentamos hemos estudiado las razones por las que los árbitros de fútbol deciden comenzar, mantenerse, cambiar o dejar el arbitraje utilizando el Cuestionario MIMCA administrado a 121 árbitros de distintas categorías pertenecientes al Comité Técnico de árbitros de Fútbol de Las Palmas. Estos colegiados declaran que las principales razones por los que se iniciaron en la actividad arbitral fueron conseguir ciertas metas y divertirse, entre los motivos para seguir arbitrando citan los relacionados con el disfrute de la actividad, con la relación de grupo o con el conocimiento técnico del arbitraje, las razones que les podrían llevar a cambiar a otra actividad o abandonar el arbitraje de fútbol son las relacionadas con la falta de apoyo por parte de los dirigentes arbitrales, las interferencias con los estudios o el trabajo, y las lesiones.In this research we have studied the reasons for which soccer referees decide to begin, to stay, to change or to leave this activity. The Questionnaire MIMCA was administered to 121 referees belonging to different categories of Las Palmas Technical Committee Referees Soccer. These referees declare that the main reasons for which they began in the refereeing activity were «to succeed in getting certain goals» and «to have a good time»; on the other hand, among the reasons to continue are related with the enjoyment of the activity, with the group relationship or with the technical knowledge of the officiating. Lastly, the reasons argued to change to another activity or to abandon soccer officiating are those related with the lack of support on the part of the refereeing leaders, the interferences with the studies or the work, and the injuries

Registro de tapir centroamericano (Tapirus bairdii) con cámaras-trampa en la sierra Madre de Oaxaca, México

ResumenEn este trabajo se presenta evidencia del tapir centroamericano (Tapirus bairdii) obtenida en la sierra Norte de Oaxaca por medio de cámaras-trampa durante marzo y abril de 2012, confirmando su presencia en esta región.AbstractThis paper presents evidence of the Baird's tapir (Tapirus bairdii) obtained in the Sierra Norte de Oaxaca by camera traps in March and April 2012, confirming its presence in this region

PODERES POLÍTICOS LOCALES, VIOLENCIA Y CONFIGURACIÓN DEL ESTADO: EL CASO DE FERNANDO ALMARIO EN EL CAQUETÁ

El Caquetá ha sido uno de los departamentos más golpeados por el conflicto armado colombiano, principalmente por ser retaguardia histórica de las FARC. Esta situación ha condicionado el ejercicio de la actividad política haciendo que los actores políticos tengan que adaptarse a la presencia de poderes armados como el insurgente, los paramilitares y el mismo estado. En este proceso violento se ha configurado el Estado regional

On the solution of strong nonlinear oscillators by applying a rational elliptic balance method

AbstractA rational elliptic balance method is introduced to obtain exact and approximate solutions of nonlinear oscillators by using Jacobi elliptic functions. To illustrate the applicability of the proposed rational elliptic forms in the solution of nonlinear oscillators, we first investigate the exact solution of the non-homogenous, undamped Duffing equation. Then, we introduce first and second order rational elliptic form solutions to obtain approximate solutions of two nonlinear oscillators. At the end of the paper, we compare the numerical integration values of the angular frequencies with approximate solution results, based on the proposed rational elliptic balance method

Enfermedades de depósito de glucógeno: informe de dos casos en la ciudad de Cartagena

Objective: to report two cases of children with type Ia glycogen storage disease compatible with Von Gierke disease, suspected in the presence of findings such as hepatomegaly, nephromegaly, hypoglycemia, and stunted growth. Method: Presentation of the clinical records of two patients referred to the diagnostic unit of innate errors of metabolism of the Faculty of Medicine in Universidad de Cartagena. Results: The first case reported was a child who debuted with acute cyanosis without widespread neurological deficit when he was eleven months old, followed by hepatomegaly at two years of age. At 4 years of age, symptoms reappeared with similar characteristics: hypoglycemia, growth failure, and persistent hepatomegaly detected on physical examination. With the precedent that an older brother that presented similar symptoms was suspected of glycogen storage disease, a biopsy was performed and confirmed liver glycogen storage with normal structure. The patient’s treatment was modification of dietary habits (small, frequent feedings during the day) and cornstarch. The second event was the older brother who consulted for the first time when he was 18 months old due to prolonged diarrhea. Hepatomegaly was documented by ultrasound study without kidney compromise and no hypoglycemia was found. Recommendations: It is necessary for the entire health team to be trained to detect rare diseases such as glycogen storage disease. If they make early diagnoses and establish support groups for interdisciplinary management of such diseases, they may change the prognosis and quality of life of these children. Objetivo: Comunicar dos casos de niños con glucogenosis compatibles con el tipo Ia o enfermedad de Von Gierke, que se debe sospechar ante la presencia de hallazgos como hepatomegalia, nefromegalia, hipoglicemia y talla baja. Método: Presentación de las historias clínicas de dos pacientes remitidos a la unidad de diagnóstico de errores innatos del metabolismo de la Facultad de Medicina de la Universidad de Cartagena. Resultados: El primer caso es un niño que a los once meses de edad hizo crisis de cianosis generalizada sin déficit neurológico, y a los dos años tuvo hepatomegalia. A los cuatro años vuelve a presentar el mismo cuadro con iguales características más hipoglicemia y al examen físico talla baja y persistencia de la hepatomegalia. Con el antecedente de un hermano mayor que mostró sintomatología similar se sospechó glucogenosis; se tomó una biopsia de hígado y se confirmó depósito de glucógeno hepático de estructura normal. Se manejó con dieta fraccionada y fécula de maíz. El segundo caso se trata del hermano mayor quien consultó por primera vez a los 18 meses de edad con diarrea prolongada. Se documentó hepatomegalia por estudio ecográfico sin compromiso renal y nunca cursó con hipoglicemia. Recomendaciones: Es necesario que todo el equipo de salud esté capacitado para descubrir enfermedades raras como la glucogenosis. Esto puede cambiar el pronóstico y calidad de vida de los niños si se hace un diagnóstico precoz y se establecen grupos de apoyo interdisciplinarios en el manejo de este grupo de enfermedades

Características epidemiológicas del cáncer de piel en un hospital de altura Huancayo 2011-2013

Objetivo: Identificar las características epidemiológicas relevantes en pacientes con cáncer de piel en un hospital de altura, atendidos en el Consultorio de Dermatología del Hospital Regional Docente Clínico Quirúrgico Daniel Alcides Carrión de Huancayo, durante los años 2011,2012,2013. Material y Métodos: Se realizó un estudio descriptivo, retrospectivo, transversal, analítico, en 141 pacientes con cáncer de piel, 85 mujeres, 56 varones, con un promedio de edad de 67 años. Resultados: Las características demográficas más relevantes se dio en mujeres, entre los 50 y 74 años, agricultoras, con instrucción primaria expuestas al sol diariamente sin protección, Z de Gauss<0.05. Las características clínicas fueron: Aumento de tamaño tumoral, promedio 1,25 cm, la ulceración, piel tipo IV, tiempo de enfermedad de hasta 12 meses, 92.9% sin antecedentes de cáncer de piel, se localizó preferentemente en áreas foto expuestas, cabeza, cara y zonas acrales: manos, pies, dedos, el lentigo y la queratosis solar fueron las lesiones más asociadas. Los canceres más frecuentes fueron: Carcinoma Basocelular (49.6%), Melanoma Maligno (25.5%), Carcinoma Epidermoide (18.4%) y otros (6.4%.). Conclusiones: Las características epidemiológicas relevantes demográficas y clínicas permiten la aparición y el incremento del cáncer de piel con una frecuencia de 47 casos al año y una incidencia de 3.83 casos por mil.Tesi

“Unos grises muy berracos” poder político local y configuración del estado en el Caquetá, 1980-2006

El Caquetá ha sido uno de los departamentos más golpeados por el conflicto armado colombiano, principalmente por ser retaguardia histórica de las FARC. Esta situación ha condicionado el ejercicio de la actividad política haciendo que los actores políticos tengan que adaptarse a la presencia de poderes armados como el insurgente, los paramilitares y el mismo estado. En este proceso violento se ha configurado el Estado regional. Esta investigación social se centra en el territorio del Caquetá y comprende los años que van desde el auge de los movimientos de izquierda en la década de los ochentas, hasta su declive, la militarización de la insurgencia y la aparición de grupos paramilitares.Abstract. Caquetá has been one of the provinces most affected by the Colombian armed conflict, mainly because the historical presence of the FARC. This situation has conditioned the political activities because the political actors have to adapt to the presence of armed powers as the insurgent, paramilitary and the state. This same violent process has configured the Regional State. This research focuses on the territory of Caquetá and includes the years since the rise of leftist movements in the eighties, until its decline, the militarization of the insurgency and the emergence of paramilitary groups in 1998-2006.Maestrí

Influence of Controlled Cooling in Bimodal Scaffold Fabrication Using Polymers with Different Melting Temperatures

Abstract: The combination of different materials and capabilities to manufacture at several scales open new possibilities in scaffold design for bone regeneration. This work is focused on bimodal scaffolds that combine polylactic acid (PLA) melt extruded strands with polycaprolactone (PCL) electrospun fibers. This type of bimodal scaffold offers better mechanical properties, compared to the use of PCL for the extruded strands, and provides potential a means for controlled drug and/or growthfactordeliverythroughtheelectrospunfibers. Thetechnologiesoffuseddepositionmodeling (FDM) and electrospinning were combined to create 3D bimodal constructs. The system uses a controlled cooling system allowing the combination of polymers with different melting temperatures to generate integrated scaffold architecture. The thermoplastic polymers used in the FDM process enhance the mechanical properties of the bimodal scaffold and control the pore structure. Integrated layers of electrospun microfibers induce an increase of the surface area for cell culture purposes, as well as potential in situ controlled drug and/or growth factor delivery. The proposed bimodal scaffolds (PLA extruded strands and PCL electrospun fibers) show appropriate morphology and better mechanical properties when compared to the use of PCL extruded strands. On average, bimodal scaffolds with overall dimensions of 30×30×2.4 mm3 (strand diameter of 0.5 mm, strand stepover of 2.5 mm, pore size of 2 mm, and layer height of 0.3 mm) showed scaffold stiffness of 23.73 MPa and compression strength of 3.85 MPa. A cytotoxicity assay based human fibroblasts showed viability of the scaffold materials. Keywords: tissue engineering; bone; bimodal scaffolds; fused deposition modeling; electrospinning; hybrid manufacturing proces