Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease

Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue-specific protein expression patterns. Global transcriptome analyses have suggested that >90% of human multiexon genes are alternatively spliced. Alterations in the splicing process cause missplicing events that lead to genetic diseases and pathologies, including various neurological disorders, cancers, and muscular dystrophies. In recent decades, research has helped to elucidate the mechanisms regulating alternative splicing and, in some cases, to reveal how dysregulation of these mechanisms leads to disease. The resulting knowledge has enabled the design of novel therapeutic strategies for correction of splicing-derived pathologies. In this review, we focus primarily on therapeutic approaches targeting splicing, and we highlight nanotechnology-based gene delivery applications that address the challenges and barriers facing nucleic acid-based therapeutics

Estudio comparativo de la cavidad de acceso radicular en conductos curvos con limas de níquel-titanio y taladros de acero inoxidable

El propósito de este estudio fue comparar la cantidad de dentina radicular removida y evaluar el mantenimiento de la forma del conducto tras la instrumentación de los dos tercios coronarios radiculares, utilizando instrumentos de acero inoxidable (taladros de Gates Glidden) y de níqueltitanio (limas GT Flare y limas Orifice Shaper). Un total de 42 dientes humanos extraídos con conductos radiculares curvos fueron divididos en tres grupos. Los conductos se instrumentaron mecánicamente usando taladros de Gates Glidden, limas Orifice Shaper o GT Flare con la técnica corono-apical. Este estudio se realizó siguiendo la técnica de Bramante modificada. Las secciones transversales de cada conducto fueron efectuadas a tres niveles horizontales diferentes (a 2, 4 y 6mm de su inicio en la cámara). Antes y después de la instrumentación fueron observados y fotografiados para luego ser medidos. A cada nivel se valoraron dos parámetros, el mantenimiento de la forma original del conducto y la cantidad de dentina removida. El análisis estadístico reveló que existían diferencias estadísticamente significativas (p<0,05) a nivel de los cortes a 4 y 6 mm en la cara interna del conducto; mientras que la preparación del mismo más prevalente fue excéntrica sin ensanchar todas las paredes del conducto

Groundwater characterization of a heterogeneous granitic rock massif for shallow tunneling

Shallow tunneling may encounter a number of problems, the most important of which is high water inflows in transmissive areas that are often associated with fractures or discontinuities. Moreover, research into shallow tunneling may be limited by the duration and cost of the civil engineering works. Two important aspects that are often overlooked are: variable groundwater behavior of faults (conduit, barrier, conduit-barrier), and role of groundwater connectivity between fractures that cross the tunnel and the rest of the rock massif. These two aspects should be taken into account in the geological and groundwater characterization to correct the tunnel design and minimize hazards. A geological study and a preliminary hydrogeological characterization (including a prior steady state investigation and cross bore-hole tests) were carried out in a granitic sector during the construction of Line 9 of the Barcelona subway (B-20 area). The hydrogeological conceptual model was constructed using a quasi-3D numerical model, and different scenarios were calibrated. Faults and dikes show a conduit-barrier behavior, which partially compartmentalized the groundwater flow. The barrier behavior, which is the most marked effect, is more prominent in faults, whereas conduit behavior is more notable in dikes. The characterization of groundwater media entailed a dewatering plan and changes in the tunnel course. This enabled us to construct the tunnel without any problems

Extensibilidad en pomadas. III. Nueva aportación a su determinación

Continuando el estudio de la extensibilidad en pomadas se propone modificar la definición de INDICE DE EXTENSIBILIDAD a «Valor del área media que determina la pomada en dos ensayos paralelos con 200 gramos de peso»; con ello se deja libertad para elegir el procedimiento de determinación del área, proponiéndose para ello un nuevo método basado en pesar un papel, se aconseja milimetrado «vegetal» por su regularidad, cortado siguiendo el perímetro determinado por la pomada

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses

Manejo correto da ordenha e qualidade do leite.

Muitas vezes o produtor se questiona quais as vantagens de adotar duas ou três ordenhas diárias. A resposta para esta pergunta tem que considerar uma série de fatores, tais como o custo da mão de obra, custos adicionais conseqüentes da realização de uma terceira ordenha (luz, material de limpeza, etc.), incremento na produção de leite obtido e o valor recebido pelo leite.bitstream/item/55815/1/CR27-02.pd

Analysis of the breakdown spot spatial distribution in Pt/HfO2/Pt capacitors using nearest neighbor statistics

The breakdown spot spatial distribution in Pt/HfO2/Pt capacitors is investigated using nearest neighbor statistics in combination with more conventional estimation methods such as the point-event and event-event distance distributions. The spots appear as a random point pattern over the top metal electrode and arise as a consequence of significant localized thermal effects caused by the application of high-voltage ramped stress to the devices. The reported study mainly involves the statistical characterization of the distances between each failure site and the nearest, second nearest,... kth nearest event and the comparison with the corresponding theoretical distributions for a complete spatial randomness (CSR) process. A method for detecting and correcting deviations from CSR based on a precise estimation of the average point intensity and the effective damaged device area is proposed. (C) 2013 AIP Publishing LLC

An approach to identify urban groundwater recharge

Evaluating the proportion in which waters from different origins are mixed in a given water sample is relevant for many hydrogeological problems, such as quantifying total recharge, assessing groundwater pollution risks, or managing water resources. Our work is motivated by urban hydrogeology, where waters with different chemical signature can be identified (losses from water supply and sewage networks, infiltration from surface runoff and other water bodies, lateral aquifers inflows, ...). The relative contribution of different sources to total recharge can be quantified by means of solute mass balances, but application is hindered by the large number of potential origins. Hence, the need to incorporate data from a large number of conservative species, the uncertainty in sources concentrations and measurement errors. We present a methodology to compute mixing ratios and end-members composition, which consists of (i) Identification of potential recharge sources, (ii) Selection of tracers, (iii) Characterization of the hydrochemical composition of potential recharge sources and mixed water samples, and (iv) Computation of mixing ratios and reevaluation of end-members. The analysis performed in a data set from samples of the Barcelona city aquifers suggests that the main contributors to total recharge are the water supply network losses (22%), the sewage network losses (30%), rainfall, concentrated in the non-urbanized areas (17%), from runoff infiltration (20%), and the Besòs River (11%). Regarding species, halogens (chloride, fluoride and bromide), sulfate, total nitrogen, and stable isotopes (&lt;sup&gt;18&lt;/sup&gt;O, &lt;sup&gt;2&lt;/sup&gt;H, and &lt;sup&gt;34&lt;/sup&gt;S) behaved quite conservatively. Boron, residual alkalinity, EDTA and Zn did not. Yet, including these species in the computations did not affect significantly the proportion estimations