A large CRISPR-induced bystander mutation causes immune dysregulation.

A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice to delete a ~360 bp intronic enhancer, here we discovered a founder line that had marked immune dysregulation caused by a 24 kb tandem duplication of the sequence adjacent to the on-target deletion. Our results suggest unintended repair of on-target genomic cuts can cause pathogenic bystander mutations that escape detection by routine targeted genotyping assays

High-speed railway tunnel monitoring using point, long gauge and distributed strain and temperature fiber optic sensors

La monitorización de estructuras es una rama de la ingeniería estructural que está captando mucha atención actualmente. Las deformaciones y temperaturas son, habitualmente, los parámetros monitorizados porque son los que mejor representan el comportamiento estructural. De todos los tipos de sensores existentes, los basados en fibra óptica resultan especialmente interesantes debido a sus ventajas comparativas sobre los sensores convencionales. En este artículo se presentan los trabajos de monitorización de la estructura de un túnel artificial de Alta Velocidad construido en Mogente (España) mediante tres tipos de sensores ópticos desarrollados por los autores. Los resultados de los sensores se comparan con los proporcionados por un modelo teórico de elementos finitos. Esta comparación confirma que los sensores reproducen notablemente bien la pauta general de comportamiento de la estructura, incluso con pequeños niveles de deformación (5µε). Por último, el artículo discute el comportamiento de los sensores, sus mediciones y sus campos de aplicación.Structural Health Monitoring (SHM) is presently having a great development. Strains and temperatures are usually the key parameters to be monitored due to their relevance when explaining structural behavior. Several types of sensors are used in SHM, but fiber optic sensors are especially interesting due to their advantages with respect to conventional sensors. In this paper, the monitoring of a high-speed train tunnel recently built in Spain using three types of fiber optic sensors developed by the authors is shown. Results given by the sensors are compared to those provided by a theoretical model built using FEM. Comparison of measurements and theoretical results confirms that the sensors reproduced remarkably well the general patterns of the tunnel structural behavior, even when strains are relatively small (around 5 µε). Finally, the paper discusses the behavior of the sensors, their measurements and their field of application which is useful for researchers and practitioners.Los autores quieren agradecer a la Universitat Politècnica de València, al Ministerio de Educación por la financiación recibida a través del proyecto BIA2011-27104 y al Ministerio de Fomento por el apoyo recibido a través del Proyecto SOPROMAC (P41/08)

Deterioro y Conservación de Materiales Geológicos del Patrimonio

La actividad investigadora desarrollada por el Instituto de Geociencias en el campo del deterioro y conservación de materiales geológicos parten siempre de la caracterización petrológica y mineralógica de los materiales utilizados en el patrimonio. Se utilizan técnicas petrográficas, geoquímicas y petrofísicas, con apoyo de técnicas mineralógicas y cristalográficas para establecer su estado de conservación y definir las causas de alteración. Los avances del conocimiento se dirigen a establecer la interrelación entre las propiedades de los materiales pétreos, tanto de superficie como internas, con el medio ambiente. Desde la petrología y la mineralogía experimental se abordan problemas referentes a la mejora de productos de conservación, en base a sus características petrofísicas y a su comportamiento en ambientes agresivos. Con estas investigaciones se pueden determinar las técnicas de conservación más eficaces e idóneas para cada tipo de material y ambientes a los que se encuentran sometidos los materiales. Por lo tanto, la investigación se inicia con la caracterización, continúa estableciendo las causas de deterioro y, por último, ofrece soluciones para mejorar la calidad de los materiales e incrementar su durabilidad, desarrollando técnicas de conservación que han generado patentes

Considerações sobre o final de análise

Na comunidade psicanalítica, o tema do final de análise sempre permeou a discussão técnico-teórica. Na Escola Lacaniana, especificamente, esse tema adquiriu especial interesse a partir do momento em que Lacan propôs um novo dispositivo de transmissão, o passe, para que novos analistas testemunhassem sobre a sua passagem à condição de analista. Desde então, diferentes concepções lacanianas sobre o final de análise têm surgido e produzido nova discussão. É nesse contexto que este artigo visa a contribuir com esse debate atual, discutindo diversos aspectos, tais como a eficácia da análise, as vicissitudes da transferência e da pulsão no processo analítico, a re-análise e o dispositivo do passe. Para tanto, parte, inicialmente, das questões levantadas pelo texto freudiano “Análise terminável e interminável” e as discute à luz dos desenvolvimentos teóricos realizados por analistas lacanianos. Após apresentar diferentes concepções sobre o final de análise, o artigo defende que há, nesse processo, um ponto de irredutibilidade, a partir do qual se é convocado a uma produção singular

Marine Aerosol Weathering of Mediterranean Calcarenite Stone: Durability of Ethyl Silicate, Nano Ca(OH)2, Nano SiO2, and Nanostructured Consolidating Products

Calcarenite stone samples from a historic building (Bizerte, Tunisia) were collected and treated under different environmental conditions with several consolidating products: alkoxysilane (ethyl silicate), a surfactant-templated novel sol–gel, Ca(OH)2, and SiO2 nanoparticles. These were subjected to marine aerosol accelerated aging cycles and studied by several non-destructive tests and techniques to assess the stability of the products. Results show that weathering caused by salt crystallization is not inhibited but it is slowed down due to the enhancement of superficial mechanical properties (surface cohesion and micro-hardness) achieved after one month of treatments application. A high or low relative humidity of the consolidation environment significantly affects the final mechanical and aesthetical physical properties and therefore conditions the durability of the treated substrates, even producing higher damage than observed in the blank specimens, depending on the product

Intraoperative Portal Flow of Less Than 1 Liter per Minute After Orthotopic Liver Transplantation Is Not Associated Per Se With an Increased Rate of Early Graft Dysfunction

The aim of this study was to determine whether a portal flow of <1,000 mL/min in orthotopic liver transplantation (OLT) is associated with a higher incidence of early graft dysfunction (EGD) and graft loss. A retrospective study was performed of 540 OLTs carried out consecutively from December 2004 to December 2013. Patients were divided into 2 groups: group A, portal flow 1,000 mL/min. We studied the incidence of EGD and graft survival. A subanalysis was performed to define the minimum acceptable portal flow/100 g of liver weight to reduce the development EGD and graft loss. Group A included 29 patients and group B, 511 patients. Group A had significantly lower-weight donors and recipients, female recipients with cholestatic disease, lower MELD scores, and lower hepatic artery flow. EGD occurred in 7 patients in group A (24.1%) versus 101 patients in group B (19.8%; P = .43). No significant differences were found in 1- and 5-year graft survival. A portal flow of <80 mL/min/100 g of liver weight was related to a significantly higher risk of developing EGD (odds ratio, 4.35; 95% confidence interval [CI], 1.46-12.91; P = .008) and graft loss (hazard ratio, 4.05; 95% CI, 1.32-12.42; P = .014). Intraoperative portal flow of <1,000 mL/min in OLT was not related per se with a higher incidence of EGD or graft loss. Significantly higher risk of developing EGD and graft loss was associated with a portal flow of <80 mL/min/100 g of liver weight