Rapid “Open-Source” Engineering of Customized Zinc-Finger Nucleases for Highly Efficient Gene Modification

Summary—Custom-made zinc-finger nucleases (ZFNs) can induce targeted genome modifications with high efficiency in cell types including Drosophila, C. elegans, plants, and humans. A bottleneck in the application of ZFN technology has been the generation of highly specific engineered zincfinger arrays. Here we describe OPEN (Oligomerized Pool ENgineering), a rapid, publicly available strategy for constructing multi-finger arrays, which we show is more effective than the previously published modular assembly method. We used OPEN to construct 37 highly active ZFN pairs which induced targeted alterations with high efficiencies (1 to 50%) at 11 different target sites located within three endogenous human genes (VEGF-A, HoxB13, CFTR), an endogenous plant gene (tobacco SuRA), and a chromosomally-integrated EGFP reporter gene. In summary, OPEN provides an “opensource” method for rapidly engineering highly active zinc-finger arrays, thereby enabling broader practice, development, and application of ZFN technology for biological research and gene therapy

Hábitat sustentable

1 archivo PDF (286 páginas) : incluye ilustraciones blanco y negro y colorConsta de cuatro artículos que plantean principios y lineamientos básicos sobre temas de sustentabilidad y 13 casos que ejemplifican intervención sustentable o que abordan temas relevantes del mismo de sitios singulares en el mundo donde estas prácticas del hábitat sustentable presentan diferentes niveles de desarrollo e instauración: Norteamérica, América Latina y Europa... PALABRAS CLAVE: Sustainable architecture. Sustainable development. City planning.1. Presentación / Sergio Padilla Galicia y Víctor Fuentes Freixanet -- 2. Estrategias y proyectos sustentable en el urbanismo internacional. Experiencias del SUI / Sergio Padilla Galicia -- 3. Conceptos para ciudades sustentables, la experiencia de Albert Speer & Partner (AS&P) / Christof Göbel -- 4. El libro verde del urbanismo: la apuesta europea de sostenibilidad / Elizabeth Espinosa Dorantes -- 5. Movilidad sustentable y equitativa / Bernardo Baranda Sepúlveda y Xavier Treviño Theesz -- 6. Densidad y calidad ambiental: lo inevitable, lo deseable y lo posible / Denise Helena Silva Duarte -- 7. El clima urbano de Oporto: oportunidad para repensar la sustentabilidad del territorio y retomar los ritmos de la naturaleza / Ana Monteiro y Helena Madureira -- 8. Áreas verdes en una ciudad sustentable: el caso de Wroclaw, Polonia / Leszek Maluga -- 9. Chicago Climate Action Plan: lo verde en la ciudad / Jorge del Arenal Fenochio -- 10. Reciclamiento urbano: arte y espacio público en Seattle / Guillermo Díaz Arellano -- 11. Hacia un desarrollo urbano sustentable en la ciudad de México / Jorge Legorreta Gutiérrez -- 12. Escenarios hacia la sustentabilidad en Tepotzotlán, Estado de México / Gloria Castorena, Aníbal Figueroa y Carl Stenitz -- 13. Desarrollos urbanos integrales sustentables (DUIS c): una opción para las futuras ciudades de México / Alfonso Rivas Cruces y Eduardo Langagne Ortega -- 14. Hacia la certificación regional de la edificación sustentable / Aníbal Figueroa Castrejón, Silvia de Schiller, Jhon Martín Evans, Bruno Stagno y Susana Colmegna -- 15. Alemanía: aplicación de estándares energéticos en la arquitectura / Michael Peters y Christof Göbel -- 16. Arquitectura responsable: la sustentabilidad en Chile / Javier del Río Ojeda -- 17. Arquitectura vernácula y sustentabilidad: dos casos del sureste mexicano / Víctor Fuentes Freixanet y Olinka González Mejía -- 18. Diseño de vivienda social en México, su adaptación al cambio climático y catástrofes naturales / Dulce Romina Gómez Menéndez

Coulomb dissociation of N 20,21

Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at

Phenotype of migraine headache and migraine aura of Richard Wagner.

Background The headache phenotype and neurological symptoms of the German composer Richard Wagner (1813–1883), whose music dramas count towards the most frequently performed operas across the world, are previously undocumented.Methods Richard Wagner’s own descriptions of his headache symptoms in his original writings and letters are investigated, as well as the complete diary records of his second wife, Cosima Wagner.Results There are manifold indications that Richard Wagner suffered from a severe headache disorder, which fulfils most likely the diagnostic criteria of migraine without aura and migraine with aura of ICHD-3 beta.Conclusions Richard Wagner’s life and opus can help to better understand the burden and suffering caused by migraine with its severe effects on the individual, familial and social life, the culture and community

Preparation of atom probe tips from (nano)particles in dispersion using (di)electrophoresis and electroplating

The behavior of catalytic particles depends on their chemical structure and morphology. To reveal this information, the characterization with atom probe tomography has huge potential. Despite progresses and papers proposing various approaches towards the incorporation of particles inside atom probe tips, no single approach has been broadly applicable to date. In this paper, we introduce a workflow that allowed us to prepare atom probe specimens from Ga particles in suspension in the size range of 50 nm up to 2 μm. By combining dielectrophoresis and electrodeposition in a suitable way, we achieve a near-tip shape geometry, without a time-consuming FIB lift-out. This workflow is a simple and quick method to prepare atom probe tips and allows for a high preparation throughput. Also, not using a lift-out allowed us to use a cryo-stage, avoiding melting of the Ga particles, while ensuring a mechanical stable atom probe tip. The specimen prepared by this workflow enable a stable measurement and low fracture rates. RESEARCH HIGHLIGHTS: Enabling cryo-preparation of (nano)particles for the atom probe. Characterization of surface and bulk elemental distribution of GaPt model SCALMS

Sex-specific differences drive temporal trends and outcomes of patients hospitalized for heart failure in Germany

Background: Despite remarkable improvements in treatment of cardiovascular disease, heart failure (HF) is still characterized by high mortality rate. Sex-specific differences in HF have been described, but underlying reasons are widely unexplored. Methods: The nationwide German inpatient sample (2005–2016) was used for this sex-specific analyses. Temporal trends on hospitalizations, mortality, and treatments were analysed and independent predictors of adverse outcomes identified. Results: The analysis comprises 4,538,977 hospitalizations due to HF (52.0%women) in Germany (2005–2016). Although women were older (median 82(IQR75–87) vs.76(69–82),P < 0.001), coronary artery disease (CAD, 50.3% vs. 30.7%,P < 0.001) was more prevalent in men, who were more often treated with percutaneous intervention (PCI;3.4% vs. 1.4%,P < 0.001) and implantable cardioverter-defibrillator (2.2% vs. 0.5%,P < 0.001). In-hospital mortality was significantly lower in men than in women (8.9% vs.10.2%,P = 0.001) and was reduced in patients who received PCI or implantation of an implantable cardioverter-defibrillator. While total numbers of hospitalizations between 2005 and 2016 increased in both men (β-estimate 7185.71 (95%CI 6502.23 to 7869.18),P < 0.001) and women (β-estimate 5297.60 (95%CI 4557.37 to 6037.83),P < 0.001) as well as almost all comorbid co-conditions, in-hospital mortality rate decreased more distinctly in women (β-estimate −0.41 (95%CI −0.42 to −0.39),P < 0.001) compared to men (β-estimate −0.29 (95%CI −0.30 to −0.27),P < 0.001). Conclusions: Interventional treatments of HF were associated with improved outcomes and equally beneficial for both sexes. However, they were more often used in male HF patients, in which CAD is significantly more frequent than in female HF patients. This may explain the higher case fatality rate of HF in females