Separation of small metabolites and lipids in spectra from biopsies by diffusion-weighted HR-MAS NMR: a feasibility study.

High Resolution Magic Angle Spinning (HR-MAS) NMR allows metabolic characterization of biopsies. HR-MAS spectra from tissues of most organs show strong lipid contributions that are overlapping metabolite regions, which hamper metabolite estimation. Metabolite quantification and analysis would benefit from a separation of lipids and small metabolites. Generally, a relaxation filter is used to reduce lipid contributions. However, the strong relaxation filter required to eliminate most of the lipids also reduces the signals for small metabolites. The aim of our study was therefore to investigate different diffusion editing techniques in order to employ diffusion differences for separating lipid and small metabolite contributions in the spectra from different organs for unbiased metabonomic analysis. Thus, 1D and 2D diffusion measurements were performed, and pure lipid spectra that were obtained at strong diffusion weighting (DW) were subtracted from those obtained at low DW, which include both small metabolites and lipids. This subtraction yielded almost lipid free small metabolite spectra from muscle tissue. Further improved separation was obtained by combining a 1D diffusion sequence with a T2-filter, with the subtraction method eliminating residual lipids from the spectra. Similar results obtained for biopsies of different organs suggest that this method is applicable in various tissue types. The elimination of lipids from HR-MAS spectra and the resulting less biased assessment of small metabolites have potential to remove ambiguities in the interpretation of metabonomic results. This is demonstrated in a reproducibility study on biopsies from human muscle.

Signal Processing for the Measurement of the Deuterium/Hydrogen Ratio in the Local Interstellar Medium

We report on a comprehensive signal processing procedure for very low signal levels for the measurement of neutral deuterium in the local interstellar medium from a spacecraft in Earth orbit. The deuterium measurements were performed with the IBEX-Lo camera on NASA’s Interstellar Boundary Explorer (IBEX) satellite. Our analysis technique for these data consists of creating a mass relation in three-dimensional time of flight space to accurately determine the position of the predicted D events, to precisely model the tail of the H events in the region where the H tail events are near the expected D events, and then to separate the H tail from the observations to extract the very faint D signal. This interstellar D signal, which is expected to be a few counts per year, is extracted from a strong terrestrial background signal, consisting of sputter products from the sensor’s conversion surface. As reference we accurately measure the terrestrial D/H ratio in these sputtered products and then discriminate this terrestrial background source. During the three years of the mission time when the deuterium signal was visible to IBEX, the observation geometry and orbit allowed for a total observation time of 115.3 days. Because of the spinning of the spacecraft and the stepping through eight energy channels the actual observing time of the interstellar wind was only 1.44 days. With the optimised data analysis we found three counts that could be attributed to interstellar deuterium. These results update our earlier work.

1H HR-MAS NMR Based Metabolic Profiling of Cells in Response to Treatment with a Hexacationic Ruthenium Metallaprism as Potential Anticancer Drug.

1H high resolution magic angle spinning (HR-MAS) NMR spectroscopy was applied in combination with multivariate statistical analyses to study the metabolic response of whole cells to the treatment with a hexacationic ruthenium metallaprism [1]6+ as potential anticancer drug. Human ovarian cancer cells (A2780), the corresponding cisplatin resistant cells (A2780cisR), and human embryonic kidney cells (HEK-293) were each incubated for 24 h and 72 h with [1]6+ and compared to untreated cells. Different responses were obtained depending on the cell type and incubation time. Most pronounced changes were found for lipids, choline containing compounds, glutamate and glutathione, nucleotide sugars, lactate, and some amino acids. Possible contributions of these metabolites to physiologic processes are discussed. The time-dependent metabolic response patterns suggest that A2780 cells on one hand and HEK-293 cells and A2780cisR cells on the other hand may follow different cell death pathways and exist in different temporal stages thereof.

Blackfolds, plane waves and minimal surfaces

Minimal surfaces in Euclidean space provide examples of possible non-compact horizon geometries and topologies in asymptotically flat space-time. On the other hand, the existence of limiting surfaces in the space-time provides a simple mechanism for making these configurations compact. Limiting surfaces appear naturally in a given space-time by making minimal surfaces rotate but they are also inherent to plane wave or de Sitter space-times in which case minimal surfaces can be static and compact. We use the blackfold approach in order to scan for possible black hole horizon geometries and topologies in asymptotically flat, plane wave and de Sitter space-times. In the process we uncover several new configurations, such as black helicoids and catenoids, some of which have an asymptotically flat counterpart. In particular, we find that the ultraspinning regime of singly-spinning Myers-Perry black holes, described in terms of the simplest minimal surface (the plane), can be obtained as a limit of a black helicoid, suggesting that these two families of black holes are connected. We also show that minimal surfaces embedded in spheres rather than Euclidean space can be used to construct static compact horizons in asymptotically de Sitter space-times.

New geometries for black hole horizons

We construct several classes of worldvolume effective actions for black holes by integrating out spatial sections of the worldvolume geometry of asymptotically flat black branes. This provides a generalisation of the blackfold approach for higher-dimensional black holes and yields a map between different effective theories, which we exploit by obtaining new hydrodynamic and elastic transport coefficients via simple integrations. Using Euclidean minimal surfaces in order to decouple the fluid dynamics on different sections of the worldvolume, we obtain local effective theories for ultraspinning Myers-Perry branes and helicoidal black branes, described in terms of a stress-energy tensor, particle currents and non-trivial boost vectors. We then study in detail and present novel compact and non-compact geometries for black hole horizons in higher-dimensional asymptotically flat space-time. These include doubly-spinning black rings, black helicoids and helicoidal p-branes as well as helicoidal black rings and helicoidal black tori in D ≥ 6.

Increased levels of choline metabolites are an early marker of docetaxel treatment response in BRCA1-mutated mouse mammary tumors: an assessment by ex vivo proton magnetic resonance spectroscopy.

BACKGROUND Docetaxel is one of the most frequently used drugs to treat breast cancer. However, resistance or incomplete response to docetaxel is a major challenge. The aim of this study was to utilize MR metabolomics to identify potential biomarkers of docetaxel resistance in a mouse model for BRCA1-mutated breast cancer. METHODOLOGY High resolution magic angle spinning (HRMAS) (1)H MR spectroscopy was performed on tissue samples obtained from docetaxel-sensitive or -resistant BRCA1-mutated mammary tumors in mice. Measurements were performed on samples obtained before treatment and at 1-2, 3-5 and 6-7 days after a 25 mg/kg dose of docetaxel. The MR spectra were analyzed by multivariate analysis, followed by analysis of the signals of individual compounds by peak fitting and integration with normalization to the integral of the creatine signal and of all signals between 2.9 and 3.6 ppm. RESULTS The HRMAS spectra revealed significant metabolic differences between sensitive and resistant tissue samples. In particular choline metabolites were higher in resistant tumors by more than 50% with respect to creatine and by more than 30% with respect to all signals between 2.9 and 3.6 ppm. Shortly after treatment (1-2 days) the normalized choline metabolite levels were significantly increased by more than 30% in the sensitive group coinciding with the time of highest apoptotic activity induced by docetaxel. Thereafter, choline metabolites in these tumors returned towards pre-treatment levels. No change in choline compounds was observed in the resistant tumors over the whole time of investigation. CONCLUSIONS Relative tissue concentrations of choline compounds are higher in docetaxel resistant than in sensitive BRCA1-mutated mouse mammary tumors, but in the first days after docetaxel treatment only in the sensitive tumors an increase of these compounds is observed. Thus both pre- and post-treatment tissue levels of choline compounds have potential to predict response to docetaxel treatment.

"Coser y cantar" : El hilar como espacio de la transmisión oral, la lira que le canta y el refrán que lo sentencia

En este artículo se estudia el acto de hilar y tejer como espacio que propicia la transmisión de la tradición oral. Además se señala la presencia de este motivo en coplas y refranes podemos encontrar testimonios acerca del acto mismo de la trasmisión, del espacio en que ocurre, del tiempo, de lo que se juzga de la buena y la mala hilandera y de cómo seducirla

"Coser y cantar" : El hilar como espacio de la transmisión oral, la lira que le canta y el refrán que lo sentencia

En este artículo se estudia el acto de hilar y tejer como espacio que propicia la transmisión de la tradición oral. Además se señala la presencia de este motivo en coplas y refranes podemos encontrar testimonios acerca del acto mismo de la trasmisión, del espacio en que ocurre, del tiempo, de lo que se juzga de la buena y la mala hilandera y de cómo seducirla

"Coser y cantar" : El hilar como espacio de la transmisión oral, la lira que le canta y el refrán que lo sentencia

En este artículo se estudia el acto de hilar y tejer como espacio que propicia la transmisión de la tradición oral. Además se señala la presencia de este motivo en coplas y refranes podemos encontrar testimonios acerca del acto mismo de la trasmisión, del espacio en que ocurre, del tiempo, de lo que se juzga de la buena y la mala hilandera y de cómo seducirla

Drained thaw-lake basin soil characteristics of cores from Barrow, Alaska

Arctic soils contain a large fraction of Earth's stored carbon. Temperature increases in the Arctic may enhance decomposition of this stored carbon, shifting the role of Arctic soils from a net sink to a new source of atmospheric CO2. Predicting the impact of Arctic warming on soil carbon reserves requires knowledge of the composition of the stored organic matter. Here, we employ solid state 13C nuclear magnetic resonance (NMR) spectroscopy and Fourier transform infrared-photoacoustic spectroscopy (FTIR-PAS) to investigate the chemical composition of soil organic matter collected from drained thaw-lake basins ranging in age from 0 to 5500 years before present (y BP). The 13C NMR and FTIR-PAS data were largely congruent. Surface horizons contain relatively large amounts of O-alkyl carbon, suggesting that the soil organic matter is rich in labile constituents. Soil organic matter decreases with depth with the relative amounts of O-alkyl carbon decreasing and aromatic carbon increasing. These data indicate that lower horizons are in a more advanced stage of decomposition than upper horizons. Nonetheless, a substantial fraction of carbon in lower horizons, even for ancient thaw-lake basins (2000-5500 y BP), is present as O-alkyl carbon reflecting the preservation of intrinsically labile organic matter constituents. Climate change-induced increases in the depth of the soil active layer are expected to accelerate the depletion of this carbon.

Seawater carbonate chemistry and Littorina obtusata biological processes during experiments, 2009

Our understanding of the effects of ocean acidification on whole organism function is growing, but most current information is for adult stages of development. Here, we show the effects of reduced pH seawater (pH 7.6) on aspects of the development, physiology and behaviour of encapsulated embryos of the marine intertidal gastropod Littorina obtusata. We found reduced viability and increased development times under reduced pH conditions, and the embryos had significantly altered behaviours and physiologies. In acidified seawater, embryos spent more time stationary, had slower rotation rates, spent less time crawling, but increased their movement periodicity compared with those maintained under control conditions. Larval and adult heart rates were significantly lower in acidified seawater, and hatchling snails had an altered shell morphology (lateral length and spiral shell length) compared to control snails. Our findings show that ocean acidification may have multiple, subtle effects during the early development of marine animals that may have implications for their survival beyond those predicted using later life stages.

Correlation Between Processing Conditions, Microstructure and Mechanical Behavior in Regenerated Silkworm Silk Fibers

Regenerated silkworm fibers spun through a wet-spinning process followed by an immersion postspinning drawing step show a work to fracture comparable with that of natural silkworm silk fibers in a wide range of spinning conditions. The mechanical behavior and microstructure of these high performance fibers have been characterized, and compared with those fibers produced through conventional spinning conditions. The comparison reveals that both sets of fibers share a common semicrystalline microstructure, but significant differences are apparent in the amorphous region. Besides, high performance fibers show a ground state and the possibility of tuning their tensile behavior. These properties are characteristic of spider silk and not of natural silkworm silk, despite both regenerated and natural silkworm silk share a common composition different from that of spider silk.

Arquitectura óptima: Cuatro medios prácticos para optimizar proyectos de arquitectura

La investigación trata de mostrar cuatro acciones habitualmente empleadas al proyectar arquitectura. La tesis narra el discurso que construyen cuatro acciones como mecanismos optimizadores, fundamentales, activos y necesarios cuando creamos nuevos proyectos. En este trabajo se estudian en profundidad cuatro acciones optimizadoras a través de numerosos casos de estudio. Se estudia también la presencia de estas acciones en otros campos creativos, como la biología, el arte, la literatura, la filosofía, la matemática o la psicología de la creatividad. Se busca qué tienen en común estas cuatro acciones y se indaga sobre la posible narración que construyen entre ellas. La mayor parte de los textos que constituyen este trabajo se escriben en un formato próximo al del ensayo, empleando tiempos verbales presentes evitando los tiempos verbales pretéritos o imperfectos para potenciar la acción a través el estilo narrativo. La investigación se ha realizado a partir de fuentes bibliográficas existentes en numerosas bibliotecas. Se han llevado a cabo estudios de campo realizados a través de entrevistas personales a interlocutores expertos, no sólo de teoría arquitectónica sino también de prácticas constructivas, así como visitas a lugares íntimamente relacionados con el tema de investigación. Se ha completado el estudio de casos con ejercicios prácticos realizados por el autor de esta tesis, para profundizar con la propia investigación por empatía con los autores estudiados. La investigación bibliográfica principal se ha desarrollado en las bibliotecas de la Universidad Politécnica de Madrid, de la Universidad de Alicante, de la Universidad Autónoma de Madrid, de la Universidad Europea de Madrid, de la Universidad Camilo José Cela, de la Universidad Complutense de Madrid, de la Columbia University, de la Harvard University, de la Delft University, de Heidelberg University, de la Biblioteca Central de Madrid y de la Regional de Murcia, así como de la del COAMU. También se ha utilizado recursos bibliográficos propios. La metodología utilizada muestra desde diferentes perspectivas el problema de las acciones optimizadoras, desde obras artísticas, pasando por ejemplos de arquitectura construida hasta ejercicios puramente intelectuales. La acumulación ha sido el método de obtención de conocimiento de esta tesis. Se han acumulado conocimientos y posteriormente se ha profundizado, reflexionando sobre los datos que se han ido obteniendo. Al profundizar se enlazan unas pruebas con otras, hilando y ensamblándolas en un discurso que hace continuo y coherente la aparición de cada caso estudiado. Estas entidades probatorias son acciones que han sido aplicadas frecuentemente por distintas generaciones de autores que proyectan utilizando alguna de estas cuatro acciones. Partimos de una extensa bibliografía general y de otra específica. A través de citas e imágenes se muestra el repertorio de objetos y textos estudiados. Los casos de estudio seleccionados exponen los efectos que produce cada acción en el ejercicio del proyectar. Se ha estudiado la necesidad de cada acción en todas y cada una de las partes del ciclo creativo del proyecto, tanto en prácticas imaginadas como en construidas, de los autores que proyectan. Se citan y se interpretan las descripciones de biólogos, sociólogos, antropólogos, psicólogos, escritores, artistas, arquitectos, matemáticos, ingenieros, físicos, médicos y filósofos en los cuales estas acciones se encuentran conscientemente incorporadas en su procedimiento de proyectar y de pensar. Por último, hemos obtenido unos resultados adecuados a la metodología empleada y a los objetivos planteados gracias a la acumulación y clasificación de pruebas. Los resultados se exponen a modo de discursos conclusivos con un intencionado carácter abierto que despliega nuevas posibles nuevas vías de investigación entorno a los temas estudiados. ABSTRACT. The research seeks to show four commonly used actions in designing architecture. Thesis recounts the speech that built four actions like optimizer, fundamental, active and necessary mechanisms when we create new projects. In this work it studies in depth four optimizer actions through numerous case studies. Also, it considers the presence of these actions in other creative fields, such as biology, art, literature, philosophy, mathematics or psychology of creativity. It is intended what these four actions have in common and it explores the possible narrative constructed among them. Most of the texts that constitute this work are written in a format close to the essay, using present tenses avoiding past or imperfect tenses of enhancing the action through the narrative style. Research has been done from literature sources available in numerous libraries. Field studies have been carried out through personal interviews with expert speakers, not just of architectonic theory but also from constructive practices, as well as visits to sites closely related to the research topic. case studies with practical exercises conducted by the author of this thesis has been completed, to deepen with the own research by empathy with the studied authors. Main bibliographical investigation has been developed in the libraries of UPM, UA, UAM, UEM, the CJC, the UCM, Columbia University, Harvard University Delft University, Heidelberg University, Madrid Central Library, Regional Murcia Library and COAMU Library. Also it has been used own bibliographical resources. Methodology shows from different perspectives the problem of optimizers actions, from art, passing through examples of architecture built up to puré intellectual exercise. Accumulation has been the method of obtaining knowledge of this thesis. it has been accumulated knowledge and later it has been deepened, reflecting on the data that have been obtained. By deepening tests are linked with other, spinning and locking into a discourse that makes continuous and consistent the development of each case study. These evidentiary entities are actions that have been frequently applied by different generations of authors who project using some of these four stocks. We leave from an extensive general bibliography and another specific one. Through quotes and pictures it shows the repertoire of objects and texts studied. The selected study cases set out the effects that each action produces in the exercise of projecting. It has studied the need of each action in every parts of creative cycle of the project, both imagined as constructed practices, by the authors who project. It is quoted and interpreted the descriptions of biologists, sociologists, anthropologists, psychologists, writers, artists, architects, mathematicians, engineers, physicists, physicians and philosophers in which these actions are consciously incorporated into his projecting and thinking procedure. Finally, we have obtained adequate results to the used methodology and to the stated objectives through the accumulation and classification of evidence. The results are presented as conclusive speeches with an intentional open character that unfolds new possible research routes around the studied topics.

Sequential origin in the high performance properties of spider dragline silk

Major ampullate (MA) dragline silk supports spider orb webs, combining strength and extensibility in the toughest biomaterial. MA silk evolved ~376 MYA and identifying how evolutionary changes in proteins influenced silk mechanics is crucial for biomimetics, but is hindered by high spinning plasticity. We use supercontraction to remove that variation and characterize MA silk across the spider phylogeny. We show that mechanical performance is conserved within, but divergent among, major lineages, evolving in correlation with discrete changes in proteins. Early MA silk tensile strength improved rapidly with the origin of GGX amino acid motifs and increased repetitiveness. Tensile strength then maximized in basal entelegyne spiders, ~230 MYA. Toughness subsequently improved through increased extensibility within orb spiders, coupled with the origin of a novel protein (MaSp2). Key changes in MA silk proteins therefore correlate with the sequential evolution high performance orb spider silk and could aid design of biomimetic fibers.