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.

Influence of muscle fiber orientation on water and metabolite relaxation times, magnetization transfer, and visibility in human skeletal muscle

PURPOSE To gain a deeper understanding of the influence of skeletal muscle fiber orientation on metabolite visibility, magnetization transfer from water, and water proton relaxation rates in (1) H MR spectra. METHODS Non-water-suppressed MR spectroscopy was performed in tibialis anterior muscle (TA) of 10 healthy adults, with the TA oriented either parallel or at the magic angle to the 3T field. Spectra were acquired with metabolite-cycled PRESS, and water inversion from 50 to 2510 ms before excitation. Water proton T2 relaxation was sampled with STEAM with echo times from 12 to 272 ms. RESULTS Apparent concentrations of total creatine (tCr), taurine, and trimethylammonium compounds were reduced by 29% to 67% when TA was parallel to B0 . Both tCr peak areas were strongly correlated to the methylene peak splitting. Magnetization transfer rates from water to tCr CH3 were not significantly different between orientations. Water T1 s were similar between orientations, but T2 s were statistically significantly shorter by 1 ms in the parallel orientation (P = 0.002). CONCLUSION Muscle metabolite visibilities in MR spectroscopy and water T2 times depend substantially on muscle fiber orientation relative to B0 . In contrast, magnetization transfer rates appear to depend on muscle composition, rather than fiber orientation. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Making business in the open: coping with economic and institutional risk and insecurity in the Kafue flats, Zambia

This paper deals with the difference between risk and insecurity from an anthropological perspective using a critical New Institutionalist approach. Risk refers to the ability to reduce undesirable outcomes, based on a range of information actors have on possible outcomes; insecurity refers to the lack of this information. With regard to the neo-liberal setting of a resource rich area in Zambia, Central Africa, local actors – men and women – face risk and insecurity in market constellations between rural and urban areas. They attempt to cope with risk using technical means and diversification of livelihood strategies. But as common-pool resources have been transformed from common property institutions to open access, also leading to unpredictability of competitors and partners in “free” markets, actors rely on magic options to reduce insecurity and transform it into risk-assessing strategies as an adaptation to modern times. Keywords: Risk, insecurity, institutional change, neo-liberal market, common pool resources, livelihood strategies, magic, Zambia.

Chemical studies of elements with Z ⩾ 104 in gas phase

Chemical investigations of superheavy elements in the gas-phase, i.e. elements with Z≥104Z≥104, allow assessing the influence of relativistic effects on their chemical properties. Furthermore, for some superheavy elements and their compounds quite unique gas-phase chemical properties were predicted. The experimental verification of these properties yields supporting evidence for a firm assignment of the atomic number. Prominent examples are the high volatility observed for HsO4 or the very weak interaction of Cn with gold surfaces. The unique properties of HsO4 were exploited to discover the doubly-magic even–even nucleus 270Hs and the new isotope 271Hs. The combination of kinematic pre-separation and gas-phase chemistry allowed gaining access to a new class of relatively fragile compounds, the carbonyl complexes of elements Sg through Mt. A not yet resolved issue concerns the interaction of Fl with gold surfaces. While competing experiments agree on the fact that Fl is a volatile element, there are discrepancies concerning its adsorption on gold surfaces with respect to its daughter Cn. The elucidation of these and other questions amounts to the fascination that gas-phase chemical investigations exert on current research at the extreme limits of chemistry today.

Patient safety in dialysis access

Not only are dialysis access creation and maintenance prone to complications, but patients suffering from end-stage renal disease and its comorbidities generally have a high risk of adverse events during their continuous treatment. Preventive strategies are key to avoid harm and to improve the outcome of the treatment of the growing number of patients with chronic kidney failure, especially as doctors and nurses are not always aware of the consequences of unsafe behavior. This publication is intended for health care professionals – nurses as well as doctors – and aims to raise the awareness of patient safety aspects, combining medical education with evidence-based medicine. After a general overview of the topic, an international panel of authors provides a diversified insight into important concepts and technical tricks essential to create and maintain a functional dialysis access. Contributions to Nephrology, Vol. 184

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.

Drought stress and carbon assimilation in a warming climate: Reversible and irreversible impacts

Abstract Global change is characterized by increased {CO2} concentration in the atmosphere, increasing average temperature and more frequent extreme events including drought periods, heat waves and flooding. Especially the impacts of drought and of elevated temperature on carbon assimilation are considered in this review. Effects of extreme events on the subcellular level as well as on the whole plant level may be reversible, partially reversible or irreversible. The photosynthetically active biomass depends on the number and the size of mature leaves and the photosynthetic activity in this biomass during stress and subsequent recovery phases. The total area of active leaves is determined by leaf expansion and senescence, while net photosynthesis per leaf area is primarily influenced by stomatal opening (stomatal conductance), mesophyll conductance, activity of the photosynthetic apparatus (light absorption and electron transport, activity of the Calvin cycle) and {CO2} release by decarboxylation reactions (photorespiration, dark respiration). Water status, stomatal opening and leaf temperature represent a "magic triangle" of three strongly interacting parameters. The response of stomata to altered environmental conditions is important for stomatal limitations. Rubisco protein is quite thermotolerant, but the enzyme becomes at elevated temperature more rapidly inactivated (decarbamylation, reversible effect) and must be reactivated by Rubisco activase (carbamylation of a lysine residue). Rubisco activase is present under two forms (encoded by separate genes or products of alternative splicing of the pre-mRNA from one gene) and is very thermosensitive. Rubisco activase was identified as a key protein for photosynthesis at elevated temperature (non-stomatal limitation). During a moderate heat stress Rubisco activase is reversibly inactivated, but during a more severe stress (higher temperature and/or longer exposure) the protein is irreversibly inactivated, insolubilized and finally degraded. On the level of the leaf, this loss of photosynthetic activity may still be reversible when new Rubisco activase is produced by protein synthesis. Rubisco activase as well as enzymes involved in the detoxification of reactive oxygen species or in osmoregulation are considered as important targets for breeding crop plants which are still productive under drought and/or at elevated leaf temperature in a changing climate.

MO visualization of Pi Orbitals

In the spirit of trying to convert people to understanding atomic orbitals centered elsewhere than the origin, we continue the discussion of visualizing molecular orbitals, so called LCAO-MO, using various plotting tricks in Maple.

Microbe Hunters Revisited – Paul de Kruif and the Beginning of Popular Science Writing

Paul de Kruif is credited with being one of the first popular science writers for the general public. He received his Ph.D. from the University of Michigan in 1916 and worked at the Rockefeller Institute under Simon Flexner. After being fired in 1922 for publishing a scathing article on medical research, de Kruif caught the attention of Sinclair Lewis, who used his scientific background to write his Pulitzer Prize winning novel, Arrowsmith. In 1926, de Kruif published Microbe Hunters which recounted the exploits and discoveries of 14 renowned microbiologists from von Leeuwenhoek to Pasteur, Ross, Paul Ehrlich and Walter Reed. Microbe Hunters became a best seller, was translated into 18 languages, and formed the basis of two Hollywood movies, "Yellow Jack" and "The Magic Bullet." Generations of young readers were captivated by the vivid protrayal of these men and their discoveries.

Las cosas por su nombre : Notas sobre la palabra en algunas novelas fantásticas

En este trabajo se plantean algunas aproximaciones a la cuestión del uso del lenguaje y sus representaciones dentro del fantasy, profundizando una investigación anterior sobre el tema (Gagliardi, 2011). En la literatura fantástica se le asigna frecuentemente a la palabra un valor mágico y performativo, en especial dentro de los relatos de la denominada "fantasía heroica". Nuestra hipótesis es que existen al menos dos representaciones diferentes sobre el rol de la palabra en estas ficciones: unas que siguen la tradición de Cratilo ("El que conoce los nombres conoce también las cosas") y otra más reciente que se cuestiona la relación unívoca entre palabra y referente, al mismo tiempo que problematiza cuestiones como la identidad. De este modo, la palabra, su valor y posibilidades dentro de las obras literarias que proponemos explorar participa de la construcción del universo ficcional, su cosmovisión y verosímil. La selección de obras literarias para esta presentación tiene como fin mostrar algunos casos representativos que puedan extenderse luego a un corpus más amplio dado que esta comunicación plantea un estado de la cuestión. Tomaremos las novelas Un mago de Terramar (Le Guin); Harry Potter y la piedra filosofal (Rowling); El nombre del viento (Rothfuss) y El dador de recuerdos (Lowry). De todas ellas analizaremos fragmentos en los cuales aparezcan las representaciones sobre el lenguaje y propondremos una clasificación tentativa al respecto

Traducción de poesía: forma, repetición y fantasma en el estudio comparado de traducciones de Emily Dickinson (Silvina Ocampo, Amelia Rosselli)

Este trabajo se inscribe en el proyecto de fundación de una Escuela de Traducción Poética, en la que nos proponemos pensar y practicar nuevos criterios específicos para traducir poesía. Las premisas teóricas de Walter Benjamin y Giorgio Agamben nos sirven para pensar nuestra tarea como una Nueva Filología. Será fundamental en ella el estudio interdisciplinario en el que confluyen filosofía, historia, psicoanálisis, estética y teoría literaria. Una filología absorta en la facticidad y la devoción mágica por los particulares, por el detalle, que Agamben destaca como fundamentales en Benjamin.

El efecto Duchamp

En una literatura en la que ha desaparecido el valor y los fantasmas perdieron consistencia, el lenguaje es un ready made de clichés. Algunas novelas actuales, sin embargo, han merecido el epíteto de verdaderas" (Jarkowski 2008) o "auténticas" (Lemus 2004). La magia ha regresado, y los narradores, aunque sus relatos sean inconclusos, indiferentes e incluso frívolos, interpelan al lector como los grandes realistas (Lukács 1971) porque el efecto de los textos es indicial. Señalan -con brutalidad o con delicia- el desfasaje entre lo que se dice y lo que se hace o lo que se deja de hacer. Nombran así, con palabras comunes y sin ninguna distancia, deseos singulares: los suyos y los nuestros (Aira 1988: 59)

Mitología y magia óptica: sobre la relación entre retraro, espejo y escritura en la poesía de Góngora

Cuando en el contexto de la magia artificialis barroca se apela a modelos míticos para describir y explicar los fenómenos ópticos, esta referencia al mito se integra esencialmente al horizonte histórico-cultural de la emergencia de complejos dispositivos de imágenes ópticas, artísticas, técnicas y científicas. Esto se manifiesta principalmente en la continuidad de tradiciones más antiguas pertenecientes a la magia de la imagen, en las que la idea de la 'vivificación' o 'animación' de imágenes se vincula en múltiples casos con las figuras míticas de los demiurgos-artistas de Prometeo y Pigmalión.