Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells

In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The amount of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1 to 5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min, and the viability of the blank DCs (i.e., without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH2+) or negative (COOH-) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the amount of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.Comment: In Press. 33 pages, 11 figure

RAM: A Relativistic Adaptive Mesh Refinement Hydrodynamics Code

We have developed a new computer code, RAM, to solve the conservative equations of special relativistic hydrodynamics (SRHD) using adaptive mesh refinement (AMR) on parallel computers. We have implemented a characteristic-wise, finite difference, weighted essentially non-oscillatory (WENO) scheme using the full characteristic decomposition of the SRHD equations to achieve fifth-order accuracy in space. For time integration we use the method of lines with a third-order total variation diminishing (TVD) Runge-Kutta scheme. We have also implemented fourth and fifth order Runge-Kutta time integration schemes for comparison. The implementation of AMR and parallelization is based on the FLASH code. RAM is modular and includes the capability to easily swap hydrodynamics solvers, reconstruction methods and physics modules. In addition to WENO we have implemented a finite volume module with the piecewise parabolic method (PPM) for reconstruction and the modified Marquina approximate Riemann solver to work with TVD Runge-Kutta time integration. We examine the difficulty of accurately simulating shear flows in numerical relativistic hydrodynamics codes. We show that under-resolved simulations of simple test problems with transverse velocity components produce incorrect results and demonstrate the ability of RAM to correctly solve these problems. RAM has been tested in one, two and three dimensions and in Cartesian, cylindrical and spherical coordinates. We have demonstrated fifth-order accuracy for WENO in one and two dimensions and performed detailed comparison with other schemes for which we show significantly lower convergence rates. Extensive testing is presented demonstrating the ability of RAM to address challenging open questions in relativistic astrophysics.Comment: ApJS in press, 21 pages including 18 figures (6 color figures

The Use of Patents to Assess National Innovation Systems: Evidences from Spanish Biotechnology

Spain’s economy recorded a high rate of growth from the mid-1990s onwards. At the same time, the resources allocated to Research and Development (R&D) grew at a much faster pace than in other European Union (EU) countries. Spain’s growth recorded an average rate of 2.93% from the early 1990s to 2004. Over the same period, the average growth in the EU was 0.46%. This circumstance, together with several sound policy decisions implemented between 2004 and 2009, ushered in a “golden age of Spanish biotechnology”. In terms of the national patent licenses issued by the Spanish Patent and Trademark Office (SPTO) between 2004 and 2009, the number in biotechnology grew from 84 to 151. However, the current economic situation in Spain, along with a series of political decisions taken over the past two or three years to cut spending on R&D, predicts a sharp downturn in the performance of Spanish biotechnology. This scenario makes Spain one of the best places to study the successes and failures of the management of science and allows transfer this experience to the other international regions. We need to analyze the influence of political decisions as a major factor with a bearing on the quality of science. Using patents as an indicator of scientific development, this paper analyzes the evolution of the biotechnology sector in Spain and its relationship with scientific policy and the management of R&D

Suppression of Tc in the (Y0.9Ca0.1)Ba2Cu4-xFexO8 system

In this paper, the effects produced by the iron substitutions in the (Y0.9Ca0.1)Ba2Cu4-xFexO8 system on the superconducting and structural properties are studied. The Rietveld fit of the crystal structure and Mossbauer spectroscopy results of (Y0.9Ca0.1)Ba2Cu4-xFexO8 samples indicate that, the iron atoms occupy the Cu(1) sites of the (Cu-O)2 double chain in fivefold coordination at low iron concentrations. Besides at high iron concentrations the iron atoms occupy the Cu(1) sites of single Cu-O chainss and Cu(2) sites in the CuO2 planes of the (Y0.9Ca0.1)Ba2Cu4-xFexO8 phase with structural defects. Simultaneouly, as iron concentration increases, a faster decrease of Tc is observed in this material comapred with the YBa2Cu3-xFexO7-y system. According to the charge transfer model proposed for YBa2Cu4O8 under pressure, the decrease in the Cu(1)-O(4) bond length in parallel to the increase in the Cu(2)-O(4) bond length may affect the charge transfer mechanism leading to the suppression of Tc.Comment: submitted to Journal of Physics: Condensed Matter on 12 October 2001, 8 figures, 2 tables, 9 page

Magneto-plasmonic nanoparticles as theranostic platforms for magnetic resonance imaging, drug delivery and NIR hyperthermia applications

PEGylated magneto-plasmonic nanoparticles with a hollow or semi-hollow interior have been successfully synthesized and their physico-chemical characteristics have been investigated. The hollow interior space can be used to store drugs or other molecules of interest whereas magnetic characterization shows their potential as contrast agents in magnetic resonance imaging (MRI) applications. In addition, their plasmonic characteristics in the near infrared (NIR) region make them efficient in photothermal applications producing high temperature gradients after short irradiation times. We show that by controlling the etching conditions the inner silica shell can be selectively dissolved to achieve a hollow or semi-hollow interior without compromising the magnetic or plasmonic characteristics of the resulting nanoparticles. Magnetic measurements and transmission electron microscopy observations have been used to demonstrate the precise control during the etching process and to select an optimal concentration of the etching reagent and contact time to preserve the inner superparamagnetic iron oxide-based nanoparticles and the plasmonic properties of the constructs. Drug loading capabilities were also evaluated for both semi-hollow and as-synthesized nanoparticles using Rhodamine B isothiocyanate as a model compound. The nanoparticles produced could be potentially used as “theranostic” nanoparticles with both imaging capabilities and a dual therapeutic function (drug delivery and hyperthermia)

Estudio acústico de la variación inter e intralocutor en la frecuencia fundamental de hablantes bilingües de catalán y de castellano

Este trabajo pretende contribuir a establecer la individualidad de la voz de los hablantes bilingües equilibrados de catalán y de castellano a partir del análisis de la frecuencia fundamental y estudiar los efectos, en el nivel acústico, que el uso de una lengua u otra produce en este parámetro. Se pretende obtener, así, parte del conocimiento fonético necesario para la mejora de los sistemas de reconocimiento, identificación o verificación automáticos del locutor y proporcionar a los especialistas en fonética judicial nuevos datos acústicos para que puedan comparar con un mayor grado de certeza locutores dubitados e indubitadosAquest treball vol contribuir a establir la individualitat de la veu dels parlants bilingües equilibrats de català i de castellà a partir de l'anàlisi de la freqüència fonamental i estudiar els efectes, en el nivell acústic, que l'ús d'una llengua o l'altra provoca en aquest paràmetre. Es vol obtenir, per tant, part del coneixement fonètic necessari per a millorar els sistemes de reconeixement, identificació o verificació automàtics del locutor i dotar els especialistes en fonètica judicial de dades acústiques noves que els permetin comparar, amb un grau més elevat de certesa, locutors dubitats i indubitat

Characterization of the spoilage microbiota of hake fillets packaged under a modified atmosphere (MAP) rich in CO2 (50% CO2/50% N2) and stored at different temperatures

The aim of this study was to characterize the spoilage microbiota of hake fillets stored under modified atmospheres (MAP) (50% CO2/50% N2) at different temperatures using high-throughput 16S rRNA gene sequencing and to compare the results with those obtained using traditional microbiology techniques. The results obtained indicate that, as expected, higher storage temperatures lead to shorter shelf-lives (the time of sensory rejection by panelists). Thus, the shelf-life decreased from six days to two days for Batch A when the storage temperature increased from 1 to 7 °C, and from five to two days—when the same increase in storage temperature was compared—for Batch B. In all cases, the trimethylamine (TMA) levels measured at the time of sensory rejection of hake fillets exceeded the recommended threshold of 5 mg/100 g. Photobacterium and Psychrobacter were the most abundant genera at the time of spoilage in all but one of the samples analyzed: Thus, Photobacterium represented between 19% and 46%, and Psychrobacter between 27% and 38% of the total microbiota. They were followed by Moritella, Carnobacterium, Shewanella, and Vibrio, whose relative order varied depending on the sample/batch analyzed. These results highlight the relevance of Photobacterium as a spoiler of hake stored in atmospheres rich in CO2. Further research will be required to elucidate if other microorganisms, such as Psychrobacter, Moritella, or Carnobacterium, also contribute to spoilage of hake when stored under MAP

Eco-innovative possibilities for improving the quality of thawed cod fillets using high-power ultrasound

In order to improve the quality of thawed cod fillets and minimize the impact of processing, an extended hydration phase is applied in the fishery product industry in order to recover the water lost during freezing and thawing. Such long phases not only compromise productivity, but increase the chances of microbial growth in fish. Ultrasound (US) is a technology that could reduce these long hydration times, thanks to its capacity to improve mass-transfer processes, thereby limiting the development of fish microbiota. This investigation studies the effect of different US intensities (25 kHz, 29.4 W/kg to 2.9 W/kg, 113.7 to 15.3 W) on weight gain (WG) in the hydration process of cod fillets. The influence of the hydration medium's pH (from pH 8.5 to 10.5) in combination with US was likewise evaluated. Microbiological and sensory analyses were carried out at the end of the hydration process in order to evaluate its impact. The higher the applied US power, the lower was the WG. US intensities of 2.9 W/kg produced the highest increments in WG (18.6%), reducing hydration time by 33% and thereby achieving the same hydration values as in control samples. The combination of US with a controlled pH of 8.5 permitted to shorten hydration time by an additional day, and also led to improved microbial quality in comparison with control samples. Sensorial analyses indicated that after 5 d of hydration, Quality Index Method (QIM) values were better than those obtained for control samples after 5 and 7 d. Specifically, color and gaping were the sensorial attributes of cod fillets better protected with the application of US

Efficacy and safety of trabectedin in metastatic uterine leiomyosarcoma: A retrospective multicenter study of the Spanish ovarian cancer research group (GEICO)

Objective: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. Methods: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracycline-containing regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Results: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5–7.3) and 18.5 months (95%CI: 11.5–25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in = 2nd line (25.3 months) than in = 3rd (15.1 months) and with ECOG performance status = 1 at trabectedin start (19.8 months) than ECOG 2–3 (6.0 months, P = 0.013). When calculating OS since diagnosis, patients had longer OS with localized disease at diagnosis (87.4 months) vs. locally advanced (30.0 months) or metastatic (44.0 months, P = 0.041); and patients who received adjuvant therapy (87.4 months) compared with those who did not (30.0 months, P = 0.003), especially when receiving radiochemotherapy (106.7 months, P = 0.027). One patient (2.8%) had a complete response (CR) and nine patients (25.0%) achieved a partial response (PR) for an objective response rate of 27.8% with median response duration of 11 months (range: 4–93). Eighteen patients (50.0%) had disease stabilization for a disease control rate (DCR) of 77.8%. More patients receiving trabectedin in 1st-line of advanced disease achieved CR (16.7%) and PR (50.0%) than those in = 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). Conclusions: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile

Pr 0.5 Ca 0.5 MnO 3 thin films deposited on LiNbO 3 substrates

Thin films of Pr 0.5 Ca 0.5 MnO 3 have been deposited on z-cut LiNbO 3 by pulsed laser ablation. The X-ray diffraction measurements showed that the films have grown highly oriented on LiNbO 3 , with a pseudocubic (111) preferred growth direction. The thicknesses of the films, measured by low angle X-ray reflectivity, are between 13 and 140 nm. Their electrical resistivity present a semiconducting-like behaviour with an anomaly around 240 K, that corresponds to the charge ordering transition. The temperature of the transition (T_CO) was estimated from ln(r) vs. (1/T) plots. The charge ordering temperature was found to be dependent on the strain induced by the lattice mismatch on the films.Fundação para a Ciência e a Tecnologia (FCT