Triggering antitumoural drug release and gene expression by magnetic hyperthermia

Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and magnetic hyperthermia as drug release and gene expression triggers for cancer therapy. Several strategies for the release of chemotherapeutic drugs from thermo-responsive matrices are discussed, providing representative examples of their application at different levels (from proof of concept to in vivo applications). The potential of magnetic hyperthermia to promote in situ expression of therapeutic genes using vectors that contain heat-responsive promoters is also reviewed in the context of cancer gene therapy

Auditory-inspired morphological processing of speech spectrograms: applications in automatic speech recognition and speech enhancement

New auditory-inspired speech processing methods are presented in this paper, combining spectral subtraction and two-dimensional non-linear filtering techniques originally conceived for image processing purposes. In particular, mathematical morphology operations, like erosion and dilation, are applied to noisy speech spectrograms using specifically designed structuring elements inspired in the masking properties of the human auditory system. This is effectively complemented with a pre-processing stage including the conventional spectral subtraction procedure and auditory filterbanks. These methods were tested in both speech enhancement and automatic speech recognition tasks. For the first, time-frequency anisotropic structuring elements over grey-scale spectrograms were found to provide a better perceptual quality than isotropic ones, revealing themselves as more appropriate—under a number of perceptual quality estimation measures and several signal-to-noise ratios on the Aurora database—for retaining the structure of speech while removing background noise. For the second, the combination of Spectral Subtraction and auditory-inspired Morphological Filtering was found to improve recognition rates in a noise-contaminated version of the Isolet database.This work has been partially supported by the Spanish Ministry of Science and Innovation CICYT Project No. TEC2008-06382/TEC.Publicad

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

Nanoparticles and bioorthogonal chemistry joining forces for improved biomedical applications

Bioorthogonal chemistry comprises chemical reactions that can take place inside complex biological environments, providing outstanding tools for the investigation and elucidation of biological processes. Its use in combination with nanotechnology can lead to further developments in diverse areas of biomedicine, such as molecular bioimaging, targeted delivery, in situdrug activation, study of cell-nanomaterial interactions, biosensing, etc.Here, we summarise the recent efforts to bring together the unique properties of nanoparticles and the remarkable features of bioorthogonal reactions to create a toolbox of new or improved biomedical applications. We show how, by joining forces, bioorthogonal chemistry and nanotechnology can overcome some of the key current limitations in the field of nanomedicine, providing better, faster and more sensitive nanoparticle-based bioimaging and biosensing techniques, as well as therapeutic nanoplatforms with superior efficacy

Foreign investment and migration: extensions of the basic model

SIGLEAvailable from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel C 152110 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman