Publications

Year 2011


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Montufar, Edgar B., Traykova, Tania, Planell, Josep A., Ginebra, Maria-Pau, (2011). Comparison of a low molecular weight and a macromolecular surfactant as foaming agents for injectable self setting hydroxyapatite foams: Polysorbate 80 versus gelatine Materials Science and Engineering: C 31, (7), 1498-1504

Hydroxyapatite foams are potential synthetic bone grafting materials or scaffolds for bone tissue engineering. A novel method to obtain injectable hydroxyapatite foams consists in foaming the liquid phase of a calcium phosphate cement. In this process, the cement powder is incorporated into a liquid foam, which acts as a template for macroporosity. After setting, the cement hardens maintaining the macroporous structure of the foam. In this study a low molecular weight surfactant, Polysorbate 80, and a protein, gelatine, were compared as foaming agents of a calcium phosphate cement. The foamability of Polysorbate 80 was greater than that of gelatine, resulting in higher macroporosity in the set hydroxyapatite foam and higher macropore interconnectivity. Gelatine produced less interconnected foams, especially at high concentrations, due to a higher liquid foam stability. However it increased the injectability and cohesion of the foamed paste, and enhanced osteoblastic-like cell adhesion, all of them important properties for bone grafting materials.

Keywords: Hydroxyapatite, Porosity, Calcium phosphate cement, Scaffolds, Foaming, Bone regeneration


Auffarth, Benjamin, Gutierrez-Galvez, Agustín, Marco, Santiago, (2011). Continuous spatial representations in the olfactory bulb may reflect perceptual categories Frontiers in Systems Neuroscience 5, (82), 1-8

In sensory processing of odors, the olfactory bulb is an important relay station, where odor representations are noise-filtered, sharpened, and possibly re-organized. An organization by perceptual qualities has been found previously in the piriform cortex, however several recent studies indicate that the olfactory bulb code reflects behaviorally relevant dimensions spatially as well as at the population level. We apply a statistical analysis on 2-deoxyglucose images, taken over the entire bulb of glomerular layer of the rat, in order to see how the recognition of odors in the nose is translated into a map of odor quality in the brain. We first confirm previous studies that the first principal component could be related to pleasantness, however the next higher principal components are not directly clear. We then find mostly continuous spatial representations for perceptual categories. We compare the space spanned by spatial and population codes to human reports of perceptual similarity between odors and our results suggest that perceptual categories could be already embedded in glomerular activations and that spatial representations give a better match than population codes. This suggests that human and rat perceptual dimensions of odorant coding are related and indicates that perceptual qualities could be represented as continuous spatial codes of the olfactory bulb glomerulus population.

Keywords: Glomeruli, Memory organization, Odor quality, Olfaction, Olfactory bulb, Perceptual categories, Population coding, Spatial coding


Trepat, X., (2011). Forcing tumor arrest Physics 4, 85

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Yue, J. J., Morgenstern, R., Morgenstern, C., Lauryssen, C., (2011). Shape memory hydrogels - A novel material for treating age-related degenerative conditions of the Spine European Musculoskeletal Review 6, (3), 184-188

Hydrogels are water-insoluble hydrophilic polymers used in a wide range of medical products such as, drug delivery, tissue replacement, heart surgery, gynaecology, ophthalmology, plastic surgery and orthopaedic surgery. These polymers exhibit low toxicity, reduced tissue adherence, and are highly biocompatible. A class of hydrogels, hydrolysed polyacrylonitriles, possess unique shape memory properties, which, when combined with biodurability, mechanical strength and viscoelasticity make them ideal for treating certain degenerative conditions of the spine. Animal and other in vitro studies have shown that the hydrogel is biocompatible and well tolerated by host tissues. This article focuses on two specific indications in spine surgery that demonstrate the potential of hydrogel-based technology to provide significant treatment advantages.

Keywords: Biocompatibility, Degenerative disc disease, Hydrolysed polyacrylonitrile, Minimally invasive surgery, Shape memory hydrogel, Spinal stenosis


Auffarth, Benjamin, Gutierrez, Agustin, Marco, Santiago, (2011). Statistical analysis of coding for molecular properties in the olfactory bulb Frontiers in Systems Neuroscience 5, (62), 1-8

The relationship between molecular properties of odorants and neural activities is arguably one of the most important issues in olfaction and the rules governing this relationship are still not clear. In the olfactory bulb (OB), glomeruli relay olfactory information to second-order neurons which in turn project to cortical areas. We investigate relevance of odorant properties, spatial localization of glomerular coding sites, and size of coding zones in a dataset of 2-deoxyglucose images of glomeruli over the entire OB of the rat. We relate molecular properties to activation of glomeruli in the OB using a nonparametric statistical test and a support-vector machine classification study. Our method permits to systematically map the topographic representation of various classes of odorants in the OB. Our results suggest many localized coding sites for particular molecular properties and some molecular properties that could form the basis for a spatial map of olfactory information. We found that alkynes, alkanes, alkenes, and amines affect activation maps very strongly as compared to other properties and that amines, sulfur-containing compounds, and alkynes have small zones and high relevance to activation changes, while aromatics, alkanes, and carboxylics acid recruit very big zones in the dataset. Results suggest a local spatial encoding for molecular properties.

Keywords: Molecular-receptive range, Odor, Olfactory bulb, Olfactory coding, Property-activity relationship, Structure-odor relationship


Tambe, Dhananjay T., Corey Hardin, C., Angelini, Thomas E., Rajendran, Kavitha, Park, Chan Young, Serra-Picamal, Xavier, Zhou, Enhua H., Zaman, Muhammad H., Butler, James P., Weitz, David A., Fredberg, Jeffrey J., Trepat, X., (2011). Collective cell guidance by cooperative intercellular forces Nature Materials 10, (6), 469-475

Cells comprising a tissue migrate as part of a collective. How collective processes are coordinated over large multi-cellular assemblies has remained unclear, however, because mechanical stresses exerted at cell–cell junctions have not been accessible experimentally. We report here maps of these stresses within and between cells comprising a monolayer. Within the cell sheet there arise unanticipated fluctuations of mechanical stress that are severe, emerge spontaneously, and ripple across the monolayer. Within that stress landscape, local cellular migrations follow local orientations of maximal principal stress. Migrations of both endothelial and epithelial monolayers conform to this behaviour, as do breast cancer cell lines before but not after the epithelial–mesenchymal transition. Collective migration in these diverse systems is seen to be governed by a simple but unifying physiological principle: neighbouring cells join forces to transmit appreciable normal stress across the cell–cell junction, but migrate along orientations of minimal intercellular shear stress.

Keywords: Biological materials, Mechanical properties


Diez-Perez, Ismael, Hihath, Joshua, Hines, Thomas, Wang, Zhong-Sheng, Zhou, Gang, Mullen, Klaus, Tao, Nongjian, (2011). Controlling single-molecule conductance through lateral coupling of [pi] orbitals Nature Nanotechnology 6, (4), 226-231

In recent years, various single-molecule electronic components have been demonstrated(1). However, it remains difficult to predict accurately the conductance of a single molecule and to control the lateral coupling between the pi orbitals of the molecule and the orbitals of the electrodes attached to it. This lateral coupling is well known to cause broadening and shifting of the energy levels of the molecule; this, in turn, is expected to greatly modify the conductance of an electrodemolecule- electrode junction(2-6). Here, we demonstrate a new method, based on lateral coupling, to mechanically and reversibly control the conductance of a single-molecule junction by mechanically modulating the angle between a single pentaphenylene molecule bridged between two metal electrodes. Changing the angle of the molecule from a highly tilted state to an orientation nearly perpendicular to the electrodes changes the conductance by an order of magnitude, which is in qualitative agreement with theoretical models of molecular pi-orbital coupling to a metal electrode. The lateral coupling is also directly measured by applying a fast mechanical perturbation in the horizontal plane, thus ruling out changes in the contact geometry or molecular conformation as the source for the conductance change.

Keywords: Junction conductance, Electron-transport, Interface, Dependence, Mechanism, Length


Simao, C., Mas-Torrent, M., Crivillers, N., Lloveras, V., Artés, Juan Manuel, Gorostiza, Pau, Veciana, Jaume, Rovira, C., (2011). A robust molecular platform for non-volatile memory devices with optical and magnetic responses Nature Chemistry 3, (5), 359-364

Bistable molecules that behave as switches in solution have long been known. Systems that can be reversibly converted between two stable states that differ in their physical properties are particularly attractive in the development of memory devices when immobilized in substrates. Here, we report a highly robust surface-confined switch based on an electroactive, persistent organic radical immobilized on indium tin oxide substrates that can be electrochemically and reversibly converted to the anion form. This molecular bistable system behaves as an extremely robust redox switch in which an electrical input is transduced into optical as well as magnetic outputs under ambient conditions. The fact that this molecular surface switch, operating at very low voltages, can be patterned and addressed locally, and also has exceptionally high long-term stability and excellent reversibility and reproducibility, makes it a very promising platform for non-volatile memory devices.

Keywords: Self-assembled monolayers, Chromophore-based monolayers, Ultrathin platinum films, Carbon free-radicals, Per-million levels, Polychlorotriphenylmethyl radicals, Electron-transfer, Surface, Logic, Quantification


Trepat, X., Fredberg, J. J., (2011). Plithotaxis and emergent dynamics in collective cellular migration Trends in Cell Biology 21, (11), 638-646

For a monolayer sheet to migrate cohesively, it has long been suspected that each constituent cell must exert physical forces not only upon its extracellular matrix but also upon neighboring cells. The first comprehensive maps of these distinct force components reveal an unexpected physical picture. Rather than showing smooth and systematic variation within the monolayer, the distribution of physical forces is dominated by heterogeneity, both in space and in time, which emerges spontaneously, propagates over great distances, and cooperates over the span of many cell bodies. To explain the severe ruggedness of this force landscape and its role in collective cell guidance, the well known mechanisms of chemotaxis, durotaxis, haptotaxis are clearly insufficient. In a broad range of epithelial and endothelial cell sheets, collective cell migration is governed instead by a newly discovered emergent mechanism of innately collective cell guidance - plithotaxis.

Keywords: Positional information, Drosophila embryo, Sheet migration, Dpp gradient, Cells, Force, Morphogenesis, Transition, Identification, Proliferation


Artés, Juan M., Díez-Pérez, Ismael, Sanz, Fausto, Gorostiza, Pau, (2011). Direct measurement of electron transfer distance decay constants of single redox proteins by electrochemical tunneling spectroscopy ACS Nano 5, (3), 2060-2066

We present a method to measure directly and at the single-molecule level the distance decay constant that characterizes the rate of electron transfer (ET) in redox proteins. Using an electrochemical tunneling microscope under bipotentiostatic control, we obtained current-distance spectroscopic recordings of individual redox proteins confined within a nanometric tunneling gap at a well-defined molecular orientation. The tunneling current decays exponentially, and the corresponding decay constant (

Keywords: Long-range electron transfer (LRET), Distance decay constant, Single-molecule electrochemistry, Redox enzyme, Metalloprotein, Blue copper protein, Azurin, Electrochemical scanning tunneling microscopy and spectroscopy, Nanoelectrodes, Debye length, Electrochemical charge screening


Angelini, Thomas E., Hannezo, Edouard, Trepat, Xavier, Marquez, Manuel, Fredberg, Jeffrey J., Weitz, David A., (2011). Glass-like dynamics of collective cell migration Proceedings of the National Academy of Sciences 108, (12), 4714-4719

Collective cell migration in tissues occurs throughout embryonic development, during wound healing, and in cancerous tumor invasion, yet most detailed knowledge of cell migration comes from single-cell studies. As single cells migrate, the shape of the cell body fluctuates dramatically through cyclic processes of extension, adhesion, and retraction, accompanied by erratic changes in migration direction. Within confluent cell layers, such subcellular motions must be coupled between neighbors, yet the influence of these subcellular motions on collective migration is not known. Here we study motion within a confluent epithelial cell sheet, simultaneously measuring collective migration and subcellular motions, covering a broad range of length scales, time scales, and cell densities. At large length scales and time scales collective migration slows as cell density rises, yet the fastest cells move in large, multicell groups whose scale grows with increasing cell density. This behavior has an intriguing analogy to dynamic heterogeneities found in particulate systems as they become more crowded and approach a glass transition. In addition we find a diminishing self-diffusivity of short-wavelength motions within the cell layer, and growing peaks in the vibrational density of states associated with cooperative cell-shape fluctuations. Both of these observations are also intriguingly reminiscent of a glass transition. Thus, these results provide a broad and suggestive analogy between cell motion within a confluent layer and the dynamics of supercooled colloidal and molecular fluids approaching a glass transition.

Keywords: Active matter, Cell mechanics, Jamming, Collective cell dynamics, Nonequilibrium


Gauthier, Nils C., Fardin, Marc Antoine, Roca-Cusachs, Pere, Sheetz, Michael P., (2011). Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading Proceedings of the National Academy of Sciences of the United States of America 108, (35), 14467-14472

Cell migration and spreading involve the coordination of membrane trafficking, actomyosin contraction, and modifications to plasma membrane tension and area. The biochemical or biophysical basis for this coordination is however unknown. In this study, we show that during cell spreading, lamellipodia protrusion flattens plasma membrane folds and blebs and, once the plasma membrane area is depleted, there is a temporary increase in membrane tension by over twofold that is followed by activation of exocytosis and myosin contraction. Further, an artificial increase in plasma membrane tension stopped lamellipodia protrusion and activated an exocytotic burst. Subsequent decrease in tension restored spreading with activation of contraction. Conversely, blebbistatin inhibition of actomyosin contraction resulted in an even greater increase in plasma membrane tension and exocytosis activation. This spatio-temporal synchronization indicates that membrane tension is the signal that coordinates membrane trafficking, actomyosin contraction, and plasma membrane area change. We suggest that cells use plasma membrane tension as a global physical parameter to control cell motility.

Keywords: Surface-area regulation, Cytoskeleton adhesion, Erythrocyte-membrane, Extensional flow, Elastic tether, Force


Cordeiro, T. N., Schmidt, H., Madrid, C., Juarez, A., Bernado, P., Griesinger, C., Garcia, J., Pons, M., (2011). Indirect DNA readout by an H-NS related protein: Structure of the DNA complex of the C-terminal domain of Ler Plos Pathogens 7, (11), 12

Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family.

Keywords: Enteropathogenic escherichia-coli, Nucleoid-associated protein, Nmr structure determination, Encoded regulator ler, Controls expression, Binding domain


Valle-Delgado, J. J., Molina-Bolívar, J. A., Galisteo-González, F., Gálvez-Ruiz, M. J., (2011). Evidence of hydration forces between proteins Current Opinion in Colloid and Interface Science 16, (6), 572-578

Proteins are fundamental molecules in biology that are also involved in a wide range of industrial and biotechnological processes. Consequently, many works in the literature have been devoted to the study of protein-protein and protein-surface interactions in aqueous solutions. The results have been usually interpreted within the frame of the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory for colloidal systems. However, against the DLVO predictions, striking evidence of repulsive forces between proteins at high salt concentrations has been observed in different works based on the analysis of the second virial coefficient or on the direct measurement of protein interaction with an atomic force microscope. Hydration forces due to the adsorption of hydrated cations onto the negatively charged protein surfaces have been invoked to rationalize this anomalous repulsion. The hydration forces between proteins provide protein-covered particles with a non-DLVO colloidal stability at high salt concentrations, as different studies in the literature has proven. This review summarizes the most relevant results published so far on the presence of hydration forces between proteins and protein-coated colloidal particles.

Keywords: Colloidal particles, Colloidal stability, Hydrated ions, Hydration forces, Proteins


Woods, N. B., Parker, A. S., Moraghebi, R., Lutz, M. K., Firth, A. L., Brennand, K. J., Berggren, W. T., Raya, A., Belmonte, J. C. I., Gage, F. H., Verma, I. M., (2011). Brief report: Efficient generation of hematopoietic precursors and progenitors from human pluripotent stem cell lines Stem Cells 29, (7), 1158-1164

By mimicking embryonic development of the hematopoietic system, we have developed an optimized in vitro differentiation protocol for the generation of precursors of hematopoietic lineages and primitive hematopoietic cells from human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs). Factors such as cytokines, extra cellular matrix components, and small molecules as well as the temporal association and concentration of these factors were tested on seven different human ESC and iPSC lines. We report the differentiation of up to 84% human CD45+ cells (average 41% +/- 16%, from seven pluripotent lines) from the differentiation culture, including significant numbers of primitive CD45+/CD34+ and CD45+/CD34+/CD38- hematopoietic progenitors. Moreover, the numbers of hematopoietic progenitor cells generated, as measured by colony forming unit assays, were comparable to numbers obtained from fresh umbilical cord blood mononuclear cell isolates on a per CD45+ cell basis. Our approach demonstrates highly efficient generation of multipotent hematopoietic progenitors with among the highest efficiencies reported to date (CD45+/CD34+) using a single standardized differentiation protocol on several human ESC and iPSC lines. Our data add to the cumulating evidence for the existence of an in vitro derived precursor to the hematopoietic stem cell (HSC) with limited engrafting ability in transplanted mice but with multipotent hematopoietic potential. Because this protocol efficiently expands the preblood precursors and hematopoietic progenitors, it is ideal for testing novel factors for the generation and expansion of definitive HSCs with long-term repopulating ability.

Keywords: Differentiation, Hematopoiesis, Hematopoietic progenitors, Pluripotent stem cells


Melchels, Ferry P. W., Tonnarelli, Beatrice, Olivares, Andy L., Martin, Ivan, Lacroix, Damien, Feijen, Jan, Wendt, David J., Grijpma, Dirk W., (2011). The influence of the scaffold design on the distribution of adhering cells after perfusion cell seeding Biomaterials 32, (11), 2878-2884

In natural tissues, the extracellular matrix composition, cell density and physiological properties are often non-homogeneous. Here we describe a model system, in which the distribution of cells throughout tissue engineering scaffolds after perfusion seeding can be influenced by the pore architecture of the scaffold. Two scaffold types, both with gyroid pore architectures, were designed and built by stereolithography: one with isotropic pore size (412 ± 13 [mu]m) and porosity (62 ± 1%), and another with a gradient in pore size (250-500 [mu]m) and porosity (35%-85%). Computational fluid flow modelling showed a uniform distribution of flow velocities and wall shear rates (15-24 s-1) for the isotropic architecture, and a gradient in the distribution of flow velocities and wall shear rates (12-38 s-1) for the other architecture. The distribution of cells throughout perfusion-seeded scaffolds was visualised by confocal microscopy. The highest densities of cells correlated with regions of the scaffolds where the pores were larger, and the fluid velocities and wall shear rates were the highest. Under the applied perfusion conditions, cell deposition is mainly determined by local wall shear stress, which, in turn, is strongly influenced by the architecture of the pore network of the scaffold.

Keywords: Scaffolds, Microstructure, Cell adhesion, Confocal microscopy, Image analysis, Computational fluid dynamics


Urban, Patricia, Estelrich, Joan, Cortés, Alfred, Fernàndez-Busquets, X., (2011). A nanovector with complete discrimination for targeted delivery to Plasmodium falciparum-infected versus non-infected red blood cells in vitro Journal of Controlled Release 151, (2), 202-211

Current administration methods of antimalarial drugs deliver the free compound in the blood stream, where it can be unspecifically taken up by all cells, and not only by Plasmodium-infected red blood cells (pRBCs). Nanosized carriers have been receiving special attention with the aim of minimizing the side effects of malaria therapy by increasing drug bioavailability and selectivity. Liposome encapsulation has been assayed for the delivery of compounds against murine malaria, but there is a lack of cellular studies on the performance of targeted liposomes in specific cell recognition and on the efficacy of cargo delivery, and very little data on liposome-driven antimalarial drug targeting to human-infecting parasites. We have used fluorescence microscopy to assess in vitro the efficiency of liposomal nanocarriers for the targeted delivery of their contents to pRBCs. 200-nm liposomes loaded with quantum dots were covalently functionalized with oriented, specific half-antibodies against P. falciparum late form-infected pRBCs. In less than 90 min, liposomes dock to pRBC plasma membranes and release their cargo to the cell. 100.0% of late form-containing pRBCs and 0.0% of non-infected RBCs in P. falciparum cultures are recognized and permeated by the content of targeted immunoliposomes. Liposomes not functionalized with antibodies are also specifically directed to pRBCs, although with less affinity than immunoliposomes. In preliminary assays, the antimalarial drug chloroquine at a concentration of 2 nM, >= 10 times below its IC50 in solution, cleared 26.7 ± 1.8% of pRBCs when delivered inside targeted immunoliposomes.

Keywords: Antimalarial chemotherapy, Chloroquine, Half-antibodies, Immunoliposomes, Malaria, Nanomedicine


Llorens, Franc, Gil, Vanessa, Antonio del Rio, Jose, (2011). Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration FASEB Journal 25, (2), 463-475

Adult mammalian central nervous system (CNS) axons have a limited regrowth capacity following injury. Myelin-associated inhibitors (MAIs) limit axonal outgrowth, and their blockage improves the regeneration of damaged fiber tracts. Three of these proteins, Nogo-A, MAG, and OMgp, share two common neuronal receptors: NgR1, together with its coreceptors [p75(NTR), TROY, and Lingo-1]; and the recently described paired immunoglobulin-like receptor B (PirB). These proteins impair neuronal regeneration by limiting axonal sprouting. Some of the elements involved in the myelin inhibitory pathways may still be unknown, but the discovery that blocking both PirB and NgR1 activities leads to near-complete release from myelin inhibition, sheds light on one of the most competitive and intense fields of neuroregeneration study in recent decades. In parallel with the identification and characterization of the roles and functions of these inhibitory molecules in axonal regeneration, data gathered in the field strongly suggest that most of these proteins have roles other than axonal growth inhibition. The discovery of a new group of interacting partners for myelin-associated receptors and ligands, as well as functional studies within or outside the CNS environment, highlights the potential new physiological roles for these proteins in processes, such as development, neuronal homeostasis, plasticity, and neurodegeneration.-Llorens, F., Gil, V., del Rio, J. A. Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration.

Keywords: MAIs, Neural stem cells, Synapse formation


Ivon Rodriguez-Villarreal, Angeles, Tarn, Mark D., Madden, Leigh A., Lutz, Julia B., Greenman, John, Samitier, Josep, Pamme, Nicole, (2011). Flow focussing of particles and cells based on their intrinsic properties using a simple diamagnetic repulsion setup Lab on a Chip 11, (7), 1240-1248

The continuous flow focussing and manipulation of particles and cells are important factors in microfluidic applications for performing accurate and reproducible procedures downstream. Many particle focussing methods require complex setups or channel designs that can limit the process and its applications. Here, we present diamagnetic repulsion as a simple means of focussing objects in continuous flow, based only on their intrinsic properties without the requirement of any label. Diamagnetic polystyrene particles were suspended in a paramagnetic medium and pumped through a capillary between a pair of permanent magnets, whereupon the particles were repelled by each magnet into the central axis of the capillary, thus achieving focussing. By investigating this effect, we found that the focussing was greatly enhanced with (i) increased magnetic susceptibility of the medium, (ii) reduced flow rate of the suspension, (iii) increased particle size, and (iv) increased residence time in the magnetic field. Furthermore, we applied diamagnetic repulsion to the flow focussing of living, label-free HaCaT cells.

Keywords: Feeble magnetic substances, On-chip, Blood-cells, Microfluidic device, Separation, Field, Levitation, Magnetophoresis, Fractionation, Nanoparticles


Giannotti, M. I., Esteban, O., Oliva, M., Garcia-Parajo, M. F., Sanz, F., (2011). pH-Responsive polysaccharide-based polyelectrolyte complexes as nanocarriers for lysosomal delivery of therapeutic proteins Biomacromolecules American Chemical Society 12, (7), 2524-2533

Nanopharmaceutics composed of a carrier and a protein have the potential to improve the activity of therapeutical proteins. Therapy for lysosomal diseases is limited by the lack of effective protein delivery systems that allow the controlled release of specific proteins to the lysosomes. Here we address this problem by developing functional polyelectrolyte-based nanoparticles able to promote acidic pH-triggered release of the loaded protein. Trimethyl chitosan (TMC) was synthesized and allowed to form polyelectrolyte complexes (PECs) with the lysosomal enzyme

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Malandrino, Andrea, Noailly, Jerome, Lacroix, Damien, (2011). The effect of sustained compression on oxygen metabolic transport in the intervertebral disc decreases with degenerative changes Plos Computational Biology 7, (8), 1-12

Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such relation, relevant to the maintenance of the tissue functional composition, would therefore link disc function with disc nutrition.

Keywords: Bovine nucleus pulposus, Human anulus fibrosus, Finite-element, Fluid-flow, Hydraulic permeability, Confined compression, Coupled diffusion, Solute transport, Water-content, Lumbar spine


Almendros, Isaac, Farre, Ramon, Planas, Anna M., Torres, Marta, Bonsignore, Maria R., Navajas, Daniel, Montserrat, Josep M., (2011). Tissue oxygenation in brain, muscle, and fat in a rat model of sleep apnea: Differential effect of obstructive apneas and intermittent hypoxia Sleep 34, (8), 1127-1133

Study Objectives: To test the hypotheses that the dynamic changes in brain oxygen partial pressure (PtO(2)) in response to obstructive apneas or to intermittent hypoxia differ from those in other organs and that the changes in brain PtO(2) in response to obstructive apneas is a source of oxidative stress. Design: Prospective controlled animal study. Setting: University laboratory. Participants: 98 Sprague-Dawley rats. Interventions: Cerebral cortex, skeletal muscle, or visceral fat tissues were exposed in anesthetized animals subjected to either obstructive apneas or intermittent hypoxia (apneic and hypoxic events of 15 s each and 60 events/h) for 1 h. Measurements and Results: Arterial oxygen saturation (spO(2)) presented a stable pattern, with similar desaturations during both stimuli. The PtO(2) was measured by a microelectrode. During obstructive apneas, a fast increase in cerebral PtO(2) was observed (38.2 +/- 3.4 vs. 54.8 +/- 5.9 mm Hg) but not in the rest of tissues. This particular cerebral response was not found during intermittent hypoxia. The cerebral content of reduced glutathione was decreased after obstructive apneas (46.2% +/- 15.2%) compared to controls (100.0% +/- 14.7%), but not after intermittent hypoxia. This antioxidant consumption after obstructive apneas was accompanied by increased cerebral lipid peroxidation under this condition. No changes were observed for these markers in the other tissues. Conclusions: These results suggest the cerebral cortex could be protected in some way from hypoxic periods caused by obstructive apneas. The increased cerebral PtO(2) during obstructive apneas may, however, cause harmful effects (oxidative stress). The obstructive apnea model appears to be more adequate than the intermittent hypoxia model for studying brain changes associated with OSA.

Keywords: Tissue oxygenation, Obstructive apnea, Intermittent hypoxia, Animal model, Oxidative stress


Carulla, Patricia, Bribian, Ana, Rangel, Alejandra, Gavin, Rosalina, Ferrer, Isidro, Caelles, Carme, Antonio del Rio, Jose, Llorens, Franc, (2011). Neuroprotective role of PrP(C) against kainate-induced epileptic seizures and cell death depends on the modulation of JNK3 activation by GluR6/7-PSD-95 binding Molecular Biology of the Cell 22, (17), 3041-3054

Cellular prion protein (PrP(C)) is a glycosyl-phosphatidylinositol-anchored glycoprotein. When mutated or misfolded, the pathogenic form (PrP(SC)) induces transmissible spongiform encephalopathies. In contrast, PrP(C) has a number of physiological functions in several neural processes. Several lines of evidence implicate PrP(C) in synaptic transmission and neuroprotection since its absence results in an increase in neuronal excitability and enhanced excitotoxicity in vitro and in vivo. Furthermore, PrP(C) has been implicated in the inhibition of N-methyl-D-aspartic acid (NMDA)-mediated neurotransmission, and prion protein gene (Prnp) knockout mice show enhanced neuronal death in response to NMDA and kainate (KA). In this study, we demonstrate that neurotoxicity induced by KA in Prnp knockout mice depends on the c-Jun N-terminal kinase 3 (JNK3) pathway since Prnp(%) Jnk3(%) mice were not affected by KA. Pharmacological blockage of JNK3 activity impaired PrP(C)-dependent neurotoxicity. Furthermore, our results indicate that JNK3 activation depends on the interaction of PrP(C) with postsynaptic density 95 protein (PSD-95) and glutamate receptor 6/7 (GluR6/7). Indeed, GluR6-PSD-95 interaction after KA injections was favored by the absence of PrP(C). Finally, neurotoxicity in Prnp knockout mice was reversed by an AMPA/KA inhibitor (6,7-dinitroquinoxaline-2,3-dione) and the GluR6 antagonist NS-102. We conclude that the protection afforded by PrP(C) against KA is due to its ability to modulate GluR6/7-mediated neurotransmission and hence JNK3 activation.

Keywords: Ischemic brain-injury, Prion protein PrP(C), Stress-inducible protein-1, Synaptic plasticity, Neurite outgrowth, Signaling module, Caspase-3 activation, Organotypic cultures, Cerebral-ischemia


Izquierdo-Useros, Nuria, Esteban, Olga, Rodriguez-Plata, Maria T., Erkizia, Itziar, Prado, Julia G., Blanco, Julia, Garcia-Parajo, Maria F., Martinez-Picado, Javier, (2011). Dynamic imaging of cell-free and cell-associated viral capture in mature dendritic cells Traffic 12, (12), 1702-1713

Dendritic cells (DCs) capture human immunodeficiency virus (HIV) through a non-fusogenic mechanism that enables viral transmission to CD4(+) T cells, contributing to in vivo viral dissemination. Although previous studies have provided important clues to cell-free viral capture by mature DCs (mDCs), dynamic and kinetic insight on this process is still missing. Here, we used three-dimensional videomicroscopy and single-particle tracking approaches to dynamically dissect both cell-free and cell-associated viral capture by living mDCs. We show that cell-free virus capture by mDCs operates through three sequential phases: virus binding through specific determinants expressed in the viral particle, polarized or directional movements toward concrete regions of the cell membrane and virus accumulation in a sac-like structure where trapped viral particles display a hindered diffusive behavior. Moreover, real-time imaging of cell-associated viral transfer to mDCs showed a similar dynamics to that exhibited by cell-free virus endocytosis leading to viral accumulation in compartments. However, cell-associated HIV type 1 transfer to mDCs was the most effective pathway, boosted throughout enhanced cellular contacts with infected CD4(+) T cells. Our results suggest that in lymphoid tissues, mDC viral uptake could occur either by encountering cell-free or cell-associated virus produced by infected cells generating the perfect scenario to promote HIV pathogenesis and impact disease progression.

Keywords: Dendritic cells, HIV-1, Live cell imaging, Trans-infection


Bohner, M., Loosli, Y., Baroud, G., Lacroix, D., (2011). Commentary: Deciphering the link between architecture and biological response of a bone graft substitute Acta Biomaterialia 7, (2), 478-484

Hundreds of studies have been devoted to the search for the ideal architecture for bone scaffold. Despite these efforts, results are often contradictory, and rules derived from these studies are accordingly vague. In fact, there is enough evidence to postulate that ideal scaffold architecture does not exist. The aim of this document is to explain this statement and review new approaches to decipher the existing but complex link between scaffold architecture and in vivo response.

Keywords: Biomaterial, Bone, Tissue engineering, Resorbable, Graft


Gustavsson, J., Ginebra, M. P., Engel, E., Planell, J., (2011). Ion reactivity of calcium-deficient hydroxyapatite in standard cell culture media Acta Biomaterialia 7, (12), 4242-4252

Solution-mediated surface reactions occur for most calcium phosphate-based biomaterials and may influence cellular response. A reasonable extrapolation of such processes observed in vitro to in vivo performance requires a deep understanding of the underlying mechanisms. We therefore systematically investigated the nature of ion reactivity of calcium-deficient hydroxyapatite (CDHA) by exposing it for different periods of time to standard cell culture media of different chemical composition (DMEM and McCoy medium, with and without osteogenic supplements and serum proteins). Kinetic ion interaction studies of principal extracellular ions revealed non-linear sorption of Ca2+ (∼50% sorption) and K+ (∼8%) as well as acidification of all media during initial contact with CDHA (48 h). Interestingly, inorganic phosphorus (Pi) was sorbed from McCoy medium (∼50%) or when using osteogenic media containing

Keywords: Hydroxyapatite, Bioactive materials, Cell culture medium, Ion exchange, Sorption models


Perut, F., Montufar, E. B., Ciapetti, G., Santin, M., Salvage, J., Traykova, T., Planell, J. A., Ginebra, M. P., Baldini, N., (2011). Novel soybean/gelatine-based bioactive and injectable hydroxyapatite foam: Material properties and cell response Acta Biomaterialia 7, (4), 1780-1787

Despite their known osteoconductivity, clinical use of calcium phosphate cements is limited both by their relatively slow rate of resorption and by rheological properties incompatible with injectability. Bone in-growth and material resorption have been improved by the development of porous calcium phosphate cements. However, injectable formulations have so far only been obtained through the addition of relatively toxic surfactants. The present work describes the response of osteoblasts to a novel injectable foamed bone cement based on a composite formulation including the bioactive foaming agents soybean and gelatine. The foaming properties of both defatted soybean and gelatine gels were exploited to develop a self-hardening soy/gelatine/hydroxyapatite composite foam able to retain porosity upon injection. After setting, the foamed paste produced a calcium-deficient hydroxyapatite scaffold, showing good injectability and cohesion as well as interconnected porosity after injection. The intrinsic bioactivity of soybean and gelatine was shown to favour osteoblast adhesion and growth. These findings suggest that injectable, porous and bioactive calcium phosphate cements can be produced for bone regeneration through minimally invasive surgery.

Keywords: Calcium phosphate cement, Composite, Bone tissue engineering, Cell viability, Bioactivity


Crona, Mikael, Torrents, Eduard, Rohr, Asmund K., Hofer, Anders, Furrer, Ernst, Tomter, Ane B., Andersson, K. Kristoffer, Sahlin, Margareta, Sjoberg, Britt-Marie, (2011). NrdH-redoxin protein mediates high enzyme activity in manganese-reconstituted ribonucleotide reductase from bacillus anthracis Journal of Biological Chemistry 286, (38), 33053-33060

Bacillus anthracis is a severe mammalian pathogen encoding a class Ib ribonucleotide reductase (RNR). RNR is a universal enzyme that provides the four essential deoxyribonucleotides needed for DNA replication and repair. Almost all Bacillus spp. encode both class Ib and class III RNR operons, but the B. anthracis class III operon was reported to encode a pseudogene, and conceivably class Ib RNR is necessary for spore germination and proliferation of B. anthracis upon infection. The class Ib RNR operon in B. anthracis encodes genes for the catalytic NrdE protein, the tyrosyl radical metalloprotein NrdF, and the flavodoxin protein NrdI. The tyrosyl radical in NrdF is stabilized by an adjacent Mn(2)(III) site (Mn-NrdF) formed by the action of the NrdI protein or by a Fe(2)(III) site (Fe-NrdF) formed spontaneously from Fe(2+) and O(2). In this study, we show that the properties of B. anthracis Mn-NrdF and Fe-NrdF are in general similar for interaction with NrdE and NrdI. Intriguingly, the enzyme activity of Mn-NrdF was approximately an order of magnitude higher than that of Fe-NrdF in the presence of the class Ib-specific physiological reductant NrdH, strongly suggesting that the Mn-NrdF form is important in the life cycle of B. anthracis. Whether the Fe-NrdF form only exists in vitro or whether the NrdF protein in B. anthracis is a true cambialistic enzyme that can work with either manganese or iron remains to be established.

Keywords: Escherichia-coli, Corynebacterium-ammoniagenes, Crystal-structure, Cofactor, Cubunit, Growth, Genes


Calvo, Daniel, Tort, Nuria, Pablo Salvador, J., Marco, M. Pilar, Centi, Fabiana, Marco, Santiago, (2011). Preliminary study for simultaneous detection and quantification of androgenic anabolic steroids using ELISA and pattern recognition techniques Analyst 136, (-----), 4045-4052

A first step towards the multidetection, identification and quantification of anabolic androgenic steroids by enzyme-linked immunosorbent assay (ELISA) has been performed in this study. This proposal combines multiple competitive ELISA assays with different cross-reactivity profiles and multivariate data analysis techniques. Data have been analyzed by principal component analysis in conjunction with a novel K-nearest line classifier. This proposal allows simultaneous detection of up to four different steroids in the range of concentration from 0.1 to 316.2 nM with a total rate of 90.6% of correct detection, even in the presence of cross-reactivities. A methodology for concentration prediction is also presented with satisfactory results.

Keywords: -----


Dols-Perez, Aurora, Fumagalli, Laura, Cohen Simonsen, Adam, Gomila, Gabriel, (2011). Ultrathin spin-coated dioleoylphosphatidylcholine lipid layers in dry conditions: A combined atomic force microscopy and nanomechanical study Langmuir 27, (21), 13165-13172

Atomic force microscopy (AFM) has been used to study the structural and mechanical properties of low concentrated spin-coated dioleoylphosphatidylcholine (DOPC) layers in dry environment (RH approximate to 0%) at the nanoscale. It is shown that for concentrations in the 0.1-1 mM range the structure of the DOPC spin-coated samples consists of an homogeneous lipid monolayer similar to 1.3 nm thick covering the whole substrate on top of which lipid bilayer (or multilayer) micro- and nanometric patches and rims are formed. The thickness of the bilayer structures is found to be similar to 4.5 nm (or multiples of this value for multilayer structures), while the lateral dimensions range from micrometers to tens of nanometer depending on the lipid concentration. The force required to break a bilayer (breakthrough force) is found to be similar to 0.24 nN. No dependence of the mechanical values on the lateral dimensions of the bilayer structures is evidenced. Remarkably, the thickness and breakthrough force values of the bilayers measured in dry environment are very similar to values reported in the literature for supported DOPC bilayers in pure water.


Sjoberg, B. M., Torrents, E., (2011). Shift in ribonucleotide reductase gene expression in pseudomonas aeruginosa during infection Infection and Immunity 79, (7), 2663-2669

The roles of different ribonucleotide reductases (RNRs) in bacterial pathogenesis have not been studied systematically. In this work we analyzed the importance of the different Pseudomonas aeruginosa RNRs in pathogenesis using the Drosophila melanogaster host-pathogen interaction model. P. aeruginosa codes for three different RNRs with different environmental requirements. Class II and III RNR chromosomal mutants exhibited reduced virulence in this model. Translational reporter fusions of RNR gene nrdA, nrdJ, or nrdD to the green fluorescent protein were constructed to measure the expression of each class during the infection process. Analysis of the P. aeruginosa infection by flow cytometry revealed increased expression of nrdJ and nrdD and decreased nrdA expression during the infection process. Expression of each RNR class fits with the pathogenicities of the chromosomal deletion mutants. An extended understanding of the pathogenicity and physiology of P. aeruginosa will be important for the development of novel drugs against infections in cystic fibrosis patients.

Keywords: Broad-host-range, Anaerobic growth, Drosophila-melanogaster, Bacterial biofilms, Escherichia-coli, Cystic-fibrosis, Model host, Virulence, Promoter, Vectors


Pedro, L., Banos, R. C., Aznar, S., Madrid, C., Balsalobre, C., Juarez, A., (2011). Antibiotics shaping bacterial genome: Deletion of an IS91 flanked virulence determinant upon exposure to subinhibitory antibiotic concentrations PLoS ONE 6, (11), 11

The nucleoid-associated proteins Hha and YdgT repress the expression of the toxin a-hemolysin. An Escherichia coli mutant lacking these proteins overexpresses the toxin a-hemolysin encoded in the multicopy recombinant plasmid pANN202-312R. Unexpectedly, we could observe that this mutant generated clones that no further produced hemolysin (Hly(-)). Generation of Hly(-) clones was dependent upon the presence in the culture medium of the antibiotic kanamycin (km), a marker of the hha allele (hha::Tn5). Detailed analysis of different Hly(-) clones evidenced that recombination between partial IS91 sequences that flank the hly operon had occurred. A fluctuation test evidenced that the presence of km in the culture medium was underlying the generation of these clones. A decrease of the km concentration from 25 mg/l to 12.5 mg/l abolished the appearance of Hly(-) derivatives. We considered as a working hypothesis that, when producing high levels of the toxin (combination of the hha ydgT mutations with the presence of the multicopy hemolytic plasmid pANN202-312R), the concentration of km of 25 mg/l resulted subinhibitory and stimulated the recombination between adjacent IS91 flanking sequences. To further test this hypothesis, we analyzed the effect of subinhibitory km concentrations in the wild type E. coli strain MG1655 harboring the parental low copy number plasmid pHly152. At a km concentration of 5 mg/l, subinhibitory for strain MG1655 (pHly152), generation of Hly(-) clones could be readily detected. Similar results were also obtained when, instead of km, ampicillin was used. IS91 is flanking several virulence determinants in different enteric bacterial pathogenic strains from E. coli and Shigella. The results presented here evidence that stress generated by exposure to subinhibitory antibiotic concentrations may result in rearrangements of the bacterial genome. Whereas some of these rearrangements may be deleterious, others may generate genotypes with increased virulence, which may resume infection.

Keywords: Promotes horizontal dissemination, Enterica serovar typhimurium, Escherichia-coli strains, Insertion-sequence IS91, H-NS, Adaptive amplification, Pathogenicity islands, Hemolysin


Llorens, Franc, Hummel, Manuela, Pastor, Xavier, Ferrer, Anna, Pluvinet, Raquel, Vivancos, Ana, Castillo, Ester, Iraola, Susana, Mosquera, Ana M., Gonzalez, Eva, Lozano, Juanjo, Ingham, Matthew, Dohm, Juliane C., Noguera, Marc, Kofler, Robert, Antonio del Rio, Jose, Bayes, Monica, Himmelbauer, Heinz, Sumoy, Lauro, (2011). Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis BMC Genomics 12, 326

Background: Epidermal Growth Factor (EGF) is a key regulatory growth factor activating many processes relevant to normal development and disease, affecting cell proliferation and survival. Here we use a combined approach to study the EGF dependent transcriptome of HeLa cells by using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer. Results: By applying a procedure for cross-platform data meta-analysis based on RankProd and GlobalAncova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We use this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we find an entirely new set of genes previously unrelated to the currently accepted EGF associated cellular functions. Conclusions: We propose that the use of global genomic cross-validation derived from high content technologies (microarrays or deep sequencing) can be used to generate more reliable datasets. This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data.

Keywords: Gene-expression measurements, Quality-control maqc, Cancer-cell-lines, Real-time pcr, Oligonucleotide microarrays, Phosphorylation dynamics, In-vivo, Networks, Signal, Technologies


Miranda Coelho, Nuno, Gonzalez-Garcia, Cristina, Salmeron-Sanchez, Manuel, Altankov, George, (2011). Arrangement of type IV collagen and laminin on substrates with controlled density of -OH groups Tissue Engineering Part A 17, (17-18), 2245-2257

Collagen IV (Col IV) and laminin (Lam) are the main structural components of the basement membrane where they form two overlapping polymeric networks. We studied the adsorption pattern of these proteins on five model surfaces with tailored density of -OH groups obtained by copolymerization of different ratios ethyl acrylate (EA) and hydroxyl EA (HEA): X(OH) = 0, X(OH) = 0.3, X(OH) = 0.5, X(OH) = 0.7, and X(OH) = 1 (where X refers the ratio of HEA). Atomic force microscopy revealed substratum-specific adsorption patterns of Col IV and Lam, ranging from single molecules deposition on more hydrophilic substrata to the formation of complex networks on hydrophobic ones. Human umbilical endothelial cells were used to study the biological performance of adsorbed proteins, following the overall cell morphology, the quantities for cell adhesion and spreading, and the development of focal adhesion complexes and actin cytoskeleton. Surprisingly, two optima in the cellular interaction were observed-one on the most hydrophilic X(OH) = 1 and other on the relatively hydrophobic X(OH) = 0.3 substrate-valid for both Col IV and Lam. When the proteins were adsorbed consecutively, a hydrophobic shift to X(OH) = 0 substratum was obtained. Collectively, these data suggest that varying with the density of -OH groups one can tailor the conformation and the functional activity of adsorbed basement membrane proteins.

Keywords: Atomic-force microscopy, Fibronectin adsorption, Basement-membranes, Polymer surfaces, Cell-adhesion, Biomaterials, Wettability, Fibrinogen


Miranda Coelho, Nuno, Gonzalez-Garcia, Cristina, Salmeron-Sanchez, Manuel, Altankov, George, (2011). Arrangement of type IV collagen on NH(2) and COOH functionalized surfaces Biotechnology and Bioengineering 108, (12), 3009-3018

Apart from the paradigm that cell-biomaterials interaction depends on the adsorption of soluble adhesive proteins we anticipate that upon distinct conditions also other, less soluble ECM proteins such as collagens, associate with the biomaterials interface with consequences for cellular response that might be of significant bioengineering interest. Using atomic force microscopy (AFM) we seek to follow the nanoscale behavior of adsorbed type IV collagen (Col IV)-a unique multifunctional matrix protein involved in the organization of basement membranes (BMs) including vascular ones. We have previously shown that substratum wettability significantly affects Col IV adsorption pattern, and in turn alters endothelial cells interaction. Here we introduce two new model surfaces based on self-assembled monolayers (SAMs), a positively charged - NH(2), and negatively charged -COOH surface, to learn more about their particular effect on Col IV behavior. AFM studies revealed distinct pattern of Col IV assembly onto the two SAMs resembling different aspects of network-like structure or aggregates (suggesting altered protein conformation). Moreover, the amount of adsorbed FITC-labeled Col IV was quantified and showed about twice more protein on NH(2) substrata. Human umbilical vein endothelial cells attached less efficiently to Col IV adsorbed on negatively charged COOH surface judged by altered cell spreading, focal adhesions formation, and actin cytoskeleton development. Immunofluorescence studies also revealed better Col IV recognition by both alpha(1) and alpha(2) integrins on positively charged NH(2) substrata resulting in higher phosphorylated focal adhesion kinase recruitment in the focal adhesion complexes. On COOH surface, no integrin clustering was observed. Taken altogether these results, point to the possibility that combined NH(2) and Col IV functionalization may support endothelization of cardiovascular implants.

Keywords: Collagen type IV, SAMs, AFM, Surface-induced protein assembly, Endothelial cells, Vascular grafts


Caballero-Briones, F., Palacios-Padrós, A., Sanz, Fausto, (2011). CuInSe2 films prepared by three step pulsed electrodeposition. Deposition mechanisms, optical and photoelectrochemical studies Electrochimica Acta 56, (26), 9556-9567

p-Type semiconducting copper indium diselenide thin films have been prepared onto In2O3:Sn substrates by a recently developed pulse electrodeposition method that consists in repeated cycles of three potential application steps. The Cu–In–Se electrochemical system and the related single component electrolytes were studied by cyclic voltammetry to identify the electrode processes and study the deposition processes. In situ atomic force microscopy measurements during the first 100 deposition cycles denote a continuous nucleation and growth mechanism. Particles removed by film sonication from some of the films were characterized by transmission electron microscopy and determined to consist in nanoscopic and crystalline CuInSe2. The remaining film is still crystalline CuInSe2, as assessed by X-ray diffraction. The chemical characterization by combined X-ray photoelectron spectroscopy, X-ray fluorescence and inductively coupled plasma optical emission spectroscopy, showed that films were Cu-poor and Se-poor. Raman characterization of the as-grown films showed that film composition varies with film thickness; thinner films are Se-rich, while thicker ones have an increased Cu–Se content. Different optical absorption bands were identified by the analysis of the UV–NIR transmittance spectra that were related with the presence of CuInSe2, ordered vacancy compounds, Se, Cu2−xSe and In2Se3. The photoelectrochemical activity confirmed the p-type character and showed a better response for the films prepared with the pulse method.

Keywords: CuInSe2, Solar cells, Electrodeposition, Optical properties, As-deposited films, ITO substrate


Garrido-Delgado, R., Arce, L., Guaman, A. V., Pardo, A., Marco, S., Valcárcel, M., (2011). Direct coupling of a gas-liquid separator to an Ion Mobility Spectrometer for the classification of different white wines using chemometrics tools Talanta 84, (2), 471-479

The potential of a vanguard technique as is the Ion Mobility Spectrometry with Ultraviolet ionization (UV-IMS) coupled to a Continuous Flow System (CFS) have been demonstrated in this work by using a Gas Phase Separator (GPS). This vanguard system (CFS-GPS-UV-IMS) has been used for the analysis of different types of white wines to obtain a characteristic profile for each type of wine and their posterior classification using different chemometric tools. Precision of the method was 3.1% expressed as relative standard deviation. A deep chemometric study was carried out for the classification of the four types of wines selected. The best classification performance was obtained by first reducing the data dimensionality by Principal Component Analysis (PCA) followed by Linear Discriminant Analysis (LDA) and finally using a K-Nearest Neighbour (kNN) classifier. The classification rate in an independent validation set were 92.0% classification rate value with confidence interval [89.0%, 95.0%] at P = 0.05 confidence level. The same white wines analyzed by using CFS-GPS-UV-IMS were analyzed by using Gas Chromatography with a Flame Detector (GC-FID) as conventional technique. The chromatographic method used for the determination of superior alcohols in wine samples shown in the Regulation CEE 1238/1992 was selected to carry out the analysis of the same samples set and later the classification using appropriate chemometric tools. In this case, strategies PCA-LDA and kNN classifier were also used for the correct classification of the wine samples. This combination showed similar results to the ones obtained with the proposed method.

Keywords: Classification, White wines, Ultraviolet-Ion Mobility Spectrometry, Gas Phase Separate, Vanguard method, Continuous Flow System, Chemometric analysis.


Manzo, C., van Zanten, T. S., Garcia-Parajo, M. F., (2011). Nanoscale fluorescence correlation spectroscopy on intact living cell membranes with NSOM probes Biophysical Journal 100, (2), L8-L10

Characterization of molecular dynamics on living cell membranes at the nanoscale is fundamental to unravel the mechanisms of membrane organization and compartmentalization. Here we demonstrate the feasibility of fluorescence correlation spectroscopy (FCS) based on the nanometric illumination of near-field scanning optical microscopy (NSOM) probes on intact living cells. NSOM-FCS applied to fluorescent lipid analogs allowed us to reveal details of the diffusion hidden by larger illumination areas. Moreover, the technique offers the unique, advantages of evanescent axial illumination and straightforward implementation of multiple color excitation. As such, NSOM-FCS represents a powerful tool to study a variety of dynamic processes occurring at the nanometer scale on cell membranes.

Keywords: Mode wave-guides, Lipid rafts, Difussion, Organization, Aperture


Perán, M., Sánchez-Ferrero, A., Tosh, D., Marchal, J. A., Lopez, E., Alvarez, P., Boulaiz, H., Rodríguez-Serrano, F., Aranega, A., (2011). Ultrastructural and molecular analyzes of insulin-producing cells induced from human hepatoma cells Cytotherapy 13, (2), 193-200

Background aims. Diabetes type I is an autoimmune disease characterized by the destruction of pancreatic insulin-producing (beta-) cells and resulting in external insulin dependence for life. Islet transplantation represents a potential treatment for diabetes but there is currently a shortage of suitable organs donors. To augment the supply of donors, different strategies are required to provide a potential source of beta-cells. These sources include embryonic and adult stem cells as well as differentiated cell types. The main goal of this study was to induce the transdifferentiation (or conversion of one type cell to another) of human hepatoma cells (HepG2 cells) to insulin-expressing cells based on the exposure of HepG2 cells to an extract of rat insulinoma cells (RIN). Methods. HepG2 cells were first transiently permeabilized with Streptolysin O and then exposed to a cell extract obtained from RIN cells. Following transient exposure to the RIN extract, the HepG2 cells were cultured for 3 weeks. Results. Acquisition of the insulin-producing cell phenotype was determined on the basis of (i) morphologic and (ii) ultrastructural observations, (iii) immunologic detection and (iv) reverse transcription (RT)-polymerase chain reaction (PCR) analysis. Conclusions. This study supports the use of cell extract as a feasible method for achieve transdifferentiation of hepatic cells to insulin-producing cells.

Keywords: Beta-cells, Diabetes, Insulin-producing cells, Transdifferentiation


de Alba, C. F., Solorzano, C., Paytubi, S., Madrid, C., Juarez, A., Garcia, J., Pons, M., (2011). Essential residues in the H-NS binding site of Hha, a co-regulator of horizontally acquired genes in Enterobacteria FEBS Letters 585, (12), 1765-1770

Proteins of the Hha/YmoA family co-regulate with H-NS the expression of horizontally acquired genes in Enterobacteria. Systematic mutations of conserved acidic residues in Hha have allowed the identification of D48 as an essential residue for H-NS binding and the involvement of E25. Mutations of these residues resulted in deregulation of sensitive genes in vivo. D48 is only partially solvent accessible, yet it defines the functional binding interface between Hha and H-NS confirming that Hha has to undergo a conformational change to bind H-NS. Exposed acidic residues, such as E25, may electrostatically facilitate and direct the approach of Hha to the positively charged region of H-NS enabling the formation of the final complex when D48 becomes accessible by a conformational change of Hha. Structured summary of protein interactions: YdgT and H-NS bind by nuclear magnetic resonance (View interaction) Hha and H-NS bind by nuclear magnetic resonance (View Interaction 1, 2, 3) Hha physically interacts with H-NS by pull down (View Interaction 1, 2).

Keywords: Nucleoid associated protein, H-NS, Hha, Transcription repression


Krishnan, Ramaswamy, Klumpers, Darinka D., Park, Chan Y., Rajendran, Kavitha, Trepat, Xavier, van Bezu, Jan, van Hinsbergh, Victor W. M., Carman, Christopher V., Brain, Joseph D., Fredberg, Jeffrey J., Butler, James P., van Nieuw Amerongen, Geerten P., (2011). Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces American Journal of Physiology - Cell Physiology 300, (1), C146-C154

A hallmark of many, sometimes life-threatening, inflammatory diseases and disorders is vascular leakage. The extent and severity of vascular leakage is broadly mediated by the integrity of the endothelial cell (EC) monolayer, which is in turn governed by three major interactions: cell-cell and cell-substrate contacts, soluble mediators, and biomechanical forces. A potentially critical but essentially uninvestigated component mediating these interactions is the stiffness of the substrate to which the endothelial monolayer is adherent. Accordingly, we investigated the extent to which substrate stiffening influences endothelial monolayer disruption and the role of cell-cell and cell-substrate contacts, soluble mediators, and physical forces in that process. Traction force microscopy showed that forces between cell and cell and between cell and substrate were greater on stiffer substrates. On stiffer substrates, these forces were substantially enhanced by a hyperpermeability stimulus (thrombin, 1 U/ml), and gaps formed between cells. On softer substrates, by contrast, these forces were increased far less by thrombin, and gaps did not form between cells. This stiffness-dependent force enhancement was associated with increased Rho kinase activity, whereas inhibition of Rho kinase attenuated baseline forces and lessened thrombin-induced inter-EC gap formation. Our findings demonstrate a central role of physical forces in EC gap formation and highlight a novel physiological mechanism. Integrity of the endothelial monolayer is governed by its physical microenvironment, which in normal circumstances is compliant but during pathology becomes stiffer.

Keywords: Contraction, Human umbilical vein endothelial cells, Permeability, Traction force, Cell-cell contact, Cell-substrate contact, Substrate stiffness, Rho kinase, Vascular endothelial cadherin, Thrombin


Sánchez-Martín, M. J., Urbán, P., Pujol, M., Haro, I., Alsina, M. A., Busquets, M. A., (2011). Biophysical investigations of GBV-C E1 peptides as potential inhibitors of HIV-1 fusion peptide ChemPhysChem 12, (15), 2816-2822

Five peptide sequences corresponding to the E1 protein of GBV-C [NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18), and AQLVGELGSLYGPLSVSA (P22)] were synthesized because they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP)-vesicle interaction. In this work the interaction of these peptides with the HIV-1 FP, as well as with membrane models, was analyzed to corroborate their inhibition ability and to understand if the interaction with the fusion peptide takes place in solution or at the membrane level. Several studies were carried out on aggregation and membrane fusion, surface Plasmon resonance, and conformational analysis by circular dichroism. Moreover, in vitro toxicity assays, including cytotoxicity studies in 3T3 fibroblasts and hemolysis assays in human red blood cells, were performed to evaluate if these peptides could be potentially used in anti-HIV-1 therapy. Results show that P10 is not capable of inhibiting membrane fusion caused by HIV-1 and it aggregates liposomes and fuses membranes, thus we decided to discard it for futures studies. P18 and P22 do not inhibit membrane fusion, but they inhibit the ability of HIV-1 FP to form pores in bilayers, thus we have not discarded them yet. P7 and P8 were selected as the best candidates for future studies because they are capable of inhibiting membrane fusion and the interaction of HIV-1 FP with bilayers. Therefore, these peptides could be potentially used in future anti-HIV-1 research. Part of the gang: Liposomes are deposited on a surface plasmon resonance chip (see AFM image of the chip) to observe the interaction of peptides corresponding to the E1 envelop protein of the hepatitis G virus with membranes to show how they reduce the interaction of the HIV-1 fusion peptide.

Keywords: HIV-1 fusion protein, Liposomes, Membranes, Peptides, Viruses


Almendros, I., Farré, R., Torres, M., Bonsignore, M. R., Dalmases, M., Ramírez, J., Navajas, D., Montserrat, J. M., (2011). Early and mid-term effects of obstructive apneas in myocardial injury and inflammation Sleep Medicine 12, (10), 1037-1040

Background: Obstructive sleep apnea (OSA) is associated with cardiovascular disorders, but the different comorbidities in OSA patients make it difficult to know their specific effects on the development of cardiovascular injury. The aim of the present study was to investigate whether recurrent obstructive apneas could lead to myocardial injury. Methods: Thirty-six male Sprague-Dawley rats (300-350. g) were either acutely (3. h) or sustainably (5. h/day, for 10. days) subjected to obstructive apneas with a pattern of 15. s each, 60. apneas/h. Corresponding control groups were formed for the acute and sustained models. To assess the induction of systemic inflammation, IL1-β was measured in plasma. Ventricular tissue injury was evaluated by histological techniques (presence of inflammatory cell infiltration, eosin autofluorescence, and detection of apoptosis). Results: After 3. h of obstructive apneas, a significant increase in IL1-β (64.9. ±. 29.6. ng/μl) were observed with respect to the controls (7.3. ±. 1.0. ng/μl), but no myocardial injury was present. Conversely to the acute model, the systemic inflammation triggered by obstructive apneas for 10. days was reduced. However, the percentage of area with enhanced eosin autofluorescence and of apoptotic cells (1.83. ±. 0.35% and 24.4. ±. 1.5%, respectively) was increased when compared to the control group (0.72. ±. 0.20% and 5.0. ±. 2.8%, respectively). Conclusions: This study suggests that obstructive apneas are a potential source of early systemic and ventricular inflammation and myocardial cell injury after sustained apneas application, which could represent an initial phase in the progression of heart disease associated with OSA.

Keywords: Animal models, Inflammation, Myocardial injury, Obstructive sleep apnea


Dellaca, Raffaele, Montserrat, Josep M., Govoni, Leonardo, Pedotti, Antonio, Navajas, Daniel, Farre, Ramon, (2011). Telemetric CPAP titration at home in patients with sleep apnea-hypopnea syndrome Sleep Medicine 12, (2), 153-157

Background: Home continuous positive airway pressure (CPAP) titration with automatic devices is not possible in a non-negligible percentage of patients with sleep apnea-hypopnea syndrome (SAHS). Objectives: To test the feasibility of a novel telemetric system for home CPAP titration. Methods: One-night home CPAP titration was carried out on 20 SAHS patients (56 +/- 3 years; BMI = 35 +/- 2 kg/m(2)). A telemetric unit, based on the conventional GPRS mobile phone network and connected to a commercial CPAP device, allowed the hospital technician to monitor flow, pressure and air leaks by remote control and titrate CPAP (elimination of apneas, hypopneas, flow limitation and snoring) in real time. After 1 week, a full hospital polysomnography was performed while the patient was subjected to the value of CPAP that was previously titrated at home via telemetry. Results: The home-titrated CPAP systematically improved patients' breathing: the apnea-hypopnea index and percentage of sleep time with arterial oxygen saturation below 90% were reduced from 58.1 +/- 5.1 to 3.8 +/- 0.6 events/h and from 19.8 +/- 1.1% to 4.4 +/- 0.7%, respectively. This CPAP value (9.15 +/- 0.47 cmH(2)O) was virtually the same as the pressure that optimized breathing during hospital polysomnography (9.20 +/- 0.41 cmH(2)O; mean difference: 0.02 cmH(2)O, limits of agreement: +/- 1.00 cmH(2)O). Conclusions: This pilot study shows that a simple telemetric system, requiring neither a special telemedicine network nor any infrastructure in the patient's home, made it possible to perform effective remote CPAP titration on SAHS patients.

Keywords: Home CPAP titration by telemetry, Telecare, Telemedicine, E-health, Obstructive sleep apnea, Point of care


Castillo-Fernandez, Oscar, Salieb-Beugelaar, Georgette B., van Nieuwkasteele, Jan W., Bomer, Johan G., Arundell, Martin, Samitier, Josep, van den Berg, Albert, Eijkel, Jan C. T., (2011). Electrokinetic DNA transport in 20 nm-high nanoslits: Evidence for movement through a wall-adsorbed polymer nanogel Electrophoresis 32, (18), 2402-2409

The electrokinetic transport behavior of lambda-DNA (48 kbp) in 20 nm-high fused-silica nanoslits in the presence of short-chain PVP is investigated. Mobility and video data show a number of phenomena that are typical of DNA transport through gels or polymer solutions, thus indicative of rigid migration obstacles in the DNA pathway. Calculations show that a several nanometer thin layer of wall-adsorbed PVP ('nano-gel') can provide such a rigid obstacle matrix to the DNA. Such ultrathin wall-adsorbed polymer layers represent a new type of matrix for electrokinetic DNA separation.

Keywords: λ-DNA, Biased reptation, Caterpillar movement, Nanoslits, Pathways, PVP


Mir, Monica, Martinez-Rodriguez, Sergio, Castillo-Fernandez, Oscar, Homs-Corbera, Antoni, Samitier, Josep, (2011). Electrokinetic techniques applied to electrochemical DNA biosensors Electrophoresis 32, (8), 811-821

Electrokinetic techniques are contact-free methods currently used in many applications, where precise handling of biological entities, such as cells, bacteria or nucleic acids, is needed. These techniques are based on the effect of electric fields on molecules suspended in a fluid, and the corresponding induced motion, which can be tuned according to some known physical laws and observed behaviours. Increasing interest on the application of such strategies in order to improve the detection of DNA strands has appeared during the recent decades. Classical electrode-based DNA electrochemical biosensors with combined electrokinetic techniques present the advantage of being able to improve the working electrode's bioactive part during their fabrication and also the hybridization yield during the sensor detection phase. This can be achieved by selectively manipulating, driving and directing the molecules towards the electrodes increasing the speed and yield of the floating DNA strands attached to them. On the other hand, this technique can be also used in order to make biosensors reusable, or reconfigurable, by simply inverting its working principle and pulling DNA strands away from the electrodes. Finally, the combination of these techniques with nanostructures, such as nanopores or nanochannels, has recently boosted the appearance of new types of electrochemical sensors that exploit the time-varying position of DNA strands in order to continuously scan these molecules and to detect their properties. This review gives an insight into the main forces involved in DNA electrokinetics and discusses the state of the art and uses of these techniques in recent years.

Keywords: Electrochemical DNA biosensors, Lab-on-a-chip (LOC), Micro-total analysis systems (mu TAS), Nanopore


Sandino, Clara, Lacroix, Damien, (2011). A dynamical study of the mechanical stimuli and tissue differentiation within a CaP scaffold based on micro-CT finite element models Biomechanics and Modeling in Mechanobiology 10, (4), 565-576

The control of the mechanical stimuli transmitted to the cells is critical for the design of functional scaffolds for tissue engineering. The objective of this study was to investigate the dynamics of the mechanical stimuli transmitted to the cells during tissue differentiation in an irregular morphology scaffold under compressive load and perfusion flow. A calcium phosphate-based glass porous scaffold was used. The solid phase and the fluid flow within the pores were modeled as linear elastic solid material and Newtonian fluid, respectively. In the fluid model, different levels of viscosity were used to simulate tissue differentiation. Compressive strain of 0.5% and fluid flow with constant inlet velocity of 10 μm/s or constant inlet pressure of 3 Pa were applied. Octahedral shear strain and fluid shear stress were used as mechano-regulatory stimuli. For constant inlet velocity, stimuli equivalent to bone were predicted in 80% of pore volume for the case of low tissue viscosity. For the cases of high viscosity, fluctuations between stimuli equivalent to tissue formation and cell death were predicted due to the increase in the fluid shear stress when tissue started to fill pores. When constant pressure was applied, stimuli equivalent to bone were predicted in 62% of pore volume when low tissue viscosity was used and 42% when high tissue viscosity was used. This study predicted critical variations of fluid shear stress when cells differentiated. If these variations are not controlled in vitro, they can impede the formation of new matured tissue.

Keywords: Engineering


Noailly, Jérôme, Planell, Josep, Lacroix, Damien, (2011). On the collagen criss-cross angles in the annuli fibrosi of lumbar spine finite element models Biomechanics and Modeling in Mechanobiology 10, (2), 203-219

In the human lumbar spine, annulus fibrosus fibres largely contribute to intervertebral disc stability. Detailed annulus models are therefore necessary to obtain reliable predictions of lumbar spine mechanics by finite element modelling. However, different definitions of collagen orientations coexist in the literature for healthy human lumbar annuli. Therefore, four annulus fibre-induced anisotropy models were built from reported anatomical descriptions, and inserted in a L3–L5 lumbar bi-segment finite element model. Annulus models were, respectively, characterized by radial, tangential, radial and tangential, and no fibre orientation gradients. The effect of rotational and axial compressive loadings was simulated and first, predictions were compared to experimental data. Then, intervertebral disc local biomechanics was studied under axial rotation and axial compression. A new parameter, i.e. the fibre contribution quality parameter, was computed in the anterior, lateral, postero-lateral, and posterior annuli of each model, in function of fibre stresses, radial load distributions, and matrix shear strains. Locally, each annulus model behaved differently, affecting intervertebral disc biomechanics and segmental motions. The fibre contribution quality parameter allowed establishing direct links between local annulus fibre organization and local annulus loadings, while other kinematical and biomechanical data did not. It was concluded that functional relations should exist between local annulus fibre orientations and overall segment morphology. The proposed fibre contribution quality parameter could be used to examine such relations and calibrate lumbar spine finite element models by locally adjusting the annulus bundle criss-cross angles. Conclusions of this study are particularly relevant to patient-specific models or artificial disc designs.

Keywords: Physics and Astronomy


Miguel Munoz, Luis, Casals, Alicia, Frigola, Manel, Amat, Josep, (2011). Motor-model-based dynamic scaling in human-computer interfaces IEEE Transactions on Systems Man and Cybernetics Part B-Cybernetics 41, (2), 435-447

This paper presents a study on how the application of scaling techniques to an interface affects its performance. A progressive scaling factor based on the position and velocity of the cursor and the targets improves the efficiency of an interface, thereby reducing the user's workload. The study uses several human-motor models to interpret human intention and thus contribute to defining and adapting the scaling parameters to the execution of the task. Two techniques addressed to vary the control-display ratio are compared, and a new method for aiding in the task of steering is proposed.

Keywords: Performance, Movements


Queiroz, Mário H., Madrid, Cristina, Paytubi, Sònia, Balsalobre, Carlos, Juárez, Antonio, (2011). Integration Host Factor alleviates H-NS silencing of the Salmonella enterica serovar Typhimurium master regulator of SPI1, hilA Microbiology-Sgm 157, (9), 2504-2514

Coordination of the expression of Salmonella enterica invasion genes on pathogenicity island 1 (SPI1) depends on a complex circuit involving several regulators that converge on expression of the hilA gene, which encodes a transcriptional activator (HilA), that modulates expression of the SPI1 virulence genes. Two of the global regulators influencing hilA expression are the nucleoid associated proteins Hha and H-NS. They interact and form a complex that modulates gene expression. A chromosomal transcriptional fusion was constructed to assess the effect of these modulators on hilA transcription under several environmental conditions as well as at different stages of the growth curve. The results obtained showed that these proteins play a relevant role in silencing hilA expression both at low temperature and low osmolarity, irrespective of the growth phase. H-NS accounts for the main repressory activity. At high temperature and osmolarity H-NS-mediated silencing completely ceases when cells enter the stationary phase, and hilA expression is induced. Mutants lacking IHF did not induce hilA in cells entering the stationary phase, and this lack of induction was dependent on the presence of H-NS. Band shift assays and in vitro transcription data evidence that for hilA induction under certain growth conditions, IHF is required to alleviate H-NS-mediated silencing.

Keywords: -----


Gugutkov, Dencho, Gonzalez-Garcia, Cristina, Altankov, George, Salmeron-Sanchez, Manuel, (2011). Fibrinogen organization at the cell-material interface directs endothelial cell behavior Journal of Bioactive and Compatible Polymers 26, (4), 375-387

Fibrinogen (FG) adsorption on surfaces with controlled fraction of -OH groups was investigated with AFM and correlated to the initial interaction of primary endothelial cells (HUVEC). The -OH content was tailored making use of a family of copolymers consisting of ethyl acrylate (EA) and hydroxyl ethyl acrylate (HEA) in different ratios. The supramolecular distribution of FG changed from an organized network-like structure on the most hydrophobic surface (-OH(0)) to dispersed molecular aggregate one as the fraction of -OH groups increases, indicating a different conformation by the adsorbed protein. The best cellular interaction was observed on the most hydrophobic (-OH(0)) surface where FG assembled in a fibrin-like appearance in the absence of any thrombin. Likewise, focal adhesion formation and actin cytoskeleton development was poorer as the fraction of hydroxy groups on the surface was increased. The biological activity of the surface-induced FG network to provide 3D cues in a potential tissue engineered scaffold, making use of electrospun PEA fibers (-OH(0)), seeded with human umbilical vein endothelial cells was investigated. The FG assembled on the polymer fibers gave rise to a biologically active network able to direct cell orientation along the fibers (random or aligned), promote cytoskeleton organization and focal adhesion formation.

Keywords: Fibrinogen, Cell-material interactions, HUVEC, Electrospun fibers, Fibrinogen organization, Cell-material interface, Endothelial cell behavior, Ethyl acrylate, Hydroxyl ethyl acrylate


Galbusera, F., Schmidt, H., Noailly, J., Malandrino, A., Lacroix, D., Wilke, H.J, Shirazi-Adl, A., (2011). Comparison of four methods to simulate swelling in poroelastic finite element models of intervertebral discs Journal of the Mechanical Behavior of Biomedical Materials 4, (7), 1234-1241

Osmotic phenomena influence the intervertebral disc biomechanics. Their simulation is challenging and can be undertaken at different levels of complexity. Four distinct approaches to simulate the osmotic behaviour of the intervertebral disc (a fixed boundary pore pressure model, a fixed osmotic pressure gradient model in the whole disc or only in the nucleus pulposus, and a swelling model with strain-dependent osmotic pressure) were analysed. Predictions were compared using a 3D poroelastic finite element model of a L4–L5 spinal unit under three different loading conditions: free swelling for 8 h and two daily loading cycles: (i) 200 N compression for 8 h followed by 500 N compression for 16 h; (ii) 500 N for 8 h followed by 1000 N for 16 h. Overall, all swelling models calculated comparable results, with differences decreasing under greater loads. Results predicted with the fixed boundary pore pressure and the fixed osmotic pressure in the whole disc models were nearly identical. The boundary pore pressure model, however, cannot simulate differential osmotic pressures in disc regions. The swelling model offered the best potential to provide more accurate results, conditional upon availability of reliable values for the required coefficients and material properties. Possible fields of application include mechanobiology investigations and crack opening and propagation. However, the other approaches are a good compromise between the ease of implementation and the reliability of results, especially when considering higher loads or when the focus is on global results such as spinal kinematics.

Keywords: Intervertebral disc, Boundary pore pressure, Osmotic pressure, Swelling, Finite element, Poroelasticity


Byrne, Damien P., Lacroix, Damien, Prendergast, Patrick J., (2011). Simulation of fracture healing in the tibia: Mechanoregulation of cell activity using a lattice modeling approach Journal of Orthopaedic Research 29, (10), 1496-1503

In this study, a three-dimensional (3D) computational simulation of bone regeneration was performed in a human tibia under realistic muscle loading. The simulation was achieved using a discrete lattice modeling approach combined with a mechanoregulation algorithm to describe the cellular processes involved in the healing process namely proliferation, migration, apoptosis, and differentiation of cells. The main phases of fracture healing were predicted by the simulation, including the bone resorption phase, and there was a qualitative agreement between the temporal changes in interfragmentary strain and bending stiffness by comparison to experimental data and clinical results. Bone healing was simulated beyond the reparative phase by modeling the transition of woven bone into lamellar bone. Because the simulation has been shown to work with realistic anatomical 3D geometry and muscle loading, it demonstrates the potential of simulation tools for patient-specific pre-operative treatment planning.

Keywords: Tissue differentiation, Computational analysis, Mechanical conditions, Bone regeneration, Weight-bearing, Proliferation, Osteoblast, Stiffness, Ingrowth, Scaffold


Banos, R. C., Aznar, S., Madrid, C., Juarez, A., (2011). Differential functional properties of chromosomal- and plasmid-encoded H-NS proteins Research in Microbiology 162, (4), 382-385

The nucleoid-associated protein H-NS can be either chromosomal- or plasmid-encoded. We provide in this report evidence indicating that chromosomal- and plasmid-encoded H-NS proteins may differ in their functional properties. The modulatory function of chromosomal H-NS is antagonized by the H-NSTEPEC protein. We show that the H-NS protein encoded by the IncHI plasmid R27 (H-NSR27) is less sensitive to H-NSTEPEC antagonism than its chromosomal counterpart. H-NSR27 plays a relevant role by modulating R27 conjugation in response to temperature. Hence, we suggest that this modulator has evolved to avoid the deregulation of R27 conjugation by H-NSTEPEC-like proteins.

Keywords: H-NS, Conjugation, R27, H-NS antagonism, H-NSTEPEC


Urban, Patricia, Estelrich, Joan, Adeva, Alberto, Cortes, Alfred, Fernàndez-Busquets, X., (2011). Study of the efficacy of antimalarial drugs delivered inside targeted immunoliposomal nanovectors Nanoscale Research Letters 6, (1), 620

Paul Ehrlich's dream of a 'magic bullet' that would specifically destroy invading microbes is now a major aspect of clinical medicine. However, a century later, the implementation of this medical holy grail continues being a challenge in three main fronts: identifying the right molecular or cellular targets for a particular disease, having a drug that is effective against it, and finding a strategy for the efficient delivery of sufficient amounts of the drug in an active state exclusively to the selected targets. In a previous work, we engineered an immunoliposomal nanovector for the targeted delivery of its contents exclusively to Plasmodium falciparum-infected red blood cells [pRBCs]. In preliminary assays, the antimalarial drug chloroquine showed improved efficacy when delivered inside immunoliposomes targeted with the pRBC-specific monoclonal antibody BM1234. Because difficulties in determining the exact concentration of the drug due to its low amounts prevented an accurate estimation of the nanovector performance, here, we have developed an HPLC-based method for the precise determination of the concentrations in the liposomal preparations of chloroquine and of a second antimalarial drug, fosmidomycin. The results obtained indicate that immunoliposome encapsulation of chloroquine and fosmidomycin improves by tenfold the efficacy of antimalarial drugs. The targeting antibody used binds preferentially to pRBCs containing late maturation stages of the parasite. In accordance with this observation, the best performing immunoliposomes are those added to Plasmodium cultures having a larger number of late form-containing pRBCs. An average of five antibody molecules per liposome significantly improves in cell cultures the performance of immunoliposomes over non-functionalized liposomes as drug delivery vessels. Increasing the number of antibodies on the liposome surface correspondingly increases performance, with a reduction of 50% parasitemia achieved with immunoliposomes encapsulating 4 nM chloroquine and bearing an estimated 250 BM1234 units. The nanovector prototype described here can be a valuable platform amenable to modification and improvement with the objective of designing a nanostructure adequate to enter the preclinical pipeline as a new antimalarial therapy.

Keywords: Plasmodium falciparum, Antimalarial drug, Nanovector, Immuno-liposomes


Barthelmebs, L., Jonca, J., Hayat, A., Prieto-Simon, B., Marty, J. L., (2011). Enzyme-Linked Aptamer Assays (ELAAs), based on a competition format for a rapid and sensitive detection of Ochratoxin A in wine Food Control 22, (5), 737-743

Ochratoxin A (OTA) is one of the most important mycotoxins because of its high toxicity to both humans and animals and its occurrence in a number of basic foods and agro-products. The need to develop high-performing methods for OTA analysis able to improve the traditional ones is evident. In this work, through in vitro SELEX (Systematic Evolution of Ligands by EXponential enrichment) two aptamers, designated H8 and H12 were produced that bind with nanomolar affinity with Ochratoxin A (OTA). Two strategies were investigated by using an indirect and a direct competitive Enzyme-Linked Aptamer Assay (ELAA) and were compared to the classical competitive Enzyme-Linked Immunosorbent Assay (ELISA) for the determination of OTA in spiked red wine samples. The limit of detection attained (1 ng/mL), the midpoint value obtained (5 ng/mL) and the analysis time needed (125 min) for the real sample analysis validate the direct competitive ELAA as useful screening tool for routine use in the control of OTA level in wine.

Keywords: Competitive Enzyme-Linked Aptamer Assay (ELAA), DNA aptamer, Ochratoxin A, SELEX, Wine analysis


Rodriguez-Segui, Santiago A., Pons Ximenez, Jose Ignacio, Sevilla, Lidia, Ruiz, Ana, Colpo, Pascal, Rossi, Francois, Martinez, Elena, Samitier, Josep, (2011). Quantification of protein immobilization on substrates for cellular microarray applications Journal of Biomedical Materials Research - Part A 98A, (2), 245-256

Cellular microarray developments and its applications are the next step after DNA and protein microarrays. The choice of the surface chemistry of the substrates used for the implementation of this technique, that must favor proper protein immobilization while avoiding cell adhesion on the nonspotted areas, presents a complex challenge. This is a key issue since usually the best nonfouling surfaces are also the ones that retain immobilized the smallest amounts of printed protein. To quantitatively assess the amount of protein immobilization, in this study several combinations of fluorescently labeled fibronectin (Fn*) and streptavidin (SA*) were microspotted, with and without glycerol addition in the printing buffer, on several substrates suitable for cellular microarrays. The substrates assayed included chemically activated surfaces as well as Poly ethylene oxide (PEO) films that are nonfouling in solution but accept adhesion of proteins in dry conditions. The results showed that the spotted Fn* was retained by all the surfaces, although the PEO surface did show smaller amounts of immobilization. The SA*, on the other hand, was only retained by the chemically activated surfaces. The inclusion of glycerol in the printing buffer significantly reduced the immobilization of both proteins. The results presented in this article provide quantitative evidence of the convenience of using a chemically activated surface to immobilize proteins relevant for cellular microarray applications, particularly when ECM proteins are cospotted with smaller factors which are more difficult to be retained by the surfaces.

Keywords: Protein immobilization, Quantification, Microarray, Substrate, Surface chemistry


Fernandez, Javier G., Samitier, Josep, Mills, Christopher A., (2011). Simultaneous biochemical and topographical patterning on curved surfaces using biocompatible sacrificial molds Journal of Biomedical Materials Research - Part A 98A, (2), 229-234

A method for the simultaneous (bio)chemical and topographical patterning of enclosed structures in poly(dimethyl siloxane) (PDMS) is presented. The simultaneous chemical and topography transference uses a water-soluble chitosan sacrificial mold to impart a predefined pattern with micrometric accuracy to a PDMS replica. The method is compared to conventional soft-lithography techniques on planar surfaces. Its functionality is demonstrated by the transference of streptavidin directly to the surface of the three-dimensional PDMS structures as well as indirectly using streptavidin-loaded latex nanoparticles. The streptavidin immobilized on the PDMS is tested for bioactivity by coupling with fluorescently labeled biotin. This proves that the streptavidin is immobilized on the PDMS surface, not in the bulk of the polymer, and is therefore accessible for use as signaling/binding element in micro and bioengineering. The use of a biocompatible polymer and processes enables the technique to be used for the chemical patterning of tissue constructions.

Keywords: Biotechnology, Chitosan, Microfabrication, MEMs, Soft lithography


Lacroix, Damien, Ramirez Patino, Juan Fernando, (2011). Finite Element Analysis of Donning Procedure of a Prosthetic Transfemoral Socket Annals of Biomedical Engineering 39, (12), 2972-2983

Lower limb amputation is a severe psychological and physical event in a patient. A prosthetic solution can be provided but should respond to a patient-specific need to accommodate for the geometrical and biomechanical specificities. A new approach to calculate the stress-strain state at the interaction between the socket and the stump of five transfemoral amputees is presented. In this study the socket donning procedure is modeled using an explicit finite element method based on the patient-specific geometry obtained from CT and laser scan data. Over stumps the mean maximum pressure is 4 kPa (SD 1.7) and the mean maximum shear stresses are 1.4 kPa (SD 0.6) and 0.6 kPa (SD 0.3) in longitudinal and circumferential directions, respectively. Locations of the maximum values are according to pressure zones at the sockets. The stress-strain states obtained in this study can be considered more reliable than others, since there are normal and tangential stresses associated to the socket donning procedure.

Keywords: Trans-tibial prosthesis, Knee residual limb, Pressure distribution, Transtibial amputees, Stump/socket interface, Mechanical conditions, Load-transfer, Soft-tissues, Stresses, Contact


Roa, J. J., Oncins, G., Diaz, J., Capdevila, X. G., Sanz, F., Segarra, M., (2011). Study of the friction, adhesion and mechanical properties of single crystals, ceramics and ceramic coatings by AFM Journal of the European Ceramic Society 31, (4), 429-449

This paper reviews commonly used methods of analyzing and interpreting friction, adhesion and nanoindentation with an AFM tip test data, with a particular emphasis of the testing of single crystals, metals, ceramics and ceramic coatings. Experimental results are reported on the friction, mechanical and adhesion properties of these materials. The popularity of AFM testing is evidenced by the large quantity of papers that report such measurements in the last decade. Unfortunately, a lot of information about these topics is scare in the literature. The present paper is aimed to present the basic physical modelling employed and also some examples using each technique.

Keywords: Mechanical properties, Plasticity, Biomedical applications, Engine components


Zalvidea, D., Claverol-Tinturé, E., (2011). Second Harmonic Generation for time-resolved monitoring of membrane pore dynamics subserving electroporation of neurons Biomedical Optics Express 2, (2), 305-314

Electroporation of neurons, i.e. electric-field induced generation of membrane nanopores to facilitate internalization of molecules, is a classic technique used in basic neuroscience research and recently has been proposed as a promising therapeutic strategy in the area of neuro-oncology. To optimize electroporation parameters, optical techniques capable of delivering time and spatially-resolved information on electroporation pore formation at the nanometer scale would be advantageous. For this purpose we describe here a novel optical method based on second harmonic generation (SHG) microscopy. Due to the nonlinear and coherent nature of SHG, the 3D radiation lobes from stained neuronal membranes are sensitive to the spatial distribution of scatterers in the illuminated patch, and in particular to nanopore formation.We used phase-array analysis to computationally study the SHG signal as a function of nanopore size and nanopore population density and confirmed experimentally, in accordance with previous work, the dependence of nanopore properties on membrane location with respect to the electroporation electric field; higher nanopore densities, lasting < 5 milliseconds, are observed at membrane patches perpendicular to the field whereas lower density is observed at partly tangent locations. Differences between near-anode and near-cathode cell poles are also measured, showing higher pore densities at the anodic pole compared to cathodic pole. This technique is promising for the study of nanopore dynamics in neurons and for the optimization of novel electroporation-based therapeutic approaches.


Pegueroles, M., Aguirre, A., Engel, E., Pavon, G., Gil, F. J., Planell, J. A., Migonney, V., Aparicio, C., (2011). Effect of blasting treatment and Fn coating on MG63 adhesion and differentiation on titanium: a gene expression study using real-time RT-PCR Journal of Materials Science: Materials in Medicine 22, (3), 617-627

Biomaterial surface properties, via alterations in the adsorbed protein layer, and the presence of specific functional groups can influence integrin binding specificity, thereby modulating cell adhesion and differentiation processes. The adsorption of fibronectin, a protein directly involved in osteoblast adhesion to the extracellular matrix, has been related to different physical and chemical properties of biomaterial surfaces. This study used blasting particles of different sizes and chemical compositions to evaluate the response of MG63 osteoblast-like cells on smooth and blasted titanium surfaces, with and without fibronectin coatings, by means of real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays. This response included (a) expression of the alpha(5), alpha(v) and alpha(3) integrin subunits, which can bind to fibronectin through the RGD binding site, and (b) expression of alkaline phosphatase (ALP) and osteocalcin (OC) as cell-differentiation markers. ALP activity and synthesis of OC were also tested. Cells on SiC-blasted Ti surfaces expressed higher amounts of the alpha(5) mRNA gene than cells on Al2O3-blasted Ti surfaces. This may be related to the fact that SiC-blasted surfaces adsorbed higher amounts of fibronectin due to their higher surface free energy and therefore provided a higher number of specific cell-binding sites. Fn-coated Ti surfaces decreased alpha(5) mRNA gene expression, by favoring the formation of other integrins involved in adhesion over alpha(5)beta(1). The changes in alpha(5) mRNA expression induced by the presence of fibronectin coatings may moreover influence the osteoblast differentiation pathway, as fibronectin coatings on Ti surfaces also decreased both ALP mRNA expression and ALP activity after 14 and 21 days of cell culture.

Keywords: -----


Aydin, E., Planell, J. A., Hasirci, V., (2011). Hydroxyapatite nanorod-reinforced biodegradable poly(l-lactic acid) composites for bone plate applications Journal of Materials Science: Materials in Medicine 22, (11), 2413-2427

Novel PLLA composite fibers containing hydroxyapatite (HAp) nanorods with or without surface lactic acid grafting were produced by extrusion for use as reinforcements in PLLA-based bone plates. Fibers containing 0-50% (w/w) HAp nanorods, aligned parallel to fiber axis, were extruded. Lactic acid surface grafting of HAp nanorods (lacHAp) improved the tensile properties of composites fibers better than the non-grafted ones (nHAp). Best tensile modulus values of 2.59, 2.49, and 4.12 GPa were obtained for loadings (w/w) with 30% lacHAp, 10% nHAp, and 50% amorphous HAp nanoparticles, respectively. Bone plates reinforced with parallel rows of these composite fibers were molded by melt pressing. The best compressive properties for plates were obtained with nHAp reinforcement (1.31 GPa Young's Modulus, 110.3 MPa compressive strength). In vitro testing with osteoblasts showed good cellular attachment and spreading on composite fibers. In situ degradation tests revealed faster degradation rates with increasing HAp content. To our knowledge, this is the first study containing calcium phosphate-polymer nanocomposite fibers for reinforcement of a biodegradable bone plate or other such implants and this biomimetic design was concluded to have potential for production of polymer-based biodegradable bone plates even for load bearing applications.


Hristova, K., Pecheva, E., Pramatarova, L., Altankov, G., (2011). Improved interaction of osteoblast-like cells with apatite-nanodiamond coatings depends on fibronectin Journal of Materials Science: Materials in Medicine 22, (8), 1891-1900

New apatite (AP)/nanodiamond (ND) coating has been developed to improve physical and biological properties of stainless steel (SS) versus single AP coating. Homogeneously electrodeposited AP-ND layer demonstrates increased mechanical strength, interlayer cohesion and ductility. In the absence of serum, osteoblast-like MG63 cells attach well but poorly spread on both AP and AP-ND substrata. Pre-adsorption with serum or fibronectin (FN) improves the cellular interaction-an effect that is better pronounced on the AP-ND coating. In single protein adsorption study fluorescein isothiocyanate-labeled FN (FITC-FN) shows enhanced deposition on the AP-ND layer consistent with the significantly improved cell adhesion, spreading and focal adhesions formation (in comparison to SS and AP), particularly at low FN adsorption concentrations (1 mu g/ml). Higher FN concentrations (20 mu g/ml) abolish this difference suggesting that the promoted cellular interaction of serum (where FN is low) is caused by the greater affinity for FN. Moreover, it is found that MG63 cells tend to rearrange both adsorbed and secreted FN on the AP-ND layer suggesting facilitated FN matrix formation.

Keywords: Extracellular-matrix, Protein adsorption, Integrins, Adhesion, Biomaterials, Surfaces, Polymerization, Composite, Implants, Titanium


Rodríguez-Hernández, Ana, Juárez, A., Engel, E., Gil, F., (2011). Streptococcus sanguinis adhesion on titanium rough surfaces: effect of shot-blasting particles Journal of Materials Science: Materials in Medicine Springer Netherlands 22, (8), 1-10

Dental implant failure is commonly associated to dental plaque formation. This problem starts with bacterial colonization on implant surface upon implantation. Early colonizers (such as Streptococcus sanguinis) play a key role on that process, because they attach directly to the surface and facilitate adhesion of later colonizers. Surface treatments have been focused to improve osseointegration, where shot-blasting is one of the most used. However the effects on bacterial adhesion on that sort of surfaces have not been elucidated at all. A methodological procedure to test bacterial adherence to titanium shot-blasted surfaces (alumina and silicon carbide) by quantifying bacterial detached cells per area unit, was performed. In parallel, the surface properties of samples (i.e., roughness and surface energy), were analyzed in order to assess the relationship between surface treatment and bacterial adhesion. Rather than roughness, surface energy correlated to physicochemical properties of shot-blasted particles appears as critical factors for S. sanguinis adherence to titanium surfaces.

Keywords: Engineering


Cagido, Viviane Ramos, Zin, Walter Araujo, Ramirez, Jose, Navajas, Daniel, Farre, Ramon, (2011). Alternating ventilation in a rat model of increased abdominal pressure Respiratory Physiology & Neurobiology 175, (3), 310-315

During alternating ventilation (AV) one lung is inflating while the other is deflating. Considering the possible respiratory and hemodynamic advantages of AV, we investigated its effects during increased intra-abdominal pressure (IAP = 10 mmHg). In Sprague-Dawley rats (n = 6, 270–375 g) the main bronchi were independently cannulated, and respiratory mechanics determined while animals underwent different ventilatory patterns: synchronic ventilation without increased IAP (SV-0), elevated IAP during SV (SV-10), and AV with elevated IAP (AV-10). Thirty-three other animals (SV-0, n = 10; SV-10, n = 11 and AV-10, n = 12) were ventilated during 3 h. Mean arterial pressure (MAP), and lung histology were assessed. Increased IAP resulted in significantly higher elastances (p < 0.001), being AV-10 lower than SV-10 (p < 0.020). SV-10 showed higher central venous pressure (p < 0.003) than S-0; no change was observed in AV-10. Wet/dry lung weight ratio was lower in AV-10 than SV-10 (p = 0.009). Application of AV reduced hemodynamic and lung impairments induced by increased IAP during SV.

Keywords: Alternating ventilation, Respiratory mechanics, Intra-abdominal pressure, Hemodynamic, Mechanical ventilation, Animal model


Carreras, Alba, Wang, Yang, Gozal, David, Montserrat, Josep M., Navajas, Daniel, Farre, Ramon, (2011). Non-invasive system for applying airway obstructions to model obstructive sleep apnea in mice Respiratory Physiology & Neurobiology 175, (1), 164-168

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstructions during sleep. The most common animal model of OSA is based on subjecting rodents to intermittent hypoxic exposures and does not mimic important OSA features, such as recurrent hypercapnia and increased inspiratory efforts. To circumvent some of these issues, a novel murine model involving non-invasive application of recurrent airway obstructions was developed. An electronically controlled airbag system is placed in front of the mouse's snout, whereby inflating the airbag leads to obstructed breathing and spontaneous breathing occurs with the airbag deflated. The device was tested on 29 anesthetized mice by measuring inspiratory effort and arterial oxygen saturation (SaO(2)). Application of recurrent obstructive apneas (6s each, 120/h) for 6h resulted in SaO(2) oscillations to values reaching 84.4 +/- 2.5% nadir, with swings mimicking OSA patients. This novel system, capable of applying controlled recurrent airway obstructions in mice, is an easy-to-use tool for investigating pertinent aspects of OSA.

Keywords: Animal model, Upper airway Obstruction, Mouse model, Non-invasive system, Model sleep apnea, Respiratory disease


Perez, R. A., Del Valle, S., Altankov, G., Ginebra, M. P., (2011). Porous hydroxyapatite and gelatin/hydroxyapatite microspheres obtained by calcium phosphate cement emulsion Journal of Biomedical Materials Research - Part B: Applied Biomaterials 97B, (1), 156-166

Hydroxyapatite and hybrid gelatine/hydroxyapatite microspheres were obtained through a water in oil emulsion of a calcium phosphate cement (CPC). The setting reaction of the CPC, in this case the hydrolysis of alpha-tricalcium phosphate, was responsible for the consolidation of the microspheres. After the setting reaction, the microspheres consisted of an entangled network of hydroxyapatite crystals, with a high porosity and pore sizes ranging between 0.5 and 5 mu m. The size of the microspheres was tailored by controlling the viscosity of the hydrophobic phase, the rotation speed, and the initial powder size of the CPC. The incorporation of gelatin increased the sphericity of the microspheres, as well as their size and size dispersion. To assess the feasibility of using the microspheres as cell microcarriers, Saos-2 cells were cultured on the microspheres. Fluorescent staining, SEM studies, and LDH quantification showed that the microspheres were able to sustain cell growth. Cell adhesion and proliferation was significantly improved in the hybrid gelatin/hydroxyapatite microspheres as compared to the hydroxyapatite ones.

Keywords: Calcium phosphate(s), Bone graft, Microspheres, Composite/hard tissue, Hydroxy(1)lapatite


Banos, R. C., Martinez, J., Polo, C., Madrid, C., Prenafeta, A., Juarez, A., (2011). The yfeR gene of Salmonella enterica serovar Typhimurium encodes an osmoregulated LysR-type transcriptional regulator Fems Microbiology Letters 315, (1), 63-71

A genetic screening for osmoregulated genes allowed us to identify the yfeR gene of Salmonella enterica serovar Typhimurium. The yfeR gene product encodes a novel LysR-type transcriptional regulator (LTTR), the expression of which decreases when external osmolarity increases. Out of the adjacent gene yfeH, YfeR modulates expression of several genes that may be required for optimal growth under low osmolarity conditions.

Keywords: YfeR, Salmonella, LysR, Osmoregulation, LTTR


Adrados, B., Julian, E., Codony, F., Torrents, E., Luquin, M., Morato, J., (2011). Prevalence and concentration of non-tuberculous Mycobacteria in cooling towers by means of quantitative PCR: A prospective study Current Microbiology 62, (1), 313-319

There is an increasing level of interest in non-tuberculous mycobacteria (NTM) due to the increasing reported rates of diseases caused by them. Although it is well known that NTM are widely distributed in the environment it is necessary to identify its reservoirs to prevent possible infections. In this study, we aimed to investigate the occurrence and levels of NTM in cooling towers to provide evidences for considering these settings as possible sources of respiratory infections. In the current study, we detected and quantified the presence of NTM by means of a rapid method in water samples taken from 53 cooling towers of an urban area (Barcelona, Spain). A genus-specific quantitative PCR (Q-PCR) assay with a quantification limit (QL) of 500 cells l(-1) was used. 56% (30) of samples were positive with a concentration range from 4.6 x 10(3) to 1.79 x 10(6) cells l(-1). In some cases (9/30), samples were positive but with levels below the QL. The colonization rate confirmed that cooling towers could be considered as a potential reservoir for NTM. This study also evaluated Q-PCR as a useful method to detect and quantify NTM in samples coming from environmental sources.

Keywords: Real-time PCR, Disease, Identification, Tuberculosis, Pathogens, Waters


Morgenstern, R., Morgenstern, C., Jané, R., Lee, S. H., (2011). Usefulness of an expandable interbody spacer for the treatment of foraminal stenosis in extremely collapsed disks preliminary clinical experience with endoscopic posterolateral transforaminal approach Journal of Spinal Disorders & Techniques 24, (8), 485-491

Study Design: Clinical series of patients with degenerative disk disease undergoing an endoscopic posterolateral transforaminal procedure that used a reaming foraminoplasty technique to enlarge the foramen coupled with insertion of the B-Twin expandable spacer. Objectives: This retrospective analysis of 107 consecutive patients sought to assess the outcome of this surgical procedure. Summary of Background Data: Reamed endoscopic foraminoplasty under direct endoscopic vision has been shown to be suitable for extremely collapsed disks (> 50% total disk height) despite the difficult access, especially at L5-S1. The authors tried to investigate the efficacy of an expandable spacer being inserted by the endoscopic transforaminal approach to solve foraminal stenosis without bone fusion techniques. Methods: The procedure consists of bone reaming under direct endoscopic control to wide the foramen followed by insertion of the B-Twin expandable device as a disk spacer to restore partially or to maintain the height of the collapsed disk. Outcome measures included visual analog scale (VAS) for pain, the Oswestry Disability Index (ODI) for functional disability, and radioimaging studies. Results: Mean follow-up was 27.2 months. Clinical outcome was considered excellent in 64 patients, good in 25, fair in 10, and poor in 8. Results were similar in single and double B-Twin spacer insertions. Postoperative mean values for VAS and ODI scores improved significantly as compared with preoperative data. Mean VAS and ODI scores were significantly higher in patients with fair or poor results than in those with excellent or good outcome. In 2 cases, clear signs of end plate bone resorption in the control computed tomographic scans at 6 months and 12 months leading to a substantial loss of disk height were documented. Conclusions: This preliminary study has shown the efficacy of an endoscopic surgical technique for the treatment of foraminal stenosis in extremely collapsed disks.

Keywords: Foraminal stenosis, B-twin expandable spacer, Endoscopic foraminoplasty, Minimally invasive surgery, Surgical technique, Spinal spacer, Lumbar, Diskectomy, Fusion, Discectomy


Fiz, José Antonio, Solà, J., Jané, Raimon, (2011). Métodos de análisis del ronquido Medicina Clínica 137, (1), 36-42

El ronquido es un sonido respiratorio que se produce durante el sueño, ya sea nocturno o diurno. El ronquido puede ser inspiratorio, espiratorio o puede ocupar todo el ciclo respiratorio. Tiene su origen en la vibración de los diferentes tejidos de la vía aérea superior. Se han descrito numerosos métodos para analizarlo, desde el simple interrogatorio, pasando por cuestionarios estándares, hasta llegar a los métodos acústicos más sofisticados, que se han desarrollado gracias al gran avance de las técnicas biomédicas en los últimos años. El presente trabajo describe el estado del arte actual en los procedimientos de análisis del ronquido.

Keywords: Ronquido, Apnea del sueño, Síndrome de apnea-hipoapnea del sueño, Snoring, Sleep apnea, Sleep Apnea and Hipoapnea Syndrome


A. Mathur, P. Roca-Cusachs, O. M. Rossier, S. J. Wind, M. P. Sheetz, J. Hone, (2011). New approach for measuring protrusive forces in cells Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures 29, (6), 06FA02

Roa, J. J., Oncins, G., Diaz, J., Sanz, F., Segarra, M., (2011). Calculation of young's modulus value by means of AFM Recent Patents on Nanotechnology 5, (1), 27-36

In the last years, Atomic Force Microscopy (AFM) has become a powerful tool not only to study the surface morphology but also the nanomechanics of all kind of samples. In this paper, the applicability of this technique is reviewed and its basic aspects of operation, advantages and drawbacks of using the AFM probe as a picoindenter (Force Spectroscopy mode, FS-AFM) are discussed. The patents concerning picoindentation measurements are discussed in the text and special attention is paid to measurements performed on hard materials as ceramics, as they have not been as thoroughly reviewed in the literature as in the case of soft matter. The possibilities of AFM in the nanomechanics field include the quantitative determination of the Young's modulus (E) and the transition force from elastic to plastic deformation regimes, the measurement of adhesion forces and deformation mechanisms while applying vertical forces in the range from tens of pN to mu N.

Keywords: Hard materials, Young's modulus, AFM-FS, Picoindentation technique


Paytubi, S., Garcia, J., Juarez, A., (2011). Bacterial Hha-like proteins facilitate incorporation of horizontally transferred DNA Central European Journal of Biology 6, (6), 879-886

Horizontal gene transfer (HGT), non-hereditary transfer of genetic material between organisms, accounts for a significant proportion of the genetic variability in bacteria. In Gram negative bacteria, the nucleoid-associated protein H-NS silences unwanted expression of recently acquired foreign DNA. This, in turn, facilitates integration of the incoming genes into the regulatory networks of the recipient cell. Bacteria belonging to the family Enterobacteriaceae express an additional protein, the Hha protein that, by binding to H-NS, potentiates silencing of HGT DNA. We provide here an overview of Hha-like proteins, including their structure and function, as well as their evolutionary relationship. We finally present available information suggesting that, by expressing Hha-like proteins, bacteria such as Escherichia coli facilitate HGT incorporation and hence, the impact of HGT in their genetic diversity.

Keywords: Hha, H-NS, HGT DNA, Enterobacteria, Nucleoid-associated proteins, Enterica serovar typhimurium, Histone-like protein, h-ns, Escherichia-coli, Yersinia-enterocolitica, Salmonella-enterica


Rodríguez, J. E., Cruz, I., Vergés, E., Ayala, D., (2011). A connected-component-labeling-based approach to virtual porosimetry Graphical Models 73, (5), 296-310

Analyzing the pore-size distribution of porous materials, made up of an aggregation of interconnected pores, is a demanding task. Mercury intrusion porosimetry (MIP) is a physical method that intrudes mercury into a sample at increasing pressures to obtain a pore-size histogram. This method has been simulated in-silice with several approaches requiring prior computation of a skeleton. We present a new approach to simulate MIP that does not require skeleton computation. Our method is an iterative process that considers the diameters corresponding to pressures. At each iteration, geometric tests detect throats for the corresponding diameter and a CCL process collects the region invaded by the mercury. Additionally, a new decomposition model called CUDB, is used. This is suitable for computing the throats and performs better with the CCL algorithm than a voxel model. Our approach obtains the pore-size distribution of the porous medium, and the corresponding pore graph.

Keywords: Micro CT, Pore map, Porous media, Skeleton, Virtual MIP


Tahirbegi, I. B., Mir, M., (2011). Slit-wave model for band structures in solid state physics Modern Physics Letters B 25, (3), 151-161

The reason behind the entire development in silicon technology was band models in solid state physics. However, the theories postulated in order to give response to this phenomenon do not explain all kinds of materials. In a bid to overcome this limitation, we approach the problem from another point of view. In this work, the wave properties of the electrons from the external orbitals of the atoms and its diffraction patterns through the lattice structure of the material have been used to explain the band structure of metals, semiconductor and insulators. In order to probe this hypothesis, a simulation has been used and according to the relation between the lattice constant and the atomic diameter, the splitting of the bands have been observed for different kind of materials, showing a strong correlation between the simulation and the experimental results.

Keywords: Electrical band structure, Band gap, Fraunhofer diffraction, Semiconductor, Insulator


Garde, A., Giraldo, B.F., Sornmo, L., Jané, R., (2011). Analysis of the respiratory flow cycle morphology in chronic heart failure patients applying principal components analysis Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 1725-1728

The study of flow cycle morphology provides new information about the breathing pattern. This study proposes the characterization of cycle morphology in chronic heart failure patients (CHF) patients, with periodic (PB) and non-periodic breathing (nPB) patterns, and healthy subjects. Principal component analysis is applied to extract a respiratory cycle model for each time segment defined by a 30-s moving window. To characterize morphology of the model waveform, a number of parameters are extracted whose significance is evaluated in terms of the following three classification problems: CHF patients with either PB or nPB, CHF patients versus healthy subjects, and nPB patients versus healthy subjects. 26 CHF patients (8 with PB and 18 with non-periodic breathing pattern (nPB)) and 35 healthy subjects are studied. The results show that a respiratory cycle compressed in time characterizes PB patients, i.e., shorter inspiratory and expiratory periods, and higher dispersion of the maximum inspiratory and expiratory flow value (accuracy of 87%). The maximal expiratory flow instant occurs earlier in CHF patients than in healthy subjects (accuracy of 87%), with a steeper slope between inspiration and expiration. It is also found that the standard deviation of the expiratory period, evaluated for each subject, is much lower in CHF patients than in healthy subjects. The maximal expiratory flow instant occurs earlier (accuracy of 84%) in nPB patients, when comparing subjects with similar respiratory pattern like nPB patients and healthy subjects.

Keywords: -----


Chaparro, J.A., Giraldo, B.F. , Caminal, P., Benito, S., (2011). Analysis of the respiratory pattern variability of patients in weaning process using autoregressive modeling techniques Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 5690-5693

One of the most challenging problems in intensive care is the process of discontinuing mechanical ventilation, called weaning process. An unnecessary delay in the discontinuation process and an early weaning trial are undesirable. This paper proposes to analysis the respiratory pattern variability of these patients using autoregressive modeling techniques: autoregressive models (AR), autoregressive moving average models (ARMA), and autoregressive models with exogenous input (ARX). A total of 153 patients on weaning trials from mechanical ventilation were analyzed: 94 patients with successful weaning (group S); 38 patients that failed to maintain spontaneous breathing (group F), and 21 patients who had successful weaning trials, but required reintubation in less than 48 h (group R). The respiratory pattern was characterized by their time series. The results show that significant differences were obtained with parameters as model order and first coefficient of AR model, and final prediction error by ARMA model. An accuracy of 86% (84% sensitivity and 86% specificity) has been obtained when using order model and first coefficient of AR model, and mean of breathing duration.

Keywords: -----


Solà, J., Fiz, J.A., Morera, J., Jané, R., (2011). Bayes classification of snoring subjects with and without Sleep Apnea Hypopnea Syndrome, using a Kernel method Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 6071-6074

The gold standard for diagnosing Sleep Apnea Hypopnea Syndrome (SAHS) is the Polysomnography (PSG), an expensive, labor-intensive and time-consuming procedure. It would be helpful to have a simple screening method that allowed to early determining the severity of a subject prior to his/her enrolment for a PSG. Several differences have been reported in the acoustic snoring characteristics between simple snorers and SAHS patients. Previous studies usually classify snoring subjects into two groups given a threshold of Apnea-Hypoapnea Index (AHI). Recently, Bayes multi-group classification with Gaussian Probability Density Function (PDF) has been proposed, using snore features in combination with apnea-related information. In this work we show that the Bayes classifier with Kernel PDF estimation outperforms the Gaussian approach and allows the classification of SAHS subjects according to their severity, using only the information obtained from snores. This could be the base of a single

Keywords: -----


Juanola-Feliu, E., Colomer-Farrarons, J., Miribel-Catala, P., Samitier, J., Valls-Pasola, J., (2011). Challenges facing academic research in commercializing event-detector implantable devices for an in-vivo biomedical subcutaneous device for biomedical analysis Proceedings of the SPIE - The International Society for Optical Engineering VLSI Circuits and Systems V (ed. -----), SPIE - The International Society for Optical Engineering, USA (Prague, Czech Republic) 8067, 80670P

It is widely recognized that the welfare of the most advanced economies is at risk, and that the only way to tackle this situation is by controlling the knowledge economies and dealing with. To achieve this ambitious goal, we need to improve the performance of each dimension in the "knowledge triangle": education, research and innovation. Indeed, recent findings point to the importance of strategies of adding-value and marketing during R+D processes so as to bridge the gap between the laboratory and the market and so ensure the successful commercialization of new technology-based products. Moreover, in a global economy in which conventional manufacturing is dominated by developing economies, the future of industry in the most advanced economies must rely on its ability to innovate in those high-tech activities that can offer a differential added-value, rather than on improving existing technologies and products. It seems quite clear, therefore, that the combination of health (medicine) and nanotechnology in a new biomedical device is very capable of meeting these requisites. This work propose a generic CMOS Front-End Self-Powered In-Vivo Implantable Biomedical Device, based on a threeelectrode amperometric biosensor approach, capable of detecting threshold values for targeted concentrations of pathogens, ions, oxygen concentration, etc. Given the speed with which diabetes can spread, as diabetes is the fastest growing disease in the world, the nano-enabled implantable device for in-vivo biomedical analysis needs to be introduced into the global diabetes care devices market. In the case of glucose monitoring, the detection of a threshold decrease in the glucose level it is mandatory to avoid critic situations like the hypoglycemia. Although the case study reported in this paper is complex because it involves multiple organizations and sources of data, it contributes to extend experience to the best practices and models on nanotechnology applications and commercialization.

Keywords: Biomedical equipment, Diseases, Nanotechnology


Pomareda, Victor, Marco, Santiago, (2011). Chemical plume source localization with multiple mobile sensors using bayesian inference under background signals Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 149-150

This work presents the estimation of a likelihood map for the location of a source of chemical plume using multiple mobile sensors and Bayesian Inference. Previously described methods use a single sensor and just binary detections (concentrations above or below a certain threshold). The main contribution of this work is to extend previous proposals to use concentration information while at the same time being robust against the presence of background signals. The algorithm has two parts. The first part, concerning Adaptive Background Estimation, uses robust statistics measurements to estimate the background level despite the intermittent presence of high concentrations due to plume statistics. The second part of the algorithm estimates likelihood functions for background and for condition plus plume. Then, the algorithm sequentially builds a likelihood probability map for the location of the source. The algorithm allows the use of multiple mobile sensors. The simulation results demonstrate that our algorithm estimates better the source location and is much more robust in the presence of false alarms.

Keywords: Sensors, Inference mechanisms, Probability, Simulation


del Moral Zamora, B., Colomer, J., Mir, M., Homs, A., Miribel, P., Samitier, J., (2011). Combined impedance and dielectrophoresis portable device for point-of-care analysis Proceedings SPIE Bioelectronics, Biomedical, and Bioinspired Systems V; and Nanotechnology V , SPIE (Prague, Czech Republic) 8068, 80680T (19)

In the 90s, efforts arise in the scientific world to automate and integrate one or several laboratory applications in tinny devices by using microfluidic principles and fabrication technologies used mainly in the microelectronics field. It showed to be a valid method to obtain better reactions efficiency, shorter analysis times, and lower reagents consumption over existing analytical techniques. Traditionally, these fluidic microsystems able to realize laboratory essays are known as Lab-On-a-Chip (LOC) devices. The capability to transport cells, bacteria or biomolecules in an aqueous medium has significant potential for these microdevices, also known as micro-Total-Analysis Systems (uTAS) when their application is of analytical nature. In particular, the technique of dielectrophoresis (DEP) opened the possibility to manipulate, actuate or transport such biological particles being of great potential in medical diagnostics, environmental control or food processing. This technique consists on applying amplitude and frequency controlled AC signal to a given microsystem in order to manipulate or sort cells. Furthermore, the combination of this technique with electrical impedance measurements, at a single or multiple frequencies, is of great importance to achieve novel reliable diagnostic devices. This is because the sorting and manipulating mechanism can be easily combined with a fully characterizing method able to discriminate cells. The paper is focused in the electronics design of the quadrature DEP generator and the four-electrode impedance measurement modules. These together with the lab-on-a-chip device define a full conception of an envisaged Point-of-Care (POC) device.


Morgenstern, C., Schwaibold, M., Randerath, W., Bolz, A., Jané, R., (2011). Comparison of upper airway respiratory resistance measurements with the esophageal pressure/airflow relationship during sleep Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 3205-3208

Measurement of upper airway resistance is of interest in sleep disordered breathing to estimate upper airway patency. Resistance is calculated with the airflow and respiratory effort signals. However, there is no consensus on a standard for upper airway resistance measurement. This study proposes a new benchmarking method to objectively compare different upper airway resistance measurement methods by objectively differentiating between breaths with inspiratory flow limitation (high resistance) and non-limited breaths (low resistance). Resistance was measured at peak-Pes, at peak-flow, at the linear portion of a polynomial equation, as an area comparative and as average resistance for an inspiration. A total of 20 patients with systematic, gold-standard esophageal pressure and nasal airflow acquisition were analyzed and 109,955 breaths were automatically extracted and evaluated. Relative resistance values in relationship to a reference resistance value obtained during wakefulness were also analyzed. The peak-Pes measurement method obtained the highest separation index with significant (p < 0.001) differences to the other methods, followed by the area comparative and the peak-flow methods. As expected, average resistances were significantly (p < 0.001) lower for the non-IFL than for the IFL group. Hence, we recommend employing the peak-Pes for accurate upper airway resistance estimation.

Keywords: -----


Amigo, L. E., Casals, A., Amat, J., (2011). Design of a 3-DoF joint system with dynamic servo-adaptation in orthotic applications Proceedings 2011 IEEE International Conference on Robotics and Automation (ICRA) , IEEE (Shanghai, China) , 3700-3705

Most exoskeleton designs rely on structures and mechanical joints that do not guarantee the right match between the orthosis and the user. This paper proposes a virtual joint model based on three active degrees of freedom aimed to emulate a human joint. This joint is capable of performing a dynamic servo-adaptation in real-time to avoid misalignments and to provide a flexible adjustment to different users' sizes in order to avoid undesirable interaction forces.

Keywords: Actuators, Elbow, Exoskeletons, Joints, Knee, Medical treatment


Punter-Villagrasa, J., Colomer-Farrarons, J., Miribel-Catala, P., Puig-Vidal, M., Samitier, J., (2011). Discrete to full custom ASIC solutions for bioelectronic applications Proceedings of the SPIE - The International Society for Optical Engineering VLSI Circuits and Systems V , SPIE - The International Society for Optical Engineering (Prague, Czech Republic) 8067, 80670Q

This paper presents a first approach on multi-pathogen detection system for portable point-of-care applications on discrete electronics field. The main interest is focused on the development of custom built electronic solutions for bioelectronics applications, from discrete devices to ASICS solutions.

Keywords: Application specific integrated circuits, Biomedical electronics, Biosensors


Sarlabous, L., Torres, A., Fiz, J.A., Gea, J., Martinez-Llorens, J.M., Morera, J., Jané, R. , (2011). Evaluation of the respiratory muscles efficiency during an incremental flow respiratory test Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 3820-3823

The aim of this study was to evaluate the respiratory muscles efficiency during a progressive incremental flow (IF) respiratory test in healthy and Chronic Obstructive Pulmonary Disease (COPD) subjects. To achieve this, the relationship between mouth Inspiratory Pressure (IP) increment, which is a measure of the force produced by respiratory muscles, and respiratory muscular activity increment, evaluated by means of Mechanomyografic (MMG) signals of the diaphragm muscle, was analyzed. Moreover, the correlation between the respiratory efficiency measure and the obstruction severity of the subjects was also examined. Data from two groups of subjects were analyzed. One group consisted of four female subjects (two healthy subjects and two moderate COPD patients) and the other consisted of ten male subjects (six severe and four very severe COPD patients). All subjects performed an easy IF respiratory test, in which small IP values were reached. We have found that there is an increase of amplitude and a displacement towards low frequencies in the MMG signals when the IP increases. Furthermore, it has also been found that respiratory muscles efficiency is lower when greater the obstructive severity of the patients is, and it is lower in women than in men. These results suggest that the information provided by MMG signals could be used to evaluate the muscular efficiency in healthy and COPD subjects.

Keywords: -----


Ziyatdinov, Andrey, Fernandez-Diaz, Eduard, Chaudry, A., Marco, Santiago, Persaud, Krishna, Perera, Alexandre, (2011). A large scale virtual gas sensor array Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 151-152

This paper depicts a virtual sensor array that allows the user to generate gas sensor synthetic data while controlling a wide variety of the characteristics of the sensor array response: arbitrary number of sensors, support for multi-component gas mixtures and full control of the noise in the system such as sensor drift or sensor aging. The artificial sensor array response is inspired on the response of 17 polymeric sensors for three analytes during 7 month. The main trends in the synthetic gas sensor array, such as sensitivity, diversity, drift and sensor noise, are user controlled. Sensor sensitivity is modeled by an optionally linear or nonlinear method (spline based). The toolbox on data generation is implemented in open source R language for statistical computing and can be freely accessed as an educational resource or benchmarking reference. The software package permits the design of scenarios with a very large number of sensors (over 10000 sensels), which are employed in the test and benchmarking of neuromorphic models in the Bio-ICT European project NEUROCHEM.

Keywords: Data analysis, Circuit noise, Data acquisition, Signal processing


Colomer-Farrarons, Jordi , Miribel-Català, Pedro Luís, Samitier, Josep , (2011). Low-voltage µpower CMOS subcutaneous biomedical implantable device for true/false applications Biomedical Engineering IASTED International Conference Biomedical Engineering (Biomed 2011) (ed. Baumgartner, C.), ACTA Press (Innsbruck, Austria) Biomedical Engineering, 424-428

Pairo, Erola, Maynou, Joan, Vallverdu, Montserrat, Caminal, Pere, Marco, Santiago, Perera, Alexandre, (2011). MEET: Motif elements estimation toolkit Engineering in Medicine and Biology Society (EMBC) 33rd Annual International Conference of the IEEE , IEEE (Boston, USA) , 6483-6486

MEET is an R package that integrates a set of algorithms for the detection of transcription factor binding sites (TFBS). The MEET R package includes five motif searching algorithms: MEME/MAST(Multiple Expectation-Maximization for Motif Elicitation), Q-residuals, MDscan (Motif Discovery scan), ITEME (Information Theory Elements for Motif Estimation) and MATCH. In addition MEET allows the user to work with different alignment algorithms: MUSCLE (Multiple Sequence Comparison by Log-Expectation), ClustalW and MEME. The package can work in two modes, training and detection. The training mode allows the user to choose the best parameters of a detector. Once the parameters are chosen, the detection mode allows to analyze a genome looking for binding sites. Both modes can combine the different alignment and detection methods, offering multiple possibilities. Combining the alignments and the detection algorithms makes possible the comparison between detection models at the same level, without having to care about the differences produced during the alignment process. The MEET R package can be downloaded from http://sisbio.recerca.upc.edu/R/MEET_1.0. tar.gz

Keywords: -----


Mesquita, J., Fiz, J.A., Solà, J., Morera, J., Jané, R., (2011). Normal non-regular snores as a tool for screening SAHS severity Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 3197-3200

Snoring is one of the earliest and most consistent sign of upper airway obstruction leading to Sleep Apnea-Hypopnea Syndrome (SAHS). Several studies on post-apneic snores, snores that are emitted immediately after an apnea, have already proven that this type of snoring is most distinct from that of normal snoring. However, post-apneic snores are more unlikely and sometimes even inexistent in simple snorers and mild SAHS subjects. In this work we address that issue by proposing the study of normal non-regular snores. They correspond to successive snores that are separated by normal breathing cycles. The results obtained establish the feasibility of acoustic parameters of normal non-regular snores as a promising tool for a prompt screening of SAHS severity.

Keywords: -----


Ziyatdinov, Andrey, Calvo, Jose Maria Blanco, Lechon, Miguel, Bermudez i Badia, Sergi, Verschure, Paul F. M. J., Marco, Santiago, Perera, Alexandre, (2011). Odour mapping under strong backgrounds with a metal oxide sensor array Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 232-233

This work describes the data from navigation experiments with the mobile robot, equipped with the sensor array of three MOX gas sensors. Performed four series of measurements aim to explore the capabilities of sensor array to build the odour map with one or two odour sources in the wind tunnel space. It was demonstrated that the method based on Independent Component Analysis (ICA) is able to discriminate two odour sources, that in future can be used in the surge-and-cast robot navigation algorithm.

Keywords: Mobile robots, Data acquisition, MIS devices, Chemioception


Arcentales, A., Giraldo, B.F., Caminal, P., Benito, S., Voss, A., (2011). Recurrence quantification analysis of heart rate variability and respiratory flow series in patients on weaning trials Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 2724-2727

Autonomic nervous system regulates the behavior of cardiac and respiratory systems. Its assessment during the ventilator weaning can provide information about physio-pathological imbalances. This work proposes a non linear analysis of the complexity of the heart rate variability (HRV) and breathing duration (TTot) applying recurrence plot (RP) and their interaction joint recurrence plot (JRP). A total of 131 patients on weaning trials from mechanical ventilation were analyzed: 92 patients with successful weaning (group S) and 39 patients that failed to maintain spontaneous breathing (group F). The results show that parameters as determinism (DET), average diagonal line length (L), and entropy (ENTR), are statistically significant with RP for TTot series, but not with HRV. When comparing the groups with JRP, all parameters have been relevant. In all cases, mean values of recurrence quantification analysis are higher in the group S than in the group F. The main differences between groups were found on the diagonal and vertical structures of the joint recurrence plot.

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Marco, Santiago, (2011). Signal processing for chemical sensing: Statistics or biological inspiration Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 145-146

Current analytical instrumentation and continuous sensing can provide huge amounts of data. Automatic signal processing and information evaluation is needed to overcome drowning in data. Today, statistical techniques are typically used to analyse and extract information from continuous signals. However, it is very interesting to note that biology (insects and vertebrates) has found alternative solutions for chemical sensing and information processing. This is a brief introduction to the developments in the European Project: Bio-ICT NEUROCHEM: Biologically Inspired Computation for Chemical Sensing (grant no. 216916) Fp7 project devoted to biomimetic olfactory systems.

Keywords: Signal processing, Chemioception, Neural nets, Computational complexity


Jané, R., Fiz, J.A., Solà, J., Mesquita, J., Morera, J., (2011). Snoring analysis for the screening of sleep apnea hypopnea syndrome with a single-channel device developed using polysomnographic and snoring databases Engineering in Medicine and Biology Society 33rd Annual International Conference of the IEEE EMBS , IEEE (Boston, USA) Engineering in Medicine and Biology Society, 8331-8333

Several studies have shown differences in acoustic snoring characteristics between patients with Sleep Apnea-Hypopnea Syndrome (SAHS) and simple snorers. Usually a few manually isolated snores are analyzed, with an emphasis on postapneic snores in SAHS patients. Automatic analysis of snores can provide objective information over a longer period of sleep. Although some snore detection methods have recently been proposed, they have not yet been applied to full-night analysis devices for screening purposes. We used a new automatic snoring detection and analysis system to monitor snoring during full-night studies to assess whether the acoustic characteristics of snores differ in relation to the Apnea-Hypopnea Index (AHI) and to classify snoring subjects according to their AHI. A complete procedure for device development was designed, using databases with polysomnography (PSG) and snoring signals. This included annotation of many types of episodes by an expert physician: snores, inspiration and exhalation breath sounds, speech and noise artifacts, The AHI of each subject was estimated with classical PSG analysis, as a gold standard. The system was able to correctly classify 77% of subjects in 4 severity levels, based on snoring analysis and sound-based apnea detection. The sensitivity and specificity of the system, to identify healthy subjects from pathologic patients (mild to severe SAHS), were 83% and 100%, respectively. Besides, the Apnea Index (AI) obtained with the system correlated with the obtained by PSG or Respiratory Polygraphy (RP) (r=0.87, p<0.05).

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Gutierrez-Galvez, Agustin, Fernandez, Luis, Marco, Santiago, (2011). Study of sensory diversity and redundancy to encode for chemical mixtures Olfaction and Electronic Nose: Proceedings of the 14th International Symposium on Olfaction and Electronic Nose AIP Conference Proceedings (ed. Perena Gouma, SUNY Stony Brook), AIP (New York City, USA) 1362, (1), 147-148

Inspired by sensory diversity and redundancy at the olfactory epithelium, we have built a large chemical sensor array based on commercial MOX sensors. Different sensor families along with temperature modulation accounts for sensory diversity, whereas sensors of the same family combined with different load resistors provide redundancy to the system. To study the encoding of odor mixtures, a data collection consisting on the response of the array to 3 binary mixtures of ethanol, acetone, and butanone with 18 different concentration ratios is obtained.

Keywords: Chemioception, Sensors, Data acquisition, Temperature measurement


Vaca, R., Aranda, J., Amat, J., Casals, A., (2011). Safe human-robot co-manipulation in assisted robotic surgery International Journal of Computer Assisted Radiology and Surgery Computer Assisted Radiology and Surgery (CARS) , Springer (Berlin, Germany) 6, S281

Mir, M., (2011). Aptamers: The new biorecognition element for proteomic biosensing Biochemistry Research Updates (ed. Baginski, Simon J.), Nova Science Publishers, Inc (Hauppauge, USA) , -----

Aptamers are single stranded artificial nucleic acid ligands that can be generated against almost any kind of target, such as ions, metabolites aminoacids, drugs, toxins, proteins or whole cells. They are isolated from combinatorial libraries of synthetic nucleic acids by an iterative process of adsorption, recovery and amplification, know as SELEX (Systematic Evolution of Ligands by EXponential enrichment) process. Aptamers, the nucleic acid equivalent to antibodies, are easy to synthesise, is not required the use of animals for its synthesis, for this reason it can be developed again toxins and small molecules that do not produce immune response in animals and can be tuned for affinity in closer to assay conditions permitting recognition out of the physiological state. So, aptamers posses numerous advantages that make them preferred candidates as biorecognition elements. In view of the advantages and simple structure of aptamers, they have been used in a wide range of applications such as therapeutics, diagnosis, chromatography, environmental detection, among other.

Keywords: Aptamers, Biosensors, Protein recognition


Serra, T., Navarro, M., Planell, J., (2011). Fabrication and characterization of biodegradable composite scaffolds for tissue engineering Innovative developments in virtual and physical prototyping: Proceedings of the 5th international conference on advanced research in virtual and rapid prototyping (ed. Bartolo, P.J.), CRC Press (Leira, Portugal) Biomanufacturing, 67

Innovative Developments in Virtual and Physical Prototyping presents essential research in the area of Virtual and Rapid Prototyping. The volume contains reviewed papers presented at the 5th International Conference on Advanced Research in Virtual and Rapid Prototyping, hosted by the Centre for Rapid and Sustainable Product Development of the Polytechnic Institute of Leiria, Portugal, from September 28 to October 1, 2011. A wide range of topics is covered, such as CAD and 3D Data Acquisition Technologies, Additive and Nano Manufacturing Technologies, Rapid Tooling & Manufacturing, Biomanufacturing, Materials for Advanced Manufacturing Processes, Virtual Environments and Simulation, Applications of Virtual and Physical Prototyping Technologies. Innovative Developments in Virtual and Physical Prototyping is intended for engineers, designers and manufacturers who are active in the areas of mechanical, industrial and biomedical engineering.

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Mateos-Timoneda, M. A., Planell, J. A., Engel, E., (2011). Modifying biomaterial surfaces for the repair and regeneration of nerve cells Surface Modification of Biomaterials: Methods Analysis and Applications (ed. Williams, R.), Woodhead Publishing (Cambridge, UK) , 325-343

This chapter discusses the use of chemical and topographical modification of biomaterials in the field of repair and regeneration of nerve tissue. The chapter first reviews briefly the methods developed to chemically and topographically modify the surface of biomaterials. The chapter then discusses how these modified surfaces interact with nerve cells and guide cellular activities.

Keywords: Chemical modification, Nerve repair, Topographical modification


van Zanten, Thomas S., Garcia-Parajo, Maria F., (2011). Near-field scanning optical microscopy of biological membranes Life at the Nanoscale: Atomic Force Microscopy of Live Cells (ed. Dufrene, Y.), Pan Stanford Publishing Pte Ltd. (Singapore) , 185-207

The nanoscale analysis of living cells using atomic force microscopy (AFM)-based techniques is an exciting, rapidly evolving research field. During the past years, there has been tremendous progress in using AFM to observe cell surfaces at high resolution, to study cellular mechanics, to localize cell surface receptors, and to measure the forces involved in cellular interactions. This timely book provides a comprehensive overview of the use of AFM and related scanning probe microscopies for cell surface analysis, from the basics to the applications. The book will appeal to anyone involved in cell biology, microbiology, biophysics, biochemistry, or nanobiosciences. It covers all cell types, from viruses and protoplasts to bacteria and animal cells, and discusses a range of advanced AFM modalities, including high-resolution imaging, nanoindentation measurements, recognition imaging, as well as single-molecule and single-cell force spectroscopy. The different chapters are authored by cutting-edge experts, each representing his or her specialized areas. Each chapter covers methodologies for sample preparation and analysis, and highlights recent examples to illustrate the power of AFM techniques in life sciences and nanomedicine.

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Gorostiza, P., Isacoff, E.Y., (2011). Photoswitchable ligand-gated ion channels Photosensitive molecules for controlling biological function (ed. Chambers, J. J. , Kramer, R. H.), Springer (Saskatoon, Canada) 55, 267-285

Ligand-activated proteins can be controlled with light by means of synthetic photoisomerizable tethered ligands (PTLs). The application of PTLs to ligand-gated ion channels, including the nicotinic acetylcholine receptor and ionotropic glutamate receptors, is reviewed with emphasis on rational photoswitch design and the mechanisms of optical switching. Recently reported molecular dynamic methods allow simulation with high reliability of novel PTLs for any ligand-activated protein whose structure is known.

Keywords: Nicotinic acetylcholine receptor, Kainate receptor, Glutamate receptor, Photoisomerizable tether ligand (PTL), Optical switch, Nanotoggle, Azobenzene, Neurobiology,, Nanoengineering, Nanomedicine


Colomer-Farrarons, Jordi, Miribel-Català, Pere LI., Rodríguez-Villarreal, A. Ivón, Samitier, Josep, (2011). Portable bio-devices: Design of electrochemical instruments from miniaturized to implantable devices New perspectives in biosensors technology and applications (ed. Andrea Serra, Pier), InTech (Rijeka, Croatia) Biomedical Engineering, 373-400

A biosensor is a detecting device that combines a transducer with a biologically sensitive and selective component. Biosensors can measure compounds present in the environment, chemical processes, food and human body at low cost if compared with traditional analytical techniques. This book covers a wide range of aspects and issues related to biosensor technology, bringing together researchers from 12 different countries. The book consists of 20 chapters written by 69 authors and divided in three sections: Biosensors Technology and Materials, Biosensors for Health and Biosensors for Environment and Biosecurity.

Keywords: Bio-Devices, Electrochemical Instruments, Miniaturized Devices, Nanobiosensor


Martinez, Elena, Samitier, Josep, (2011). Soft lithography and variants Generating micro- and nanopatterns on polymeric materials (ed. del Campo, Aranzazu , Arzt, Eduard), Wiley-VCH Verlag GmbH&Co (Weinheim) , 57-66

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