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Sanchez-Herrero, J. F., Bernabeu, M., Prieto, A., Hüttener, M., Juárez, A., (2020). Gene duplications in the genomes of staphylococci and enterococci Frontiers in Molecular Biosciences 7, 160

Gene duplications are a feature of bacterial genomes. In the present work we analyze the extent of gene duplications in the genomes of three microorganisms that belong to the Firmicutes phylum and that are etiologic agents of several nosocomial infections: Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis. In all three groups, there is an irregular distribution of duplications in the genomes of the strains analyzed. Whereas in some of the strains duplications are scarce, hundreds of duplications are present in others. In all three species, mobile DNA accounts for a large percentage of the duplicated genes: phage DNA in S. aureus, and plasmid DNA in the enterococci. Duplicates also include core genes. In all three species, a reduced group of genes is duplicated in all strains analyzed. Duplication of the deoC and rpmG genes is a hallmark of S. aureus genomes. Duplication of the gene encoding the PTS IIB subunit is detected in all enterococci genomes. In E. faecalis it is remarkable that the genomes of some strains encode duplicates of the prgB and prgU genes. They belong to the prgABCU cluster, which responds to the presence of the peptide pheromone cCF10 by expressing the surface adhesins PrgA, PrgB, and PrgC.

Keywords: Bacterial genomics, Enterococcus faecalis, Enterococcus faecium, Gene duplication, Staphylococcus aureus

Xu, D., Wang, Y., Liang, C., You, Y., Sanchez, S., Ma, X., (2020). Self-propelled micro/nanomotors for on-demand biomedical cargo transportation Small 16, (27), 1902464

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on-demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self-propelled MNMs for on-demand biomedical cargo transportation, including their self-propulsion mechanisms, guidance strategies, as well as proof-of-concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.

Keywords: Biomedical applications, Cargo transportation, Guidance strategies, Micro/nanomotors, Self-propulsion

Samitier, Josep, Correia, A., (2019). Biomimetic Nanotechnology for Biomedical Applications (NanoBio&Med 2018) Biomimetics MDPI

Emerging nanobiotechnologies can offer solutions to the current and future challenges in medicine. By covering topics from regenerative medicine, tissue engineering, drug delivery, bionanofabrication, and molecular biorecognition, this Special Issue aims to provide an update on the trends in nanomedicine and drug delivery using biomimetic approaches, and the development of novel biologically inspired devices for the safe and effective diagnosis, prevention, and treatment of disease.

Keywords: Bioinspired nanotechnologies, Bionanofabrication, Bio-nano measurement and microscopy, Nanomaterials for biological and medical applications, Nanoassemblies, Nanostructured surfaces, Drug delivery, Nanobioelectronics, Integrated systems/nanobiosensors, Nanotoxicology, Graphene-based applications

Simmchen, Juliane, Baeza, Alejandro, Miguel-Lopez, Albert, Stanton, Morgan M., Vallet-Regi, Maria, Ruiz-Molina, Daniel, Sánchez, Samuel, (2017). Dynamics of novel photoactive AgCl microstars and their environmental applications ChemNanoMat 3, (1), 65-71

In the field of micromotors many efforts are taken to find a substitute for peroxide as fuel. While most approaches turn towards other toxic high energy chemicals such as hydrazine, we introduce an energy source that is widely used in nature: light. Light is an ideal source of energy and some materials, such as AgCl, have the inherent property to transform light energy for chemical processes, which can be used to achieve propulsion. In the case of silver chloride, one observed process after light exposure is surface modification which leads to the release of ions generating chemo-osmotic gradients. Here we present endeavours to use those processes to propel uniquely shaped micro objects of micro star morphology with a high surface to volume ratio, study their dynamics and present approaches to go towards real environmental applications.

Keywords: Self-propellers, Silver chloride, Environmental applications, Photoactive colloids, Anti bacterial

Ballester, Rubio Belén, Nirme, Jens, Camacho, Irene, Duarte, Esther, Rodríguez, Susana, Cuxart, Ampar, Duff, Armin, Verschure, F. M. J. Paul, (2017). Domiciliary VR-based therapy for functional recovery and cortical reorganization: Randomized controlled trial in participants at the chronic stage post stroke JMIR Serious Games , 5, (3), e15

Background: Most stroke survivors continue to experience motor impairments even after hospital discharge. Virtual reality-based techniques have shown potential for rehabilitative training of these motor impairments. Here we assess the impact of at-home VR-based motor training on functional motor recovery, corticospinal excitability and cortical reorganization. Objective: The aim of this study was to identify the effects of home-based VR-based motor rehabilitation on (1) cortical reorganization, (2) corticospinal tract, and (3) functional recovery after stroke in comparison to home-based occupational therapy. Methods: We conducted a parallel-group, controlled trial to compare the effectiveness of domiciliary VR-based therapy with occupational therapy in inducing motor recovery of the upper extremities. A total of 35 participants with chronic stroke underwent 3 weeks of home-based treatment. A group of subjects was trained using a VR-based system for motor rehabilitation, while the control group followed a conventional therapy. Motor function was evaluated at baseline, after the intervention, and at 12-weeks follow-up. In a subgroup of subjects, we used Navigated Brain Stimulation (NBS) procedures to measure the effect of the interventions on corticospinal excitability and cortical reorganization. Results: Results from the system?s recordings and clinical evaluation showed significantly greater functional recovery for the experimental group when compared with the control group (1.53, SD 2.4 in Chedoke Arm and Hand Activity Inventory). However, functional improvements did not reach clinical significance. After the therapy, physiological measures obtained from a subgroup of subjects revealed an increased corticospinal excitability for distal muscles driven by the pathological hemisphere, that is, abductor pollicis brevis. We also observed a displacement of the centroid of the cortical map for each tested muscle in the damaged hemisphere, which strongly correlated with improvements in clinical scales. Conclusions: These findings suggest that, in chronic stages, remote delivery of customized VR-based motor training promotes functional gains that are accompanied by neuroplastic changes. Trial Registration: International Standard Randomized Controlled Trial Number NCT02699398 (Archived by at

Keywords: Stroke, Movement disorder, Recovery of function, neuroplasticity, Transcranial magnetic stimulation, Physical therapy, Hemiparesis, Computer applications software

Cuervo, A., Dans, P. D., Carrascosa, J. L., Orozco, M., Gomila, G., Fumagalli, L., (2014). Direct measurement of the dielectric polarization properties of DNA Proceedings of the National Academy of Sciences of the United States of America 111, (35), E3624-E3630

The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (εr ~ 2–4), we found that the DNA dielectric constant is ~ 8, considerably higher than the value of ~ 3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson–Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.

Keywords: Atomic force microscopy, Atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, capsid protein, DNA, double stranded DNA, amino acid composition, article, atomic force microscopy, bacteriophage, bacteriophage T7, dielectric constant, dipole, DNA binding, DNA packaging, DNA structure, electron microscopy, ligand binding, nonhuman, polarization, priority journal, protein analysis, protein DNA interaction, scanning probe microscopy, static electricity, virion, virus capsid, virus particle, atomic force microscopy, atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, Bacteriophage T7, Capsid, Cations, Dielectric Spectroscopy, DNA, DNA, Viral, DNA-Binding Proteins, Electrochemical Techniques, Ligands, Microscopy, Atomic Force, Models, Chemical, Nuclear Proteins

Gomila, G., Gramse, G., Fumagalli, L., (2014). Finite-size effects and analytical modeling of electrostatic force microscopy applied to dielectric films Nanotechnology 25, (25), 255702 (11)

A numerical analysis of the polarization force between a sharp conducting probe and a dielectric film of finite lateral dimensions on a metallic substrate is presented with the double objective of (i) determining the conditions under which the film can be approximated by a laterally infinite film and (ii) proposing an analytical model valid in this limit. We show that, for a given dielectric film, the critical diameter above which the film can be modeled as laterally infinite depends not only on the probe geometry, as expected, but mainly on the film thickness. In particular, for films with intermediate to large thicknesses (>100 nm), the critical diameter is nearly independent from the probe geometry and essentially depends on the film thickness and dielectric constant following a relatively simple phenomenological expression. For films that can be considered as laterally infinite, we propose a generalized analytical model valid in the thin-ultrathin limit (<20-50 nm) that reproduces the numerical calculations and the experimental data. Present results provide a general framework under which accurate quantification of electrostatic force microscopy measurements on dielectric films on metallic substrates can be achieved.

Keywords: Dielectric constant, Dielectric films, Electrostatic force microscopy, Quantification, Analytical models, Electric force microscopy, Electrostatic force, Film thickness, Permittivity, Probes, Substrates, Ultrathin films, Accurate quantifications, Electrostatic force microscopy, Finite size effect, Lateral dimension, Metallic substrate, Numerical calculation, Polarization forces, Quantification, Dielectric films

Mir, M., Lugo, R., Tahirbegi, I. B., Samitier, J., (2014). Miniaturizable ion-selective arrays based on highly stable polymer membranes for biomedical applications Sensors 14, (7), 11844-11854

Poly(vinylchloride) (PVC) is the most common polymer matrix used in the fabrication of ion-selective electrodes (ISEs). However, the surfaces of PVC-based sensors have been reported to show membrane instability. In an attempt to overcome this limitation, here we developed two alternative methods for the preparation of highly stable and robust ion-selective sensors. These platforms are based on the selective electropolymerization of poly(3,4-ethylenedioxythiophene) (PEDOT), where the sulfur atoms contained in the polymer covalently interact with the gold electrode, also permitting controlled selective attachment on a miniaturized electrode in an array format. This platform sensor was improved with the crosslinking of the membrane compounds with poly(ethyleneglycol) diglycidyl ether (PEG), thus also increasing the biocompatibility of the sensor. The resulting ISE membranes showed faster signal stabilization of the sensor response compared with that of the PVC matrix and also better reproducibility and stability, thus making these platforms highly suitable candidates for the manufacture of robust implantable sensors.

Keywords: Biomedicine, Electrochemistry, Endoscope, Implantable device, Ion-selective electrode (ISE) sensor, Ischemia, pH detection, Biocompatibility, Chemical sensors, Electrochemistry, Electrodes, Electropolymerization, Endoscopy, Functional polymers, Implants (surgical), Ion selective electrodes, Medical applications, Polyvinyl chlorides, Stabilization, Biomedical applications, Biomedicine, Implantable devices, Ion selective sensors, Ischemia, Membrane instability, pH detection, Poly(3 ,4 ethylenedioxythiophene) (PEDOT), Ion selective membranes

Redondo-Morata, L., Giannotti, M. I., Sanz, F., (2014). Structural impact of cations on lipid bilayer models: Nanomechanical properties by AFM-force spectroscopy Molecular Membrane Biology , 31, (1), 17-28

Atomic Force Microscopy (AFM) has become an invaluable tool for studying the micro-and nanoworlds. As a stand-alone, high-resolution imaging technique and force transducer, it defies most other surface instrumentation in ease of use, sensitivity and versatility. The main strength of AFM relies on the possibility to operate in an aqueous environment on a wide variety of biological samples, from single molecules-DNA or proteins-to macromolecular assemblies like biological membranes. Understanding the effect of mechanical stress on membranes is of primary importance in biophysics, since cells are known to perform their function under a complex combination of forces. In the later years, AFM-based Force-Spectroscopy (AFM-FS) has provided a new vista on membrane mechanics in a confined area within the nanometer realm, where most of the specific molecular interactions take place. Lipid membranes are electrostatically charged entities that physiologically coexist with electrolyte solutions. Thus, specific interactions with ions are a matter of considerable interest. The distribution of ions in the solution and their interaction with the membranes are factors that substantially modify the structure and dynamics of the cell membranes. Furthermore, signaling processes are modified by the membrane capability of retaining ions. Supported Lipid Bilayers (SLBs) are a versatile tool to investigate phospholipid membranes mimicking biological surfaces. In the present contribution, we review selected experiments on the mechanical stability of SLBs as models of lipid membranes by means of AFM-FS, with special focus on the effect of cations and ionic strength in the overall nanomechanical stability.

Keywords: Atomic force microscopy, Cations, Force spectroscopy, Lipid bilayer, Mechanical stability

Mendes, A. C., Smith, K. H., Tejeda-Montes, E., Engel, E., Reis, R. L., Azevedo, H. S., Mata, Alvaro, (2013). Co-assembled and microfabricated bioactive membranes Advanced Functional Materials 23, (4), 430-438

The fabrication of hierarchical and bioactive self-supporting membranes, which integrate physical and biomolecular elements, using a single-step process that combines molecular self-assembly with soft lithography is reported. A positively charged multidomain peptide (with or without the cell-adhesive sequence arginine-glycine-aspartic acid-serine (RGDS)) self-assembles with hyaluronic acid (HA), an anionic biopolymer. Optimization of the assembling conditions enables the realization of membranes with well-controlled and easily tunable features at multiple size scales including peptide sequence, building-block co-assembly, membrane thickness, bioactive epitope availability, and topographical pattern morphology. Membrane structure, morphology, and bioactivity are investigated according to temperature, assembly time, and variations in the experimental setup. Furthermore, to evaluate the physical and biomolecular signaling of the self-assembled microfabricated membranes, rat mesenchymal stem cells are cultured on membranes exhibiting various densities of RGDS and different topographical patterns. Cell adhesion, spreading, and morphology are significantly affected by the surface topographical patterns and the different concentrations of RGDS. The versatility of the combined bottom-up and top-down fabrication processes described may permit the development of hierarchical macrostructures with precise biomolecular and physical properties and the opportunity to fine tune them with spatiotemporal control.

Keywords: Membrane scaffolds, Mesenchymal stem cells, Microfabrication, Self-assembly, Topography

Giraldo, B. F., Chaparro, J. A., Caminal, P., Benito, S., (2013). Characterization of the respiratory pattern variability of patients with different pressure support levels Engineering in Medicine and Biology Society (EMBC) 35th Annual International Conference of the IEEE , IEEE (Osaka, Japan) , 3849-3852

One of the most challenging problems in intensive care is still the process of discontinuing mechanical ventilation, called weaning process. Both an unnecessary delay in the discontinuation process and a weaning trial that is undertaken too early are undesirable. In this study, we analyzed respiratory pattern variability using the respiratory volume signal of patients submitted to two different levels of pressure support ventilation (PSV), prior to withdrawal of the mechanical ventilation. In order to characterize the respiratory pattern, we analyzed the following time series: inspiratory time, expiratory time, breath duration, tidal volume, fractional inspiratory time, mean inspiratory flow and rapid shallow breathing. Several autoregressive modeling techniques were considered: autoregressive models (AR), autoregressive moving average models (ARMA), and autoregressive models with exogenous input (ARX). The following classification methods were used: logistic regression (LR), linear discriminant analysis (LDA) and support vector machines (SVM). 20 patients on weaning trials from mechanical ventilation were analyzed. The patients, submitted to two different levels of PSV, were classified as low PSV and high PSV. The variability of the respiratory patterns of these patients were analyzed. The most relevant parameters were extracted using the classifiers methods. The best results were obtained with the interquartile range and the final prediction errors of AR, ARMA and ARX models. An accuracy of 95% (93% sensitivity and 90% specificity) was obtained when the interquartile range of the expiratory time and the breath duration time series were used a LDA model. All classifiers showed a good compromise between sensitivity and specificity.

Keywords: autoregressive moving average processes, feature extraction, medical signal processing, patient care, pneumodynamics, signal classification, support vector machines, time series, ARX, autoregressive modeling techniques, autoregressive models with exogenous input, autoregressive moving average model, breath duration time series, classification method, classifier method, discontinuing mechanical ventilation, expiratory time, feature extraction, final prediction errors, fractional inspiratory time, intensive care, interquartile range, linear discriminant analysis, logistic regression analysis, mean inspiratory flow, patient respiratory volume signal, pressure support level, pressure support ventilation, rapid shallow breathing, respiratory pattern variability characterization, support vector machines, tidal volume, weaning trial, Analytical models, Autoregressive processes, Biological system modeling, Estimation, Support vector machines, Time series analysis, Ventilation

Penon, O., Novo, S., Duran, S., Ibanez, E., Nogues, C., Samitier, J., Duch, M., Plaza, J. A., Perez-Garcia, L., (2012). Efficient biofunctionalization of polysilicon barcodes for adhesion to the zona pellucida of mouse embryos Bioconjugate Chemistry , 23, (12), 2392-2402

Cell tracking is an emergent area in nano-biotechnology, promising the study of individual cells or the identification of populations of cultured cells. In our approach, microtools designed for extracellular tagging are prepared, because using biofunctionalized polysilicon barcodes to tag cell membranes externally avoids the inconveniences of cell internalization. The crucial covalent biofunctionalization process determining the ultimate functionality was studied in order to find the optimum conditions to link a biomolecule to a polysilicon barcode surface using a self-assembled monolayer (SAM) as the connector. Specifically, a lectin (wheat germ agglutinin, WGA) was used because of its capacity to recognize some specific carbohydrates present on the surface of most mammalian cells. Self-assembled monolayers were prepared on polysilicon surfaces including aldehyde groups as terminal functions to study the suitability of their covalent chemical bonding to WGA. Some parameters, such as the polysilicon surface roughness or the concentration of WGA, proved to be crucial for successful biofunctionalization and bioactivity. The SAMs were characterized by contact angle measurements, time-of-flight secondary ion mass spectrometry (TOF-SIMS), laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS), and atomic force microscopy (AFM). The biofunctionalization step was also characterized by fluorescence microscopy and, in the case of barcodes, by adhesion experiments to the zona pellucida of mouse embryos. These experiments showed high barcode retention rates after 96 h of culture as well as high embryo viability to the blastocyst stage, indicating the robustness of the biofunctionalization and, therefore, the potential of these new microtools to be used for cell tagging.

Keywords: Self-assembled monolayers, Wheat-germ-agglutinin, Protein immobilization strategies, Mass-spectrometry, Cell-surface, Petide, Binding, Identifications, Nanoparticles, Recognition

Serra, T., Navarro, M., Planell, J. A., (2012). Fabrication and characterization of biodegradable composite scaffolds for tissue engineering Innovative Developments in Virtual and Physical Prototyping 5th International Conference on Advanced Research and Rapid Prototyping (ed. Margarida, T., Ferreira, D.), Taylor & Francis (Leiria, Portugal) VR@P, 67-72

In this study, polylactic acid (PLA) and polyethylene glycol (PEG) were combined with soluble CaP glass particles and processed by rapid prototyping to obtain fully biodegradable structures for Tissue Engineering applications. The obtained 3D biodegradable structures were characterized in terms of their architecture and mechanical properties. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using Scanning Electron Microscopy (SEM), micro-computed tomography (micro-CT) and mechanical testing, respectively. Well defined structures with pore size of 350-400μm (in the axial view), struts width of approximately 70-80μm, and a porosity ranging between 60-65% were obtained. The combination RP and PLA/PEG/CaP glass turned into promising fully degradable, mechanically stable, bioactive and biocompatible composite scaffolds for TE.

Keywords: Axial view, Biodegradable composites, Composite scaffolds, Glass particles, Mechanically stable, Micro architectures, Micro computed tomography (micro-CT), Poly lactic acid, Scaffold morphology, Tissue engineering applications, Well-defined structures, Bioactive glass, Mechanical properties, Mechanical testing, Polyethylene glycols, Polymer blends, Rapid prototyping, Scaffolds (biology), Scanning electron microscopy, Computerized tomography

Chaparro, J.A., Giraldo, B.F., Caminal, P., Benito, S., (2012). Performance of respiratory pattern parameters in classifiers for predict weaning process Engineering in Medicine and Biology Society (EMBC) 34th Annual International Conference of the IEEE , IEEE (San Diego, USA) , 4349-4352

Weaning trials process of patients in intensive care units is a complex clinical procedure. 153 patients under extubation process (T-tube test) were studied: 94 patients with successful trials (group S), 38 patients who failed to maintain spontaneous breathing and were reconnected (group F), and 21 patients with successful test but that had to be reintubated before 48 hours (group R). The respiratory pattern of each patient was characterized through the following time series: inspiratory time (TI), expiratory time (TE), breathing cycle duration (TTot), tidal volume (VT), inspiratory fraction (TI/TTot), half inspired flow (VT/TI), and rapid shallow index (f/VT), where f is respiratory rate. Using techniques as autoregressive models (AR), autoregressive moving average models (ARMA) and autoregressive models with exogenous input (ARX), the most relevant parameters of the respiratory pattern were obtained. We proposed the evaluation of these parameters using classifiers as logistic regression (LR), linear discriminant analysis (LDA), support vector machines (SVM) and classification and regression tree (CART) to discriminate between patients from groups S, F and R. An accuracy of 93% (98% sensitivity and 82% specificity) has been obtained using CART classification.

Keywords: Accuracy, Indexes, Logistics, Regression tree analysis, Support vector machines, Time series analysis, Autoregressive moving average processes, Medical signal processing, Pattern classification, Pneumodynamics, Regression analysis, Sensitivity, Signal classification, Support vector machines, Time series, SVM, T-tube testing, Autoregressive models-with-exogenous input, Autoregressive moving average models, Breathing cycle duration, Classification-and-regression tree, Expiratory time, Extubation process, Half inspired flow, Inspiratory fraction, Inspiratory time, Intensive care units, Linear discriminant analysis, Logistic regression, Rapid shallow index, Respiratory pattern parameter performance, Sensitivity, Spontaneous breathing, Support vector machines, Tidal volume, Time 48 hr, Time series, Weaning process classifiers

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

Rajzer, I., Castano, O., Engel, E., Planell, J. A., (2010). Injectable and fast resorbable calcium phosphate cement for body-setting bone grafts Journal of Materials Science-Materials in Medicine , 21, (7), 2049-2056

In this work a calcium phosphate (CPC)/polymer blend was developed with the advantage of being moldable and capable of in situ setting to form calcium deficient hydroxyapatite under physiological conditions in an aqueous environment at body temperature. The CPC paste consists in a mix of R cement, glycerol as a liquid phase carrier and a biodegradable hydrogel such as Polyvinyl alcohol, which acts as a binder. Microstructure and mechanical analysis shows that the CPC blend can be used as an injectable implant for low loaded applications and fast adsorption requirements. The storage for commercial distribution was also evaluated and the properties of the materials obtained do not significantly change during storage at -18A degrees C.

Keywords: Clinical-applications, Composites, Regeneration, Behavior, Scaffold, Repair

Morgenstern, C., Schwaibold, M., Randerath, W., Bolz, A., Jané, R., (2010). Automatic non-invasive differentiation of obstructive and central hypopneas with nasal airflow compared to esophageal pressure Engineering in Medicine and Biology Society (EMBC) 32nd Annual International Conference of the IEEE , IEEE (Buenos Aires, Argentina) , 6142-6145

The differentiation of obstructive and central respiratory events is a major challenge in the diagnosis of sleep disordered breathing. Esophageal pressure (Pes) measurement is the gold-standard method to identify these events but its invasiveness deters its usage in clinical routine. Flattening patterns appear in the airflow signal during episodes of inspiratory flow limitation (IFL) and have been shown with invasive techniques to be useful to differentiate between central and obstructive hypopneas. In this study we present a new method for the automatic non-invasive differentiation of obstructive and central hypopneas solely with nasal airflow. An overall of 36 patients underwent full night polysomnography with systematic Pes recording and a total of 1069 hypopneas were manually scored by human experts to create a gold-standard annotation set. Features were automatically extracted from the nasal airflow signal to train and test our automatic classifier (Discriminant Analysis). Flattening patterns were non-invasively assessed in the airflow signal using spectral and time analysis. The automatic non-invasive classifier obtained a sensitivity of 0.71 and an accuracy of 0.69, similar to the results obtained with a manual non-invasive classification algorithm. Hence, flattening airflow patterns seem promising for the non-invasive differentiation of obstructive and central hypopneas.

Keywords: Practical, Experimental/ biomedical measurement, Feature extraction, Flow measurement, Medical disorders, Medical signal processing, Patient diagnosis, Pneumodynamics, Pressure measurement, Signal classification, Sleep, Spectral analysis/ automatic noninvasive differentiation, Obstructive hypopnea, Central hypopnea, Inspiratory flow limitation, Nasal airflow, Esophageal pressure, Polysomnography, Feature extraction, Discriminant analysis, Spectral analysis

Correa, L. S., Laciar, E., Mut, V., Giraldo, B. F., Torres, A., (2010). Multi-parameter analysis of ECG and Respiratory Flow signals to identify success of patients on weaning trials Engineering in Medicine and Biology Society (EMBC) 32nd Annual International Conference of the IEEE , IEEE (Buenos Aires, Argentina) -----, 6070-6073

Statistical analysis, power spectral density, and Lempel Ziv complexity, are used in a multi-parameter approach to analyze four temporal series obtained from the Electrocardiographic and Respiratory Flow signals of 126 patients on weaning trials. In which, 88 patients belong to successful group (SG), and 38 patients belong to failure group (FG), i.e. failed to maintain spontaneous breathing during trial. It was found that mean values of cardiac inter-beat and breath durations give higher values for SG than for FG; Kurtosis coefficient of the spectrum of the rapid shallow breathing index is higher for FG; also Lempel Ziv complexity mean values associated with the respiratory flow signal are bigger for FG. Patients were then classified with a pattern recognition neural network, obtaining 80% of correct classifications (81.6% for FG and 79.5% for SG).

Keywords: Electrocardiography, Medical signal processing, Neural nets, Pattern recognition, Pneumodynamics, Signal classification, Statistical analysis, ECG, Kurtosis coefficient, Lempel Ziv complexity, Breath durations, Cardiac interbeat durations, Electrocardiography, Multiparameter analysis, Pattern recognition neural network, Power spectral density, Respiratory flow signals, Signal classification, Spontaneous breathing, Statistical analysis, Weaning trials

Amigo, L.E., Casals, A., Amat, J., (2010). Polyarticulated architecture for the emulation of an isocentric joint in orthetic applications BioRob 2010 3rd IEEE RAS & EMBS International Conference on Biomedical Robotics and Biomechatronics , IEEE (Tokyo, Japan) , 825-830

The design of orthotic devices that tries to fit to the anthropomorphic structure of human limbs faces the problem of achieving the highest approximation to the anatomical kinematics. This paper studies the main characteristics and performances of orthotic devices, mainly focusing on the upper limbs, and proposes a solution to the problem of the superposition of rotation and displacement of some joints, as the shoulder, elbow or knee. A 3 DoF virtual joint is proposed to emulate a human joint, solving the isocentricity and size adaptation of most current orthosis.

Keywords: Prosthetics and other practical applications, Prosthetics and orthotics, Prosthetic and orthotic control systems, Robotics, Biomechanics (mechanical engineering), Robot and manipulator mechanics

Casamitjana, M., Pérez, M. C., Aranda, J., Montseny, E., Martin, E. X., (2010). Reliable 3D reconstruction extending pixel-level certainty measures IEEE International Conference on Fuzzy 2010 IEEE World Congress on Computational Intelligence , IEEE (Barcelona, Spain) , 1-7

A new method for obtaining a three-dimensional volumetric reconstruction from a set of views improving the classical Shape from Silhouette method (SFS) is presented. SFS approaches can be easily accelerated through hardware and software techniques but they are very sensible to errors arising during calibration and segmentation processes so they present difficulties when dealing with real images. This paper proposes a new algorithm which uses the information about pixel segmentation uncertainty contained in each view in order to get a reliable 3D reconstruction of the scene. Aggregation of the projected uncertainties permits to classify scene's voxels by means of a decision rule but also makes it possible to create a three-dimensional confidence map of the scene. As a consequence, the regions where more information is needed can be foreseen. Sample reconstructions from real image sets are presented and evaluated.

Keywords: Calibration, Image classification, Image reconstruction, Image segmentation, 3D reconstruction, Calibration process, Decision rule, Hardware technique, Pixel segmentation, Pixel-level certainty measures, Scene voxel classification, Segmentation process, Shape from silhouette method, Software technique, Three-dimensional confidence map, Three-dimensional volumetric reconstruction

Andonovski, B., Ponsa, P., Casals, A., (2010). Towards the development of a haptics guideline in human-robot systems 3rd International Conference on Human System Interactions (HSI) 3rd International Conference on Human System Interactions (HSI) (ed. Pardela, T.), IEEE (Rzeszow, Poland) , 380-387

The main goal of this work is to propose a haptics guideline in human-robot systems focused on the relationship between the human and robot task, the use of a physical interface and the object to manipulate. With this aim, this guideline presents two main parts: a set of heuristic indicators and a qualitative evaluation. In order to assess its ergonomic validation, an application over a well known haptics interface is presented. The final goal of this work is the study of possible applications in regular laboratory conditions in order to improve the design and use of human-robot haptic interfaces in telerobotics applications.

Keywords: Haptic interface design, Human-robot interaction, Surgical applications, Teleoperation

Lundin, Daniel, Torrents, Eduard, Poole, Anthony, Sjoberg, Britt-Marie, (2009). RNRdb, a curated database of the universal enzyme family ribonucleotide reductase, reveals a high level of misannotation in sequences deposited to Genbank BMC Genomics 10, (1), 589

BACKGROUND:Ribonucleotide reductases (RNRs) catalyse the only known de novo pathway for deoxyribonucleotide synthesis, and are therefore essential to DNA-based life. While ribonucleotide reduction has a single evolutionary origin, significant differences between RNRs nevertheless exist, notably in cofactor requirements, subunit composition and allosteric regulation. These differences result in distinct operational constraints (anaerobicity, iron/oxygen dependence and cobalamin dependence), and form the basis for the classification of RNRs into three classes.DESCRIPTION:In RNRdb (Ribonucleotide Reductase database), we have collated and curated all known RNR protein sequences with the aim of providing a resource for exploration of RNR diversity and distribution. By comparing expert manual annotations with annotations stored in Genbank, we find that significant inaccuracies exist in larger databases. To our surprise, only 23% of protein sequences included in RNRdb are correctly annotated across the key attributes of class, role and function, with 17% being incorrectly annotated across all three categories. This illustrates the utility of specialist databases for applications where a high degree of annotation accuracy may be important. The database houses information on annotation, distribution and diversity of RNRs, and links to solved RNR structures, and can be searched through a BLAST interface. RNRdb is accessible through a public web interface at is a specialist database that provides a reliable annotation and classification resource for RNR proteins, as well as a tool to explore distribution patterns of RNR classes. The recent expansion in available genome sequence data have provided us with a picture of RNR distribution that is more complex than believed only a few years ago; our database indicates that RNRs of all three classes are found across all three cellular domains. Moreover, we find a number of organisms that encode all three classes.

Keywords: Enzymology (Biochemistry and Molecular Biophysics), Computer Applications (Computational Biology)

Merolli, A., Rocchi, L., Catalano, F., Planell, J., Engel, E., Martinez, E., Sbernardori, M. C., Marceddu, S., Leali, P. T., (2009). In vivo regeneration of rat sciatic nerve in a double-halved stitch-less guide: a pilot-study Microsurgery , 29, (4), 310-318

It is about 20 years that tubular nerve guides have been introduced into clinical practice as a reliable alternative to autograft, in gaps not-longer-than 20 mm, bringing the advantage of avoiding donor site sacrifice and morbidity. There are limitations in the application of tubular guides. First, tubular structure in itself makes surgical implantation difficult; second, stitch sutures required to secure the guide may represent a site of unfavorable fibroblastic reaction; third, maximum length and diameter of the guide correlate with the occurrence of a poorer central vascularization of regenerated nerve. We report on the in vivo testing of a new concept of nerve-guide (named NeuroBox) which is double-halved, not-degradable, rigid, and does not require any stitch to be held in place, employing acrylate glue instead. Five male Wistar rats had the new guide implanted in a 4-mm sciatic nerve defect; two guides incorporated a surface constituted of microtrenches aligned longitudinally. Further five rats had the 4-mm gap left without repair. Contralateral intact nerves were used as controls. After 2 months, nerve regeneration occurred in all animals treated by the NeuroBox; fine blood vessels were well represented. There was no regeneration in the un-treated animals. Even if the limited number of animals does not allow to draw definitive conclusions, some result can be highlighted: an easy surgical technique was associated with the box-shaped guide and acrylate glue was easily applied; an adequate intraneural vascularization was found concurrently with the regeneration of the nerve and no adverse fibroblastic proliferation was present.

Keywords: Peripheral-nerve, Polyglycolic acid, Guidance cues, Collagen tube, Median nerve, Repair, Growth, Cyanoacrylate, Complications, Anastomosis

Casals, A., Frigola, M., Amat, J., (2009). Robotics, a valuable tool in surgery Revista Iberoamericana de Automatica e Informatica Industrial , 6, (1), 5-19

Continuous advances on diagnostic techniques based on medical images, as well as the incorporation of new techniques in surgical instruments are progressively changing the new surgical procedures. Also, new minimally invasive techniques, which are currently highly consolidated, have produced significant advances, both from the technological and from the surgical treatment perspectives. The limitations that the manual realization of surgical interventions implies, in what refers to precision and accessibility, can be tackled with the help of robotics. In the same way, sensor based robot control techniques are opening new possibilities for the introduction of more improvements in these procedures, either relying on teleoperation, in which the surgeon and the robot establish their best synergy to get the optimal results, or by means of the automation of some specific actions or tasks. In this article the effect of robotics in the evolution of surgical techniques is described. Starting with a review of the robotics application fields, the article continues analyzing the methods and technologies involved in the process of robotizing surgical procedures, as well as the surgeon-robot interaction systems.

Keywords: Robotics, Medical Applications, Teleoperation, Biomedical Systems, Computer Aided Surgery, Human-Machine Interaction

Gutierrez, A., Marco, S., (2009). Biologically inspired signal processing for chemical sensing Studies in Computational Intelligence GOSPEL Workshop on Bio-inspired Signal Processing (ed. Gutierrez, A., Marco, S.), Springer (Barcelona, Spain) -----, (188), -----

This 167-page book is volume 188 in the series 'Studies in computational intelligence.' This volume contain 9 extensive chapters written in English. This volume presents a collection of research advances in biologically inspired signal processing for chemical sensing. The olfactory system, and the gustatory system to a minor extent, has been taken in the last decades as a source of inspiration to develop artificial sensing systems. The recognition of odors by the olfactory system entails a number of signal processing functions such as preprocessing, dimensionality reduction, contrast enhancement, and classification. Using mathematical models to mimic the architecture of the olfactory system, these processing functions can be applied to chemical sensor signals. This book provides background on the olfactory system including a review on information processing in the insect olfactory system along with a proposed signal processing architecture based on the mammalian cortex. It also provides some bio-inspired approaches to process chemical sensor signals such as an olfactory mucosa to improve odor separation and a model of olfactory receptor neuron convergence to correlated sensor responses to an odor and his organoleptic properties. This book will useful to those working or studying in the areas of sensory reception and computational biology.

Keywords: Nervous System (Neural Coordination), Computer Applications (Computational Biology), Sense Organs (Sensory Reception)

Crespo, C., Gallego, J., Cot, A., Falcón, C., Bullich, S., Pareto, D., Aguiar, P., Sempau, J., Lomeña, F., Calviño, F., Pavía, J., Ros, D., (2008). Quantification of dopaminergic neurotransmission SPECT studies with 123I-labelled radioligands. A comparison between different imaging systems and data acquisition protocols using Monte Carlo simulation European Journal of Nuclear Medicine and Molecular Imaging , 35, (7), 1334-1342

Purpose: 123I-labelled radioligands are commonly used for single-photon emission computed tomography (SPECT) imaging of the dopaminergic system to study the dopamine transporter binding. The aim of this work was to compare the quantitative capabilities of two different SPECT systems through Monte Carlo (MC) simulation. Methods: The SimSET MC code was employed to generate simulated projections of a numerical phantom for two gamma cameras equipped with a parallel and a fan-beam collimator, respectively. A fully 3D iterative reconstruction algorithm was used to compensate for attenuation, the spatially variant point spread function (PSF) and scatter. A post-reconstruction partial volume effect (PVE) compensation was also developed. Results: For both systems, the correction for all degradations and PVE compensation resulted in recovery factors of the theoretical specific uptake ratio (SUR) close to 100%. For a SUR value of 4, the recovered SUR for the parallel imaging system was 33% for a reconstruction without corrections (OSEM), 45% for a reconstruction with attenuation correction (OSEM-A), 56% for a 3D reconstruction with attenuation and PSF corrections (OSEM-AP), 68% for OSEM-AP with scatter correction (OSEM-APS) and 97% for OSEM-APS plus PVE compensation (OSEM-APSV). For the fan-beam imaging system, the recovered SUR was 41% without corrections, 55% for OSEM-A, 65% for OSEM-AP, 75% for OSEM-APS and 102% for OSEM-APSV. Conclusion: Our findings indicate that the correction for degradations increases the quantification accuracy, with PVE compensation playing a major role in the SUR quantification. The proposed methodology allows us to reach similar SUR values for different SPECT systems, thereby allowing a reliable standardisation in multicentric studies.

Keywords: Brain SPECT, Monte Carlo methods, Receptor imaging, Reconstruction quantification, SPECT instrumentation and algorithms

Mills, C. A., Fernandez, Javier G., Errachid, A., Samitier, J., (2008). The use of high glass temperature polymers in the production of transparent, structured surfaces using nanoimprint lithography Microelectronic Engineering , 85, (9), 1897-1901

Polymers with high glass transition temperatures, fluorinated ethylene propylene copolymer (FEP) and poly(ethylene naphthalate) (PEN), have been used in imprint lithography as a protective support layer and as a secondary mould, to imprint superficial structures into a polymer with a lower glass transition temperature, namely poly(methyl methacrylate) (PMMA). As a support layer, FEP replaces fragile silicon based supports for the production of freestanding, structured sheets of PMMA, useful, for example, in biomedical applications where transmittance optical microscopy is required. Secondary PEN moulds, produced by imprinting using silicon-based primary moulds, have been used to transfer sub-micrometer tall structures to a freestanding PMMA sheet. Similarly, hole structures, with different dimensions, have been embossed in both sides of a PMMA sheet simultaneously.

Keywords: Polymer engineering, Embossing, Nanoimprint lithography, Biomedical applications

Garde, A., Giraldo, B. F., Jané, R., Diaz, I., Herrera, S., Benito, S., Domingo, M., Bayes-Genis, A., (2008). Characterization of periodic and non-periodic breathing pattern in chronic heart failure patients IEEE Engineering in Medicine and Biology Society Conference Proceedings 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (ed. IEEE), IEEE (Vancouver, Canada) 1-8, 3227-3230

Periodic breathing (PB) has a high prevalence in chronic heart failure (CHF) patients with mild to moderate symptoms and poor ventricular function. This work proposes the analysis and characterization of the respiratory pattern to identify periodic breathing pattern (PB) and non-periodic breathing pattern (nPB) through the respiratory flow signal. The respiratory pattern analysis is based on the extraction and the study of the flow envelope signal. The flow envelope signal is modelled by an autoregressive model (AR) whose coefficients would characterize the respiratory pattern of each group. The goodness of the characterization is evaluated through a linear and non linear classifier applied to the AR coefficients. An adaptive feature selection is used before the linear and non linear classification, employing leave-one-out cross validation technique. With linear classification the percentage of well classified patients (8 PB and 18 nPB patients) is 84.6% using the statistically significant coefficients whereas with non linear classification, the percentage of well classified patients increase to more than 92% applying the best subset of coefficients extracted by a forward selection algorithm.

Keywords: Clinical-implications, Sleep

Pla, M., Fernandez, Javier G., Mills, C. A., Martinez, E., Samitier, J., (2007). Micro/nanopatterning of proteins via contact printing using high aspect ratio PMMA stamps and NanoImprint apparatus Langmuir 23, (16), 8614-8618

Micro- and nanoscale protein patterns have been produced via a new contact printing method using a nanoimprint lithography apparatus. The main novelty of the technique is the use of poly(methyl methacrylate) (PMMA) instead of the commonly used poly(dimethylsiloxane) (PDMS) stamps. This avoids printing problems due to roof collapse, which limits the usable aspect ratio in microcontact printing to 10:1. The rigidity of the PMMA allows protein patterning using stamps with very high aspect ratios, up to 300 in this case. Conformal contact between the stamp and the substrate is achieved because of the homogeneous pressure applied via the nanoimprint lithography instrument, and it has allowed us to print lines of protein similar to 150 nm wide, at a 400 nm period. This technique, therefore, provides an excellent method for the direct printing of high-density sub-micrometer scale patterns, or, alternatively, micro-/nanopatterns spaced at large distances. The controlled production of these protein patterns is a key factor in biomedical applications such as cell-surface interaction experiments and tissue engineering.

Keywords: Soft lithography, Cell-adhesion, Microstructures, Fabrication, Stability, Patterns

Mills, C. A., Pla, M., Martin, C., Lee, M., Kuphal, M., Sisquella, X., Martinez, E., Errachid, A., Samitier, J., (2007). Structured thin organic active layers and their use in electrochemical biosensors Measurement & Control , 40, (3), 88-91