Simulation of 1d and 2d electrophoretic separations in microfluidics chips

Electrophoretic separations comprise a group of analytical techniques such as capillary zone electrophoresis (CZE), isoelectric focusing (IEF), isotachophoresis (ITP) and free flow electrophoresis (FFE). In all cases, separation is based on the dissimilar mobility of ionic species under the action of an external electric field. These techniques, which are widely used in chemical and biochemical analysis, have been miniaturized in the last years and now represent one of the most important applications of the lab-on-a-chip technology. In a previous work, a generalized numerical model of electrophoresis on microfluidic devices was presented. The model is based on the set of equations that governs electrical phenomena (Poisson equation), fluid dynamics (Navier-Stokes equations), mass transport (Nerst-Planck equation) and chemical reactions. Also the relationship between the buffer characteristics (ionic strength, pH) and surface potential of channel walls is taken into consideration. In this work, three application examples are presented: (a) an IEF assay with immobilized pH gradient (IPG) including the influence of electro-osmotic flow on its performance, (b) an IEF assay involving ampholyte-based pH gradient, and (c) a 2D electrophoresis, involving FFIEF plus CZE. The numerical simulation is carried out by using PETSc-FEM (Portable Extensible Toolkit for Scientific Computation - Finite Elements Method), in a Python environment developed at CIMEC using high performance parallel computing and solving techniques based on domain decomposition methods.Fil: Kler, Pablo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Guarnieri, Fabio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Universidad Nacional de Entre Rios; ArgentinaFil: Berli, Claudio Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas; Argentin

Numerical simulation of electrokinetic flow in microfluidic chips

Microfluidic chips are miniaturized analytical devices used in chemical, biological and medical applications. In most cases, fluids are conducted through microchannels by applying electric potentials and/or pressure gradients. This growing lab-on-a-chip technology requires numerical simulations to assist the design, control and optimization of analytical manipulations. The present work deals with FEM-based calculations of the dynamics of electrolyte solutions in cross-shaped microchannels, where the flow is driven by the action of external electric fields. A theoretical modeling of electrokinetic and transport phenomena in the system is carried out in the framework of continuum fluid mechanics. Calculations ground on conservation equations of mass, momentum and electrical charge, considering effects in three dimensions. Operations normally performed in analytical systems are discussed, such as loading, focusing, and injection of samples. Numerical simulations carried out in this work can be a valuable tool to control and optimize practical manipulations in microfluidic chips.Fil: Guarnieri, Fabio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Kler, Pablo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Berli, Claudio Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Generalized numerical model for the simulation of electrophoretic methods in microfluidic chips

Electrophoretic methods are separation techniques based on the mobility of ions under the action of an external electric field. These techniques, which are widely used in chemical and biochemical analysis, have been miniaturized in the last years and now represent one of the most important applications of the lab-on-a-chip technology. In this work, a generalized numerical model of electrophoresis on microfluidic devices is presented. The model is based on the set of equations that governs electrical phenomena (Poisson equation), fluid dynamics (Navier-Stokes equations), mass transport (Nerst-Planck equation) and chemical reactions. The model is said to be generalized because it covers different techniques such as capillary eletrophoresis and isoelectric focusing, and allows to simulate processes involving multiple analytes and complex electrolytes buffers. Moreover, the relationship between the buffer characteristics (ionic strength, pH) and physicochemical properties of channel walls is taken into consideration. The numerical simulation is carried out by using PETSC-FEM (Portable, Extensible Toolkit for Scientific Computation - Finite Elements Method), in a Python environment developed at CIMEC using high performance parallel computing and solving techniques based on domain decomposition methods. Finally, examples of interest involving electrophoresis on chips are considered as study cases.Fil: Kler, Pablo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Guarnieri, Fabio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Berli, Claudio Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Nitric oxide can function as either a killer molecule or an antiapoptotic effector in cardiomyocytes

AbstractCaspase enzymes are a family of cysteine proteases that play a central role in apoptosis. Recently, it has been demonstrated that caspases can be S-nitrosylated and inhibited by nitric oxide (NO). The present report shows that in chick embryo heart cells (CEHC), NO donor molecules such as S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione, spermine-NO or sodium nitroprusside inhibit caspase activity in both basal and staurosporine-treated cells. However, the inhibitory effect of NO donors on caspase activity is accompanied by a parallel cytotoxic effect, that precludes NO to exert its antiapoptotic capability. N-Acetylcysteine (NAC) at a concentration of 10 mM blocks depletion of cellular glutathione and cell death in SNAP-treated CEHC, but it poorly affects the ability of SNAP to inhibit caspase activity. Consequently, in the presence of NAC, SNAP attenuates not only caspase activity but also cell death of staurosporine-treated CEHC. These data show that changes in the redox environment may inhibit NO-mediated toxicity, without affecting the antiapoptotic capability of NO, mediated by inhibition of caspase enzymes. NO may thus be transformed from a killer molecule into an antiapoptotic agent

Priming adult stem cells by hypoxic pretreatments for applications in regenerative medicine

The efficiency of regenerative medicine can be ameliorated by improving the biological performances of stem cells before their transplantation. Several ex-vivo protocols of non-damaging cell hypoxia have been demonstrated to significantly increase survival, proliferation and post-engraftment differentiation potential of stem cells. The best results for priming cultured stem cells against a following, otherwise lethal, ischemic stress have been obtained with brief intermittent episodes of hypoxia, or anoxia, and reoxygenation in accordance with the extraordinary protection afforded by the conventional maneuver of ischemic preconditioning in severely ischemic organs. These protocols of hypoxic preconditioning can be rather easily reproduced in a laboratory; however, more suitable pharmacological interventions inducing stem cell responses similar to those activated in hypoxia are considered among the most promising solutions for future applications in cell therapy. Here we want to offer an up-to-date review of the molecular mechanisms translating hypoxia into beneficial events for regenerative medicine. To this aim the involvement of epigenetic modifications, microRNAs, and oxidative stress, mainly activated by hypoxia inducible factors, will be discussed. Stem cell adaptation to their natural hypoxic microenvironments (niche) in healthy and neoplastic tissues will be also considered

Evidence that AMP-activated protein kinase can negatively modulate Ornithine decarboxylase activity in cardiac myoblasts

AbstractThe responses of AMP-activated protein kinase (AMPK) and Ornithine decarboxylase (ODC) to isoproterenol have been examined in H9c2 cardiomyoblasts, AMPK represents the link between cell growth and energy availability whereas ODC, the key enzyme in polyamine biosynthesis, is essential for all growth processes and it is thought to have a role in the development of cardiac hypertrophy. Isoproterenol rapidly induced ODC activity in H9c2 cardiomyoblasts by promoting the synthesis of the enzyme protein and this effect was counteracted by inhibitors of the PI3K/Akt pathway. The increase in enzyme activity became significant between 15 and 30min after the treatment. At the same time, isoproterenol stimulated the phosphorylation of AMPKα catalytic subunits (Thr172), that was associated to an increase in acetyl coenzyme A carboxylase (Ser72) phosphorylation. Downregulation of both α1 and α2 isoforms of the AMPK catalytic subunit by siRNA to knockdown AMPK enzymatic activity, led to superinduction of ODC in isoproterenol-treated cardiomyoblasts. Downregulation of AMPKα increased ODC activity even in cells treated with other adrenergic agonists and in control cells. Analogue results were obtained in SH-SY5Y neuroblastoma cells transfected with a shRNA construct against AMPKα. In conclusion, isoproterenol quickly activates in H9c2 cardiomyoblasts two events that seem to contrast one another. The first one, an increase in ODC activity, is linked to cell growth, whereas the second, AMPK activation, is a homeostatic mechanism that negatively modulates the first. The modulation of ODC activity by AMPK represents a mechanism that may contribute to control cell growth processes

PROSPECÇÃO TECNOLÓGICA DE CONCRETO COM ADIÇÃO DE FIBRAS

Este artigo tem como abordagem o tema inovações na engenharia civil, visando um estudo de prospecção tecnológica da utilização de fibras ao concreto. Hoje em dia, há uma grande quantidade de mistura de diversos tipos de fibras para reforço do concreto, onde cada uma proporciona ao material melhorias em diferentes propriedades. São utilizadas desde fibras de aço para melhorar a ductilidade, microfibras poliméricas para aumentar a eficiência do concreto sob altas temperaturas e uma variação na forma e superfície para obtenção de melhores resultados. Para melhor analisar a evolução desta tecnologia, foi realizada uma pesquisa através de prospecção em bases de patentes, objetivando verificar a quantidade e diversidade de depósitos existentes. Houve a constatação de desenvolvimento deste setor em alguns países, em especial, os resultados mostram que a República da Coréia possui um forte investimento em Pesquisa e Desenvolvimento (P&E) nesta área. Com o estudo é possível observar os demais países que se destacam, as tipologias de fibras mais utilizadas e a apropriação de informações derivadas da prospecção tecnológica sobre o tema

Nutraceutical Characteristics of Ancient Malus x domestica Borkh. Fruits Recovered across Siena in Tuscany

Background: A diet rich in fruits and vegetables contributes to lowering the risk of chronic diseases. The fruits of Malus x domestica are a rich dietary source of bioactive compounds, namely vitamins and antioxidants, with recognized action on human health protection. Tuscany is known for its rich plant biodiversity, especially represented by ancient varieties of fruit trees. Particularly noteworthy are the many ancient Tuscan varieties of apple trees. Methods: Sugar quantification via HPLC and spectrophotometric assays to quantify the antioxidant power and total polyphenol content revealed interesting differences in 17 old varieties of Malus x domestica Borkh. recovered in Siena (Tuscany). Results: The quantification of antioxidants, polyphenols, and the main free sugars revealed that their content in the old fruits was often superior to the widespread commercial counterparts (‘Red Delicious’ and ‘Golden Delicious’). Such differences were, in certain cases, dramatic, with 8-fold higher values. Differences were also present for sugars and fibers (pectin). Most ancient fruits displayed low values of glucose and high contents of xylitol and pectin. Conclusions: The results reported here suggest the possible use of ancient apple varieties from Siena for nutraceutical purposes and draw attention to the valorization of local old varieties

Cooperative Coherent Multistatic Imaging and Phase Synchronization in Networked Sensing

Coherent multistatic radio imaging represents a pivotal opportunity for forthcoming wireless networks, which involves distributed nodes cooperating to achieve accurate sensing resolution and robustness. This paper delves into cooperative coherent imaging for vehicular radar networks. Herein, multiple radar-equipped vehicles cooperate to improve collective sensing capabilities and address the fundamental issue of distinguishing weak targets in close proximity to strong ones, a critical challenge for vulnerable road users protection. We prove the significant benefits of cooperative coherent imaging in the considered automotive scenario in terms of both probability of correct detection, evaluated considering several system parameters, as well as resolution capabilities, showcased by a dedicated experimental campaign wherein the collaboration between two vehicles enables the detection of the legs of a pedestrian close to a parked car. Moreover, as \textit{coherent} processing of several sensors' data requires very tight accuracy on clock synchronization and sensor's positioning -- referred to as \textit{phase synchronization} -- (such that to predict sensor-target distances up to a fraction of the carrier wavelength), we present a general three-step cooperative multistatic phase synchronization procedure, detailing the required information exchange among vehicles in the specific automotive radar context and assessing its feasibility and performance by hybrid Cram\'er-Rao bound.Comment: 13 page

Immediate or delayed retrieval of the displaced third molar : A review

The displacement of a third molar is a rare occurrence, but it could lead to serious and/or life threatening complication. Aim of this review is to understand the most correlated causes of displacement and the possible solutions proposed in literature to avoid and solve this complication for maxillary and mandibular third molars at the appropriate time. A search for ?third molar displacement? was performed by using Pubmed database. Articles referred to soft tissues displacement, from 1957 to 2018, were included in the review. The references lists of all eligible articles were examined and additional studies were added to the review only if indexed on Pubmed. All the articles on maxillary sinus displacement and the dislocation of dental fragments or surgical equipment were excluded. From a total of 134 results, 68 articles were examined for satisfying inclusion criteria. 18 articles were excluded because not inherent with the topic; 19 articles on infratemporal space, 11 on sublingual space, 9 on submandibular space, 11 on lateral pharyngeal space displacement were considered congruent for the review and included. The displacement of the third molar in deeper tissues could be avoided by the use of proper surgical procedures and instrumentarium. If displacement occurs, and the operator could not reach the tooth in safe conditions, the patient should be immediately referred to a maxillo-facial surgeon, because of the possibility of further displacement or the onset of hazardous or potentially fatal infections in vital regions