Conformal Cytocompatible Ferrite Coatings Facilitate the Realization of a Nanovoyager in Human Blood

Controlled motion of artificial nanomotors in biological environments, such as blood, can lead to fascinating biomedical applications, ranging from targeted drug delivery to microsurgery and many more. In spite of the various strategies used in fabricating and actuating nanomotors, practical issues related to fuel requirement, corrosion, and liquid viscosity have limited the motion of nanomotors to model systems such as water, serum, or biofluids diluted with toxic chemical fuels, such as hydrogen peroxide. As we demonstrate here, integrating conformal ferrite coatings with magnetic nanohelices offer a promising combination of functionalities for having controlled motion in practical biological fluids, such as chemical stability, cytocompatibility, and the generated thrust. These coatings were found to be stable in various biofluids, including human blood, even after overnight incubation, and did not have significant influence on the propulsion efficiency of the magnetically driven nanohelices, thereby facilitating the first successful ``voyage'' of artificial nanomotors in human blood. The motion of the ``nanovoyager'' was found to show interesting stick-slip dynamics, an effect originating in the colloidal jamming of blood cells in the plasma. The system of magnetic ``nanovoyagers'' was found to be cytocompatible with C2C12 mouse myoblast cells, as confirmed using MTT assay and fluorescence microscopy observations of cell morphology. Taken together, the results presented in this work establish the suitability of the ``nanovoyager'' with conformal ferrite coatings toward biomedical applications.

Levels of Alpha-Toxin Correlate with Distinct Phenotypic Response Profiles of Blood Mononuclear Cells and with agr Background of Community-Associated Staphylococcus aureus Isolates

Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of alpha-toxin than did the proliferative supernatants. Addition of alpha-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, delta-toxin or phenol soluble modulin alpha-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes.

Remotely triggered micro-shock wave responsive drug delivery system for resolving diabetic wound infection and controlling blood sugar levels

A novel, micro-shock wave responsive spermidine and dextran sulfate microparticle was developed. Almost 90% of the drug release was observed when the particles were exposed to micro-shock waves 5 times. Micro-shock waves served two purposes; of releasing the antibiotic from the system and perhaps disrupting the S. aureus biofilm in the skin infection model. A combination of shock waves with ciprofloxacin loaded microparticles could completely cure the S. aureus infection lesion in a diabetic mouse model. As a proof of concept insulin release was triggered using micro-shock waves in diabetic mice to reduce the blood glucose level. Insulin release could be triggered for at least 3 days by exposing subcutaneously injected insulin loaded particles.

Quantitative metabolic profiling of NMR spectral signatures of branched chain amino acids in blood serum

Branched Chain Amino Acids (BCAAs) are related to different aspects of diseases like pathogenesis, diagnosis and even prognosis. While in some diseases, levels of all the BCAAs are perturbed; in some cases, perturbation occurs in one or two while the rest remain unaltered. In case of ischemic heart disease, there is an enhanced level of plasma leucine and isoleucine but valine level remains unaltered. In `Hypervalinemia', valine is elevated in serum and urine, but not leucine and isoleucine. Therefore, identification of these metabolites and profiling of individual BCAA in a quantitative manner in body-fluid like blood plasma/serum have long been in demand. H-1 NMR resonances of the BCAAs overlap with each other which complicates quantification of individual BCAAs. Further, the situation is limited by the overlap of broad resonances of lipoprotein with the resonances of BCAAs. The widely used commercially available kits cannot differentially estimate the BCAAs. Here, we have achieved proper identification and characterization of these BCAAs in serum in a quantitative manner employing a Nuclear Magnetic Resonance-based technique namely T-2-edited Correlation Spectroscopy (COSY). This approach can easily be extended to other body fluids like bile, follicular fluids, saliva, etc.

Reservoir Operation with Fuzzy State Variables for Irrigation of Multiple Crops

This paper presents the development and application of a stochastic dynamic programming model with fuzzy state variables for irrigation of multiple crops. A fuzzy stochastic dynamic programming (FSDP) model is developed in which the reservoir storage and soil moisture of the crops are considered as fuzzy numbers, and the reservoir inflow is considered as a stochastic variable. The model is formulated with an objective of minimizing crop yield deficits, resulting in optimal water allocations to the crops by maintaining storage continuity and soil moisture balance. The standard fuzzy arithmetic method is used to solve all arithmetic equations with fuzzy numbers, and the fuzzy ranking method is used to compare two or more fuzzy numbers. The reservoir operation model is integrated with a daily-based water allocation model, which results in daily temporal variations of allocated water, soil moisture, and crop deficits. A case study of an existing Bhadra reservoir in Karnataka, India, is chosen for the model application. The FSDP is a more realistic model because it considers the uncertainty in discretization of state variables. The results obtained using the FSDP model are found to be more acceptable for the case study than those of the classical stochastic dynamic model and the standard operating model, in terms of 10-day releases from the reservoir and evapotranspiration deficit. (C) 2015 American Society of Civil Engineers.

Cybernetic Modeling Revisited: A Method for Inferring the Cybernetic Variables u(i) from Experimental Data

The cybernetic modeling framework for the growth of microorganisms provides for an elegant methodology to account for the unknown regulatory phenomena through the use of cybernetic variables for enzyme induction and activity. In this paper, we revisit the assumption of limited resources for enzyme induction (Sigma u(i) = 1) used in the cybernetic modeling framework by presenting a methodology for inferring the individual cybernetic variables u(i) from experimental data. We use this methodology to infer u(i) during the simultaneous consumption of glycerol and lactose by Escherichia coli and then model the fitness trade-offs involved in the recently discovered predictive regulation strategy of microorganisms.

Studies on Carbon Mediated Paste Screen Printed Sensors for Blood Glucose Sensing Application

Ready-to-use screen printed glucose sensors are fabricated using Prussian Blue (PB) and Cobalt Phthalocyanine (CoPC) mediated carbon inks as working electrodes. The reference and counter electrodes are screen printed using silver/silver chloride and graphitic carbon paste respectively. The screen printed reference electrodes (internal reference electrode (IRE)) are found to be stable for more than 60 minutes when examined with saturated calomel electrode. Optimal operating voltage for PB and CoPC screen printed sensors are determined by hydrodynamic voltammetric technique. Glucose oxidase is immobilized on the working electrodes by cross-linking method. PB mediated glucose sensor exhibits a sensitivity of 5.60 mA cm(-2)/mM for the range, 10 to 1000 mu M. Sensitivity of CoPC mediated glucose sensor is found to be 5.224 mu A cm(-2)/mM and amperometeric response is linear for the range, 100 to 1500 mu M. Interference studies on the fabricated glucose sensors are conducted with species like uric acid and ascorbic acid. PB mediated sensors showed a completely interference-free behavior. The sensing characteristics of PB mediated glucose sensors are also studied in diluted human serum samples and the results are compared with the values obtained through standard clinical method. The co-efficient of variation is found to be less than 5%. (C) 2015 The Electrochemical Society. All rights reserved.

A Viscoelastic Constitutive Model with Nonlinear Evolutionary Internal Variables

Based on the internal variable theory, a viscoelastic constitutive model of a highly deformable continuous medium is proposed. A set of second rank tensorial internal state variables corresponding to Biot's strain is introduced, and a nonlinear evolution

Diagnostico de prevalencia a leptospirosis canina con respecto a las variables edad, sexo y raza, en ocho barrios del distrito 2 de la ciudad de Managua Septiembre 2007 - Enero 2008

La leptospirosis es considerada una de las zoonosis más difundidas en el mundo entero. El perro actúa como un potencial diseminador de esta enfermedad ya que mantiene una estrecha relación con el hombre, y al mismo tiempo con otros animales tanto domésticos como salvajes. Con el objetivo de conocer la presencia de leptospirosis canina, se realizó estudio en ocho barrios del distrito dos de la cuidad de Managua entre 8 de septiembre al 9 de diciembre 2007. Se realizó un muestreo de 76 canes, correspondiente al 5% del total de canes en los ocho barrios. Se extrajo 3ml de sangre de la vena safena externa, luego de procesarlas para separar el suero sanguíneo del plasma mediante centrifugación, fueron trasladadas al laboratorio del Centro Veterinario de Diagnóstico e Investigación CEVEDI, UNAN-León, para su análisis mediante los métodos ELISA y MAT. De acuerdo con los resultados obtenidos mediante la prueba ELISA un 93.4%, 71 canes, son negativos y un 6.6%, o bien 5 especímenes, son seropositivos a Leptospira spp. Según los resultados de la prueba de micro aglutinación MAT, el 96.1% de la población muestreada es negativa y el 3.9% es positiva a leptospirosis encontrándose los siguientes serovares canico/a, icterohemorragiae, pyrogenes.

Comportamiento de variables de crecimiento y rendimiento en maiz (Zea mays L.) var. NB-6 bajo practicas de fertilizacion, organica y convencional en la Finca El Plantel 2007-2008

El presente trabajo de investigación se estableció entre los meses de Noviembre 2007-Marzo 2008, bajo sistema de riego en la estación experimental El Plantel propiedad de la Universidad Nacional Agraria (UNA), ubicada en el km 42 ½ de la carretera Tipitapa–Masaya, municipio de Tisma en las coordenadas 12 o 07’ 3.84’’ latitud norte y 86 o 05’ 26.085’’ longitud oeste a una altura de 200 msnm. Con el objetivo de comparar el crecimiento y rendimiento del cultivo maíz, variedad NB-6, se establecierondos tratamientos, con prácticas de manejo convencional y orgánico, el tamaño de la parcela experimental fué de 432m2 (16 m x 27 m) y el tamaño de cada parcela útil fue de 46.8 m2 (6 m x 7.8 m), en ambos manejos. Las variables evaluadas fueron; altura de planta, diámetro de tallo, número de hojas, área foliar, longitud de mazorca, diámetro de mazorca, número de hileras por mazorca, número de granos por hileras, número de granos por mazorca, peso de mil granos y rendimiento. Los datos fueron analizados con el programa estadístico SAS versión 9.1, año 2006; realizando comparaciones de medias para cada variable en las dos prácticas de manejo. Los resultados muestran que no hubo diferencia significativa para las variables de crecimiento, tomadas en momentos diferentes. Se encontró diferencia significativa para las variables de rendimiento; longitud de la mazorca y diámetro de la mazorca. El manejo orgánico obtuvo los mayores rendimientos con un total de 3869.78kgha-1, seguido del manejo convencional con 3060.29 kgha-1.

Quantifying Cell Binding Kinetics Mediated By Surface-Bound Blood Type B Antigen To Immobilized Antibodies

Cell adhesion is crucial to many biological processes, such as inflammatory responses, tumor metastasis and thrombosis formation. Recently a commercial surface plasmon resonance (SPR)-based BIAcore biosensor has been extended to determine cell binding mediated by surface-bound biomolecular interactions. How such cell binding is quantitatively governed by kinetic rates and regulating factors, however, has been poorly understood. Here we developed a novel assay to determine the binding kinetics of surface-bound biomolecular interactions using a commercial BIAcore 3000 biosensor. Human red blood cells (RBCs) presenting blood group B antigen and CM5 chip bearing immobilized anti-B monoclonal antibody (mAb) were used to obtain the time courses of response unit, or sensorgrams, when flowing RBCs over the chip surface. A cellular kinetic model was proposed to correlate the sensorgrams with kinetic rates. Impacts of regulating factors, such as cell concentration, flow duration and rate, antibody-presenting level, as well as pH value and osmotic pressure of suspending medium were tested systematically, which imparted the confidence that the approach can be applied to kinetic measurements of cell adhesion mediated by surface-bound biomolecular interactions. These results provided a new insight into quantifying cell binding using a commercial SPR-based BIAcore biosensor.

Identificación de variables en modelización de líneas de producción industrial y su análisis mediante redes neuronales artificiales

Resumen: En el marco de la integración de etapas en procesos de producción industrial en serie, se identifican, clasifican y caracterizan las variables que permiten modelizar dicho proceso, como estrategia con vistas a su optimización. El estudio se aplica en el ámbito de la industria metalúrgica, a partir de los datos de un conjunto de empresas de la región centro y sur de Santa Fe. La estructura secuencial de un proceso industrial hace que cualquier falla en una etapa cause demoras o reducción de calidad en el producto final obtenido. Como herramienta integradora de análisis, se plantea la implementación de un sistema de redes neuronales artificiales.