Protamine-carboxymethyl cellulose magnetic nanocapsules for enhanced delivery of anticancer drugs against drug resistant cancers

Multidrug resistance is a major therapeutic challenge faced in the conventional chemotherapy. Nanocarriers are beneficial in the transport of chemotherapeutics by their ability to bypass the P-gp efflux in cancers. Most of the P-gp inhibitors under phase II clinical trial are facing failures and hence there is a need to develop a suitable carrier to address P-gp efflux in cancer therapy. Herein, we prepared novel protamine and carboxymethyl cellulose polyelectrolyte multi-layered nanocapsules modified with Fe3O4 nanoparticles for the delivery of doxorubicin against highly drug resistant HeLa cells. The experimental results revealed that improved cellular uptake, enhanced drug intensity profile with greater percentage of apoptotic cells was attained when doxorubicin loaded magnetic nanocapsules were used in the presence of external magnetic field. Hence, we conclude that this magnetic field assisted nanocapsule system can be used for delivery of chemotherapeutics for potential therapeutic efficacy at minimal dose in multidrug resistant cancers. From the Clinical Editor: Many cancer drugs fail when cancer cells become drug resistant. Indeed, multidrug resistance (MDR) is a major therapeutic challenge. One way that tumor cells attain MDR is by over expression of molecular pumps comprising of P-glycoprotein (P-gp) and multidrug resistant proteins (MRP), which can expel chemotherapeutic drugs out of the cells. In this study, the authors prepared novel protamine and carboxymethyl cellulose polyelectrolyte multi-layered nanocapsules modified with Fe3O4 nanoparticles for the delivery of doxorubicin. The results show that there was better drug delivery and efficacy even against MDR tumor cells. (C) 2015 Elsevier Inc. All rights reserved.

Wireless Aircraft Fuel Quantity Indication System

A wireless fuel quantity indication system (FQIS) has been developed using an RFID-enabled sensing platform. The system comprises a fully passive tag, modified reader protocol, capacitive fuel probe, and auxiliary antenna for additional energy harvesting. Results of fluid testing show sensitivity to changes in fluid height of less than 0.25in. An RF-DC harvesting circuit was developed, which delivers up to 5dBm of input power through a remote radio frequency (RF) source. Testing was conducted in a loaded reverberation chamber to emulate the fuel tank environment. Results demonstrate feasibility of the remote source to power the sensor with less than 1W of maximum transmit power and under 100ms dwell time (100mW average power) into the tank. This indicates adequate coverage for large transport aircraft at safe operating levels with a sample rate of up to 1 sample/s.

Discharge Plasma Combined With Bauxite Residue for Biodiesel Exhaust Cleaning: A Case Study on NOx Removal

Experiments were conducted at laboratory level to treat the oxides of nitrogen (NOx) present in raw and dry biodiesel exhaust utilizing a combination of electric discharge plasma and bauxite residue, i. e., red mud, an industrial waste byproduct from the aluminum industry. In this paper, the adsorption and a possible catalytic property of bauxite residue are discussed. Nonthermal plasma was generated using dielectric barrier discharges initiated by ac/repetitive pulse energization. The effect of corona electrodes on the plasma generation was qualitatively studied through NOx cleaning. The plasma reactor and adsorbent reactors were connected in cascade while treating the exhaust. The diesel generator, running on biodiesel fuel, was electrically loaded to study the effectiveness of the cascade system in cleaning the exhaust. Interestingly, under the laboratory conditions studied, plasma-bauxite residue combination has shown good synergistic properties and enhanced the NOx removal up to about 90%. With proper scaling up, the suggested cascade system may become an economically feasible option to treat the exhaust in larger installations. The results were discussed emphasizing the role of bauxite residue as an adsorbent and as a room temperature catalyst.

Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

Three-dimensional numerical analysis of geocell-reinforced soft clay beds by considering the actual geometry of geocell pockets

Due to its complex honeycomb structure, the numerical modeling of the geocell has always been a big challenge. Generally, the equivalent composite approach is used to model the geocells. In the equivalent composite approach, the geocellsoil composite is treated as the soil layer with improved strength and stiffness values. Though this approach is very simple, it is unrealistic to model the geocells as the soil layer. This paper presents a more realistic approach of modeling the geocells in three-dimensional (3D) framework by considering the actual curvature of the geocell pocket. A square footing resting on geocell reinforced soft clay bed was modeled using the ``fast Lagrangian analysis of continua in 3D'' (FLAC(3D)) finite difference package. Three different material models, namely modified Cam-clay, Mohr-Coulomb, and linear elastic were used to simulate the behaviour of foundation soil, infill soil and the geocell, respectively. It was found that the geocells distribute the load laterally to the wider area below the footing as compared to the unreinforced case. More than 50% reduction in the stress was observed in the clay bed in the presence of geocells. In addition to geocells, two other cases, namely, only geogrid and geocell with additional basal geogrid cases were also simulated. The numerical model was systematically validated with the results of the physical model tests. Using the validated numerical model, parametric studies were conducted to evaluate the influence of various geocell properties on the performance of reinforced clay beds.

Thermal test method for high power three-phase grid-connected inverters

Semiconductor device junction temperatures are maintained within datasheet specified limits to avoid failure in power converters. Burn-in tests are used to ensure this. In inverters, thermal time constants can be large and burn-in tests are required to be performed over long durations of time. At higher power levels, besides increased production cost, the testing requires sources and loads that can handle high power. In this study, a novel method to test a high power three-phase grid-connected inverter is proposed. The method eliminates the need for high power sources and loads. Only energy corresponding to the losses is consumed. The test is done by circulating rated current within the three legs of the inverter. All the phase legs being loaded, the method can be used to test the inverter in both cases of a common or independent cooling arrangement for the inverter phase legs. Further, the method can be used with different inverter configurations - three- or four-wire and for different pulse width modulation (PWM) techniques. The method has been experimentally validated on a 24 kVA inverter for a four-wire configuration that uses sine-triangle PWM and a three-wire configuration that uses conventional space vector PWM.

In-situ synthesized poly(vinyl butyral)/MMT-clay nanocomposites: The role of degree of acetalization and clay content on thermal, mechanical and permeability properties of PVB matrix

Poly(vinyl butyral) - MMT clay nanocomposites were synthesized in situ with three different degrees of acetalization and with varying clay content for each vinyl butyral polymer ratio. The clay nano-platelet galleries were expanded, as determined by X-ray diffraction and TEM analysis. The glass transition temperature of the polymer nanocomposites were found to be similar to 56 degrees C and similar to 52 degrees C for the neat polymer and the 4% clay loaded samples, respectively. The 4 wt% clay loaded film showed higher strength and low strain to failure. The dynamic mechanical analysis also confirmed the improved stability of the matrix. The matrix with 0.5 butyral to alcohol ratio for 4 wt% clay exhibited good water vapor transmission compared to all other compositions. The encapsulated devices with 2.5 and 4 wt% clay loaded films increases the device life time and the efficiencies of these films were 50% higher than their encapsulated pristine polymer films. (C) 2015 Elsevier Ltd. All rights reserved.

Tailoring energy absorption capacity of CNT forests through application of electric field

This study examines the effect of electric field on energy absorption capacity of carbon nanotube forests (CNTFs), comprising of vertically aligned multiwalled carbon nanotubes, under both quasistatic (strain rate, (epsilon) over dot = 10(-3) s(-1)) and dynamic ((epsilon) over dot = similar to 10(3) s(-1)) loading conditions. Under quasistatic condition, the CNTFs were cyclically loaded and unloaded while electric field was applied along the length of carbon nanotube (CNT) either throughout the loading cycle or explicitly during either the loading or the unloading segment. The energy absorbed per cycle by CNTF increased monotonically with electric field when the field was applied only during the loading segment: A 7 fold increase in the energy absorption capacity was registered at an electric field of 1 kV/m whereas no significant change in it was noted for other schemes of electro-mechanical loading. The energy absorption capacity of CNTF under dynamic loading condition also increased monotonically with electric field; however, relative to the quasistatic condition, less pronounced effect was observed. This intriguing strain rate dependent effect of electric field on energy absorption capacity of CNTF is explained in terms of electric field induced strengthening of CNTF, originating from the time dependent electric field induced polarization of CNT. (C) 2015 Elsevier Ltd. All rights reserved.

Stimuli-responsive weak polyelectrolyte multilayer films: A thin film platform for self triggered multi-drug delivery

Polyelectrolyte multilayer (PEM) thin film composed of weak polyelectrolytes was designed by layer-by-layer (LbL) assembly of poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) for multi-drug delivery applications. Environmental stimuli such as pH and ionic strength showed significant influence in changing the film morphology from pore-free smooth structure to porous structure and favored triggered release of loaded molecules. The film was successfully loaded with bovine serum albumin (BSA) and ciprofloxacin hydrochloride (CH) by modulating the porous polymeric network of the film. Release studies showed that the amount of release could be easily controlled by changing the environmental conditions such as pH and ionic strength. Sustained release of loaded molecules was observed up to 8 h. The fabricated films were found to be biocompatible with epithelial cells during in-vitro cell culture studies. PEM film reported here not only has the potential to be used as self-responding thin film platform for transdermal drug delivery, but also has the potential for further development in antimicrobial or anti-inflammatory coatings on implants and drug-releasing coatings for stents. (C) 2015 Elsevier B.V. All rights reserved.

Fiber Bragg Grating Sensor Package for Submicron Level Displacement Measurements

In this article, the design and development of a Fiber Bragg Grating (FBG) based displacement sensor package for submicron level displacement measurements are presented. A linear shift of 12.12 nm in Bragg wavelength of the FBG sensor is obtained for a displacement of 6 mm with a calibration factor of 0.495 mu m/pm. Field trials have also been conducted by comparing the FBG displacement sensor package against a conventional dial gauge, on a five block masonry prism specimen loaded using three-point bending technique. The responses from both the sensors are in good agreement, up to the failure of the masonry prism. Furthermore, from the real-time displacement data recorded using FBG, it is possible to detect the time at which early creaks generated inside the body of the specimen which then prorogate to the surface to develop visible surface cracks; the respective load from the load cell can be obtained from the inflection (stress release point) in the displacement curve. Thus the developed FBG displacement sensor package can be used to detect failures in structures much earlier and to provide an adequate time to exercise necessary action, thereby avoiding the possible disaster.

Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles

Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate. Using high-resolution microscopy techniques including electron microscopy and single molecule imaging, we found that the BoNT/A binding domain is internalized within a subset of vesicles that only partially co-localize with cholera toxin B-subunit and have markedly reduced VAMP2 immunoreactivity. Synaptic vesicles loaded with pHrodo-BoNT/A-Hc exhibited a significantly reduced ability to fuse with the plasma membrane in mouse hippocampal nerve terminals when compared with pHrodo-dextran-containing synaptic vesicles and pHrodo-labeled anti-GFP nanobodies bound to VAMP2-pHluorin or vGlut-pHluorin. Similar results were also obtained at the amphibian neuromuscular junction. These results reveal that BoNT/A is internalized in a subpopulation of synaptic vesicles that are not destined to recycle, highlighting the existence of significant molecular and functional heterogeneity between synaptic vesicles.

Conceptual design of three-dimensional scaffolds of powder-based materials for bone tissue engineering applications

Purpose - The purpose of this paper is to investigate the possibility to construct tissue-engineered bone repair scaffolds with pore size distributions using rapid prototyping techniques. Design/methodology/approach - The fabrication of porous scaffolds with complex porous architectures represents a major challenge in tissue engineering and the design aspects to mimic complex pore shape as well as spatial distribution of pore sizes of natural hard tissue remain unexplored. In this context, this work aims to evaluate the three-dimensional printing process to study its potential for scaffold fabrication as well as some innovative design of homogeneously porous or gradient porous scaffolds is described and such design has wider implication in the field of bone tissue engineering. Findings - The present work discusses biomedically relevant various design strategies with spatial/radial gradient in pore sizes as well as with different pore sizes and with different pore geometries. Originality/value - One of the important implications of the proposed novel design scheme would be the development of porous bioactive/biodegradable composites with gradient pore size, porosity, composition and with spatially distributed biochemical stimuli so that stem cells loaded into scaffolds would develop into complex tissues such as those at the bone-cartilage interface.

How much Dillenia indica seed predation occurs from Asian elephant dung?

Elephants are thought to be effective seed dispersers, but research on whether elephant dung effectively protects seeds from seed predation is lacking. Quantifying rates of seed predation from elephant dung will facilitate comparisons between elephants and alternative dispersers, helping us understand the functional role of megaherbivores in ecosystems. We conducted an experiment to quantify the predation of Dillenia indica seeds from elephant dung in Buxa Reserve, India from December 2012 to April 2013. Using dung boluses from the same dung pile, we compared the number of seeds in boluses that are a) opened immediately upon detection (control boluses), b) made available only to small seed predators (<= 3 mm wide) for 1-4 months, and c) made available to all seed predators and secondary dispersers for 1-4 months. Using a model built on this experiment, we estimated that seed predation by small seed predators (most likely ants and termites) destroys between 82.9% and 96.4% of seeds in elephant dung between the time of defecation and the median germination date for D. indica. Exposure to larger seed predators and secondary dispersers did not lead to a significant additional reduction in the number of seeds per dung bolus. Our findings suggest that post-dispersal seed predation by small insects (<3 mm) substantially reduces but does not eliminate the success of elephants as dispersers of D. indica in a tropical moist forest habitat. (C) 2015 Elsevier Masson SAS. All rights reserved.

Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents

Enzyme-and pH-responsive polyelectrolyte nanocapsules having diameters in the range of 200 +/- 20 nm were fabricated by means of Layer-by-Layer assembly of biopolymers, protamine, and heparin, and then loaded with anticancer drug doxorubicin. The incorporation of the FDA-approved peptide drug protamine as a wall component rendered the capsules responsive to enzyme stimuli. The stimuli-responsive drug release from these nanocapsules was evaluated, and further modulation of capsule permeability to avoid premature release was demonstrated by crosslinking the wall components. The interaction of the nanocapsules with cancer cells was studied using MCF-7 breast cancer cells. These capsules were readily internalized and disintegrated inside the cells, culminating in the release of the loaded doxorubicin and subsequent cell death as observed by confocal microscopy and MTT Assay. The bioavailability studies performed using BALB/c mice revealed that the encapsulated doxorubicin exhibited enhanced bioavailability compared to free doxorubicin. Our results indicate that this stimuli-responsive system fabricated from clinically used FDA-approved molecules and exhibiting minimal premature release has great potential for drug-delivery applications.

Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents

Enzyme-and pH-responsive polyelectrolyte nanocapsules having diameters in the range of 200 +/- 20 nm were fabricated by means of Layer-by-Layer assembly of biopolymers, protamine, and heparin, and then loaded with anticancer drug doxorubicin. The incorporation of the FDA-approved peptide drug protamine as a wall component rendered the capsules responsive to enzyme stimuli. The stimuli-responsive drug release from these nanocapsules was evaluated, and further modulation of capsule permeability to avoid premature release was demonstrated by crosslinking the wall components. The interaction of the nanocapsules with cancer cells was studied using MCF-7 breast cancer cells. These capsules were readily internalized and disintegrated inside the cells, culminating in the release of the loaded doxorubicin and subsequent cell death as observed by confocal microscopy and MTT Assay. The bioavailability studies performed using BALB/c mice revealed that the encapsulated doxorubicin exhibited enhanced bioavailability compared to free doxorubicin. Our results indicate that this stimuli-responsive system fabricated from clinically used FDA-approved molecules and exhibiting minimal premature release has great potential for drug-delivery applications.