Novel strategy for encapsulation and targeted delivery of poorly water-soluble active substances

Carriers for targeted delivery and controlled release of poorly water-soluble active substances (PWSAS) are facing three challenges: (a) the encapsulation issues, (b) limitations of PWSAS water solubility, and (c) burst drug release which can be pharmacologically dangerous and economically inefficient. The present study brings a novel strategy for encapsulation and controlled release of PWSAS—caffeine in concentrations which are higher than its maximal water solubility without the possibility of burst effect. The modification of hydrophilic carrier based on poly(methacylic acid) was done using casein and liposomes. To further increase the maximal caffeine loading inside the carrier nicotinamide was used. The release study of the encapsulated PWSAS was elaborated with respect to morphology of the carriers and interactions that could be established between its structural components. The carriers swelling and the release of caffeine and nicotinamide were also investigated depending on caffeine concentration, the presence of different liposomal formulations and the volume ratio of liposomal formulation, in three media with different pH simulating the path of the carrier through the human gastrointestinal tract. The synthesized carriers are promising candidates for encapsulation of PWSAS in concentrations which are higher than its maximal water solubility and for the targeted delivery of those dosages.     

Circuits and techniques for high-resolution measurement of on-chip power supply noise

This paper presents a technique for characterizing the statistical properties and spectrum of power supply noise using only two on-chip low-throughput samplers. The samplers utilize a voltage-controlled oscillator to perform high-resolution analog-to-digital conversion with minimal hardware. The measurement system is implemented in a 0.13-/spl mu/m process along with a high-speed link transceiver. Measured results from this chip validate the accuracy of the measurement system and elucidate several aspects of power supply noise, including its cyclostationary nature.     

A multi-agent architecture for dynamic scheduling of steel hot rolling

Steel production is a complex process and finding coherent and effective schedules for the wide variety of production steps, in a dynamic environment, is a challenging task. In this paper, we propose a multi-agent architecture for integrated dynamic scheduling of the hot strip mill (HSM) and the continuous caster. The scheduling systems of these processes have very different objectives and constraints, and operate in an environment where there is a substantial quantity of real-time information concerning production failures and customer requests. Each process is assigned to an agent which independently, seeks an optimal dynamic schedule at a local level taking into account local objectives, real-time information and information received from other agents. Each agent can react to real-time events in order to fix any problems that occur. We focus here, particularly, on the HSM agent which uses a tabu search heuristic to create good predictive–reactive schedules quickly. The other agents simulate the production of the coil orders and the real-time events, which occur during the scheduling process. When real-time events occur on the HSM, the HSM agent might decide whether to repair the current schedule or reschedule from scratch. To address this problem, a range of schedule repair and complete rescheduling strategies are investigated and their performance is assessed with respect to measures of utility, stability and robustness, using an experimental simulation framework.     

Finite element modelling of skeletal muscles coupled with fatigue

In this study, Hill's muscle theory coupled with fatigue was proposed to describe mechanical behaviours of skeletal muscles. The force developed by a fatigued muscle was described by a muscle fatigue formula which was a time function of the activation α_a and the stretch λ. The modified Hill's muscle theory was hence incorporated into a three-dimensional (3D) finite element model using the PAK finite element code. In this paper, the theoretical derivation of the 3D muscle model was firstly described. After presenting the method of establishing the finite element programme, a case example of studying the mechanical response of a frog gastrocnemius muscle was used to illustrate the applicability of the proposed methodology. The effects of the muscle fatigue on the deformation as well as the stress and strain distribution of the frog muscle subject to a cyclic activation function have been determined. An experiment capturing the real-time shape change of a frog muscle was also conducted to assess the applicability of the proposed method. A comparison between the deformed shapes of the predictive model and the frog muscles was also made. It was shown that the method is capable of providing a reasonable model for describing the mechanical behaviour of skeletal muscles.     

Bead-based polymerase chain reaction on a microchip

We present a bead-based approach to microfluidic polymerase chain reaction (PCR), enabling fluorescent detection and sample conditioning in a single microchamber. Bead-based PCR, while not extensively investigated in microchip format, has been used in a variety of bioanalytical applications in recent years. We leverage the ability of bead-based PCR to accumulate fluorescent labels following DNA amplification to explore a novel DNA detection scheme on a microchip. The microchip uses an integrated microheater and temperature sensor for rapid control of thermal cycling temperatures, while the sample is held in a microchamber fabricated from (poly)dimethylsiloxane and coated with Parylene. The effects of key bead-based PCR parameters, including annealing temperature and concentration of microbeads in the reaction mixture, are studied to achieve optimized device sensitivity and detection time. The device is capable of detecting a synthetically prepared section of the Bordetella pertussis genome in as few as 10 temperature cycles with times as short as 15?min. We then demonstrate the use of the procedure in an integrated device; capturing, amplifying, detecting, and purifying template DNA in a single microfluidic chamber. These results show that this method is an effective method of DNA detection which is easily integrated in a microfluidic device to perform additional steps such as sample pre-conditioning.     

Altered mRNA and Protein Expression of Monocarboxylate Transporter MCT1 in the Cerebral Cortex and Cerebellum of Prion Protein Knockout Mice

The effect of a cellular prion protein (PrP^c) deficiency on neuroenergetics was primarily analyzed via surveying the expression of genes specifically involved in lactate/pyruvate metabolism, such as monocarboxylate transporters (MCT1, MCT2, MCT4). The aim of the present study was to elucidate a potential involvement of PrP^c in the regulation of energy metabolism in different brain regions. By using quantitative real-time polymerase chain reaction (qRT-PCR), we observed a marked reduction in MCT1 mRNA expression in the cortex of symptomatic Zürich I Prnp^−/− mice, as compared to their wild-type (WT) counterparts. MCT1 downregulation in the cortex was accompanied with significantly decreased expression of the MCT1 functional interplayer, the Na⁺/K⁺ ATPase α2 subunit. Conversely, the MCT1 mRNA level was significantly raised in the cerebellum of Prnp^−/− vs. WT control group, without a substantial change in the Na⁺/K⁺ ATPase α2 subunit expression. To validate the observed mRNA findings, we confirmed the observed change in MCT1 mRNA expression level in the cortex at the protein level. MCT4, highly expressed in tissues that rely on glycolysis as an energy source, exhibited a significant reduction in the hippocampus of Prnp^−/− vs. WT mice. The present study demonstrates that a lack of PrP^c leads to altered MCT1 and MCT4 mRNA/protein expression in different brain regions of Prnp^−/− vs. WT mice. Our findings provide evidence that PrP^c might affect the monocarboxylate intercellular transport, which needs to be confirmed in further studies.     

Environmental Hazard Analysis - a Variant of Preliminary Hazard Analysis for Autonomous Mobile Robots

Robot manufacturers will be required to demonstrate objectively that all reasonably foreseeable hazards have been identified in any robotic product design that is to be marketed commercially. This is problematic for autonomous mobile robots because conventional methods, which have been developed for automatic systems do not assist safety analysts in identifying non-mission interactions with environmental features that are not directly associated with the robot’s design mission, and which may comprise the majority of the required tasks of autonomous robots. In this paper we develop a new variant of preliminary hazard analysis that is explicitly aimed at identifying non-mission interactions by means of new sets of guidewords not normally found in existing variants. We develop the required features of the method and describe its application to several small trials conducted at Bristol Robotics Laboratory in the 2011–2012 period.     

Robust Kalman filtering for nonlinear multivariable stochastic systems in the presence of non‐Gaussian noise

The presence of outliers can considerably degrade the performance of linear recursive algorithms based on the assumptions that measurements have a Gaussian distribution. Namely, in measurements there are rare, inconsistent observations with the largest part of population of observations (outliers). Therefore, synthesis of robust algorithms is of primary interest. The Masreliez–Martin filter is used as a natural frame for realization of the state estimation algorithm of linear systems. Improvement of performances and practical values of the Masreliez‐Martin filter as well as the tendency to expand its application to nonlinear systems represent motives to design the modified extended Masreliez–Martin filter. The behaviour of the new approach to nonlinear filtering, in the case when measurements have non‐Gaussian distributions, is illustrated by intensive simulations. Copyright © 2015 John Wiley & Sons, Ltd.     

Validation of plant part measurements using a 3D reconstruction method suitable for high-throughput seedling phenotyping

In plant phenotyping, there is a demand for high-throughput, non-destructive systems that can accurately analyse various plant traits by measuring features such as plant volume, leaf area, and stem length. Existing vision-based systems either focus on speed using 2D imaging, which is consequently inaccurate, or on accuracy using time-consuming 3D methods. In this paper, we present a computer-vision system for seedling phenotyping that combines best of both approaches by utilizing a fast three-dimensional (3D) reconstruction method. We developed image processing methods for the identification and segmentation of plant organs (stem and leaf) from the 3D plant model. Various measurements of plant features such as plant volume, leaf area, and stem length are estimated based on these plant segments. We evaluate the accuracy of our system by comparing the measurements of our methods with ground truth measurements obtained destructively by hand. The results indicate that the proposed system is very promising.     

Application of ionic liquids for the removal of heavy metals from wastewater and activated sludge

This paper presents the results of adsorption studies on the removal of heavy metals (Cr, Cu, Cd, Ni, Pb and Zn) from standard solutions, real wastewater samples and activated sewage sludge using a new technique of liquid-liquid extraction using quaternary ammonium and phosphonium ionic liquids (ILs). Batch sorption experiments were conducted using the ILs [PR4][TS], [PR4][MTBA], [A336][TS] and [A336][MTBA]. Removal of these heavy metals from standard solutions were not effective, however removal of heavy metals from the industrial effluents/wastewater treatment plants were satisfactory, indicating that the removal depends mainly on the composition of the wastewater and cannot be predicted with standard solutions. Removal of heavy metals from activated sludge proved to be more successful than conventional methods such as incineration, acid extraction, thermal treatment, etc. For the heavy metals Cu, Ni and Zn, ≥90% removal was achieved.