Water Pipeline Leak Measurement Using Wavelet Packet-based Adaptive ICA

Water Resources Management - The localization of the leaks is estimated using the time difference method in the past decade. Generalized and Basic Cross-correlation techniques are frequently...     

Simultaneous fractionation of multiple classes of polyphenols from honeybush tea using solid-phase extraction

The structural diversity of polyphenols and the inherent limitations of current extraction techniques pose a challenge to extract polyphenols using a simple and green method. Hence, in this study, a method was developed to simultaneously fractionate multiple classes of polyphenols by only varying ethanol-water solutions. Honeybush tea, which is rich in polyphenols, was selected as a model for this study. Solvent extraction followed by solid-phase extraction (SPE) was developed to obtain a polyphenol-rich fraction from six honeybush samples. Based on a gradient elution programme (10%, 30%, 50%, 70% and 90% (v/v) ethanol-water solution) of SPE, the Strata X cartridge showed a better recovery of most targeted polyphenols under 0.9 mL of the drying volume and 1 mL min⁻¹ of the dispensing speed. The elution programme for fractionating most polyphenols was as follows: single elution with 50% ethanol, followed by twice elution with 70% ethanol. The antioxidant capacity was used to analyse the differences among the polyphenol-rich fractions from six honeybush samples. Principal component analysis (PCA) revealed that unfermented C. genistoides (GG) has the greatest antioxidant capacity among the honeybush species studied. Additionally, mangiferin, isomangiferin and vicenin-2 were the main contributors to the antioxidant capacity in six honeybush fractions according to the correlation study.     

The in vitro and in vivo investigation of inhaled migraine therapies using a novel aerosol delivery system consisting of an air pressurized capsule device (APCD) in combination with a pMDI spacer for endotracheal dosing into beagle dogs

Abstract

Context: Aerosol delivery to animals in preclinical settings has historically been very challenging, requiring the use of techniques, such as intratracheal instillation and dry powder insufflation, that are somewhat invasive, inefficient and not representative of clinical inhalation.

Objective: The objective of this work is to develop a system to deliver dry powder to dogs in an efficient and effective manner for the study of new anti-migraine compounds in development.

Materials and methods: The new device uses a metered aliquot of a dry gas to force dry powder drug from a pre-filled HPMC capsule into an AeroChamber® spacer for subsequent inhalation by the animal.

Results: The delivery of two invesigational migraine drugs via the new device was assessed in vitro using abbreviated Andersen cascade impaction and showed the device is capable of generating a reproducible delivered dose of up to ～68% with more than 50% of the dose in the respirable range. In vivo studies have also been performed showing that this device effectively delivered the migraine drugs to spontaneously breathing dogs using a proprietary validated dog inhalation model.

Discussion: Results confirmed that the air pressurized capsule device (APCD) was effective in delivering the APIs to lungs of the animals. The in vivo data verified the advantages of inhaled delivery over oral delivery for this class of drugs and were used to establish the cardiopulmonary and respiratory side effect liability profile for these compounds.

Conclusions: This work has demonstrated the utility of this device for quick and accurate screening of prospective drug candidates, representing a significant improvement in ease of use and reprodicibility over current delivery methods.     

Ultrasound-mediated drug delivery

Although ultrasound-based drug delivery has only seen limited clinical use for transdermal drug delivery, there has been considerable momentum in research aimed at using ultrasound for a wide variety of medical applications. Ultrasound-mediated gene therapy using sonoporation and targeted delivery has progressed from in vitro proof-of-concept studies to produce biological effects in angiogenesis and diabetes studies. These techniques have also been used for cancer therapy, thrombolysis, and disruption of the blood-brain barrier in animal models. It is also worth noting that ultrasound can facilitate targeted drug delivery through thermal means, in addition to the mechanisms associated with cavitation. Ultrasound hyperthermia can be used to target thermally sensitive drug-carrying liposomes or to induce gene expression through localized heat shock response.     

The efficacy and safety of mivacurium in children in Singapore

AIM: The aim of this study was to evaluate the clinical use of mivacurium, a short-acting, non-depolarising muscle relaxant, in the paediatric population in Singapore. METHODS: Twenty children between the ages of 2 and 12 years were given mivacurium to maintain neuromuscular blockade during nitrous oxide-halothane anaesthesia. Reversal from neuromuscular blockade was spontaneous. The onset, ease of intubation after different doses of mivacurium, and the ease of reversal were evaluated. RESULTS: Different intubating doses of mivacurium did not result in significantly different times of onset. The mean recovery index (25% to 75% recovery) was 4.1 minutes. There were no adverse reactions. CONCLUSIONS: Mivacurium provided rapid and efficacious onset of neuromuscular blockade in the local paediatric population. Rapid spontaneous recovery obviated the need for reversal agents.     

Combination of computational prescreening and experimental library construction can accelerate enzyme optimization by directed evolution

Chiral compounds can be produced efficiently by using biocatalysts. However, wild-type enzymes often do not meet the requirements of a production process, making optimization by rational design or directed evolution necessary. Here, we studied the lipase-catalyzed hydrolysis of the model substrate 1-(2-naphthyl)ethyl acetate both theoretically and experimentally. We found that a computational equivalent of alanine scanning mutagenesis based on QM/MM methodology can be applied to identify amino acid positions important for the activity of the enzyme. The theoretical results are consistent with concomitant experimental work using complete saturation mutagenesis and high-throughput screening of the target biocatalyst, a lipase from Bacillus subtilis. Both QM/MM-based calculations and molecular biology experiments identify histidine 76 as a residue that strongly affects the catalytic activity. The experiments demonstrate its important influence on enantioselectivity.     

The syntactic role of pauses in the speech of schizophrenic patients with alogia.

Examined the relation between alogia and pausing. The authors analyzed the flow of speech of 17 male schizophrenic patients during an interview, particularly the pauses that occurred within and between syntactic clauses and those that occurred as the turn switched from the interviewer's question to the patient's response. The strongest predictor of alogia ratings was the duration of switching pauses; the frequency of long within-clause pauses was also significantly related to alogia, but the frequency of between-clause pauses showed a trend toward a negative relation with alogia. Words following within-clause pauses were more likely to be content words than function words, and the content words were less frequent in the English language than the speaker's other words. This suggests that alogic patients have difficulty in word finding and in thought formulation, as well as a general increase in the duration of all pauses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biochemical markers of the mechanical quality of engineered hyaline cartilage

The aim of this study was to determine whether or not biochemical markers can be used as surrogate measures for the mechanical quality of tissue engineered cartilage. The biochemical composition of tissue engineered cartilage constructs were altered by varying either (i) the initial cell seeding density of the scaffold (seeding density protocol) or (ii) the length of time the engineered tissue was cultured (culture period protocol). The aggregate or Young’s moduli of the constructs were measured (by confined or unconfined compression respectively), and compared with the composition of the extracellular matrix by quantitative measurement of the glycosaminoglycan (GAG), hydroxyproline, collagen I and collagen II and collagen cross-links. The aggregate modulus correlated positively with both GAG and collagen II content, but not with collagen I content. Young’s modulus correlated positively with GAG, collagen II and collagen I content, and the ratio of mature to immature cross-links. There was no significant correlation of Young’s Modulus with total collagen measured as hydroxyproline content. These results suggested that hydroxyproline determination may be an unreliable indicator of mechanical quality of tissue engineered cartilage, and that a measure of collagen II and GAG content is required to predict the biomechanical quality of tissue engineered cartilage.