424 research outputs found
Theme of blood-consciousness in Shakespeare's plays: The class-oriented modifications of his sources
A 3-D DETERMINATION AND ANALYSIS OF THE SWING PLANE IN GOLF
INTRODUCTION: The direction and ball carry distance of a golf shot are determined by the trajectory of the clubhead near the impact and the impact conditions such as the clubhead speed, club face angle and orientation at impact. Swing plane, one of the most frequently used terms in golf coaching lately, is also one of the most controversial and misleading concepts: single-plane, multi-plane, one-plane, two-plane, on-plane, etc. The purpose of this study was twofold:
(a) to develop a method to determine the true swing plane based on the clubhead motion (trajectory), and
(b) to obtain a biomechanical profile of the swing planes of professional golfers through the swing plane analysis
An Active and Soft Hydrogel Actuator to Stimulate Live Cell Clusters by Self-folding
The hydrogels are widely used in various applications, and their successful uses depend on controlling the mechanical properties. In this study, we present an advanced strategy to develop hydrogel actuator designed to stimulate live cell clusters by self-folding. The hydrogel actuator consisting of two layers with different expansion ratios were fabricated to have various curvatures in self-folding. The expansion ratio of the hydrogel tuned with the molecular weight and concentration of gel-forming polymers, and temperature-sensitive molecules in a controlled manner. As a result, the hydrogel actuator could stimulate live cell clusters by compression and tension repeatedly, in response to temperature. The cell clusters were compressed in the 0.7-fold decreases of the radius of curvature with 1.0 mm in room temperature, as compared to that of 1.4 mm in 37 degrees C. Interestingly, the vascular endothelial growth factor (VEGF) and insulin-like growth factor-binding protein-2 (IGFBP-2) in MCF-7 tumor cells exposed by mechanical stimulation was expressed more than in those without stimulation. Overall, this new strategy to prepare the active and soft hydrogel actuator would be actively used in tissue engineering, drug delivery, and micro-scale actuators
AAD-2004, a potent spin trapping molecule and microsomal prostaglandin E synthase-1 inhibitor, shows safety and efficacy in a mouse model of ALS
While free radicals and inflammation constitute major routes of neuronal injury occurring in neurodegenerative diseases, neither antioxidants nor nonsteroidal anti-inflammatory drugs (NSAIDs) have shown significant efficacy in human clinical trials. To explore the possibility that concurrent blockade of free radicals and PGE2-mediated inflammation might constitute a safe and effective therapeutic approach to certain neurodegenerative diseases, we have developed 2-hydroxy-5-[2-(4-trifluoromethylphenyl)-ethylaminobezoic acid (AAD-2004) as a derivative of aspirin. AAD-2004 completely removed free radicals at 50 nM as a potent spin trapping molecule and inhibited microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 230 nM. Oral administration of AAD-2004 blocked free radical formation, PGE2 formation, and microglial activation in the spinal motor neurons of SOD1G93A mice. As a consequence, AAD-2004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD-2004 was superior to ibuprofen or riluzole. Gastric bleeding was not induced by AAD-2004 even at a dose 400-fold higher than that required to obtain maximal therapeutic efficacy in SOD1G93A mice. Targeting both mPGES-1 and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases
3D garment digitisation for virtual wardrobe using a commodity depth sensor
5-Aminovaleric acid (5AVA) is an important five-carbon platform chemical that can be used for the synthesis of polymers and other chemicals of industrial interest. Enzymatic conversion of L-lysine to 5AVA has been achieved by employing lysine 2-monooxygenase encoded by the davB gene and 5-aminovaleramidase encoded by the davA gene. Additionally, a recombinant Escherichia coli strain expressing the davB and davA genes has been developed for bioconversion of L-lysine to 5AVA. To use glucose and xylose derived from lignocellulosic biomass as substrates, rather than L-lysine as a substrate, we previously examined direct fermentative production of 5AVA from glucose by metabolically engineered E. coli strains. However, the yield and productivity of 5AVA achieved by recombinant E. coli strains remain very low. Thus, Corynebacterium glutamicum, a highly efficient L-lysine producing microorganism, should be useful in the development of direct fermentative production of 5AVA using L-lysine as a precursor for 5AVA. Here, we report the development of metabolically engineered C. glutamicum strains for enhanced fermentative production of 5AVA from glucose.Various expression vectors containing different promoters and origins of replication were examined for optimal expression of Pseudomonas putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. Among them, expression of the C. glutamicum codon-optimized davA gene fused with His-Tag at its N-Terminal and the davB gene as an operon under a strong synthetic H promoter (plasmid p36davAB3) in C. glutamicum enabled the most efficient production of 5AVA. Flask culture and fed-batch culture of this strain produced 6.9 and 19.7\ua0g/L (together with 11.9\ua0g/L glutaric acid as major byproduct) of 5AVA, respectively. Homology modeling suggested that endogenous gamma-aminobutyrate aminotransferase encoded by the gabT gene might be responsible for the conversion of 5AVA to glutaric acid in recombinant C. glutamicum. Fed-batch culture of a C. glutamicum gabT mutant-harboring p36davAB3 produced 33.1\ua0g/L 5AVA with much reduced (2.0\ua0g/L) production of glutaric acid.Corynebacterium glutamicum was successfully engineered to produce 5AVA from glucose by optimizing the expression of two key enzymes, lysine 2-monooxygenase and delta-aminovaleramidase. In addition, production of glutaric acid, a major byproduct, was significantly reduced by employing C. glutamicum gabT mutant as a host strain. The metabolically engineered C. glutamicum strains developed in this study should be useful for enhanced fermentative production of the novel C5 platform chemical 5AVA from renewable resources
Pharmacokinetics of Amitriptyline Demethylation;A Crossover Study with Single Doses of Amitriptyline and Nortriptyline
A single dose crossover pharmacokinetic study of amitriptyline and nortriptyline
was done to find out the extent of first-pass metabolism to nortriptyline after amitripyline
administration, and the contribution of nortriptyline during amitriptyline therapy. Six healthy
male volunteers took part in this study and were given single doses (50 mg) of amitriptyline
and nortriptyline at more than three-week intervals. Plasma concentrations of the drugs were
measured up to 48 hours. Total area under the plasma concentration-time curve (AUe) of
amitriptyline (744.6±258.4 ng/ml·hl was smaller than that of nortriptyline (l497.3±589.8
ng/ml'h), and the mean terminal half-life of amitriptyline (21.8±3.9 hr) was shorter than
that of nortriptyline (36.8±5.9 h). The total area under the plasma concentration-time curve
of nortriptyline produced by amitriptyline administration was 498.1 ±274.5 ng/ml·h, and the
fraction produced by the first-pass of amitriptyline was 33.7 ± 10.5%.
From this data, it can be estimated that the average nortriptyline concentration could be
about 40% of the total tricyclic antidepressants present in the plasma of patients taking
multiple amitriptyline therapy at steady state. About 34% of nortriptyline is produced by
first- pass effect during gastrointestinal absorption of amitriptyline to systemic circulation resulting
from N-demethylation of amitriptyline in the liver. Then, the rest of the nortriptyline is
formed continuously at a rate proportional to the rate of amitriptyline elimination
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