Amperometric Glucose Biosensor Based on Glucose Oxidase Encapsulated in Carbon Nanotube–Titania–Nafion Composite Film on Platinized Glassy Carbon Electrode

A highly sensitive and selective glucose biosensor has been developed based on immobilization of glucose oxidase within mesoporous carbon nanotube–titania–Nafion composite film coated on a platinized glassy carbon electrode. Synergistic electrocatalytic activity of carbon nanotubes and electrodeposited platinum nanoparticles on electrode surface resulted in an efficient reduction of hydrogen peroxide, allowing the sensitive and selective quantitation of glucose by the direct reduction of enzymatically‐liberated hydrogen peroxide at ?0.1 V versus Ag/AgCl (3 M NaCl) without a mediator. The present biosensor responded linearly to glucose in the wide concentration range from 5.0×10^?5 to 5.0×10^?3 M with a good sensitivity of 154 mA M^?1cm^?2. Due to the mesoporous nature of CNT–titania–Nafion composite film, the present biosensor exhibited very fast response time within 2 s. In addition, the present biosensor did not show any interference from large excess of ascorbic acid and uric acid.     

A serpentine laminating micromixer combining splitting/recombination and advection

Mixing enhancement has drawn great attention from designers of micromixers, since the flow in a microchannel is usually characterized by a low Reynolds number (Re) which makes the mixing quite a difficult task to accomplish. In this paper, a novel integrated efficient micromixer named serpentine laminating micromixer (SLM) has been designed, simulated, fabricated and fully characterized. In the SLM, a high level of efficient mixing can be achieved by combining two general chaotic mixing mechanisms: splitting/recombination and chaotic advection. The splitting and recombination (in other terms, lamination) mechanism is obtained by the successive arrangement of "F"-shape mixing units in two layers. The advection is induced by the overall three-dimensional serpentine path of the microchannel. The SLM was realized by SU-8 photolithography, nickel electroplating, injection molding and thermal bonding. Mixing performance of the SLM was fully characterized numerically and experimentally. The numerical mixing simulations show that the advection acts favorably to realize the ideal vertical lamination of fluid flow. The mixing experiments based on an average mixing color intensity change of phenolphthalein show a high level of mixing performance was obtained with the SLM. Numerical and experimental results confirm that efficient mixing is successfully achieved from the SLM over the wide range of Re. Due to the simple and mass producible geometry of the efficient micromixer, SLM proposed in this study, the SLM can be easily applied to integrated microfluidic systems, such as micro-total-analysis-systems or lab-on-a-chip systems.     

Self-assembled metallocycles with two interactive binding domains

Five metallocycles 1 a-e have been self-assembled from S-shaped bispyridyl ligands 2 a-e and a palladium complex, [Pd(dppp)(OTf)(2)] (dppp=1,3-bis(diphenylphosphanyl)propane), and have been characterized by elemental analysis and various spectroscopic methods including (1)H NMR spectroscopy and electrospray ionization (ESI) mass spectrometry. These metallocycles all are monocyclic compounds, but can fold to generate two binding domains bearing hydrogen-bonding sites based on pyridine-2,6-dicarboxamide units. The binding properties of the metallocycles with N,N,N',N'-tetramethylterephthalamide (G) have been probed by means of ESI mass spectrometry and (1)H NMR spectroscopy. The results both in the gas phase and in solution are consistent with the fact that the metallocycles accommodate two molecules of the guest G. Thus, the ESI mass spectra clearly show fragments corresponding to the 1:2 complexes in all cases. (1)H NMR studies on 1 a and G support the formation of a 1:2 complex in solution; the titration curves are nicely fitted to a 1:2 binding isotherm, but not to a 1:1 binding isotherm. In addition, a Job plot also suggests a 1:2 binding mode between 1 a and G, showing maximum complexation at approximately 0.33 mol fraction of the metallocycle 1 a in CDCl(3). The binding constants K(1) and K(2) are calculated to be 1600 and 1400 M(-1) (+/-10 %), respectively, at 25 degrees C in CDCl(3), indicative of positively cooperative binding. This positive cooperativity was confirmed by the Hill equation, affording a Hill coefficient of n = 1.6. Owing to insufficient solubility in CDCl(3), for comparison purposes the binding properties of the metallocycles 1 b-e were investigated in a more polar medium, 3 % CD(3)CN/CDCl(3). (1)H NMR titrations revealed that the metallocycles all bind two molecules of the guest G with Hill coefficients ranging from 1.4 to 1.8. This positive cooperativity may be attributed to a structural reorganization of the second binding cavity when the first guest binds to either one of the subcavities present in the metallocycles.     

NBS-Promoted reactions of symmetrically hindered methylphenols via p-benzoquinone methide

Symmetrically hindered methylphenols 1 react smoothly with NBS to form transient intermediates, p-benzoquinone methides (BM), which can be further processed to give hydroxybenzaldehydes in the presence of DMSO. This reaction is initiated by the formation of the phenoxy radical, followed by disproportionation to afford BM. None of the side-chain-brominated product is observed. The existence of BM is supported by the following observations: the formation of BM in solution can be monitored by GC and GC-MS; the electrophilic methine part participates in electrophilic aromatic substitution with anisoles to give hydroxybenzylated products 15; and the double bond character of the exocyclic methine plays a role in [4 + 2] cycloaddition with diene to afford Diels-Alder adducts. In contrast, unsymmetrically hindered or simple methylphenol (p-cresol) with NBS gives the nuclear brominated products, as usual. The energies of symmetrically hindered BMs, unsymmetrically hindered BM, and simple BM were calculated using density functional theories. Relative stabilization energies calculated at the B3LYP/6-31G//B3LYP/6-31G level by an isodesmic equation are enhanced 3-6 kcal/mol for symmetrically hindered BMs.     

Stacking sequence effect of aramid–UHMPE hybrid composites by flexural test method: MATERIAL PROPERTIES

Aramid fibre–ultra-high modulus polyethylene (UHMPE) fibre interply hybrid composites were fabricated with changes in the stacking sequence. The flexural strength and modulus of hybrid composites were measured in order to investigate the effect of stacking sequence. Scanning electron microscopy (SEM) was used to examine the fracture surface of interply hybrid composites. When aramid fibre was at the compressive side and dispersion extent of fibers was small, the higher flexural strength and positive hybrid effect were observed. In addition, the different stacking sequence resulted in a change in flexural failure mechanism which had an effect on the flexural strength. As the dispersion extent of fibers decreased, the introduction of cohesive failure in aramid–aramid interface and PE–PE interface improved the flexural strength of hybrid composites.     

Chelators for radioimmunotherapy: I. NMR and ab initio calculation studies on 1,4,7,10-tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr)

This work describes the modification of the chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N' ',N' "-tetraacetic acid (DOTA) to improve the rate of metal loading for radioimmunotherapy applications. Previous ab initio calculations predicted that the compounds 1,4,7,10-tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr) have a ca. 2000-fold improvement in yttrium metal loading rates compared to those of DOTA (Jang, Y. H.; Blanco, M.; Dasgupta, S.; Keire, D. A.; Shively, J. E.; Goddard, W. A., III. J. Am. Chem. Soc. 1999, 121, 6142-6151). In this study, we report the synthesis, purification, (1)H-NMR chemical shift assignments, pK(a) values, metal loading rate measurements, and additional ab initio calculations of these two compounds. The yttrium loading rates of DO3A1Pr are approximately twice those of DOTA, at pH 4.6 and 37 degrees C. The NMR data indicates that the DO4Pr analogue forms a stable type I complex but does not form a type II complex. The new ab initio calculations performed on DO4Pr and DO3A1Pr indicate that the rate-determining step is the deprotonation of the first macrocycle amine proton, not the second proton as assumed in the previous calculations. The new calculations predict an improvement in the rate of metal loading that more closely matches the experimentally observed change in the rate.     

Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases

The last decade has revealed new roles for Cullin-RING ubiquitin ligases (CRLs) in a myriad of cellular processes, including cell cycle progression. In addition to CRL1, also named SCF (SKP1-Cullin 1-F box protein), which has been known for decades as an important factor in the regulation of the cell cycle, it is now evident that all eight CRL family members are involved in the intricate cellular pathways driving cell cycle progression. In this review, we summarize the structure of CRLs and their functions in driving the cell cycle. We focus on how CRLs target key proteins for degradation or otherwise alter their functions to control the progression over the various cell cycle phases leading to cell division. We also summarize how CRLs and the anaphase-promoting complex/cyclosome (APC/C) ligase complex closely cooperate to govern efficient cell cycle progression.Subject terms: Drug development, Targeted therapies, Origin firing, Chromatin remodelling, Post-translational modifications     

Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells

Earlier report showed that expression of a splice variant of CD99 transmembrane protein increases invasive ability of human breast cancer cells. Cell motility was also significantly enhanced by the CD99 splice variant expression. In an effort to identify the cellular components that mediate a signal transduction pathway triggered by the CD99 splice variant, known signal path inhibitors were examined for their effects on the motility of the CD99 splice variant-transfected MDA-MB-231 breast cancer cells. Phenylarsine oxide, an inhibitor of phosphatase specific for focal adhesion kinase, and PP1, an inhibitor of src kinase family, significantly suppressed motility of the cells. Among different types of src transfectant clones generated, kinase-negative mutant src transfectant cells were 80% less motile than the mock cells transfected with an empty-vector, while v-src and c-src transfectants exhibited cell motility levels at or slightly above the mock transfectant. These results suggest that src and focal adhesion kinase mediate the intracellular signaling pathway of a CD99 splice variant for the induction of motility of human breast cancer cells.