Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

Strong flexoelectric behavior in bimesogenic liquid crystals

In this paper, we demonstrate strong flexoelectric coupling in bimesogenic liquid crystals. This strong coupling is determined via the flexoelectro-optic effect in chiral nematic liquid crystals based on bimesogenic mixtures that are doped with low concentrations of high twisting power chiral additive. Two mixtures were examined: one had a pitch length of p∼300nm, the other had a pitch length of p∼600nm. These mixtures exhibit enantiotropic chiral nematic phases close to room temperature. We found that full-intensity modulation, that is, a rotation of the optic axis of 45° between crossed polarizers, could be achieved at significantly lower applied electric fields (E<5Vμm -1) than previously reported. In fact, for the condition of full-intensity modulation, the lowest electric-field strength recorded was E=2Vμm-1. As a result of a combination of the strong flexoelectric coupling and a divergence in the pitch, tilt angles of the optic axis up to 87°, i.e., a rotation of the optic axis through 174°, were observed. Furthermore, the flexoelastic ratios, which may be considered as a figure-of-merit parameter, were calculated from the results and found to be large, ranging from 1.3to2C/Nm for a temperature range of up to 40°C. © 2006 American Institute of Physics.

Instability in threshold voltage and subthreshold behavior in Hf-In-Zn-O thin film transistors induced by bias-and light-stress

Electrical bias and light stressing followed by natural recovery of amorphous hafnium-indium-zinc-oxide (HIZO) thin film transistors with a silicon oxide/nitride dielectric stack reveals defect density changes, charge trapping and persistent photoconductivity (PPC). In the absence of light, the polarity of bias stress controls the magnitude and direction of the threshold voltage shift (Δ VT), while under light stress, VT consistently shifts negatively. In all cases, there was no significant change in field-effect mobility. Light stress gives rise to a PPC with wavelength-dependent recovery on time scale of days. We observe that the PPC becomes more pronounced at shorter wavelengths. © 2010 American Institute of Physics.

Non-aqueous phase liquid behavior in the subsurface: Transportation, source zone characterization and remediation

Contaminant behaviour in soils and fractured rock is very complex, not least because of the heterogeneity of the subsurface environment. For non-aqueous phase liquids (NAPLs), a liquid density contrast and interfacial tension between the contaminant and interstitial fluid adds to the complexity of behaviour, increasing the difficulty of predicting NAPL behaviour in the subsurface. This paper outlines the need for physical model tests that can improve fundamental understanding of NAPL behaviour in the subsurface, enhance risk assessments of NAPL contaminated sites, reduce uncertainty associated with NAPL source remediation and improve current technologies for NAPL plume remediation. Four case histories are presented to illustrate physical modelling approaches that have addressed problems associated with NAPL transport, remediation and source zone characterization. © 2006 Taylor & Francis Group, London.

New (1R,4R)-2-arylidene-p-menthan-3-ones with a bridging ester group in the arylidene fragment. Synthesis and behavior in liquid-crystalline systems

(1R,4R)-2-(4-Hydroxybenzylidene)- and (1R,4R)-2-(4′-hydroxybiphenyl- 4-yl)methylene-p-menthan-3-ones were synthesized by condensation of (-)-menthone with O-tetrahydropyran-2-yl derivatives of 4-hydroxybenzaldehyde and 4′-hydroxy-4-formylbiphenyl, respectively, in a DMSO - base medium followed by the removal of the protective group. The reactions of these hydroxy derivatives with 4-alkylbenzoic, 4-alkyloxybenzoic, trans-4-alkylcyclohexane-4- carboxylic, and 4′-alkylbiphenyl-4-carboxylic acids afforded three series of new chiral esters. Compounds containing the arylidene moiety with three benzene rings were found to exhibit liquid-crystalline properties. The characteristic features of these compounds are discussed based on the results of studies by polarizing microscopy, differential scanning calorimetry, and small-angle X-ray scattering. It was found that the mesomorphic compounds under study can form a smectic A mesophase, twist grain boundary mesophases (TGBA), and blue phases in a wide temperature range. Upon dissolution of certain of chiral compounds in 4′-cyano-4-pentylbiphenyl, a rather high twisting power and the thermal stabilizing effect on mesophases were observed.

Flux line lattice structure and behavior in antiphase boundary free vicinal YBa2Cu3O7-delta thin films

Field angle dependent critical current, magneto-optical microscopy and high resolution electron microscopy studies have been performed on YBa2Cu3O7-delta thin films grown on miscut substrates. High resolution electron microscopy images show that the films studied exhibited clean epitaxial growth with a low density of antiphase boundaries and stacking faults. Any antiphase boundaries (APBs) formed near the film substrate interface rapidly healed rather than extending through the thickness of the film. Unlike vicinal films grown on annealed substrates, which contain a high density of antiphase boundaries, magneto-optical imaging showed no filamentary flux penetration in the films studied. The flux penetration is, however, asymmetric. This is associated with intrinsic pinning of flux strings by the tilted a-b planes and the dependence of the pinning force on the angle between the local field and the a-b planes. Field angle dependent critical current measurements exhibited the striking vortex channeling effect previously reported in vicinal films. By combining the results of three complementary characterization techniques it is shown that extended APB free films exhibit markedly different critical current behavior compared to APB rich films. This is attributed to the role of APB sites as strong pinning centers for Josephson string vortices between the a-b planes. (C) 2003 American Institute of Physics.

Differences between FRP bond behavior in cracked and uncracked regions

Based on an analysis of the experimental results of a proposed bond test method, significant differences are shown to exist between the local FRP bond stress-slip relationships in the uncracked anchorage regions and in the regions between cracks. The proposed method simulates the bond behavior between the flexural cracks and anchorage regions of a flexurally FRP-strengthened RC beam. The boundary conditions, including the presence of cracks and steel, are shown to have significant effects on the local bond stress-slip models. The results showed that, at the same force, the bond stresses in the regions between cracks were lower than in regions outside the cracks, so the debonding formed in the anchorage regions. The local bond stress-slip models in the anchorage regions can be obtained from the conventional bond test methods but these do not mimic the conditions between the cracks.