Cytotoxicity of tocopherols and their quinones in drug-sensitive and multidrug-resistant leukemia cells

Cytotoxicities of tocopherols (α-T, γ-T, δ-T), their para (α-TQ, γ-TQ, δ-TQ)-and ortho (Tocored)-quinone oxidation products, the synthetic quinone analog of γ-TQ containing a methyl group substituted for the phytyl side-chain (TMCQ) and the synthetic quinone analog of Tocored containing a methyl group substituted for the phytyl side-chain (PR) were measured in acute lymphoblastic leukemia cell lines that are drug-sensitive (CEM) and multidrug-resistant (CEM/VLB₁₀₀). Among tocopherols, only δ-T exhibited cytotoxicity. Among para quinones, α-TQ showed no cytotoxicity, while γ-TQ and δ-TQ were highly cytotoxic in both CEM and CEM/VLB₁₀₀ cell lines (LD₅₀<10 μM). δ-TQ and γ-TQ were more cytotoxic than the widely studied chemotherapeutic agent doxorubicin, which also showed selective cytotoxicity to CEM cells. The orthoquinone Tocored was less cytotoxic than doxorubicin in drug-sensitive cells but more cytotoxic than doxorubicin in multidrug-resistant cells. Cytotoxicity was not a function of the phytyl side-chain since both TMCQ and PR were cytotoxic in leukemia cells. Cytotoxic para and ortho quinones were electrophiles that formed adducts with nucleophilic thiol groups in glutathione and 2-mercaptoethanol. Cytotoxicity was enhanced when the glutathione pool was depleted by preincubation with buthionine-[S,R]-sulfoximine, but cytotoxicity was diminished by the addition of N-acetylcysteine to cultures. α-T also diminished the cytotoxicity of para- and or-thoquinones. Buthionine-[S,R]-sulfoximine did not block the inhibitory effect of either N-acetylcysteine or α-T, showing that these agents did not act solely by maintaining the glutathione pool as an essential antioxidant system. In conclusion, tocopherylquinones represent a new class of alkylating electrophilic quinones that function as highly cytotoxic agents and escape multidrug resistance in acute lymphoblastic leukemia cell lines.     

Epitaxial growth of NiTiO3 with a distorted ilmenite structure

MTiO₃ (M = Fe, Mn, Ni) compounds have received recent attention as possible candidates for multiferroic materials capable of magnetization switching by application of an electric field. In an attempt to stabilize NiTiO₃ in the rhombohedral R3 structure, epitaxial Ni_1 − xTi_1 − yO₃ films of different thickness and composition were deposited on Al₂O₃(0001) by pulsed laser deposition, and characterized using several techniques. Structural parameters for ilmenite-type NiTiO₃ and the metastable LiNbO₃-type NiTiO₃ structure with the space group R3c were predicted using density functional theory calculations, and compared with the experimental results. Our structural data from X-ray diffraction and X-ray absorption spectroscopy indicate that epitaxial ilmenite-type NiTiO₃ films were grown. Furthermore, lattice strain exerted by the sapphire substrate results in a distorted ilmenite structure similar to the LiNbO₃-type one. While R3c NiTiO₃, the desired structure based on recent theory, cannot be claimed at this point, our results demonstrate the potential of oxide heteroepitaxy to stabilize metastable multiferroic phases that may be difficult to prepare or are inaccessible in the bulk.     

Sliding and sticking vapour bubbles under inclined plane and curved surfaces

In flow boiling heat is transferred by the combined effects of nucleate boiling, with local generation of bubbles, and evaporative and convective cooling by the passage of bubbles generated elsewhere. In this study, nucleate boiling was eliminated by measuring the heat transfer near injected steam bubbles sliding under an inclined plate heated to low superheats, using liquid crystal thermography combined with high speed video recording and computerised image analysis. Heat was transferred by evaporation of the thin liquid film between the bubble and the wall and by enhanced convection in a wake region wider than the bubble and many bubble diameters long. Evaporation was the dominant mechanism for large, easily deformed, slow-moving bubbles. For small, faster-moving bubbles the reduction in evaporation was offset by an improvement in convection.     

Differential sparing of depth perception, orienting, and optokinetic nystagmus after neonatal versus adult lesions of cortical areas 17, 18, and 19 in the cat.

Performance by cats with lesions of the visual cortex made in infancy or adulthood was examined on tasks of visually guided behavior that do not require specific training. Cats with lesions confined to areas 17, 18, and 19 made during the 1st postnatal week showed more sparing of function on a visual cliff, at orienting to targets suddenly appearing in the visual field, and at optokinetic nystagmus than did cats with equivalent damage incurred as adults. Cats with lesions that included areas 17, 18, 19 and most of the contiguous visual areas were severely impaired at all tasks whether the lesions were incurred neonatally or in adulthood. These findings suggest that sparing of vision after neonatal lesions of cortical areas 17, 18, and 19 is not confined to pattern learning tasks and that remaining lateral cortical visual areas are importantly involved in such sparing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The amplified quantum Fourier transform: solving the local period problem

This paper creates and analyzes a new quantum algorithm called the Amplified Quantum Fourier Transform (QFT) for solving the following problem: The Local Period Problem: Let L = {0,1 . . . N?1} be a set of N labels and let A be a subset of M labels of period P, i.e. a subset of the form $$A=\{j:j=s+rP,r=0,1\ldots M-1\}$$ where ${P\leq \sqrt{N}}$ and ${M \ll N}$ , and where M is assumed known. Given an oracle f : L→ {0,1} which is 1 on A and 0 elsewhere, find the local period P and the offset s. The first part of this paper defines the Amplified QFT algorithm. The second part of the paper summarizes the main results and compares the new algorithm against the QFT and QHS algorithms when solving the local period problem. It is shown that the new algorithm is, on average, quadratically faster than both the QFT and QHS algorithms.     

Augmented KCa2.3 Channel Feedback Regulation of Oxytocin Stimulated Uterine Strips from Nonpregnant Mice

Uterine contractions prior to 37 weeks gestation can result in preterm labor with significant risk to the infant. Current tocolytic therapies aimed at suppressing premature uterine contractions are largely ineffective and cause serious side effects. Calcium (Ca²⁺) dependent contractions of uterine smooth muscle are physiologically limited by the opening of membrane potassium (K⁺) channels. Exploiting such inherent negative feedback mechanisms may offer new strategies to delay labor and reduce risk. Positive modulation of small conductance Ca²⁺-activated K⁺ (K_Ca2.3) channels with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), effectively decreases uterine contractions. This study investigates whether the receptor agonist oxytocin might solicit K_Ca2.3 channel feedback that facilitates CyPPA suppression of uterine contractions. Using isometric force myography, we found that spontaneous phasic contractions of myometrial tissue from nonpregnant mice were suppressed by CyPPA and, in the presence of CyPPA, oxytocin failed to augment contractions. In tissues exposed to oxytocin, depletion of internal Ca²⁺ stores with cyclopiazonic acid (CPA) impaired CyPPA relaxation, whereas blockade of nonselective cation channels (NSCC) using gadolinium (Gd³⁺) had no significant effect. Immunofluorescence revealed close proximity of K_Ca2.3 channels and ER inositol trisphosphate receptors (IP₃Rs) within myometrial smooth muscle cells. The findings suggest internal Ca²⁺ stores play a role in K_Ca2.3-dependent feedback control of uterine contraction and offer new insights for tocolytic therapies.     

An isocaloric PUFA diet enhances lipid uptake and weight gain in aging rats

Aging is associated with a change in the morphology and absorptive capacity of the small intestine. In young rats, feeding a semisynthetic diet containing saturated FA (SFA) increases nutrient uptake, as compared with an isocaloric diet containing polyunsaturated FA (PUFA). We tested the hypotheses that (i) aging is associated with a decline in lipid absorption in the Fischer 344 rat; (ii) this decline can be corrected by manipulating the fat composition of the diet; and (iii) the age-and diet-associated variations in lipid uptake are associated with changes in the ileal lipid-binding protein (ILBP) or the intestinal or liver FA-binding proteins (l-or L-FABP, respectively) in the cytosol of the enterocyte. In rats fed SFA or PUFA, aging was associated with a decline in the in vitro uptake of stearic acid (18∶0) when expressed on the basis of intestinal or mucosal weight. In contrast, age had no effect on lipid uptake when expressed on the basis of serosal surface area, whereas lipid uptake increased with age when expressed on the basis of mucosal surface area. The age-associated variations in lipid uptake were not associated with changes in protein abundance and/or expression of ILBP, I-FABP, or L-FABP. In 24-mon-old rats, when uptake of lipids was expressed on the basis of mucosal surface area, feeding PUFA enhanced lipid uptake and body weight gain as compared with rats fed SFA. Future studies must determine whether the enhanced lipid uptake and body weight gain observed in older animals fed PUFA have any therapeutic benefit.     

Simulations of the elastic response of single-walled carbon nanotubes

Using the Tersoff-Brenner potential we have performed molecular dynamics simulations of nanotubes under axial strain, analyzing both compression and stretching forces. These large-scale simulations were carried out on a MasPar massively parallel computer. The elastic response is investigated and expressions for various elastic constants are derived from the simulations. Typical failure modes are also shown and discussed.     

Three-dimensional temperature measurement of combustion flames using a single monochromatic CCD camera

This paper presents an imaging-based instrumentation system for three-dimensional (3-D) temperature measurement of a combustion flame. A combination of image-processing techniques and two-color radiation thermometry is used to first reconstruct band-limited grayscale representations of the flame and then to determine its temperature distribution. The reconstruction process assumes rotational symmetry in the structure of the flame. A series of experiments has been conducted on a laboratory-scale combustion rig to evaluate the performance of the system. The results obtained demonstrate the capability of the system to determine flame temperature on a 3-D basis.