Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility

Background  

Protein kinase D (PKD) has been implicated in a wide range of cellular processes and pathological conditions including cancer. However, targeting PKD therapeutically and dissecting PKD-mediated cellular responses remains difficult due to lack of a potent and selective inhibitor. Previously, we identified a novel pan-PKD inhibitor, CID755673, with potency in the upper nanomolar range and high selectivity for PKD. In an effort to further enhance its selectivity and potency for potential in vivo application, small molecule analogs of CID755673 were generated by modifying both the core structure and side-chains.     

Error estimation and adaptation for functional outputs in time-dependent flow problems

The paper presents an adjoint-based approach for determining global error in the time domain that is relevant to functional outputs from unsteady flow simulations. The algorithm is derived for the unsteady Euler equations that are discretized for second-order accuracy in both space and time and takes into account the effect of dynamic meshes. In addition to error due to temporal resolution, the formulation also takes into account algebraic error arising from partial convergence of the governing equations at each implicit time-step. The resulting error distributions are then used to drive adaptation of the temporal resolution and the convergence tolerances for the governing equations at each time-step. The method is demonstrated in the context of both time-integrated and instantaneous functionals and the results are compared against traditional adaptation methods.     

Sharp gradient estimates for quasilinear elliptic equations with p(x) growth on nonsmooth domains

In this paper, we study quasilinear elliptic equations with the nonlinearity modelled after the $p(x)$-Laplacian on nonsmooth domains and obtain sharp Calderón–Zygmund type estimates in the variable exponent setting. In a recent work of [12], the estimates obtained were strictly above the natural exponent and hence there was a gap between the natural energy estimates and estimates above $p(x)$, see (1.3) and (1.4). Here, we bridge this gap to obtain the end point case of the estimates obtained in [12], see (1.5). In order to do this, we have to obtain significantly improved a priori estimates below $p(x)$, which is the main contribution of this paper. We also improve upon the previous results by obtaining the estimates for a larger class of domains than what was considered in the literature.     

Measurement of thermal conductivity of fluids using 3-<Emphasis Type="Italic">ω</Emphasis> method in a suspended micro wire

A thermally controlled, compact device employing the 3-ω technique, used to measure the thermal conductivity of fluids, is designed, developed, and presented in this paper. The 3-ω method, which analyzes temperature oscillations data in the frequency domain, requires a microscopic sample and extremely low heating power. The functionality is derived from the approximate solutions of temperature oscillations of a line heater based on the infinite line-heater model over an empirically and analytically chosen range of frequencies. The method is devoid of errors related to transient measurements, fluid thermal stratification and mobility errors, which pose difficulties in other methods. A platinum (99.99% pure) wire of 50 μm diameter and a length of 30 mm, suspended in a sample volume of 25 μl of the test fluid, serves simultaneously as the heater and thermometer. Structure-wise, the device is designed to support measurements over a range of temperatures and fluid pressures providing modularity and flexibility to the instrument. The device is successfully employed to measure the thermal conductivity of de-ionized water for temperatures between 15 and 35°C with an accuracy of ±1.2% inmeasurement.     

Observing capillarity in hydrophobic silica nanotubes

The development of template-synthesized silica nanotubes has created a unique opportunity for studying confined fluids by providing nanometer-scale containers in which the inner diameter (i.d.) and surface chemistry can be systematically and independently varied. An interesting question to be answered is the following: do solvents wet nanometer-scale tubes in the same way they wet ordinary capillaries? To answer this question, we have conducted studies to explore the wettability of the hydrophobic interiors of individual nanotubes. In these studies, single nanotubes with i.d.'s of either 30 or 170 nm were investigated over a range of water/methanol mixtures. These studies provide a direct route for comparing wetting phenomena in nanotubes with conventional macroscopic theories of capillarity. Our observations reveal four important aspects of capillary wetting in the 30-170 nm regime, a size range where the application of the Young-Laplace theory has not been experimentally investigated for hydrophobic pores. They are (i) a sharp transition between wetting and nonwetting conditions induced by addition of a cosolvent, (ii) invariance of this transition between nanotubes of 30 and 170 nm pore diameter, (iii) failure of the Young-Laplace equation to accurately predict the cosolvent's (methanol) mol fraction where the transition occurs, and (iv) reversibility of the observed wetting. The first two aspects conform to conventional capillarity (Young-Laplace), but the latter two do not. These measurements were complemented with ensemble experiments. The difference between theory and experiment is likely due to reliance on macroscopic values of contact angles or to liquid-phase instability within the hydrophobic pore.     

Temperature-dependent micellar structures in poly(styrene-b-isoprene) diblock copolymer solutions near the critical micelle temperature

The temperature dependence of the micelle structures formed by poly(styrene-b-isoprene) (SI) diblock copolymers in the selective solvents diethyl phthalate (DEP) and tetradecane (C14), which are selective for the PS and PI blocks, respectively, have been investigated by small angle neutron scattering (SANS). Two nearly symmetric SI diblock copolymers, one with a perdeuterated PS block and the other with a perdeuterated PI block, were examined in both DEP and C14. The SANS scattering length density of the solvent was matched closely to either the core or the corona block. The resulting core and corona contrast data were fitted with a detailed model developed by Pedersen and co-workers. The fits provide quantitative information on micellar characteristics such as aggregation number, core size, overall size, solvent fraction in the core, and corona thickness. As temperature increases, the solvent selectivity decreases, leading to substantial solvent swelling of the core and a decrease in the aggregation number and core size. Both core and corona chains are able to relax their conformations near the critical micelle temperature due to a decrease in the interfacial tension, even though the corona chains are always under good solvent conditions.     

Relative energies of alpha and beta isomers of Keggin dodecatungstogallate

The relative energies of beta Keggin heteropolytungstates, X(n+) W12O40(8-n)-, decrease as X(n+) is varied within period 3, from P5+ to Si4+ to Al3+. With heating of alpha-H5Ga3+ W12O40 at 200 degrees C in water, an equilibrated mixture of alpha (T(d); one 183W NMR signal) and beta (C(3v); three signals; 1:2:1 ratio) isomers is obtained. From deltaG(exp) = -RT ln K(beta-->alpha), in which (from 71Ga NMR spectra) K(beta-->alpha) (= [alpha]/[beta]) = 5.0, beta-GaW12O40(5-) is 0.65 kcal mol(-1) higher in energy than alpha-GaW12O40(5-). This finding is evaluated by analysis of the X-ray crystal structure alpha-K2Na3[GaW12O40] x 9.3 H2O [trigonal, space group P3(2)21, a = 18.9201(13) A, b = 18.9201(13) A, c = 12.5108(12) A, Z = 3, T = 100(2)K], comparison of the Shannon and Prewitt radii and Pauling electronegativities of Al3+ and Ga3+, and insight from density functional theory calculations, which predicted Ebeta - Ealpha = 0.32 kcal mol(-1).     

Optical stimulation of neural tissue in vivo

For more than a century, the traditional method of stimulating neural activity has been based on electrical methods, and it remains the gold standard to date. We report a technological breakthrough in neural activation in which low-level, pulsed infrared laser light is used to elicit compound nerve and muscle potentials in mammalian peripheral nerve in vivo. Optically induced neural action potentials are spatially precise, artifact free, and damage free and are generated by use of energies well below tissue ablation threshold. Thus optical stimulation presents a simple yet novel approach to contact-free in vivo neural activation that has major implications for clinical neurosurgery, basic neurophysiology, and neuroscience.     

Exact solutions to one-dimensional acoustic fields with temperature gradient and mean flow

An exact solution for one-dimensional acoustic fields in ducts in the presence of an axial mean temperature gradient and mean flow is presented in this paper. The analysis is valid for mean Mach numbers such that the square of the mean Mach number is much less than one. The one-dimensional wave equation for ducts with axial mean temperature gradient and mean flow is derived. By appropriate transformations, the wave equation is reduced to an analytically solvable hypergeometric differential equation for the case of a linear mean temperature profile. The developed solution is applied to investigate the dependence of sound propagation in a duct on factors such as temperature gradient and mean flow. The results obtained using the analytical solution compare very well with the numerical results. The developed solution is also compared with an existing analytical solution.     

Temperature-dependent magnetic anomalies of CuO nanoparticles

Copper oxide (CuO) nanoparticles with an average size of 25 nm were prepared by a sol-gel method. A detailed study was made of the magnetization of CuO nanoparticles using a maximum field of 60 kOe for temperatures between 8 and 300 K. Antiferromagnetic CuO nanoparticles exhibit anomalous magnetic properties, such as enhanced coercivity and magnetic moments. Significantly, the magnitude of the hysteresis component tends to weaken upon increase in temperature (>8 K). In addition, a hysteresis loop shift and coercivity enhancement are observed at 8 K in the field-cooled (FC, at 50 kOe) case. It is thought that the change in hysteresis behavior is due to the uncompensated surface spins of the CuO nanoparticles. The susceptibility (χ) plot showed that χ varied substantially at temperatures below 12 K, and this transition is due to the exchange interactions between the neighboring atoms at the nanoscale.