TOF-SIMS characterization and imaging of controlled-release drug delivery systems

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for the analysis of multilayer drug beads that serve as controlled-release drug delivery systems. TOF-SIMS analysis of a cross section of each bead system allowed molecular chemical information to be gained from all of the layers simultaneously, in situ. The integrity of each of the layers was evaluated through imaging of specific ion species for the drug, excipient, and coating materials. The three beads in this study each showed a unique distribution of ingredients. Images of the parent molecular ion for each drug (theophylline, paracetamol, prednisolone) showed their distribution ranged from micrometer-sized particles in one bead cross section to almost homogeneous in another bead cross section. The chemical composition of each of the layers in the beads was evaluated through mass spectrometry; the ingredients did not always match the manufacturer's specification. In addition, many common drug bead ingredients were analyzed as pure substances, providing TOF-SIMS reference spectra of these materials for the first time.     

A long-term ultraviolet aging procedure on foamed WMA mixtures

Long-term thermal and ultraviolet (UV) aging procedures of asphalt mixtures are complicated, but can be simulated in the laboratory. The objective of this study was to investigate the influence of long-term thermal and UV aging on foamed warm-mix asphalt (WMA) mixtures. Rut resistance, indirect tensile strength (ITS), deformation, dissipated elastic energy, and fracture energy were measured for all mixtures. The experimental design included two aggregate sources; three aging states (unaged, thermal and UV aging); one water-bearing WMA additive and water foaming technology; two PG 64-22 binders, and three air void contents (2, 4, and 7 %). A total of 24 mixtures were evaluated and 144 specimens were made and tested in this study. The test results indicated that thermal and UV aging procedures had limited contribution in improving the rut resistance of a mixture as air void content was low. Unaged samples had the highest ITS values amongst three aging states while UV aged samples had the lowest. In addition, UV aged mixtures generally had greater dissipated energy than thermal aged mixtures regardless of foaming technology, aggregate source, and air void. Moreover, the foaming technology might reduce the stored elastic energy of the mixture due to additional water or released water from water-bearing additive. Furthermore, UV aging generally reduces the fracture resistance of an asphalt mixture than standard thermal aging. In addition, when using WMA foaming technology, aggregate source affects the fracture resistance of the asphalt mixture.     

Union Cases Based on Designs by Bertel Thorvaldsen

Abstract

The recent article¹ on the use of Thorvaldsen's medallion designs by Peck for the decoration of two of the Peck and Hdvorsen cases made no reference to its use by other manufacturers. We have a case (see illustration), not recorded by Rinhart², nominally of quarter plate size, of fine quality and bearing the moulded legend contained within an oval ‘SMITH'S PATENT. 1860’. (Indicated ‘A’ on illustration.) It bears the title ‘Morning’ and there appears to be no indication of the engraver of the die. The paper label contained within is merely printed     

Recent progress in source development for extreme UV lithography

The continuation of Moore's law for semiconductor fabrication envisages the introduction of extreme ultraviolet lithography (EUVL) based on a source wavelength of 13.5?nm for high-volume manufacturing within the next few years. While exposure tools have already been developed and the feasibility of the technology well demonstrated, the key source requirement in terms of power output remains to be achieved. Currently, sources based on laser-produced plasmas from tin droplet targets appear to be the most promising and are being deployed in manufacturing tools. Progress in CO₂ laser design aimed at increasing conversion efficiency to close to 5% should make possible the attainment of greater than 200?W of in-band optical power. Recently, research has commenced on the development of sources operating at a wavelength near 6.7?nm for beyond 13.5?nm lithography and gadolinium has been identified as the fuel of choice. The results of these experiments are described and show many similarities to the behavior of tin plasmas as essentially the same atomic and plasma processes are involved, albeit at an electron temperature close to a factor of three higher.     

Estimating correlation with multiply censored data arising from the adjustment of singly censored data

Environmental data frequently are left censored due to detection limits of laboratory assay procedures. Left censored means that some of the observations are known only to fall below a censoring point (detection limit). This presents difficulties in statistical analysis of the data. In this paper, we examine methods for estimating the correlation between variables each of which is censored at multiple points. Multiple censoring frequently arises due to adjustment of singly censored laboratory results for physical sample size. We discuss maximum likelihood (ML) estimation of the correlation and introduce a new method (cp.mle2) that, instead of using the multiply censored data directly, relies on ML estimates of the covariance of the singly censored laboratory data. We compare the ML methods with Kendall's tau-b (ck.taub) which is a modification Kendall's tau adjusted for ties, and several commonly used simple substitution methods: correlations estimated with nondetects set to the detection limit divided by 2 and correlations based on detects only (cs.det) with nondetects setto missing. The methods are compared based on simulations and real data. In the simulations, censoring levels are varied from 0 to 90%, p from -0.8 to 0.8, and v (variance of physical sample size) is set to 0 and 0.5, for a total of 550 parameter combinations with 1000 replications at each combination. We find that with increasing levels of censoring most of the correlation methods are highly biased. The simple substitution methods in general tend toward zero if singly censored and one if multiply censored. ck.taub tends toward zero. Least biased is cp.mle2, however, it has higher variance than some of the other estimators. Overall, cs.det performs the worst and cp.mle2 the best.     

乌得勒支In Lumine Tuo 荷兰乌得勒支

<正>对于获奖理念,我们用光作为叙述工具,将14世纪标志性的大教堂塔与相邻的大教堂(圣马丁大教堂)以及大教堂广场连接起来,以永久庆祝乌得勒支条约签订300周年。设计理念便始于这三个要素的抽象视图,三个要素被视为乌特勒支社会积极且重要的成员。光让建筑彼此相连,与城市居民交流着城市的记忆,回忆起这座城市的悠久历史。     

Factors controlling stripping voltammetry of lead at polycrystalline boron doped diamond electrodes: new insights from high-resolution microscopy

We report wide-ranging studies to elucidate the factors and issues controlling stripping voltammetry of metal ions on solid electrodes using the well-known Pb/Pb(2+) couple on polycrystalline boron doped diamond (pBDD) as an exemplar system. Notably, high-resolution microscopy techniques have revealed new insights into the features observed in differential pulse anodic stripping voltammetry (DPV-ASV) which provide a deeper understanding of how best to utilize this technique. DPV-ASV was employed in an impinging wall-jet configuration to detect Pb(2+) in the nanomolar to micromolar concentration range at a pBDD macrodisk electrode. The deposition process was driven to produce a grain-independent homogeneous distribution of Pb nanoparticles (NPs) on the electrode surface; this resulted in the observation of narrow stripping peaks. Lower calibration gradients of current or charge versus concentration were found for the low concentrations, correlating with a lower than expected (from consideration of the simple convective-diffusive nature of the deposition process) amount of Pb deposited on the surface. This was attributed to the complex nature of nucleation and growth at solid surfaces in this concentration regime, complicating mass transport. Furthermore, a clear shift negative in the stripping peak potential with decreasing concentration was seen correlating with a change in the size of the deposited NP, suggesting an NP size-dependent redox potential for the Pb/Pb(2+) couple. At high concentrations a nonlinear response was observed, with less Pb detected than expected, in addition to the observation of a second stripping peak. Atomic force microscopy (AFM) and field emission scanning electron microscopy revealed the second peak to be due to a change in deposition morphology from isolated NPs to grain-independent heterogeneous structures comprising both thin films and NPs; the second peak is associated with stripping from the thin-film structures. AFM also revealed a substantial amount of Pb remaining on the surface after stripping at high concentration, explaining the nonlinear relationship between stripping peak current (or charge) and concentration. Finally, the use of an in situ cleaning procedure between each measurement was advocated to ensure a clean Pb-free surface (verified by AFM and X-ray photoelectron spectroscopy analysis) between each run. The studies herein highlight important and complex physicochemical processes involved in the electroanalysis of heavy metals at solid electrodes, such as pBDD, that need to be accounted for when using stripping voltammetry methods.     

Determination of the physical properties of room temperature ionic liquids using a Love wave device

In this work, we have shown that a 100 MHz Love wave device can be used to determine whether room temperature ionic liquids (RTILs) are Newtonian fluids and have developed a technique that allows the determination of the density-viscosity product, ρη, of a Newtonian RTIL. In addition, a test for a Newtonian response was established by relating the phase change to insertion loss change. Five concentrations of a water-miscible RTIL and seven pure RTILs were measured. The changes in phase and insertion loss were found to vary linearly with the square root of the density-viscosity product for values up to (ρη)(1/2) ~ 10 kg m(-2) s(-1/2). The square root of the density-viscosity product was deduced from the changes in either phase or insertion loss using glycerol as a calibration liquid. In both cases, the deduced values of ρη agree well with those measured using viscosity and density meters. Miniaturization of the device, beyond that achievable with the lower-frequency quartz crystal microbalance approach, to measure smaller volumes is possible. The ability to fabricate Love wave and other surface acoustic wave sensors using planar metallization technologies gives potential for future integration into lab-on-a-chip analytical systems for characterizing ionic liquids.     

Morphology of the stifle in agouti (Dasyprocta prymnolopha,Wagler 1831)

The agouti (Dasyprocta prymnolopha, Wagler 1831) is a wild rodent of great zootechnical potential, a fact that enables anatomical and morphological studies to support management actions with this animal. In this perspective, this study aimed to describe the anatomy and histology of the agouti stifle joint. Four adult agoutis were used, two females and two males. The animals were submitted to dissection and identification of the structures of the stifle joint. For light microscopy study, samples of the patellar ligament, cranial and caudal cruciate ligaments, medial and lateral collateral ligaments were used. Agouti has a highly congruent patellofemoral joint; elongated patella; medial and lateral fabellae at the proximal insertion of the gastrocnemius muscle; medial and lateral meniscus with lunula; in addition to the presence of the following ligament structures: patellar ligament, cranial and caudal cruciate ligaments, medial and lateral collateral ligaments, meniscofemoral ligament, caudal meniscal ligament of the medial meniscus, and medial and lateral cranial ligaments. The patellar ligament presents bundles of parallel collagen fibers with a straight path and coated fibroblasts; collateral and cruciate ligaments had loose and dense connective tissue, coated fibroblasts and collagen bundle undulations, the latter most expressive in the caudal cruciate ligament. Thus, except for the shape and angulation of the stifle, which allows specific movements, the agouti stifle has structures analogous to that of other rodents and domestic animals.