Hydrodynamic effects of an arch-shaped fiber optic probe in a dissolution testing apparatus 2

Dissolution testing is widely used in the pharmaceutical industry to evaluate newly developed drug formulations and as a quality control method to insure that solid dosage forms have consistent dissolution property. Typically, samples are manually drawn from the dissolution vessel prior to analysis. An approach to overcome the limitations of manual sampling consists in the use of sampling probes, such as fiber optic probes, permanently inserted in the dissolution medium and continually sampling the drug concentration in it as the solid dosage form dissolves. Despite their advantages, permanently inserted fiber optic probes can alter the normal fluid flow within the vessel and produce different dissolution testing results. In this study, the hydrodynamic effects introduced by an arch-shaped fiber optic probe in a USP Dissolution Testing Apparatus 2 are studied by: (1) conducting dissolution tests, with and without the probe, using Prednisone tablets fixed at nine different locations at the bottom of the vessel and comparing the dissolution profiles obtained using statistical tools; and (2) experimentally determining the velocity profiles in the vessel, with and without the probe, using Particle Image Velocimetry (PIV) and quantifying changes in the flow velocities on selected horizontal iso-surfaces. The results show that the arch shaped fiber optic probe does have a baffling effect on the hydrodynamics in the dissolution vessel. This effect results in changes in the velocities in the fluid flow, and therefore in changes in the dissolution rate of the tablets undergoing testing. The baffle effect is observed mainly in the region where the probe is inserted. However, this perturbation is also found to reach the region below the impeller and to change the velocity profile there, resulting in differences in dissolution profiles when the tablets are fixed at positions that are downstream of the probe and within the low velocity region below the impeller. On the other hand, the hydrodynamic effect generated by the probe does not appear to be particularly strong. In most dissolution testing runs, the changes in dissolution profile are not large enough to fail the tests, according to the FDA criteria (f1 and f2 values). The PIV measurements additionally show that the baffle effect is not strong enough to break the overall flow pattern, or to affect the region around the impeller, which is dominated by the main flow generated by the impeller. It can be concluded that the hydrodynamic effects generated by the arch-shaped fiber optic probe are real and observable, resulting in slightly modification of the fluid flow in the dissolution vessel and therefore in detectable differences in the dissolution profiles. However, these effects are limited and do not typically lead to dissolution testing failures

THE ENDOGENEITY OF THE OPTIMUM CURRENCY AREA: BUSINESS CYCLES CORRELATION TRADE INTENSITY INTRA­INDUSTRY TRADE AND TRADE PATTERN IN THE EUROPEAN MONETARY UNION

The concern of a sovereign debt crisis in the euro zone has become particularly intense since 2010, as several countries’ sovereign debts have increased sharply due to bank bailouts. The Optimum Currency Area (OCA) theory suggests that countries that have close trade links, similar business cycles, labor mobility across the region, and a risk sharing system such as an automatic fiscal transfer mechanism are suitable candidates to form a common currency union. A study by Frankel and Rose (1998) claims that trade intensity and business cycles correlation are endogenous and strongly correlated. Hence, a country is more likely to satisfy the criteria for entry into a currency union “ex post” than “ex ante”. This paper aims to investigate the determinants of the correlation of business cycles in the euro zone. My hypothesis is that trade structure causes the convergence of business cycles, and only countries with similar trade structures are suitable candidates for a common monetary union. My regression model is based on the endogeneity hypothesis of the OCA criteria pioneered by Frankel and Rose (1998). The dataset is a time‐series panel data for 17 euro zone members from 2002‐2010. The dependent variable is business cycle correlation, and the independent variables include trade intensity, intra‐industry trade, and trade structure. The regression results suggest that trade structure heavily influences the correlation of business cycles, while intra‐industry trade has no direct impact on the correlation of business cycles

Plant invasions in China : an emerging hot topic in invasion science

China has shown a rapid economic development in recent decades, and several drivers of this change are known to enhance biological invasions, a major cause of biodiversity loss. Here we review the current state of research on plant invasions in China by analyzing papers referenced in the ISI Web of Knowledge. Since 2001, the number of papers has increased exponentially, indicating that plant invasions in China are an emerging hot topic in invasion science. The analyzed papers cover a broad range of methodological approaches and research topics. While more that 250 invasive plant species with negative impacts have been reported from China, only a few species have been considered in more than a handful of papers (in order of decreasing number of references: Spartina alterniflora, Ageratina adenophora, Mikania micrantha, Alternanthera philoxeroides, Solidago canadensis, Eichhornia crassipes). Yet this selection might rather reflect the location of research teams than the most invasive plant species in China. Considering the previous achievements in China found in our analysis research in plant invasions could be expanded by (1) compiling comprehensive lists of non-native plant species at the provincial and national scales and to include species that are native to one part of China but non-native to others in these lists; (2) strengthening pathways studies (primary introduction to the country, secondary releases within the country) to enhance prevention and management; and (3) assessing impacts of invasive species at different spatial scales (habitats, regions) and in relation to conservation resources

A Statistical STT-RAM Design View and Robust Designs at Scaled Technologies

Rapidly increased demands for memory in electronic industry and the significant technical scaling challenges of all conventional memory technologies motivated the researches on the next generation memory technology. As one promising candidate, spin-transfer torque random access memory (STT-RAM) features fast access time, high density, non-volatility, and good CMOS process compatibility. In recent years, many researches have been conducted to improve the storage density and enhance the scalability of STT-RAM, such as reducing the write current and switching time of magnetic tunneling junction (MTJ) devices. In parallel with these efforts, the continuous increasing of tunnel magneto-resistance(TMR) ratio of the MTJ inspires the development of multi-level cell (MLC) STT-RAM, which allows multiple data bits be stored in a single memory cell. Two types of MLC STT-RAM cells, namely, parallel MLC and series MLC, were also proposed. However, like all other nanoscale devices, the performance and reliability of STT-RAM cells are severely affected by process variations, intrinsic device operating uncertainties and environmental fluctuations. The storage margin of a MLC STT-RAM cell, i.e., the distinction between the lowest and highest resistance states, is partitioned into multiple segments for multi-level data representation. As a result, the performance and reliability of MLC STT-RAM cells become more sensitive to the MOS and MTJ device variations and the thermal-induced randomness of MTJ switching. In this work, we systematically analyze the impacts of CMOS and MTJ process variations, MTJ resistance switching randomness that induced by intrinsic thermal fluctuations, and working temperature changes on STT-RAM cell designs. The STT-RAM cell reliability issues in both read and write operations are first investigated. A combined circuit and magnetic simulation platform is then established to quantitatively study the persistent and non-persistent errors in STT-RAM cell operations. Then, we analyzed the extension of STT-RAM cell behaviors from SLC (single-level- cell) to MLC (multi-level- cell). On top of that, we also discuss the optimal device parameters of the MLC MTJ for the minimization of the operation error rate of the MLC STT-RAM cells from statistical design perspective. Our simulation results show that under the current available technology, series MLC STT-RAM demonstrates overwhelming benefits in the read and write reliability compared to parallel MLC STT-RAM and could potentially satisfy the requirement of commercial practices. Finally, with the detail analysis study of STT-RAM cells, we proposed several error reduction design, such as ADAMS structure, and FA-STT structure

Marginal Structural Illness-Death Models for Semi-Competing Risks Data

The three-state illness death model has been established as a general approach for regression analysis of semi-competing risks data. For observational data the marginal structural models (MSM) are a useful tool, under the potential outcomes framework to define and estimate parameters with causal interpretations. In this paper we introduce a class of marginal structural illness death models for the analysis of observational semi competing risks data. We consider two specific such models, the usual Markov illness death MSM and the general Markov illness death MSM where the latter incorporates a frailty term. For interpretation purposes, risk contrasts under the MSMs are defined. Inference under the usual Markov MSM can be carried out using estimating equations with inverse probability weighting, while inference under the general Markov MSM requires a weighted EM algorithm. We study the inference procedures under both MSMs using extensive simulations, and apply them to the analysis of mid-life alcohol exposure on late life cognitive impairment as well as mortality using the Honolulu-Asia Aging Study data set. The R codes developed in this work have been implemented in the R package semicmprskcoxmsm that is publicly available on CRAN