Optimization and design of reactive crystallization process

Crystallization is an important process used in a wide range of industries, which has made it the main process in the primary manufacturing stage, and thereby the quality of crystals produced has a major impact on downstream processes such as filtration, milling and drying, as well as transport and storage processes. Organic reactive crystallization, which is widely used in the production of active pharmaceutical ingredients (APIs), has many unique features that make it different from cooling or anti-solvent crystallization, even leading to some concepts and methods not directly applicable to this process. A survey of the literature reveals that previous research on reactive crystallization has mainly been conducted for inorganic materials which are known to be simpler than crystallization of organic materials. For example, it is known that compared with inorganic materials, organic materials tend more to aggregation and form amorphous. In addition, the published literature in this research area is often concerned with laboratory scale crystallization, rather than industrial scale processes. The focus of this research project is to carry out research on the process design, optimization, simulation and scale-up of organic reactive pharmaceutical crystallization. The objective is to research the process and crystallizer design which takes advantage of the features of the reactive crystallization process and on simulation, optimization and scale-up techniques with the aim of manufacturing high quality products measured by the products’ crystallinity, stability, purity, and processability. Process analytical technology (PAT) is used as a supporting tool to achieve the above stated objectives. An off-patent drug, sodium cefuroxime which is considered as a second generation antibiotic, is used as the case study drug. Firstly, on-line Attenuated Total Reflection-Fourier Transform InfraRed spectroscopy (ATR-FTIR) was used to monitor the change in the supersaturation in order to optimize the flow rate of the anti-solvent during the anti-solvent re-crystallization process of sodium cefuroxime. The solubility of sodium cefuroxime under various temperatures T, pH values and solvents was measured and correlated in models. The effect of the anti-solvent (95% ethanol) flow rate on crystallinity was examined and the results showed that appropriate anti-solvent flow rate could improve the stability of sodium cefuroxime. The optimized anti-solvent re-crystallization process provided a new method to obtain high-quality seeds of sodium cefuroxime. Secondly, Process Analytical Technology (PAT) based on Focused Beam Reflectance Measurement (FBRM) was used to optimize the parameters of the reactive synthesis process of sodium cefuroxime, such as the feed order, the reaction temperature, the stirring speed, the feed rate/speed and the amount of seeds. An impinging jet mixer, which could provide rapid mixing effectiveness of reactants, was applied and optimized. After that, the optimized process was scaled-up from 1L to 10L with a volumetric scaling-up factor of 10. The product had superior crystallinity, uniform size distribution, higher stability and purity, which indicated that this optimization methodology and impinging jet mixer design could be applied in other similar reactive crystallization processes. Finally, Process Analytical Technology (PAT) including Ultraviolet–Visible Spectrometry (UV) and FBRM was used to study the reaction kinetics and the mechanism of crystal growth in the reactive synthesis process of sodium cefuroxime. A process and crystallizer was designed based on the data obtained above. This process provided two reactors in series for conducting a rapid reactive crystallization process of pharmaceutical compounds in continuous mode. It involved a tank reactor with the use of an impinging jet mixer and stirrer to create intensive mixing of the reactants before nucleation and a tubular reactor with suitable length to avoid back mixing of the products. The results showed that by using this process, the product had uniform size distribution, higher stability and superior crystallinity, in both laboratory scale and 50L scaled-up processes

An extension of the Beurling-Chen-Hadwin-Shen theorem for noncommutative Hardyspaces associated with finite von Neumann algebras

In 2015, Yanni Chen, Don Hadwin and Junhao Shen proved a noncommutative version of Beurling\u27s theorem for a continuous unitarily invariant norm α on a tracial von Neumann algebra (M,τ)such that α is one dominating with respect to τ. The role of H^∞ is played by a maximal subdiagonal algebra A . In the talk, we first will show that if α is a continuous normalized unitarily invariant norm on (M,τ), then there exists a faithful normal tracial state ρ on M and a constant c \u3e0 such that α is a c times one norm-dominating norm on (M,ρ). Moreover, ρ (x)= τ (xg), where x in M, g is positive in L^1 (Z,τ), where Z is the center of M . Here c and ρ are not unique. However, if there is a c and ρ so that the Fuglede-Kadison determinant of g is positive, then Beurling-Chen-Hadwin-Shen theorem holds for L^(α ) (M,τ). The key ingredients in the proof of our result include a factorization theorem and a density theorem for for L^(α ) (M,ρ)

THE IMPLICATIONS OF SCIENCE AND TECHNOLOGY FOR CHINESE WOMEN: A CULTURAL STUDY OF THE CHINESE ERA OF REFORMS

Abstract This dissertation addresses the gendered implications of science and technology in the era of reforms. It argues that in this era, which began in 1978 and continues today, science and technology are highly romanticized as nearly omnipotent. This results in its being embedded not only into ordinary Chinese people’s lives, hoping to bring them positive changes, but also into the Chinese government’s political practices, hoping to achieve its political purposes through science and technology. It also points out that in the era of reforms, Chinese women’s lived experiences are full of tensions, struggles, and conflicts, as evidenced by the expectations for them to become virtuous wives, caring mothers, and, at the same time, successful professionals. The veneration of science and technology in Chinese culture and the Chinese government’s strict control over science and technology further complicate Chinese women’s experiences. To illustrate these points, I mainly use the analytical methods “articulation” and “mapping” from cultural studies to explore the impacts of Chinese myth, Confucianism and Daoism, Chinese language, Chinese political practices, and media and popular discourses to explain the status of science and technology and the living situation of Chinese women in the era of reforms. I analyze the cases of the development and use of science and technology: to promote marriage and family, for population control and family design, to promote the discourse of the super mother, and to help women gain independence and fight against sexual violence. I focus on the gendered implications of some specific scientific and technological artifacts, including dating websites, in vitro fertilization (IVF), breast pumps, social media, and many others. This dissertation contributes to understanding Chinese women and science and technology in contemporary China. It reveals that although Chinese women’s living situations have improved significantly, many of them are still trapped and subordinated. Science and technology, which are always articulated with other elements, especially the Chinese government’s politics, the traditional patriarchal culture, and many Chinese women’s demands for gender equality, aggravate many women’s suffering while also offering some of them extra job opportunities and access to virtual spaces to engage in social activism

Multirate Frequency Transformations: Wideband AM-FM Demodulation with Applications to Signal Processing and Communications

The AM-FM (amplitude & frequency modulation) signal model finds numerous applications in image processing, communications, and speech processing. The traditional approaches towards demodulation of signals in this category are the analytic signal approach, frequency tracking, or the energy operator approach. These approaches however, assume that the amplitude and frequency components are slowly time-varying, e.g., narrowband and incur significant demodulation error in the wideband scenarios. In this thesis, we extend a two-stage approach towards wideband AM-FM demodulation that combines multirate frequency transformations (MFT) enacted through a combination of multirate systems with traditional demodulation techniques, e.g., the Teager-Kasiser energy operator demodulation (ESA) approach to large wideband to narrowband conversion factors. The MFT module comprises of multirate interpolation and heterodyning and converts the wideband AM-FM signal into a narrowband signal, while the demodulation module such as ESA demodulates the narrowband signal into constituent amplitude and frequency components that are then transformed back to yield estimates for the wideband signal. This MFT-ESA approach is then applied to the various problems of: (a) wideband image demodulation and fingerprint demodulation, where multidimensional energy separation is employed, (b) wideband first-formant demodulation in vowels, and (c) wideband CPM demodulation with partial response signaling, to demonstrate its validity in both monocomponent and multicomponent scenarios as an effective multicomponent AM-FM signal demodulation and analysis technique for image processing, speech processing, and communications based applications

An Appraisal Analysis of the Discourse of Foreign English Teachers: a Case Study at a Private School in Ratchaburi, Thailand.

In recent years, many Thai schools have started to hire foreign English speakers to teach Thai students the skill of speaking English. This study aims to investigate how the foreign English teachers express their attitudes about teaching English in Thailand, and further explore the teaching beliefs, culture and language ideology implicit in these teachers’ attitudes. An ‘Appraisal’ system (Martin 2007& Rose) was applied to analyze the attitudes, such as affect (people’s feelings), judgment (people’s character and behavior) and appreciation (the value of things), being conveyed in the discourse of the foreign English teachers in Thailand.The findings of this study indicated the similarities and differences in these foreign English teachers’ attitudes about their motivation, challenges and future aspiration of teaching in Thailand. Furthermore, this study revealed that different culture background and language ideologies influenced the teachers’ teaching beliefs and classroom teaching approaches.