A study of real-time spindle error compensation in single-point diamond turning of optical micro-structured patterns on precision rollers

Micro-structured patterns are widely used in optics since the optical performance can be significantly improved in many applications [1]. One of the most common methods to fabricate the micro-structure is using Single-Point Diamond Turning on Precision Rollers [2]. The accuracy requirement of the Precision Rollers is stringent because the dimension of the microstructure is very small (pitch lengths and depths 10-100μm) and surface finishing is ultra-smooth (Ra<3nm) [2]. In order to achieve this level of accuracy, the manufacturing errors of the machine tool are required to be reduced while error compensation methods are needed to be developed. Spindle errors can be classified as synchronous error and asynchronous error [3]. Synchronous error occurs at integer times of spindle rotation frequency and can be represented as repeatable error while asynchronous error occurs at noninteger times of spindle rotation frequency and can be represented as non-repeatable error. Most of the existing error compensation techniques are based on offline error compensation methods (OECM) which can only compensate the synchronous error [4,5]. The asynchronous error is fluctuating without a predictable value and it is different from the synchronous error so it cannot be eliminated using OECM. One of the most promising methods to compensate the asynchronous error is real-time error compensation method (RECM). Some researchers have studied the RECM and their results showed that it was effective to enhance the machine accuracy [6,7]. However, most of the previous research work is focused on the machine tools with a relatively low accuracy and there is relatively few studies focused on the Single-Point Diamond Turning. Kim and Kim developed a feed-forward control of fast tool servo system for real-time correction of spindle error for diamond turning of flat surfaces [8]. A capacitive displacement sensor was used to measurement the spindle axial error motion and the motion error was compensated using a fast tool servo. A flatness of 0.1μm was achieved with a 100mm diameter aluminum specimen. However, the study only considered the axial error, when it is diamond turned on precision rollers, both the radial error and axial error have to be compensated. This paper attempts to investigate the RECM in Single-Point Diamond Turning of Optical Microstructured Patterns on Precision Rollers. The radial error and axial error were simulated and the compensated results of OECM and RECM were presented considering both synchronous errors and asynchronous errors in radial and axial directions. The results of OECM and RECM were also compared and discussed. Furthermore, the effects of time delay in RECM were studied. An adaptive time-series modeling method was also proposed to predict the realtime error to reduce the time delay effect of RECM. The results show that the RECM is effective and promising to further improve the accuracy of the Single-Point Diamond Turning Precision Rollers

Metabolic profiling of HepG2 cells incubated with S(−) and R(+) enantiomers of anti-coagulating drug warfarin

Warfarin is a commonly prescribed oral anticoagulant with narrow therapeutic index. It achieves anti-coagulating effects by interfering with the vitamin K cycle. Warfarin has two enantiomers, S(−) and R(+) and undergoes stereoselective metabolism, with the S(−) enantiomer being more effective. We reported the intracellular metabolic profile in HepG2 cells incubated with S(−) and R(+) warfarin by GCMS. Chemometric method PCA was applied to analyze the individual samples. A total of 80 metabolites which belong to different categories were identified. Two batches of experiments (with and without the presence of vitamin K) were designed. In samples incubated with S(−) and R(+) warfarin, glucuronic acid showed significantly decreased in cells incubated with R(+) warfarin but not in those incubated with S(−) warfarin. It may partially explain the lower bio-activity of R(+) warfarin. And arachidonic acid showed increased in cells incubated with S(−) warfarin but not in those incubated with R(+) warfarin. In addition, a number of small molecules involved in γ-glutamyl cycle displayed ratio variations. Intracellular glutathione detection further validated the results. Taken together, our findings provided molecular evidence on a comprehensive metabolic profile on warfarin-cell interaction which may shed new lights on future improvement of warfarin therapy

VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker

Recognizing specific protein changes in response to drug administration in humans has the potential for the development of personalized medicine. Such changes can be identified by pharmacoproteomics approach based on proteomic technologies. It can also be helpful in matching a particular target-based therapy to a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism. Warfarin is a commonly prescribed oral anticoagulant in patients with prosthetic valve disease, venous thromboembolism and stroke.We used a combined pharmacogenetics and iTRAQ-coupled LC-MS/MS pharmacoproteomics approach to analyze plasma protein profiles of 53 patients, and identified significantly upregulated level of transthyretin precursor in patients receiving low dose of warfarin but not in those on high dose of warfarin. In addition, real-time RT-PCR, western blotting, human IL-6 ELISA assay were done for the results validation.This combined pharmacogenomics and pharmacoproteomics approach may be applied for other target-based therapies, in matching a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism

Resolution of chiral compounds by crystallization

Objectives of this project are: (1) Understanding of the factors that control the formation of enantiomerically pure and racemic crystals. (2) Development of a reliable racemic species characterization method. (3) Development and optimization of chiral crystallization processes for different racemic species of commercial interest. In this project, a systematic approach has been developed and applied to preferential crystallization of chiral molecules by integration of system thermodynamics, crystallization kinetics, optimal operation and in-situ monitoring. Three types of racemate crystals were identified with thermal analysis and structural characterizations. Their metastable zone widths in solution were found as an additional characteristic to identify racemic species. Primary nucleation order variations with enantiomeric excess suggested there exists a critical supersaturation beyond which the nucleation of opposite isomer could occur. A dynamic method was developed and used to measure the crystallization kinetics of several systems. With combination of thermodynamics and crystallization kinetics, a detailed mathematical modeling was established to predict the operation strategy. The product's optical purity, crystal morphology and in-situ observations, all suggested that the critical supersaturation control was essential and the systematic approach was successful and applicable for preferential crystallization of chiral compounds.ARC6/0

Development of a novel technology to immobilise enzymes in the mesoporous Zr02 matrix and applications in the large scale asymmetric resolution of chiral compounds

Our study has demonstrated for the first time that zirconia nanoparticles modified by a simple carboxylic surfactant of a very long alkyl chain can significantly enhance the activity of the immobilized lipases for asymmetric synthesis in organic media. Zirconia nanoparticles of ca. 20 nm in diameter were grafted with carboxylic surfactant modifiers from Tween 85 and erucic acid. The surface of nanoparticles was successfully changed from hydrophilic to hydrophobic. Lipases from Candida rugosa and Pseudomonas cepacia were immobilized on the modified zirconia nanoparticles by adsorption in aqueous solution. The immobilized lipases were used for the resolution of (R,S)-ibuprofen and (R,S)-1-phenylethanol through esterification and acylation, respectively, in isooctane organic solvent. When immobilized on erucic acid modified zirconia, both lipases gave significantly higher activity and enantiomeric excess compared with those from their corresponding crude lipase powders. The nanohybrid biocatalysts are stable and can be reused for eight cycles without loss in activity and selectivity. The interaction between the hydrophobic surface of zirconia support and lipases probably induces the conformational rearrangement of lipases into an active and stable form.RG2/0

Enzymatic and protein crystallization and structure study

In this work, we aimed to develop practical techniques and theoretical basis for protein crystallization to improve the success rate to obtain protein crystals with good quality. The effects of ionic strength, liquid-liquid phase separation and different chemically modified solid surfaces/substrates on the nucleation of protein crystals were investigated. Micro-batch crystallization experiments were conducted to study the mechanism of nucleation of protein crystals. An optical microscope with a heating/cooling stage was applied to determine the liquid-liquid co-existence curve, measure the initial nucleation rate and observe the liquid-liquid phase separation and subsequent crystallization process. A model was proposed to correlate and predict the cloud point temperature as a function of lysozyme concentration at fixed salt concentrations. In this model, the Random Phase Approximation, in conjunction with a square-well potential, was modified by assuming the square-well depth to be temperature dependent. The modified model was found to predict the liquid-liquid co-existence curve very well. Micro-batch crystallization experiments were also conducted on the microscope glass slides that were treated with poly-L-glutamic acid (PLG), poly(2-hydroxyethyl methacrylate) (P2HEMA), poly(methyl methacrylate) (PMMA), poly(4-vinyl pyridine) (P4VP) and (3-aminopropyl)triethoxysilane (APTES). The induction time of heterogeneous nucleation was measured. The surface topography and roughness were characterized by atomic force microscope (AFM). Contact angles for crystallization solution on the investigated surfaces were measured by contact angle meter. Theoretical analysis and experimental results show that, the surface roughness and topography can remarkably affect the free energy required for the formation of critical nucleus. Furthermore, hydrophobicity, electrostatic and antibacterial property of surface also greatly affected protein nucleation.RG122/0

Mechanism of polymorphism for pharmaceutical crystallization

The objectives of this work are to investigate the mechanism and progression of polymorphic transformation and crystallization, study the effect of additives, solvents, and experimental conditions, and develop effective polymorph controlling strategy for pharmaceutical manufacture. The nucleation and transformation of two polymorphs of glycine (α- and γ-forms) have been investigated. The influence of additive, solvent and process parameters such as saturated temperature, seed size and stirring speed on the transformation behavior from metastable form to stable form were examined. The different polymorphs were unambiguously examined by using Powder XRD, Raman microscope, FTIR, TGA and DSC. The polymorphic transition temperature was determined by both DSC and solubility measurements. The in-situ Raman spectroscopy was used to monitor the polymorphic transformation process and the solid-phase polymorphic composition was quantitatively calculated using multivariate analysis. The polymorphic transformation in solvent was also in-situ inspected using microscope with heating/cooling stage. The integration of the different off-line and in-situ measurement and controlling techniques will be valuable in studying the crystallization and transformation mechanism of polymorphic systems and developing a robust crystallization process to obtain the desired polymorphic crystal products.RG48/0

Population dynamics of cyanomyovirus in a tropical eutrophic reservoir

10.1264/jsme2.ME14039Microbes and Environments30112-2

Combinatorial assembly of large biochemical pathways into yeast chromosomes for improved production of value-added compounds

10.1021/sb500079fACS Synthetic Biology4123-3