Apply adsorption technology to solve the UV sensor instability of dynamic control on periodic counter current purification system

Cell culture media are a source of major nutrients that provide cell growth and synthesis of proteins. Researchers and suppliers use combine media components test continually in an attempt to find more suitable cell culture media for use in continuous cell culture processes. Commercial media components are a black box for downstream purification researchers who cannot predict the effects of their constituents on resin affinity, absorbability, even for interference with UV instrument. To more effectively utilize in dynamic continuous purification system, the loading product percentage of resin absorbability is typically controlled at 40-60% maximum binding capacity. It is often five times more than traditional batch purification. Therefore, the swing of UV percentage caused by color material in the bulk harvest is the key process parameter in the periodic counter current purification system. We compared different commercial quaternary ammonium adsorbent matrix (such as Stabilized Regenerated Cellulose, Agarose and Styrene Divinyl Benzene Copolymer) to observe their effects on the swing of the UV amplitude. The results show that agarose group has better de-coloration efficacy than the other two commercial quaternary ammonium groups. Please click Additional Files below to see the full abstract

Current-induced Spin Polarization in Two-Dimensional Hole Gas

We investigate the current-induced spin polarization in the two-dimensional hole gas (2DHG) with the structure inversion asymmetry. By using the perturbation theory, we re-derive the effective $k$-cubic Rashba Hamiltonian for 2DHG and the generalized spin operators accordingly. Then based on the linear response theory we calculate the current-induced spin polarization both analytically and numerically with the disorder effect considered. We have found that, quite different from the two-dimensional electron gas, the spin polarization in 2DHG depends linearly on Fermi energy in the low doping regime, and with increasing Fermi energy, the spin polarization may be suppressed and even changes its sign. We predict a pronounced peak of the spin polarization in 2DHG once the Fermi level is somewhere between minimum points of two spin-split branches of the lowest light-hole subband. We discuss the possibility of measurements in experiments as regards the temperature and the width of quantum wells.Comment: 13 pages, 8 figures, submitted to PR

Critical quality attributes (CQAs) of a therapeutic antibody produced from integrated continuous bioprocessing

The integrated continuous bioprocess provides an innovative way to produce protein drugs with flexibility and efficiency. However, during the long-term cultivation and complicated production, how to ensure the process stability and product quality is critically important. In this study, the monoclonal antibody (mAb) was produced in a bioreactor operated in a perfusion mode utilizing the ATF cell retention system for up to 32 days. The 2L harvest per day starting at day 10 was continuously purified using the 3-column periodic counter-current (PCC) chromatography system. The first protein A capture purification was performed with the dynamic binding capacity of 50% breakthrough around 60 mg mAb/mL of resin (vs 20 mg/mL resin for batch purification) for 120 cycles or 360 column operations followed by a polishing step of mixed mode chromatography for 20 cycles. The process and quality attributes were monitored daily. The results demonstrate consistency in both the purification process and the mAb qualities (in the aspects of product integrity, aggregates, and glycan profile) between PCC and batch purifications. Culture-related charge heterogeneity was observed accompanied by an increase of bioreactor harvest time using both batch and PCC purification processes. In addition, the impurities such as endotoxin and HCP were also monitored while under this high capacity utilization of chromatography resins. By sharing the insights of process and quality attributes, we hope to provide better understanding on the process-related heterogeneity between batch and continuous production and/or purification

Generation and Evolution of Spin Entanglement in NRQED

A complete analysis on the generation of spin entanglement from NRQED is presented. The results of entanglement are obtained with relativistic correction to the leading order of (v/c)^2. It is shown that to this order the degree of entanglement of a singlet state does not change under time evolution whereas the triplet state can change.Comment: 8 pages, 1 figure, to appear in Phys. Rev.

Principal inpatient diagnostic cost group model for Medicare risk adjustment

The Balanced Budget Act (BBA) of 1997 required HCFA to implement health-status-based risk adjustment for Medicare capitation payments for managed care plans by January 1, 2000. In support of this mandate, HCFA has been collecting inpatient encounter data from health plans since 1997. These data include diagnoses and other information that can be used to identify chronic medical problems that contribute to higher costs, so that health plans can be paid more when they care for sicker patients. In this article, the authors describe the risk-adjustment model HCFA is implementing in the year 2000, known as the Principal Inpatient Diagnostic Cost Group (PIPDCG) model

Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation

Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13skc4 mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13skc4 mice

Constitutive Expression of Thermobifida fusca Thermostable Acetylxylan Esterase Gene in Pichia pastoris

A gene encoding the thermostable acetylxylan esterase (AXE) in Thermobifida fusca NTU22 was amplified by PCR, sequenced and cloned into the Pichia pastoris X-33 host strain using the vector pGAPZαA, allowing constitutive expression and secretion of the protein. Recombinant expression resulted in high levels of extracellular AXE production, as high as 526 U/mL in the Hinton flask culture broth. The purified enzyme showed a single band at about 28 kDa by SDS-polyacrylamide gel electrophoresis after being treated with endo-β-N-acetylglycosaminidase H; this agrees with the predicted size based on the nucleotide sequence. About 70% of the original activity remained after heat treatment at 60 °C for three hours. The optimal pH and temperature of the purified enzyme were 8.0 and 60 °C, respectively. The properties of the purified AXE from the P. pastoris transformant are similar to those of the AXE from an E. coli transformant

Fifteen-Year Population Attributable Fractions and Causal Pies of Risk Factors for Newly Developed Hepatocellular Carcinomas in 11,801 Men in Taiwan

Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ∼15% (or ∼5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions

Sequence Variants of ADIPOQ

Diabetes is a serious global health problem. Large-scale genome-wide association studies identified loci for type 2 diabetes mellitus (T2DM), including adiponectin (ADIPOQ) gene and transcription factor 7-like 2 (TCF7L2), but few studies clarified the effect of genetic polymorphisms of ADIPOQ and TCF7L2 on risk of T2DM. We attempted to elucidate association between T2DM and polymorphic variations of both in Taiwan’s Chinese Han population, with our retrospective case-control study genotyping single nucleotide polymorphisms (SNPs) in ADIPOQ and TCF7L2 genes both in 149 T2DM patients and in 139 healthy controls from Taiwan. Statistical analysis gauged association of these polymorphisms with risk of T2DM to show ADIPOQ rs1501299 polymorphism variations strongly correlated with T2DM risk (P=0.042), with rs2241766 polymorphism being not associated with T2DM (P=0.967). However, both polymorphisms rs7903146 and rs12255372 of TCF7L2 were rarely detected in Taiwanese people. This study avers that ADIPOQ rs1501299 polymorphism contributes to risk of T2DM in the Taiwanese population