Advance chromatin extraction enhances performance and productivity of cation exchange chromatography-based capture of Immunoglobulin G monoclonal antibodies

AbstractThe impact of host cell-derived chromatin was investigated on the performance and productivity of cation exchange chromatography as a method for capture-purification of an IgG monoclonal antibody. Cell culture supernatant was prepared for loading by titration to pH 6.0, dilution with water to a conductivity of 4mS/cm, then microfiltration to remove solids. DNA content was reduced 99% to 30ppm, histone host cell protein content by 76% to 6300ppm, non-histone host cell protein content by 15% to 321,000ppm, and aggregates from 33% to 15%. IgG recovery was 83%. An alternative preparation was performed, adding octanoic acid, allantoin, and electropositive particles to the harvest at pH 5.3, then removing solids. DNA content was reduced to<1 ppb, histones became undetectable, non-histones were reduced to 24,000ppm, and aggregates were reduced to 2.4%. IgG recovery was 95%. This treatment increased dynamic capacity (DBC) of cation exchange capture to 173g/L and enabled the column to reduce non-histone host proteins to 671ppm. Step recovery was 99%. A single multimodal polishing step further reduced them to 15ppm and aggregates to <0.1%. Overall process recovery was 89%. Productivity at feed stream IgG concentrations of 5–10g/L was roughly double the productivity of a same-size protein A column with a DBC of 55g/L

Intensification of inclusion body processing via surface refolding with chemical extraction

Ph.DDOCTOR OF PHILOSOPH

Can onshore spot market progress influence offshore N.D.F. market development for the C.N.Y?

This study utilises a time-varying wavelet analysis to examine the relationship between the onshore spot market and the offshore non-deliverable forward (N.D.F.) market of the Chinese Yuan (C.N.Y.). Given the presence of structural changes in the two markets, we did not find any stable causality during the sample period. However, in some sub-samples, we found that there is a strong nonlinear causal relationship running from the onshore spot market to the offshore N.D.F. market. Ties between the two markets are closer after the widening of the onshore trading band, first in April 2012, second in March 2014 and again in August 2015. The onshore spot market is heavily influenced by interventions by the People’s Bank of China (P.B.C.). These findings imply that offshore N.D.F. market development is not divorced from onshore development, as developments in the onshore spot market influence the offshore N.D.F. market. The results show that the exchange rate markets for the C.N.Y. are not efficient. Thus, to successfully internationalise the C.N.Y., financial expansion of the onshore spot market should keep pace with the growing offshore N.D.F. market to minimise destabilisation of the C.N.Y

A below-knee compression garment reduces fatigue-induced strength loss but not knee joint position sense errors

Purpose We examined the possibility that wearing a below-knee compression garment (CG) reduces fatigue-induced strength loss and joint position sense (JPS) errors in healthy adults. Methods Subjects (n = 24, age = 25.5 +/- 4 years) were allocated to either one of the treatment groups that performed 100 maximal isokinetic eccentric contractions at 30 degrees(-1)with the right-dominant knee extensors: (1) with (EXPCG) or (2) without CG (EXP) or to (3) a control group (CONCG:CG, no exercise). Changes in JPS errors, and maximal voluntary isometric contraction (MVIC) torque were measured immediately post-, 24 h post-, and 1 week post-intervention in each leg. All testing was done without the CG. Results CG afforded no protection against JPS errors. Mixed analysis of variance (ANOVA) revealed that absolute JPS errors increased post-intervention in EXPCG and EXP not only in the right-exercised (52%,p = 0.013; 57%,p = 0.007, respectively) but also in the left non-exercised (55%,p = 0.001; 58%,p = 0.040, respectively) leg. Subjects tended to underestimate the target position more in the flexed vs. extended knee positions (75-61 degrees: - 4.6 +/- 3.6 degrees, 60-50 degrees: - 4.2 +/- 4.3 degrees, 50-25 degrees: - 2.9 +/- 4.2 degrees), irrespective of group and time. Moreover, MVIC decreased in EXP but not in EXPCG and CONCG at immediately post-intervention (p = 0.026,d = 0.52) and 24 h post-intervention (p = 0.013,d = 0.45) compared to baseline. Conclusion Altogether, a below-knee CG reduced fatigue-induced strength loss at 80 degrees knee joint position but not JPS errors in healthy younger adults

LARSEN-ELM: Selective Ensemble of Extreme Learning Machines using LARS for Blended Data

Extreme learning machine (ELM) as a neural network algorithm has shown its good performance, such as fast speed, simple structure etc, but also, weak robustness is an unavoidable defect in original ELM for blended data. We present a new machine learning framework called LARSEN-ELM for overcoming this problem. In our paper, we would like to show two key steps in LARSEN-ELM. In the first step, preprocessing, we select the input variables highly related to the output using least angle regression (LARS). In the second step, training, we employ Genetic Algorithm (GA) based selective ensemble and original ELM. In the experiments, we apply a sum of two sines and four datasets from UCI repository to verify the robustness of our approach. The experimental results show that compared with original ELM and other methods such as OP-ELM, GASEN-ELM and LSBoost, LARSEN-ELM significantly improve robustness performance while keeping a relatively high speed.Comment: Accepted for publication in Neurocomputing, 01/19/201

3-Phenyl-2-(prop-2-yn­yloxy)-1-benzofuro[3,2-d]pyrimidin-4(3H)-one

In the title compound, C19H12N2O3, the 1-benzofuro[3,2-d]pyrimidinone unit is approximately planar, the maximum deviation from the mean plane being 0.045 (1) Å. The attached phenyl ring makes a dihedral angle of 86.73 (6)° with the fused ring system. The packing of the mol­ecules in the crystal structure is mainly governed by C—H⋯π hydrogen-bonding inter­actions

AUV SLAM and experiments using a mechanical scanning forward-looking sonar

Navigation technology is one of the most important challenges in the applications of autonomous underwater vehicles (AUVs) which navigate in the complex undersea environment. The ability of localizing a robot and accurately mapping its surroundings simultaneously, namely the simultaneous localization and mapping (SLAM) problem, is a key prerequisite of truly autonomous robots. In this paper, a modified-FastSLAM algorithm is proposed and used in the navigation for our C-Ranger research platform, an open-frame AUV. A mechanical scanning imaging sonar is chosen as the active sensor for the AUV. The modified-FastSLAM implements the update relying on the on-board sensors of C-Ranger. On the other hand, the algorithm employs the data association which combines the single particle maximum likelihood method with modified negative evidence method, and uses the rank-based resampling to overcome the particle depletion problem. In order to verify the feasibility of the proposed methods, both simulation experiments and sea trials for C-Ranger are conducted. The experimental results show the modified-FastSLAM employed for the navigation of the C-Ranger AUV is much more effective and accurate compared with the traditional methods

The changes of CD4+CD25+/CD4+ proportion in spleen of tumor-bearing BALB/c mice

CD4+CD25+ regulatory T lymphocytes (T(R)) constitute 5–10% of peripheral CD4+ T cells in naive mice and humans, and play an important role in controlling immune responses. Accumulating evidences show that T(R )cells are involved in some physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer, and might be a promising therapeutic target for these diseases. To evaluate the change of CD4+CD25+ T(R )cells in mouse tumor models, CD4+CD25+ subset in peripheral blood and spleen lymphocytes from normal or C26 colon-carcinoma-bearing BABL/c mice were analyzed by flow cytometry using double staining with CD4 and CD25 antibodies. The proportion of CD4+CD25+/CD4+ in spleen lymphocytes was found to be higher than that in peripheral blood lymphocytes in normal mice. No difference was observed in the proportion in peripheral blood lymphocytes between tumor bearing mice and normal mice, while there was a significant increase in the proportion in spleen lymphocytes in tumor bearing mice as compared with normal mice. Moreover, the proportion increased in accordance with the increase in the tumor sizes. The increase in the proportion was due to the decrease in CD4+ in lymphocytes, which is resulted from decreased CD4+CD25- subset in lymphocytes. Our observation suggests the CD4+CD25+/CD4+ proportion in spleen lymphocytes might be a sensitive index to evaluate the T(R )in tumor mouse models, and our results provide some information on strategies of antitumor immunotherapy targeting CD4+CD25+ regulatory T lymphocytes