Flux-ratio anomalies from discs and other baryonic structures in the Illustris simulation

The flux ratios in the multiple images of gravitationally lensed quasars can provide evidence for dark matter substructure in the halo of the lensing galaxy if the flux ratios differ from those predicted by a smooth model of the lensing galaxy mass distribution. However, it is also possible that baryonic structures in the lensing galaxy, such as edge-on discs, can produce flux-ratio anomalies. In this work, we present the first statistical analysis of flux-ratio anomalies due to baryons from a numerical simulation perspective. We select galaxies with various morphological types in the Illustris simulation and ray-trace through the simulated halos, which include baryons in the main lensing galaxies but exclude any substructures, in order to explore the pure baryonic effects. Our ray-tracing results show that the baryonic components can be a major contribution to the flux-ratio anomalies in lensed quasars and that edge-on disc lenses induce the strongest anomalies. We find that the baryonic components increase the probability of finding high flux-ratio anomalies in the early-type lenses by about 8% and by about 10 - 20% in the disc lenses. The baryonic effects also induce astrometric anomalies in 13% of the mock lenses. Our results indicate that the morphology of the lens galaxy becomes important in the analysis of flux-ratio anomalies when considering the effect of baryons, and that the presence of baryons may also partially explain the discrepancy between the observed (high) anomaly frequency and what is expected due to the presence of subhalos as predicted by the CDM simulations.Comment: 16 pages, 11 figures, accepted by MNRA

SHARP -- VII. New constraints on the dark matter free-streaming properties and substructure abundance from gravitationally lensed quasars

We present an analysis of seven strongly gravitationally lensed quasars and the corresponding constraints on the properties of dark matter. Our results are derived by modelling the lensed image positions and flux-ratios using a combination of smooth macro models and a population of low-mass haloes within the mass range 10^6 to 10^9 Msun. Our lens models explicitly include higher-order complexity in the form of stellar discs and luminous satellites, as well as low-mass haloes located along the observed lines of sight for the first time. Assuming a Cold Dark Matter (CDM) cosmology, we infer an average total mass fraction in substructure of f_sub = 0.012^{+0.007}_{-0.004} (68 per cent confidence limits), which is in agreement with the predictions from CDM hydrodynamical simulations to within 1 sigma. This result is closer to the predictions than those from previous studies that did not include line-of-sight haloes. Under the assumption of a thermal relic dark matter model, we derive a lower limit on the particle relic mass of m th > 5.58 keV (95 per cent confidence limits), which is consistent with a value of m_th > 5.3 keV from the recent analysis of the Ly-alpha forest. We also identify two main sources of possible systematic errors and conclude that deeper investigations in the complex structure of lens galaxies as well as the size of the background sources should be a priority for this field.Comment: 14 pages, 7 figures, accepted for publication in MNRA

Bioprocess intelligent for the improvements and prediction on fed-batch cell culture in bioreactor

With advances in biotechnology, the antibody productivity is not the only issue in biopharmaceutical manufacturing; moreover, how to control the quality and quantity of antibody production in bioprocess has become prominent. In typical fed-batch cell culture, it is not easy to control the dynamic cultivation and feeding conditions. The study is to present an intelligent bioprocess make use of design of experiments (DOE) and multivariate data analysis (MVDA). In the culture medium optimization, we performed the medium screening with the DOE method in shake spin tubes and shake flasks. DOE provides a cost-effective methodology for medium development and optimization, and furthermore we utilized multivariate data analysis methodology to build up the fed-batch intelligence bioprocess in 5 L bioreactor. We analyzed mass data transferred from 5 L bioreactor process and established the fed-batch culture model with SIMCA software. Combination of the batch process and big data sets, we can be easy to do batch-to-batch comparison, cell culture profile prediction, and key parameter finding to improve the process performance with more steady product quality and less error. In this fed-batch culture model, we achieved more than 5 g/L cell productivity consistently and predictably in 5 L bioreactor cultivation with CRISPR-mediated targeted gene site-specific integration CHO cell line

Enhancing crispr-mediated CHO cell antibody productivity through concentrated fed- batch or continuous perfusion

Integrated continuous bioprocessing technology has high productivity and cost saving benefit, which combines the upstream (Cell culture) and downstream (Purification) processing. The continuous bioprocessing based biopharmaceutical manufacturing is more profitable than traditional batch/fed-batch processing in increasing quality and quantity. The goal of this study focuses on the upstream continuous process development with crispr-mediated targeted gene integration CHO cell line producing monoclonal antibody. In the upstream processing, we developed concentrated fed-batch culture (CFB) and high density perfusion culture in 2-5 L bioreactor with a cell retention device (alternating tangential flow, ATF). With our concentrated fed-batch culture system, the VCD achieved 8.4x107 cells/m in 11days operation with 1VVD producing antibody 3.3-fold that of fed-batch culture system; in the high density perfusion culture system, the VCD achieved 5x107 cells/ml in 28 days operation with 1 VVD producing antibody greater than 1g/L/day with on the Day10 and keep the cell density, viability and productivity more than 1 month

Pilot Scheme of Health Policy in Stroke Adjuvant Acupuncture Therapy for Acute and Subacute Ischemic Stroke in Taiwan

To reduce the health care burden of strokes, the Taiwan Department of Health launched the Pilot Scheme of the Health Policy in Stroke Adjuvant Acupuncture Therapy (HPSAAT) in 2006. This cross-sectional, hospital-based, match-controlled study at Chang Gung Memorial Hospital-Kaohsiung Medical Center during 2006∼2008 retrospectively evaluated the clinical characteristics of acute and subacute ischemic stroke patients who electively joined the HPSAAT. The study also evaluated the safety and clinical benefits of adjuvant acupuncture in treating acute and subacute ischemic stroke patients. Twenty-six HPSAAT participants and 52 age-sex matched random controls were enrolled. The stroke baseline of the HPSAAT participants was more severe than the non-HPSAAT controls. Although the stroke severity closely correlates to mortality and comorbidity, this study noted no significant complications in the HPSAAT participants during the acupuncture treatment course. Adjuvant acupuncture was considered safe at the acute and subacute stages of ischemic stroke. Due to uneven baseline severity, the clinical benefits in reducing neurological deficits and functional recovery were not concluded in this study

RNA Editing and Drug Discovery for Cancer Therapy

RNA editing is vital to provide the RNA and protein complexity to regulate the gene expression. Correct RNA editing maintains the cell function and organism development. Imbalance of the RNA editing machinery may lead to diseases and cancers. Recently, RNA editing has been recognized as a target for drug discovery although few studies targeting RNA editing for disease and cancer therapy were reported in the field of natural products. Therefore, RNA editing may be a potential target for therapeutic natural products. In this review, we provide a literature overview of the biological functions of RNA editing on gene expression, diseases, cancers, and drugs. The bioinformatics resources of RNA editing were also summarized

Comparison and Identification of Estrogen-Receptor Related Gene Expression Profiles in Breast Cancer of Different Ethnic Origins

The interactions between genetic variants in estrogen receptor (ER) have been identified to be associated with an increased risk of breast cancer. Available evidence indicates that genetic variance within a population plays a crucial role in the occurrence of breast cancer. Thus, the comparison and identification of ER-related gene expression profiles in breast cancer of different ethnic origins could be useful for the development of genetic variant cancer therapy. In this study, we performed microarray experiment to measure the gene expression profiles of 59 Taiwanese breast cancer patients; and through comparative bioinformatics analysis against published U.K. datasets, we revealed estrogen-receptor (ER) related gene expression between Taiwanese and British patients. In addition, SNP databases and statistical analysis were used to elucidate the SNPs associated with ER status. Our microarray results indicate that the expression pattern of the 65 genes in ER+ patients was dissimilar from that of the ER- patients. Seventeen mutually exclusive genes in ER-related breast cancer of the two populations with more than one statistically significant SNP in genotype and allele frequency were identified. These 17 genes and their related SNPs may be important in population-specific ER regulation of breast cancer. This study provides a global and feasible approach to study population-unique SNPs in breast cancer of different ethnic origins

Recombinant lipidated dengue-4 envelope protein domain III elicits protective immunity

AbstractThe combination of recombinant protein antigens with an immunostimulator has the potential to greatly increase the immunogenicity of recombinant protein antigens. In the present study, we selected the dengue-4 envelope protein domain III as a dengue vaccine candidate and expressed the protein in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-4 envelope protein domain III folded into the proper conformation and competed with the dengue-4 virus for cellular binding sites. Mice immunized with lipidated dengue-4 envelope protein domain III without exogenous adjuvant had higher frequencies of dengue-4 envelope protein domain III-specific B cells secreting antibodies than mice immunized with the nonlipidated form. Importantly, lipidated dengue-4 envelope protein domain III-immunized mice demonstrated a durable neutralizing antibody response and had reduced viremia levels after challenge. The study demonstrates that lipidated dengue-4 envelope protein domain III is immunogenic and may be a potential dengue vaccine candidate. Furthermore, the lipidation strategy can be applied to other serotypes of dengue virus

High-yield antibody production using targeted integration and engineering CHO host

To identify the high expression sites in the CHO cells, we employed NGS to analyze the integration sites of a high producing cell line (titer \u3e 3g/L). The pair-end reads with one read mapped to the vector and the other read mapped to the CHO reference genome are extracted to identify the integration sites. To test the expression activity of the integration sites, we employed CRISPR/Cas9 to specifically integrate the antibody gene into CHO genome for expression. Our data showed 4 integration sites are in the high producing cell line. Among the 4 integration site, one integration site was tested by CRISPR/Cas9 for target integration of antibody gene for expression. The target integrated cell pool present higher expression level (130 mg/L/copy) and less copy number when compared other integration sites. Through single-copy integration method, we can also achieve 60-150 mg/L/copy in a batch culture. About 80% of the single-copy cell clones were stable at generation 60. We have also applied the CHO-specific microarray transcriptomics technology to identify genes that contribute to high productivity. Transfection of our proprietary dual promoter vector J 1.0 resulting in 1.65 to 2.4 fold increase in the expression in engineered CHO DXB11 host. Through fed-batch process development, 3 – 5 g/L mAb productivity can be achieved through targeted integration and engineered CHO host