CGBayesNets: Conditional Gaussian Bayesian Network Learning and Inference with Mixed Discrete and Continuous Data

Bayesian Networks (BN) have been a popular predictive modeling formalism in bioinformatics, but their application in modern genomics has been slowed by an inability to cleanly handle domains with mixed discrete and continuous variables. Existing free BN software packages either discretize continuous variables, which can lead to information loss, or do not include inference routines, which makes prediction with the BN impossible. We present CGBayesNets, a BN package focused around prediction of a clinical phenotype from mixed discrete and continuous variables, which fills these gaps. CGBayesNets implements Bayesian likelihood and inference algorithms for the conditional Gaussian Bayesian network (CGBNs) formalism, one appropriate for predicting an outcome of interest from, e.g., multimodal genomic data. We provide four different network learning algorithms, each making a different tradeoff between computational cost and network likelihood. CGBayesNets provides a full suite of functions for model exploration and verification, including cross validation, bootstrapping, and AUC manipulation. We highlight several results obtained previously with CGBayesNets, including predictive models of wood properties from tree genomics, leukemia subtype classification from mixed genomic data, and robust prediction of intensive care unit mortality outcomes from metabolomic profiles. We also provide detailed example analysis on public metabolomic and gene expression datasets. CGBayesNets is implemented in MATLAB and available as MATLAB source code, under an Open Source license and anonymous download at http://www.cgbayesnets.com

Lutein Protects against Methotrexate-Induced and Reactive Oxygen Species-Mediated Apoptotic Cell Injury of IEC-6 Cells

Purpose High-dose chemotherapy using methotrexate (MTX) frequently induces side effects such as mucositis that leads to intestinal damage and diarrhea. Several natural compounds have been demonstrated of their effectiveness in protecting intestinal epithelial cells from these adverse effects. In this paper, we investigated the protection mechanism of lutein against MTX-induced damage in IEC-6 cells originating from the rat jejunum crypt. Methods: The cell viability, induced-apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential in IEC-6 cells under MTX treatment were examined in the presence or absence of lutein. Expression level of Bcl2, Bad and ROS scavenging enzymes (including SOD, catalase and Prdx1) were detected by quantitative RT-PCR. Results: The cell viability of IEC-6 cells exposed to MTX was decreased in a dose- and time-dependent manner. MTX induces mitochondrial membrane potential loss, ROS generation and caspase 3 activation in IEC-6 cells. The cytotoxicity of MTX was reduced in IEC-6 cells by the 24 h pre-treatment of lutein. We found that pre-treatment of lutein significantly reduces MTX-induced ROS and apoptosis. The expression of SOD was up-regulated by the pre-treatment of lutein in the MTX-treated IEC-6 cells. These results indicated that lutein can protect IEC-6 cells from the chemo-drugs induced damage through increasing ROS scavenging ability. Conclusion: The MTX-induced apoptosis of IEC-6 cells was shown to be repressed by the pre-treatment of lutein, which may represent a promising adjunct to conventional chemotherapy for preventing intestinal damages

Inhibitory Effects of Resveratrol on PDGF-BB-Induced Retinal Pigment Epithelial Cell Migration via PDGFRβ, PI3K/Akt and MAPK Pathways

Purpose: In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue. Methods: The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay. Results: Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor β (PDGFRβ) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFRα and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration. Conclusions: These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRβ, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin

Reliability of flexible low temperature poly-silicon thin film transistor

This work reports the effect of mechanical stress-induced degradation in flexible low-temperature polycrystalline-silicon thin-film transistors. After 100,000 iterations of channel-width-direction mechanical compression at R=2mm, a significant shift of extracted threshold voltage and an abnormal hump at the subthreshold region were found. Simulation reveals that both the strongest mechanical stress and electrical field takes place at both sides of the channel edge, between the polycrystalline silicon and gate insulator. The gate insulator suffered from a serious mechanical stress and result in a defect generation in the gate insulator. The degradation of the threshold voltage shift and the abnormal hump can be ascribed to the electron trapping in these defects. In addition, this work introduced three methods to reduce the degradation cause by the mechanical stress, including the quality improvement of the gate insulator, organic trench structure and active layer with a wing structure. Please click Additional Files below to see the full abstract

Strong and broadly tunable plasmon resonances in thick films of aligned carbon nanotubes

Low-dimensional plasmonic materials can function as high quality terahertz and infrared antennas at deep subwavelength scales. Despite these antennas' strong coupling to electromagnetic fields, there is a pressing need to further strengthen their absorption. We address this problem by fabricating thick films of aligned, uniformly sized carbon nanotubes and showing that their plasmon resonances are strong, narrow, and broadly tunable. With thicknesses ranging from 25 to 250 nm, our films exhibit peak attenuation reaching 70%, quality factors reaching 9, and electrostatically tunable peak frequencies by a factor of 2.3x. Excellent nanotube alignment leads to the attenuation being 99% linearly polarized along the nanotube axis. Increasing the film thickness blueshifts the plasmon resonators down to peak wavelengths as low as 1.4 micrometers, promoting them to a new near-infrared regime in which they can both overlap the S11 nanotube exciton energy and access the technologically important infrared telecom band.Comment: 19 pages, 5 figures, main text followed by supporting informatio

Intramuscular electroporation with the pro-opiomelanocortin gene in rat adjuvant arthritis

Endogenous opioid peptides have an essential role in the intrinsic modulation and control of inflammatory pain, which could be therapeutically useful. In this study, we established a muscular electroporation method for the gene transfer of pro-opiomelanocortin (POMC) in vivo and investigated its effect on inflammatory pain in a rat model of rheumatoid arthritis. The gene encoding human POMC was inserted into a modified pCMV plasmid, and 0–200 μg of the plasmid-POMC DNA construct was transferred into the tibialis anterior muscle of rats treated with complete Freund's adjuvant (CFA) with or without POMC gene transfer by the electroporation method. The safety and efficiency of the gene transfer was assessed with the following parameters: thermal hyperalgesia, serum adrenocorticotropic hormone (ACTH) and endorphin levels, paw swelling and muscle endorphin levels at 1, 2 and 3 weeks after electroporation. Serum ACTH and endorphin levels of the group into which the gene encoding POMC had been transferred were increased to about 13–14-fold those of the normal control. These levels peaked 1 week after electroporation and significantly decreased 2 weeks after electroporation. Rats that had received the gene encoding POMC had less thermal hypersensitivity and paw swelling than the non-gene-transferred group at days 3, 5 and 7 after injection with CFA. Our promising results showed that transfer of the gene encoding POMC by electroporation is a new and effective method for its expression in vivo, and the analgesic effects of POMC cDNA with electroporation in a rat model of rheumatoid arthritis are reversed by naloxone

The Estimation of First-Phase Insulin Secretion by Using Components of the Metabolic Syndrome in a Chinese Population

Aims. There are two phases of insulin secretion, the first (FPIS) and second phase (SPIS). In this study, we built equations to predict FPIS with metabolic syndrome (MetS) components and fasting plasma insulin (FPI). Methods. Totally, 186 participants were enrolled. 75% of participants were randomly selected as the study group to build equations. The remaining 25% of participants were selected as the external validation group. All participants received a frequently sampled intravenous glucose tolerance test, and acute insulin response after the glucose load (AIRg) was obtained. The AIRg was considered as FPIS. Results. When MetS components were only used, the following equation was built: log (FPIS) = 1.477 − 0.119 × fasting plasma glucose (FPG) + 0.079 × body mass index (BMI) − 0.523 × high-density lipoprotein cholesterol (HDL-C). After FPI was added, the second equation was formulated: log (FPIS) = 1.532 − 0.127 × FPG + 0.059 × BMI - 0.511 × HDL-C + 0.375 × log (FPI), which provided a better accuracy than the first one. Conclusions. Using MetS components, the FPIS could be estimated accurately. After adding FPI into the equation, the predictive power increased further. We hope that these equations could be widely used in daily practice