Reconsideration of In-Silico siRNA Design Based on Feature Selection: A Cross-Platform Data Integration Perspective

RNA interference via exogenous short interference RNAs (siRNA) is increasingly more widely employed as a tool in gene function studies, drug target discovery and disease treatment. Currently there is a strong need for rational siRNA design to achieve more reliable and specific gene silencing; and to keep up with the increasing needs for a wider range of applications. While progress has been made in the ability to design siRNAs with specific targets, we are clearly at an infancy stage towards achieving rational design of siRNAs with high efficacy. Among the many obstacles to overcome, lack of general understanding of what sequence features of siRNAs may affect their silencing efficacy and of large-scale homogeneous data needed to carry out such association analyses represents two challenges. To address these issues, we investigated a feature-selection based in-silico siRNA design from a novel cross-platform data integration perspective. An integration analysis of 4,482 siRNAs from ten meta-datasets was conducted for ranking siRNA features, according to their possible importance to the silencing efficacy of siRNAs across heterogeneous data sources. Our ranking analysis revealed for the first time the most relevant features based on cross-platform experiments, which compares favorably with the traditional in-silico siRNA feature screening based on the small samples of individual platform data. We believe that our feature ranking analysis can offer more creditable suggestions to help improving the design of siRNA with specific silencing targets. Data and scripts are available at http://csbl.bmb.uga.edu/publications/materials/qiliu/siRNA.html

Effect of vitamin E (Tri E®) on antioxidant enzymes and DNA damage in rats following eight weeks exercise

<p>Abstract</p> <p>Background</p> <p>Exercise is beneficial to health, but during exercise the body generates reactive oxygen species (ROS) which are known to result in oxidative stress. The present study analysed the effects of vitamin E (Tri E^®) on antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (Cat) activity and DNA damage in rats undergoing eight weeks exercise.</p> <p>Methods</p> <p>Twenty four <it>Sprague-Dawley </it>rats (weighing 320-370 gm) were divided into four groups; a control group of sedentary rats which were given a normal diet, second group of sedentary rats with oral supplementation of 30 mg/kg/d of Tri E^®, third group comprised of exercised rats on a normal diet, and the fourth group of exercised rats with oral supplementation of 30 mg/kg/d of Tri E^®. The exercising rats were trained on a treadmill for 30 minutes per day for 8 weeks. Blood samples were taken before and after 8 weeks of the study to determine SOD, GPx, Cat activities and DNA damage.</p> <p>Results</p> <p>SOD activity decreased significantly in all the groups compared to baseline, however both exercised groups showed significant reduction in SOD activity as compared to the sedentary groups. Sedentary control groups showed significantly higher GPx and Cat activity compared to baseline and exercised groups. The supplemented groups, both exercised and non exercised groups, showed significant decrease in Cat activity as compared to their control groups with normal diet. DNA damage was significantly higher in exercising rats as compared to sedentary control. However in exercising groups, the DNA damage in supplemented group is significantly lower as compared to the non-supplemented group.</p> <p>Conclusions</p> <p>In conclusion, antioxidant enzymes activity were generally reduced in rats supplemented with Tri E^®probably due to its synergistic anti-oxidative defence, as evidenced by the decrease in DNA damage in Tri E^®supplemented exercise group.</p

Discrete Kinetic Models from Funneled Energy Landscape Simulations

A general method for facilitating the interpretation of computer simulations of protein folding with minimally frustrated energy landscapes is detailed and applied to a designed ankyrin repeat protein (4ANK). In the method, groups of residues are assigned to foldons and these foldons are used to map the conformational space of the protein onto a set of discrete macrobasins. The free energies of the individual macrobasins are then calculated, informing practical kinetic analysis. Two simple assumptions about the universality of the rate for downhill transitions between macrobasins and the natural local connectivity between macrobasins lead to a scheme for predicting overall folding and unfolding rates, generating chevron plots under varying thermodynamic conditions, and inferring dominant kinetic folding pathways. To illustrate the approach, free energies of macrobasins were calculated from biased simulations of a non-additive structure-based model using two structurally motivated foldon definitions at the full and half ankyrin repeat resolutions. The calculated chevrons have features consistent with those measured in stopped flow chemical denaturation experiments. The dominant inferred folding pathway has an “inside-out”, nucleation-propagation like character

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

A Hybrid Deep Learning Model to Predict Business Closure from Reviews and User Attributes Using Sentiment Aligned Topic Model

Business closure is a very good indicator for success or failure of a business. This will help investors and banks as to whether to invest or lend to a particular business for future growth and benefits. Traditional machine learning techniques require extensive manual feature engineering and still do not perform satisfactorily due to significant class imbalance problem and little difference in the attributes for open and closed businesses. We have used historical data besides taking care of the class imbalance problem. Transfer learning also has been used to tackle the issue of having small categorical datasets. A hybrid deep learning model has been proposed to predict whether a business would be shut down within a specific period of time. Sentiment Aligned Topic Model (SATM) is used to extract aspect-wise sentiment scores from user reviews. Our results show a marked improvement over traditional machine learning techniques. It also shows how the aspect-wise sentiment scores corresponding to each business, computed using SATM, help to give better results. © 2018 IEEE

Evaluation of coating performance using break point frequency

Break point frequency values were used to evaluate the degradation of alkyd and epoxy coatings on. rolled steel panels. Panels of size 6 " x 4 " were given the following coatings. 1. Alkyd primer(35 mu m) 2. Phosphating (10 mu m) + Alkyd primer (35 mu m) 3. Phosphating (10 mu m)+Alkyd primer (35 mu m) + Alkyd top coat (35 mu m) 4. Epoxy primer (50 mu m) 5. Phosphating (10 mu m) + Epoxy primer (50 mu m) 6. Phosphating (10 mu m) + Epoxy primer (50 mu m) + Epoxy top, coat (50 mu m). Corrosion of these panels was accelerated by exposing the coated panels to a neutral salt spray of 5% NaCl solution for long exposure times and impedance measurements were carried out at various intervals of time. The break point frequency values were found to increase with the time of exposure to the corrosive environment There was a correlation between the number of blisters; the average blister area and the break point frequency. Various coating systems were ranked on the basis of break point frequency values

Evaluation of coating performance using break point frequency

Break point frequency values were used to evaluate the degradation of alkyd and epoxy coatings on rolled steel panels. Panels of size 6'' x 4'' were given the following coatings. 1. Alkyd primer(35 mu m) 2. Phosphating (10 mu m) + Alkyd primer (35 mu m) 3. Phosphating (10 mu m) + Alkyd primer (35 mu m) + Alkyd top coat (35 mu m) 4. Epoxy primer (50 mu m) 5. Phosphating (10 mu m) + Epoxy primer (50 mu m) 6. Phosphating (10 mu m) + Epoxy primer (50 mu m) + Epoxy top, coat (50 mu m) Corrosion of these panels was accelerated by exposing the coated panels to a neutral salt spray of 5% NaCl solution for long exposure times and impedance measurements were carried out at various intervals of time. The break point frequency values were found to increase with the time of exposure to the corrosive environment. There was a correlation between the number of blisters, the average blister area and the break point frequency. Various coating systems were ranked on the basis of break point frequency values

Evaluation of blistering performance of pigmented and unpigmented alkyd coatings using electrochemical impedance spectroscopy

The influence of pigment on the blistering behaviour of alkyd coating system was investigated using electrochemical impedance spectroscopy, salt spray, visual observation and adhesion techniques. The results showed that the pigment initially enhanced the migration of the environment promoting more number of blisters than the unpigmented system. Over a long period of exposure, however, the unpigmented system was found to be more susceptible to permeation of the environment.© Elsevie