REMAS: a new regression model to identify alternative splicing events from exon array data

<p>Abstract</p> <p>Background</p> <p>Alternative splicing (AS) is an important regulatory mechanism for gene expression and protein diversity in eukaryotes. Previous studies have demonstrated that it can be causative for, or specific to splicing-related diseases. Understanding the regulation of AS will be helpful for diagnostic efforts and drug discoveries on those splicing-related diseases. As a novel exon-centric microarray platform, exon array enables a comprehensive analysis of AS by investigating the expression of known and predicted exons. Identifying of AS events from exon array has raised much attention, however, new and powerful algorithms for exon array data analysis are still absent till now.</p> <p>Results</p> <p>Here, we considered identifying of AS events in the framework of variable selection and developed a regression method for AS detection (REMAS). Firstly, features of alternatively spliced exons were scaled by reasonably defined variables. Secondly, we designed a hierarchical model which can represent gene structure and transcriptional influence to exons, and the lasso type penalties were introduced in calculation because of huge variable size. Thirdly, an iterative two-step algorithm was developed to select alternatively spliced genes and exons. To avoid negative effects introduced by small sample size, we ranked genes as parameters indicating their AS capabilities in an iterative manner. After that, both simulation and real data evaluation showed that REMAS could efficiently identify potential AS events, some of which had been validated by RT-PCR or supported by literature evidence.</p> <p>Conclusion</p> <p>As a new lasso regression algorithm based on hierarchical model, REMAS has been demonstrated as a reliable and effective method to identify AS events from exon array data.</p

A Recalibrated Molecular Clock and Independent Origins for the Cholera Pandemic Clones

Cholera, caused by Vibrio cholerae, erupted globally from South Asia in 7 pandemics, but there were also local outbreaks between the 6th (1899–1923) and 7th (1961–present) pandemics. All the above are serotype O1, whereas environmental or invertebrate isolates are antigenically diverse. The pre 7th pandemic isolates mentioned above, and other minor pathogenic clones, are related to the 7th pandemic clone, while the 6th pandemic clone is in the same lineage but more distantly related, and non-pathogenic isolates show no clonal structure. To understand the origins and relationships of the pandemic clones, we sequenced the genomes of a 1937 prepandemic strain and a 6th pandemic isolate, and compared them with the published 7th pandemic genome. We distinguished mutational and recombinational events, and allocated these and other events, to specific branches in the evolutionary tree. There were more mutational than recombinational events, but more genes, and 44 times more base pairs, changed by recombination. We used the mutational single-nucleotide polymorphisms and known isolation dates of the prepandemic and 7th pandemic isolates to estimate the mutation rate, and found it to be 100 fold higher than usually assumed. We then used this to estimate the divergence date of the 6th and 7th pandemic clones to be about 1880. While there is a large margin of error, this is far more realistic than the 10,000–50,000 years ago estimated using the usual assumptions. We conclude that the 2 pandemic clones gained pandemic potential independently, and overall there were 29 insertions or deletions of one or more genes. There were also substantial changes in the major integron, attributed to gain of individual cassettes including copying from within, or loss of blocks of cassettes. The approaches used open up new avenues for analysing the origin and history of other important pathogens

Study on the Heat of Hydration and Strength Development of Cast-In-Situ Foamed Concrete

This study aims to investigate the relationship between the heat of hydration and the strength development of cast-in-situ foamed concrete. First, indoor model tests are conducted to determine the effects of the casting density and the fly ash content on the hydration heat of foamed concrete in semiadiabatic conditions. Second, compression tests are carried out to evaluate the development of the compressive strength with the curing time under standard curing conditions and temperature matched curing conditions. Third, the hydration heat development of the foamed concrete is tested in four projects. The results showed that the peak temperature, the maximum temperature change rate, and the maximum temperature difference increased with the increase in the casting density at different positions in the foamed concrete. For the same casting density of the foamed concrete, the peak temperature, the maximum temperature change rate, and the maximum temperature difference decreased with the increase in the fly ash content. For the foamed concrete without the admixture, the early strength was significantly higher under temperature matched curing conditions than under standard curing conditions, but the temperature matched curing conditions had a clear inhibitory effect on the strength of the foamed concrete. The strengths during the early stage and the later stage were both improved under temperature matched curing conditions after adding the fly ash, and the greater the fly ash content, the larger the effect. The maximum temperature increments were higher in the indoor model test than in the field tests for the same casting density. Reasonable cooling measures and the addition of fly ash decreased the maximum temperature increments and increased the corresponding casting times

REMAS: a new regression model to identify alternative splicing events from exon array data

Abstract Background Alternative splicing (AS) is an important regulatory mechanism for gene expression and protein diversity in eukaryotes. Previous studies have demonstrated that it can be causative for, or specific to splicing-related diseases. Understanding the regulation of AS will be helpful for diagnostic efforts and drug discoveries on those splicing-related diseases. As a novel exon-centric microarray platform, exon array enables a comprehensive analysis of AS by investigating the expression of known and predicted exons. Identifying of AS events from exon array has raised much attention, however, new and powerful algorithms for exon array data analysis are still absent till now. Results Here, we considered identifying of AS events in the framework of variable selection and developed a regression method for AS detection (REMAS). Firstly, features of alternatively spliced exons were scaled by reasonably defined variables. Secondly, we designed a hierarchical model which can represent gene structure and transcriptional influence to exons, and the lasso type penalties were introduced in calculation because of huge variable size. Thirdly, an iterative two-step algorithm was developed to select alternatively spliced genes and exons. To avoid negative effects introduced by small sample size, we ranked genes as parameters indicating their AS capabilities in an iterative manner. After that, both simulation and real data evaluation showed that REMAS could efficiently identify potential AS events, some of which had been validated by RT-PCR or supported by literature evidence. Conclusion As a new lasso regression algorithm based on hierarchical model, REMAS has been demonstrated as a reliable and effective method to identify AS events from exon array data.http://deepblue.lib.umich.edu/bitstream/2027.42/112933/1/12859_2009_Article_3201.pd

Analysis of Behaviors of the Railway Subgrade with a New Waterproof Seal Layer

This study proposes a new waterproof sealing layer to reduce the impact of water on subgrade beds. The proposed waterproof sealing layer is composed of a polyurethane adhesive (PA) mixture, which aims to control interlaminar deformation and prevent seepage. A variety of laboratory tests were first performed to analyze the attenuation characteristics and mechanical properties of various polyurethane polymer (PP)-improved gravel mixtures under thermohydraulic coupling effects. In addition, a waterproof performance model test of the PP-improved gravel layer was conducted to investigate its waterproof and drainage performance and hydraulic damage mechanism. Finally, the feasibility and effectiveness of the surface structure of the waterproof drainage subgrade bed containing the PA mixture was tested in combination with the treatment project of the Ciyaowan station of the Baoshen heavy-haul railway. According to the experimental and model results, (1) the waterproof layer containing the polyurethane mixture exhibited satisfactory stiffness, elasticity and flexibility. The waterproof layer containing the polyurethane mixture also controlled the deformation between layers, and its mechanical properties remained stable. (2) The waterproof layer with the dense polyurethane mixture performed well in terms of the waterproof aspect, and no infiltration occurred under cyclic load (3). Long-term field monitoring revealed that the effect of the implementation of a PP-improved gravel layer to treat mud pumping was remarkable. The settlement of the PP-improved gravel layer only reached 13.21 mm, and the settlement remained stable in the later stage

In Situ Experimental Study of Natural Diatomaceous Earth Slopes under Alternating Dry and Wet Conditions

Very few studies have focused on diatomaceous earth slopes along high-speed railways, and the special properties of diatomaceous earth under alternating dry and wet conditions are unknown. This paper studies diatomaceous earth in the Shengzhou area, through which the newly built Hangzhou–Taizhou high-speed railway passes, and the basic physical and hydraulic properties of diatomaceous earth are analyzed by indoor test methods. A convenient, efficient, and controllable high-speed railway slope artificial rainfall simulation system is designed, and in situ comprehensive monitoring and fissure observation are performed on site to analyze the changes in various diatomaceous soil slope parameters under rainfall infiltration, and to explore the cracking mechanisms of diatomaceous earth under alternating dry and wet conditions. The results indicate extremely poor hydrophysical properties of diatomaceous earth in the Shengzhou area; the disintegration resistance index values of natural diatomaceous earth samples subjected to dry and wet cycles are 1.8–5.6%, and the disintegration is strong. Comprehensive indoor tests and water content monitoring show that natural diatomaceous earth has no obvious influence when it contacts water, but it disintegrates and cracks under alternating dry and wet conditions. The horizontal displacement of both slope types mainly occurs within 0.75–2.75 m of the surface layer, indicating shallow surface sliding; after testing, natural slope crack widths of diatomaceous earth reach 10–25 mm, and their depths reach 40–60 cm. To guarantee safety during high-speed railway engineering construction, implementing proper protection for diatomaceous earth slopes is recommended

Ignition and combustion behavior of single micron-sized iron particle in hot gas flow

This work investigated the ignition and combustion process of single micron-sized iron particles in the hot gas flow of burned methane-oxygen-nitrogen mixture. The particle emission intensity was recorded by a high-speed camera in different flame conditions. Particle temperature was derived through two-color pyrometry method employing an ICCD camera equipped with a stereoscope. Based on scanning electron microscopy (SEM) image, the microstructure change of iron particles was investigated. Results showed that the temperature of burning particle rose rapidly and was much higher than the ambient temperature. The fresh iron particles mainly went through several stages in hot gas flow: heating, melting, rapid combustion and cooling. Some of them became bright again after cooling. According to the above combustion process, combustion parameters including ignition delay time, accelerated burning time, total burning time and second stage of combustion time were defined. All the above defined parameters were almost linearly increasing with the increase of particle size under the same oxygen concentration. For iron particles with roughly the same size, the ignition delay time, accelerated burning time and total burning time decreased as the effective oxygen concentration increased especially for particle size larger than 40 µm. The second stage of combustion time for particles with similar size were almost the same under different oxygen concentrations. After combustion, most of the particles change from irregular shape to spherical or ellipsoidal shape, and some of them showed hollow shell structure. A phenomenon of nano-sized particles releasing during the iron particles combustion had been identified. The frequently observed luminous tail was attributed to coming from the thermal radiation of the formed nanoparticles, which was supported by the SEM sampling analysis of the combustion products