Homologous Gene Finding with a Hidden Markov Model

The homology search problem and the gene finding problem are two fundamental problems in bioinformatics. The homology search problem is to find the homologous regions of two biological sequences; the gene finding problem is to find all the genes in both strands of a genomic sequence. Recently, gene finding research has demonstrated that homology search results can be used to improve the accuracy of gene finding. By combining the two problems, we define a new problem called the homologous gene finding problem. The homologous gene finding problem is to find homologous genes of a query gene in a target genomic sequence. Consequently, we present a new homologous gene finding algorithm in this thesis. We borrow the idea of gene mapping and alignment algorithms, and apply existing seed-based homology search algorithms and hidden Markov model-based (HMM-based) gene finding algorithms to solve the homologous gene finding problem. After we find high-scoring segment pairs (HSPs) between the query gene and the target genomic sequence, we locate target regions that we believe contain a gene homologous to the query gene. Then, we extend existing HMM-based gene finding algorithms to find homologous gene candidates. To improve the accuracy of homologous gene finding, we train a HMM to be biased toward the query gene. We also introduce a new coding sequence (CDS) length penalty as a measure of how the CDS lengths of the query gene and its homologous gene vary to further improve the accuracy. We use the new CDS length penalty together with our enhanced Viterbi algorithm and our flexible finish condition to improve the speed of homologous gene fining without harming the accuracy. Finally, we use protein alignment to pick and rank the best homologous gene candidates. In this thesis, we also describe several experiments to evaluate and support our homologous gene finding algorithm

Towards a Confucian CSR: Reimagining Corporate Social Responsibility from a Chinese Philosophical Perspective

Although many companies have made efforts to adopt corporate social responsibility (CSR), the notion of CSR is confined by philosophical assumptions and concepts. How then might Chinese companies express their CSR set within a Chinese culture influenced by Confucian philosophy? This research aims to explore the possibility of a Confucian CSR model. Instead of replacing the current prevailing instrumental CSR, this Confucian CSR model intends to complement the weakness of the Western instrumental CSR model by implementing three conditions, namely, the exemplary CEO, a supportive environment, and an ethical education based on Confucian principles of benevolence (ren 仁) and righteousness (yi 義). The construction of Confucian CSR has three steps: Firstly, through an exploration of Confucian philosophy, this research clarifies the value system and ethical teaching of Confucian philosophy, which provides a theoretical foundation for the discussion of the Confucian corporation and its specific form of CSR. Secondly, by comparing the differences of current CSR reports between Chinese companies and US companies, this research examines the characteristics of Chinese CSR reports and performance and finds out to what extent they are impacted by Confucian philosophy. Finally, this research compares Confucian principles with the principles of Western instrumental CSR. Through the comparison, the people-centred and harmony-oriented Confucian CSR model is built in contrast to the profit-centred competitive CSR model. From a practical perspective, the outline of the implementation of Confucian CSR is provided at both the national level and corporate level. In addition, this research also provides recommendations for the corresponding CSR reporting. To conclude, based on the integration of Confucian wisdom with the worldwide development of CSR, this research may not only contribute to the CSR development in China but also can shed light on CSR development in the world

Finding Similar Protein Structures Efficiently and Effectively

To assess the similarities and the differences among protein structures, a variety of structure alignment algorithms and programs have been designed and implemented. We introduce a low-resolution approach and a high-resolution approach to evaluate the similarities among protein structures. Our results show that both the low-resolution approach and the high-resolution approach outperform state-of-the-art methods. For the low-resolution approach, we eliminate false positives through the comparison of both local similarity and remote similarity with little compromise in speed. Two kinds of contact libraries (ContactLib) are introduced to fingerprint protein structures effectively and efficiently. Each contact group from the contact library consists of one local or two remote fragments and is represented by a concise vector. These vectors are then indexed and used to calculate a new combined hit-rate score to identify similar protein structures effectively and efficiently. We tested our ContactLibs on the high-quality protein structure subset of SCOP30, which contains 3,297 protein structures. For each protein structure of the subset, we retrieved its neighbor protein structures from the rest of the subset. The best area under the ROC curve, archived by a ContactLib, is as high as 0.960. This is a significant improvement over 0.747, the best result achieved by the state-of-the-art method, FragBag. For the high-resolution approach, our PROtein STructure Alignment method (PROSTA) relies on and verifies the fact that the optimal protein structure alignment always contains a small subset of aligned residue pairs, called a seed, such that the rotation and translation (ROTRAN), which minimizes the RMSD of the seed, yields both the optimal ROTRAN and the optimal alignment score. Thus, ROTRANs minimizing the RMSDs of small subsets of residues are sampled, and global alignments are calculated directly from the sampled ROTRANs. Moreover, our method incorporates remote information and filters similar ROTRANs (or alignments) by clustering, rather than by an exhaustive method, to overcome the computational inefficiency. Our high-resolution protein structure alignment method, when applied to optimizing the TM-score and the GDT-TS score, produces a significantly better result than state-of-the-art protein structure alignment methods. Specifically, if the highest TM-score found by TM-align is lower than 0.6 and the highest TM-score found by one of the tested methods is higher than 0.5, our alignment method tends to discover better protein structure alignments with (up to 0.21) higher TM-scores. In such cases, TM-align fails to find TM-scores higher than 0.5 with a probability of 42%; however, our alignment method fails the same task with a probability of only 2%. In addition, existing protein structure alignment scoring functions focus on atom coordinate similarity alone and simply ignore other important similarities, such as sequence similarity. Our scoring function has the capacity for incorporating multiple similarities into the scoring function. Our result shows that sequence similarity aids in finding high quality protein structure alignments that are more consistent with HOMSTRAD alignments, which are protein structure alignments examined by human experts. When atom coordinate similarity itself fails to find alignments with any consistency to HOMSTRAD alignments, our scoring function remains capable of finding alignments highly similar to, or even identical to, HOMSTRAD alignments

Study on the microstructural evolution of different component alloys consisting of B2-NiSc intermetallics

Ni-50%Sc and Ni-51%Sc alloy were prepared with a vacuum arc smelting and water cooled copper mold suction-casting machine. The results showed that the two component alloys consisted of the primary phase B2-NiSc and lamellar (Ni2Sc+NiSc)eutectic due to the loss of Sc duringmelting. Two groups of alloys underwent (970 ℃, 72 h) homogenization heat treatment, and spherical or plate shape Ni2Sc particles were dispersed on the B2-NiSc matrix. With the increase of Sc content from50% to 51%, the amount of the second phase in the alloy decreases, the microstructure becomes uniform, and the grain gradually changes from long bar to a spherical particle. According to the Jackson boundary theory, the Jackson factor α of B2-NiSc =0.5 < 2, so the interface is rough, which explains that the growth pattern of the B2-NiSc phase is anon-faceted growth. It is consistent with the dendritic growth pattern of the B2-NiSc phase, which is observed from the experiment. After a longheat treatment, the number of vacancies decreases and the microstructure became uniform. The loss rate of Sc in rapidly quenched solidification was higher than that after the heat treatment

Microstructures and properties of AZ31 magnesium alloys formed by multi-channel porthole extrusion

This study investigated the effects of different extrusion temperatures and extrusion ratios on the microstructures and properties of AZ31 magnesium alloys formed by multi-channel porthole extrusion. The experimental results showed that equiaxed grains were formed during the dynamic recrystallization process and that alloy grains were refined by extrusion. Increased extrusion temperatures (from 340 ℃ to 420 ℃) resulted in larger alloy grains and decreased tensile strength of the alloy. Increased extrusion ratios (from 9 to 25) resulted in refined alloy grains and increased tensile strength of the alloy. Under conditions of low extrusion temperature and high extrusion ratio, the tensile strength and elongation of magnesium alloys were effectively improved. AZ31 magnesium alloys produced by multi-channel porthole extrusion at the extrusion temperature of 340℃ and the extrusion ratio of 25 possessed the finest average grain sizes (1.6 μm in the weld zone, 6.6 μm in the non-weld zone ) and the maximum tensile strength (290 MPa) and elongation (20.8 %)

Effect of cooling rate on microstructure of B2-NiSc intermetallics

Ni-50at%Sc alloy was prepared by centrifugal casting method. Volume fraction, the actual content of B2-NiSc and second phase Ni2Sc in alloy were analyzed with an Image-Pro Plus software. The cooling rates for the solidified thin plate with thickness of 2.65mm, 1.2mm, 0.75mm and 0.35 mm are 1164, 2570, 4112 and 8811 K·s- 1, respectively. It is found that d=0.5 mm was an critical dimension which corresponds to an abrupt change in the solidification rate. It is also found that (Ni2Sc+NiSc)eutectic was dispersed at grain boundary or between dendritic arms due to the loss of Sc element during melting. While d＞ 0.5mm (corresponding to the thin plate with thickness of 0.75mm, 1.20mm and 2.65 mm), the solidification structure consists of primary phase B2-NiSc and (Ni2Sc+NiSc)eutectic. While d ＜ 0.5mm (corresponding to the thin plate with thickness of 0.35 mm), the solidification structure is composed of fine globular B2-NiSc and relatively small amounts of (Ni2Sc+NiSc)eutectic. Based on the phase volumetric analyzing of the microstructure with an Image-Pro Plus software, the loss of Sc element during melting was about 3.01~3.10 at%. The eutectic NiSc in the lamellar eutectic structure together with the primary phase B2-NiSc form a larger single phase NiSc, while Ni2Sc with the form of particles is distributed on the grain boundaries after (970 ℃, 72 h) homogenization heat treatment

The effect of multiple genetic variants in predicting the risk of type 2 diabetes

While recently performed genome-wide association studies have advanced the identification of genetic variants predisposing to type 2 diabetes (T2D), the potential application of these novel findings for disease prediction and prevention has not been well studied. Diabetes prediction and prevention have become urgent issues owing to the rapidly increasing prevalence of diabetes and its associated mortality, morbidity, and health care cost. New prediction approaches using genetic markers could facilitate early identification of high risk sub-groups of the population so that appropriate prevention methods could be effectively applied to delay, or even prevent, disease onset