Interruptional Activity and Simulation of Transposable Elements

Transposable elements (TEs) are interspersed DNA sequences that can move or copy to new positions within a genome. The active TEs along with the remnants of many transposition events over millions of years constitute 46.69% of the human genome. TEs are believed to promote speciation and their activities play a significant role in human disease. The 22 AluY and 6 AluS TE subfamilies have been the most active TEs in recent human history, whose transposition has been implicated in several inherited human diseases and in various forms of cancer by integrating into genes. Therefore, understanding the transposition activities is very important. Recently, there has been some work done to quantify the activity levels of active Alu transposable elements based on variation in the sequence. Here, given this activity data, an analysis of TE activity based on the position of mutations is conducted. Two different methods/simulations are created to computationally predict so-called harmful mutation regions in the consensus sequence of a TE; that is, mutations that occur in these regions decrease the transposition activities dramatically. The methods are applied to AluY, the youngest and most active Alu subfamily, to identify the harmful regions laying in its consensus, and verifications are presented using the activity of AluY elements and the secondary structure of the AluYa5 RNA, providing evidence that the method is successfully identifying harmful mutation regions. A supplementary simulation also shows that the identified harmful regions covering the AluYa5 RNA functional regions are not occurring by chance. Therefore, mutations within the harmful regions alter the mobile activity levels of active AluY elements. One of the methods is then applied to two additional TE families: the Alu family and L1 family, in detecting the harmful regions in these elements computationally. Understanding and predicting the evolution of these TEs is of interest in understanding their powerful evolutionary force in shaping their host genomes. In this thesis, a formal model of TE fragments and their interruptions is devised that provides definitions that are compatible with biological nomenclature, while still providing a suitable formal foundation for computational analysis. Essentially, this model is used for fixing terminology that was misleading in the literature, and it helps to describe further TE problems in a precise way. Indeed, later chapters include two other models built on top of this model: the sequential interruption model and the recursive interruption model, both used to analyze their activity throughout evolution. The sequential interruption model is defined between TEs that occur in a genomic sequence to estimate how often TEs interrupt other TEs, which has been shown to be useful in predicting their ages and their activity throughout evolution. Here, this prediction from the sequential interruptions is shown to be closely related to a classic matrix optimization problem: the Linear Ordering Problem (LOP). By applying a well-studied method of solving the LOP, Tabu search, to the sequential interruption model, a relative age order of all TEs in the human genome is predicted from a single genome. A comparison of the TE ordering between Tabu search and the method used in [47] shows that Tabu search solves the TE problem exceedingly more efficiently, while it still achieves a more accurate result. As a result of the improved efficiency, a prediction on all human TEs is constructed, whereas it was previously only predicted for a minority fraction of the set of the human TEs. When many insertions occurred throughout the evolution of a genomic sequence, the interruptions nest in a recursive pattern. The nested TEs are very helpful in revealing the age of the TEs, but cannot be fully represented by the sequential interruption model. In the recursive interruption model, a specific context- free grammar is defined, describing a general and simple way to capture the recursive nature in which TEs nest themselves into other TEs. Then, each production of the context-free grammar is associated with a probability to convert the context-free grammar into a stochastic context-free grammar that maximizes the applications of the productions corresponding to TE interruptions. A modified version of an algorithm to parse context-free grammars, the CYK algorithm, that takes into account these probabilities is then used to find the most likely parse tree(s) predicting the TE nesting in an efficient fashion. The recursive interruption model produces small parse trees representing local TE interruptions in a genome. These parse trees are a natural way of grouping TE fragments in a genomic sequence together to form interruptions. Next, some tree adjustment operations are given to simplify these parse trees and obtain more standard evolutionary trees. Then an overall TE-interaction network is created by merging these standard evolutionary trees into a weighted directed graph. This TE-interaction network is a rich representation of the predicted interactions between all TEs throughout evolution and is a powerful tool to predict the insertion evolution of these TEs. It is applied to the human genome, but can be easily applied to other genomes. Furthermore, it can also be applied to multiple related genomes where common TEs exist in order to study the interactions between TEs and the genomes. Lastly, a simulation of TE transpositions throughout evolution is developed. This is especially helpful in understanding the dynamics of how TEs evolve and impact their host genomes. Also, it is used as a verification technique for the previous theoretical models in the thesis. By feeding the simulated TE remnants and activity data into the theoretical models, a relative age order is predicted using the sequential interruption model, and a quantified correlation between this predicted order and the input age order in the simulation can be calculated. Then, a TE-interaction network is constructed using the recursive interruption model on the simulated data, which can also be converted into a linear age order by feeding the adjacency matrix of the network to Tabu search. Another correlation is calculated between the predicted age order from the recursive interruption model and the input age order. An average correlation of ten simulations is calculated for each model, which suggests that in general, the recursive interruption model performs better than the sequential interruption model in predicting a correct relative age order of TEs. Indeed, the recursive interruption model achieves an average correlation value of ρ = 0.939 with the correct simulated answer

Multiple sequence alignment augmented by expert user constraints

Sequence alignment has become one of the most common tasks in bioinformatics. Most of the existing sequence alignment methods use general scoring schemes. But these alignments are sometimes not completely relevant because they do not necessarily provide the desired information. It would be extremely difficult, if not impossible, to include any possible objective into an algorithm. Our goal is to allow a working biologist to augment a given alignment with additional information based on their knowledge and objectives.In this thesis, we will formally define constraints and compatible constraint sets for an alignment which require some positions of the sequences to be aligned together. Using this approach, one can align some specific segments such as domains within protein sequences by inputting constraints (the positions of the segments on the sequences), and the algorithm will automatically find an optimal alignment in which the segments are aligned together.A necessary prerequisite of calculating an alignment is that the constraints inputted be compatible with each other, and we will develop algorithms to check this condition for both pairwise and multiple sequence alignments. The algorithms are based on a depth-first search on a graph that is converted from the constraints and the alignment. We then develop algorithms to perform pairwise and multiple sequence alignments satisfying these compatible constraints.Using straightforward dynamic programming for pairwise sequence alignment satisfying a compatible constraint set, an optimal alignment corresponds to a path going through the dynamic programming matrix, and as we are only using single-position constraints, a constraint can be represented as a point on the matrix, so a compatible constraint set is a set of points. We try to determine a new path, rather than the original path, that achieves the highest score which goes through all the compatible constraint set points. The path is a concatenation of sub-paths, so that only the scores in the sub-matrices need to be calculated. This means the time required to get the new path decreases as the number of constraints increases, and it also varies as the positions of the points change. It can be further reduced by using the information from the original alignment, which can offer a significant speed gain.We then use exact and progressive algorithms to find multiple sequence alignments satisfying a compatible constraint set, which are extensions of pairwise sequence alignments. With exact algorithms for three sequences, where constraints are represented as lines, we discuss a method to force the optimal path to cross the constraint lines. And with progressive algorithms, we use a set of pairwise alignments satisfying compatible constraints to construct multiple sequence alignments progressively. Because they are more complex, we leave some extensions as future work

The Air War versus The Ground Game: An Analysis of Multi-Channel Marketing in U.S. Presidential Elections

Firms increasingly use both mass-media advertising and targeted personal selling to successfully promote products and brands in the marketplace. In this study, we jointly examine the effect of mass-media advertising and personal selling in the context of U.S. presidential elections, where the former is referred to as the “air war” and the latter the “ground game.” Specifically, we look at how different types of advertising―candidate own ads vs. outside ads―and personal selling―in the form of utilizing field offices―affect voter preferences. Further, we ask how these various campaign activities affect the outcome of elections through their diverse effects on various types of people. We find that personal selling has a stronger effect among partisan voters, while candidate's own advertising is better received by non-partisans. We also find that personal selling accounted for the Democratic victories in the 2008 and 2012 elections, and that advertising was critical only in a close election, such as the one in 2004. Interestingly, had the Democrats received more outside advertising in 2004, the election would have ended up in a 269-269 tie. Our findings generate insights on how to allocate resources across and within channels

Helicity Dependent Directional Surface Plasmon Polariton Excitation Using A Metasurface with Interfacial Phase Discontinuity

Surface plasmon polaritons (SPPs) have been widely exploited in various scientific communities, ranging from physics, chemistry to biology, due to the strong confinement of light to the metal surface. For many applications it is important that the free space photon can be coupled to SPPs in a controllable manner. In this Letter, we apply the concept of interfacial phase discontinuity for circularly polarizations on a metasurface to the design of a novel type of polarization dependent SPP unidirectional excitation at normal incidence. Selective unidirectional excitation of SPPs along opposite directions is experimentally demonstrated at optical frequencies by simply switching the helicity of the incident light. This approach, in conjunction with dynamic polarization modulation techniques, opens gateway towards integrated plasmonic circuits with electrically reconfigurable functionalities.Comment: 17 pages, 5 figures. Published on <Light:Science & Applications

STUDY ON THE ADSORPTION CHARACTERISTICS OF CONGO RED BY SYCAMORE BARK ACTIVATED CARBON

The activated carbon was prepared from sycamore bark by activation of zinc chloride. The absorbing effect of activated carbon on Congo red wastewater is studied. The characteristics of sycamore bark activated carbon were characterized by SEM and BET. The effects of adsorbent dosage, time, and shaking speed on the adsorption properties of Congo red by sycamore bark activated carbon were studied. The isotherm, kinetics, and thermodynamics of adsorption were explored. The results revealed that the activated carbon contain a large apparent mesopores. Adsorption efficiency was increased with enhancing the adsorption dosage and time. The removal rate of Conge red reached to 98.2% under room temperature with adsorbent dosage of 3.0 g/L, adsorption time of 120 min, shaking speed of 60r/min. The adsorption of Congo red on sycamore bark activated carbon was followed Langmuir isotherm model and Lagergren pseudo-second order kinetics model. The adsorption was spontaneous, endothermic, and the entropy was increasing in the adsorption process

Acupuncture in Treatment of Chronic Functional Constipation

Constipation is not only a symptom but is a predominant presenting symptom in many diseases. The prevalence is between 3 and 27% worldwide, and is especially prevalent in the elderly population. The aetiology is multifactorial. Laxative abuse or enema use are usually a norm in patients’ constipation. Patients tend not to seek further medical aid after several unsuccessful therapies and this can seriously affect their quality of life

Particle Deposition in Microfluidic Devices at Elevated Temperatures

In microchannels, interaction and transport of micro-/nanoparticles and biomolecules are crucial phenomena for many microfluidic applications, such as nanomedicine, portable food processing devices, microchannel heat exchangers, etc. The phenomenon that particles suspended in liquid are captured by a solid surface (e.g., microchannel wall) is referred to as particle deposition. Particle deposition is of importance in numerous practical applications and is also of fundamental interest to the field of colloid science. This chapter presents researches on fouling and particle deposition in microchannels, especially the effects of temperature and temperature gradient, which have been frequently ‘ignored’ but are important factors for thermal-driven particle deposition and fouling processes at elevated temperatures

Strategic Channel Selection with Online Platforms: An Empirical Analysis of the Daily Deal Industry

The platform—a business model that creates value by connecting groups of users—is increasingly popular in many industries. Extant papers largely assume that platforms dominate the pricing decision, whereas in practice, prices in business-to-business transactions are often determined by a bargaining process. We study how the relative bargaining power of business partners affects pricing and competition in a two-sided market. We compile a unique and comprehensive dataset using sales data from the US daily deal market and specify a structural model based on Nash bargaining solutions. We find that Groupon, the larger deal platform, has more price-bargaining power than LivingSocial and that larger and chain merchants have more bargaining power than smaller and independent merchants. The difference in bargaining power between different types of merchant, interestingly, is more substantial on LivingSocial than on Groupon. Therefore, the size of a platform has two faces: while a larger customer base helps attract merchants, the platform’s bargaining power may motivate some merchants to work with its smaller competitors, over which they have more influence on price setting. Our counterfactual results show that the allocation of price-bargaining power plays an important role in the daily deal markets and that merchants are significantly worse off if platforms have higher price-bargaining power during the negotiation. Furthermore, as it increases the bargaining power, LivingSocial would be able to boost its profits but lose its attraction in acquiring merchants