Bionano-Interfaces through Peptide Design

The clinical success of restoring bone and tooth function through implants critically depends on the maintenance of an infection-free, integrated interface between the host tissue and the biomaterial surface. The surgical site infections, which are the infections within one year of surgery, occur in approximately 160,000-300,000 cases in the US annually. Antibiotics are the conventional treatment for the prevention of infections. They are becoming ineffective due to bacterial antibiotic-resistance from their wide-spread use. There is an urgent need both to combat bacterial drug resistance through new antimicrobial agents and to limit the spread of drug resistance by limiting their delivery to the implant site. This work aims to reduce surgical site infections from implants by designing of chimeric antimicrobial peptides to integrate a novel and effective delivery method. In recent years, antimicrobial peptides (AMPs) have attracted interest as natural sources for new antimicrobial agents. By being part of the immune system in all life forms, they are examples of antibacterial agents with successfully maintained efficacy across evolutionary time. Both natural and synthetic AMPs show significant promise for solving the antibiotic resistance problems. In this work, AMP1 and AMP2 was shown to be active against three different strains of pathogens in Chapter 4. In the literature, these peptides have been shown to be effective against multi-drug resistant bacteria. However, their effective delivery to the implantation site limits their clinical use. In recent years, different groups adapted covalent chemistry-based or non-specific physical adsorption methods for antimicrobial peptide coatings on implant surfaces. Many of these procedures use harsh chemical conditions requiring multiple reaction steps. Furthermore, none of these methods allow the orientation control of these molecules on the surfaces, which is an essential consideration for biomolecules. In the last few decades, solid binding peptides attracted high interest due to their material specificity and self-assembly properties. These peptides offer robust surface adsorption and assembly in diverse applications. In this work, a design method for chimeric antimicrobial peptides that can self-assemble and self-orient onto biomaterial surfaces was demonstrated. Three specific aims used to address this two-fold strategy of self-assembly and self-orientation are: 1) Develop classification and design methods using rough set theory and genetic algorithm search to customize antibacterial peptides; 2) Develop chimeric peptides by designing spacer sequences to improve the activity of antimicrobial peptides on titanium surfaces; 3) Verify the approach as an enabling technology by expanding the chimeric design approach to other biomaterials. In Aim 1, a peptide classification tool was developed because the selection of an antimicrobial peptide for an application was difficult among the thousands of peptide sequences available. A rule-based rough-set theory classification algorithm was developed to group antimicrobial peptides by chemical properties. This work is the first time that rough set theory has been applied to peptide activity analysis. The classification method on benchmark data sets resulted in low false discovery rates. The novel rough set theory method was combined with a novel genetic algorithm search, resulting in a method for customizing active antibacterial peptides using sequence-based relationships. Inspired by the fact that spacer sequences play critical roles between functional protein domains, in Aim 2, chimeric peptides were designed to combine solid binding functionality with antimicrobial functionality. To improve how these functions worked together in the same peptide sequence, new spacer sequences were engineered. The rough set theory method from Aim 1 was used to find structure-based relationships to discover new spacer sequences which improved the antimicrobial activity of the chimeric peptides. In Aim 3, the proposed approach is demonstrated as an enabling technology. In this work, calcium phosphate was tested and verified the modularity of the chimeric antimicrobial self-assembling peptide approach. Other chimeric peptides were designed for common biomaterials zirconia and urethane polymer. Finally, an antimicrobial peptide was engineered for a dental adhesive system toward applying spacer design concepts to optimize the antimicrobial activity

Dealing with uncertain entities in ontology alignment using rough sets

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2012 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.Ontology alignment facilitates exchange of knowledge among heterogeneous data sources. Many approaches to ontology alignment use multiple similarity measures to map entities between ontologies. However, it remains a key challenge in dealing with uncertain entities for which the employed ontology alignment measures produce conflicting results on similarity of the mapped entities. This paper presents OARS, a rough-set based approach to ontology alignment which achieves a high degree of accuracy in situations where uncertainty arises because of the conflicting results generated by different similarity measures. OARS employs a combinational approach and considers both lexical and structural similarity measures. OARS is extensively evaluated with the benchmark ontologies of the ontology alignment evaluation initiative (OAEI) 2010, and performs best in the aspect of recall in comparison with a number of alignment systems while generating a comparable performance in precision

Rough matroids based on coverings

The introduction of covering-based rough sets has made a substantial contribution to the classical rough sets. However, many vital problems in rough sets, including attribution reduction, are NP-hard and therefore the algorithms for solving them are usually greedy. Matroid, as a generalization of linear independence in vector spaces, it has a variety of applications in many fields such as algorithm design and combinatorial optimization. An excellent introduction to the topic of rough matroids is due to Zhu and Wang. On the basis of their work, we study the rough matroids based on coverings in this paper. First, we investigate some properties of the definable sets with respect to a covering. Specifically, it is interesting that the set of all definable sets with respect to a covering, equipped with the binary relation of inclusion $\subseteq$, constructs a lattice. Second, we propose the rough matroids based on coverings, which are a generalization of the rough matroids based on relations. Finally, some properties of rough matroids based on coverings are explored. Moreover, an equivalent formulation of rough matroids based on coverings is presented. These interesting and important results exhibit many potential connections between rough sets and matroids.Comment: 15page

A comparative study of the AHP and TOPSIS methods for implementing load shedding scheme in a pulp mill system

The advancement of technology had encouraged mankind to design and create useful equipment and devices. These equipment enable users to fully utilize them in various applications. Pulp mill is one of the heavy industries that consumes large amount of electricity in its production. Due to this, any malfunction of the equipment might cause mass losses to the company. In particular, the breakdown of the generator would cause other generators to be overloaded. In the meantime, the subsequence loads will be shed until the generators are sufficient to provide the power to other loads. Once the fault had been fixed, the load shedding scheme can be deactivated. Thus, load shedding scheme is the best way in handling such condition. Selected load will be shed under this scheme in order to protect the generators from being damaged. Multi Criteria Decision Making (MCDM) can be applied in determination of the load shedding scheme in the electric power system. In this thesis two methods which are Analytic Hierarchy Process (AHP) and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) were introduced and applied. From this thesis, a series of analyses are conducted and the results are determined. Among these two methods which are AHP and TOPSIS, the results shown that TOPSIS is the best Multi criteria Decision Making (MCDM) for load shedding scheme in the pulp mill system. TOPSIS is the most effective solution because of the highest percentage effectiveness of load shedding between these two methods. The results of the AHP and TOPSIS analysis to the pulp mill system are very promising