[Show abstract][Hide abstract] ABSTRACT: Synthetic drugs such as allopurinol and benzbromarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase and cyclooxygenase-2 enzymes. In this study, we report the screening of nine compounds of flavonoids from the ZINC and PubChem databases (containing 2092 flavonoids) using the igemdock software tool against the xanthine oxidase and cyclooxygenase-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase-2. Myricetin and luteolin were found to be the potential dual inhibitors of xanthine oxidase and cyclooxygenase-2 as demonstrated by IC50 : 62.7 and 3.29 μg/mL (xanthine oxidase)/70.8 and 16.38 μg/mL (cyclooxygenase-2), respectively. In addition, structure-activity relationships and other important factors of the flavonoids binding to the active site of xanthine oxidase and cyclooxygenase-2 were discussed, which is expected for further rational drug design.
Full-text · Article · Apr 2013 · Chemical Biology & Drug Design
[Show abstract][Hide abstract] ABSTRACT: The copious volumes of biomedical literature being generated have created a need for the development of text mining algorithms to identify and extract and pertinent biological information. This pilot study demonstrates a computational linguistics approach to identifying genes, proteins, and other biological factors that are associated with the development and progression of lung cancer.
[Show abstract][Hide abstract] ABSTRACT: Synthetic drugs such as allopurinol and benzbroarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase (XO) and cyclooxygenase 2 (COX-2) enzymes. In this study, we report the screening of 9 compounds of flavonoids from the ZINC and PubChem databases (containing 2,092 flavonoids) using the iGEMDOCK software tool against the XO and COX-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of XO and COX-2. Myricetin and luteolin were found to be the potential dual inhibitors of XO and COX-2 as demonstrated by IC50: 62.7 and 3.29μg/mL (XO) / 70.8 and 16.38μg/mL (COX-2), respectively. In addition, structure activity relationships and other important factors of the flavonoids binding to the active site of XO and COX-2 were discussed, which is expected for further rational drug design.
No preview · Article · Oct 2011 · Chemical Biology & Drug Design
[Show abstract][Hide abstract] ABSTRACT: NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%–55% of these patients develop recurrence within 5 years. Therefore, markers that can be used to accurately classify early-stage NSCLC patients into different prognostic groups may be helpful in selecting patients who should receive specific therapies.
A previously published dataset was used to evaluate gene expression profiles of different NSCLC subtypes. A moderated two-sample t-test was used to identify differentially expressed genes between all tumor samples and cancer-free control tissue, between SCC samples and AC/BC samples and between stage I tumor samples and all other tumor samples. Gene expression microarray measurements were validated using qRT-PCR.
Bayesian regression analysis and Kaplan-Meier survival analysis were performed to determine metagenes associated with survival. We identified 599 genes which were down-regulated and 402 genes which were up-regulated in NSCLC compared to the normal lung tissue and 112 genes which were up-regulated and 101 genes which were down-regulated in AC/BC compared to the SCC. Further, for stage Ib patients the metagenes potentially associated with survival were identified.
Genes that expressed differently between normal lung tissue and cancer showed enrichment in gene ontology terms which were associated with mitosis and proliferation. Bayesian regression and Kaplan-Meier analysis showed that gene-expression patterns and metagene profiles can be applied to predict the probability of different survival outcomes in NSCLC patients.
Full-text · Article · Jun 2011 · Cancer informatics
[Show abstract][Hide abstract] ABSTRACT: In this study, we reported the screening of 9 compounds of flavonoids from the ZINC and PubChem databases (containing 2 092 flavonoids) using the iGEMDOCK software tool against the COX-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of COX-2. Centaureidin and luteolin were found to be the potential inhibitors of COX-2 as demonstrated by IC50: 45 and 36.6 μmol·L−1, respectively. In addition, structure activity relationships and other important factors of the flavonoids binding to the active site of COX-2 were discussed, which is expected for further rational drug design.
No preview · Article · Mar 2011 · Chinese Journal of Natural Medicines
[Show abstract][Hide abstract] ABSTRACT: The Web represents one of the largest repositories of information ever compiled by mankind and as such search techniques are essential to navigating its depths and returning pertinent information. Typically the search techniques employed in search engines such as Google entail the use of keywords in which Web pages containing the specified keywords are sought out and then ranked using an algorithm such as PageRank. While keywords are suitable for many search tasks, certain types of data cannot be readily searched using keywords alone. Regular expression based pattern matching allows for enhanced search capability in that it allows for a textual pattern to be specified and matching to be performed against the pattern. Regular expressions have been developed that allow for the identification of common CC++ code structures such a loops, conditionals and functions. These regular expressions are then integrated into a Perl program that performs a keyword based search of the Yahoo Search engine and used to extract any code elements that match those patterns. Thus an algorithm or programming technique can be specified with keywords, the Yahoo search used to identify Web pages pertinent to those keywords, and the regular expressions used to identify and extract any CC++ code found in the resultant Web pages. Application of this technique would likely be of great benefit towards creating specialized search capabilities for software developers.
[Show abstract][Hide abstract] ABSTRACT: The advent of the biotechnology industry as well as the continued usage of enzymes in the bioprocess industries have resulted in increased demand for the creation of proteins with enhanced properties as well as the desire to create proteins of novel functionalities. Protein engineering is the field that is concerned with achieving such goals. Over the course of the last decade protein engineering efforts have come to increasingly rely on computational means. This review seeks to highlight computational methods of protein engineering that appear in recently issued patents.
No preview · Article · Jan 2010 · Recent Patents on Biomedical Engineering
[Show abstract][Hide abstract] ABSTRACT: The World Wide Web has grown to become one of the most pervasive and comprehensive information repositories available today and many compare the knowledge contained within it to a modern day library of Alexandria. Yet, despite its vastness, one of the downsides to using Web-based information sources is that the information contained in most Web pages has never been reviewed for accuracy or quality and thus it is often considered unsuitable for application where accuracy is of critical importance. While sites of questionable quality clearly should be avoided, one cannot deny the utility and advantages of Web based resources, and thus a methodology has been developed to identify expert vetted health-related Web resources. The resultant computer software searches for biomedical abstracts via Pubmed that pertain to a health topic of interest and via regular expression based pattern matching extracts all of the URLs that appear in the article abstracts. Given that articles that appear in Pubmed typically endure peer-review processes it can be assumed that all of the resources referenced by these articles have a reasonable level of quality, since they are being cited by experts. Thus the program is able to compile a list of quality Web resources pertaining to health topics. This system has successfully been used to create a list of Influenza related Web resources as a means of illustrating its utility.
[Show abstract][Hide abstract] ABSTRACT: The biomedical literature has always played a critical role in the development of hypotheses to test, experimental design, and the analysis of study results. Yet, the ever-expanding body of biomedical literature is starting to present new challenges, in which locating pertinent literature from among the millions of published research articles is often a challenging task. A regular expression-based pattern matching method has been developed to profile the various gene and protein factors that may play a role in various tissues contained within an organism. This methodology has been demonstrated through the profiling of the various factors that are involved in the development of the inner ear, and is shown to be both effective and accurate.
No preview · Article · Jan 2010 · Advances in Experimental Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: Homeodomain containing proteins are a broad class of DNA binding proteins that are believed to primarily function as transcription factors. Electrostatics interactions have been demonstrated to be critical for the binding of the homeodomain to DNA. An examination of the electrostatic state of homeodomain residues involved in DNA phosphate binding has demonstrated the conserved presence of upward shifted pKa values among the basic residue of lysine and arginine. It is believed that these pKa perturbations work to facilitate binding to DNA since they ensure that the basic residues always retain a positive charge. Comment: Frenz, C.M. & Lefebvre, P.P. (2009) Presence of pKa Perturbations Among Homeodomain Residues Facilitates DNA Binding, Proceedings of the 2009 International Conference on Bioinformatics and Computational Biology (BIOCOMP '09), 198-203
[Show abstract][Hide abstract] ABSTRACT: Digital logic forms the functional basics of most modern electronic equipment and as such the creation of novel digital logic circuits is an active area of computer engineering research. This study demonstrates that genetic algorithms can be used to evolve functionally useful sets of logic gate interconnections to create useful digital logic circuits. The efficacy of this approach is illustrated via the evolution of AND, OR, XOR, NOR, and XNOR functionality from sets of NAND gates, thereby illustrating that evolutionary methods have the potential be applied to the design of digital electronics. Comment: Frenz, C.M., Peters, S., Julien, W. (2009) Evolution of Digital Logic Functionality via a Genetic Algorithm, Proceedings of the 2009 International Conference on Genetic and Evolutionary Methods (GEM 2009), 99-101
[Show abstract][Hide abstract] ABSTRACT: Elevator traffic comprises the movement of individuals from the floor from which they called the elevator to their destination floor. This project seeks to improve elevator call time responsiveness by utilizing the concept that traffic flows generally form definable patterns that can be used to predict future traffic flow behaviors. A feed-forward neural network-based control algorithm has been developed that can approximate elevator call patterns by learning to associate time of day with specific call locations. This algorithm was tested against fuzzy patterns of elevator calls in which the randomly generated calls were biased towards certain floors at certain times of day. When the average neural network controlled call times of 10 such fuzzy sets were compared to the typical scenario of the elevator returning to the first floor after each call, a 42% improvement in elevator call time responsiveness was observed. It is thereby suggested that a machine learning enabled-elevator control system could result in increased user satisfaction by reducing wait times by helping to ensure that the elevator is at the most likely place the elevator will be called from prior to an individual even pushing the call button. The utility of such an algorithm is likely further enhanced, however, by the fact that having the elevator in the most likely call location can also lead to significant energy savings in that the elevator will need to travel less to pick up prospective passengers.
[Show abstract][Hide abstract] ABSTRACT: Protein electrostatics have been demonstrated to play a vital role in protein functionality, with many functionally important amino acid residues exhibiting an electrostatic state that is altered from that of a normal amino acid residue. Residues with altered electrostatic states can be identified by the presence of a pKa value that is perturbed by 2 or more pK units, and such residues have been demonstrated to play critical roles in catalysis, ligand binding, and protein stability. Within the HCV helicase and polymerase, as well as the HIV reverse transcriptase, highly conserved regions were demonstrated to possess a greater number and magnitude of perturbations than lesser conserved regions, suggesting that there is an interrelationship present between protein electrostatics and evolution.
[Show abstract][Hide abstract] ABSTRACT: The explosive rate of information growth and availability often makes it increasingly difficult to locate information pertinent to your needs. These problems are often compounded when keyword based search methodologies are not adequate for describing the information you seek. In many instances, information such as Web site URLs, phone numbers, etc. can often be better identified through the use of a textual pattern than by keyword. For example, many more phone numbers could be picked up by a search for the pattern (XXX) XXX-XXXX, where X could be any digit, than would be by a search for any specific phone number (i.e. the keyword approach). Programming languages typically allow for the matching of textual patterns via the usage of regular expressions. This tutorial will provide an introduction to the basics of programming regular expressions as well as provide an introduction to how regular expressions can be applied to data processing tasks such as information extraction and search refinement.
[Show abstract][Hide abstract] ABSTRACT: ESPSim is an open source JAVA program that enables the comparisons of protein electrostatic potential maps via the computation of an electrostatic similarity measure. This program has been utilized to demonstrate a high degree of electrostatic similarity among the potential maps of lysozyme proteins, suggesting that protein electrostatic states are conserved within lysozyme proteins. ESPSim is freely available under the AGPL License from http://www.bioinformatics.org/project/?group_id=830
[Show abstract][Hide abstract] ABSTRACT: Protein electrostatic states have been demonstrated to play crucial roles in catalysis, ligand binding, protein stability, and in the modulation of allosteric effects. Electrostatic states are demonstrated to appear conserved among DEAD-box motifs and evidence is presented that the structural changes that occur to DEAD box proteins upon ligand binding alter the DEAD-box motif electrostatics in a way the facilitates the catalytic role of the DEAD-box glutatmate.
[Show abstract][Hide abstract] ABSTRACT: The POU4F3 transcription factor is expressed in the cochlear and vestibular hair cells of the inner ear and its targeted deletion results in a loss of inner ear hair cells. The DFNA15 truncation mutation has been demonstrated to result in a loss of transcriptional activity, but an increase in the stability of the protein. Molecular modelling is utilised to propose a mechanism of stability enhancement, via an interaction between the truncated POU(HD) domain and the POU(S) domain of the transcription factor.
No preview · Article · Jan 2008 · International Journal of Computational Biology and Drug Design
[Show abstract][Hide abstract] ABSTRACT: Based on current calculations using tens of terafiops on the LLNL BG/L supercomputer, our proposed simulation would require 128x more computing power - in other words, several petafiops for approximately three months. This level of computing could provide a glimpse of the early universe as we've never seen it before and lead to a dramatic improvement in our understanding of the interactions of nature's smallest particles - quarks - which also comprise its largest visible structures.
Preview · Article · Dec 2007 · Computing in Science and Engineering