950 research outputs found

    Position dependencies in transcription factor binding sites

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    Motivation: Most of the available tools for transcription factor binding site prediction are based on methods which assume no sequence dependence between the binding site base positions. Our primary objective was to investigate the statistical basis for either a claim of dependence or independence, to determine whether such a claim is generally true, and to use the resulting data to develop improved scoring functions for binding-site prediction. Results: Using three statistical tests, we analyzed the number of binding sites showing dependent positions. We analyzed transcription factor-DNA crystal structures for evidence of position dependence. Our final conclusions were that some factors show evidence of dependencies whereas others do not. We observed that the conformational energy (Z-score) of the transcription factor-DNA complexes was lower (better) for sequences that showed dependency than for those that did not (P < 0.02). We suggest that where evidence exists for dependencies, these should be modeled to improve binding-site predictions. However, when no significant dependency is found, this correction should be omitted. This may be done by converting any existing scoring function which assumes independence into a form which includes a dependency correction. We present an example of such an algorithm and its implementation as a web tool. Availability: http://promoterplot.fmi.ch/cgi-bin/dep.html Contact: [email protected] Supplementary information: Supplementary data (1, 2, 3, 4, 5, 6, 7 and 8) are available at Bioinformatics onlin

    Quality estimation of multiple sequence alignments by Bayesian hypothesis testing

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    Summary: In this work we present a web-based tool for estimating multiple alignment quality using Bayesian hypothesis testing. The proposed method is very simple, easily implemented and not time consuming with a linear complexity. We evaluated method against a series of different alignments (a set of random and biologically derived alignments) and compared the results with tools based on classical statistical methods (such as sFFT and csFFT). Taking correlation coefficient as an objective criterion of the true quality, we found that Bayesian hypothesis testing performed better on average than the classical methods we tested. This approach may be used independently or as a component of any tool in computational biology which is based on the statistical estimation of alignment quality. Availability: http://www.fmi.ch/groups/functional.genomics/tool.htm Contact: [email protected] Supplementary information: Supplementary data are available from http://www.fmi.ch/groups/functional.genomics/tool-Supp.ht

    Teaching in the Times of Pandemic

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    The changes in academia are typically slow but very purposeful, they are carefully reviewed and strategically implemented, that is, until unpredictable massive tectonic shifts occur in society. Historically, academia has not experienced major distress on a global scale that would require a fundamental change and adaptation to new set of circumstances, until the world faced COVID-19 pandemic of proportions which caused academia to rapidly adjust to new realities and make major changes. The time frame in which the changes needed to be done, weeks and months, were so short that academia was placed under the significant stress to which it is unaccustomed, but it did change in numerous innovative ways and delivered exceptional results. This paper presents some of the lessons learned by the authors from this global pandemic which could be added to the toolbox of measures to deal with the future tectonic changes, and yet these same lessons can also serve to improve student learning experiences in the times of normalcy.Teaching approaches discussed in this paper are related to authors’ extensive experiences in delivering courses in synchronous and asynchronous distance modalities. These experiences allowed authors to seamlessly and effortlessly transition to new conditions facing academia. In addition, the students who were exposed to similar learning experiences prior to pandemic had equally seamless and effortless transition.The results indicate that students benefited significantly from the applied approach which included flipped classroom and asynchronous learning amongst other approaches. In addition, the “any-time” and “any-where” access to course material helped students manage numerous obligations outside the coursework during the challenging and uncertain times when they had to deal with personal and professional issues.The pre-Covid and during-Covid analysis has been performed on the student success. The results indicate that students mastered the material at the same or even higher level of comprehension compared to traditional lecture environment. It can be concluded that methods applied to improve student learning using non-traditional methods can help students succeed in mastering material and help universities manage stress of a considerable magnitude

    New discotic liquid crystals based on large polycyclic aromatic hydrocarbons as materials for molecular electronics

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    A series of new columnar discotic liquid crystalline materials based on the superphenalene (C96) core has been synthesized by oxidative cyclodehydrogenation with iron(III) chloride of suitable three-dimensional oligophenylene precursors. These compounds were investigated by means of differential scanning calorimetry (DSC), polarized optical microscopy (POM) and wide angle X-ray scattering (WAXS), and showed highly ordered supramolecular arrays and mesophase behavior over a broad temperature range. Good solubility, through the introduction of long alkyl chains, and the fact that these new superphenalene derivatives were found to be liquid crystalline at room temperature enabled the formation of highly ordered films (using the zone-casting technique), a requirement for application in organic electronic devices. The one-dimensional, intracolumnar charge carrier mobilities of superphenalene derivatives were determined using the pulse-radiolysis time-resolved microwave conductivity technique (PR-TRMC). Electrical properties of different C96-C12 architectures on mica surfaces were examined by using Electrostatic Force Microscopy (EFM) and Kelvin Probe Force Microscopy (KPFM). Hexa-peri-hexabenzocoronene (C42) derivatives substituted at the periphery with six branched alkyl ether chains were also synthesized. It was found that the introduction of ether groups within the side chains enhances the affinity of the discotic molecules towards polar surfaces, resulting in homeotropic self-assembly (as shown by POM and 2D-WAXS) when the compounds are processed from the isotropic state between two surfaces. A new, insoluble, superphenalene building block bearing six reactive sites was prepared, and was further used for the preparation of dendronized superphenalenes with bulky dendritic substituents around the core. UV/Vis and fluorescence experiments suggest reduced π-π stacking of the superphenalene cores as a result of steric hindrance between the peripheral dendritic units. A new family of graphitic molecules with partial ”zig-zag” periphery has been established. The incorporation of ”zig-zag” edges was shown to have a strong influence on the electronic properties of the new molecules (as studied by solution and solid-state UV/Vis, and fluorescence spectroscopy), leading to a significant bathochromic shift with respect to the parent PAHs (C42 and C96). The reactivity of the additional double bonds was examined. The attachment of long alkyl chains to a ” zig-zag” superphenalene core afforded a new, processable, liquid crystalline material

    An intuitionistic approach to scoring DNA sequences against transcription factor binding site motifs

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    Background: Transcription factors (TFs) control transcription by binding to specific regions of DNA called transcription factor binding sites (TFBSs). The identification of TFBSs is a crucial problem in computational biology and includes the subtask of predicting the location of known TFBS motifs in a given DNA sequence. It has previously been shown that, when scoring matches to known TFBS motifs, interdependencies between positions within a motif should be taken into account. However, this remains a challenging task owing to the fact that sequences similar to those of known TFBSs can occur by chance with a relatively high frequency. Here we present a new method for matching sequences to TFBS motifs based on intuitionistic fuzzy sets (IFS) theory, an approach that has been shown to be particularly appropriate for tackling problems that embody a high degree of uncertainty. Results: We propose SCintuit, a new scoring method for measuring sequence-motif affinity based on IFS theory. Unlike existing methods that consider dependencies between positions, SCintuit is designed to prevent overestimation of less conserved positions of TFBSs. For a given pair of bases, SCintuit is computed not only as a function of their combined probability of occurrence, but also taking into account the individual importance of each single base at its corresponding position. We used SCintuit to identify known TFBSs in DNA sequences. Our method provides excellent results when dealing with both synthetic and real data, outperforming the sensitivity and the specificity of two existing methods in all the experiments we performed. Conclusions: The results show that SCintuit improves the prediction quality for TFs of the existing approaches without compromising sensitivity. In addition, we show how SCintuit can be successfully applied to real research problems. In this study the reliability of the IFS theory for motif discovery tasks is proven

    Applying Technology to Improve Student Learning Outcomes in Dynamics Course

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    Motivating and stimulating students to learn material in required core engineering courses is difficult and yet essential in assuring student success. Traditional methods of teaching and learning need to be reconsidered and modified to meet student expectations and their continuously evolving ways of interaction with technology and social networks. Numerous faculty have been experimenting with various approaches which are taking advantages of both technology and student interaction with technology, with various degrees of success. In this paper authors present another comprehensive method applied in teaching/learning of core engineering mechanics course. It has been observed over a long period of time that Dynamics is one of the more difficult courses in the Mechanical Engineering and Technology programs where students are experiencing certain difficulty in mastering the material. Authors integrated technology into learning experiences in order to stimulate and motivate students to master the material, which proved to be very successful. It has been observed that new approach improved the final scores in the course as well as student satisfaction with this approach of presenting material as well as testing their understanding of the required material. The paper presents results from two years of teaching the course with the current approach, along with lessons learned from this experience
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