Short Deoxyribonucleic Acid Research Articles

Specificity of DNA damage formation induced by femtosecond near-infrared laser filamentation in water

We investigated the deoxyribonucleic acid (DNA) damage induced by laser filamentation, which was generated by focusing femtosecond near-infrared Ti:Sapphire laser light in water at several repetition rates ranging from 1000 Hz to 10 Hz. Using plasmid DNA (pUC19), the single-strand break, double-strand break, nucleobase lesions, and the fragmented DNA were analyzed and quantified by agarose gel electrophoresis. Additionally, the H2O2 concentration after irradiation was determined. We observed that (1) the DNA damage per laser shot and (2) the enzyme-sensitive base lesions per total DNA damage decreased as the laser repetition rate increased. Furthermore, (3) extraordinarily short DNA fragments were likely to be produced, compared with those produced using X-rays, and (4) most OH radicals could be eliminated by recombination to generate H2O2, preventing them from damaging the DNA. The Monte-Carlo simulation of the strand break formation implies that the observed dependency of strand break efficiency on the laser repetition rate is mainly due to diffusion of DNA molecules. These findings quantitatively and qualitatively revealed that an intense laser pulse induces a specific DNA damage profile that is not induced by X-rays, a sparsely ionizing radiation source.

Design and simulation of a wireframe DNA origami nanoactuator.

This paper explores the use of deoxyribonucleic acid (DNA) origami structures as nanorobot components. Investigating the functional properties of DNA origami structures can facilitate the fabrication of DNA origami-based nanorobots. The wireframe structure stands out as one of the most interesting DNA origami structures. Hence, the present study aims to employ these structures to create DNA origami nanoactuators. The research delves into the design of DNA origami structures with the aim of opening under specific temperature conditions. Short DNA strands (staples) are one of the crucial parts of DNA origami structures, and the appropriate design of these strands can lead to the creation of structures with different properties. Thus, the components of the DNA origami nanoactuator are tailored to enable intentional opening at specific temperatures while maintaining stability at lower temperatures. This structural modification showcases the functional property of the DNA origami structure. The engineered DNA origami nanoactuator holds potential applications in medicine. By carrying drugs under specific temperature conditions and releasing them under different temperature conditions, it can serve as a platform for smart drug delivery purposes.

Monte Carlo-Based Nanoscale Dosimetry Holds Promise for Radiopharmaceutical Therapy Involving Auger Electron Emitters.

Radiopharmaceutical therapy (RPT) is evolving as a promising strategy for treating cancer. As interest grows in short-range particles, like Auger electrons, understanding the dose-response relationship at the deoxyribonucleic acid (DNA) level has become essential. In this study, we used the Geant4-DNA toolkit to evaluate DNA damage caused by the Auger-electron-emitting isotope I-125. We compared the energy deposition and single strand break (SSB) yield at each base pair location in a short B-form DNA (B-DNA) geometry with existing simulation and experimental data, considering both physical direct and chemical indirect hits. Additionally, we evaluated dosimetric differences between our high-resolution B-DNA target and a previously published simple B-DNA geometry. Overall, our benchmarking results for SSB yield from I-125 decay exhibited good agreement with both simulation and experimental data. Using this simulation, we then evaluated the SSB and double strand break (DSB) yields caused by a theranostic Br-77-labeled poly ADP ribose polymerase (PARP) inhibitor radiopharmaceutical. The results indicated a predominant contribution of chemical indirect hits over physical direct hits in generating SSB and DSB. This study lays the foundation for future investigations into the nano-dosimetric properties of RPT.

Pre-analytical Associated Factors of Foreign DNA Detection Beneath Deceased’s Fingernails

Objective: To assess the pre-analytical factors including hand-side, representative collection technique and individual forensic physician for foreign deoxyribonucleic acid (DNA) detection in specimen collected from deceased’s fingernails. Material and Methods: This cross-sectional study, of an initial 164 samples from the fingernails of both hands, of 82 deceased caseworks; from 2010 to 2018, at the Forensic Unit, Faculty of Medicine, Prince of Songkla University. The autosomal short tandem repeats profile fingernail DNA results, pre-analytical factors, and the deceased’s characteristics were obtained from the records. The fingernail DNA outcomes were evaluated and ranked into five groups, i.e., high-level profile, low-level profile, or residual profile; if foreign alleles of more than 11 alleles, 4 to 11 alleles, or less than 4 alleles were detected, respectively. The non-specific profile group consisted of foreign DNA being detected; however the peak signals were below the decisional threshold. The unidentified group consisted of no foreign DNA being detected. The full model underwent both directional stepwise model selection, and the resulting model with the lowest Akaike information criterion was selected as the final model. The final model was analyzed by ordinal logistic regression for significant associated factors: at a 95% confidence level. Results: The representative collection technique is an associated factor, via the use of fingernail swabs (adjusted odds ratio (ORa)=13.44, 95% confidence interval (CI)=2.89–62.45), and had a larger effect size than using fingernail cuttings (ORa=6.84, 95% CI=1.47–31.86). Conclusion: At post-mortem examination, for the collection of foreign DNA from fingernails, the use of fingernail swabs, as a collection technique, is of particular interest.

Entropy of DNA sequences and leukemia patients mortality

Introduction. Deoxyribonucleic acid (DNA) is not a random sequence of four nucleotides combinations: comprehensive reviews [1, 2] persuasively shows long- and short-range correlations in DNA, periodic properties and correlations structure of sequences. Information theory methods, like Entropy, imply quantifying the amount of information contained in sequences. the relationship between entropy and patient survival is widespread in some branches of medicine and medical researches: cardiology, neurology, surgery, trauma. Therefore, it appears there is a necessity for implementing advantages of information theory methods for exploration of relationship between mortality of some category of patients and entropy of their DNA sequences. Aim of the research. The goal of this paper is to provide a reliable formula for calculating entropy accurately for short DNA sequences and to show how to use existing entropy analysis to examine the mortality of leukemia patients. Materials and Methods. We used University of Barcelona (UB) leukemia patient’s data base (DB) with 117 anonymized records that consists: Date of patient’s diagnosis, Date of patient’s death, Leukemia diagnoses, Patient’s DNA sequence. Average time for patient death after diagnoses: 99 ± 77 months. The formal characteristics of DNA sequences in UB leukemia patient’s DB are: average number of bases N = 496 ± 69; min (N) = 297 bases; max(N) = 745 bases. The generalized form of the Robust Entropy Estimator (EnRE) for short DNA sequences was proposed and key EnRE futures was showed. The Survival Analysis has been done using statistical package IBM SPSS 27 by Kaplan-Meier survival analysis and Cox Regressions survival modelling. Results. The accuracy of the proposed EnRE for calculating entropy was proved for various lengths of time series and various types of random distributions. It was shown, that in all cases for N = 500, relative error in calculating the precise value of entropy does not exceed 1 %, while the magnitude of correlation is no worse than 0.995. In order to yield the minimum EnRE standard deviation and coefficient of variation, an initial DNA sequence's alphabet code was converted into an integer code of bases using an optimization rule for only one minimal numerical decoding around zero. Entropy EnRE were calculated for leukemia patients for two samples: 2 groups divided by median EnRE = 1.47 and 2 groups of patients were formed according to their belonging to 1st (EnRE ≤ 1.448) and 4th (EnRE ≥ 1.490) quartiles. The result of Kaplan-Meier survival analysis and Cox Regressions survival modelling are statistically significant: p < 0,05 for median groups and p < 0,005 for patient’s groups formed of 1st and 4th quartiles. The death hazard for a patient with EnRE below median is 1.556 times that of a patient with EnRE over median and that the death hazard for a patient of 1st entropy quartile (lowest EnRE) is 2.143 times that of a patient of 4th entropy quartile (highest EnRE). Conclusions. The transition from widen (median) to smaller (quartile) patients’ groups with more EnRE differentiation confirmed the unique significance of the entropy of DNA sequences for leukemia patient’s mortality. This significance is proved statistically by increasing hazard and decreasing of average time of death after diagnoses for leukemia patients with lower entropy of DNA sequences.

The use of touch DNA analysis in forensic identification focusing on Short Tandem Repeat- Combined DNA Index System loci THO1, CSF1PO and TPOX.

Forensic identification through DNA analysis is an accurate diagnostic tool. Deoxyribonucleic Acid (DNA) analysis is via DNA repetitive regions with less than 1 kb base size is called ‘microsatellite’ or Short Tandem Repeat (STR). At the crime scene, the perpetrator’s skin may accidentally be in contact with surrounding objects, thereby transferring trace evidence to the objects. In this study DNA was obtained using “touch DNA” from two buccal smears and two smear from watches and cellphones from volunteers who had signed the consent form. Samples were isolated using DNAzol. The quantity of DNA obtained will be measured using a UV spectrophotometer. For DNA amplification using 3 STR CODIS loci namely TH01, CSF1PO, and TPOX. The last step is visualization using acrylamide gel and silver staining. Mean levels of DNA (UVVisible Spectrophotometer) were 167.89±85.71 μg/mL for the buccal swab, 59.19±5.58 μg/mL for the watch swab, and 38.09±2.12 μg/mL for the mobile swab; the purity of the buccal swab DNA was 1.79±0.71, of the watch swab 1.69±0.76, and of the mobile swab 1.53±0.56. Visualization of PCR products on Polyacrylamide Agarose Composite Gel Electrophoresis stained with Silver and amplified using the standard primers THOI, TPOX and CSF1PO for STR Combined DNA Index System (CODIS) showed a 100% detection of amplicons. Both the buccal swab, watch swab and handphone swabs had trace amount of DNA that was sufficient to be isolated and amplified by using Polymerase Chain Reaction on the STR CODIS loci THO1, CSF1PO and TPOX.

Poly[oligo(ethylene glycol) methacrylate]-b-poly[(vinyl benzyl trimethylammonium chloride)] Based Multifunctional Hybrid Nanostructures Encapsulating Magnetic Nanoparticles and DNA.

We report on the preparation of novel and multifunctional hybrid spherical-shaped nanostructures involving a double-hydrophilic block copolymer, namely the neutral cationic poly[oligo(ethylene glycol) methacrylate]-b-poly[(vinyl benzyl trimethylammonium chloride)] (POEGMA-b-PVBTMAC) diblock copolymer, initially complexed with hydrophilic anionic magnetic nanoparticles (MNPs), and subsequently, with short deoxyribonucleic acid (113 bases DNA). The POEGMA-b-PVBTMAC copolymer, the copolymer/MNPs and the copolymer/MNPs/DNA tricomponent hybrid electrostatic complexes were studied by dynamic/electrophoretic light scattering (DLS/ELS) and cryogenic transmission electron microscopy (cryo-TEM) techniques for the determination of their structure and solution properties. The MNPs were complexed efficiently with the oppositely charged diblock chains, leading to well-defined hybrid organic–inorganic spherical-shaped nanostructures. A significant aggregation tendency of the MNPs is noticed in cryo-TEM measurements after the electrostatic complexation of DNA, implying an accumulation of the DNA macromolecules on the surface of the hybrid tricomponent complexes. Magnetophoretic experiments verified that the MNPs maintain their magnetic properties after the complexation initially with the copolymer, and subsequently, within the block polyelectrolyte/MNPs/DNA nanostructures.

Ensemble of Deep Recurrent Neural Networks for Identifying Enhancers via Dinucleotide Physicochemical Properties.

Enhancers are short deoxyribonucleic acid fragments that assume an important part in the genetic process of gene expression. Due to their possibly distant location relative to the gene that is acted upon, the identification of enhancers is difficult. There are many published works focused on identifying enhancers based on their sequence information, however, the resulting performance still requires improvements. Using deep learning methods, this study proposes a model ensemble of classifiers for predicting enhancers based on deep recurrent neural networks. The input features of deep ensemble networks were generated from six types of dinucleotide physicochemical properties, which had outperformed the other features. In summary, our model which used this ensemble approach could identify enhancers with achieved sensitivity of 75.5%, specificity of 76%, accuracy of 75.5%, and MCC of 0.51. For classifying enhancers into strong or weak sequences, our model reached sensitivity of 83.15%, specificity of 45.61%, accuracy of 68.49%, and MCC of 0.312. Compared to the benchmark result, our results had higher performance in term of most measurement metrics. The results showed that deep model ensembles hold the potential for improving on the best results achieved to date using shallow machine learning methods.

Screening of Oligonucleotide Aptamers and Application in Detection of Pesticide and Veterinary Drug Residues

Aptamers are a type of single stranded short deoxyribonucleic acid or ribonucleic acid sequences screened from a random oligonucleotide library, which have high affinity and specific recognition for specific target molecules. Since the advent of screening process called the systematic evolution of ligands by exponential enrichment (SELEX), there have been various SELEX-based improved screening processes and capillary electrophoresis-based SELEX or non-SELEX selection processes. As a molecular recognition element similar to antibody, aptamers have been applied to the detection of residues of pesticide and veterinary drugs associated with food and environmental safety. In these applications, aptamers are usually formed composite probes with other materials to produce signals, such as gold nanoparticles, quantum dots, or constitute sensors with electrochemical electrode. These screening methods and the applications of aptamers in the detection of pesticide and veterinary drug residues are summarized to provide a helpful reference for these issues.

Design of a Low-cost Hydrogel made of RNA-origami for 3D Bioprinting Applications

Hydrogels are three-dimensional polymer networks that swell to some extent in aqueous solutions (Ahmed et al. 2015). Their physical properties allow for applications ranging from contact lenses, wound dressing, drug delivery and tissue engineering (Calo et al. 2015). The latter application requires biocompatible and biodegradable hydrogels that are designed to have sufficient mechanical strength and stability in human physiological conditions to allow time for cells to build their own scaffold. Nucleic acid-based hydrogels have already proven their efficiency and a variety of designs have been explored since the first deoxyribonucleic acid (DNA) hydrogel was published (Um et al. 2006). DNA-hydrogels were reported to assemble using mixtures of anywhere from 1 to 5 oligomers. For instance, 3 oligomers forming a Y-shape structure are mixed with a linker solution consisting of 2 complementary oligomers with overhangs that may bridge the Y-shapes together (Xing et al. 2011). DNA-origamis may also be generated from stapling the single-stranded genome of the M13 phage with short DNA oligomers to make it to adopt pre-designed 2D- or 3D-structures (Rothemund et al. 2006, Dietz et al. 2009). However, the production of single-stranded DNA remains extremely costly and most of these experiments cannot be conducted on the larger scales necessary to assess biocompatibility with cell cultures. Ribonucleic acid (RNA), an intermediary compound in the genetic flow of information is mainly produced in single-stranded form, and may be mass-produced in any laboratory by in vitro transcription using recombinant T7 RNA polymerase from bacteriophage, and a double-stranded DNA template obtained by molecular cloning. The use of an RNA-hydrogel would therefore allow for properties similar to those of DNA-hydrogels at a fraction of the cost. So far, only one study succeeded in producing what they call an RNA hydrogel (Huang et al. 2017). They report the chance discovery of an RNA aptamer that self-assembles into a viscoelastic solution at low temperature (5°C). Ideally, the hydrogel should exist at body temperature (37ºC) and gelation should be controllable by some trigger, such as pH, temperature, light, or the mixing of two solutions for downstream 3D printing applications. We designed a simple X-structure using 2 RNA oligomers that bind to each other using a complementary sequence. This type of configuration was reported previously for a DNA hydrogel called “Takumi” using 33-mers that bind to each other by a 13-nt complementary sequence (Nishida et al. 2016). Using custom code and biopython (Cock et al. 2009), we generated 2,000 random RNA blocks of 20 nucleotides (nt) with melting temperatures between 58°C and 62°C to increase our chances of obtaining a gel that is stable at physiological temperature. These building blocks of 20nt were assembled at random into 60nt-long oligomers to form a library. Each oligo was associated with a partner for which the middle 20nt block is the reverse complement sequence (Fig. 1A). The sequences were then tested using RNAfold included in the Galaxy RNA Workbench (Access et al. 2011, Afgan et al. 2016) and the sequences sorted by folding energy (∆G) to rule out intramolecular secondary structures. The best candidate RNA oligomer pairs were double-checked using the freely available OligoCalc (Kibbe et al. 2007) and Multiple Primer Dimer Analyzer (Thermo Fisher Scientific, Inc.) to rule out any RNA oligomers with unwanted intra- or intermolecular structures. Finally, we modelled the binding of the two RNA oligomers using simRNA (Bioniecki et al. 2015), a coarse-grained model specialized for RNA structures. The different conformations clustered to show possible interaction behaviors in 3D. Fig. 1C shows the 3D model of the sequences we finally selected. The design was first tested with DNA oligomers mixed at an equimolar concentration of 500µM each. The mixture was then subjected to a step-down temperature gradient in a thermocycler, starting at 95°C for 5 min and cooled down in steps of 2°C every 3min20s until the solution reached room temperature (21°C). The solution obtained was viscoelastic and remained on one side of the tube after flicking. We are currently working on the optimization of the gelation process and the mass production of RNA. Figure 1

The kinetics of force-dependent hybridization and strand-peeling of short DNA fragments

Deoxyribonucleic acid (DNA) carries the genetic information in all living organisms. It consists of two interwound single-stranded (ss) strands, forming a double-stranded (ds) DNA with a right-handed double-helical conformation. The two strands are held together by highly specific basepairing interactions and are further stabilized by stacking between adjacent basepairs. A transition from a dsDNA to two separated ssDNA is called melting and the reverse transition is called hybridization. Applying a tensile force to a dsDNA can result in a particular type of DNA melting, during which one ssDNA strand is peeled away from the other. In this work, we studied the kinetics of strand-peeling and hybridization of short DNA under tensile forces. Our results show that the force-dependent strand-peeling and hybridization can be described with a simple two-state model. Importantly, detailed analysis of the force-dependent transition rates revealed that the transition state consists of several basepairs dsDNA.

Photo-thermal effects in gold nanorods/DNA complexes

An ingenious combination of plasmonic nanomaterials and one of the most relevant biological systems, deoxyribonucleic acid (DNA) is achieved by bioconjugating gold nanorods (GNRs) with DNA via electrostatic interaction between positively charged GNRs and negatively charged short DNA. The obtained system is investigated as a function of DNA concentration by means of gel electrophoresis, zeta-potential, DNA melting and morphological analysis. It turns out that the obtained bioconjugated systems present both effective electric charge and aggregate size that are particularly amenable for gene therapy and nanomedicine applications. Finally, the effect of the localized (photo-thermal heating) and delocalized temperature variation on the DNA melting by performing both light induced bio-transparent optical heating experiments and a thermographic analysis is investigated, demonstrating that the developed system can be exploited for monitoring nanoscale temperature variation under optical illumination with very high sensitivity.

Haloarcula hispanica CRISPR authenticates PAM of a target sequence to prime discriminative adaptation.

The prokaryotic immune system CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated genes) adapts to foreign invaders by acquiring their short deoxyribonucleic acid (DNA) fragments as spacers, which guide subsequent interference to foreign nucleic acids based on sequence matching. The adaptation mechanism avoiding acquiring ‘self’ DNA fragments is poorly understood. In Haloarcula hispanica, we previously showed that CRISPR adaptation requires being primed by a pre-existing spacer partially matching the invader DNA. Here, we further demonstrate that flanking a fully-matched target sequence, a functional PAM (protospacer adjacent motif) is still required to prime adaptation. Interestingly, interference utilizes only four PAM sequences, whereas adaptation-priming tolerates as many as 23 PAM sequences. This relaxed PAM selectivity explains how adaptation-priming maximizes its tolerance of PAM mutations (that escape interference) while avoiding mis-targeting the spacer DNA within CRISPR locus. We propose that the primed adaptation, which hitches and cooperates with the interference pathway, distinguishes target from non-target by CRISPR ribonucleic acid guidance and PAM recognition.

DNA Barcode of Thief Ant Complex (Hymenoptera: Formicidae)

The thief ant, Solenopsis molesta (Say), a common nuisance species found throughout the United States is genetically related to red imported fire ants, S. invicta Buren. Therefore, its identification at the molecular level is very important. The deoxyribonucleic acid (DNA) barcoding, a recent technique was used to identify thief ant complex at species and subspecies levels using a short DNA sequence from the cytochrome oxidase subunit 1 (COI) mitochondrial region. The DNA from thief ants collected from 9 states was extracted using Qiagen's Gentra PUREGENE® DNA Isolation Kit. The polymerase chain reactions (PCR) were run on the extracted DNA to amplify partial sequence of COI using primers Lep-F1 (forward) and Lep-R1 (reverse). The resulting DNA products were concentrated, purified and sequenced. The 600 bp sequences of the COI generated were submitted to GenBank that issued accessions numbers from HM179641 to HM179653. The sequences associated with these accession numbers were used as DNA barcodes for distinguishing species and subspecies. Based on this molecular analysis, thief ants collected from New York, Indiana and 1 location in Nebraska were separated in 1 group as S. molesta validiuscula (Emery) and another with ants from Louisiana identified as S. carolinensis (Forel). The third group was comprised of ants from South Dakota, Washington, New Jersey, Tennessee, Kansas and 2 other locations in Nebraska was identified as S. molesta molesta (Say).

Nanowire Fabrication by DNA Metallization and Positioning

Deoxyribonucleic acid (DNA) has the appropriate molecular recognition property that makes it a suitable building block for the construction of nanoscale electronic devices. In particular, DNA employed as conducting wires is expected to be an alternative to optical lithography, which has resolution limits and requires high cost steppers. Nano-oxidation experiments were conducted on a silicon substrate by atomic force microscopy (AFM) to produce nanosized dots as anchors for DNA fixing. Short strand DNA molecules were then fixed on the anchors, which can recognize a specific complementary sequence. After the substrate was treated with a solution containing specific DNAs, which can hybridize with the short strand DNAs at the DNA sticky end, the anchors were connected to the DNAs by a self-assembly processes of DNA hybridization. Finally, silver was plated along the DNA molecules by a chemical treatment to introduce electrical conductivity. This method is expected to have potential for the integration of nanosized building blocks applicable to nanodevice construction.

Alignment of the columnar liquid crystal phase of nano-DNA by confinement in channels

We demonstrate that topographic confinement in micro-channels can produce aligned domains of the columnar liquid crystal phase of complementary duplex short deoxyribonucleic acid (DNA) oligomers. Optical microscopy probing birefringence and fluorescence polarisation showed that the columnar liquid crystal phase of a 1:1 mixture of the complementary dodecamers 5′–CCTCAAAACTCC–3′ and 5′–GGAGTTTTGAGG–3′ in aqueous solution was aligned with the duplex DNA chains oriented normal to the channel axis.

Species identification of Rhododendron (Ericaceae) using the chloroplast deoxyribonucleic acid PsbA-trnH genetic marker.

Background:Rhododendron is a group of famous landscape plants with high medicinal value. However, there is no simple or universal manner to discriminate the various species of this group. Deoxyribonucleic acid (DNA) barcoding technique is a new biological tool that can accurately and objectively identify species by using short and standard DNA regions.Objective:To choose a suitable DNA marker to authenticate the Rhododendron species.Materials and Methods:Four candidate DNA barcodes (rbcL, matK, psbAtrnH, and ITS2 intergenic spacer) were tested on 68 samples of 38 species.Results:The psbAtrnH candidate barcode yielded 86.8% sequencing efficiency. The highest interspecific divergence was provided by the psbA-trnH intergenic spacer, based on six parameters, and the Wilcoxon signed rank tests. Although there was not a clear barcoding gap, the Wilcoxon Two sample tests indicated that the interspecific divergence of the psbA-trnH intergenic spacer was significantly higher than the relevant intraspecific variation. The psbA-trnH DNA barcode possessed the highest species identification efficiency at 100% by the BLAST1 method. The present results showed that the psbA-trnH intergenic spacer was the most promising one of the four markers for barcoding the Rhododendron species. To further evaluate the ability of the psbA-trnH marker, to discriminate the closely related species, the samples were expanded to 94 samples of 53 species in the genus, and the rate of successful identification was 93.6%. The psbA-trnH region would be useful even for unidentified samples, as it could significantly narrow their possible taxa to a small area.Conclusion:The psbA-trnH intergenic region is a valuable DNA marker for identifying the Rhododendron species.

Electrophoresis of long deoxyribonucleic acid in curved channels: The effect of channel width on migration dynamics

We investigated the dynamics of long deoxyribonucleic acid (DNA) migrating through curved channels under electric fields. Long DNA exhibits large conformational changes in the curved channels because of the inhomogeneity of the electric fields around curves. Two kinds of channel shapes were used for the examination. One (type I) has the same width in the curved region as in the straight region. The other (type II) is wider in the curved region than in the straight region. The difference in migration rates between long DNA and short DNA was larger in type II than in type I chips. We discuss the separation mechanism of the type II chip.

Theoretical Prescriptions for Improving Conductances of Short DNA Segments Sandwiched between Metal Electrodes

In the band-resonant tunneling regime, we studied by theoretical simulations the effects of mechanical deformation and gate modulation on the electronic transport properties through short (34 Å-long) deoxyribonucleic acid (DNA) segments sandwiched between two aluminum electrodes. We found that the structural deformation of DNA, such as the tilting of the guanine (G)–cytosine (C) base pairs, causes the upper shifts of their occupied energy levels. When these energy levels cross the Fermi level and the excess charge flows out to the electrodes, the hole is injected into the G–C base pairs, dominantly into the guanine array. In addition, we found that by applying the negative gate bias voltages, the occupied energy levels are raised across the Fermi level and the hole is injected into the guanine array. By these carrier injections, the conductances of the short DNA molecule improve dramatically in both cases.

Functional bioinformatics of microarray data: from expression to regulation

Using microarrays is a powerful technique to monitor the expression of thousands of genes in a single experiment. From series of such experiments, it is possible to identify the mechanisms that govern the activation of genes in an organism. Short deoxyribonucleic acid patterns (called binding sites) near the genes serve as switches that control gene expression. As a result similar patterns of expression can correspond to similar binding site patterns. Here we integrate clustering of coexpressed genes with the discovery of binding motifs. We overview several important clustering techniques and present a clustering algorithm (called adaptive quality-based clustering), which we have developed to address several shortcomings of existing methods. We overview the different techniques for motif finding, in particular the technique of Gibbs sampling, and we present several extensions of this technique in our Motif Sampler. Finally, we present an integrated web tool called INCLUSive (available online at http://www.esat.kuleuven.ac.be//spl sim/dna/BioI/Software.html) that allows the easy analysis of microarray data for motif finding.