79 research outputs found

    DNA Computing: Modelling in Formal Languages and Combinatorics on Words, and Complexity Estimation

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    DNA computing, an essential area of unconventional computing research, encodes problems using DNA molecules and solves them using biological processes. This thesis contributes to the theoretical research in DNA computing by modelling biological processes as computations and by studying formal language and combinatorics on words concepts motivated by DNA processes. It also contributes to the experimental research in DNA computing by a scaling comparison between DNA computing and other models of computation. First, for theoretical DNA computing research, we propose a new word operation inspired by a DNA wet lab protocol called cross-pairing polymerase chain reaction (XPCR). We define and study a word operation called word blending that models and generalizes an unexpected outcome of XPCR. The input words are uwx and ywv that share a non-empty overlap w, and the output is the word uwv. Closure properties of the Chomsky families of languages under this operation and its iterated version, the existence of a solution to equations involving this operation, and its state complexity are studied. To follow the XPCR experimental requirement closely, a new word operation called conjugate word blending is defined, where the subwords x and y are required to be identical. Closure properties of the Chomsky families of languages under this operation and the XPCR experiments that motivate and implement it are presented. Second, we generalize the sequence of Fibonacci words inspired by biological concepts on DNA. The sequence of Fibonacci words is an infinite sequence of words obtained from two initial letters f(1) = a and f(2)= b, by the recursive definition f(n+2) = f(n+1)*f(n), for all positive integers n, where * denotes word concatenation. After we propose a unified terminology for different types of Fibonacci words and corresponding results in the extensive literature on the topic, we define and explore involutive Fibonacci words motivated by ideas stemming from theoretical studies of DNA computing. The relationship between different involutive Fibonacci words and their borderedness and primitivity are studied. Third, we analyze the practicability of DNA computing experiments since DNA computing and other unconventional computing methods that solve computationally challenging problems often have the limitation that the space of potential solutions grows exponentially with their sizes. For such problems, DNA computing algorithms may achieve a linear time complexity with an exponential space complexity as a trade-off. Using the subset sum problem as the benchmark problem, we present a scaling comparison of the DNA computing (DNA-C) approach with the network biocomputing (NB-C) and the electronic computing (E-C) approaches, where the volume, computing time, and energy required, relative to the input size, are compared. Our analysis shows that E-C uses a tiny volume compared to that required by DNA-C and NB-C, at the cost of the E-C computing time being outperformed first by DNA-C and then by NB-C. In addition, NB-C appears to be more energy efficient than DNA-C for some input sets, and E-C is always an order of magnitude less energy efficient than DNA-C

    RAPD-based detection of genomic instability in cucumber plants derived from somatic embryogenesis

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    Random amplified polymorphic DNA (RAPD) markers were used to evaluate genetic stability of regenerants of cucumber plants obtained through somatic embryogenesis. Somatic embryo plants and plants of F1 hybrids, from which they were derived, were compared during weaning, early growth, flowering, fruiting and at maturity. No differences in phenotype were observed, by simple observation. Banding patterns were scored for the presence (+) or absence (-) of a DNA band, there were no visually detectable differences between the somatic embryo derived plants compared to their F1 parents in the Random Amplified Polymorphic DNA (RAPD) test using five primers OP-C10, OP-G14, OP-H05, OP-Y03 and OP-AT01. The results indicate the usefulness of RAPD markers to detect genetic instability in cucumber primary regenerant plants derived from somatic embryogenesis, and as a certification tool for monitoring genetic stability during the generation process

    Association of Short Tandem Repeat Polymorphism in the Promoter of Prostate Cancer Antigen 3 Gene with the Risk of Prostate Cancer

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    BACKGROUND: PCA3 (prostate cancer antigen 3) gene is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 mRNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In our study, we evaluated whether there is polymorphism in PCA3 promoter region and also assess the association of the polymorphism with prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: We designed a specific primer set to screen the promoter of PCA3 gene by polymerase chain reaction (PCR)-based cloning and sequencing with the DNA extracted from peripheral blood samples of prostate cancer (PCa) cases (n = 186) and healthy control cases (n = 135). Genotype-specific risks were estimated as odds ratios (ORs) with associated 95% confidence intervals (CIs) by chi-square test. Possible deviation of the genotype frequencies from controls and PCa cases expected under Hardy-Weinberg equilibrium was assessed by the chi-square test. Short tandem repeat polymorphism of TAAA was found in the promoter region of PCA3 gene, five polymorphisms and eight genotypes were identified. The eight genotypes were divided into three groups: ≤10TAAA, 11TAAA, ≥12TAAA. The group 11TAAA and ≥12TAAA were associated with higher relative risk for prostate cancer than group ≤10TAAA (OR = 1.76, 95%CI = 1.07-2.89[for group 11TAAA]; OR = 5.28, 95%CI = 1.76-15.89[for group ≥12TAAA]). CONCLUSIONS/SIGNIFICANCE: The presence of the (TAAA)n short tandem repeat polymorphisms in the PCA3 promoter region may be a risk factor for prostate cancer in the Chinese population

    Formal models of the extension activity of DNA polymerase enzymes

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    The study of formal language operations inspired by enzymatic actions on DNA is part of ongoing efforts to provide a formal framework and rigorous treatment of DNA-based information and DNA-based computation. Other studies along these lines include theoretical explorations of splicing systems, insertion-deletion systems, substitution, hairpin extension, hairpin reduction, superposition, overlapping concatenation, conditional concatenation, contextual intra- and intermolecular recombinations, as well as template-guided recombination. First, a formal language operation is proposed and investigated, inspired by the naturally occurring phenomenon of DNA primer extension by a DNA-template-directed DNA polymerase enzyme. Given two DNA strings u and v, where the shorter string v (called the primer) is Watson-Crick complementary and can thus bind to a substring of the longer string u (called the template) the result of the primer extension is a DNA string that is complementary to a suffix of the template which starts at the binding position of the primer. The operation of DNA primer extension can be abstracted as a binary operation on two formal languages: a template language L1 and a primer language L2. This language operation is called L1-directed extension of L2 and the closure properties of various language classes, including the classes in the Chomsky hierarchy, are studied under directed extension. Furthermore, the question of finding necessary and sufficient conditions for a given language of target strings to be generated from a given template language when the primer language is unknown is answered. The canonic inverse of directed extension is used in order to obtain the optimal solution (the minimal primer language) to this question. The second research project investigates properties of the binary string and language operation overlap assembly as defined by Csuhaj-Varju, Petre and Vaszil as a formal model of the linear self-assembly of DNA strands: The overlap assembly of two strings, xy and yz, which share an overlap y, results in the string xyz. In this context, we investigate overlap assembly and its properties: closure properties of various language families under this operation, and related decision problems. A theoretical analysis of the possible use of iterated overlap assembly to generate combinatorial DNA libraries is also given. The third research project continues the exploration of the properties of the overlap assembly operation by investigating closure properties of various language classes under iterated overlap assembly, and the decidability of the completeness of a language. The problem of deciding whether a given string is terminal with respect to a language, and the problem of deciding if a given language can be generated by an overlap assembly operation of two other given languages are also investigated

    Single nucleotide polymorphism detection by polymerase chain reaction-restriction fragment length polymorphism

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    ArticleNATURE PROTOCOLS. 2(11): 2857-2864 (2007)journal articl

    Detection and identification methods and new tests as developed and used in the framework of cost 873 for bacteria pathogenic to stone fruits and nuts

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    Xanthomonas arboricola pv. pruni (Xap), the causal agent of bacterial spot disease of stone fruits and almond, is regulated as a quarantine pathogen in the European Union and the European and Mediterranean Plant Protection Organization (EPPO). Xap can have an epiphytic phase and/or be latent and, consequently, it can be transmitted by different types of plant material. Effective quarantine measures require specific, sensitive and rapid methods to detect Xap in propagative material or new reservoirs. Laborious and time-consuming methods for the diagnosis of Xap are recommended in the current EPPO standard protocol. However, new several pathogen-specific PCR and quantitative realtime PCR assays have been developed that enable direct detection of Xap in symptomatic and symptomless plant samples. A concise resource of current methods for Xap detection and identification, based on assessment and development activities within the framework of COST 873, is presented

    Microsatellite fingerprinting of grapevine (Vitis vinifera L.) varieties of the Carpathian Basin

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    Altogether 101 Vitis vinifera L. genotypes were analysed at 6 microsatellite loci (Scu8vv, Scu10vv, VVMD21, VVMD36, ssrVRZAG64, ssrVRZAG79). Ninety-seven were autochthonous accessions of the Carpathian Basin and 4 were international cultivars. The allele composition and sizes obtained with the 6 microsatellite primer pairs were appropriate for discrimination of 95 cultivars. Berry colour-variants of cvs Gohér (Gohér fehér-white and Gohér piros-red), Lisztes (Lisztes fehér and Lisztes piros) as well as the cvs Bakator (Bakator piros and Bakator tüdőszín - light red) were exceptions.

    Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): Study protocol for a multicenter randomized Phase II non-inferiority clinical trial

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    Background: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials.Methods/design: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018.Conclusion: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood.Fil: Molina Morant, D.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Fernández, M. L.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; ArgentinaFil: Bosch Nicolau, P.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Sulleiro, E.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Bangher, M.. Instituto de Cardiologia de Corrientes Juana Francisca Cabral.; ArgentinaFil: Salvador, F.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Sanchez Montalva, A.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Ribeiro, A.L.P.. Universidade Federal de Minas Gerais; BrasilFil: De Paula, A.M.B.. Universidad Federal de Montes Claros; BrasilFil: Eloi, S.. Universidade Federal de Minas Gerais; BrasilFil: Oliveira Correa, Ronaldo. Fundación Oswaldo Cruz; BrasilFil: Villar, J. C.. Instituto de Cardiología; ColombiaFil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Molina, I.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; Españ

    Chimeric binding peptide library screening method

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