Characterization of dengue virus serotype 1 in epidemics in Porto Velho, Rondônia, in 2001-2003

The first dengue fever epidemic in the State of Rondônia (western region of Brazil) was recorded in 1997, without laboratory confirmation. Following this, there was an epidemic in Manaus, in the neighboring State of Amazon, in 1998, in which DENV-1 and DENV-2 viruses were isolated from patients. In the present paper, the serotype characterization of the dengue virus isolated from patients with clinically suspected dengue in Porto Velho, Rondônia, between 2001 and 2003 is described. One hundred and fifty blood samples were collected between the first and fifth days of symptoms. Seventy samples of virus isolates were subjected to dengue identification by means of RT-PCR using universal primers for the NS1 gene of DENV, which amplifies a 419 bp fragment. The amplicons obtained were subjected to enzymatic digestion to characterize the viral serotypes. All the samples analyzed were DENV-1. A nucleotide sequence randomly selected from one amplicon, which was also DENV-1, presented 98% similarity to sequences from Southeast Asia that were obtained from GenBank.

Genetic characterization of rabies virus isolated from bovines and equines between 2007 and 2008, in the States of São Paulo and Minas Gerais

INTRODUCTION: Rabies is an acute disease of the central nervous system and is responsible for the deaths of thousands of humans, wild animals and livestock, particularly cattle, as well as causing major economic losses. This study describes the genetic characterization of rabies virus variants that circulate in Desmodus rotundus populations and are transmitted to herbivores. METHODS: Fifty rabies virus isolates from bovines and equines in the States of São Paulo and Minas Gerais, Brazil, were genetically characterized and compared with sequences retrieved from GenBank. RESULTS: Two clusters (I and II) with mean nucleotide identities of 99.1 and 97.6% were found. The first of these contained nearly all the samples analyzed. Lineages from other Brazilian states grouped in cluster II. CONCLUSIONS: Analysis of the amino acid sequences of the N proteins revealed the existence of genetic markers that may indicate possible variations between geographic regions, although the biologically active regions are conserved within the species over space and time.

Development and validation of gold nanoprobes for human SNP detection towards commercial application

Conventional molecular techniques for detection and characterization of relevant nucleic acid (i.e. DNA) sequences are, nowadays, cumbersome, expensive and with reduced portability. The main objective of this dissertation consisted in the optimization and validation of a fast and low-cost colorimetric nanodiagnostic methodology for the detection of single nucleotide polymorphisms (SNPs). This was done considering SNPs associated to obesity of commercial interest for STAB VIDA, and subsequent evaluation of other clinically relevant targets. Also, integration of this methodology into a microfluidic platform envisaging portability and application on points-of-care (POC) was achieved. To warrant success in pursuing these objectives, the experimental work was divided in four sections: i) genetic association of SNPs to obesity in the Portuguese population; ii) optimization and validation of the non-cross-linking approach for complete genotype characterization of these SNPs; iii) incorporation into a microfluidic platform; and iv) translation to other relevant commercial targets. FTO dbSNP rs#:9939609 carriers had higher body mass index (BMI), total body fat mass, waist perimeter and 2.5 times higher risk to obesity. AuNPs functionalized with thiolated oligonucleotides (Au-nanoprobes) were used via the non-cross-linking to validate a diagnostics approach against the gold standard technique - Sanger Sequencing - with high levels of sensitivity (87.50%) and specificity (91.67%). A proof-of-concept POC microfluidic device was assembled towards incorporation of the molecular detection strategy. In conclusion a successful framework was developed and validated for the detection of SNPs with commercial interest for STAB VIDA, towards future translation into a POC device.

Learning joint representations for order and timing of perceptual-motor sequences: a dynamic neural field approach

Many of our everyday tasks require the control of the serial order and the timing of component actions. Using the dynamic neural field (DNF) framework, we address the learning of representations that support the performance of precisely time action sequences. In continuation of previous modeling work and robotics implementations, we ask specifically the question how feedback about executed actions might be used by the learning system to fine tune a joint memory representation of the ordinal and the temporal structure which has been initially acquired by observation. The perceptual memory is represented by a self-stabilized, multi-bump activity pattern of neurons encoding instances of a sensory event (e.g., color, position or pitch) which guides sequence learning. The strength of the population representation of each event is a function of elapsed time since sequence onset. We propose and test in simulations a simple learning rule that detects a mismatch between the expected and realized timing of events and adapts the activation strengths in order to compensate for the movement time needed to achieve the desired effect. The simulation results show that the effector-specific memory representation can be robustly recalled. We discuss the impact of the fast, activation-based learning that the DNF framework provides for robotics applications.

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.

Crosscorrelation properties between perfect sequences

Binary sequence, perfect sequence, autocorrelation, crosscorrelation, Hadamard transform

Characteristics of the P2Y 11 nucleotide receptor : ligand binding characteristics and P2Y 11-P2Y 1 receptor

Purinergic receptors, nucleotides, P2Y, diastereoselectivity, potency, mutagenesis, ligand recognition, heterooligomerization, endocytosis, co-pulldown

Hand gesture spotting and recognition using HMMs and CRFs in color image sequences

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2010

Vision-based representation and recognition of human activities in image sequences

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2013

Low autocorrelation sequences and flat polynomials

Magdeburg, Univ., Fak. für Mathematik, Habil.-Schr., 2014

Analysis of functional impairments of the human P2Y 11 nucleotide receptor with the alanine-87 - threonine mutation, and development of novel agonists specific for the human P2Y 11 and P2Y 6 receptors

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2015

A nonlinear threshold model for the dependence of extremes of stationary sequences

One of the main implications of the efficient market hypothesis (EMH) is that expected future returns on financial assets are not predictable if investors are risk neutral. In this paper we argue that financial time series offer more information than that this hypothesis seems to supply. In particular we postulate that runs of very large returns can be predictable for small time periods. In order to prove this we propose a TAR(3,1)-GARCH(1,1) model that is able to describe two different types of extreme events: a first type generated by large uncertainty regimes where runs of extremes are not predictable and a second type where extremes come from isolated dread/joy events. This model is new in the literature in nonlinear processes. Its novelty resides on two features of the model that make it different from previous TAR methodologies. The regimes are motivated by the occurrence of extreme values and the threshold variable is defined by the shock affecting the process in the preceding period. In this way this model is able to uncover dependence and clustering of extremes in high as well as in low volatility periods. This model is tested with data from General Motors stocks prices corresponding to two crises that had a substantial impact in financial markets worldwide; the Black Monday of October 1987 and September 11th, 2001. By analyzing the periods around these crises we find evidence of statistical significance of our model and thereby of predictability of extremes for September 11th but not for Black Monday. These findings support the hypotheses of a big negative event producing runs of negative returns in the first case, and of the burst of a worldwide stock market bubble in the second example. JEL classification: C12; C15; C22; C51 Keywords and Phrases: asymmetries, crises, extreme values, hypothesis testing, leverage effect, nonlinearities, threshold models

Effect of single nucleotide polymorphisms in cytochrome P450 isoenzyme and N-acetyltransferase 2 genes on the metabolism of artemisinin-based combination therapies in malaria patients from Cambodia and Tanzania.

The pharmacogenetics of antimalarial agents are poorly known, although the application of pharmacogenetics might be critical in optimizing treatment. This population pharmacokinetic-pharmacogenetic study aimed at assessing the effects of single nucleotide polymorphisms (SNPs) in cytochrome P450 isoenzyme genes (CYP, namely, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) and the N-acetyltransferase 2 gene (NAT2) on the pharmacokinetics of artemisinin-based combination therapies in 150 Tanzanian patients treated with artemether-lumefantrine, 64 Cambodian patients treated with artesunate-mefloquine, and 61 Cambodian patients treated with dihydroartemisinin-piperaquine. The frequency of SNPs varied with the enzyme and the population. Higher frequencies of mutant alleles were found in Cambodians than Tanzanians for CYP2C9*3, CYP2D6*10 (100C → T), CYP3A5*3, NAT2*6, and NAT2*7. In contrast, higher frequencies of mutant alleles were found in Tanzanians for CYP2D6*17 (1023C → T and 2850C → T), CYP3A4*1B, NAT2*5, and NAT2*14. For 8 SNPs, no significant differences in frequencies were observed. In the genetic-based population pharmacokinetic analyses, none of the SNPs improved model fit. This suggests that pharmacogenetic data need not be included in appropriate first-line treatments with the current artemisinin derivatives and quinolines for uncomplicated malaria in specific populations. However, it cannot be ruled out that our results represent isolated findings, and therefore more studies in different populations, ideally with the same artemisinin-based combination therapies, are needed to evaluate the influence of pharmacogenetic factors on the clearance of antimalarials.

Segmentation and Clustering of Textual Sequences: a Typological Approach

The long term goal of this research is to develop a program able to produce an automatic segmentation and categorization of textual sequences into discourse types. In this preliminary contribution, we present the construction of an algorithm which takes a segmented text as input and attempts to produce a categorization of sequences, such as narrative, argumentative, descriptive and so on. Also, this work aims at investigating a possible convergence between the typological approach developed in particular in the field of text and discourse analysis in French by Adam (2008) and Bronckart (1997) and unsupervised statistical learning.