Alinhamento primário e secundário de sequências biológicas em arquiteturas de alto desempenho

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Exatas, Departamento de Ciência da Computação, 2017.O alinhamento múltiplo primário de sequências biológicas é um problema muito importante em Biologia Molecular, pois permite que sejam detectadas similaridades e diferenças entre um conjunto de sequências. Esse problema foi provado NP-Completo e, por essa razão, geralmente algoritmos heurísticos são usados para resolvê-lo. No entanto, a obtenção da solução ótima é bastante desejada e, por essa razão, existem alguns algoritmos exatos que solucionam esse problema para um número reduzido de sequências. As sequências de RNA, diferente do DNA, não possuem dupla-hélice e podem dobrar-se, pois seus nucleotídeos podem formar pares de bases. É conhecido na Biologia Molecular que a função dessa estrutura está ligada à sua conformação espacial, e não à composição de seus nucleotídeos. Obter a estrutura secundária (2D) de uma sequência de RNA também exige uma grande quantidade de recursos computacionais, até mesmo para um pequeno número de sequências. Desta forma, as arquiteturas de alto desempenho são muito importantes para a obtenção dos resultados em um tempo factível. A presente tese visa investigar os problemas do alinhamento múltiplo primário e do alinhamento em pares secundário, utilizando arquiteturas de alto desempenho para acelerar a obtenção de resultados. Para o alinhamento primário ótimo de múltiplas sequências, propusemos na presente Tese o PA-Star, uma estratégia multithreaded baseada no algoritmo A-Star que usa uma política sensível à localidade de atribuição de trabalho às threads. De modo a lidar com o alto uso de memória, nossa estratégia PA-Star usa tanto memória RAM como disco. Para o alinhamento estrutural (2D) de sequências de RNA, propusemos o Foldalign 2.5, que é uma estratégia multithreaded heurística baseada no algoritmo exato de Sankoff, capaz de obter o alinhamento estrutural de grandes sequências em tempo reduzido. Finalmente, propusemos o CUDA-Sankoff, que é capaz de obter o alinhamento estrutural ótimo entre duas sequências de RNA em GPU (Graphics Processing Unit).Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).The primary multiple sequence Alignment is a very important problem in Molecular Biology since it is able to detect similarities and differences in a set of sequences. This problem has been proven NP-Hard and, for this reason, heuristic algorithms are usually used to solve it. Nevertheless, obtaining the optimal solution is highly desirable and there are indeed some exact algorithms that solve this problem for a reduced number of sequences. The RNA sequences are different than the DNA, they do not have double helix, their nucleotides can form base pairs and the sequence can fold on itself. It is known in the Molecular Biology that, the function of the RNA is related to its spatial structure. Calculating the secondary structure of RNA sequences also demand a high amount of computational resources, even for a small number of sequences. The High Performance Computing (HPC) Platforms can be used in order to produce results faster. The current thesis aims to investigate the primary multiple sequence alignment and the secondary pairwise sequence alignment, using High Performance Architectures to accelerate and obtaining results in reasonable time. For the primary multiple sequence alignment, we propose the PA-Star, a multithreaded solution based on the A-Star algorithm using a locality sensitive hash to distribute the workload among the threads. Due to the high RAM memory usage required by the algorithm, our strategy can also uses disk. For the RNA structural alignment, we proposed the Foldalign 2.5, a multithreaded solution that uses heuristics to reduce the Sankoff Algorithm complexity, and can obtain the pairwise structural alignment of large sequences in reduced time. Finally, we proposed CUDASankoff, that obtains the optimal pairwise structural alignment for RNA sequences using a GPU (Graphics Processing Unit)

Estratégia paralela exata para o alinhamento múlltiplo de sequências biológicas utilizando Unidades de Processamento Gráfico (GPU)

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Exatas, Departamento de Ciência da Computação, 2012.O alinhamento múltiplo de sequências biológicas é um problema muito importante em Biologia Molecular, pois permite que sejam detectadas similaridades e diferenças entre um conjunto de sequências. Esse problema foi provado NP-Difícil e, por essa razão, geralmente algoritmos heurísticos são usados para resolvê-lo. No entanto, a obtenção da solucão ótima é bastante desejada e, por essa razão, existem alguns algoritmos exatos que solucionam esse problema para um número reduzido de sequências. Dentre esses algoritmos, destaca-se o método exato Carrillo-Lipman, que permite reduzir o espaço de busca utilizando um limite inferior e superior. Mesmo com essa redução, o algoritmo com Carrillo-Lipman executa-se em tempo exponencial. Com o objetivo de acelerar a obtenção de resultados, plataformas computacionais de alto desempenho podem ser utilizadas para resolver o problema do alinhamento múltiplo. Dentre essas plataformas, destacam-se as Unidades de Processamento Gráfico (GPU) devido ao seu potencial para paralelismo massivo e baixo custo. O objetivo dessa dissertação de mestrado é propor e avaliar uma estratégia paralela para execução do algoritmo Carrillo-Lipman em GPU. A nossa estratégia permite a exploração do paralelismo em granularidade na, onde o espaço de busca é percorrido por várias threads em um cubo tridimensional, divido em janelas de processamento que são diagonais projetadas em duas dimensões. Os resultados obtidos com a comparação de conjuntos de 3 sequências reais e sintéticas de diversos tamanhos mostram que speedups de até 8,60x podem ser atingidos com a nossa estratégia. ______________________________________________________________________________ ABSTRACTMultiple Sequence Alignment is a very important problem in Molecular Biology since it is able to detect similarities and di erences in a set of sequences. This problem has been proven NP-Hard and, for this reason, heuristic algorithms are usually used to solve it. Nevertheless, obtaining the optimal solution is highly desirable and there are indeed some exact algorithms that solve this problemfor a reduced number of sequences. Carrillo-Lipman is a well-known exact algorithmfor the Multiple Sequence Alignment problemthat is able to reduce the search space by using inferior and superior bounds. Even with this reduction, the Carrillo-Lipman algorithm executes in exponential time. High Performance Computing (HPC) Platforms can be used in order to produce results faster. Among the existing HPC platforms, GPUs (Graphics Processing Units) are receiving a lot of attention due to their massive parallelism and low cost. The goal of this MsC dissertation is to propose and evaluate a parallel strategy to execute the Carrillo-Lipman algorithm in GPU. Our strategy explores parallelism at ne granularity, where the search space is a tridimensional cube, divided on processing windows with bidimensional diagonals, explored by multiple threads. The results obtained when comparing several sets of 3 real and synthetic sequences show that speedups of 8.60x can be obtained with our strategy

Genomic bases of non-syndromic basal cell carcinoma: literature review

Introduction: Non-melanoma skin neoplasms represent the most frequent type in both sexes globally, with basal cell carcinoma being the most prevalent, representing 75 to 80% of cases. In Brazil, the number of new cases expected for the triennium 2020-2022 will be 83,770 in men and 93,160 in women, corresponding to an estimated risk of 80.12 new cases for 100,000 men and 86.65 new cases for 100,000 women. This data demonstrates the great importance of genomic knowledge in the genesis of sporadic basal cell carcinoma. Objective: To describe the main genes and molecular markers involved in the predisposition and pathogenesis of non-syndromic basal cell carcinoma. Methods: Literature review in the main databases NCBI-GTR, ClinVar, ClinGen, MedGen, OMIM and GeneReviews, using as descriptors: "BCC" and "basal cell carcinoma". Inclusion criteria: Portuguese or EnGLIsh language, articles on sporadic BCC. Results: Thirteen articles were selected for analysis. The analysis revealed a robust hedgehog pathway link in the genesis of sporadic basal cell carcinoma, with the main genes involved represented by PATCH1, PATCH2 and smoothened. The variants with the highest clinical significance were SMO-M2, PTCH1 and PTCH2-Δ22. The mutation most found was related to the action of UVB, being represented by the substitution of C>T or CC>TT at the pyrimidine site, both in PTCH and in SMO. Conclusion: Extremely important to professionals working in the diagnosis and treatment of BCC, including plastic surgeons, as this way they can better conduct their cases, with more accurate diagnoses and prevention approaches based on the individual susceptibility of each patient, as well as targeted therapies and individualized with better success rates

Microabrasion in tooth enamel discoloration defects: three cases with long-term follow-ups

Superficial irregularities and certain intrinsic stains on the dental enamel surfaces can be resolved by enamel microabrasion, however, treatment for such defects need to be confined to the outermost regions of the enamel surface. Dental bleaching and resin-based composite repair are also often useful for certain situations for tooth color corrections. This article presented and discussed the indications and limitations of enamel microabrasion treatment. Three case reports treated by enamel microabrasion were also presented after 11, 20 and 23 years of follow-ups224347354sem informaçã

Microabrasion in tooth enamel discoloration defects: three cases with long-term follow-ups

Superficial irregularities and certain intrinsic stains on the dental enamel surfaces can be resolved by enamel microabrasion, however, treatment for such defects need to be confined to the outermost regions of the enamel surface. Dental bleaching and resin-based composite repair are also often useful for certain situations for tooth color corrections. This article presented and discussed the indications and limitations of enamel microabrasion treatment. Three case reports treated by enamel microabrasion were also presented after 11, 20 and 23 years of follow-ups

Conservative reconstruction of the smile by orthodontic, bleaching, and restorative procedures

The following is a clinical case report of a patient whose chief complaint was the presence of generalized spacing in the maxillary anterior segment following orthodontic treatment. After meticulous clinical analyses and discussions of the clinical procedures to be adopted, dental bleaching was performed in both arches with 10% hydrogen peroxide (Opalescence Trèswhite Supreme 10% Hydrogen Peroxide - Ultradent Products, Inc., South Jordan, USA) after the conclusion and stabilization of orthodontic treatment. Then, the orthodontic appliance was removed and the diastemas in the maxillary anterior teeth were closed with Amelogen Plus (Ultradent Products, Inc., South Jordan, USA) resin composite. It was observed that the association of orthodontic, bleaching, and restorative procedures was capable of restoring dental shape, function, and esthetics, allowing the patient to smile without hesitation

Influence of daily usage times on patients’ compliance during at-home bleaching : a randomized clinical trial

The effectiveness of at-home dental bleaching treatments depends on the time that bleaching products are in contact with the teeth surface and, consequently, on the adequate use of associated custom acetate trays. Objective: This randomized single-blinded trial aimed to analyze if the daily usage time of these products influences the patient’s compliance behavior when submitted to monitored at-home dental bleaching. Secondary outcomes were color change and tooth sensitivity. Methodology: Sixty-six volunteers were randomly distributed into three groups (n=22): patients were instructed to use the trays for 2 (G2), 4 (G4), and 8 (G8) hours daily. The daily dental bleaching compliance behavior was measured using a microsensor inserted into the trays. Subjective and objective color evaluation assessments were adopted at baseline (T0), one (T1), two (T2), and three weeks (T3) after the beginning of the bleaching treatment, as well as two weeks after the treatment (T4). Tooth sensitivity was analyzed using the VAS scale, ranging from T1 to T4. Results: G2 showed a greater degree of cooperation than G8 and cooperation was inversely proportional to the recommended usage time. Significantly higher color change was observed in the upper arch for G8 when compared to G2 in subjective analysis, from T1 to T4. There were no statistical differences between the groups in objective analysis. Conclusion: Shorter recommended usage time of the bleaching product may improve the patient's compliance with at-home dental bleaching treatments. However, increased daily usage time may promote better subjective color change. Bleaching sensitivity was more significant in the first week for a longer time of use

Foldalign 2.5:multithreaded implementation for pairwise structural RNA alignment

Motivation: Structured RNAs can be hard to search for as they often are not well conserved in their primary structure and are local in their genomic or transcriptomic context. Thus, the need for tools which in particular can make local structural alignments of RNAs is only increasing. Results: To meet the demand for both large-scale screens and hands on analysis through web servers, we present a new multithreaded version of Foldalign. We substantially improve execution time while maintaining all previous functionalities, including carrying out local structural alignments of sequences with low similarity. Furthermore, the improvements allow for comparing longer RNAs and increasing the sequence length. For example, lengths in the range 2000–6000 nucleotides improve execution up to a factor of five. Availability and implementation: The Foldalign software and the web server are available at http://rth.dk/resources/foldalign Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

The Effect Of Hydrofluoric Acid Concentration And Heat On The Bonding To Lithium Disilicate Glass Ceramic

The aim of this study was to evaluate the effects of hydrofluoric acid (HF) concentration and previous heat treatment (PHT) on the surface morphology and micro-shear bond strength (mSBS) of a lithium disilicate glass ceramic (EMX) to resin cement. One hundred four EMX specimens were randomly assigned to two groups (n=52) according to the HF concentration: 5% and 10%. A new random distribution was made according to the PHTs (n=13): control (no PHT); previously heated HF (70 °C); previously heated EMX surface (85 °C); the combination of heated HF + heated EMX surface. The etching time was set at 20 s. All EMX blocks were silanated and received a thin layer of an unfilled resin. Five resin cement cylinders were made on each EMX surface using Tygon tubes as matrices, and then stored for 24 h at 37 °C. One random etched EMX sample from each group was analyzed using field-emission scanning electron microscopy (FE-SEM). The data were subjected to two-way ANOVA and multiple comparisons were performed using the Tukey post hoc test (a=0.05). For the control groups, 5% HF showed statistically lower mSBS values when compared to 10% HF (p<0.05). PHT increased the mSBS values for 5% HF, yielding statistically similar results to non-PHT 10% HF (p<0.05). FE-SEM images showed increased glassy matrix removal when PHT was applied to HF 5%, but not to the same degree as for 10% HF. PHT has the potential to improve the bond strength of 5% HF concentration on lithium disilicate glass ceramic.27672773

Oxandrolone use in adult burn patients. Systematic review and meta-analysis

PURPOSE:This study is a systematic literature review and meta-analysis concerning the use of a testosterone synthetic analog, oxandrolone, and its use in severe adult burns.METHODS:Randomized prospective clinical studies, in English, Portuguese or Spanish, were sought on the following databases: MEDLINE, COCHRANE, EMBASE and LILACS. There was no restriction in relation to the publication date.RESULTS: This search produced 24 studies on MEDLINE and twelve articles were presented on the COCHRANE database .Sixteen were excluded due to the title not being related to this search or by including children. Of the eigth residual studies, after adaptation to the inclusion criteria, only four were selected. After analyzing the results, two were discarded since they did not present adequate patient characterization and the facts on these articles were analyzed differently from the others, hindering the meta-analysis.CONCLUSION:The analysis of the available data demonstrated significant benefits (p<0.05) considering lesser loss of corporal mass, lesser nitrogen loss, and shorter donor area healing time, when Oxandrolone was used, comparatively with the control group (placebo or not).Federal University of São PauloUNIFESPSciEL