The capsid proteins VP2 and VP3 of infectious bursal disease virus, a birnavirus, are derived fro... more The capsid proteins VP2 and VP3 of infectious bursal disease virus, a birnavirus, are derived from the processing of a large polyprotein: NH2-pVP2-VP4-VP3-COOH. Although the primary cleavage sites at the pVP2-VP4 and VP4-VP3 junctions have been identified, the proteolytic cascade involved in the processing of this polyprotein is not yet fully understood, particularly the maturation of pVP2. By using different approaches, we showed that the processing of pVP2 (residues 1 to 512) generated VP2 and four small peptides (residues 442 to 487, 488 to 494, 495 to 501, and 502 to 512). We also showed that in addition to VP2, at least three of these peptides (residues 442 to 487, 488 to 494, and 502 to 512) were associated with the viral particles. The importance of the small peptides in the virus cycle was assessed by reverse genetics. Our results showed that the mutants lacking the two smaller peptides were viable, although the virus growth was affected. In contrast, deletions of the domain...
Reconciling scene realism with interactivity has emerged as one of the most important areas in ma... more Reconciling scene realism with interactivity has emerged as one of the most important areas in making virtual reality feasible for large-scale mechanical CAD datasets consisting of several millions of primitives. This paper surveys our research and related work for achieving interactivity without sacri cing realism in virtual reality w alkthroughs and ythroughs of polygonal CAD datasets. We outline our recent w ork on e cient generation of triangle strips from polygonal models that takes advantage of compression of connectivity information. This results in substantial savings in rendering, transmission, and storage. We outline our work on genus-reducing simpli cations as well as real-time view-dependent simpli cations that allow on-they selection amongst multiple levels of detail, based upon lighting and viewing parameters. Our method allows multiple levels of detail to coexist on the same object at di erent regions and to merge seamlessly without any cracks or shading artifacts. We also present a n o v erview of our work on hardware-assisted imagebased rendering that allows interactive exploration of computergenerated scenes.
2018 IEEE International Conference on Fuzzy Systems (FUZZ-IEEE), 2018
In this paper, we propose an approach to automatic detection of attacks on computer networks usin... more In this paper, we propose an approach to automatic detection of attacks on computer networks using data that combine the traffic generated with 'live' intra-cloud virtual-machine (VM) migration. The method used in this work is the recently introduced typicality and eccentricity data analytics (TEDA) framework. We compare the results of applying TEDA with the traditionally used methods such as statistical analysis, such as k-means clustering. One of the biggest challenges in computer network analysis using statistical or numerical methods is the fact that the protocol information is composed of integer/string values and, thus, not easy to handle by traditional pattern recognition methods that deal with real values. In this study we consider as features the tuple {IP source, IP destination, Port source and Port destination} extracted from the network flow data in addition to the traditionally used real values that represent the number of packets per time or quantity of bytes per time. Using entropy of the IP data helps to convert the integer raw data into real valued signatures. The proposed solution permit to build a real-time anomaly detection system and reduce the number of information that is necessary for evaluation. In general, the systems based on traffic are fast and are used in real time but they do not produce good results in attacks that produce a flow hidden within the background traffic or within a high traffic that is produced by other application. We validate our approach an a dataset which includes attacks on the network port scan (NPS) and network scan (NS) that permit hidden flow within the normal traffic and see this attacks together with live migration which produces a higher traffic flow.
Background: Pneumatization of the anterior clinoid process (ACP) affects paraclinoid region surge... more Background: Pneumatization of the anterior clinoid process (ACP) affects paraclinoid region surgery, this anatomical variation occurs in 6.6–27.7% of individuals, making its preoperative recognition essential given the need for correction based on the anatomy of the pneumatized process. This study was conducted to evaluate the reproducibility of an optic strut-based ACP pneumatization classification by presenting radiological examinations to a group of surgeons. Methods: Thirty cranial computer tomography (CT) scans performed from 2013 to 2014 were selected for analysis by neurosurgery residents and neurosurgeons. The evaluators received Google Forms with questionnaires on each scan, DICOM files to be manipulated in the Horos software for multiplanar reconstruction, and a collection of slides demonstrating the steps for classifying each type of ACP pneumatization. Interobserver agreement was calculated by the Fleiss kappa test. Results: Thirty CT scans were analyzed by 37 evaluators...
In this paper we propose an algorithm for online clustering of data stream. This algorithm is cal... more In this paper we propose an algorithm for online clustering of data stream. This algorithm is called AutoCloud and it is based on the recently introduced concept of Typicality and Eccentricity Data Analytics, mainly used for anomaly detection tasks. AutoCloud is an evolving, online and recursive technique that does not need training or prior knowledge about the data set to be processed. Thus, AutoCloud is fully online, requiring no offline processing. It allows creation and merging of clusters in an autonomous manner as new data observations become available. The clusters created by AutoCloud are called data clouds, which are structures without pre-defined shape or boundaries. Auto-Cloud allows each data sample to belong to multiple data clouds simultaneously using fuzzy concepts. AutoCloud is also able to handle concept drift and concept evolution, which are problems that are inherent to data streams in general. Since the algorithm is recursive and online, its suitable for applications that requires real-time
Genome-Scale Metabolic Models have shown promising results in biomedical applications, such as un... more Genome-Scale Metabolic Models have shown promising results in biomedical applications, such as understanding cancer metabolism and drug discovery. However, to take full advantage of these models there is the need to address the representation and simulation of the metabolic phenotypes of distinct cell types. With this aim, several algorithms have been recently proposed to reconstruct tissue-specific metabolic models based on available data. Here, the most promising were implemented and used to reconstruct models for two case studies, using omics data from distinct sources. The set of obtained models were compared and analyzed, being shown they are highly variable and that no combination of algorithm and data source can achieve models with acceptable phenotype predictions. We propose an algorithm to achieve a consensus model from the set of models available for a given tissue/cell line, and to improve it given functional data (e.g. known metabolic tasks). The results show that the re...
Didelphis albiventris, gambá-de-orelha-branca, é um marsupial de hábitos crepusculares e noturnos... more Didelphis albiventris, gambá-de-orelha-branca, é um marsupial de hábitos crepusculares e noturnos que se alimenta de frutos, insetos, pequenos répteis e anfíbios, filhotes de aves e pequenos mamíferos. Com a destruição de seu "habitat" natural devido às queimadas e desmatamentos, esses animais têm-se aproximado, cada vez mais, das regiões peridomiciliar e domiciliar, onde procuram abrigo e alimentos. Com o objetivo de conhecer a diversidade de parasitos de D. albiventris e relatar os que apresentam potencial zoonótico, foram examinados 30 exemplares desta espécie, através de necropsia, para coleta de ectoparasitos da superfície externa do corpo e helmintos dos órgãos e conteúdos estomacal e intestinal. Os sifonápteros foram removidos da superfície externa dos animais, conservados em álcool etílico a 70°GL, clarificados em líquido de Nesbitt, desidratados em etanol, diafanizados em creosoto de Faya e montados em lâminas com bálsamo do Canadá para identificação. Os carrapatos foram removidos da superfície externa dos animais, conservados em álcool etílico a 70°GL e identificados ao estereomicroscópio, segundo chaves específicas de Aragão & Fonseca (1961) e Guimarães et al. (2001). Os helmintos foram recolhidos com auxílio de estiletes e pinças, clarificados em lactofenol e montados entre lâminas e lamínulas com bálsamo do Canadá para identificação ao microscópio. Do total de animais examinados, 70% estavam infestados com pulgas das espécies Polygenis (Neopolygenis) atopus, Polygenis (Polygenis) rimatus, Polygenis (Polygenis) roberti roberti, Polygenis (Polygenis) sp., Craneopsylla minerva minerva e Ctenocephalides felis felis, todas essas registradas pela primeira vez sobre D. albiventris e, exceto C. felis felis, são também registradas pela primeira vez no estado do Rio Grande do Sul. Carrapatos foram encontrados em 43,33% dos animais examinados, representados pelas espécies Ixodes loricatus, Amblyomma aureolatum e Amblyomma sp, sendo A. aureolatum registrado pela primeira vez parasitando D. albiventris no Brasil. Os helmintos encontrados foram: Filo Nematoda-Capillaria spp. (esôfago, traquéia, faringe e pulmão), Didelphostrongylus hayesi (pulmão), Turgida turgida (estômago), Gnathostoma sp. (estômago e fígado), Travassostrongylus orloffi, Viannaia hamata e Trichuris minuta no intestino delgado e Trichuris didelphis, Cruzia tentaculata e Aspidodera raillieti no intestino grosso; Classe Trematoda-Echinostoma revolutum, Plagiorchis didelphidis, Rhopalias coronatus, R. baculifer, Brachylaema migrans e Didelphodiplostomum variabile, todos no intestino delgado; Classe Cestoda-exemplares da família Diphyllobotriidae, no intestino delgado; e Filo Acanthocephala-Hamanniella microcephala e Centrorhynchus sp., ambos no intestino delgado. Dos helmintos encontrados, os que apresentam potencial zoonótico segundo a literatura são T. turgida, Gnathostoma sp., Capillaria spp., B. migrans, E. revolutum e Família Diphyllobotriidae. Além disso, os sifonápteros e ixodídeos encontrados são potenciais vetores de patógenos que infectam humanos. D. albiventris, portanto, apresenta grande diversidade parasitária, incluindo espécies que podem potencialmente atingir o homem, alertando para a importância destes marsupiais na disseminação de doenças entre animais e humanos.
Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting speci... more Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown. WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional effects and . Phospho-kinase arrays and TCF/LEF reporter assays were used to identify WNT6-signaling pathways, and significant associations with stem cell features and cancer-related pathways were validated in patients. Survival analyses were performed with Cox regression and Log-rank tests. Meta-analyses were used to calculate the estimated pooled effect. We show that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6 increases typi...
Intracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the... more Intracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the world and these ruptures are associated with a high mortality. Some risk factors, such as age, gender, smoking, alcohol, hypertension and familial history are associated with the number of aneurysms and their size. In addition, inflammatory processes within the blood vessels of the brain can activate matrix metalloproteinase-9 (MMP-9), which degrades various components of the extracellular matrix, such as elastin. Thereby, this work has aimed at evaluating the relationship between plasma MMP-9 levels and the risk factors that are associated with intracranial aneurysm, as well as investigating the aneurysm statuses (ruptured and unruptured) and comparing them with the control volunteers. Between August 2014 to June 2016, blood samples were collected from 282 patients (204 ruptured and 78 unruptured saccular intracranial aneurysms) and 286 control volunteers. The MMP-9 plasma levels were ...
Develop a platform composed of labeled dendrimer nanoparticles (NPs) and a microfluidic device fo... more Develop a platform composed of labeled dendrimer nanoparticles (NPs) and a microfluidic device for real-time monitoring of cancer cells fate. Carboxymethylchitosan/poly(amidoamine) dendrimer NPs were labeled with fluorescein-5(6)-isothiocyanate and characterized using different physicochemical techniques. After, HeLa, HCT-116 and U87MG were cultured in the presence of NPs, and cell viability and internalization efficiency in static (standard culture) and dynamic (microfluidic culture) conditions were investigated. Cancer cells cultured with NPs in dynamic conditions were viable and presented higher internalization levels as compared with static 2D cultures. This work demonstrated that the proposed microfluidic-based platform allows real-time monitoring, which upon more studies, namely, the assessment of an anticancer drug release effect could be used for cancer theranostics.
2016 IEEE Conference on Evolving and Adaptive Intelligent Systems (EAIS), 2016
In this paper, we propose a new approach to fuzzy data clustering. We present a new algorithm, ca... more In this paper, we propose a new approach to fuzzy data clustering. We present a new algorithm, called TEDA-Cloud, based on the recently introduced TEDA approach to outlier detection. TEDA-Cloud is a statistical method based on the concepts of typicality and eccentricity able to group similar data observations. Instead of the traditional concept of clusters, the data is grouped in the form of granular unities called data clouds, which are structures with no pre-defined shape or set boundaries. TEDA-Cloud is a fully autonomous and self-evolving algorithm that can be used for data clustering of online data streams and applications that require real-time response. Since it is fully autonomous, TEDA-Cloud is able to "start from scratch" (from an empty knowledge basis), create, update and merge data clouds, in a fully autonomous manner, without requiring any user-defined parameters (e.g. number of clusters, size, radius) or previous training. Moreover, TEDA-Cloud, unlike most of the traditional statistical approaches, does not rely on a specific data distribution or on the assumption of independence of data samples. The results, obtained from multiple data sets that are very well known in literature, are very encouraging.
2015 IEEE International Conference on Fuzzy Systems (FUZZ-IEEE), 2015
Outlier detection is a problem that has been largely studied in the past few years due to its gre... more Outlier detection is a problem that has been largely studied in the past few years due to its great applicability in real world problems (e.g. financial, social, climate, security). Fault detection in industrial processes is one of these problems. In that context, several methods have been proposed in literature to address fault detection. In this paper we propose a comparative analysis of three recently introduced outlier detection methods: RDE, RDE with Forgetting and TEDA. Such methods were applied to the data set provided in DAMADICS benchmark, a very well-known real data tool for fault detection applications. The results, however, can be extended to similar problems of the area. Therewith, in this work we compare the main features of each method as well as the results obtained with them.
International Journal of Developmental Neuroscience, 2015
Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investig... more Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome −46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55 ± 0.38) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98 ± 0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the deregulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic deregulation of the MECP2 may be present in other RTT-like patients.
Glioblastoma is the most malignant brain tumor, exhibiting remarkable resistance to treatment. He... more Glioblastoma is the most malignant brain tumor, exhibiting remarkable resistance to treatment. Here we investigated the oncogenic potential of HOXA9 in gliomagenesis, the molecular and cellular mechanisms by which HOXA9 renders glioblastoma more aggressive, and how HOXA9 affects response to chemotherapy and survival. The prognostic value of HOXA9 in glioblastoma patients was validated in two large datasets from TCGA and Rembrandt, where high HOXA9 levels were associated with shorter survival. Transcriptomic analyses identified novel HOXA9-target genes with key roles in cancer-related processes, including cell proliferation, DNA repair, and stem cell maintenance. Functional studies with HOXA9-overexpressing and HOXA9-silenced glioblastoma cell models revealed that HOXA9 promotes cell viability, stemness and invasion, and inhibits apoptosis. Additionally, HOXA9 promoted the malignant transformation of human immortalized astrocytes in an orthotopic in vivo model, and caused tumor-assoc...
We characterized tellina virus 1 (TV-1), a birnavirus isolated from the marine bivalve mollusk Te... more We characterized tellina virus 1 (TV-1), a birnavirus isolated from the marine bivalve mollusk Tellina tenuis. Genome sequence analysis established that TV-1 is representative of a viral cluster distant from other birnaviruses. The maturation process of the polyprotein encoded by the genomic segment A was delineated with the identification of the N-termini of the viral protease VP4 and the ribonucleoprotein VP3, and the characterization of peptides deriving from the processing of pVP2, the VP2 capsid protein precursor. One of these peptides was shown to possess a membrane-disrupting domain. Like the blotched snakehead virus, the polyprotein exhibits a non-structural polypeptide (named [X]) located between pVP2 and VP4. Mutagenesis analysis allowed the identification in VP4 of a catalytic Ser-Lys dyad that does not possess the common Gly-X-Ser signature of the serine hydrolases. The genomic segment B encodes the viral RNA-dependent RNA-polymerase VP1 with the unique sequence motif arrangement identified in other birnavirus VP1s.
In this paper we introduce the concept of a graphical object, the abstraction paradigms to study ... more In this paper we introduce the concept of a graphical object, the abstraction paradigms to study them, as well as their applications in computer graphics. Intuitively, a graphical object encompasses all the entities which are manipulated in a graphics system. This notion makes it possible to unify similar research topics that have appeared in the literature in a rather separated way. As an application, we use the concept of a graphical object to study the problem of object metamorphosis, which includes as a particular case the problem of image metamorphosis. Although we are not primarily concerned with implementation issues in this paper, the concepts we introduce can be exploited for systems design and development using object oriented programming.
Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus... more Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrif icus. A common gene ancestry and structural similarity with the antimicrobial β-defensins (identical disulfide bond pattern and highly positive net charge) suggested potential antimicrobial activities for this snake toxin. Although crotamine demonstrated low activity against both Gram-positive and Gram-negative bacteria, a pronounced antifungal activity was observed against Candida spp., Trichosporon spp., and Cryptococcus neoformans. Crotamine's selective antimicrobial properties, with no observable hemolytic activity, stimulated us to evaluate the potential applications of this polypeptide as an antiyeast or candicidal agent for medical and industrial application. Aiming to understand the mechanism(s) of action underlying crotamine antimicrobial activity and its selectivity for fungi, we present herein studies using membrane model systems (i.e., large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs), with different phospholipid compositions. We show here that crotamine presents a higher lytic activity on negatively charged membranes compared with neutral membranes, with or without cholesterol or ergosterol content. The vesicle burst was not preceded by membrane permeabilization as is generally observed for pore forming peptides. Although such a property of disrupting lipid membranes is very important to combat multiresistant fungi, no inhibitory activity was observed for crotamine against biofilms formed by several Candida spp. strains, except for a limited effect against C. krusei biofilm.
Table of conTenTs 6... DACA aneurysm locations 6..2. Aneurysm size and dome orientation 6... Aneu... more Table of conTenTs 6... DACA aneurysm locations 6..2. Aneurysm size and dome orientation 6... Aneurysm base and associated branches 6..4. ACA anomalies 6..5. Associated aneurysms and AVMs 6..6. ICHs from ruptured DACA aneurysms 6..7. Imaging of DACA aneurysms and CTA 6.2. treatment of Daca aneurysms 6.2.. Clipping of DACA aneurysms 6.2.2. Coiling of DACA aneurysms 6.3. outcome 6... Ruptured DACA aneurysms 6.3.1.1. One year outcome 6.3.1.2. Predictors of outcome at one year 6.3.1.3. Neurological deficits 6..2. Unruptured DACA aneurysms 6.4. long-term follow-uP 6.4.. Rebleeding from clipped DACA aneurysms 6.4.2. Recurrent SAH and de novo aneurysms 6.4.. Mortality 6.4.4. Excess mortality 6.4.5. Long-term angiographic screening 8 6.5. future trenDs 7. Conclusions List of 12 supplementary videos on microneurosurgery of DACA aneurysms Acknowledgments
The capsid of infectious bursal disease virus (IBDV), a nonenveloped virus of the family Birnavir... more The capsid of infectious bursal disease virus (IBDV), a nonenveloped virus of the family Birnaviridae , has a T=13l icosahedral shell constituted by a single protein, VP2, and several disordered peptides, all derived from the precursor pVP2. In this study, we show that two of the peptides, pep11 and pep46, control virus assembly and cell entry. Deletion of pep11 or even simple substitution of most of its residues blocks the capsid morphogenesis. Removal of pep46 also prevents capsid assembly but leads to the formation of subviral particles formed by unprocessed VP2 species. Fitting with the VP2 atomic model into three-dimensional reconstructions of these particles demonstrates that the presence of uncleaved pep46 causes a steric hindrance at the vertices, blocking fivefold axis formation. Mutagenesis of the pVP2 maturation sites confirms that C terminus processing is necessary for VP2 to acquire the correct icosahedral architecture. All peptides present on virions are accessible to ...
The capsid proteins VP2 and VP3 of infectious bursal disease virus, a birnavirus, are derived fro... more The capsid proteins VP2 and VP3 of infectious bursal disease virus, a birnavirus, are derived from the processing of a large polyprotein: NH2-pVP2-VP4-VP3-COOH. Although the primary cleavage sites at the pVP2-VP4 and VP4-VP3 junctions have been identified, the proteolytic cascade involved in the processing of this polyprotein is not yet fully understood, particularly the maturation of pVP2. By using different approaches, we showed that the processing of pVP2 (residues 1 to 512) generated VP2 and four small peptides (residues 442 to 487, 488 to 494, 495 to 501, and 502 to 512). We also showed that in addition to VP2, at least three of these peptides (residues 442 to 487, 488 to 494, and 502 to 512) were associated with the viral particles. The importance of the small peptides in the virus cycle was assessed by reverse genetics. Our results showed that the mutants lacking the two smaller peptides were viable, although the virus growth was affected. In contrast, deletions of the domain...
Reconciling scene realism with interactivity has emerged as one of the most important areas in ma... more Reconciling scene realism with interactivity has emerged as one of the most important areas in making virtual reality feasible for large-scale mechanical CAD datasets consisting of several millions of primitives. This paper surveys our research and related work for achieving interactivity without sacri cing realism in virtual reality w alkthroughs and ythroughs of polygonal CAD datasets. We outline our recent w ork on e cient generation of triangle strips from polygonal models that takes advantage of compression of connectivity information. This results in substantial savings in rendering, transmission, and storage. We outline our work on genus-reducing simpli cations as well as real-time view-dependent simpli cations that allow on-they selection amongst multiple levels of detail, based upon lighting and viewing parameters. Our method allows multiple levels of detail to coexist on the same object at di erent regions and to merge seamlessly without any cracks or shading artifacts. We also present a n o v erview of our work on hardware-assisted imagebased rendering that allows interactive exploration of computergenerated scenes.
2018 IEEE International Conference on Fuzzy Systems (FUZZ-IEEE), 2018
In this paper, we propose an approach to automatic detection of attacks on computer networks usin... more In this paper, we propose an approach to automatic detection of attacks on computer networks using data that combine the traffic generated with 'live' intra-cloud virtual-machine (VM) migration. The method used in this work is the recently introduced typicality and eccentricity data analytics (TEDA) framework. We compare the results of applying TEDA with the traditionally used methods such as statistical analysis, such as k-means clustering. One of the biggest challenges in computer network analysis using statistical or numerical methods is the fact that the protocol information is composed of integer/string values and, thus, not easy to handle by traditional pattern recognition methods that deal with real values. In this study we consider as features the tuple {IP source, IP destination, Port source and Port destination} extracted from the network flow data in addition to the traditionally used real values that represent the number of packets per time or quantity of bytes per time. Using entropy of the IP data helps to convert the integer raw data into real valued signatures. The proposed solution permit to build a real-time anomaly detection system and reduce the number of information that is necessary for evaluation. In general, the systems based on traffic are fast and are used in real time but they do not produce good results in attacks that produce a flow hidden within the background traffic or within a high traffic that is produced by other application. We validate our approach an a dataset which includes attacks on the network port scan (NPS) and network scan (NS) that permit hidden flow within the normal traffic and see this attacks together with live migration which produces a higher traffic flow.
Background: Pneumatization of the anterior clinoid process (ACP) affects paraclinoid region surge... more Background: Pneumatization of the anterior clinoid process (ACP) affects paraclinoid region surgery, this anatomical variation occurs in 6.6–27.7% of individuals, making its preoperative recognition essential given the need for correction based on the anatomy of the pneumatized process. This study was conducted to evaluate the reproducibility of an optic strut-based ACP pneumatization classification by presenting radiological examinations to a group of surgeons. Methods: Thirty cranial computer tomography (CT) scans performed from 2013 to 2014 were selected for analysis by neurosurgery residents and neurosurgeons. The evaluators received Google Forms with questionnaires on each scan, DICOM files to be manipulated in the Horos software for multiplanar reconstruction, and a collection of slides demonstrating the steps for classifying each type of ACP pneumatization. Interobserver agreement was calculated by the Fleiss kappa test. Results: Thirty CT scans were analyzed by 37 evaluators...
In this paper we propose an algorithm for online clustering of data stream. This algorithm is cal... more In this paper we propose an algorithm for online clustering of data stream. This algorithm is called AutoCloud and it is based on the recently introduced concept of Typicality and Eccentricity Data Analytics, mainly used for anomaly detection tasks. AutoCloud is an evolving, online and recursive technique that does not need training or prior knowledge about the data set to be processed. Thus, AutoCloud is fully online, requiring no offline processing. It allows creation and merging of clusters in an autonomous manner as new data observations become available. The clusters created by AutoCloud are called data clouds, which are structures without pre-defined shape or boundaries. Auto-Cloud allows each data sample to belong to multiple data clouds simultaneously using fuzzy concepts. AutoCloud is also able to handle concept drift and concept evolution, which are problems that are inherent to data streams in general. Since the algorithm is recursive and online, its suitable for applications that requires real-time
Genome-Scale Metabolic Models have shown promising results in biomedical applications, such as un... more Genome-Scale Metabolic Models have shown promising results in biomedical applications, such as understanding cancer metabolism and drug discovery. However, to take full advantage of these models there is the need to address the representation and simulation of the metabolic phenotypes of distinct cell types. With this aim, several algorithms have been recently proposed to reconstruct tissue-specific metabolic models based on available data. Here, the most promising were implemented and used to reconstruct models for two case studies, using omics data from distinct sources. The set of obtained models were compared and analyzed, being shown they are highly variable and that no combination of algorithm and data source can achieve models with acceptable phenotype predictions. We propose an algorithm to achieve a consensus model from the set of models available for a given tissue/cell line, and to improve it given functional data (e.g. known metabolic tasks). The results show that the re...
Didelphis albiventris, gambá-de-orelha-branca, é um marsupial de hábitos crepusculares e noturnos... more Didelphis albiventris, gambá-de-orelha-branca, é um marsupial de hábitos crepusculares e noturnos que se alimenta de frutos, insetos, pequenos répteis e anfíbios, filhotes de aves e pequenos mamíferos. Com a destruição de seu "habitat" natural devido às queimadas e desmatamentos, esses animais têm-se aproximado, cada vez mais, das regiões peridomiciliar e domiciliar, onde procuram abrigo e alimentos. Com o objetivo de conhecer a diversidade de parasitos de D. albiventris e relatar os que apresentam potencial zoonótico, foram examinados 30 exemplares desta espécie, através de necropsia, para coleta de ectoparasitos da superfície externa do corpo e helmintos dos órgãos e conteúdos estomacal e intestinal. Os sifonápteros foram removidos da superfície externa dos animais, conservados em álcool etílico a 70°GL, clarificados em líquido de Nesbitt, desidratados em etanol, diafanizados em creosoto de Faya e montados em lâminas com bálsamo do Canadá para identificação. Os carrapatos foram removidos da superfície externa dos animais, conservados em álcool etílico a 70°GL e identificados ao estereomicroscópio, segundo chaves específicas de Aragão & Fonseca (1961) e Guimarães et al. (2001). Os helmintos foram recolhidos com auxílio de estiletes e pinças, clarificados em lactofenol e montados entre lâminas e lamínulas com bálsamo do Canadá para identificação ao microscópio. Do total de animais examinados, 70% estavam infestados com pulgas das espécies Polygenis (Neopolygenis) atopus, Polygenis (Polygenis) rimatus, Polygenis (Polygenis) roberti roberti, Polygenis (Polygenis) sp., Craneopsylla minerva minerva e Ctenocephalides felis felis, todas essas registradas pela primeira vez sobre D. albiventris e, exceto C. felis felis, são também registradas pela primeira vez no estado do Rio Grande do Sul. Carrapatos foram encontrados em 43,33% dos animais examinados, representados pelas espécies Ixodes loricatus, Amblyomma aureolatum e Amblyomma sp, sendo A. aureolatum registrado pela primeira vez parasitando D. albiventris no Brasil. Os helmintos encontrados foram: Filo Nematoda-Capillaria spp. (esôfago, traquéia, faringe e pulmão), Didelphostrongylus hayesi (pulmão), Turgida turgida (estômago), Gnathostoma sp. (estômago e fígado), Travassostrongylus orloffi, Viannaia hamata e Trichuris minuta no intestino delgado e Trichuris didelphis, Cruzia tentaculata e Aspidodera raillieti no intestino grosso; Classe Trematoda-Echinostoma revolutum, Plagiorchis didelphidis, Rhopalias coronatus, R. baculifer, Brachylaema migrans e Didelphodiplostomum variabile, todos no intestino delgado; Classe Cestoda-exemplares da família Diphyllobotriidae, no intestino delgado; e Filo Acanthocephala-Hamanniella microcephala e Centrorhynchus sp., ambos no intestino delgado. Dos helmintos encontrados, os que apresentam potencial zoonótico segundo a literatura são T. turgida, Gnathostoma sp., Capillaria spp., B. migrans, E. revolutum e Família Diphyllobotriidae. Além disso, os sifonápteros e ixodídeos encontrados são potenciais vetores de patógenos que infectam humanos. D. albiventris, portanto, apresenta grande diversidade parasitária, incluindo espécies que podem potencialmente atingir o homem, alertando para a importância destes marsupiais na disseminação de doenças entre animais e humanos.
Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting speci... more Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown. WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional effects and . Phospho-kinase arrays and TCF/LEF reporter assays were used to identify WNT6-signaling pathways, and significant associations with stem cell features and cancer-related pathways were validated in patients. Survival analyses were performed with Cox regression and Log-rank tests. Meta-analyses were used to calculate the estimated pooled effect. We show that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6 increases typi...
Intracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the... more Intracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the world and these ruptures are associated with a high mortality. Some risk factors, such as age, gender, smoking, alcohol, hypertension and familial history are associated with the number of aneurysms and their size. In addition, inflammatory processes within the blood vessels of the brain can activate matrix metalloproteinase-9 (MMP-9), which degrades various components of the extracellular matrix, such as elastin. Thereby, this work has aimed at evaluating the relationship between plasma MMP-9 levels and the risk factors that are associated with intracranial aneurysm, as well as investigating the aneurysm statuses (ruptured and unruptured) and comparing them with the control volunteers. Between August 2014 to June 2016, blood samples were collected from 282 patients (204 ruptured and 78 unruptured saccular intracranial aneurysms) and 286 control volunteers. The MMP-9 plasma levels were ...
Develop a platform composed of labeled dendrimer nanoparticles (NPs) and a microfluidic device fo... more Develop a platform composed of labeled dendrimer nanoparticles (NPs) and a microfluidic device for real-time monitoring of cancer cells fate. Carboxymethylchitosan/poly(amidoamine) dendrimer NPs were labeled with fluorescein-5(6)-isothiocyanate and characterized using different physicochemical techniques. After, HeLa, HCT-116 and U87MG were cultured in the presence of NPs, and cell viability and internalization efficiency in static (standard culture) and dynamic (microfluidic culture) conditions were investigated. Cancer cells cultured with NPs in dynamic conditions were viable and presented higher internalization levels as compared with static 2D cultures. This work demonstrated that the proposed microfluidic-based platform allows real-time monitoring, which upon more studies, namely, the assessment of an anticancer drug release effect could be used for cancer theranostics.
2016 IEEE Conference on Evolving and Adaptive Intelligent Systems (EAIS), 2016
In this paper, we propose a new approach to fuzzy data clustering. We present a new algorithm, ca... more In this paper, we propose a new approach to fuzzy data clustering. We present a new algorithm, called TEDA-Cloud, based on the recently introduced TEDA approach to outlier detection. TEDA-Cloud is a statistical method based on the concepts of typicality and eccentricity able to group similar data observations. Instead of the traditional concept of clusters, the data is grouped in the form of granular unities called data clouds, which are structures with no pre-defined shape or set boundaries. TEDA-Cloud is a fully autonomous and self-evolving algorithm that can be used for data clustering of online data streams and applications that require real-time response. Since it is fully autonomous, TEDA-Cloud is able to "start from scratch" (from an empty knowledge basis), create, update and merge data clouds, in a fully autonomous manner, without requiring any user-defined parameters (e.g. number of clusters, size, radius) or previous training. Moreover, TEDA-Cloud, unlike most of the traditional statistical approaches, does not rely on a specific data distribution or on the assumption of independence of data samples. The results, obtained from multiple data sets that are very well known in literature, are very encouraging.
2015 IEEE International Conference on Fuzzy Systems (FUZZ-IEEE), 2015
Outlier detection is a problem that has been largely studied in the past few years due to its gre... more Outlier detection is a problem that has been largely studied in the past few years due to its great applicability in real world problems (e.g. financial, social, climate, security). Fault detection in industrial processes is one of these problems. In that context, several methods have been proposed in literature to address fault detection. In this paper we propose a comparative analysis of three recently introduced outlier detection methods: RDE, RDE with Forgetting and TEDA. Such methods were applied to the data set provided in DAMADICS benchmark, a very well-known real data tool for fault detection applications. The results, however, can be extended to similar problems of the area. Therewith, in this work we compare the main features of each method as well as the results obtained with them.
International Journal of Developmental Neuroscience, 2015
Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investig... more Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome −46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55 ± 0.38) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98 ± 0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the deregulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic deregulation of the MECP2 may be present in other RTT-like patients.
Glioblastoma is the most malignant brain tumor, exhibiting remarkable resistance to treatment. He... more Glioblastoma is the most malignant brain tumor, exhibiting remarkable resistance to treatment. Here we investigated the oncogenic potential of HOXA9 in gliomagenesis, the molecular and cellular mechanisms by which HOXA9 renders glioblastoma more aggressive, and how HOXA9 affects response to chemotherapy and survival. The prognostic value of HOXA9 in glioblastoma patients was validated in two large datasets from TCGA and Rembrandt, where high HOXA9 levels were associated with shorter survival. Transcriptomic analyses identified novel HOXA9-target genes with key roles in cancer-related processes, including cell proliferation, DNA repair, and stem cell maintenance. Functional studies with HOXA9-overexpressing and HOXA9-silenced glioblastoma cell models revealed that HOXA9 promotes cell viability, stemness and invasion, and inhibits apoptosis. Additionally, HOXA9 promoted the malignant transformation of human immortalized astrocytes in an orthotopic in vivo model, and caused tumor-assoc...
We characterized tellina virus 1 (TV-1), a birnavirus isolated from the marine bivalve mollusk Te... more We characterized tellina virus 1 (TV-1), a birnavirus isolated from the marine bivalve mollusk Tellina tenuis. Genome sequence analysis established that TV-1 is representative of a viral cluster distant from other birnaviruses. The maturation process of the polyprotein encoded by the genomic segment A was delineated with the identification of the N-termini of the viral protease VP4 and the ribonucleoprotein VP3, and the characterization of peptides deriving from the processing of pVP2, the VP2 capsid protein precursor. One of these peptides was shown to possess a membrane-disrupting domain. Like the blotched snakehead virus, the polyprotein exhibits a non-structural polypeptide (named [X]) located between pVP2 and VP4. Mutagenesis analysis allowed the identification in VP4 of a catalytic Ser-Lys dyad that does not possess the common Gly-X-Ser signature of the serine hydrolases. The genomic segment B encodes the viral RNA-dependent RNA-polymerase VP1 with the unique sequence motif arrangement identified in other birnavirus VP1s.
In this paper we introduce the concept of a graphical object, the abstraction paradigms to study ... more In this paper we introduce the concept of a graphical object, the abstraction paradigms to study them, as well as their applications in computer graphics. Intuitively, a graphical object encompasses all the entities which are manipulated in a graphics system. This notion makes it possible to unify similar research topics that have appeared in the literature in a rather separated way. As an application, we use the concept of a graphical object to study the problem of object metamorphosis, which includes as a particular case the problem of image metamorphosis. Although we are not primarily concerned with implementation issues in this paper, the concepts we introduce can be exploited for systems design and development using object oriented programming.
Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus... more Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrif icus. A common gene ancestry and structural similarity with the antimicrobial β-defensins (identical disulfide bond pattern and highly positive net charge) suggested potential antimicrobial activities for this snake toxin. Although crotamine demonstrated low activity against both Gram-positive and Gram-negative bacteria, a pronounced antifungal activity was observed against Candida spp., Trichosporon spp., and Cryptococcus neoformans. Crotamine's selective antimicrobial properties, with no observable hemolytic activity, stimulated us to evaluate the potential applications of this polypeptide as an antiyeast or candicidal agent for medical and industrial application. Aiming to understand the mechanism(s) of action underlying crotamine antimicrobial activity and its selectivity for fungi, we present herein studies using membrane model systems (i.e., large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs), with different phospholipid compositions. We show here that crotamine presents a higher lytic activity on negatively charged membranes compared with neutral membranes, with or without cholesterol or ergosterol content. The vesicle burst was not preceded by membrane permeabilization as is generally observed for pore forming peptides. Although such a property of disrupting lipid membranes is very important to combat multiresistant fungi, no inhibitory activity was observed for crotamine against biofilms formed by several Candida spp. strains, except for a limited effect against C. krusei biofilm.
Table of conTenTs 6... DACA aneurysm locations 6..2. Aneurysm size and dome orientation 6... Aneu... more Table of conTenTs 6... DACA aneurysm locations 6..2. Aneurysm size and dome orientation 6... Aneurysm base and associated branches 6..4. ACA anomalies 6..5. Associated aneurysms and AVMs 6..6. ICHs from ruptured DACA aneurysms 6..7. Imaging of DACA aneurysms and CTA 6.2. treatment of Daca aneurysms 6.2.. Clipping of DACA aneurysms 6.2.2. Coiling of DACA aneurysms 6.3. outcome 6... Ruptured DACA aneurysms 6.3.1.1. One year outcome 6.3.1.2. Predictors of outcome at one year 6.3.1.3. Neurological deficits 6..2. Unruptured DACA aneurysms 6.4. long-term follow-uP 6.4.. Rebleeding from clipped DACA aneurysms 6.4.2. Recurrent SAH and de novo aneurysms 6.4.. Mortality 6.4.4. Excess mortality 6.4.5. Long-term angiographic screening 8 6.5. future trenDs 7. Conclusions List of 12 supplementary videos on microneurosurgery of DACA aneurysms Acknowledgments
The capsid of infectious bursal disease virus (IBDV), a nonenveloped virus of the family Birnavir... more The capsid of infectious bursal disease virus (IBDV), a nonenveloped virus of the family Birnaviridae , has a T=13l icosahedral shell constituted by a single protein, VP2, and several disordered peptides, all derived from the precursor pVP2. In this study, we show that two of the peptides, pep11 and pep46, control virus assembly and cell entry. Deletion of pep11 or even simple substitution of most of its residues blocks the capsid morphogenesis. Removal of pep46 also prevents capsid assembly but leads to the formation of subviral particles formed by unprocessed VP2 species. Fitting with the VP2 atomic model into three-dimensional reconstructions of these particles demonstrates that the presence of uncleaved pep46 causes a steric hindrance at the vertices, blocking fivefold axis formation. Mutagenesis of the pVP2 maturation sites confirms that C terminus processing is necessary for VP2 to acquire the correct icosahedral architecture. All peptides present on virions are accessible to ...
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Papers by Bruno costa