Thiago Fonseca Silva

Association of −308 TNF-α promoter polymorphism with clinical aggressiveness in patients with head and neck squamous cell carcinoma

Genetic polymorphisms in the promoter region of the tumour necrosis factor-α (TNF-α) gene are involved in the regulation of the expression levels of its cytokine. Besides, these polymorphisms have been associated with the clinical behaviour of cancer. We investigated the -308 promoter region polymorphisms of the TNF-α gene and its association with the clinicopathological factors of a head and neck squamous cell carcinoma (HNSCC) sample. Furthermore, we analysed the impact of all the variables on the overall survival of patients. A sample of HNSCC (n=89) was evaluated. Clinicopathological factors and overall survival data were gathered. The TNF-α gene was analysed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data analyses were performed by using bivariate and multivariate statistical tests. Significance was set at p<0.05. HNSCC subjects carrying the A allele (GA/AA) exhibited associations with poor performance status (OR=2.82, p=0.039), lesions located on posterior areas (OR=4.02, p=0.002), and large-size tumours (OR=2.91, p=0.015). Subjects carrying only AA genotype exhibited association with poor performance status (OR=6.667, p=0.007). A worse overall survival was noted in subjects with large tumours (OR=4.87, p=0.005) and locoregional metastatic disease (OR=2.50, p=0.018). Our data suggests that the presence of the A allele/AA haplotype in HNSCC individuals might contribute to the higher clinical aggressiveness of malignant disease.

Analysis of the normative conditions of oral health, depression and serotonin‐transporter‐linked promoter region polymorphisms in an elderly population

Aim:  To investigate the association between depression, the normative conditions of oral health and serotonin‐transporter‐linked promoter region (5‐HTTLPR) polymorphisms in a community‐dwelling elderly sample.

Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading

The present study aimed to compare levels of VEGFR2 and MMP-9 among control, epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) groups. We analyzed 48 patients with oral leukoplakia (OL), 20 patients with OSCC and 21 patients without OL and OSCC. Immunohistochemistry of VEGFR2 and MMP9 were performed and compared among groups. Analysis of tissue immunolocalization of VEGFR2 and MMP-9 assumed non-parametrical distribution and comparison between groups was performed using the Mann-Whitney and Kruskal-Wallis statistical tests. VEGFR2 and MMP9 immunoexpression appeared to correlate with the degree of dysplasia and was observed to increase in lesions with more severe dysplasia as compared to those with lower degrees of dysplasia. Immunoreactivity of MMP-9 was lower in the OL samples compared to the OSCC samples (p = 0.004). We observed no difference in VEGFR2 protein levels between OL and OSCC samples. A positive correlation was found between VEGFR2 and MMP-9 in OL samples (r = +0.452, p = 0.001), however, no correlation was found in OSCC samples (r = -0.042, p = 0.861). In conclusion, the results of the current study suggest that expression of MMP9 and VEGFR2 is associated with ED grading and MMP9 levels are increased in OSCC.

Methylation Pattern of IFNG in Periapical Granulomas and Radicular Cysts

INTRODUCTION Interferon-γ plays an important role in the pathogenesis of periapical lesions, and the methylation of IFNG has been associated with transcriptional inactivation. The purpose of the present study was to investigate IFNG promoter methylation in association with gene transcription and protein levels in periapical granulomas and radicular cysts. METHODS Methylation-specific polymerase chain reaction was used to assess the DNA methylation pattern of the IFNG gene in 16 periapical granulomas and 13 radicular cyst samples. The transcription levels of IFNG mRNA were verified by quantitative real-time polymerase chain reaction, and protein expression was evaluated by immunohistochemistry. RESULTS All the periapical lesion samples exhibited partial or total methylation of the IFNG gene. In addition, an increased methylation profile was found in radicular cysts compared with periapical granulomas. Increased IFNG mRNA expression was observed in the partially methylated periapical lesion samples relative to the samples that were completely methylated. CONCLUSIONS The present study provides the first evidence of the possible impact of IFNG methylation on IFNG transcription in periapical lesions.

Efficient Allocation of Verification Resources using Revision History Information

Verifying large industrial designs is getting harder each day. The current verification methodologies are not able to guarantee bug free designs. Some recurrent questions during a design verification are: Which modules are most likely to contain undetected bugs? In which modules the verification team should concentrate their effort? This information is very useful, because it is better to start verifying the most bug-prone modules. In this work we present a novel approach to answer these questions. In order to identify these bug-prone modules, the revision history of the design is used. Using information of an academic experiment, we demonstrate that there is a close relationship between bugs/changes history and future bugs. Our results show that allocating modules for verification based on bugs/changes leaded to the coverage of 91.67% of future bugs, while random based strategy covered only 37.5% of the future bugs.

Tracking hardware evolution

Software evolution is the term used to describe the process of developing and updating software systems. Software repositories such as versioning systems and bug tracking systems are used to manage the evolution of software projects. The mining of this information is used to support predictions and improve design and reuse. Integrated circuit development can also benefit from these techniques. Nowadays, both software and hardware development use repositories and bug tracking systems. There are many hardware open source projects such as SUNs OpenSparc and designs at Opencores.org. We propose a methodology to track specific HDL metrics in order to improve design quality. Our results present a case study that correlates HDL metrics and bug proneness of Verilog HDL modules. We also present EyesOn, an open source framework designed to automate historical and complexity metrics tracking of HDL projects.

Expression of EGF and its receptor and histomorphometric analysis of epithelial tissue in gingival fibromatosis

Gingival fibromatosis, a relatively rare condition, develops as a slowly progressing, benign, and localized or generalized enlargement of keratinized gingiva. The purpose of this study was to investigate the expression of epidermal growth factor and the epidermal growth factor receptor and perform histomorphometric analysis of epithelial tissue in gingival fibromatosis. Immunohistochemistry with antibodies against the aforementioned antigens was performed in gingival tissues from a family with hereditary gingival fibromatosis and a family with syndromic dental anomaly-associated gingival fibromatosis ; normal gingiva was used for comparison. The height of epithelial papillae and area and perimeter of epithelial layers were measured for histomorphometric analysis. Immunoreactivity to epidermal growth factor was found in the cytoplasm of epithelial cells, and immunopositivity for epidermal growth factor receptor was detected in the cytoplasm and membrane of epithelial cells. No differences in the expression of these proteins were observed among the groups. The gingival fibromatosis groups had higher epithelial papillae and larger epithelial areas that the normal gingiva group. Our findings suggest that enlargement of epithelial layers is associated with both forms of gingival fibromatosis.

A cache based algorithm to predict HDL modules faults

Verification is the most challenging and time consuming stage in the integrated circuit development cycle. As designs complexities double every two years, novel verification methodologies are needed. We propose an algorithm that dynamically builds and updates an HDL module error proneness list. This list can be used to assist the development team to allocate resources during verification stage. The algorithm is build up using the idea that problematic modules usually hide many uncovered errors. Thus, our algorithm caches the most frequently modified and fixed modules. In an academic experiment composed by 17 modules, using a cache of size 3, we were able to correctly predict almost 80% of the faults occurrences.