On a fast bilateral filtering formulation using functional rearrangements

We introduce an exact reformulation of a broad class of neighborhood filters, among which the bilateral filters, in terms of two functional rearrangements: the decreasing and the relative rearrangements. Independently of the image spatial dimension (one-dimensional signal, image, volume of images, etc.), we reformulate these filters as integral operators defined in a one-dimensional space corresponding to the level sets measures. We prove the equivalence between the usual pixel-based version and the rearranged version of the filter. When restricted to the discrete setting, our reformulation of bilateral filters extends previous results for the so-called fast bilateral filtering. We, in addition, prove that the solution of the discrete setting, understood as constant-wise interpolators, converges to the solution of the continuous setting. Finally, we numerically illustrate computational aspects concerning quality approximation and execution time provided by the rearranged formulation.Comment: 29 pages, Journal of Mathematical Imaging and Vision, 2015. arXiv admin note: substantial text overlap with arXiv:1406.712

Well-posedness of a nonlinear integro-differential problem and its rearranged formulation

We study the existence and uniqueness of solutions of a nonlinear integro-differential problem which we reformulate introducing the notion of the decreasing rearrangement of the solution. A dimensional reduction of the problem is obtained and a detailed analysis of the properties of the solutions of the model is provided. Finally, a fast numerical method is devised and implemented to show the performance of the model when typical image processing tasks such as filtering and segmentation are performed.Comment: Final version. To appear in Nolinear Analysis Real World Applications (2016

Clinical and molecular characterization of DSD patients: Impact of Next Generation Sequencing in diagnosis

317 p.Disorders of sex development (DSD) encompass a high heterogeneous range of conditionsin which the optimal clinical management of the individuals comprise clinical description, biochemicaltesting and genetic analysis. With the arrival of next-generation sequencing (NGS) new genes andpathways have been implicated in the pathogenesis of the disease. However, only 50% of the 46,XY DSDpatients will receive a definitive diagnosis. The aim of this work is the clinical and molecularcharacterization of a DSD cohort. Patients and methods: Blood samples or DNA from a total of 125independent patients with a DSD referred from several Spanish centres and one Swiss hospital werestudied. Clinical characterization was done after examination of the data sheet provided by the clinicians.The molecular study was performed either by single-gene testing or NGS using a targeted gene panel of48 DSD-related genes. Parents were also analysed when possible. Genetic variants were analysed usingin silico prediction programmes and were classified according to its potential pathogenicity. Furtherfunctional studies of the genetic changes identified in three genes were also performed. Results: Overall,we made a genetic diagnosis in 4.4% of the individuals. In 46,XY DSD, the diagnostic rate increased upto 46.5% while in 46.XX DSD it was 29.2%. Novel changes classified as pathogenic or likely pathogenicwere mostly located in the NR5A1 and LHCGR genes. Functional impact of variants in NR5A1 andLHCGR showed a significant reduced transactivation activity while the variant of unknown significancein GATA4 showed similar activity compared to wild type. Conclusions: The heterogeneous phenotypesencompassed in this condition difficult the clinical diagnosis and highlight the need of a genetic study.The molecular analysis of DSD-related genes identified a causative genetic variant in the 40.2% of thepatients analysed in this cohort. Targeted gene sequencing panel is useful for the detection of singlenucleotidevariants, however further improvements are needed to detect copy number variations.Functional studies are a valuable tool to confirm the effect of a variant in the pathogenesis of the disease

Clinical and molecular characterization of DSD patients: Impact of Next Generation Sequencing in diagnosis

317 p.Disorders of sex development (DSD) encompass a high heterogeneous range of conditionsin which the optimal clinical management of the individuals comprise clinical description, biochemicaltesting and genetic analysis. With the arrival of next-generation sequencing (NGS) new genes andpathways have been implicated in the pathogenesis of the disease. However, only 50% of the 46,XY DSDpatients will receive a definitive diagnosis. The aim of this work is the clinical and molecularcharacterization of a DSD cohort. Patients and methods: Blood samples or DNA from a total of 125independent patients with a DSD referred from several Spanish centres and one Swiss hospital werestudied. Clinical characterization was done after examination of the data sheet provided by the clinicians.The molecular study was performed either by single-gene testing or NGS using a targeted gene panel of48 DSD-related genes. Parents were also analysed when possible. Genetic variants were analysed usingin silico prediction programmes and were classified according to its potential pathogenicity. Furtherfunctional studies of the genetic changes identified in three genes were also performed. Results: Overall,we made a genetic diagnosis in 4.4% of the individuals. In 46,XY DSD, the diagnostic rate increased upto 46.5% while in 46.XX DSD it was 29.2%. Novel changes classified as pathogenic or likely pathogenicwere mostly located in the NR5A1 and LHCGR genes. Functional impact of variants in NR5A1 andLHCGR showed a significant reduced transactivation activity while the variant of unknown significancein GATA4 showed similar activity compared to wild type. Conclusions: The heterogeneous phenotypesencompassed in this condition difficult the clinical diagnosis and highlight the need of a genetic study.The molecular analysis of DSD-related genes identified a causative genetic variant in the 40.2% of thepatients analysed in this cohort. Targeted gene sequencing panel is useful for the detection of singlenucleotidevariants, however further improvements are needed to detect copy number variations.Functional studies are a valuable tool to confirm the effect of a variant in the pathogenesis of the disease

Bioinformatics for personal genomics: development and application of bioinformatic procedures for the analysis of genomic data

In the last decade, the huge decreasing of sequencing cost due to the development of high-throughput technologies completely changed the way for approaching the genetic problems. In particular, whole exome and whole genome sequencing are contributing to the extraordinary progress in the study of human variants opening up new perspectives in personalized medicine. Being a relatively new and fast developing field, appropriate tools and specialized knowledge are required for an efficient data production and analysis. In line with the times, in 2014, the University of Padua funded the BioInfoGen Strategic Project with the goal of developing technology and expertise in bioinformatics and molecular biology applied to personal genomics. The aim of my PhD was to contribute to this challenge by implementing a series of innovative tools and by applying them for investigating and possibly solving the case studies included into the project. I firstly developed an automated pipeline for dealing with Illumina data, able to sequentially perform each step necessary for passing from raw reads to somatic or germline variant detection. The system performance has been tested by means of internal controls and by its application on a cohort of patients affected by gastric cancer, obtaining interesting results. Once variants are called, they have to be annotated in order to define their properties such as the position at transcript and protein level, the impact on protein sequence, the pathogenicity and more. As most of the publicly available annotators were affected by systematic errors causing a low consistency in the final annotation, I implemented VarPred, a new tool for variant annotation, which guarantees the best accuracy (>99%) compared to the state-of-the-art programs, showing also good processing times. To make easy the use of VarPred, I equipped it with an intuitive web interface, that allows not only a graphical result evaluation, but also a simple filtration strategy. Furthermore, for a valuable user-driven prioritization of human genetic variations, I developed QueryOR, a web platform suitable for searching among known candidate genes as well as for finding novel gene-disease associations. QueryOR combines several innovative features that make it comprehensive, flexible and easy to use. The prioritization is achieved by a global positive selection process that promotes the emergence of the most reliable variants, rather than filtering out those not satisfying the applied criteria. QueryOR has been used to analyze the two case studies framed within the BioInfoGen project. In particular, it allowed to detect causative variants in patients affected by lysosomal storage diseases, highlighting also the efficacy of the designed sequencing panel. On the other hand, QueryOR simplified the recognition of LRP2 gene as possible candidate to explain such subjects with a Dent disease-like phenotype, but with no mutation in the previously identified disease-associated genes, CLCN5 and OCRL. As final corollary, an extensive analysis over recurrent exome variants was performed, showing that their origin can be mainly explained by inaccuracies in the reference genome, including misassembled regions and uncorrected bases, rather than by platform specific errors

Automated Analysis of Time-resolved X-ray data using Optical Flow Methods

We develop a general-purpose framework for analysis of time-resolved X-ray data based on optical flow. We perform a systematic evaluation of state-of-the-art optical flow techniques and their components. On the top of motion estimation we provide an extensive data analysis toolkit. All the devised techniques can be applied in 4D (3D + time). The implementation employs advanced numerical schemes and computations on GPU. We present the application of the optical flow methods to a number of scientific problems from various research fields

The strategic shift of U.S. firms towards Vietnam at the expense of China: A business system analysis

In the recent past, Vietnam has dramatically increased its investment relationship and trade with the United States. At the same time, United States foreign direct investment and trade with China has been decreasing. This is even more significant when we are in a period of internal growth within the United States. Using comparative business system analysis theory and a mixed method approach we conclude that Vietnam is turning into the new China for United States firms due to the fewer differences that exist between their business systems. The Chinese business system has major differences when compared with the economic system of the United States, whereas the Vietnam system has closer resemblance to the United States system. We have laid out inferences of our arguments for future research, particularly in the area of institutional comparative advantage