Numerical Solution of Diffusion Models in Biomedical Imaging on Multicore Processors

In this paper, we consider nonlinear partial differential equations (PDEs) of diffusion/advection type underlying most problems in image analysis. As case study, we address the segmentation of medical structures. We perform a comparative study of numerical algorithms arising from using the semi-implicit and the fully implicit discretization schemes. Comparison criteria take into account both the accuracy and the efficiency of the algorithms. As measure of accuracy, we consider the Hausdorff distance and the residuals of numerical solvers, while as measure of efficiency we consider convergence history, execution time, speedup, and parallel efficiency. This analysis is carried out in a multicore-based parallel computing environment

Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics

Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic dierences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants

Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants.

Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function

Ricostruzione e segmentazione di immagini 3D: dal modello allo sviluppo del software in ambiente di calcolo parallelo

Nella società moderna le immagini rivestono un ruolo sempre più importante: l'immagine è uno strumento potente e ampiamente usato nella comunicazione ed anche un mezzo semplice, compatto e diffuso per la rappresentazione del mondo fisico. Anche nel mondo scientifico ed in particolare nella CSE (Computational Science and Engineering) l'immagine riveste un ruolo fondamentale essendo alla base della simulazione e visualizzazione di grandi quantità di dati. Appare allora evidente il crescente interesse per le tecniche e i metodi numerici che consentono di rappresentare un'immagine e permettono di migliorarla o estrarne informazioni. Tali tecniche sono alla base dell'Image Processing e dell'Image Analysis. Fino a pochi anni fa le tecniche utilizzate erano basate su metodi euristici ed approcci ``ad hoc''. La svolta significativa nell'Image Processing e Analysis si è avuta con l’introduzione di modelli e metodi matematici. Alla base di tali modelli c’è la classe dei Problemi Inversi, nei quali a partire dalle note caratteristiche (f) dello strumento ottico utilizzato nell'acquisizione (telecamera, macchina ecografica etc.), dal rumore random additivo k e dall'immagine degradata z, con z=f(u)+k, si vuole ricostruire un'approssimazione della soluzione ideale u=f--1 (z-k) in modo tale che , con opportuna. Una caratteristica di tali problemi è la perdita di informazioni significative nel passare dal dato u al risultato z; ad esempio, si passa dalla scena reale u nello spazio 3D all'immagine acquisita z definita nello spazio 2D, con un'evidente perdita di informazioni. Per compensare la perdita di informazioni occorre assegnare informazioni aggiuntive, occorre cioè regolarizzare il problema inverso. A partire dall'idea di Tikhonov nel 1977 sono stati introdotti molti operatori di regolarizzazione con l'intento di fornire modelli matematici sempre più affidabili e aderenti alle caratteristiche effettive di un'immagine. Definito il modello matematico (M(P)) il suo effettivo utilizzo in applicazioni concrete necessita la messa a punto di metodi numerici per la realizzazione del corrispondente problema discreto M_h(P) , di algoritmi e software efficienti che permettano di ottenere la soluzione desiderata in tempo utile. E’ a questo livello che si inserisce il mio lavoro di tesi, nel quale, partendo dall'equazione di diffusione del flusso a curvatura media, assunta come modello matematico del problema di ricostruzione e segmentazione di una immagine, vengono analizzati, discussi e implementati tutti i passi computazionali necessari allo sviluppo dell'elemento di software in un ambiente di calcolo parallelo ad alte prestazioni. Dopo una breve introduzione ai problemi del denoising e della segmentazione d'immagini 3D, nel Capitolo 1 si illustra il legame presente tra le PDE e l'Image Processing ed Analysis, ponendo particolare attenzione ai modelli di diffusione non lineari (Modelli di flusso a curvatura media - Modelli Level Set). Nel Capitolo 2 sono analizzati nel dettaglio il denoising e la segmentazione di immagini 3D: dal modello matematico fino alla loro discretizzazione. Nel Capitolo 3 è descritto il metodo numerico utilizzato per la risoluzione del nucleo computazionale di base: il JFNK (Jacobian-Free Newton-Krylov). Nel Capitolo 4 è introdotto l'ambiente di sviluppo dell'algoritmo: la libreria PETSc ( Portable, Exstensible Toolkit for Scientific Computation). Nel Capitolo 5 vengono descritti i dettagli implementativi del software parallelo e della sua applicazione ad immagini mediche ecografiche. In fine nel Capitolo 6 vengono illustrati alcuni esperimenti

A numerical algorithm for image sequence inpainting that preserves fine-textures

International audienceWe describe a fast, reliable and automatic algorithm for image sequence inpainting that combines a spatio-temporal interpolation with a fine texture preservation inside missing areas. The algorithm provides an estimate of the inpainting error by using an automatic geometric recognition of missing regions. Computational kernels are sparse linear systems solved using GMRES iterative method equipped with AMG multigrid preconditioner. Experiments on synthetic and real data are discussed

Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics.

Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic differences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants

Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics.

Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic differences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants

FoxO3a Inhibits Tamoxifen-Resistant Breast Cancer Progression by Inducing Integrin α5 Expression

Resistance to endocrine therapy is still a major clinical challenge in the management of estrogen receptor α-positive (ERα+) breast cancer (BC). Here, the role of the Forkhead box class O (FoxO)3a transcription factor in tumor progression has been evaluated in tamoxifen-resistant BC cells (TamR), expressing lower levels of FoxO3a compared to sensitive ones. FoxO3a re-expression reduces TamR motility (wound-healing and transmigration assays) and invasiveness (matrigel transwell invasion assays) through the mRNA (qRT-PCR) and protein (Western blot) induction of the integrin α5 subunit of the α5β1 fibronectin receptor, a well-known membrane heterodimer controlling cell adhesion and signaling. The induction occurs through FoxO3a binding to a specific Forkhead responsive core sequence located on the integrin α5 promoter (cloning, luciferase, and ChIP assays). Moreover, FoxO3a failed to inhibit migration and invasion in integrin α5 silenced (siRNA) cells, demonstrating integrin α5 involvement in both processes. Finally, using large-scale gene expression data sets, a strong positive correlation between FoxO3a and integrin α5 in ERα+, but not in ER-negative (ERα−), BC patients emerged. Altogether, our data show how the oncosuppressor FoxO3a, by increasing the expression of its novel transcriptional target integrin α5, reverts the phenotype of endocrine-resistant BC toward a lower aggressiveness