Continuous dependence on the constitutive functions for a class of problems describing fluid flow in porous media

Abstract. — In this paper we consider the PDE describing the fluid flow in a porous medium, focusing on the solution’s dependence upon the choice of the saturation curve and the hydraulic conductivity. Basically, we consider two different saturation curves (say y1 and y2) and two different hydraulic conductivities (K1 and K2) which are both ‘‘close’’ in the L2 loc-norm. Then we find estimates to prove a constitutive stability for the solutions of the corresponding problems with the same boundary and initial conditions

BoBafit: A copy number clustering tool designed to refit and recalibrate the baseline region of tumors’ profiles

Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples. Output data need to be analyzed with bioinformatic approaches and particularly by employing computational algorithms. Molecular biology tools estimate the baseline region by comparing either the mean probe signals, or the number of reads to the reference genome. However, when tumors display complex karyotypes, this type of approach could fail the baseline region estimation and consequently cause errors in the CNAs call. To overcome this issue, we designed an R-package, BoBafit, able to check and, eventually, to adjust the baseline region, according to both the tumor-specific alterations’ context and the sample-specific clustered genomic lesions. Several databases have been chosen to set up and validate the designed package, thus demonstrating the potential of BoBafit to adjust copy number (CN) data from different tumors and analysis techniques. Relevantly, the analysis highlighted that up to 25% of samples need a baseline region adjustment and a redefinition of CNAs calls, thus causing a change in the prognostic risk classification of the patients. We support the implementation of BoBafit within CN analysis bioinformatics pipelines to ensure a correct patient's stratification in risk categories, regardless of the tumor type

Joining participatory approach and spatially-based modelling tools for groundwater resource management.

Although a lot of science has been produced on Water Resource Management (WRM) in the Information and Communication Technology (ICT) sector, WRM is still poorly addressed via scientific means. Some reasons for this may be: the underrated importance given to this topic at political and decision-making level; the low-capacity of the research environment to transfer results; and missing numerical modelling capacities at agencies and governing authorities. ICT may provide tools for water planning and management, as discussed within the ICT4WATER cluster initiative. Among these, GIS-integrated numerical modeling is a robust method to represent hydrological systems and to provide answers to problems of protection of groundwater resources. Because these tools require a high level of knowledge pertaining to various disciplines, they are often disregarded as complex “tricky games” providing unrealistic results. This is a barrier to the uptake of technologies for water management. To overcome this issue, the application of ICT tools has been combined with an innovative participatory approach, and large capacity building activities, in the framework of the H2020 FREEWAT project (FREE and open source software tools for WATer resource management; www.freewat.eu). The major result of the project consists in an open source and public domain, QGIS-integrated modeling platform for promoting WRM. FREEWAT capabilities have been demonstrated at 14 case studies in EU and non-EU Countries, where the effectiveness of few measures foreseen in River Basin Management Plans for achieving good status of water bodies was tested. At each case study, a Focus Group (FG) participated by local stakeholders (e.g., river basin authorities, research institutions, environmental protection agencies, environmental associations) was formed and seven meetings were organized. During these meetings, the objective of each case study, the methodology to be adopted, including definition of the conceptual model and of data needed, were discussed. The FG also took decisions on scenarios to be simulated for testing the feasibility of the foreseen measures. FGs aimed at demonstrating that WRM may be performed with open source and public domain software and participants’ perception on using ICT tools for WRM was discussed. Some of the implemented models are now being used for operational purposes: Vrbansky plato (Slovenia), where FREEWAT is used to monitor remediation of heating oil spillage and the water supply company intends to maintain and use developed groundwater flow model for managed groundwater recharge with induced riverbank filtration; the Bremerhaven case study (Germany), where the local water authority intends to use the developed groundwater flow model for predictions; the Scarlino-Follonica case study (Italy), where the model will be used by the regional authority to manage private groundwater remediation projects in a large industrial contaminated site; the Gozo case study (Malta), where the model is being developed to support the assessment of good groundwater quantitative status as part of the implementation of the Water Framework Directive

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways' genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells' differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells' phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future

Blood coagulation dynamics: mathematical modeling and stability results

The hemostatic system is a highly complex multicomponent biosystem that under normal physiologic conditions maintains the fluidity of blood. Coagulation is initiated in response to endothelial surface vascular injury or certain biochemical stimuli, by the exposure of plasma to Tissue Factor (TF), that activates platelets and the coagulation cascade, inducing clot formation, growth and lysis. In recent years considerable advances have contributed to understand this highly complex process and some mathematical and numerical models have been developed. However, mathematical models that are both rigorous and comprehensive in terms of meaningful experimental data, are not available yet. In this paper a mathematical model of coagulation and fibrinolysis in flowing blood that integrates biochemical, physiologic and rheological factors, is revisited. Three-dimensional numerical simulations are performed in an idealized stenosed blood vessel where clot formation and growth are initialized through appropriate boundary conditions on a prescribed region of the vessel wall. Stability results are obtained for a simplified version of the clot model in quiescent plasma, involving some of the most relevant enzymatic reactions that follow Michaelis-Menten kinetics, and having a continuum of equilibria.CEMAT/IST through FCT [PTDC/MAT/68166/2006]; Czech Science Foundation [201/09/0917]; Grant Agency of the Academy of Sciences of the CR [IAA100190804]; Ministry of Education of Czech Republic [6840770010]info:eu-repo/semantics/publishedVersio

ICT tools for enhancing sustainable water management in rural environments

Numerical models are relevant tools to achieve the proper application of the Water Framework Directive (WFD, EU 2000). Their major advantage is to foster a full characterization of the involved flow terms and contaminant transport pathways. Thanks to their predictive function, numerical models can help also to address planning and management activities. Many hydrological codes developed so far have faced the problem of tackling multiscale territorial planning (e.g., Bergez et al. 2012). We introduce here the GIS-integrated FREEWAT platform aimed at providing a unique modeling environment to simulate multiple hydrological processes, with a focus on the sustainable management of conjunctive use of surface- and ground-water resources in rural environments. FREEWAT (FREE and open source software tools for WATer resource management; Rossetto et al., 2015) is an EU HORIZON 2020 project, whose main goal is to simplify the application of EU water-related Directives. It aims at integrating a simulation platform in a Geographic Information System (GIS), coupling the power of GIS geo-processing and post-processing tools in spatial data analysis to that of simulation codes. The FREEWAT platform is being developed within the QGIS free open source software package and fosters the simulation of the whole hydrological cycle using open source numerical codes mainly belonging to the USGS MODFLOW family

Distribution of laminin and fibronectin isoforms in oral mucosa and oral squamous cell carcinoma

The expression of laminin and fibronectin isoforms varies with cellular maturation and differentiation and these differences may well influence cellular processes such as adhesion and motility. The basement membrane (BM) of fetal oral squamous epithelium contains the laminin chains, α2, α3, α5, β1, β2, β3, γ1 and γ2. The BM of adult normal oral squamous epithelium comprises the laminin chains, α3, α5, β1, β3, γ1 and γ2. A re-expression of the laminin α2 and β2 chains could be shown in adult hyperproliferative, dysplastic and carcinomatous lesions. In dysplasia and oral squamous cell carcinoma (OSCC), multifocal breaks of the BM are present as indicated by laminin chain antibodies. These breaks correlate to malignancy grade in their extent. Moreover, in the invasion front the α3 and γ2 chain of laminin-5 can immunohistochemically be found outside the BM within the cytoplasm of budding carcinoma cells and in the adjacent stroma. The correlation between the morphological pattern of invasive tumour clusters and a laminin-5 immunostaining in the adjacent stroma may suggest, first, that a laminin-5 deposition outside the BM is an immunohistochemical marker for invasion and second, that OSCC invasion is guided by the laminin-5 matrix. Expression of oncofetal fibronectins (IIICS de novo glycosylated fibronectin and ED-B fibronectin) could be demonstrated throughout the stromal compartment. However, the ED-B fibronectin synthesizing cells (RNA/RNA in situ hybridization) are confined to small stroma areas and to single stroma and inflammatory cells in the invasion front. A correlation of the number of ED-B fibronectin synthesizing cells to malignancy grade could not be seen. ED-B fibronectin mRNA-positive cells seem to be concentrated in areas of fibrous stroma recruitment with a linear alignment of stromal fibro-/myofibroblasts (desmoplasia). Double staining experiments (ED-B fibronectin in situ hybridization and α-smooth muscle actin immunohistochemistry) indicated that the stroma myofibroblasts are a preferential source of ED-B fibronectin. In conclusion, in OSCC, a fetal extracellular matrix conversion is demonstrable. Tumour cells (laminin α2 and β2 chain) and recruited stromal myofibroblasts (oncofetal ED-B fibronectin) contribute to the fetal extracellular matrix milieu. © 1999 Cancer Research Campaig

A high‐resolution view of the coordination environment in a paramagnetic metalloprotein from its magnetic properties

Metalloproteins constitute a significant fraction of the proteome of all organisms and their characterization is critical for both basic sciences and biomedical applications. A large portion of metalloproteins bind paramagnetic metal ions, and paramagnetic NMR spectroscopy has been widely used in their structural characterization. However, the signals of nuclei in the immediate vicinity of the metal center are often broadened beyond detection. In this work, we show that it is possible to determine the coordination environment of the paramagnetic metal in the protein at a resolution inaccessible to other techniques. Taking the structure of a diamagnetic analogue as a starting point, a geometry optimization is carried out by fitting the pseudocontact shifts obtained from first principles quantum chemical calculations to the experimental ones