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Variance component analysis to assess protein quantification in biomarker discovery. Application to MALDI-TOF mass spectrometry.
2017
International audience; Controlling the technological variability on an analytical chain is critical for biomarker discovery. The sources of technological variability should be modeled, which calls for specific experimental design, signal processing, and statistical analysis. Furthermore, with unbalanced data, the various components of variability cannot be estimated with the sequential or adjusted sums of squares of usual software programs. We propose a novel approach to variance component analysis with application to the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology and use this approach for protein quantification by a classical signal processing algori…
A heuristic, iterative algorithm for change-point detection in abrupt change models
2017
Change-point detection in abrupt change models is a very challenging research topic in many fields of both methodological and applied Statistics. Due to strong irregularities, discontinuity and non-smootheness, likelihood based procedures are awkward; for instance, usual optimization methods do not work, and grid search algorithms represent the most used approach for estimation. In this paper a heuristic, iterative algorithm for approximate maximum likelihood estimation is introduced for change-point detection in piecewise constant regression models. The algorithm is based on iterative fitting of simple linear models, and appears to extend easily to more general frameworks, such as models i…
Collective Cell Migration in a Fibrous Environment: A Hybrid Multiscale Modelling Approach
2021
International audience; The specific structure of the extracellular matrix (ECM), and in particular the density and orientation of collagen fibres, plays an important role in the evolution of solid cancers. While many experimental studies discussed the role of ECM in individual and collective cell migration, there are still unanswered questions about the impact of nonlocal cell sensing of other cells on the overall shape of tumour aggregation and its migration type. There are also unanswered questions about the migration and spread of tumour that arises at the boundary between different tissues with different collagen fibre orientations. To address these questions, in this study we develop …
Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS
2017
Background and aims Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis. Methods We considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free an…
Search of Chemical Scaffolds for Novel Antituberculosis Agents
2005
3 A method to identify chemical scaffolds potentially active against Mycobacterium tuberculosis is presented. The molecular features of a set of structurally heterogeneous antituberculosis drugs were coded by means of structural invariants. Three tech- niques were used to obtain equations able to model the antituberculosis activity: linear discriminant analysis, multilinear re- gression, and shrinkage estimation-ridge regression. The model obtained was statistically validated through leave-n-out test, and an external set and was applied to a database for the search of new active agents. The selected compounds were assayed in vitro, and among those identified as active stand reserpine, N,N,N…
Metal Ions and Metal Complexes in Alzheimer's Disease.
2015
Background: Alzheimer’s disease (AD) is the most common form of dementia that seriously affects daily life. Even if AD pathogenesis is still subject of debate, it is generally accepted that cerebral cortex plaques formed by aggregated amyloid-β (Aβ) peptides can be considered a characteristic pathological hallmark. It is well known that metal ions play an important role in the aggregation process of Aβ. Methods: This review focuses on the anti-Aβ aggregation activity of chelating ligands as well as on the use of metal complexes as diagnostic probes and as potential drugs. Conclusion: While chelating agents, such as curcumin or flavonoid derivatives, are currently used to capture metal ions …
Fluorinated Chaperone−β-Cyclodextrin Formulations for β-Glucocerebrosidase Activity Enhancement in Neuronopathic Gaucher Disease
2017
Amphiphilic glycomimetics encompassing a rigid, undistortable nor-tropane skeleton based on 1,6-anhydro-L-idonojirimycin and a polyfluorinated antenna, when formulated as the corresponding inclusion complexes with β-cyclodextrin (βCD), have been shown to behave as pharmacological chaperones (PCs) that efficiently rescue lysosomal β- glucocerebrosidase mutants associated to the neuronopathic variants of Gaucher disease (GD), including the highly refractory L444P/L444P and L444P/P415R single nucleotide polymorphs, in patient fibroblasts. The body of work here presented includes the design criteria for the PC prototype, the synthesis of a series of candidates, the characterization of the PC:βC…
Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei
2016
A series of dipeptide nitriles known as inhibitors of mammalian cathepsins were evaluated for inhibition of rhodesain, the cathepsin L-like protease of Trypanosoma brucei. Compound 35 consisting of a Leu residue fitting into the S2 pocket and a triarylic moiety consisting of thiophene, a 1,2,4-oxadiazole and a phenyl ring fitting into the S3 pocket, and compound 33 with a 3-bromo-Phe residue (S2) and a biphenyl fragment (S3) were found to inhibit rhodesain in the single-digit nanomolar range. The observed steep structure-activity relationship could be explained by covalent docking simulations. With their high selectivity indices (ca. 200) and the good antitrypanosomal activity (8μM) the com…
A method for structure prediction of metal-ligand interfaces of hybrid nanoparticles
2019
Hybrid metal nanoparticles, consisting of a nano-crystalline metal core and a protecting shell of organic ligand molecules, have applications in diverse areas such as biolabeling, catalysis, nanomedicine, and solar energy. Despite a rapidly growing database of experimentally determined atom-precise nanoparticle structures and their properties, there has been no successful, systematic way to predict the atomistic structure of the metal-ligand interface. Here, we devise and validate a general method to predict the structure of the metal-ligand interface of ligand-stabilized gold and silver nanoparticles, based on information about local chemical environments of atoms in experimental data. In …
GABAergic System in Action: Connection to Gastrointestinal Stress-related Disorders.
2017
Background: Currently, treatment of stress-related gastrointestinal disorders, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), is mainly symptomatic since there is no drug on the market that solves effectively diverse disease symptoms and comorbid states. Thus, recently GABA receptors have been identified within gastrointestinal system and it has been recognized that among various GABAergic drugs some of them influence gastrointestinal stress-related diseases. Firstly, benzodiazepines have been investigated due to their diverse effects: neuroimmunomodulatory, relief of visceral pain and anxiolytic action. Conclusion: The present review brings findings on the exp…