250 research outputs found
An anisotropic unstructured triangular adaptive mesh algorithm based on error and error gradient information
No full textIn this paper, an algorithm based on unstructured triangular meshes using standard refinement patterns for anisotropic adaptive meshes is presented. It consists of three main actions: anisotropic refinement, solution-weighted smoothing and patch unrefinement. Moreover, a hierarchical mesh formulation is used. The main idea is to use the error and error gradient on each mesh element to locally control the anisotropy of the mesh. The proposed algorithm is tested on interpolation and boundary-value problems with a discontinuous solution. (C) 2008 IMACS. Published by Elsevier B.V. All rights reserved
Double-stage discretization approaches for biomarker-based bladder cancer survival modeling
No full textBioinformatic techniques targeting gene expression data require specific analysis pipelines with the aim of studying properties, adaptation, and disease outcomes in a sample population. Present investigation compared together results of four numerical experiments modeling survival rates from bladder cancer genetic profiles. Research showed that a sequence of two discretization phases produced remarkable results compared to a classic approach employing one discretization of gene expression data. Analysis involving two discretization phases consisted of a primary discretizer followed by refinement or pre-binning input values before the main discretization scheme. Among all tests, the best model encloses a sequence of data transformation to compensate skewness, data discretization phase with class-attribute interdependence maximization algorithm, and final classification by voting feature intervals, a classifier that also provides discrete interval optimization
The long non-coding RNAs in neurodegenerative diseases : novel mechanisms of pathogenesis
No full textBackground: Long-non-coding RNAs (lncRNAs), RNA molecules longer than 200 nucleotides, have been involved in several biological processes and in a growing number of diseases, controlling gene transcription, pre-mRNA processing, the transport of mature mRNAs to specific cellular compartments, the regulation of mRNA stability, protein translation and turnover. The fundamental role of lncRNAs in central nervous system (CNS) is becoming increasingly evident. LncRNAs are abundantly expressed in mammalian CNS in a specific spatio-temporal manner allowing a quick response to environmental/molecular changes. Methods: This article reviews the biology and mechanisms of action of lncRNAs underlying their potential role in CNS and in some neurodegenerative diseases. Results: an increasing number of studies report on lncRNAs involvement in different molecular mechanisms of gene expression modulation in CNS, from neural stem cell differentiation mainly by chromatin remodeling, to control of neuronal activities. More recently, lncRNAs have been implicated in neurodegenerative diseases, including Alzheimer’s Disease, where the role of BACE1-AS lncRNA has been widely defined. BACE1-AS levels are up-regulated in AD brains where BACE1-AS acts by stabilizing BACE1 mRNA thereby increasing BACE1 protein content and Aβ42 formation. In Frontotemporal dementia and Amyotrophic lateral sclerosis the lncRNAs NEAT1_2 and MALAT1 co-localize at nuclear paraspeckles with TDP-43 and FUS proteins and their binding to TDP-43 is markedly increased in affected brains. In Parkinson’s Disease the lncRNA UCHL1-AS1 acts by directly promoting translation of UCHL1 protein leading to perturbation of the ubiquitin-proteasome system. Different lncRNAs, such as HTT-AS, BDNF-AS and HAR1, were found to be dysregulated in their expression also in Huntington’s Disease. In Fragile X syndrome (FXS) and Fragile X tremor/ataxia syndrome (FXTAS) patients, the presence of CGG repeats expansion alters the expression of the lncRNAs FMR1-AS1 and FMR6. Interestingly, they are expressed in peripheral blood leukocytes, suggesting these lncRNAs may represent biomarkers for FXS/FXTAS early detection and therapy. Finally, the identification of the antisense RNAs SCAANT1-AS and ATXN8OS in spinocerebellar ataxia 7 and 8, respectively, suggests that very different mechanisms of action driven by lncRNAs may trigger neurodegeneration in these disorders. The emerging role of lncRNAs in neurodegenerative diseases suggests that their dysregulation could trigger neuronal death via still unexplored RNA-based regulatory mechanisms which deserve further investigation. The evaluation of their diagnostic significance and therapeutic potential could also address the setting up of novel treatments in diseases where no cure is available to date
Uncertainty quantification in a hydrogen production system based on the solar hybrid sulfur process
No full textWater splitting through the Hybrid Sulfur (HyS) process powered by solar energy is a promising pathway to the production of green hydrogen. The main challenges to the development of this process are related to the intrinsic variability of the solar resource, which, besides requiring the deployment of innovative process solutions, introduces significant elements of uncertainty in the plant design. In this paper, the Polynomial Chaos Expansion (PCE) method is applied for the uncertainty quantification (UQ) in this kind of systems. In particular, a forward analysis dealing with the evaluation of the output probability distributions is performed. This is carried out in terms of the input probability distributions, and the analysis is focused on how uncertainty is propagated from the input to the output. Moreover, a comparison between the PCE method and the standard Monte Carlo analysis (using the Latin Hypercube Sampling method) is performed. The obtained results show the advantage of the PCE approach in terms of convergence rate and the number of function evaluations. Finally, a sensitivity analysis through Sobol’ indices has been carried out, which highlighted the influence of each variation in the input on the output
Psychiatric Disorders and lncRNAs: A Synaptic Match
No full textPsychiatric disorders represent a heterogeneous class of multifactorial mental diseases whose origin entails a pathogenic integration of genetic and environmental influences. Incidence of these pathologies is dangerously high, as more than 20% of the Western population is affected. Despite the diverse origins of specific molecular dysfunctions, these pathologies entail disruption of fine synaptic regulation, which is fundamental to behavioral adaptation to the environment. The synapses, as functional units of cognition, represent major evolutionary targets. Consistently, fine synaptic tuning occurs at several levels, involving a novel class of molecular regulators known as long non-coding RNAs (lncRNAs). Non-coding RNAs operate mainly in mammals as epigenetic modifiers and enhancers of proteome diversity. The prominent evolutionary expansion of the gene number of lncRNAs in mammals, particularly in primates and humans, and their preferential neuronal expression does represent a driving force that enhanced the layering of synaptic control mechanisms. In the last few years, remarkable alterations of the expression of lncRNAs have been reported in psychiatric conditions such as schizophrenia, autism, and depression, suggesting unprecedented mechanistic insights into disruption of fine synaptic tuning underlying severe behavioral manifestations of psychosis. In this review, we integrate literature data from rodent pathological models and human evidence that proposes the biology of lncRNAs as a promising field of neuropsychiatric investigation
IncliMed.“Dispositivo di misura dell’inclinazione della colonna vertebrale”. Un dispositivo di misura di superficie degli angoli di assetto statico del rachide e delle ampiezze di movimento articolare.
No full textSearching for centaurin-α2 interacting proteins: evidence of interaction with tubulin-β
No full textCentaurin-α2 belongs to the centaurin family and is characterized by a
zinc binding domain similar to Arf-GAP and by two PH domains. Its expression
pattern and function have not yet been extensively investigated.
Centaurin-α2 was shown to bind PIP2 and PIP3 and to localize at
plasma membrane, promoting the release of GTP and the consequent
inactivation of Arf-6, a protein involved in the regulation of intracellular
vesicular trafficking and in cytoskeletal rearrangement. We recently
studied the expression profile of CENTA2 mRNA by in situ hybridization,
during mouse embryo development and we found it is expressed
in early developmental stages of encephalon and heart.
With the final aim of elucidating the centaurin-α2 molecular pathways
and its biological role/s, we searched for interactors by means of the
yeast two-hybrid assay.
An interaction with the C-terminal region of tubulin-β has been observed
and confirmed by co-immunoprecipitation. This portion of tubulin-
β is involved in the binding of MAPs and motor proteins. Considering
that tubulin-β was found to bind phospholipase Cγ1 through
its PH domains, we hypothesized an interaction between centaurin-α2
mediated by this domain.
The yeast two-hybrid assay allowed us also to detect an interaction
with nucleoporin NUP53, a component of the nuclear pore complex,
that will be confirmed by co-immunoprecipitation.
According to our evidence, that will be further investigated, we propose
that centaurin-α2 can be localized at the plasma membrane, the cytoplasm and the perinuclear region, and can translocate through microtubules
anchoring, according to its hypothesized role in vesicular
trafficking
Inexact constraint preconditioners for linear systems arising in interior point methods
No full textInterior-point methods, Iterative solvers, Preconditioners, Approximate Jacobian,
Ricerca di interattori molecolari della centaurina-α2 : evidenze di associazione con la tubulina β
No full textImpact of cigarette smoke on vascular smooth muscle cell senescence
No full textAging and smoking are major risk factors for cardiovascular diseases. One characteristic of aging is the accumulation of senescent cells (e.g. cells that permanently lose the ability to divide). Senescent vascular smooth muscle cells (VSMCs) are present in atherosclerotic plaques, inducing an inflammatory environment and contributing to plaque instability and atherosclerotic complications.
Traditional cigarette (TC) smoke is a known exacerbator of age-related diseases and the combustion of tobacco releases thousands of toxic chemicals. To reduce the harm associated with TC, alternative products, such as tobacco heating-not-burning products (THPs), have been developed.
In our study, we compared, in the context of aging, the effects of aqueous extracts (AEs) from TC and THP on senescent VSMCs. Doxorubicin-induced senescent (DIS) VSMCs have been used as a positive control. VSMCs passaged 5 to 7 times (non-senescent cells) were incubated for 48h with 10% TC and THP AEs or doxorubicin 100 nM. Then, we measured several typical senescence markers, such as: senescence associated-β-galactosidase (SA-β-gal) activity, cell proliferation, cell cycle, senescence-associated genes and proteins expression, reactive oxygen species (ROS) production, and morphological changes.
TC increased SA-β-gal positive cells, slowed down cell proliferation, and down-regulated proliferation cell nuclear antigen (PCNA) expression, similar to what we observed in the DIS VSMCs. Instead, THP did not affect cell proliferation or PCNA expression. Expression of cell cycle inhibitors was upregulated in both TC and THP, but only TC arrested cells at the G2/M phase. Moreover, only TC significantly induced the expression of inflammatory markers (IL1, IL6, IL8, and MMP3) and increased mitochondrial and intracellular ROS production. Finally, TC, but not THP, increased the number of large and regular nuclei, a typical feature of senescent cells.
In conclusion, traditional cigarette smoke induces senescence in VSMCs similar to what we observed in doxorubicin-treated VSMCs. On the contrary, THP lacked most TC and doxorubicin-related functional, structural, and molecular effects on senescence, demonstrating a significantly reduced impact on VSMC senescence
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