110 research outputs found
Topology optimization of multiple anisotropic materials, with application to self-assembling diblock copolymers
We propose a solution strategy for a multimaterial minimum compliance
topology optimization problem, which consists in finding the optimal allocation
of a finite number of candidate (possibly anisotropic) materials inside a
reference domain, with the aim of maximizing the stiffness of the body. As a
relevant and novel application we consider the optimization of self-assembled
structures obtained by means of diblock copolymers. Such polymers are a class
of self-assembling materials which spontaneously synthesize periodic
microstructures at the nanoscale, whose anisotropic features can be exploited
to build structures with optimal elastic response, resembling biological
tissues exhibiting microstructures, such as bones and wood. For this purpose we
present a new generalization of the classical Optimality Criteria algorithm to
encompass a wider class of problems, where multiple candidate materials are
considered, the orientation of the anisotropic materials is optimized, and the
elastic properties of the materials are assumed to depend on a scalar
parameter, which is optimized simultaneously to the material allocation and
orientation. Well-posedness of the optimization problem and well-definition of
the presented algorithm are narrowly treated and proved. The capabilities of
the proposed method are assessed through several numerical tests
Link Prediction in Criminal Networks: A Tool for Criminal Intelligence Analysis
The problem of link prediction has recently received increasing attention from scholars in network science. In social network analysis, one of its aims is to recover missing links, namely connections among actors which are likely to exist but have not been reported because data are incomplete or subject to various types of uncertainty. In the field of criminal investigations, problems of incomplete information are encountered almost by definition, given the obvious anti-detection strategies set up by criminals and the limited investigative resources. In this paper, we work on a specific dataset obtained from a real investigation, and we propose a strategy to identify missing links in a criminal network on the basis of the topological analysis of the links classified as marginal, i.e. removed during the investigation procedure. The main assumption is that missing links should have opposite features with respect to marginal ones. Measures of node similarity turn out to provide the best characterization in this sense. The inspection of the judicial source documents confirms that the predicted links, in most instances, do relate actors with large likelihood of co-participation in illicit activitie
Multiphysics simulation of corona discharge induced ionic wind
Ionic wind devices or electrostatic fluid accelerators are becoming of
increasing interest as tools for thermal management, in particular for
semiconductor devices. In this work, we present a numerical model for
predicting the performance of such devices, whose main benefit is the ability
to accurately predict the amount of charge injected at the corona electrode.
Our multiphysics numerical model consists of a highly nonlinear strongly
coupled set of PDEs including the Navier-Stokes equations for fluid flow,
Poisson's equation for electrostatic potential, charge continuity and heat
transfer equations. To solve this system we employ a staggered solution
algorithm that generalizes Gummel's algorithm for charge transport in
semiconductors. Predictions of our simulations are validated by comparison with
experimental measurements and are shown to closely match. Finally, our
simulation tool is used to estimate the effectiveness of the design of an
electrohydrodynamic cooling apparatus for power electronics applications.Comment: 24 pages, 17 figure
The construction of a Quality of Life Wellbeing Index for cancer patients in follow-up: the ONCORELIEF project
ONCORELIEF aims to improve post-treatment health status, wellbeing, and follow-up care of cancer patients in a patient-centric way: independent of the specific treatment and pathway points, but specific to each patient’s experience and needs, incorporating the patient’s illness experience and the psychosocial context
Extramitochondrial porin: Facts and hypotheses
Mitochondrial porin, or VDAC, is a pore-forming protein abundant in the outer mitochondrial membrane. Several publications have reported extramitochondrial localizations as well, but the evidence was considered insufficient by many, and the presence of porin in nonmitochondrial cellular compartments has remained in doubt for a long time. We have now obtained new data indicating that the plasma membrane of hematopoietic cells contains porin, probably located mostly in caveolae or caveolae-like domains. Porin was purified from the plasma membrane of intact cells by a procedure utilizing the membrane-impermeable labeling reagent NH-SS-biotin and streptavidin affinity chromatography, and shown to have the same properties as mitochondrial porin. A channel with properties similar to that of isolated VDAC was observed by patch-clamping intact cells. This review discusses the evidence supporting extramitochondrial localization, the putative identification of the plasma membrane porin with the 'maxi' chloride channel, the hypothetical mechanisms of sorting porin to various cellular membrane structures, and its possible functions
Expression of Caveolin-1 Is Required for the Transport of Caveolin-2 to the Plasma Membrane RETENTION OF CAVEOLIN-2 AT THE LEVEL OF THE GOLGI COMPLEX
Caveolins-1 and -2 are normally co-expressed, and they form a hetero-oligomeric complex in many cell types. These caveolin hetero-oligomers are thought to represent the assembly units that drive caveolae formation in vivo. However, the functional significance of the interaction between caveolins-1 and -2 remains unknown. Here, we show that caveolin-1 co-expression is required for the transport of caveolin-2 from the Golgi complex to the plasma membrane. We identified a human erythroleukemic cell line, K562, that expresses caveolin-2 but fails to express detectable levels of caveolin-1. This allowed us to stringently assess the effects of recombinant caveolin-1 expression on the behavior of endogenous caveolin-2. We show that expression of caveolin-1 in K562 cells is sufficient to reconstitute the de novo formation of caveolae in these cells. In addition, recombinant expression of caveolin-1 allows caveolin-2 to form high molecular mass oligomers that are targeted to caveolae-enriched membrane fractions. In striking contrast, in the absence of caveolin-1 expression, caveolin-2 forms low molecular mass oligomers that are retained at the level of the Golgi complex. Interestingly, we also show that expression of caveolin-1 in K562 cells dramatically up-regulates the expression of endogenous caveolin-2. Northern blot analysis reveals that caveolin-2 mRNA levels remain constant under these conditions, suggesting that the expression of caveolin-1 stabilizes the caveolin-2 protein. Conversely, transient expression of caveolin-2 in CHO cells is sufficient to up-regulate endogenous caveolin-1 expression. Thus, the formation of a hetero-oligomeric complex between caveolins-1 and -2 stabilizes the caveolin-2 protein product and allows caveolin-2 to be transported from the Golgi complex to the plasma membrane
Neopterin levels are independently associated with cardiac remodeling in patients with chronic heart failure
Neopterin, a marker of inflammation and monocyte activation, is found increased in patients with heart failure (HF). This study investigates whether neopterin levels correlate with left ventricular (LV) remodeling and brain natriuretic peptide (BNP), a marker of cardiac stress, in chronic HF (CHF) patients with different severity of disease. The relationship between elevated neopterin levels and LV enlargement in CHF patients suggests a crucial role of monocyte activation in the development of cardiac dysfunction in CHF patients. Assessment of neopterin levels is a potential biomarker to evaluate the progression of LV remodeling in CHF patients
FGF-trapping hampers cancer stem-like cells in uveal melanoma
Background: Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required. Methods: Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients' clusters. Results: By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes. Conclusions: Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM
Runx2 stimulates neoangiogenesis through the Runt domain in melanoma
Runx2 is a transcription factor involved in melanoma cell migration and proliferation. Here, we extended the analysis of Runt domain of Runx2 in melanoma cells to deepen understanding of the underlying mechanisms. By the CRISPR/Cas9 system we generated the Runt KO melanoma cells 3G8. Interestingly, the proteome analysis showed a specific protein signature of 3G8 cells related to apoptosis and migration, and pointed out the involvement of Runt domain in the neoangiogenesis process. Among the proteins implicated in angiogenesis we identified fatty acid synthase, chloride intracellular channel protein-4, heat shock protein beta-1, Rho guanine nucleotide exchange factor 1, D-3-phosphoglycerate dehydrogenase, myosin-1c and caveolin-1. Upon querying the TCGA provisional database for melanoma, the genes related to these proteins were found altered in 51.36% of total patients. In addition, VEGF gene expression was reduced in 3G8 as compared to A375 cells; and HUVEC co-cultured with 3G8 cells expressed lower levels of CD105 and CD31 neoangiogenetic markers. Furthermore, the tube formation assay revealed down-regulation of capillary-like structures in HUVEC co-cultured with 3G8 in comparison to those with A375 cells. These findings provide new insight into Runx2 molecular details which can be crucial to possibly propose it as an oncotarget of melanoma
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