Euler-Richardson method preconditioned by weakly stochastic matrix algebras : a potential contribution to Pagerank computation

Let S be a column stochastic matrix with at least one full row. Then S describes a Pagerank-like random walk since the computation of the Perron vector x of S can be tackled by solving a suitable M-matrix linear system Mx = y, where M = I − τ A, A is a column stochastic matrix and τ is a positive coefficient smaller than one. The Pagerank centrality index on graphs is a relevant example where these two formulations appear. Previous investigations have shown that the Euler- Richardson (ER) method can be considered in order to approach the Pagerank computation problem by means of preconditioning strategies. In this work, it is observed indeed that the classical power method can be embedded into the ER scheme, through a suitable simple preconditioner. Therefore, a new preconditioner is proposed based on fast Householder transformations and the concept of low complexity weakly stochastic algebras, which gives rise to an effective alternative to the power method for large-scale sparse problems. Detailed mathematical reasonings for this choice are given and the convergence properties discussed. Numerical tests performed on real-world datasets are presented, showing the advantages given by the use of the proposed Householder-Richardson method

INVESTIGATION ACTIVITY ABOUT A COLLAPSED STEEL STRUCTURE SUBJECTED TO A REAL FIRE, Fire scenarios and structural behaviour of a real steel structure

The paper describes the behaviour ofa real steel structure collapsed under a fire event. 3D structural analyses were performed with SAFIR program (J-M Franssen, 2005). Different modellingare implemented with some fire load models and analyses of thebehaviour of the whole structure. The main purpose of this work was to investigate the failure types of a warehouse structure under fire conditions. Different fire conditions were applied to the steel frame sections, with ISOcurve (ISO EN 834-8:2002) and zone model approach. The analyses show that with unprotected steel sections, horizontal structures are more critical than columns. Trough applying a performance basedapproach,structure has 30 minutes of fire resistance

The Eps15 homology (EH) domain

AbstractThe Eps15 homology (EH) domain was originally identified as a motif present in three copies at the NH2-termini of Eps15 and of the related molecule Eps15R. Both of these molecules are substrates for the tyrosine kinase activity of the epidermal growth factor receptor and hence the name ‘Eps15 homology’ or EH domain [Wong et al. (1994) Oncogene 9, 1591–1597; Wong et al. (1995) Proc. Natl. Acad. Sci. USA 92, 9530–9534; Fazioli et al. (1993) Mol. Cell. Biol. 13, 5814–5828] was derived. The motif was subsequently found in several proteins from yeast to nematode, thus establishing its evolutionary conservation. Initial studies with filter-binding assays and phage-displayed libraries demonstrated its protein:protein interaction abilities and identified specific ligands. Subsequently, structural analyses established the molecular bases of recognition between EH domains and cognate peptides. To date, several EH-containing and EH-binding proteins have been identified, which establish in the cell a network of protein:protein interactions, defined as the EH network. This network coordinates cellular functions connected with endocytosis, actin remodeling and intracellular transduction of signals

Peri-Implant Bone Loss and Overload: A Systematic Review Focusing on Occlusal Analysis through Digital and Analogic Methods.

The present review aimed to assess the possible relationship between occlusal overload and peri-implant bone loss. In accordance with the PRISMA guidelines, the MEDLINE, Scopus, and Cochrane databases were searched from January 1985 up to and including December 2021. The search strategy applied was: (dental OR oral) AND implants AND (overload OR excessive load OR occlusal wear) AND (bone loss OR peri-implantitis OR failure). Clinical studies that reported quantitative analysis of occlusal loads through digital contacts and/or occlusal wear were included. The studies were screened for eligibility by two independent reviewers. The quality of the included studies was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. In total, 492 studies were identified in the search during the initial screening. Of those, 84 were subjected to full-text evaluation, and 7 fulfilled the inclusion criteria (4 cohort studies, 2 cross-sectional, and 1 case-control). Only one study used a digital device to assess excessive occlusal forces. Four out of seven studies reported a positive correlation between the overload and the crestal bone loss. All of the included studies had moderate to serious overall risk of bias, according to the ROBINS-I tool. In conclusion, the reported data relating the occlusal analysis to the peri-implant bone level seem to reveal an association, which must be further investigated using new digital tools that can help to standardize the methodology

Tyrosine Phosphorylation of Eps15 Is Required for Ligand-Regulated, but Not Constitutive, Endocytosis

Membrane receptors are internalized either constitutively or upon ligand engagement. Whereas there is evidence for differential regulation of the two processes, little is known about the molecular machinery involved. Previous studies have shown that an unidentified kinase substrate is required for endocytosis of the epidermal growth factor receptor (EGFR), the prototypical ligand-inducible receptor, but not of the transferrin receptor (TfR), the prototypical constitutively internalized receptor. Eps15, an endocytic protein that is tyrosine phosphorylated by EGFR, is a candidate for such a function. Here, we show that tyrosine phosphorylation of Eps15 is necessary for internalization of the EGFR, but not of the TfR. We mapped Tyr 850 as the major in vivo tyrosine phosphorylation site of Eps15. A phosphorylation-negative mutant of Eps15 acted as a dominant negative on the internalization of the EGFR, but not of the TfR. A phosphopeptide, corresponding to the phosphorylated sequence of Eps15, inhibited EGFR endocytosis, suggesting that phosphotyrosine in Eps15 serves as a docking site for a phosphotyrosine binding protein. Thus, tyrosine phosphorylation of Eps15 represents the first molecular determinant, other than those contained in the receptors themselves, which is involved in the differential regulation of constitutive vs. regulated endocytosis

In-Vivo Real-Time Control of Protein Expression from Endogenous and Synthetic Gene Networks

We describe an innovative experimental and computational approach to control the expression of a protein in a population of yeast cells. We designed a simple control algorithm to automatically regulate the administration of inducer molecules to the cells by comparing the actual protein expression level in the cell population with the desired expression level. We then built an automated platform based on a microfluidic device, a time-lapse microscopy apparatus, and a set of motorized syringes, all controlled by a computer. We tested the platform to force yeast cells to express a desired fixed, or time-varying, amount of a reporter protein over thousands of minutes. The computer automatically switched the type of sugar administered to the cells, its concentration and its duration, according to the control algorithm. Our approach can be used to control expression of any protein, fused to a fluorescent reporter, provided that an external molecule known to (indirectly) affect its promoter activity is available

An Atlas of Altered Expression of Deubiquitinating Enzymes in Human Cancer

BACKGROUND: Deubiquitinating enzymes (DUBs) are proteases that process ubiquitin (Ub) or ubiquitin-like gene products, remodel polyubiquitin(-like) chains on target proteins, and counteract protein ubiquitination exerted by E3 ubiquitin-ligases. A wealth of studies has established the relevance of DUBs to the control of physiological processes whose subversion is known to cause cellular transformation, including cell cycle progression, DNA repair, endocytosis and signal transduction. Altered expression of DUBs might, therefore, subvert both the proteolytic and signaling functions of the Ub system. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we report the first comprehensive screening of DUB dysregulation in human cancers by in situ hybridization on tissue microarrays (ISH-TMA). ISH-TMA has proven to be a reliable methodology to conduct this kind of study, particularly because it allows the precise identification of the cellular origin of the signals. Thus, signals associated with the tumor component can be distinguished from those associated with the tumor microenvironment. Specimens derived from various normal and malignant tumor tissues were analyzed, and the "normal" samples were derived, whenever possible, from the same patients from whom tumors were obtained. Of the ∼90 DUBs encoded by the human genome, 33 were found to be expressed in at least one of the analyzed tissues, of which 22 were altered in cancers. Selected DUBs were subjected to further validation, by analyzing their expression in large cohorts of tumor samples. This analysis unveiled significant correlations between DUB expression and relevant clinical and pathological parameters, which were in some cases indicative of aggressive disease. CONCLUSIONS/SIGNIFICANCE: The results presented here demonstrate that DUB dysregulation is a frequent event in cancer, and have implications for therapeutic approaches based on DUB inhibition

Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis

The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis. Although altered Notch signaling has been linked to human diseases, including cancer, evidence for a substantial involvement of Notch in human tumors has remained elusive. Here, we show that Numb-mediated control on Notch signaling is lost in ∼50% of human mammary carcinomas, due to specific Numb ubiquitination and proteasomal degradation. Mechanistically, Numb operates as an oncosuppressor, as its ectopic expression in Numb-negative, but not in Numb-positive, tumor cells inhibits proliferation. Increased Notch signaling is observed in Numb-negative tumors, but reverts to basal levels after enforced expression of Numb. Conversely, Numb silencing increases Notch signaling in normal breast cells and in Numb-positive breast tumors. Finally, growth suppression of Numb-negative, but not Numb-positive, breast tumors can be achieved by pharmacological inhibition of Notch. Thus, the Numb/Notch biological antagonism is relevant to the homeostasis of the normal mammary parenchyma and its subversion contributes to human mammary carcinogenesis

Detection of Antibodies to Human Herpesvirus 8 (HHV-8) among Women of Child-Bearing Age in the Apulia Region (South-Eastern Italy):

In this study the authors investigated the presence of serum antibodies to Human Herpesvirus 8 (HHV-8) in a group of women of child-bearing age in the Apulia region (South Eastern Italy). A seroprevalence of 16.8% was observed, increasing, although non significantly, with the age of the women (10.6% in women between 19 and 25 years, 25.3% in women aging more than 35 years). The presence of antibodies to Hepatitis C Virus (HCV) was significantly associated to the detection of antibodies to HHV-8. Possible mother-to-child transmission of HHV-8 as well as the outcome of fetuses or children born to HHV-8 positive mothers are still a matter of debate. This study, showing the wide diffusion of HHV-8 infection in healthy women of child-bearing age in our geographical area, highlights the urgency of studies aimed to better clarify these relevant topics