Experimental and Numerical Analysis of Soil–Pipe Interaction

Cases of pipeline damage caused by landslides are common in coastal or mountainous regions, where a continuous monitoring/repair activity is planned in order to maintain their serviceability. The analysis of the soil–structure interaction phenomenon can be invoked to improve the planning and design of buried pipelines, to guide monitoring, and to reduce the risk of damage or failure. Two different approaches are considered in this paper: small scale laboratory tests and numerical simulations using the distinct element method (DEM). The experimental setup consists of a box filled with sand and water. Several experiments were performed, in which the diameter and the depth of the tube varied. The numerical simulations are divided in two separate series: in the first, the numerical model is calibrated and its reliability in reproducing the experimental tests is checked; in the second series, the direction of the relative displacement between the tube and the surrounding “numerical soil” varies over the range ±90° with respect to the horizontal. In the latter, both vertical and horizontal components of the drag force are measured and the corresponding interaction diagrams are constructed. The DEM simulations provide useful information about the shape of the failure mechanisms and the force transfer within the soil.     

Flow,Thermal and Microstructural Analysis during Cast Rolling of Steel in In‐line Strip Production Process

A mathematical model was developed to describe the in‐line hot rolling deformation and recrystallization behaviour of austenite after the solidification on a thin slab casting plant. The most significant features of the cast rolling process were taken into consideration: through‐thickness thermal gradients, inhomogeneous stress and strain, temperature discontinuity between the strip and the rolls. A HSLA (High Strength Low Alloy) steel has been chosen to perform the experiments of cast rolling. The characteristic constants ruling the microstructural evolution of that steel were computed and integrated into the computational module which manages the structural stress‐strain and strain rate computation. The developed approach is based on the Navier‐Stokes’ equations which were used to compute the speed field in the strip during the deformation. Then a model providing a proper constitutive equation was structured on the basis of the Yada's model based on evolution of the dislocation populations. The use of the Navier‐Stokes’ formalism allows to reach the resolution of the structural problem from the data measured easily during the industrial practice (i.e. speed of the rolled product at the entry and at the exit of a stand, the temperature of the rolled material). The validation of this computational approach was obtained by a comparison between the prior austenite grain size of the strip in different positions of the hot rolling process, as well as by a comparison between the computed deformation power and the measured one provided by the engines moving the rolls.     

Mass spectrometry for detection of 4-hydroxy-trans-2-nonenal (HNE) adducts with peptides and proteins

Despite the great technical advancement of mass spectrometry, this technique has contributed in a limited way to the discovery and quantitation of specific/precocious markers linked to free radical-mediated diseases. Unsaturated aldehydes generated by free radical-induced lipid peroxidation of polyunsaturated fatty acids, and in particular 4-hydroxy-trans-2 nonenal (HNE), are involved in the onset and progression of many pathologies such as cardiovascular (atherosclerosis, long-term complications of diabetes) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of HNE are attributed to the capacity of HNE to react with the nucleophilic sites of proteins and peptides (other than nucleic acids), to form covalently modified biomolecules that can disrupt important cellular functions and induce mutations. By considering the emerging role of HNE in several human diseases, an unequivocal analytical approach as mass spectrometry to detect/elucidate the structure of protein-HNE adducts in biological matrices is strictly needed not only to understand the reaction mechanism of HNE, but also to gain a deeper insight into the pathological role of HNE. This with the aim to provide intermediate diagnostic biomarkers for human diseases. This review sheds focus on the "state-of-the-art" of mass spectrometric applications in the field of HNE-protein adducts characterization, starting from the fundamental early studies and discussing the different MS-based approaches that can provide detailed information on the mechanistic aspects of HNE-protein interaction. In the last decade, the increases in the accessible mass ranges of modern instruments and advances in ionization methods have made possible a fundamental improvement in the analysis of protein-HNE adducts by mass spectrometry, and in particular by matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) tandem mass spectrometry. The recent developments and uses of combined analytical approaches to detect and characterize the type/site of interaction have been highlighted, and several other aspects, including sample preparation methodologies, structure elucidation, and data analysis have also been considered.     

Magnetoelastic Stability of Magnetic Axial Bearings

Permanent magnet bearings offer no wear and no mechanical friction. Recently, Rare Earth (RE) permanent magnets have been used, which give rise to force fields 20 times greater than those of common magnets. RE also allows to build magnets suitable for bearings of every shape. RE bearings are then profitable. On the other hand, permanent magnet bearings are unstable. For example, the levitated ring of the axial bearing with opposite magnetic fields of Fig. 1 is stable axially, but unstable radially. It has been, however, verified that a permanent magnet system may become stable under peculiar conditions. As an example, if the above-mentioned levitated ring is subjected to a parametric axial excitation, its radial instability can be removed. In our opinion, it may also be possible that stability is obtained by exploiting microstructural properties of ferromagnetic materials, especially of RE, like dimensional and magnetic changes if subjected to mechanical stresses. Then, in this paper, the stability of the levitated member of an RE axial ring bearing is investigated by a suitable exploitation of magnetoelastic properties of the ring.

Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS-induced protein modifications. During the last few years, mass spectrometry (MS)-based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun.     

Solving the electricity production planning problem by a column generation based heuristic

This paper presents a heuristic method based on column generation for the EDF (Electricité De France) long-term electricity production planning problem proposed as subject of the ROADEF/EURO 2010 Challenge. This is to our knowledge the first-ranked method among those methods based on mathematical programming, and was ranked fourth overall. The problem consists in determining a production plan over the whole time horizon for each thermal power plant of the French electricity company, and for nuclear plants, a schedule of plant outages which are necessary for refueling and maintenance operations. The average cost of the overall outage and production planning, computed over a set of demand scenarios, is to be minimized. The method proceeds in two stages. In the first stage, dates for outages are fixed once for all for each nuclear plant. Data are aggregated with a single average scenario and reduced time steps, and a set-partitioning reformulation of this aggregated problem is solved for fixing outage dates with a heuristic based on column generation. The pricing problem associated with each nuclear plant is a shortest path problem in an appropriately constructed graph. In the second stage, the reload level is determined at each date of an outage, considering now all scenarios. Finally, the production quantities between two outages are optimized for each plant and each scenario by solving independent linear programming problems.     

Simplified seismic analysis of piping or equipment mounted on two points of a multistory structure

A simplified procedure is presented to calculate the maximum earthquake response of light mechanical or electrical equipment supported at two arbitrary points of a building structure. The procedure is derived on the basis of the application of the response spectrum method to a combined structure-equipment system, but, in an effort to avoid the complications of such an approach, it is formulated in terms of the dynamic characteristics of the two independent components. It fully takes into account the interaction between the two subsystems, and avoids the generation of floor response spectra and the need to consider two different support excitations. The formulation is attained by using Hurty's component mode synthesis technique and Rayleigh's principle. Linear systems with classical modes of vibration and small structure to equipment mass ratios are considered. The simplicity of the method is demonstrated by a numerical example, and its accuracy verified by a comparative study. In this comparative study, the suggested procedure estimates correct solutions with an average error of about 2%.     

Identification of Candidate mRNA Isoforms for Prostate Cancer-Risk SNPs Utilizing Iso-eQTL and sQTL Methods

Single nucleotide polymorphisms (SNPs) impacting the alternative splicing (AS) process (sQTLs) or isoform expression (iso-eQTL) are implicated as important cancer regulatory elements. To find the sQTL and iso-eQTL, we retrieved prostate cancer (PrCa) tissue RNA-seq and genotype data originating from 385 PrCa European patients from The Cancer Genome Atlas. We conducted RNA-seq analysis with isoform-based and splice event-based approaches. The MatrixEQTL was used to identify PrCa-associated sQTLs and iso-eQTLs. The overlap between sQTL and iso-eQTL with GWAS loci and those that are differentially expressed between cancer and normal tissue were identified. The cis-acting associations (FDR < 0.05) for PrCa-risk SNPs identified 42, 123, and 90 PrCa-associated cassette exons, intron retention, and mRNA isoforms belonging to 25, 95, and 83 genes, respectively; while assessment of trans-acting association (FDR < 0.05) yielded 59, 65, and 196 PrCa-associated cassette exons, intron retention and mRNA isoforms belonging to 35, 55, and 181 genes, respectively. The results suggest that functional PrCa-associated SNPs can play a role in PrCa genesis by making an important contribution to the dysregulation of AS and, consequently, impacting the expression of the mRNA isoforms.     

IsomiR-eQTL: A Cancer-Specific Expression Quantitative Trait Loci Database of miRNAs and Their Isoforms

The identification of expression quantitative trait loci (eQTL) is an important component in efforts to understand how genetic variants influence disease risk. MicroRNAs (miRNAs) are short noncoding RNA molecules capable of regulating the expression of several genes simultaneously. Recently, several novel isomers of miRNAs (isomiRs) that differ slightly in length and sequence composition compared to their canonical miRNAs have been reported. Here we present isomiR-eQTL, a user-friendly database designed to help researchers find single nucleotide polymorphisms (SNPs) that can impact miRNA (miR-eQTL) and isomiR expression (isomiR-eQTL) in 30 cancer types. The isomiR-eQTL includes a total of 152,671 miR-eQTLs and 2,390,805 isomiR-eQTLs at a false discovery rate (FDR) of 0.05. It also includes 65,733 miR-eQTLs overlapping known cancer-associated loci identified through genome-wide association studies (GWAS). To the best of our knowledge, this is the first study investigating the impact of SNPs on isomiR expression at the genome-wide level. This database may pave the way for researchers toward finding a model for personalised medicine in which miRNAs, isomiRs, and genotypes are utilised.     

TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients

The survival of patients with glioblastoma (GBM) is poor. The main cause is the presence of glioma stem cells (GSCs), exceptionally resistant to temozolomide (TMZ) treatment. This last may be related to the heterogeneous expression of ion channels, among them TRPML2. Its mRNA expression was evaluated in two different neural stem cell (NS/PC) lines and sixteen GBM stem-like cells by qRT-PCR. The response to TMZ was evaluated in undifferentiated or differentiated GSCs, and in TRPML2-induced or silenced GSCs. The relationship between TRPML2 expression and responsiveness to TMZ treatment was evaluated by MTT assay showing that increased TRPML2 mRNA levels are associated with resistance to TMZ. This research was deepened by qRT-PCR and western blot analysis. PI3K/AKT and JAK/STAT pathways as well as ABC and SLC drug transporters were involved. Finally, the relationship between TRPML2 expression and overall survival (OS) and progression-free survival (PFS) in patient-derived GSCs was evaluated by Kaplan–Meier analysis. The expression of TRPML2 mRNA correlates with worse OS and PFS in GBM patients. Thus, the expression of TRPML2 in GSCs influences the responsiveness to TMZ in vitro and affects OS and PFS in GBM patients.