IGF-IR cooperates with ERα to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules

IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERα-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERα signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies

Mechanical Behavior of Steel Pipe Bends; An Overview.

An overview of the mechanical behavior of steel pipe (elbows) is offered, based on previously reported analytical solutions, numerical results, and experimental data. The behavior of pipe bends is characterized by significant deformations and stresses, quite higher than the ones developed in straight pipes with the same cross section. Under bending loading (in-plane and out-of-plane), the main feature of the response is cross-sectional ovalization, which influences bending capacity and is affected by the level of internal pressure. Bends subjected to cyclic in-plane bending exhibit fatigue damage, leading to base metal cracking at the elbow flank. Using advanced finite-element tools, the response of pipe elbows in buried pipelines subjected to ground-induced actions is also addressed, with emphasis on soil-pipeline interaction. Finally, the efficiency of special-purpose finite elements for modeling pipes and elbows is briefly discussed. © 2016 by ASME

Influence of variability of material mechanical properties on seismic performance of steel and steel-concrete composite structures

Modern standards for constructions in seismic zones allow the construction of buildings able to dissipate the energy of the seismic input through an appropriate location of cyclic plastic deformations involving the largest possible number of structural elements, forming thus a global collapse mechanisms without failure and instability phenomena both at local and global level. The key instrument for this purpose is the capacity design approach, which requires an appropriate selection of the design forces and an accurate definition of structural details within the plastic hinges zones, prescribing at the same time the oversizing of non-dissipative elements that shall remain in the elastic field during the earthquake. However, the localization of plastic hinges and the development of the global collapse mechanism is strongly influenced by the mechanical properties of materials, which are characterized by an inherent randomness. This variability can alter the final structural behaviour not matching the expected performance. In the present paper, the influence of the variability of material mechanical properties on the structural behaviour of steel and steel/concrete composite buildings is analyzed, evaluating the efficiency of the capacity design approach as proposed by Eurocode 8 and the possibility of introducing an upper limitation to the nominal yielding strength adopted in the design

Steel-based applications in earthquake-prone areas

Steel-Earth project aims at distributing among technicians, engineers, design companies and standardization bodies the results of three past RFCS projects (Steel-Retro [3], Opus [2] and PrecaSteel [1]), providing useful tools for the design and for the retrofit of existing buildings. Technical documents and practical applications to case studies, regarding design of steel and composite steel/concrete buildings and innovative steel-based techniques for the retrofit of existing r.c. and masonry constructions, have been elaborated and collected into a volume distributed during the final workshop of the dissemination project. Pre-normative and background documents concerning the design of steel and composite structures and the rehabilitation of existing constructions have been prepared. A lot of attention has been paid to the analysis of the influence of overstrength factors on the seismic design of steel and composite structures. The prepared documents have been distributed to the attending people and to the members of WG 2 (CEN/TC 250/SC 8/WG 2 “Steel and Composite Structures”) during the final workshop of the project. Technical sheets, working examples and background documents have been translated into several languages (German, French, Italian, Romanian and Greek) and are free available on the website of the project (https://www.steelconstruct.com/site/), where information regarding Steel-Earth are also presented.11 Workshops in Italy, Greece, Germany, Belgium, Portugal, Spain and Romania and 5 conferences in Emilia-Romagna have been organized, as well as 2 practical courses for engineers and academic people in Pavia (Italy). Flash-drives with the technical documents and applications elaborated in Steel-Earth have been distributed to the attending people