1,721,355 research outputs found
The Role of the Tumor Suppressor Gene Protein Tyrosine Phosphatase Gamma in Cancer
Full text linkMembers of the Protein Tyrosine Phosphatase (PTPs) family are associated with growth regulation and cancer development. Acting as natural counterpart of tyrosine kinases (TKs), mainly involved in crucial signaling pathways such as regulation of cell cycle, proliferation, invasion and angiogenesis, they represent key parts of complex physiological homeostatic mechanisms. Protein tyrosine phosphatase gamma (PTPRG) is classified as a R5 of the receptor type (RPTPs) subfamily and is broadly expressed in various isoforms in different tissues. PTPRG is considered a tumor-suppressor gene (TSG) mapped on chromosome 3p14-21, a region frequently subject to loss of heterozygosity in various tumors. However, reported mechanisms of PTPRG downregulation include missense mutations, ncRNA gene regulation and epigenetic silencing by hypermethylation of CpG sites on promoter region causing loss of function of the gene product. Inactive forms or total loss of PTPRG protein have been described in sporadic and Lynch syndrome colorectal cancer, nasopharyngeal carcinoma, ovarian, breast, and lung cancers, gastric cancer or diseases affecting the hematopoietic compartment as Lymphoma and Leukemia. Noteworthy, in Central Nervous System (CNS) PTPRZ/PTPRG appears to be crucial in maintaining glioblastoma cell-related neuronal stemness, carving out a pathological functional role also in this tissue. In this review, we will summarize the current knowledge on the role of PTPRG in various human cancers
A new flexural-tensegrity bow
No full textThe bow is a simple machine now representing a paradigmatic example for demonstrating the applicability of the structural concept of flexural tensegrity, as chains of segments in unilateral contact coupled by unbonded prestressing tendons. The nonlinear and nonlocal constitutive laws for bending are dictated by the tendon prestress and, explicitly, by the shape of the contact surfaces between segments. Optimization requires functionally graded elastic properties fulfilling different objective functions, in terms of energetic efficiency, arrow exit speed, shooting accuracy, archer's comfort. An innovative non-recurve composite bow, called FlexTen bow, is theoretically analyzed, prototyped and tested, under static and dynamic conditions. Two different designs are considered, identical except for the shape of the contact surfaces between segments, so that the lever arm of the internal couple is either a linear or a sub-linear function of relative rotation. The FlexTen bow with sub-linear behavior outperforms classical bows, but the advantages, yet to be fully appreciated, also consist in the modular construction and the possibility of packaging
Transparent hybrid glass-steel bracing to improve the seismic capacity of historic buildings with colonnades
No full textAny seismic retrofitting plan on historical monuments has to follow the principles of minimal intervention, recognizability and reversibility. A feasibility study is here proposed for a new type of glass-based bracing, particularly suitable to strengthen soft storeys, typically represented by the presence of colonnades. This has the advantages of being stiff, slender and, most of all, transparent, recognizable and completely reversible. The bracing is a large laminated glass pane contoured by a thin steel lamina (frame), which confines the glass and provides a restraint against the pane rotation under horizontal actions. Since glass is a brittle material, we propose a system of gaskets and aluminum inserts, specifically designed to avoid contact stress concentration, especially at the corners of the glass pane. A paradigmatic case study, corresponding to a colonnade extrapolated from a representative historic building, has been analyzed in detail. Discrete element modeling has been used to simulate the dynamic response of the ancient masonry composed of stone blocks under horizontal seismic-like ground motion. Since the glass-based bracing represents a source of concentrated stiffness, we evaluate its correct placement inside the colonnade in order to avoid hammering effects, otherwise the bracing could even worsen the seismic capacity of the original structure. Another crucial issue is the connection of the bracing to the old masonry and foundations, for which possible technical details are provided. We show that a correct design and positioning of the bracing can improve the seismic capacity of the system with minimal visual impact
Flextegrity simple cubic lattices
Full text linkFlextegrity lattices are spatial grids composed of stiff segments kept in contact by compliant pre-tensioned tendons. The kinematic skeleton is sensible to the orientation of the segments, since their relative rotation produces the straining of the tendons to an amount that depends upon the angle of rotation and the shape of the pitch surfaces of the contact joints: these dictate the constitutive properties of the lattice in response to external actions. Two- and three-dimensional lattices are investigated, in which the contact pitch surfaces, obtained with axial-symmetric toothed conjugate profiles, mimic the kinematics of spheres, centred at the nodes of a simple cubic lattice, in pure rolling motion. The allowed mechanisms are discussed under infinitesimal deformation, to recognize possible eigenstress states in the lattice. The response under finite deformations is worked out for two-dimensional lattices under symmetric and asymmetric loading. The theoretical predictions are compared with experimental results on 3D-printed physical models. Possible extensions are discussed for lattices with segments of varying size, different arrangements and multi-stable contact joints. The flextegrity microstructure can represent a mesoscopic model for homogeneous crystals composed of non-pointwise molecules, but it could actually be manufactured in metamaterials with peculiar properties
Equilibrium of bi-stable flexural-tensegrity segmental beams
No full textOne dimensional discrete systems composed of a simple chain of bi-stable springs, with nearest neighbor interaction, have been used to interpret the complex equilibrium states of materials supporting multiple crystallographic phases, foldable macromolecules and biological structures. A discrete system is here proposed for bending within the broad class of flexural-tensegrity beams, which consist of segments in unilateral contact, with tailored-shaped contact surfaces, pre-stressed by an unbonded tendon. Any contact joint shows a bi-stable response to its relative rotation such as a snap-spring hinge, thanks to the internal carving of the segments that increases the mobility of the tendon within them. The constitutive response is nonlocal, because the tendon is free to slide within well lubricated sheaths. The case of pure bending, representing the counterpart of uniaxial tension in the one-dimensional lattice chain, shows that the system can support stable and metastable configurations, possibly containing one snap-spring hinge in the spinodal part of the energy landscape. Remarkably, not only the maximum hysteresis paths, but also the Maxwell paths, are strain-hardening in type. This is due to the nonlocal effect from the unbonded tendon: the rotation of any contact joint stiffens all the other joints, so that the orderly snaps of the spring-hinges occur at an increasing bending moment. An experimental program has been conducted on 3D printed physical models either in a hard or soft device. Symmetric and non-symmetric equilibrium configurations are obtained that are in perfect agreement with the theoretical predictions. Possible applications are envisaged, but they are yet to be fully appreciated
A nonlocal elastica inspired by flexural tensegrity
Full text linkA nonlocal theory is presented for the bending in large deformations under applied loads of an initially straight rod. This has similarities with the classical Euler's elastica in the sense that the bending stiffness remains homogeneously constant, but it depends on an integral average of the entire curvature field. The discretized form of the equilibrium equations is identical to those governing the response of structural systems already called flexural tensegrity beams, composed of a chain of segments in unilateral contact, whose integrity under flexion is due to prestressing tendons and to the shape of the contact surfaces. An analytical method of solution is proposed modulo the calculation of elliptic integrals, which is compared in paradigmatic examples with the numerical approach, or with an approximation of the curvature field with shape functions. The comparison between the continuum theory and the discrete case of flexural tensegrity highlights the physical role of the constitutive parameters, paving the way for a tailored design of innovative devices and the modelling of complex biological structures, based on the capability of transforming the mechanical properties with very small changes at the level of the underlying micro-constituents
Nonlinear effects in the vibrations of flexural tensegrity beams
No full textFlexural tensegrity is a structural principle for which the integrity under flexure of a beam formed by a chain of segments in unilateral contact is provided by an unbonded prestressing tendon anchored to the end segments, with the possible interposition of linear springs and linear dashpots. These are activated by the inflexion of the beam as a consequence of the particular shape of the contact surfaces of adjacent segments, so to induce a nonlinear dependence of the bending stiffness and structural damping on the amplitude of the inflexion. Under simplifying hypotheses, these nonlinear effects are analyzed for the nonlinear vibrations under harmonic excitation, also considering the effects of an initial camber. A variation of the tensile force in the tendon, via an actuator, can likewise modify the bending stiffness of the beam. A harmonic variation can provoke phenomena of parametric resonance, whereas an active control permits to annihilate pre-existing vibrations. The possibility of taking advantage of the nonlinear character of the damping through the optimization of the dissipated energy is also explored
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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