Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

Electro-elastic analysis of a coated spherical piezoceramic sensor

none2siNowadays, piezoceramics are widely used in sensor technology. However, due to their brittle nature, they can be cracked either in severe environmental conditions or during careless installation. Besides, the abrasion of their surface is a challenging problem in some applications. Hereby, the usage of a protective layer can prolong their effective working life. In this study, we analyze the electro-elastic behavior of a spherical piezoceramic sensor coated by a homogeneous protective layer. Then, with the motivation of reducing possible interfacial problems across the sensor/coating interface, and also improving the sensing ability of the coated sensor, material gradation concept is utilized. For this intent, two sensor/coating systems are studied: a piezoelectric sensor coated with a functionally graded material, and a functionally graded piezoelectric sensor coated with a homogeneous material. The governing equations are derived within the context of electro-elasticity theory and closed-form solutions are presented for coated sensors. It is concluded that a piezoceramic sensor protected with a functionally graded coating can improve the interfacial condition of the coated sensor, as well as enhancing its sensing ability.openSburlati, Roberta; Atashipour, Seyed AbdolrahimSburlati, Roberta; Atashipour, Seyed Abdolrahi

Reduction of the stress concentration factor in a homogeneous panel with hole by using a functionally graded layer

none3siThis work aims at understanding the effect of a radially heterogeneous layer around the hole in a homogeneous plate on the stress concentration factor. The problem concerns a single hole in a plate under different far-field in-plane loading conditions. By assuming a radial power law variation of Young’s modulus and constant value for Poisson’s ratio, the governing differential equations for plane stress conditions, and general in-plane loading conditions are studied. The elastic solutions are obtained in closed form and, in order to describe localized interface damage between the ring and the plate, two different interface conditions (perfectly bonded and frictionless contact) are studied. The formulae for the stress concentration factors are explicitly given for uniaxial, biaxial and shear in-plane loading conditions and comparisons with interface hoop stress values are performed. The solutions are investigated to understand the role played by the geometric and graded constitutive parameters. The results are validated with numerical finite element simulations in which some simplified hypotheses assumed in the analytical model, are relaxed to explore the range of validity of the elastic solution presented. In this way the results obtained are useful in tailoring the parameters for specific applications.openSburlati, Roberta; Atashipour, Seyed Rasoul; Atashipour, Seyed AbdolrahimSburlati, Roberta; Atashipour, Seyed Rasoul; Atashipour, Seyed Abdolrahi

Elastic analysis of thick-walled pressurized spherical vessels coated with functionally graded materials

In recent years, functionally graded material (FGM) has been widely explored in coating technology amongst both academic and industry communities. FGM coatings are suitable substitutes for many typical conventional coatings which are susceptible to cracking, debonding and eventual functional failure due to the mismatch of material properties at the coating/substrate interface. In this study, a thick spherical pressure vessel with an inner FGM coating subjected to internal and external hydrostatic pressure is analyzed within the context of three-dimensional elasticity theory. Young’s modulus of the coating is assumed to vary linearly or exponentially through the thickness, while Poisson’s ratio is considered as constant. A comparative numerical study of FGM versus homogeneous coating is conducted for the case of vessel under internal pressure, and the dependence of stress and displacement fields on the type of coating is examined and discussed