1,721,077 research outputs found
Function-structure relationship of PHT(1-11) analogues
Full text linkParathyroid hormone (PTH) is an 84 amino acid peptide hormone produced in the parathyroid glands. It acts primarily on bone and kidney to maintain extracellular calcium levels within normal limits. It has been shown that the 1-34 N-terminal fragment of PTH is sufficient to bind and activate the PTH type I receptor (PTH1R). The study of reduced-size PTH agonist and antagonist analogues has been the subject of extensive research for the development of bone anabolic drugs. Recent investigations focusing on the interaction of N-terminal fragments of PTH with PTH1R showed that some modifications can increase signalling potency in peptides as short as 11 amino acid residues (e.g. S3→A3, N10→Q10, L11→R11).
This work of PhD thesis represents our effort to investigate the role of side chains and structural characteristics of N-terminal domain of PTH(1-11). We applied the hierarchical approach and some peptidomimetics concepts to synthesize specific libraries of peptide to obtain information about hormone/receptor interaction. With these information, we have been able to project a first example of peptidomimetic of PTH. The strategical role of Val2 in the interaction with the
PTH1R receptor was demonstrated and confirmed. We have observed that guanidine group in C-terminus has a specific role in the binding to the receptor for the shortest PTH(1-11) fragment. We have shown that substitutions with alpha-MeNle
at positions 8 can increase helix stability which can be also stabilized and promoted through a bridge between 6 and 10 positions. We synthesized a group of active analogues which are characterized by a stable alpha-helix in all peptide sequences and have the correct orientation of essential esidues 2, 5, 8 and 11
Resistenza a taglio sperimentale di travi di calcestruzzo armate con barre longitudinali di GFRP
No full textIndagine sperimentale sulla resistenza a taglio di travi di calcestruzzo armate con barre longitudinali di GFRP
No full textNumerical analysis of composites with inclusions periodically arranged in non-orthogonal coordinate system
No full text
Predictive model for the collapse load of masonry assemblage with two piers joined by a spandrel
No full text
Micromechanical analysis of periodic composites by prescribing the average stress
No full textA new method for the micromechanical finite element analysis of unidirectional composites is presented. The method is especially effective in time-dependent analyses, as those involving viscoplasticity and viscoelasticity. The microstructure of the composites under consideration is characterized by periodicity and central symmetry, which allow analysing half of a unit cell for solving the micromechanical problem. Half of the unit cell contains only half of the continuous fibre and this makes the numerical analyses inexpensive in terms of computer memory usage and processing time. New boundary conditions are presented in order to prescribe the average stress on half of the unit cell of hexagonal and rectangular distributions of heterogeneities in the case of static analysis. Then, the new boundary conditions are used to prescribe the precise rate of the average stress in time-dependent analyses. With respect to other existing procedures, the proposed method is easy to adopt in commercial software and it does not require the modification of parts of the source code that are not usually accessible to the user. The proposed method is applied to the interesting case of composites with aligned long fibres imperfectly bonded to a viscoelastic matrix. The numerical simulations carried out in this work provide the loci of the average stress and strain corresponding to the initiation of the fibre-matrix debonding, which determines a considerable decay of the composite stiffness and strength. The influence of the geometrical properties of the microstructure is evaluated by analysing both hexagonal and rectangular distributions of fibres. The numerical results show how the inelastic behaviour of the matrix affects the loci corresponding to the initiation of the debonding
- …
