1,722,206 research outputs found
Gilt stuccoes of the italian baroque
C. Colombo, L. Toniolo, S. Bruni, P. Fermo, A. Casoli, G. Palla, C. L. Bianchi, Gilt stuccoes of the italian baroque. Studies in Conservation, 43, 1998, 201-208
Synthesis of Unnatural Alfa-N-linked Glycopeptides with Potential Antifreeze Activity
The synthesis of neo-glycoconjugates has been gaining much attention in recent years due to the relevance of glycopeptides and glycoproteins in many biological processes.[i] Our group has been actively dedicating its efforts to the synthesis of α-N-linked glycosylamides and glycopeptides.[ii] α-N-linked glycopeptides are unnatural molecules, since they display an α linkage between the peptide side chain and the sugar moiety, unlike natural glycopeptides which connect the peptide to the glycan through a β-N-glycosidic bond. This novel type of glycosylation of peptides could introduce modifications that can mimic and/or interfere with molecular recognition events.[iii] Direct glycosylation of peptide chains is not viable for the synthesis of molecules with α-N-linked configuration, since the corresponding α-glycosyl amines isomerise to the β-anomers. Only very recently Nα-Fmoc-protected glycosyl amino acids have been efficiently and stereoselectively synthesized and linearly incorporated into a peptide sequence.[iii] In the present paper these novel building blocks have been employed for the synthesis of complex structures that resemble antifreeze glycopeptides (Figure 1).[iv] These sequences were prepared using solid phase synthesis with Fmoc protocol, experimenting with different conditions and also using microwave assisted solid phase synthesis, in an effort to enhance the reactivity of our unnatural building block. The α-N-linked glycopeptides were obtained with modest yields, their secondary structure was assessed by circular dichroism and their antifreeze properties were evaluated in the group of Prof. Robert N. Ben. Despite the fact that our compounds do not show significant antifreeze activity, this work constitutes the first attempt towards the synthesis of complex α-N-linked glycopeptides and has been useful to understand the behaviour, sometimes unexpected, of these molecules, in terms of reactivity and stability. [i] D. P. Gamblin, E. M. Scanlan, B. G. Davis, Chem. Rev. 2009, 109, 131-163. [ii] a) F. Nisic, A. Bernardi, Carbohydr. Res. 2011,346, 465-71. b) C. Colombo, A. Bernardi,Eur. J. Org. Chem. 2011, 3911–3919. [iii] F. Marcelo, F. J. Cañada, S. André, C. Colombo, F. Doro, H. J. Gabius, A. Bernardi, J. Jiménez-Barbero. Organic & Biomolecular Chemistry 2012, DOI: 10.1039/C2OB07135E. [iv] a) Garner, J.; Harding, M. M. ChemBioChem 2010, 11 2489-2498. b) Leclere, M; Kwok, K. B.; Luke K. W.; Allan, D. S.; Ben, R. N. Bioconjugate Chem. 2011, 22, 1804-1810
Mutation-targeted personalised medicine for cystic fibrosis
Comment on Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST)
Liver disease in cystic fibrosis
PURPOSE OF REVIEW: This review highlights recent developments in liver disease associated with cystic fibrosis. RECENT FINDINGS: The broad spectrum of hepatobiliary problems in cystic fibrosis includes specific alterations ascribable to the underlying defect as well as lesions of iatrogenic origin or that reflect the effects of a disease process occurring outside the liver. Focal biliary cirrhosis, resulting from biliary obstruction and progressive periportal fibrosis, is the most clinically relevant problem, because extension of the initially focal fibrogenic process may lead to multilobular biliary cirrhosis, portal hypertension and eventually liver failure. Cystic fibrosis associated liver disease is presently classified among genetic cholangiopathies and results from lack or dysfunction of the cystic fibrosis transmembrane regulator at the apical membrane of bile duct cells. Major advances have been achieved regarding characterization of natural history, risk factors, diagnostic modalities and treatment options. SUMMARY: Liver disease is a relatively frequent and early complication of cystic fibrosis. The pathogenesis is apparently multifactorial, with contributions from environmental and genetic determinants. Its impact on quality of life and survival will increase in future years, and its early detection and treatment will become increasingly important issues. Ursodeoxycholic acid is the only treatment currently available, but novel therapeutic options are being evaluated. [References: 72
Thermal methods for fatigue characterization of components
In recent years, the thermographic technique has been regarded as a key tool to investigate the fatigue behavior of materials instead of time and cost consuming traditional methods. One way to assess the fatigue as an irreversible process is studying the temperature signature due to the heat dissipation during the cyclic loading. Numerous studies have suggested that the shift from anelastic to inelastic strains results in a significant level of intrinsic dissipation, indicating the presence of the fatigue damage.
The primary objective of this study is to explore heat dissipation in fatigue tests through a combination of experimental methods and numerical models by utilizing the fundamental temperature component related to dissipation, the second amplitude harmonic (SAH) of the temperature. The proposed hybrid approach integrates experiments with a numerical model to pinpoint the specific volume generating heat during the fatigue test. The investigation also delves into the impact of loading frequency on the fundamental temperature component associated with dissipation.
In experimental part of the study, a comprehensive campaign was carried out to capture the material's response under both static and cyclic loading conditions. The experimental data are employed for comparing the accuracy of different thermal indices in fatigue limit estimation and establishing the numerical model, act as reference data for comparison.
In the numerical part of the study, models are established in COMSOL Multiphysics 5.6 to simulate the temperature distribution on the surface of the specimen. After the verification with analytical solution of 1-D heat equation, a model is proposed for heat source identification. One of the main controversial issues in fatigue characterization is addressed in this study, whether the entire gauge volume dissipates or not. Additionally, the effect of loading frequency on SAH of temperature reveals its limitation in thermographic measurement and fatigue assessment
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