לוח שנה משולב

Materials that exhibit a "yield" phenomenon response elastically to small strains or stresses, but at some critical value of the stress they yield mechanically and exhibit a complex plastic flow. The search of criteria to distinguish the properties of the material before and after the yield was long and futile; none of the standard signatures like correlation functions, Voronoi tesselations or any other "structural" measure succeeded to clarify the difference between pre-yield and post-yield configurations. I willexplain in this talk how to construct a new order parameter that allows us to show that the yield phenomenon is a bona-fide first order thermodynamic phase transition, shedding an entirely new light on the
phenomenon.

Materials that exhibit a "yield" phenomenon response elastically to small strains or stresses, but at some critical value of the stress they yield mechanically and exhibit a complex plastic flow. The search of criteria to distinguish the properties of the material before and after the yield was long and futile; none of the standard signatures like correlation functions, Voronoi tesselations or any other "structural" measure succeeded to clarify the difference between pre-yield and post-yield configurations. I willexplain in this talk how to construct a new order parameter that allows us to show that the yield phenomenon is a bona-fide first order thermodynamic phase transition, shedding an entirely new light on the
phenomenon.

Type I interferons serve as first line of defense against pathogen invasion. Binding of IFNs to its receptors, IFNAR1 and IFNAR2, is leading to activation of the IFN response. To determine whether structural perturbations observed during binding are propagated to the cytoplasmic domain, multiple mutation were introduced to the transmembrane helix (TMD) and it’s surrounding. Insertion of one to five alanine residues near either the N or C-terminus of the TMD promotes a rotation of 1000 and a translation of 1.5Å per added residue. Surprisingly, the added alanines had little effect on the binding affinity of IFN to the cell surface receptors, STAT phosphorylation or gene induction. Similarly, substitution of the juxtamembrane residues of the TMD with alanines, or replacement of the TMD of IFNAR1 with that of IFNAR2, did not effect IFN binding or activity. Finally, only addition of ten serine residues (but not 2 or 4) between the extracellular domain of IFNAR1 and the TMD had some effect on signaling. Bioinformatic analysis shows a correlation between high sequence conservation of TMDs of cytokine receptors and the ability to transmit structural signals. The sequence conservation near the TMD of IFNAR1 is low, suggesting limited functional importance for this region. Our results suggest that IFN binding to the extracellular domains of IFNAR1 and IFNAR2 promotes proximity between the intracellular domains, and that differential signaling is a function of duration of activation and affinity of binding rather than specific conformational changes transmitted from the outside to the inside of the cell.