The N-terminal length and side-chain composition of CXCL13 affect crystallization, structure and functional activity

CXCL13 is the cognate chemokine agonist of CXCR5, a class A G-protein-coupled receptor (GPCR) that is essential for proper humoral immune responses. Using a `methionine scanning' mutagenesis method on the N-terminus of CXCL13, which is the chemokine signaling region, it was shown that minor length alterations and side-chain substitutions still result in CXCR5 activation. This observation indicates that the orthosteric pocket of CXCR5 can tolerate these changes without severely affecting the activity. The introduction of bulk on the ligand was well tolerated by the receptor, whereas a loss of contacts was less tolerated. Furthermore, two crystal structures of CXCL13 mutants were solved, both of which represent the first uncomplexed structures of the human protein. These structures were stabilized by unique interactions formed by the N-termini of the ligands, indicating that CXCL13 exhibits substantial N-terminal flexibility while the chemokine core domain remains largely unchanged. Additionally, it was observed that CXCL13 harbors a large degree of flexibility in the C-terminal extension of the ligand. Comparisons with other published structures of human and murine CXCL13 validate the relative rigidity of the core domain as well as the N- and C-terminal mobilities. Collectively, these mutants and their structures provide the field with additional insights into how CXCL13 interacts with CXCR5.

Adaptable metamaterials based on biodegradable composites for bone tissue regeneration

The influence of lattice and shell type architecture on the mechanical properties of biodegradable polymer scaffolds designed to create structures for bone tissue engineering is investigated. Varying the topology of nodal connections allows you to control the relative rigidity of the metamaterial in the range from 0.004 to 0.123. The possibility of creating permeable scaffolds using thermally extruded 3D printing based on polymers of different elasticities - polylactide and polyurethane is shown. The use of “unit cells” of various types makes it possible to fabricate structures such as shells based on polylactide with a compressive strength of 1.5 to 19.7 MPa. Shells with a cubic type architecture based on polyurethane can be almost reversibly deformed at values of technical deformation of more than 50 %. The developed approaches for obtaining polymer metamaterials and modifying their surface with calcium phosphate layer using an artificial interstitial fluid can increase the hydrophilicity of materials.

Measuring Amendment Difficulty

Which constitution is the world’s most difficult to amend? Scholars of comparative constitutional law almost uniformly have the same answer: the U.S. Constitution. It has been amended relatively few times since its creation in 1787, thousands of amendment proposals have failed, and today it seems virtually impossible to amend. Is this enough to prove that the U.S. Constitution is the hardest to amend? This chapter examines rankings of amendment difficulty that focus on the codified rules of amendment, and concludes that none of them is a reliable ordering of relative rigidity and moreover that all of them have a fatal flaw: they fail to account for nontextual sources of amendment ease or difficulty. These nontextual sources include uncodified changes to formal amendment rules, popular veneration for the constitution, temporal variability in amendment difficulty, and prevailing cultures of amendment. The chapter shows that three different cultures of amendment can either exacerbate or assuage amendment difficulty: amendment culture as an accelerator of change, as a redirector of change, and as an incapacitator of change. This chapter also illustrates how and theorizes why formal amendment rules are sometimes modified in ways that ultimately remain invisible to scholars who take a narrow text-based approach to measure amendment difficulty. The chapter concludes both that rankings of amendment difficulty are doomed to failure and that they may not be worth the effort. This chapter considers constitutions from around the globe.

Interaction of a Circular Cylindrical Shell with an Elastic Foundation

The problem of static analysis of a circular cylindrical shell, which is located on elastic Winkler foundation and reinforced by the longitudinal edges are considered. There is rib stiffness of rectangular cross section. Exposure is represented evenly distributed along the longitudinal axis forces. The forces acting on the edges of the rigidity of the upper structure. Agreed that the ends of the envelope is flat, vertical walls, giving the contour of the absolute rigidity in the transverse direction and does not prevent the longitudinal displacement of points of the envelope. To solve the problem, the total moment theory of circular cylindrical shell was used. To implement the proposed algorithm is the calculation of computer program. With the help of the program is executed a number of examples of calculation. In these examples, analyze the impact of stress on the shell of such factors as the relative length and thickness, angle mortar shell, the value of the relative rigidity of airborne elements and other.

Shape-persistent poly-porphyrins assembled by a central truxene: synthesis, structure, and singlet energy transfer behaviors

Four dyad systems composed of a central truxene and either one or three β-substituted zinc(II) porphyrins (ZnP: TruZnP (7) and TruTriZnP (9)) or free-bases (H2P: TruP (6) and TruTriP (8)) have been prepared. The presence of β-methyl groups minimizes π-conjugation through the quasi right angle made by the porphyrin and the truxene planes, and renders these dyads relatively rigid. The position of the absorption and emission 0–0 peaks confirms the role of the truxene and porphyrin as the energy donor and acceptor, respectively. Selective excitation of the truxene results in an efficient singlet energy transfer (S1 ET) from the truxene to the porphyrin unit. The rates for S1 ET (k ET ) are extracted from the change in the fluorescence lifetime of truxene in the presence and absence of the acceptor, and are temperature independent, (TruP (6), TruTriP (8), TruZnP (7) and TruTriZnP (9) are 5.0, 1.4, 1.0 and 1.4 at 298 K and 5.9, 1.3, 2.6, and 0.86 (ns)-1 at 77 K, respectively), consistent with their relative rigidity. These k ET 's are similar to other related but more flexible systems reported by one of us (Inorg. Chem.2011, 50, 11493–11505). The k ET 's time scale was assumed, based on modeling, to be related with hindered rotations about the truxene-porphyrin C–C bonds due to steric hexyl–hexyl interactions. This work confirms this earlier conclusion was correct.

Study on Collision Damage Behavior of Ship

Ship collision is a kind of dangerous accident which may result in serious damage of struck hull structure during shipping process. The damage of ship depends on the relative rigidity of striking ship and the capabilities of crash resistance of ship structures. The rigidity of bow is always considered as higher than that of side, so the structure of bow is regarded as rigid body. But this method is so conservative that the result of numerical simulation may be wrong when the rigidity of side of one ship is higher than that of bow of another ship. The process of collision of two ships is simulated, in which the structures of two ships are all defined as elastic body. The behavior of side is studied and some useful results are found.

“The Notorious Mrs. Clem”: Gender, Class, and Criminality in Gilded Age America

This essay explores the story of Nancy Clem, an outwardly respectable Indianapolis confidence woman and alleged murderess, in the context of changing constructions of class, gender, and criminality. It examines various ways in which lawyers, newspaper reporters, and ordinary citizens struggled to understand a woman who did not fit preexisting conceptions of gender and crime. A series of high-profile cases involving bourgeois criminals and (more than likely) Clem's own social aspirations allowed cultural commentators to portray her as a “genteel murderess.” Upon her release from prison after an abortive fifth trial, Clem could not sustain her newly acquired social identity, in part because her erstwhile refinement was a journalistic creation and in part because the changing nature of class, gender, and space in Gilded Age Indianapolis provided her with fewer opportunities for self-fashioning. Clem's social odyssey from half-literate “Butternut” to genteel murderess to uncultured “capitalist” reflects slippery, yet significant, transitions between social fluidity and relative rigidity, antebellum respectability and Gilded Age gentility.