B cell responses to a peptide epitope. VIII. Immune complex-mediated regulation of memory B cell generation within germinal centers

Using an in vivo reconstitution assay, we examine here the role of immune complexes in both formation of germinal centers (GC) and processes that occur subsequently within. The presence of Ag, as immune complexes, was found not to constitute a limiting requirement for the initiation of GC formation. No detrimental effect either on numbers or sizes of the resulting GC was observed when Ag-containing immune complexes were omitted during reconstitution. Thus, both recruitment and proliferation of Ag-activated B cells within GC appear not to be limited by Ag concentrations. In contrast, the presence of immune complexes was observed to be obligatory for the generation of Ag-specific memory B cells. This optimally required immune complexes to be constituted by IgG-class Abs with epitope specificities that were homologous to those of the GC B cells. The GC reaction was also found to be characterized by an enhancement of Ab specificity for the homologous epitope. Although some improvement in specificity was noted in recall responses from immune complex-deficient GC, the presence of appropriate immune complexes served to further optimize the outcome. Here again, isotype and epitope-specificity of the Ab constituent in immune complexes proved to be important

Investigating the uses of corporate reputation and its effects on brand segmentation, brand differentiation and brand positioning: evidence from the Taiwanese pharmaceutical industry

This study advances current knowledge on building a brand strategy that includes corporate reputation. It employs three theories – value creation, strategic resources and corporate communication – to study the uses of corporate reputation and its effect on brand segmentation, brand differentiation and brand positioning. In the context of the Taiwanese pharmaceutical industry, a sequential mixed method approach is applied and data are analyzed using PLS SEM. Findings demonstrate the relative impacts of three uses of corporate reputation (value creation, strategic resources and corporate communication) on brand image strategy (brand segmentation, brand differentiation and brand positioning) and the implications are evaluated. This study discovers that the inclusion of medicine prices is necessary and that it negatively moderates the impact of the overall uses of corporate reputation on overall brand image strategy. This research contributes empirically as one of the few that tests reputation-and-branding-building models outside the USA and Europe

Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions) into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions

Structural Damping Using a Four Layer Sandwich

A serious limitation in the use of sandwich type damping with a single viscoelastic material is that the effectiveness is very frequency dependent. Practical applications demand a high overall loss factor over a wide frequency range. It is shown that this requirement can be met with a dual core made from two viscoelastic layers with very different values for the shear modulus, one to be at least 100 times greater than the other. This makes the construction asymmetric and the equations of motion have been derived using Hamilton’s energy principle. The solution cannot be given in closed form but computer results have been verified by experiment. Comparison with unconstrained layer damping and with 3-layer construction with an equal thickness damping layer has demonstrated the much wider frequency effectiveness of the 4-layer sandwich.</jats:p

Extensional Effects in Constrained Viscoelastic Layer Damping

SummaryThe vibration damping in unsymmetrical, multi-layer beams is obtained by the combined effects of extensional and shear stresses in the viscoelastic layer. The shear stress distribution is not constant across such a layer, although previous work has ignored this. The error in an estimate based on the previous work of the overall loss factor can be large, in particular for the lower resonant modes of long beams with a stiff damping layer.</jats:p

Unbalance response and stability of a rotating system with viscoelastically supported bearings

Dynamic analysis of a rotating system, with bearings supported on viscoelastic suspensions, has been given using the finite element method. Unbalance response studies relating to a rotor system with journal or rolling element bearings, are reported and the effect of stiffness and damping parameters of the viscoelastic supports for the unbalance response reduction is analysed. In order to incorporate the frequency dependent effect of viscoelastic material characteristics and to study the stability behaviour of the system with hydrodynamic journal bearings, a four element type model is assumed. It is shown that with a suitable choice of support characteristics, unbalance response may be reduced and instability of the system eliminated

Inverse kinematics of manipulator using weighted fuzzy clustering method for fuzzy training data

The inverse kinematics of redundant manipulator is considered. A model-free regression approach based on weighted fuzzy clustering method is formulated. For the adopted technique, the observed or training data pair is fuzzy instead of crisp for known value of joint variables to enhance the practicability of inverse kinematics solutions, since the real-time data collected by the sensors is generally fuzzy or vague instead of crisp. Simulation results indicate that this method has higher identifying precision and better real-time ability. Therefore, a new way for solving the inverse kinematics of manipulator for fuzzy data is proposed