No abstract

A Computationai Constitutive Modei for Giass Subjected to Large Strains, High Strain Rates and High PressuresThis article presents a computational constitutive model for f^la.ss subjected to large strains, high strain rates and high pressures. The model has similarities to a previottsly developed model for brittle materials by Johnson. Holmquist and Beissel (JHB model), hut thete ate significatit differences. This new glass model provides a material sttength that is depetulent on the location and/or condition of the matetial. Ptovisions are made for the .sttength to be depetidetit on whether it is in the intetior, on the sutface (different sutface finishes can be accommodated), adjacent to failed material, or if it is failed. The intact and failed sttengths are also dependetit on the pressure atid the strain täte. Tlietmal softening, damage softening, time-dependent softening, and the effect of the third invariant are also inchided. The shear modttlus can be constant or variable. The pressure-vohtme relationship includes permanent densification and bulking. Damage is accumulated based on plastic strain, ptessure and strain täte. Simple (sitigle-element) e.xamples are presented to illusttate the capabilities of the model. Compttted results for more complex ballistic impact configttrations are also ptesented atid compared to expetitnental data.

The incidences of chronic inflammatory disorders have increased significantly over the past three decades1. Recent shifts in dietary consumption are believed to have contributed importantly to this surge, but how dietary consumption modulates inflammatory disease is poorly defined. Pstpip2cmo mice that express a homozygous L98P missense mutation in the Pombe Cdc15 homology (PCH) family proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) phosphatase spontaneously develop osteomyelitis that resembles chronic recurrent multifocal osteomyelitis (CRMO) in humans2-4. Recent reports demonstrated osteomyelitis to critically rely on IL-1β, but deletion of the inflammasome components caspase-1 and NLRP3 failed to rescue Pstpip2cmo mice from inflammatory bone disease5,6. Thus, the upstream mechanisms controlling IL-1β production in Pstpip2cmo mice remain to be identified. In addition, the environmental factors driving IL-1β-dependent inflammatory bone erosion are unknown. Here, we show that the intestinal microbiota of diseased Pstpip2cmo mice was characterized by an outgrowth of Prevotella. Notably, Pstpip2cmo mice that were fed a diet rich in fat and cholesterol maintained a normal body weight, but were markedly protected against inflammatory bone disease and bone erosion. Diet-induced protection against osteomyelitis was accompanied by marked reductions in intestinal Prevotella levels and significantly reduced proIL-1β expression in distant neutrophils. Furthermore, proIL-1β expression was also decreased in antibiotics-treated Pstpip2cmo mice, and in wildtype mice that were kept under germfree conditions. We further demonstrated that combined deletion of caspases 1 and 8 was required for protection against IL-1β-dependent inflammatory bone disease, whereas deletion of each caspase alone, elastase or neutrophil proteinase-3 failed to prevent inflammatory disease. Collectively, this work reveals diet-associated changes in the intestinal microbiome as a critical factor regulating inflammasome- and caspase-8-mediated maturation of IL-1β and osteomyelitis in Pstpip2cmo mice.

No abstract