Metalloproteinases and their inhibitors—diagnostic and therapeutic opportunities in orthopedics

Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of musculoskeletal conditions such as tendinopathy, arthritis, Dupuytren's disease, degenerative disc disease, and bone and soft tissue healing suggest that MMPs have prominant roles. Importantly, MMPs are amenable to inhibition by cheap, safe, and widely available drugs such as the tetracycline antibiotics and the bisphosphonates. This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice

Viscoelastic behavior of polymer thin-films under thermal stresses

Stresses and deformation in microelectronic packaging are affected by the viscoelastic behavior of polymer materials during manufacture or operation. Predicting and measuring these thermo-mechanical effects is important for new devices, components, and materials. The viscoelastic response of Nycoa 851 polyimide thin-films during thermal loading is investigated. The time-dependent relaxation of polyimide films was measured in-situ, focusing on the change in thermo-mechanical properties based on the thickness of the polyimide layer. The curvature change of the multilayer structure (silver-polyimide-quartz heterostructure) was obtained for different temperatures and polymer film thicknesses. The polyimide relaxation time constant and activation energy were determined. Results indicate that the thermo-mechanical properties of polyimide thin films are dependent on the thickness of the polymer layer

Viscoelastic behavior of polymer thin-films under thermal stresses

Stresses and deformation in microelectronic packaging are affected by the viscoelastic behavior of polymer materials during manufacture or operation. Predicting and measuring these thermo-mechanical effects is important for new devices, components, and materials. The viscoelastic response of Nycoa 851 polyimide thin-films during thermal loading is investigated. The time-dependent relaxation of polyimide films was measured in-situ, focusing on the change in thermo-mechanical properties based on the thickness of the polyimide layer. The curvature change of the multilayer structure (silver-polyimide-quartz heterostructure) was obtained for different temperatures and polymer film thicknesses. The polyimide relaxation time constant and activation energy were determined. Results indicate that the thermo-mechanical properties of polyimide thin films are dependent on the thickness of the polymer layer

Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence

Candida parapsilosis is a major cause of human disease, yet little is known about the pathogen’s virulence. We have developed an efficient gene deletion system for C. parapsilosis based on the repeated use of the dominant nourseothricin resistance marker (caSAT1) and its subsequent deletion by FLP-mediated, site-specific recombination. Using this technique, we deleted the lipase locus in the C. parapsilosis genome consisting of adjacent genes CpLIP1 and CpLIP2. Additionally we reconstructed the CpLIP2 gene, which restored lipase activity. Lipolytic activity was absent in the null mutants, whereas the WT, heterozygous, and reconstructed mutants showed similar lipase production. Biofilm formation was inhibited with lipase-negative mutants and their growth was significantly reduced in lipid-rich media. The knockout mutants were more efficiently ingested and killed by J774.16 and RAW 264.7 macrophage-like cells. Additionally, the lipase-negative mutants were significantly less virulent in infection models that involve inoculation of reconstituted human oral epithelium or murine intraperitoneal challenge. These studies represent what we believe to be the first targeted disruption of a gene in C. parapsilosis and show that C. parapsilosis–secreted lipase is involved in disease pathogenesis. This efficient system for targeted gene deletion holds great promise for rapidly enhancing our knowledge of the biology and virulence of this increasingly common invasive fungal pathogen