The early host and material response of hydroxyapatite/β-tricalciumphosphate porous ceramics after implantation into the femur of rats

The early responses of host and hydroxyapatite/-tricalciumphosphate (HA-TCP) porous ceramic implants were studied using light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) at 3, 7, 14, 21, and 28 days after implantation into the femur of rats. Micropores (<5 m) and macropores of the implant surface provided effective structures for anchoring of various tissue components. Mineralization started directly on the implant surface and was observed in macropores and micropores, suggesting bone-bonding by epitaxis. Bone-bonding was observed with and without an amorphous intervening interface layer. The composition of this layer and the mechanisms guiding its production are not yet fully understood. Extracellular matrix filled up the clefts between HA-TCP crystal grain clusters. These processes contributed to the mechanical stabilization of the interface. Slight changes of implant grain surface morphology were observed which were explained by leaching of impurities, such as TCP and/or by dissolution acting on single grains. Diameters of pores and HA-TCP grains did not change in a period up to 28 days, which seems to be related to the relatively short periods of insertion and the material properties. Leaching and degradation were observed and loose particles of implant origin were phagocytosed by macrophages and multinuclear giant cells which dominated at non-bonding interfaces.     

L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide synthases

Nitric-oxide synthase (NOS) catalyzes the oxidation of L-arginine to citrulline and nitric oxide (NO). The enzyme is inhibited by a variety of N omega-monosubstituted L-arginine analogs, and some of these compounds are useful in reversing pathologies associated with the overproduction of NO (e.g. the hypotension of septic shock). We report here that L-thiocitrulline (gamma-thioureido-L-norvaline) is a potent, stereospecific inhibitor of the constitutive brain and endothelial isoforms of NOS as well as the isoform induced in vascular smooth muscle cells by lipopolysaccharide and interferon-gamma. Steady state kinetic studies show L-thiocitrulline inhibition is competitive with L-arginine (Ki approximately 4-20% of KArgm), indicating that initial binding is as a substrate/product analog. In contrast to L-arginine and N omega-methyl-L-arginine, the prototypic NOS inhibitor, L-thiocitrulline binding elicits a "Type II" difference spectrum, indicating a high spin to low spin transition of the iron in the heme cofactor. This finding suggests that L-thiocitrulline is contributing the sixth ligand to heme iron, probably through the thioureido sulfur. Such interaction with heme iron neither stimulates nor inhibits the direct flavin-mediated cytochrome c reduction activity of the enzyme, but it does inhibit heme-dependent superoxide formation. In vivo, L-thiocitrulline is a potent pressor agent in both normal and endotoxemic rats, the latter finding suggesting utility in treating the hypotension of septic shock.     

3-Methyl-α-himachalene: Proposed structure for novel homosesquiterpene sex pheromone ofLutzomyia longipalpis (diptera: Psychodidae) from Jacobina,Brazil

The principal behaviorally active volatile component (ca. 90% +) of the sex pheromone glands ofLutzomyia longipalpis from Jacobina. Brazil, has been isolated and characterized as a novel homosesquiterpene with the structure 3-methyl--himachalene (C₁₆H₂₆). A minor component (ca. 10%) of the gland extract has also been identified as the sesquiterpene-himachalene (C₁₅H₂₄). This work confirms that there are at least 3 members of theL. longipalpis species complex.     

Conformations and folding of lysozyme ions in vacuo

Proton transfer reactivity of isolated charge states of the protein hen egg-white lysozyme shows that multiple distinct conformations of this protein are stable in the gas phase. The reactivities of the 9+ and 10+ charge state ions, formed by electrospray ionization of "native" (disulfide-intact) and "denatured" (disulfide-reduced) solutions, are consistent with values calculated for ions in their crystal structure and fully denatured conformations, respectively. Charge states below 8+ of both forms, formed by proton stripping, have similar or indistinguishable reactivities, indicating that the disulfide-reduced ions fold in the gas phase to a more compact conformation.     

Adaptive autonomous underwater vehicles for littoral surveillance

Autonomous underwater vehicles (AUVs) have gained more interest in recent years for military as well as civilian applications. One potential application of AUVs is for the purpose of undersea surveillance. As research into undersea surveillance using AUVs progresses, issues arise as to how an AUV acquires, acts on, and shares information about the undersea battle space. These issues naturally touch on aspects of vehicle autonomy and underwater communications, and need to be resolved through a spiral development process that includes at sea experimentation. This paper presents a recent AUV implementation for active anti-submarine warfare tested at sea in the summer of 2010. On-board signal processing capabilities and an adaptive behavior are discussed in both a simulation and experimental context. The implications for underwater surveillance using AUVs are discussed.     

SEBS elastomers for fabrication of microfluidic devices with reduced drug absorption by injection molding and extrusion

The majority of microfluidic devices used for cell culture, including Organ-on-a-Chips (Organ Chips), are fabricated using polydimethylsiloxane (PDMS) polymer because it is flexible, optically clear, and easy to mold. However, PDMS possesses significant challenges for high volume manufacturing and its tendency to absorb small hydrophobic compounds limits its usefulness as a material in devices used for drug evaluation studies. Here, we demonstrate that a subset of optically clear, elastomeric, styrenic block copolymers based on styrene-ethylene-butylene-styrene exhibit reduced absorption of small hydrophobic molecules and drug compounds compared to PDMS and that they can be fabricated into microfluidic devices with fine features and the flexibility required for Organ Chips using mass production techniques of injection molding and extrusion.     

Urinary proteomic analysis of chronic allograft nephropathy

The pathogenesis of progressive renal allograft injury, which is termed chronic allograft nephropathy (CAN), remains obscure and is currently defined by histology. Prospective protocol-biopsy trials have demonstrated that clinical and standard laboratory tests are insufficiently sensitive indicators of the development and progression of CAN. The study aim was to determine if CAN could be characterized by urinary proteomic data and identify the proteins associated with disease. The urinary proteome of 75 renal transplant recipients and 20 healthy volunteers was analyzed using surface enhanced laser desorption and ionization MS. Patients could be classified into subgroups with normal histology and Banff CAN grades 2-3 with a sensitivity of 86% and a specificity of 92% by applying the classification algorithm Adaboost to urinary proteomic data. Several urinary proteins associated with advanced CAN were identified including α1-microglobulin, β2-microglobulin, prealbumin, and endorepellin, the antiangiogenic C-terminal fragment of perlecan. Increased urinary endorepellin was confirmed by ELISA and increased tissue expression of the endorepellin/perlecan ratio by immunofluoresence analysis of renal biopsies. In conclusion, analysis of urinary proteomic data has further characterized the more severe CAN grades and identified urinary endorepellin, as a potential biomarker of advanced CAN.