A novel ex vivo model for investigation of fluid displacements in bone after endoprosthesis implantation

Tissue perfusion and mass transport in the vicinity of implant surfaces prior to integration or bonding may play a crucial role in modulating cellular activities associated with bone remodeling, in particular, at early stages of the integration process. Furthermore, fluid displacements have been postulated to transduct mechanical stress signals to bone cells via loading-dependent flow of interstitial fluid through the lacunocanalicular network of bone. Thus, an understanding and new possibilities for influencing these processes may be of great importance for implant success. An ex vivo model was developed and validated for investigation of fluid displacements in bone after endoprosthesis implantation. This model serves to explicate the effects of surgical intervention as well as mechanical loading of the implant-bone construct on load-induced fluid flow in the vicinity of the implant. Using this model, we intend to quantify perfusion and extravascular flow dynamics in the vicinity of implants and define optimal conditions for enhancing molecular transport of osteotropic agents from the implant surface to apposing bone as well as from the blood supply to the implant surface. Furthermore, the elucidation of main transport pathways may help in understanding the distribution of wear particles in bone surrounding implant, a process which has been postulated to cause osteolysis and implant loosenin

Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism

Zymoseptoria tritici is the causative agent of Septoria tritici blotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide classes, and the rate of discovery and development of new fungicides has stalled, demanding new approaches and insights. Here we investigate a potential mechanism of targeting an important wheat pathogen Z. tritici via inhibition of N-myristoyltransferase (NMT). We characterize Z. tritici NMT biochemically for the first time, profile the in vivo Z. tritici myristoylated proteome and identify and validate the first Z. tritici NMT inhibitors. Proteomic investigation of the downstream effects of NMT inhibition identified an unusual and novel mechanism of defense against chemical toxicity in Z. tritici through the application of comparative bioinformatics to deconvolute function from the previously largely unannotated Z. tritici proteome. Research into novel fungicidal modes-of-action is essential to satisfy an urgent unmet need for novel fungicide targets, and we anticipate that this study will serve as a useful proteomics and bioinformatics resource for researchers studying Z. tritici

Conformal blocks and generalized theta functions

Let M(r) be the moduli space of rank r vector bundles with trivial determinant on a Riemann surface X . This space carries a natural line bundle, the determinant line bundle L . We describe a canonical isomorphism of the space of global sections of L^k with a space known in conformal field theory as the ``space of conformal blocks", which is defined in terms of representations of the Lie algebra sl(r, C((z))).Comment: 43 pages, Plain Te

Composites Materials and Manufacturing Technologies for Space Applications

Composite materials offer significant advantages in space applications. Weight reduction is imperative for deep space systems. However, the pathway to deployment of composites alternatives is problematic. Improvements in the materials and processes are needed, and extensive testing is required to validate the performance, qualify the materials and processes, and certify components. Addressing these challenges could lead to the confident adoption of composites in space applications and provide spin-off technical capabilities for the aerospace and other industries. To address the issues associated with composites applications in space systems, NASA sponsored a Technical Interchange Meeting (TIM) entitled, "Composites Materials and Manufacturing Technologies for Space Applications," the proceedings of which are summarized in this Conference Publication. The NASA Space Technology Mission Directorate and the Game Changing Program chartered the meeting. The meeting was hosted by the National Center for Advanced Manufacturing (NCAM)-a public/private partnership between NASA, the State of Louisiana, Louisiana State University, industry, and academia, in association with the American Composites Manufacturers Association. The Louisiana Center for Manufacturing Sciences served as the coordinator for the TIM

Transient absorption and reshaping of ultrafast XUV light by laser-dressed helium

We present a theoretical study of transient absorption and reshaping of extreme ultraviolet (XUV) pulses by helium atoms dressed with a moderately strong infrared (IR) laser field. We formulate the atomic response using both the frequency-dependent absorption cross section and a time-frequency approach based on the time-dependent dipole induced by the light fields. The latter approach can be used in cases when an ultrafast dressing pulse induces transient effects, and/or when the atom exchanges energy with multiple frequency components of the XUV field. We first characterize the dressed atom response by calculating the frequency-dependent absorption cross section for XUV energies between 20 and 24 eV for several dressing wavelengths between 400 and 2000 nm and intensities up to 10^12 W/cm^2. We find that for dressing wavelengths near 1600 nm, there is an Autler-Townes splitting of the 1s ---> 2p transition that can potentially lead to transparency for absorption of XUV light tuned to this transition. We study the effect of this XUV transparency in a macroscopic helium gas by incorporating the time-frequency approach into a solution of the coupled Maxwell-Schr\"odinger equations. We find rich temporal reshaping dynamics when a 61 fs XUV pulse resonant with the 1s ---> 2p transition propagates through a helium gas dressed by an 11 fs, 1600 nm laser pulse.Comment: 13 pages, 8 figures, 1 table, RevTeX4, revise

Development of photocrosslinking probes based on Huwentoxin-IV to map the site of interaction on Nav1.7

Voltage-gated sodium (Nav) channels respond to changes in the membrane potential of excitable cells through the concerted action of four voltage-sensor domains (VSDs). Subtype Nav1.7 plays an important role in the propagation of signals in pain-sensing neurons and is a target for the clinical development of novel analgesics. Certain inhibitory cystine knot (ICK) peptides produced by venomous animals potently modulate Nav1.7, however the molecular mechanisms underlying their selective binding and activity remain elusive. This study reports on the design of a library of photoprobes based on the potent spider toxin Huwentoxin-IV and the determination of the toxin binding interface on VSD2 of Nav1.7 through a photocrosslinking and tandem mass spectrometry approach. Our Huwentoxin-IV probes selectively crosslink to extracellular loop S1-2 and helix S3 of VSD2 in a chimeric channel system. Our results provide a strategy that will enable mapping of sites of interaction of other ICK peptides on Nav channels

Polyamine stress at high pH in Escherichia coli K-12

BACKGROUND: Polyamines such as spermine and spermidine are required for growth of Escherichia coli; they interact with nucleic acids, and they bind to ribosomes. Polyamines block porins and decrease membrane permeability, activities that may protect cells in acid. At high concentrations, however, polyamines impair growth. They impair growth more severely at high pH, probably due to their increased uptake as membrane-permeant weak bases. The role of pH is critical in understanding polyamine stress. RESULTS: The effect of polyamines was tested on survival of Escherichia coli K-12 W3110 in extreme acid or base (pH conditions outside the growth range). At pH 2, 10 mM spermine increased survival by 2-fold, and putrescine increased survival by 30%. At pH 9.8, however, E. coli survival was decreased 100-fold by 10 mM spermine, putrescine, cadaverine, or spermidine. At pH 8.5, spermine decreased the growth rate substantially, whereas little effect was seen at pH 5.5. Spermidine required ten-fold higher concentrations to impair growth. On proteomic 2-D gels, spermine and spermidine caused differential expression of 31 different proteins. During log-phase growth at pH 7.0, 1 mM spermine induced eight proteins, including PykF, GlpK, SerS, DeaD, OmpC and OmpF. Proteins repressed included acetate-inducible enzymes (YfiD, Pta, Lpd) as well as RapA (HepA), and FabB. At pH 8.5, spermine induced additional proteins: TnaA, OmpA, YrdA and NanA (YhcJ) and also repressed 17 proteins. Four of the proteins that spermine induced (GlpK, OmpA, OmpF, TnaA) and five that were repressed (Lpd, Pta, SucB, TpiA, YfiD) show similar induction or repression, respectively, in base compared to acid. Most of these base stress proteins were also regulated by spermidine, but only at ten-fold higher concentration (10 mM) at high pH (pH 8.5). CONCLUSION: Polyamines increase survival in extreme acid, but decrease E. coli survival in extreme base. Growth inhibition by spermine and spermidine requires neutral or higher pH. At or above pH 7, spermine and spermidine regulate specific proteins, many of which are known to be regulated by base stress. High pH amplifies polyamine stress; and naturally occurring polyamines may play an important role in base stress