The cyclotide MCoTI-II is a powerful trypsin inhibitor recently isolated from the seeds of Momordica cochinchinensis, a plant member of cucurbitaceae family. We report for the first time the in vivo biosynthesis of natively-folded MCoTI-II inside live E. coli cells. Our biomimetic approach involves the intracellular backbone cyclization of a linear cyclotide-intein fusion precursor mediated by a modified protein splicing domain. The cyclized peptide then spontaneously folds into its native conformation. The use of genetically engineered E. coli cells containing mutations in the glutathione and thioredoxin reductase genes considerably improves the production of folded MCoTI-II in vivo. Biochemical and structural characterization of the recombinant MCoTI-II confirmed its identity. Biosynthetic access to correctly-folded cyclotides allows the possibility of generating cell-based combinatorial libraries that can be screened inside living cells for their ability to modulate or inhibit cellular processes.

Many experimental approaches in biology and biophysics, as well as applications in diagnosis and drug discovery, require proteins to be immobilized on solid supports. Protein microarrays, for example, provide a high-throughput format to study biomolecular interactions. The technique employed for protein immobilization is a key to the success of these applications. Recent biochemical developments are allowing, for the first time, the selective and traceless immobilization of proteins generated by cell-free systems without the need for purification and/or reconcentration prior to the immobilization step.

An overview of the Lawrence Discrete Element Code (LDEC) is presented, and results from a study investigating the effect of explosive and impact loading on geologic materials using the Livermore Distinct Element Code (LDEC) are detailed. LDEC was initially developed to simulate tunnels and other structures in jointed rock masses using large numbers of polyhedral blocks. Many geophysical applications, such as projectile penetration into rock, concrete targets, and boulder fields, require a combination of continuum and discrete methods in order to predict the formation and interaction of the fragments produced. In an effort to model this class of problems, LDEC now includes implementations of Cosserat point theory and cohesive elements. This approach directly simulates the transition from continuum to discontinuum behavior, thereby allowing for dynamic fracture within a combined finite element/discrete element framework. In addition, a Smooth Particle Hydrodynamics (SPH) capability has been incorporated into LDEC, permitting the simulation of fluid-structure interaction. We will present results from a study of detonation-induced fracture and fragmentation of geologic media surrounding a tunnel using LDEC.

Samarium-neodymium isotopic analyses of unleached and acid-leached mineral fractions from the recently identified olivine-bearing shergottite Northwest Africa 1195 yield a crystallization age of 348 {+-} 19 Ma and an {var_epsilon}{sub Nd}{sup 143} value of +40.1 {+-} 1.3. Maskelynite fractions do not lie on the Sm-Nd isochron and appear to contain a martian surface component with low {sup 147}Sm/{sup 144}Nd and {sup 143}Nd/{sup 144}Nd ratios that was added during shock. The Rb-Sr system is disturbed and does not yield an isochron. Terrestrial Sr appears to have affected all of the mineral fractions, although a maximum initial {sup 87}Sr/{sup 86}Sr ratio of 0.701614 {+-} 16 is estimated by passing a 348 Ma reference isochron through the maskelynite fraction that is least affected by contamination. The high initial {var_epsilon}{sub Nd}{sup 143} value and the low initial {sup 87}Sr/{sup 86}Sr ratio, combined with the geologically young crystallization age, indicate that Northwest Africa 1195 is derived from a source region characterized by a long-term incompatible element depletion. The age and initial Sr and Nd isotopic compositions of Northwest Africa 1195 are very similar to those of Queen Alexandra Range 94201, indicating these samples were derived from source regions with nearly identical Sr-Nd isotopic systematics. These …

An important problem in porous media involves the ability of micron and submicron-sized biological particles such as viruses or bacteria to move in groundwater systems through geologic media characterized by rock or mixed gravel, clay and sand materials. Current simulation capabilities require properly upscaled (continuum) models of colloidal filtration and adsorption to augment existing theories of fluid flow and chemical transport. Practical models typically address flow and transport behavior in aquifers over distances of 1 to 10 km where, for example, fluid momentum balance is governed by the simple Darcy's Law as a function of a pressure gradient, elevation gradient and a medium-dependent permeability parameter. In addition to fluid advection, there are multiple transport processes occurring in these systems including diffusion, dispersion and chemical interactions with solids or other aqueous chemical species. Particle transport is typically modeled in the same way as dissolved species, except that additional loss terms are incorporated to model particle filtration (physical interception), adsorption (chemical interception) and inactivation. Proper resolution of these processes at the porous medium continuum scale constitutes an important closure problem in subsurface science. We present a new simulation capability based on enabling technologies developed for microfluidics applications to model transport of colloidal-sized …

A proof-of-principle electron electric dipole moment (e-EDM)experiment using slow cesium atoms, nulled magnetic fields, and electricfield quantization has been performed. With the ambient magnetic fieldsseen by the atoms reduced to less than 200 pT, an electric field of 6MV/m lifts the degeneracy between states of unequal lbar mF rbar and,along with the low (approximately 3 m/s) velocity, suppresses thesystematic effect from the motional magnetic field. The low velocity andsmall residual magnetic field have made it possible to induce transitionsbetween states and to perform state preparation, analysis, and detectionin regions free of applied static magnetic and electric fields. Thisexperiment demonstrates techniques that may be used to improve the e-EDMlimit by two orders of magnitude, but it is not in itself a sensitivee-EDM search, mostly due to limitations of the laser system.

Biodetection instrumentation that is capable of functioning effectively outside the controlled laboratory environment is critical for the detection of health threats, and is a crucial technology for Health Security. Experience in bringing technologies from the basic research laboratory to integrated fieldable instruments suggests lessons for the engineering of these systems. This overview will cover several classes of such devices, with examples from systems developed for homeland security missions by Lawrence Livermore National Laboratory (LLNL). Recent trends suggest that front-end sample processing is becoming a critical performance-determining factor for many classes of fieldable biodetection devices. This paper introduces some results of a recent study that was undertaken to assess the requirements and potential technologies for next-generation integrated sample processing.