The rheology of dense, polydisperse granular fluids under shear

The solution of the Enskog equation for the one-body velocity distribution of a moderately dense, arbitrary mixture of inelastic hard spheres undergoing planar shear flow is described. A generalization of the Grad moment method, implemented by means of a novel generating function technique, is used so as to avoid any assumptions concerning the size of the shear rate. The result is illustrated by using it to calculate the pressure, normal stresses and shear viscosity of a model polydisperse granular fluid in which grain size, mass and coefficient of restitution varies amoungst the grains. The results are compared to a numerical solution of the Enskog equation as well as molecular dynamics simulations. Most bulk properties are well described by the Enskog theory and it is shown that the generalized moment method is more accurate than the simple (Grad) moment method. However, the description of the distribution of temperatures in the mixture predicted by Enskog theory does not compare well to simulation, even at relatively modest densities.Comment: 8 postscript figures Replaced with new version correcting an error in the SME calculations and misc. small corrections. Second replacement with final correction of SME calculation

Unanticipated differences between α- and γ-diaminobutyric acid-linked hairpin polyamide-alkylator conjugates

Hairpin polyamide–chlorambucil conjugates containing an {alpha}-diaminobutyric acid ({alpha}-DABA) turn moiety are compared to their constitutional isomers containing the well-characterized {gamma}-DABA turn. Although the DNA-binding properties of unconjugated polyamides are similar, the {alpha}-DABA conjugates display increased alkylation specificity and decreased rate of reaction. Treatment of a human colon carcinoma cell line with {alpha}-DABA versus {gamma}-DABA hairpin conjugates shows only slight differences in toxicities while producing similar effects on cell morphology and G2/M stage cell cycle arrest. However, striking differences in animal toxicity between the two classes are observed. Although mice treated with an {alpha}-DABA hairpin polyamide do not differ significantly from control mice, the analogous {gamma}-DABA hairpin is lethal. This dramatic difference from a subtle structural change would not have been predicted

Chapman-Enskog expansion about nonequilibrium states: the sheared granular fluid

The Chapman-Enskog method of solution of kinetic equations, such as the Boltzmann equation, is based on an expansion in gradients of the deviations fo the hydrodynamic fields from a uniform reference state (e.g., local equilibrium). This paper presents an extension of the method so as to allow for expansions about \emph{arbitrary}, far-from equilibrium reference states. The primary result is a set of hydrodynamic equations for studying variations from the arbitrary reference state which, unlike the usual Navier-Stokes hydrodynamics, does not restrict the reference state in any way. The method is illustrated by application to a sheared granular gas which cannot be studied using the usual Navier-Stokes hydrodynamics.Comment: 23 pages, no figures. Submited to PRE Replaced to correct misc. errors Replaced to correct misc. errors, make notation more consistant, extend discussio

Field-test of a robust, portable, frequency-stable laser

We operate a frequency-stable laser in a non-laboratory environment where the test platform is a passenger vehicle. We measure the acceleration experienced by the laser and actively correct for it to achieve a system acceleration sensitivity of $\Delta f / f$ = $11(2) \times 10^{-12}$/g, $6(2) \times 10^{-12}$/g, and $4(1) \times 10^{-12}$/g for accelerations in three orthogonal directions at 1 Hz. The acceleration spectrum and laser performance are evaluated with the vehicle both stationary and moving. The laser linewidth in the stationary vehicle with engine idling is 1.7(1) Hz

Inherent Rheology of a Granular Fluid in Uniform Shear Flow

In contrast to normal fluids, a granular fluid under shear supports a steady state with uniform temperature and density since the collisional cooling can compensate locally for viscous heating. It is shown that the hydrodynamic description of this steady state is inherently non-Newtonian. As a consequence, the Newtonian shear viscosity cannot be determined from experiments or simulation of uniform shear flow. For a given degree of inelasticity, the complete nonlinear dependence of the shear viscosity on the shear rate requires the analysis of the unsteady hydrodynamic behavior. The relationship to the Chapman-Enskog method to derive hydrodynamics is clarified using an approximate Grad's solution of the Boltzmann kinetic equationComment: 10 pages, 4 figures; substantially enlarged version; to be published in PR

Statics and dynamics of single DNA molecules confined in nanochannels

The successful design of nanofluidic devices for the manipulation of biopolymers requires an understanding of how the predictions of soft condensed matter physics scale with device dimensions. Here we present measurements of DNA extended in nanochannels and show that below a critical width roughly twice the persistence length there is a crossover in the polymer physics

Two New Pimelic Diphenylamide HDAC Inhibitors Induce Sustained Frataxin Upregulation in Cells from Friedreich's Ataxia Patients and in a Mouse Model

BACKGROUND: Friedreich's ataxia (FRDA), the most common recessive ataxia in Caucasians, is due to severely reduced levels of frataxin, a highly conserved protein, that result from a large GAA triplet repeat expansion within the first intron of the frataxin gene (FXN). Typical marks of heterochromatin are found near the expanded GAA repeat in FRDA patient cells and mouse models. Histone deacetylase inhibitors (HDACIs) with a pimelic diphenylamide structure and HDAC3 specificity can decondense the chromatin structure at the FXN gene and restore frataxin levels in cells from FRDA patients and in a GAA repeat based FRDA mouse model, KIKI, providing an appealing approach for FRDA therapeutics. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to further improve the pharmacological profile of pimelic diphenylamide HDACIs as potential therapeutics for FRDA, we synthesized additional compounds with this basic structure and screened them for HDAC3 specificity. We characterized two of these compounds, 136 and 109, in FRDA patients' peripheral blood lymphocytes and in the KIKI mouse model. We tested their ability to upregulate frataxin at a range of concentrations in order to determine a minimal effective dose. We then determined in both systems the duration of effect of these drugs on frataxin mRNA and protein, and on total and local histone acetylation. The effects of these compounds exceeded the time of direct exposure in both systems. CONCLUSIONS/SIGNIFICANCE: Our results support the pre-clinical development of a therapeutic approach based on pimelic diphenylamide HDACIs for FRDA and provide information for the design of future human trials of these drugs, suggesting an intermittent administration of the drug.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Small molecules targeting histone H4 as potential therapeutics for chronic myelogenous leukemia

We recently identified a polyamide-chlorambucil conjugate, 1R-Chl, which alkylates and down-regulates transcription of the human histone H4c gene and inhibits the growth of several cancer cell lines in vitro and in a murine SW620 xenograft model, without apparent animal toxicity. In this study, we analyzed the effects of 1R-Chl in the chronic myelogenous leukemia cell line K562 and identified another polyamide conjugate, 6R-Chl, which targets H4 genes and elicits a similar cellular response. Other polyamide conjugates that do not target the H4 gene do not elicit this response. In a murine model, both 1R-Chl and 6R-Chl were found to be highly effective in blocking K562 xenograft growth with high-dose tolerance. Unlike conventional and distamycin-based alkylators, little or no cytotoxicities and animal toxicities were observed in mg/kg dosage ranges. These results suggest that these polyamide alkylators may be a viable treatment alternative for chronic myelogenous leukemia

CO\u3csub\u3e2\u3c/sub\u3e-Fixing One-Carbon Metabolism in a Cellulose-Degrading Bacterium \u3cem\u3eClostridium thermocellum\u3c/em\u3e

Clostridium thermocellum can ferment cellulosic biomass to formate and other end products, including CO2. This organism lacks formate dehydrogenase (Fdh), which catalyzes the reduction of CO2 to formate. However, feeding the bacterium 13C-bicarbonate and cellobiose followed by NMR analysis showed the production of 13C-formate in C. thermocellum culture, indicating the presence of an uncharacterized pathway capable of converting CO2 to formate. Combining genomic and experimental data, we demonstrated that the conversion of CO2 to formate serves as a CO2 entry point into the reductive one-carbon (C1) metabolism, and internalizes CO2 via two biochemical reactions: the reversed pyruvate: ferredoxin oxidoreductase (rPFOR), which incorporates CO2 using acetyl-CoA as a substrate and generates pyruvate, and pyruvate- formate lyase (PFL) converting pyruvate to formate and acetyl-CoA. We analyzed the labeling patterns of proteinogenic amino acids in individual deletions of all five putative PFOR mutants and in a PFL deletion mutant. We identified two enzymes acting as rPFOR, confirmed the dual activities of rPFOR and PFL crucial for CO2 uptake, and provided physical evidence of a distinct in vivo “rPFOR-PFL shunt” to reduce CO2 to formate while circumventing the lack of Fdh. Such a pathway precedes CO2 fixation via the reductive C1 metabolic pathway in C. thermocellum. These findings demonstrated the metabolic versatility of C. thermocellum, which is thought of as primarily a cellulosic heterotroph but is shown here to be endowed with the ability to fix CO2 as well