Frequency filtering in disordered granular chains

The study of disorder-induced frequency filtering is presented for one-dimensional systems composed of random, pre-stressed masses interacting through both linear and nonlinear (Hertzian) repulsive forces. An ensemble of such systems is driven at a specified frequency, and the spectral content of the propagated disturbance is examined as a function of distance from the source. It is shown that the transmitted signal contains only low-frequency components, and the attenuation is dependent on the magnitude of disorder, the input frequency, and the contact model. It is found that increased disorder leads to a narrower bandwidth of transmitted frequencies at a given distance from the source and that lower input frequencies exhibit less sensitivity to the arrangement of the masses. Comparison of the nonlinear and linear contact models reveals qualitatively similar filtering behavior; however, it is observed that the nonlinear chain produces transmission spectrums with a greater density at the lowest frequencies. In addition, it is shown that random masses sampled from normal, uniform, and binary distributions produce quantitatively indistinguishable filtering behavior, suggesting that knowledge of only the distribution’s first two moments is sufficient to characterize the bulk signal transmission behavior. Finally, we examine the wave number evolution of random chains constrained to move between fixed end-particles and present a transfer matrix theory in wave number space, and an argument for the observed filtering based on the spatial localization of the higher-frequency normal modes

Collisional features in a model of a planetary ring

Images taken by the Cassini spacecraft display numerous “propellers”, telltale disturbances detected in Saturn’s outer A ring. In conventionally accepted models (Seiß, M., Spahn, F., Sremčević, M., Salo, H. [2005]. Geophys. Res. Lett. 32, L11205; Lewis, M., Stewart, G. [2009]. Icarus 199, 387–412), unseen moonlets are considered to generate these structures by gravitationally stirring the shearing Kepler flow of ring particles. The morphology and scale of these structures likely depend on both gravity and collisions. However, with a goal to understand one aspect of the development of real propellers, and motivated by similar features observed in terrestrial granular systems, we here study only the collisional effects on propeller-like feature formation, entirely omitting the gravitational attraction between the moonlet and the particles.\ud \ud Our investigation employs a combination of simulation and continuum analysis to examine the extent to which dissipative collisions between ring particles and with a large obstacle might cause such features to form. Our simple, heuristic two-dimensional numerical simulations demonstrate that propeller-like features having many of the features seen in gravitating systems can form. Our continuum theory predicts that, at observed ring densities, the magnitudes of relative particle speeds and thermal speeds (i.e., kinetic granular temperatures) imply that the flow with respect to the moonlet is supersonic. As a consequence, these propeller-like features could be interpreted as the locus of a granular shock across which the flow experiences significant, almost discontinuous, changes in flow properties\u

Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing

High-acuity αβT cell receptor (TCR) recognition of peptides bound to major histocompatibility complex molecules (pMHCs) requires mechanosensing, a process whereby piconewton (pN) bioforces exert physical load on αβTCR–pMHC bonds to dynamically alter their lifetimes and foster digital sensitivity cellular signaling. While mechanotransduction is operative for both αβTCRs and pre-TCRs within the αβT lineage, its role in γδT cells is unknown. Here, we show that the human DP10.7 γδTCR specific for the sulfoglycolipid sulfatide bound to CD1d only sustains a significant load and undergoes force-induced structural transitions when the binding interface-distal γδ constant domain (C) module is replaced with that of αβ. The chimeric γδ–αβTCR also signals more robustly than does the wild-type (WT) γδTCR, as revealed by RNA-sequencing (RNA-seq) analysis of TCR-transduced Rag2−/− thymocytes, consistent with structural, single-molecule, and molecular dynamics studies reflective of γδTCRs as mediating recognition via a more canonical immunoglobulin-like receptor interaction. Absence of robust, force-related catch bonds, as well as γδTCR structural transitions, implies that γδT cells do not use mechanosensing for ligand recognition. This distinction is consonant with the fact that their innate-type ligands, including markers of cellular stress, are expressed at a high copy number relative to the sparse pMHC ligands of αβT cells arrayed on activating target cells. We posit that mechanosensing emerged over ∼200 million years of vertebrate evolution to fulfill indispensable adaptive immune recognition requirements for pMHC in the αβT cell lineage that are unnecessary for the γδT cell lineage mechanism of non-pMHC ligand detection

Shocks In Granular Flows- Analytical And Computational Studies

This dissertation concerns the analytical and numerical modeling of compressible shock in granular systems and its applications. Kinetic theory and classical thermodynamic arguments suggest that granular flows with low agitation (granular temperature) may be characterized as supersonic, experiencing almost discontinuous changes in flow properties across shock fronts created by obstructing bodies. Uniform and non-uniform flows are studied analytically and with discrete element numerical simulations in different geometries. We derive a set of algebraic relations to describe property changes local to the shock and expand the analysis with use of a system of coupled shock depth-averaged differential equations. These expressions are applied to uniform flow incident on straight wedge obstructions and comparison with simulations reveals good quantitative agreement. Finally we make use of discrete element simulations and apply kinetic theory analysis to shear flow about circular bodies to explain the production of propeller-shaped density features about embedded moons in the rings of Saturn. These density features are interpreted as being predominantly created by collisional processes, in contrast to prior studies where gravitation is incorporated. We adapt the general depth- averaged differential equations for application to this system and find reasonable qualitative predictions for the shock front

Mass-disorder effects on the frequency filtering in one-dimensional particle systems

We numerically study the effects of mass–disorder on the signal transmission properties of one–dimensional linearly coupled granular systems. By driving such systems at a specified input frequency, we are able to investigate the disorder–induced high–frequency filtering of signals downstream from the excitation source. We consider ensembles of systems composed of random masses selected from normal, uniform, and binary distributions and find that the transmitted frequency content is not sensitive to the particular distribution or arrangement of the random masses. Rather, only knowledge of the moments of the mass distribution is necessary to quantify the bandwidth of transmitted frequencies

Transcriptional elongation requires DNA break-induced signalling

We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28 and γH2AX on serum-induced genes and the important function of DNA-PK for Pol II pause release and transcriptional activation-coupled DDR signalling on these genes. γH2AX accumulation decreases when P-TEFb is inhibited, confirming that DDR signalling results from transcriptional elongation. In addition, transcriptional elongation-coupled DDR signalling involves topoisomerase II because inhibiting this enzyme interferes with Pol II pause release and γH2AX accumulation. Our findings propose that DDR signalling is required for effective Pol II pause release and transcriptional elongation through a novel mechanism involving TRIM28, DNA-PK and topoisomerase II

Estradiol induces allosteric coupling and partitioning of sex-hormone-binding globulin monomers among conformational states

Summary: Sex-hormone-binding globulin (SHBG) regulates the transport and bioavailability of estradiol. The dynamics of estradiol's binding to SHBG are incompletely understood, although it is believed that estradiol binds to each monomer of SHBG dimer with identical affinity (Kd ∼2 nM). Contrary to the prevalent view, we show that estradiol's binding to SHBG is nonlinear, and the ''apparent'' Kd changes with varying estradiol and SHBG concentrations. Estradiol's binding to each SHBG monomer influences residues in the ligand-binding pocket of both monomers and differentially alters the conformational and energy landscapes of both monomers. Monomers are not energetically or conformationally equivalent even in fully bound state.Estradiol's binding to SHBG involves bidirectional, inter-monomeric allostery that changes the distribution of both monomers among various energy and conformational states. Inter-monomeric allostery offers a mechanism to extend the binding range of SHBG and regulate hormone bioavailability as estradiol concentrations vary widely during life

Serum testosterone and estradiol modify risk of anal HPV16/18 infections but only estradiol influences risk for histological high-grade squamous intraepithelial lesions (HSIL)

Background: We reported higher serum free testosterone (FT) and increased anal-HPV16/18 infection prevalence in MSM. Associations between serum-FT and -estradiol and anal-HPV16/18 infections and histological HSIL (hHSIL) are unclear. Methods: Two cross-sectional analyses were performed. 340 HIV-infected/HIV-uninfected Multicenter AIDS Cohort MSM were tested for anal HPVs; another 214 men were evaluated using HRA/biopsy with multiple assessments for some totaling 336 HRAs. Serum specimens collection preceded HPV and HRA visits by 24(+9) months and were tested for albumin, SHBG (radioimmunoassay), and total testosterone and estradiol (TE2) (LC/MS); serum-FT (pg/mL) was estimated. Anal swabs were tested for 37 HPVs (PCR) and classified: HPV16/18+, other Group-1 and -2 high-risk HPVs+ (hrHPVs); low-risk HPVs+ (lrHPVs), vs. none. Biopsies were evaluated as hHSIL vs. <hHSIL. Multivariable-adjusted GEE logistic regression models assessed relationships between loge-transformed FT and TE2, and HPV16/18+ and hHSIL, separately. Sociodemographic/behavioral covariates were included. Results: Adjusted estimates showed higher FT increased odds of HPV16/18-infection (OR=1.9 (1.2–2.9)), but odds were inversely associated with TE2 (OR=0.68 (0.49–0.94)). White race and other Group-1-hrHPVs+ increased odds for HPV16/18 infection (OR=2.6 (1.2–5.9) and (OR=1.7 (1.1–2.5)), but neither HIV-infection/CD4+count, receptive anal intercourse partnerships; exogenous-testosterone nor tobacco use increased HPV16/18-infection odds. Serum-FT was not associated with odds of hHSIL (OR=1.1 (0.7, 1.8)), but serum-TE2 and hHSIL was: OR=0.5 (0.3, 0.9). Men testing HPV16/18+ alone showed higher odds of hHSIL than hrHPV-negative men (OR=4.3 (1.7, 10.7)). Conclusions: Higher serum-FT increased odds of anal HPV16/18-infection but not hHSIL. Consistent across both analyses, and unexpectely, higher serum-TE2 lowered odds of both HPV16/18+ and hHSIL in these MSM