Vectorial Loading of Processive Motor Proteins: Implementing a Landscape Picture

Individual processive molecular motors, of which conventional kinesin is the most studied quantitatively, move along polar molecular tracks and, by exerting a force ${\bm F} = (F_x,F_y,F_z)$ on a tether, drag cellular cargoes, {\em in vivo}, or spherical beads, {\em in vitro}, taking up to hundreds of nanometer-scale steps. From observations of velocities and the dispersion of displacements with time, under measured forces and controlled fuel supply (typically ATP), one may hope to obtain insight into the molecular motions undergone in the individual steps. In the simplest situation, the load force ${\bm F}$ may be regarded as a scalar resisting force, $F_x < 0$, acting parallel to the track: however, experiments, originally by Gittes {\em et al.} (1996), have imposed perpendicular (or vertical) loads, $F_z > 0$, while more recently Block and coworkers (2002, 2003) and Carter and Cross (2005) have studied {\em assisting} (or reverse) loads, $F_x > 0$, and also sideways (or transverse) loads $F_y \neq 0$

Replication stress by Py–Im polyamides induces a non-canonical ATR-dependent checkpoint response

Pyrrole–imidazole polyamides targeted to the androgen response element were cytotoxic in multiple cell lines, independent of intact androgen receptor signaling. Polyamide treatment induced accumulation of S-phase cells and of PCNA replication/repair foci. Activation of a cell cycle checkpoint response was evidenced by autophosphorylation of ATR, the S-phase checkpoint kinase, and by recruitment of ATR and the ATR activators RPA, 9-1-1, and Rad17 to chromatin. Surprisingly, ATR activation was accompanied by only a slight increase in single-stranded DNA, and the ATR targets RPA2 and Chk1, a cell cycle checkpoint kinase, were not phosphorylated. However, ATR activation resulted in phosphorylation of the replicative helicase subunit MCM2, an ATR effector. Polyamide treatment also induced accumulation of monoubiquitinated FANCD2, which is recruited to stalled replication forks and interacts transiently with phospho-MCM2. This suggests that polyamides induce replication stress that ATR can counteract independently of Chk1 and that the FA/BRCA pathway may also be involved in the response to polyamides. In biochemical assays, polyamides inhibit DNA helicases, providing a plausible mechanism for S-phase inhibition

Excitation of the molecular gas in the nuclear region of M82

We present high resolution HIFI spectroscopy of the nucleus of the archetypical starburst galaxy M82. Six 12CO lines, 2 13CO lines and 4 fine-structure lines are detected. Besides showing the effects of the overall velocity structure of the nuclear region, the line profiles also indicate the presence of multiple components with different optical depths, temperatures and densities in the observing beam. The data have been interpreted using a grid of PDR models. It is found that the majority of the molecular gas is in low density (n=10^3.5 cm^-3) clouds, with column densities of N_H=10^21.5 cm^-2 and a relatively low UV radiation field (GO = 10^2). The remaining gas is predominantly found in clouds with higher densities (n=10^5 cm^-3) and radiation fields (GO = 10^2.75), but somewhat lower column densities (N_H=10^21.2 cm^-2). The highest J CO lines are dominated by a small (1% relative surface filling) component, with an even higher density (n=10^6 cm^-3) and UV field (GO = 10^3.25). These results show the strength of multi-component modeling for the interpretation of the integrated properties of galaxies.Comment: Accepted for publication in A&A Letter

Structure and relaxations in liquid and amorphous Selenium

We report a molecular dynamics simulation of selenium, described by a three-body interaction. The temperatures T_g and T_c and the structural properties are in agreement with experiment. The mean nearest neighbor coordination number is 2.1. A small pre-peak at about 1 AA^-1 can be explained in terms of void correlations. In the intermediate self-scattering function, i.e. the density fluctuation correlation, classical behavior, alpha- and beta-regimes, is found. We also observe the plateau in the beta-regime below T_g. In a second step, we investigated the heterogeneous and/or homogeneous behavior of the relaxations. At both short and long times the relaxations are homogeneous (or weakly heterogeneous). In the intermediate time scale, lowering the temperature increases the heterogeneity. We connect these different domains to the vibrational (ballistic), beta- and alpha-regimes. We have also shown that the increase in heterogeneity can be understood in terms of relaxations

Phase diagram of the metal-insulator transition in 2D electronic systems

We investigated the interdependence of the effects of disorder and carrier correlations on the metal-insulator transition in two-dimensional electronic systems. We present a quantitative metal-insulator phase diagram. Depending on the carrier density we find two different types of metal-insulator transition - a continuous localization for rs=<8 and a discontinuous transition at higher rs. The critical level of disorder at the transition decreases with decreasing carrier density. At very low carrier densities we find that the system is always insulating. The value of the conductivity at the transition is consistent with recent experimental measurements. The self-consistent method which we have developed includes the effects of both disorder and correlations on the transition, using a density relaxation theory with the Coulomb correlations determined from numerical simulation data.Comment: 4 pages, RevTeX + epsf, 5 figures. New comments on conducting phase and on the conductivity. References updated and correcte

MicroRNA-221 and -222 modulate intestinal inflammatory Th17 cell response as negative feedback regulators downstream of interleukin-23

Mikami et al. examine the role of miR-221/222 in helper T cells in the gut. MiR-221/222 are induced by IL-23 and suppressed by TGFβ, targeting Maf and IL23r for degradation. During inflammation, these miRNAs serve as a negative feedback rheostat to constrain IL23-Th17 cell responses

On the Evolution of and High-Energy Emission from GHz-Peaked-Spectrum Sources

Here we discuss evolution and broad-band emission of compact (< kpc) lobes in young radio sources. We propose a simple dynamical description for these objects, consisting of a relativistic jet propagating into a uniform gaseous medium in the central parts of an elliptical host. In the framework of the proposed model, we follow the evolution of ultrarelativistic electrons injected from a terminal hotspot of a jet to expanding lobes, taking into account their adiabatic energy losses as well as radiative cooling. This allows us to discuss the broad-band lobe emission of young radio sources. In particular, we argue that the observed spectral turnover in the radio synchrotron spectra of these objects cannot originate from the synchrotron self-absorption process but is most likely due to free-free absorption effects connected with neutral clouds of interstellar medium engulfed by the expanding lobes and photoionized by active centers. We also find a relatively strong and complex high-energy emission component produced by inverse-Compton up-scattering of various surrounding photon fields by the lobes' electrons. We argue that such high energy radiation is strong enough to account for several observed properties of GHz-peaked-spectrum (GPS) radio galaxies at UV and X-ray frequencies. In addition, this emission is expected to extend up to GeV (or possibly even TeV) photon energies and can thus be probed by several modern gamma-ray instruments. In particular, we suggest that GPS radio galaxies should constitute a relatively numerous class of extragalactic sources detected by GLAST.Comment: 32 pages, 3 figures included. Revised version, accepted for publication in Ap

How the Kano model contributes to Kansei engineering in services

Recent studies show that products and services hold great appeal if they are attractively designed to elicit emotional feelings from customers. Kansei engineering (KE) has good potential to provide a competitive advantage to those able to read and translate customer affect and emotion in actual product and services. This study introduces an integrative framework of the Kano model and KE, applied to services. The Kano model was used and inserted into KE to exhibit the relationship between service attribute performance and customer emotional response. Essentially, the Kano model categorises service attribute quality into three major groups (must-be [M], one-dimensional [O] and attractive [A]). The findings of a case study that involved 100 tourists who stayed in luxury 4- and 5-star hotels are presented. As a practical matter, this research provides insight on which service attributes deserve more attention with regard to their significant impact on customer emotional needs. Statement of Relevance: Apart from cognitive evaluation, emotions and hedonism play a big role in service encounters. Through a focus on delighting qualities of service attributes, this research enables service providers and managers to establish the extent to which they prioritise their improvement efforts and to always satisfy their customer emotions beyond expectation. Keywords: Kansei engineering, emotional feelings, Kano model, service

Muon capture by 3He nuclei followed by proton and deuteron production

The paper describes an experiment aimed at studying muon capture by ${}^{3}\mathrm{He}$ nuclei in pure ${}^{3}\mathrm{He}$ and $\mathrm{D}_2 + {}^{3}\mathrm{He}$ mixtures at various densities. Energy distributions of protons and deuterons produced via $\mu^-+{}^{3}\mathrm{He}\to p+n+n + \nu_{\mu }$ and $\mu^-+{}^{3} \mathrm{He} \to d+n + \nu_{\mu}$ are measured for the energy intervals $10 - 49$ MeV and $13 - 31$ MeV, respectively. Muon capture rates, $\lambda_\mathrm{cap}^p (\Delta E_p)$ and $\lambda_\mathrm{cap}^d (\Delta E_d)$ are obtained using two different analysis methods. The least--squares methods gives $\lambda_\mathrm{cap}^p = (36.7\pm 1.2) {s}^{- 1}$, $\lambda_\mathrm{cap}^d = (21.3 \pm 1.6) {s}^{- 1}$. The Bayes theorem gives $\lambda_\mathrm{cap}^p = (36.8 \pm 0.8) {s}^{- 1}$, $\lambda_\mathrm{cap}^d = (21.9 \pm 0.6) {s}^{- 1}$. The experimental differential capture rates, $d\lambda_\mathrm{cap}^p (E_p) / dE_p$ and $d\lambda_\mathrm{cap}^d (E_d) / dE_d$, are compared with theoretical calculations performed using the plane--wave impulse approximation (PWIA) with the realistic NN interaction Bonn B potential. Extrapolation to the full energy range yields total proton and deuteron capture rates in good agreement with former results.Comment: 17 pages, 13 figures, accepted for publication in PR

Left gaze bias in humans, rhesus monkeys and domestic dogs

While viewing faces, human adults often demonstrate a natural gaze bias towards the left visual field, that is, the right side of the viewee’s face is often inspected first and for longer periods. Using a preferential looking paradigm, we demonstrate that this bias is neither uniquely human nor limited to primates, and provide evidence to help elucidate its biological function within a broader social cognitive framework. We observed that 6-month-old infants showed a wider tendency for left gaze preference towards objects and faces of different species and orientation, while in adults the bias appears only towards upright human faces. Rhesus monkeys showed a left gaze bias towards upright human and monkey faces, but not towards inverted faces. Domestic dogs, however, only demonstrated a left gaze bias towards human faces, but not towards monkey or dog faces, nor to inanimate object images. Our findings suggest that face- and species-sensitive gaze asymmetry is more widespread in the animal kingdom than previously recognised, is not constrained by attentional or scanning bias, and could be shaped by experience to develop adaptive behavioural significance