Concerted activities of Mcm4, Sld3 and Dbf4 in control of origin activation and DNA replication fork progression

Eukaryotic chromosomes initiate DNA synthesis from multiple replication origins in a temporally specific manner during S phase. The replicative helicase Mcm2-7 functions in both initiation and fork progression and thus is an important target of regulation. Mcm4, a helicase subunit, possesses an unstructured regulatory domain that mediates control from multiple kinase signaling pathways, including the Dbf4-dependent Cdc7 kinase (DDK). Following replication stress in S phase, Dbf4 and Sld3, an initiation factor and essential target of Cyclin-Dependent Kinase (CDK), are targets of the checkpoint kinase Rad53 for inhibition of initiation from origins that have yet to be activated, so-called late origins. Here, whole genome DNA replication profile analysis is employed to access under various conditions the effect of mutations that alter the Mcm4 helicase regulatory domain and the Rad53 targets, Sld3 and Dbf4. Late origin firing occurs under genotoxic stress when the controls on Mcm4, Sld3 and Dbf4 are simultaneously eliminated. The regulatory domain of Mcm4 plays an important role in the timing of late origin firing, both in an unperturbed S phase and dNTP limitation. Furthermore, checkpoint control of Sld3 impacts fork progression under replication stress. This effect is parallel to the role of the Mcm4 regulatory domain in monitoring fork progression. Hypomorph mutations in sld3 are suppressed by a mcm4 regulatory domain mutation. Thus, in response cellular conditions, the functions executed by Sld3, Dbf4 and the regulatory domain of Mcm4 intersect to control origin firing and replication fork progression, thereby ensuring genome stability

Domain within the helicase subunit Mcm4 integrates multiple kinase signals to control DNA replication initiation and fork progression

Eukaryotic DNA synthesis initiates from multiple replication origins and progresses through bidirectional replication forks to ensure efficient duplication of the genome. Temporal control of initiation from origins and regulation of replication fork functions are important aspects for maintaining genome stability. Multiple kinase-signaling pathways are involved in these processes. The Dbf4-dependent Cdc7 kinase (DDK), cyclin-dependent kinase (CDK), and Mec1, the yeast Ataxia telangiectasia mutated/Ataxia telangiectasia mutated Rad3-related checkpoint regulator, all target the structurally disordered N-terminal serine/threonine-rich domain (NSD) of mini-chromosome maintenance subunit 4 (Mcm4), a subunit of the mini-chromosome maintenance (MCM) replicative helicase complex. Using whole-genome replication profile analysis and single-molecule DNA fiber analysis, we show that under replication stress the temporal pattern of origin activation and DNA replication fork progression are altered in cells with mutations within two separate segments of the Mcm4 NSD. The proximal segment of the NSD residing next to the DDK-docking domain mediates repression of late-origin firing by checkpoint signals because in its absence late origins become active despite an elevated DNA damage-checkpoint response. In contrast, the distal segment of the NSD at the N terminus plays no role in the temporal pattern of origin firing but has a strong influence on replication fork progression and on checkpoint signaling. Both fork progression and checkpoint response are regulated by the phosphorylation of the canonical CDK sites at the distal NSD. Together, our data suggest that the eukaryotic MCM helicase contains an intrinsic regulatory domain that integrates multiple signals to coordinate origin activation and replication fork progression under stress conditions

Immobilization of Polyethylene Oxide Surfactants for Non-Fouling Biomaterial Surfaces Using an Argon Glow Discharge Treatment

A non-fouling (protein-resistant) polymer surface is achieved by the covalent immobilization of polyethylene oxide (PEO) surfactants using an inert gas discharge treatment. Treated surfaces have been characterized using electron spectroscopy for chemical analysis (ESCA), static secondary ion mass spectrometry (SSIMS), water contact angle measurement, fibrinogen adsorption, and platelet adhesion. This paper is intended to review our recent work in using this simple surface modification process to obtain wettable polymer surfaces in general, and non-fouling biomaterial surfaces in particular

Operator algebra quantum homogeneous spaces of universal gauge groups

In this paper, we quantize universal gauge groups such as SU(\infty), as well as their homogeneous spaces, in the sigma-C*-algebra setting. More precisely, we propose concise definitions of sigma-C*-quantum groups and sigma-C*-quantum homogeneous spaces and explain these concepts here. At the same time, we put these definitions in the mathematical context of countably compactly generated spaces as well as C*-compact quantum groups and homogeneous spaces. We also study the representable K-theory of these spaces and compute it for the quantum homogeneous spaces associated to the universal gauge group SU(\infty).Comment: 14 pages. Merged with [arXiv:1011.1073

Impurity Band Conduction in a High Temperature Ferromagnetic Semiconductor

The band structure of a prototypical dilute ferromagnetic semiconductor, Ga$_{1-x}$Mn$_{x}$As, is studied across the phase diagram via optical spectroscopy. We prove that the Fermi energy ($E_{F}$) resides in a Mn induced impurity band (IB). This conclusion is based upon careful analysis of the frequency and temperature dependence of the optical conductivity ($\sigma_{1}(\omega,T)$). From our analysis of $\sigma_{1}(\omega,T)$ we infer a large effective mass ($m^*$) of the carriers, supporting the view that conduction occurs in an IB. Our results also provide useful insights into the transport properties of Mn-doped GaAs.Comment: 4 pages, 4 figure

Flux through a hole from a shaken granular medium

We have measured the flux of grains from a hole in the bottom of a shaken container of grains. We find that the peak velocity of the vibration, vmax, controls the flux, i.e., the flux is nearly independent of the frequency and acceleration amplitude for a given value of vmax. The flux decreases with increasing peak velocity and then becomes almost constant for the largest values of vmax. The data at low peak velocity can be quantitatively described by a simple model, but the crossover to nearly constant flux at larger peak velocity suggests a regime in which the granular density near the container bottom is independent of the energy input to the system.Comment: 14 pages, 4 figures. to appear in Physical Review

Capping-induced suppression of annealing in Ga(1-x)Mn(x)As epilayers

We have studied the effects of capping ferromagnetic Ga(1-x)Mn(x)As epilayers with a thin layer of undoped GaAs, and we find that even a few monolayers of GaAs have a significant effect on the ferromagnetic properties. In particular, the presence of a capping layer only 10 monolayers thick completely suppresses the enhancement of the ferromagnetism associated with low temperature annealing. This result, which demonstrates that the surface of a Ga(1-x)Mn(x)As epilayer strongly affects the defect structure, has important implications for the incorporation of Ga(1-x)Mn(x)As into device heterostructures.Comment: 13 pages with figures attatche

Stochastic Ballistic Annihilation and Coalescence

We study a class of stochastic ballistic annihilation and coalescence models with a binary velocity distribution in one dimension. We obtain an exact solution for the density which reveals a universal phase diagram for the asymptotic density decay. By universal we mean that all models in the class are described by a single phase diagram spanned by two reduced parameters. The phase diagram reveals four regimes, two of which contain the previously studied cases of ballistic annihilation. The two new phases are a direct consequence of the stochasticity. The solution is obtained through a matrix product approach and builds on properties of a q-deformed harmonic oscillator algebra.Comment: 4 pages RevTeX, 3 figures; revised version with some corrections, additional discussion and in RevTeX forma

Magnetothermopower and Magnetoresistivity of RuSr2Gd1-xLaxCu2O8 (x=0, 0.1)

We report measurements of magnetothermopower and magnetoresistivity as a function of temperature on RuSr2Gd1-xLaxCu2O8 (x = 0, 0.1). The normal-state thermopower shows a dramatic decrease after applying a magnetic field of 5 T, whereas the resistivity shows only a small change after applying the same field. Our results suggest that RuO2 layers are conducting and the magnetic field induced decrease of the overall thermopower is caused by the decrease of partial thermopower decrease associated with the spin entropy decrease of the carriers in the RuO2 layers.Comment: 21 pages, 6 figure

Quartic scaling of sound attenuation with frequency in vitreous silica

Several theoretical approaches to disordered media predict that acoustic waves should undergo a quartic increase in their attenuation coefficient with increasing frequency in the sub-terahertz region. Such Rayleigh-type scattering would be related to the anomalous low-temperature plateau in the thermal conductivity and to the so-called boson peak, i.e. an excess of vibrational modes above the Debye density of states at around 1 THz. Brillouin scattering of light allows the measurement of sound absorption and velocity dispersion up to about 0.1 THz while inelastic x-ray scattering is limited to frequencies larger than about 1 THz. We take advantage of the advent of ultrafast optical techniques to explore the acoustical properties of amorphous SiO2 layers in the difficult but crucial frequency region within this gap. A quartic scaling law with frequency is clearly revealed between 0.2 and 0.9 THz, which is further shown to be independent of temperature. This strongly damped regime is accompanied by a decrease in the sound velocity already starting from about 0.5 THz, in line with theories. Our study assists to clarify the anomalous acoustical properties in glasses at frequencies entering the boson peak region.Comment: 4 figures, 11 page