Claspin and the Activated Form of ATR-ATRIP Collaborate in the Activation of Chk1

Claspin is necessary for the ATR-dependent activation of Chk1 in Xenopus egg extracts containing incompletely replicated DNA. ATR possesses a regulatory partner called ATRIP. We have studied the respective roles of ATR-ATRIP and Claspin in the activation of Chk1. ATR-ATRIP bound well to various DNA templates in Xenopus egg extracts. ATR-ATRIP bound to a single-stranded DNA template was weakly active. By contrast, the ATR-ATRIP complex on a DNA template containing both single- and double-stranded regions displayed a large increase in kinase activity. This observation suggests that ATR-ATRIP normally undergoes activation upon association with specific nucleic acid structures at DNA replication forks. Without Claspin, activated ATR-ATRIP phosphorylated Chk1 weakly in a cell-free reaction. The addition of Claspin to this reaction strongly stimulated the phosphorylation of Chk1 by ATR-ATRIP. Claspin also induced significant autophosphorylation of Chk1 in the absence of ATR-ATRIP. Taken together, these results indicate that the checkpoint-dependent phosphorylation of Chk1 is a multistep process involving activation of the ATR-ATRIP complex at replication forks and presentation of Chk1 to this complex by Claspin

Dynamic transition and Shapiro-step melting in a frustrated Josephson-junction array

We consider a two-dimensional fully frustrated Josephson-junction array driven by combined direct and alternating currents. Interplay between the mode locking phenomenon, manifested by giant Shapiro steps in the current-voltage characteristics, and the dynamic phase transition is investigated at finite temperatures. Melting of Shapiro steps due to thermal fluctuations is shown to be accompanied by the dynamic phase transition, the universality class of which is also discussed

Combination of tocainide and quinidine for better tolerance and additive effects in patients with coronary artery disease

The efficacy and tolerance of tocainide used alone and in combination with quinidine were studied in 20 patients with coronary artery disease and frequent (≥30/h) ventricular premature complexes. Holter electrocardiographic monitoring was performed at baseline and during therapy with tocainide alone, quinidine alone and a combination of tocainide and quinidine. During single drug therapy, the dose of tocainide was 1,680 ± 437 mg/day and that of quinidine was 1,340 ± 235 mg/day. During combination therapy, with smaller doses of tocainide (1,350 ± 394 mg/day) and quinidine (1,060 ± 268 mg/day) in many patients, no patient had side effects. At baseline before therapy, the mean ventricular premature complexes/h were 629 ± 567, couplets/h were 23.9 ± 29.7 and nonsustained ventricular tachycardias/ 24 h were 60.5 ± 152.2. Compared with baseline values (100%), the frequency of ventricular premature complexes was reduced to 33 ± 44% with quinidine, 39 ± 30% with tocainide and 10 ± 16% with combination therapy (p < 0.01 for combination versus quinidine or tocainide alone; p = NS for quinidine versus tocainide). Individually, an effective regimen (>83% reduction of ventricular premature complexes and abolition of non-sustained ventricular tachycardia) was found in 3 (15%) of 20 patients receiving tocainide alone, in 6 (30%) receiving quinidine alone and in 16 (80%) receiving combination therapy (p < 0.01 for tocainide versus combination, quinidine versus combination; p = NS for tocainide versus quinidine).Thus, the antiarrhythmic effects of quinidine and tocainide are additive. A combination of quinidine and tocainide in smaller and well tolerated doses may avoid dose-related side effects and is more effective than either drug used alone at higher doses. Therefore, when quinidine or tocainide is ineffective because dose-related side effects limit the maximal tolerated dose, combination therapy in smaller and tolerable doses may avoid side effects and may be more effective than either drug alone at the maximal tolerated dose

The Globular Cluster System of M60 (NGC 4649). II. Kinematics of the Globular Cluster System

We present a kinematic analysis of the globular cluster (GC) system in the giant elliptical galaxy (gE) M60 in the Virgo cluster. Using the photometric and spectroscopic database of 121 GCs (83 blue GCs and 38 red GCs), we have investigated the kinematics of the GC system. We have found that the M60 GC system shows a significant overall rotation. The rotation amplitude of the blue GCs is slightly smaller than or similar to that of the red GCs, and their angles of rotation axes are similar. The velocity dispersions about the mean velocity and about the best fit rotation curve for the red GCs are marginally larger than those for the blue GCs. Comparison of observed stellar and GC velocity dispersion profiles with those calculated from the stellar mass profile shows that the mass-to-light ratio should be increased as the galactocentric distance increases, indicating the existence of an extended dark matter halo. The entire sample of GCs in M60 is found to have a tangentially biased velocity ellipsoid unlike the GC systems in other gEs. Two subsamples appear to have different velocity ellipsoids. The blue GC system has a modest tangentially biased velocity ellipsoid, while the red GC system has a modest radially biased or an isotropic velocity ellipsoid. From the comparison of the kinematic properties of the M60 GC system to those of other gEs (M87, M49, NGC 1399, NGC 5128, and NGC 4636), it is found that the velocity dispersion of the blue GC system is similar to or larger than that of the red GC system except for M60, and the rotation of the GC system is not negligible. The entire sample of each GC system shows an isotropic velocity ellipsoid except for M60, while the subsamples show diverse velocity ellipsoids. We discuss the implication of these results for the formation models of the GC system in gEs.Comment: 48 pages, 16 figures. To appear in Ap

Complementarity of Resonant Scalar, Vector-Like Quark and Superpartner Searches in Elucidating New Phenomena

The elucidation of the nature of new phenomena requires a multi-pronged approach to understand the essential physics that underlies it. As an example, we study the simplified model containing a new scalar singlet accompanied by vector-like quarks, as motivated by the recent diphoton excess at the LHC. To be specific, we investigate three models with $SU(2)_L$-doublet, vector-like quarks with Yukawa couplings to a new scalar singlet and which also couple off-diagonally to corresponding Standard Model fermions of the first or third generation through the usual Higgs boson. We demonstrate that three classes of searches can play important and complementary roles in constraining this model. In particular, we find that missing energy searches designed for superparticle production, supply superior sensitivity for vector-like quarks than the dedicated new quark searches themselves.Comment: References added; small bug found in model and analysis implementation, numerical results slightly modified, conclusions unchange

Holographic interacting dark energy in the braneworld cosmology

We investigate a model of brane cosmology to find a unified description of the radiation-matter-dark energy universe. It is of the interacting holographic dark energy with a bulk-holographic matter $\chi$. This is a five-dimensional cold dark matter, which plays a role of radiation on the brane. Using the effective equations of state $\omega^{\rm eff}_{\rm \Lambda}$ instead of the native equations of state $\omega_{\rm \Lambda}$, we show that this model cannot accommodate any transition from the dark energy with $\omega^{\rm eff}_{\rm \Lambda}\ge-1$ to the phantom regime $\omega^{\rm eff}_{\rm \Lambda}<-1$. Furthermore, the case of interaction between cold dark matter and five dimensional cold dark matter is considered for completeness. Here we find that the redshift of matter-radiation equality $z_{\rm eq}$ is the same order as $z^{\rm ob}_{\rm eq}=2.4\times10^{4} \Omega_{\rm m}h^2$. Finally, we obtain a general decay rate $\Gamma$ which is suitable for describing all interactions including the interaction between holographic dark energy and cold dark matter.Comment: 17 pages, 4 figure

The Globular Cluster System of M60 (NGC 4649). I. CFHT MOS Spectroscopy and Database

We present the measurement of radial velocities for globular clusters in M60, giant elliptical galaxy in the Virgo cluster. Target globular cluster candidates were selected using the Washington photometry based on the deep 16\arcmin \times 16\arcmin images taken at the KPNO 4m and using the $VI$ photometry derived from the HST/WFPC2 archive images. The spectra of the target objects were obtained using the Multi-Object Spectrograph (MOS) at the Canada-France-Hawaii Telescope (CFHT). We have measured the radial velocity for 111 objects in the field of M60: 93 globular clusters (72 blue globular clusters with $1.0\le(C-T_1)<1.7$ and 21 red globular clusters with $1.7\le(C-T_1)<2.4$), 11 foreground stars, 6 small galaxies, and the nucleus of M60. The measured velocities of the 93 globular clusters range from $\sim 500$ km s$^{-1}$ to $\sim 1600$ km s$^{-1}$, with a mean value of $1070_{-25}^{+27}$ km s$^{-1}$, which is in good agreement with the velocity of the nucleus of M60 ($v_{\rm gal}=1056$ km s$^{-1}$). Combining our results with data in the literature, we present a master catalog of radial velocities for 121 globular clusters in M60. The velocity dispersion of the globular clusters in the master catalog is found to be $234_{-14}^{+13}$ km s$^{-1}$ for the entire sample, $223_{-16}^{+13}$ km s$^{-1}$ for 83 blue globular clusters, and $258_{-31}^{+21}$ km s$^{-1}$ for 38 red globular clusters.Comment: 29 pages, 8 figures. To appear in Ap