Probing Small-Molecule Microarrays with Tagged Proteins in Cell Lysates

The technique of small-molecule microarray (SMM) screening is based on the ability of small molecules to bind to various soluble proteins. This type of interaction is easily detected by the presence of a fluorescence signal produced by labeled antibodies that specifically recognize a unique sequence (tag) present on the target protein. The fluorescent signal intensity values are determined based on signal-to-noise ratios (SNRs). SMM screening is a high-throughput, unbiased method that can rapidly identify novel direct ligands for various protein targets. This binding-based assay format is generally applicable to most proteins, but it is especially useful for protein targets that do not possess an enzymatic activity. SMMs enable screening a protein in a purified form or in the context of a cellular lysate, likely providing a more physiologically relevant screening environment.National Cancer Institute (U.S.) (CA160860

Structural Phase Transitions and Sodium Ordering in Na0.5CoO2: a Combined Electron Diffraction and Raman Spectroscopy Study

The nonstoichiometric NaxCoO2 system exhibits extraordinary physical properties that correlate with temperature and Na concentration in its layered lattice without evident long-range structure modification when conventional crystallographic techniques are applied. For instance, Na0.7CoO2, a thermodynamically stable phase, shows large thermoelectric power; water-intercalated Na0.33CoO2.1.3H2O is a newly discovered superconductor with Tc ~ 4K, and Na0.5CoO2 exhibits an unexpected charge ordering transition at around Tco ~ 55 K. Recent studies suggest that the transport and magnetic properties in the NaxCoO2 system strongly depend on the charge carrier density and local structural properties. Here we report a combined variable temperature transmission electron microscopy and Raman scattering investigation on structural transformations in Na0.5CoO2 single crystals. A series of structural phase transitions in the temperature range from 80 K to 1000 K are directly identified and the observed superstructures and modulated phases can be interpreted by Na-ordering. The Raman scattering measurements reveal phase separation and a systematic evolution of active modes along with phase transitions. Our work demonstrates that the high mobility and ordering of sodium cations among the CoO2 layers are a key factor for the presence of complex structural properties in NaxCoO2 materials, and also demonstrate that the combination of electron diffraction and Raman spectroscopy measurements is an efficient way for studying the cation ordering and phase transitions in related systems.Comment: 22 pages, 5 figure

Overview of mathematical approaches used to model bacterial chemotaxis I: the single cell

Mathematical modeling of bacterial chemotaxis systems has been influential and insightful in helping to understand experimental observations. We provide here a comprehensive overview of the range of mathematical approaches used for modeling, within a single bacterium, chemotactic processes caused by changes to external gradients in its environment. Specific areas of the bacterial system which have been studied and modeled are discussed in detail, including the modeling of adaptation in response to attractant gradients, the intracellular phosphorylation cascade, membrane receptor clustering, and spatial modeling of intracellular protein signal transduction. The importance of producing robust models that address adaptation, gain, and sensitivity are also discussed. This review highlights that while mathematical modeling has aided in understanding bacterial chemotaxis on the individual cell scale and guiding experimental design, no single model succeeds in robustly describing all of the basic elements of the cell. We conclude by discussing the importance of this and the future of modeling in this area

The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function

Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Energy and system size dependence of \phi meson production in Cu+Cu and Au+Au collisions

We study the beam-energy and system-size dependence of \phi meson production (using the hadronic decay mode \phi -- K+K-) by comparing the new results from Cu+Cu collisions and previously reported Au+Au collisions at \sqrt{s_NN} = 62.4 and 200 GeV measured in the STAR experiment at RHIC. Data presented are from mid-rapidity (|y|<0.5) for 0.4 < pT < 5 GeV/c. At a given beam energy, the transverse momentum distributions for \phi mesons are observed to be similar in yield and shape for Cu+Cu and Au+Au colliding systems with similar average numbers of participating nucleons. The \phi meson yields in nucleus-nucleus collisions, normalised by the average number of participating nucleons, are found to be enhanced relative to those from p+p collisions with a different trend compared to strange baryons. The enhancement for \phi mesons is observed to be higher at \sqrt{s_NN} = 200 GeV compared to 62.4 GeV. These observations for the produced \phi(s\bar{s}) mesons clearly suggest that, at these collision energies, the source of enhancement of strange hadrons is related to the formation of a dense partonic medium in high energy nucleus-nucleus collisions and cannot be alone due to canonical suppression of their production in smaller systems.Comment: 20 pages and 5 figure

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at $\sqrt{s_{NN}} = 200$ GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, $\eta/s$, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of $\eta/s$ that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.

High pTp_{T} non-photonic electron production in pp+pp collisions at s\sqrt{s} = 200 GeV

We present the measurement of non-photonic electron production at high transverse momentum ($p_T >$ 2.5 GeV/$c$) in $p$ + $p$ collisions at $\sqrt{s}$ = 200 GeV using data recorded during 2005 and 2008 by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The measured cross-sections from the two runs are consistent with each other despite a large difference in photonic background levels due to different detector configurations. We compare the measured non-photonic electron cross-sections with previously published RHIC data and pQCD calculations. Using the relative contributions of B and D mesons to non-photonic electrons, we determine the integrated cross sections of electrons ($\frac{e^++e^-}{2}$) at 3 GeV/$c < p_T <~$10 GeV/$c$ from bottom and charm meson decays to be ${d\sigma_{(B\to e)+(B\to D \to e)} \over dy_e}|_{y_e=0}$ = 4.0$\pm0.5$({\rm stat.})$\pm1.1$({\rm syst.}) nb and ${d\sigma_{D\to e} \over dy_e}|_{y_e=0}$ = 6.2$\pm0.7$({\rm stat.})$\pm1.5$({\rm syst.}) nb, respectively.Comment: 17 pages, 17 figure

Longitudinal scaling property of the charge balance function in Au + Au collisions at 200 GeV

We present measurements of the charge balance function, from the charged particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au collisions at 200 GeV using the STAR detector at RHIC. We observe that the balance function is boost-invariant within the pseudorapidity coverage [-1.3, 1.3]. The balance function properly scaled by the width of the observed pseudorapidity window does not depend on the position or size of the pseudorapidity window. This scaling property also holds for particles in different transverse momentum ranges. In addition, we find that the width of the balance function decreases monotonically with increasing transverse momentum for all centrality classes.Comment: 6 pages, 3 figure