The rockefeller university

We present a measurement of the W-boson mass, M-W, using data corresponding to 2.2 fb(-1) of integrated luminosity collected in p (p) over bar collisions at root s = 1.96 TeV with the CDF II detector at the Fermilab Tevatron. The selected sample of 470 126 W -> ev candidates and 624 708 W -> mu nu candidates yields the measurement M-W = 80387 +/- 12 (stat) +/- 15(syst) = 80387 +/- 19 MeV/c(2). This is the most precise single measurement of the W-boson mass to date.

Bisindolylmaleimides represent a naturally occurring class of metabolites that are of interest because of their protein kinase inhibition activity. From a metagenomic library constructed with soil DNA, we identified the four gene mar cluster, a bisindolylmaleimide gene cluster that encodes for methylarcyriarubin (1) production. Heterologous expression of the mar gene cluster in E. coli revealed that the Rieske dioxygenase MarC facilitates the oxidative decarboxylation of a chromopyrrolic acid (CPA) intermediate to yield the bisindolylmaleimide core. The characterization of the mar cluster defines a new role for CPA in the biosynthesis of structurally diverse bacterial tryptophan dimers.

Quadratic ordering of rectangular real matrices implies Chebyshev's inequality: If Ai, Ar are m x n real matrices and B-1, ... , B-r are n x q real matrices such that, for all i, j with 1 <= i, j <= r, elementwise (A(i) - A(j))(B-i - B-j) >= 0(mxq), then for any real pj >= 0, j = 1, ... , r, Sigma(j)p(j) = 1, elementwise (Sigma(j)p(j)A(j))(Sigma(j)p(j)B(j)) <= Sigma(j)p(j)A(j)B(j). Further, linear ordering of rectangular real matrices implies Gruss's inequality: If, elementwise, A(j) <= A(j+1), j = 1,..., r - 1 and elementwise B-j <= Bj+1 = 1,..., r - 1 then elementwise Sigma(j)p(j)A(j)B(j) - (Sigma(j)p(j)A(j))(Sigma(j)p(j)B(j)) <= 1/4(A(r) - A(1))(B-r - B-1). The bounds are sharp. These inequalities lead to inequalities for the spectral radius of nonnegative matrices. Linear ordering and quadratic ordering are equivalent for real scalars but not for real matrices, (C) 2013 Elsevier Inc. All rights reserved.

Measurements are presented by the CMS Collaboration at the Large Hadron Collider (LHC) of the higher-order harmonic coefficients that describe the azimuthal anisotropy of charged particles emitted in root s(NN) = 2.76 TeV PbPb collisions. Expressed in terms of the Fourier components of the azimuthal distribution, the n = 3-6 harmonic coefficients are presented for charged particles as a function of their transverse momentum (0.3 < p(T) < 8.0 GeV/c), collision centrality (0%-70%), and pseudorapidity (|eta| < 2.0). The data are analyzed using the event plane, multiparticle cumulant, and Lee-Yang zeros methods, which provide different sensitivities to initial-state fluctuations. Taken together with earlier LHC measurements of elliptic flow (n = 2), the results on higher-order harmonic coefficients develop a more complete picture of the collective motion in high-energy heavy-ion collisions and shed light on the properties of the produced medium.

Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control.

Hearing loss is most commonly caused by the destruction of mechanosensory hair cells in the ear. This condition is usually permanent: Despite the presence of putative hair-cell progenitors in the cochlea, hair cells are not naturally replenished in adult mammals. Unlike those of the mammalian ear, the progenitor cells of nonmammalian vertebrates can regenerate hair cells throughout life. The basis of this difference remains largely unexplored but may lie in molecular dissimilarities that affect how progenitors respond to hair-cell death. To approach this issue, we analyzed gene expression in hair-cell progenitors of the lateral-line system. We developed a transgenic line of zebrafish that expresses a red fluorescent protein in the presumptive hair-cell progenitors known as mantle cells. Fluorescence-activated cell sorting from the skins of transgenic larvae, followed by microarray-based expression analysis, revealed a constellation of transcripts that are specifically enriched in these cells. Gene expression analysis after hair-cell ablation uncovered a cohort of genes that are differentially regulated early in regeneration, suggesting possible roles in the response of progenitors to hair-cell death. These results provide a resource for studying hair-cell regeneration and the biology of sensory progenitor cells.

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump-mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified.

We use ideas from kinetic proofreading, an error-correcting mechanism in biology, to identify new kinetic regimes in nonequilibrium systems. These regimes are defined by the sensitivity of the occupancy of a state of the system to a change in its energy. In biological contexts, higher sensitivity corresponds to stronger discrimination between molecular substrates with different energetics competing in the same reaction. We study this discriminatory ability in systems with discrete states that are connected by a general network of transitions. We find multiple regimes of different discriminatory ability when the energy of a given state of the network is varied. Interestingly, the occupancy of the state can even increase with its energy, corresponding to an "antiproofreading" regime. The number and properties of such discriminatory regimes are limited by the topology of the network. Finally, we find that discriminatory regimes can be changed without modifying any "hard-wired" structural aspects of the system but rather by simply changing external chemical potentials.

The Clinical and Translational Science Awards (CTSA) program represents a significant public investment. To realize its major goal of improving the public's health and reducing health disparities, the CTSA Consortium's Community Engagement Key Function Committee has undertaken the challenge of developing a taxonomy of community health indicators. The objective is to initiate a unified approach for monitoring progress in improving population health outcomes. Such outcomes include, importantly, the interests and priorities of community stakeholders, plus the multiple, overlapping interests of universities and of the public health and health care professions involved in the development and use of local health care indicators. The emerging taxonomy of community health indicators that the authors propose supports alignment of CTSA activities and facilitates comparative effectiveness research across CTSAs, thereby improving the health of communities and reducing health disparities. The proposed taxonomy starts at the broadest level, determinants of health; subsequently moves to more finite categories of community health indicators; and, finally, addresses specific quantifiable measures. To illustrate the taxonomy's application, the authors have synthesized 21 health indicator projects from the literature and categorized them into international, national, or local/special jurisdictions. They furthered categorized the projects within the taxonomy by ranking indicators with the greatest representation among projects and by ranking the frequency of specific measures. They intend for the taxonomy to provide common metrics for measuring changes to population health and, thus, extend the utility of the CTSA Community Engagement Logic Model. The input of community partners will ultimately improve population health.