Structures of an apo and a binary complex of an evolved archeal b family DNA polymerase capable of synthesising highly cy-dye labelled DNA

Thermophilic DNA polymerases of the polB family are of great importance in biotechnological applications including high-fidelity PCR. Of particular interest is the relative promiscuity of engineered versions of the exo- form of polymerases from the Thermo- and Pyrococcales families towards non-canonical substrates, which enables key advances in Next-generation sequencing. Despite this there is a paucity of structural information to guide further engineering of this group of polymerases. Here we report two structures, of the apo form and of a binary complex of a previously described variant (E10) of Pyrococcus furiosus (Pfu) polymerase with an ability to fully replace dCTP with Cyanine dye-labeled dCTP (Cy3-dCTP or Cy5-dCTP) in PCR and synthesise highly fluorescent “CyDNA” densely decorated with cyanine dye heterocycles. The apo form of Pfu-E10 closely matches reported apo form structures of wild-type Pfu. In contrast, the binary complex (in the replicative state with a duplex DNA oligonucleotide) reveals a closing movement of the thumb domain, increasing the contact surface with the nascent DNA duplex strand. Modelling based on the binary complex suggests how bulky fluorophores may be accommodated during processive synthesis and has aided the identification of residues important for the synthesis of unnatural nucleic acid polymers

Punctuated equilibria and 1/f noise in a biological coevolution model with individual-based dynamics

We present a study by linear stability analysis and large-scale Monte Carlo simulations of a simple model of biological coevolution. Selection is provided through a reproduction probability that contains quenched, random interspecies interactions, while genetic variation is provided through a low mutation rate. Both selection and mutation act on individual organisms. Consistent with some current theories of macroevolutionary dynamics, the model displays intermittent, statistically self-similar behavior with punctuated equilibria. The probability density for the lifetimes of ecological communities is well approximated by a power law with exponent near -2, and the corresponding power spectral densities show 1/f noise (flicker noise) over several decades. The long-lived communities (quasi-steady states) consist of a relatively small number of mutualistically interacting species, and they are surrounded by a ``protection zone'' of closely related genotypes that have a very low probability of invading the resident community. The extent of the protection zone affects the stability of the community in a way analogous to the height of the free-energy barrier surrounding a metastable state in a physical system. Measures of biological diversity are on average stationary with no discernible trends, even over our very long simulation runs of approximately 3.4x10^7 generations.Comment: 20 pages RevTex. Minor revisions consistent with published versio

Treatment as Prevention-Provider Knowledge and Counseling Lag Behind Global Campaigns

INTRODUCTION In 2011, the landmark HIV Prevention Trials Network (HPTN) 052 trial found that early initiation of antiretroviral treatment (ART) in persons living with HIV (PLHIV) reduced viral transmission to uninfected partners by 96%. Treatment as prevention (TasP), whereby HIV transmission is prevented by consistent use of HIV treatment and durable viral suppression, has ushered in a new era in worldwide HIV prevention. The combined health benefits of averting new infections and preserving/improving health for PLHIV have translated into rapid scale-up in treatment access across the globe

Probing star formation and ISM properties using galaxy disk inclination: III. Evolution in dust opacity and clumpiness between redshift 0.0 < z < 0.7 constrained from UV to NIR

Interstellar matter and star formatio

ALICE: The Ultraviolet Imaging Spectrograph aboard the New Horizons Pluto-Kuiper Belt Mission

The New Horizons ALICE instrument is a lightweight (4.4 kg), low-power (4.4 Watt) imaging spectrograph aboard the New Horizons mission to Pluto/Charon and the Kuiper Belt. Its primary job is to determine the relative abundances of various species in Pluto's atmosphere. ALICE will also be used to search for an atmosphere around Pluto's moon, Charon, as well as the Kuiper Belt Objects (KBOs) that New Horizons hopes to fly by after Pluto-Charon, and it will make UV surface reflectivity measurements of all of these bodies as well. The instrument incorporates an off-axis telescope feeding a Rowland-circle spectrograph with a 520-1870 angstroms spectral passband, a spectral point spread function of 3-6 angstroms FWHM, and an instantaneous spatial field-of-view that is 6 degrees long. Different input apertures that feed the telescope allow for both airglow and solar occultation observations during the mission. The focal plane detector is an imaging microchannel plate (MCP) double delay-line detector with dual solar-blind opaque photocathodes (KBr and CsI) and a focal surface that matches the instrument's 15-cm diameter Rowland-circle. In what follows, we describe the instrument in greater detail, including descriptions of its ground calibration and initial in flight performance.Comment: 24 pages, 29 figures, 2 tables; To appear in a special volume of Space Science Reviews on the New Horizons missio

Ralph: A Visible/Infrared Imager for the New Horizons Pluto/Kuiper Belt Mission

The New Horizons instrument named Ralph is a visible/near infrared multi-spectral imager and a short wavelength infrared spectral imager. It is one of the core instruments on New Horizons, NASA's first mission to the Pluto/Charon system and the Kuiper Belt. Ralph combines panchromatic and color imaging capabilities with IR imaging spectroscopy. Its primary purpose is to map the surface geology and composition of these objects, but it will also be used for atmospheric studies and to map the surface temperature. It is a compact, low-mass (10.5 kg), power efficient (7.1 W peak), and robust instrument with good sensitivity and excellent imaging characteristics. Other than a door opened once in flight, it has no moving parts. These characteristics and its high degree of redundancy make Ralph ideally suited to this long-duration flyby reconnaissance mission.Comment: 18 pages, 15 figures, 4 tables; To appear in a special volume of Space Science Reviews on the New Horizons missio

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters