Probing ion channel functional architecture and domain recombination compatibility by massively parallel domain insertion profiling

Protein domains are the basic units of protein structure and function. Comparative analysis of genomes and proteomes showed that domain recombination is a main driver of multidomain protein functional diversification and some of the constraining genomic mechanisms are known. Much less is known about biophysical mechanisms that determine whether protein domains can be combined into viable protein folds. Here, we use massively parallel insertional mutagenesis to determine compatibility of over 300,000 domain recombination variants of the Inward Rectifier K+ channel Kir2.1 with channel surface expression. Our data suggest that genomic and biophysical mechanisms acted in concert to favor gain of large, structured domain at protein termini during ion channel evolution. We use machine learning to build a quantitative biophysical model of domain compatibility in Kir2.1 that allows us to derive rudimentary rules for designing domain insertion variants that fold and traffic to the cell surface. Positional Kir2.1 responses to motif insertion clusters into distinct groups that correspond to contiguous structural regions of the channel with distinct biophysical properties tuned towards providing either folding stability or gating transitions. This suggests that insertional profiling is a high-throughput method to annotate function of ion channel structural regions

Co-opting the state: how weak parties can make stable party systems

Conventional understandings of party system institutionalisation assume that institutionalised parties are necessary for interparty competition to stabilise. However, this approach neglects the role of the state in shaping party competition. Using survey data from Bangladesh, India and Pakistan, it is shown that weakly institutionalised parties can lead to institutionalised party systems if parties are able to successfully co-opt the state and use state resources to supplement party deficiencies. By developing a relationship that intertwines parties with the state, parties in young democracies do not need to institutionalise for stable party systems to form

Air fluorescence measurements in the spectral range 300-420 nm using a 28.5 GeV electron beam

Measurements are reported of the yield and spectrum of fluorescence, excited by a 28.5 GeV electron beam, in air at a range of pressures of interest to ultra-high energy cosmic ray detectors. The wavelength range was 300 - 420 nm. System calibration has been performed using Rayleigh scattering of a nitrogen laser beam. In atmospheric pressure dry air at 304 K the yield is 20.8 +/- 1.6 photons per MeV.Comment: 29 pages, 10 figures. Submitted to Astroparticle Physic

Search for Point Sources of Ultra-High Energy Cosmic Rays Above 40 EeV Using a Maximum Likelihood Ratio Test

We present the results of a search for cosmic ray point sources at energies above 40 EeV in the combined data sets recorded by the AGASA and HiRes stereo experiments. The analysis is based on a maximum likelihood ratio test using the probability density function for each event rather than requiring an a priori choice of a fixed angular bin size. No statistically significant clustering of events consistent with a point source is found.Comment: 7 pages, 7 figures. Accepted for publication in The Astrophysical Journa

An upper limit on the electron-neutrino flux from the HiRes detector

Air-fluorescence detectors such as the High Resolution Fly's Eye (HiRes) detector are very sensitive to upward-going, Earth-skimming ultrahigh energy electron-neutrino-induced showers. This is due to the relatively large interaction cross sections of these high-energy neutrinos and to the Landau-Pomeranchuk-Migdal (LPM) effect. The LPM effect causes a significant decrease in the cross sections for bremsstrahlung and pair production, allowing charged-current electron-neutrino-induced showers occurring deep in the Earth's crust to be detectable as they exit the Earth into the atmosphere. A search for upward-going neutrino-induced showers in the HiRes-II monocular dataset has yielded a null result. From an LPM calculation of the energy spectrum of charged particles as a function of primary energy and depth for electron-induced showers in rock, we calculate the shape of the resulting profile of these showers in air. We describe a full detector Monte Carlo simulation to determine the detector response to upward-going electron-neutrino-induced cascades and present an upper limit on the flux of electron-neutrinos.Comment: 13 pages, 3 figures. submitted to Astrophysical Journa

Observation of the Ankle and Evidence for a High-Energy Break in the Cosmic Ray Spectrum

We have measured the cosmic ray spectrum at energies above $10^{17}$ eV using the two air fluorescence detectors of the High Resolution Fly's Eye experiment operating in monocular mode. We describe the detector, PMT and atmospheric calibrations, and the analysis techniques for the two detectors. We fit the spectrum to models describing galactic and extragalactic sources. Our measured spectrum gives an observation of a feature known as the ``ankle'' near $3\times 10^{18}$ eV, and strong evidence for a suppression near $6\times 10^{19}$ eV.Comment: 14 pages, 9 figures. To appear in Physics Letters B. Accepted versio

Search for Correlations between HiRes Stereo Events and Active Galactic Nuclei

We have searched for correlations between the pointing directions of ultrahigh energy cosmic rays observed by the High Resolution Fly's Eye experiment and Active Galactic Nuclei (AGN) visible from its northern hemisphere location. No correlations, other than random correlations, have been found. We report our results using search parameters prescribed by the Pierre Auger collaboration. Using these parameters, the Auger collaboration concludes that a positive correlation exists for sources visible to their southern hemisphere location. We also describe results using two methods for determining the chance probability of correlations: one in which a hypothesis is formed from scanning one half of the data and tested on the second half, and another which involves a scan over the entire data set. The most significant correlation found occurred with a chance probability of 24%.Comment: 13 pages, 1 table, 5 figure

Comparison of air fluorescence and ionization measurements of E.M. shower depth profiles: test of a UHECR detector technique

Measurements are reported on the fluorescence of air as a function of depth in electromagnetic showers initiated by bunches of 28.5 GeV electrons. The light yield is compared with the expected and observed depth profiles of ionization in the showers. It validates the use of atmospheric fluorescence profiles in measuring ultra high energy cosmic rays.Comment: 22 pages, 11 figures. Submitted to Astroparticle Physic