Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis.

MinK-related peptide 2 (MiRP2) and Kv3.4 subunits assemble in skeletal muscle to create subthreshold, voltage-gated potassium channels. MiRP2 acts on Kv3.4 to shift the voltage dependence of activation, speed recovery from inactivation, suppress cumulative inactivation and increase unitary conductance. We previously found an R83H missense mutation in MiRP2 that segregated with periodic paralysis in two families and diminished the effects of MiRP2 on Kv3.4. Here we show that MiRP2 has a single, functional PKC phosphorylation site at serine 82 and that normal MiRP2-Kv3.4 function requires phosphorylation of the site. The R83H variant does not prevent PKC phosphorylation of neighboring S82; rather, the change shifts the voltage dependence of activation and endows MiRP2-Kv3.4 channels with sensitivity to changes in intracellular pH across the physiological range. Thus, current passed by single R83H channels decreases as internal pH is lowered (pK(a) approximately 7.3, consistent with histidine protonation) whereas wild-type channels are largely insensitive. These findings identify a key regulatory domain in MiRP2 and suggest a mechanistic link between acidosis and episodes of periodic paralysis

A determination of the spin-orbit alignment of the anomalously dense planet orbiting HD 149026

We report 35 radial velocity measurements of HD 149026 taken with the Keck Telescope. Of these measurements, 15 were made during the transit of the companion planet HD 149026b, which occurred on 2005 June 25. These velocities provide a high-cadence observation of the Rossiter-McLaughlin effect, the shifting of photospheric line profiles that occurs when a planet occults a portion of the rotating stellar surface. We combine these radial velocities with previously published radial velocity and photometric data sets and derive a composite best-fit model for the star-planet system. This model confirms and improves previously published orbital parameters, including the remarkably small planetary radius, the planetary mass, and the orbital inclination, found to be Rp/RJup = 0.718 ± 0.065, Mp/MJup = 0.352 ± 0.025, and I = 86.1° ± 1.4°, respectively. Together the planetary mass and radius determinations imply a mean planetary density of 1.18(-0.30)(+0.38)g cm(-3). The new data also allow for the determination of the angle between the apparent stellar equator and the orbital plane, which we constrain to be λ = -12° ± 15°

Sub-Saturn Planet Candidates to HD 16141 and HD 46375

Precision Doppler measurements from the Keck/HIRES spectrometer reveal periodic Keplerian velocity variations in the stars HD 16141 and HD 46375. HD 16141 (G5 IV) has a period of 75.8 d and a velocity amplitude of 11 m/s, yielding a companion having Msini = 0.22 Mjup and a semimajor axis, a = 0.35 AU. HD 46375 (K1 IV/V) has a period of 3.024 d and a velocity amplitude of 35 m/s, yielding a companion with Msini=0.25 Mjup, a semimajor axis of a = 0.041 AU, and an eccentricity of 0.04 (consistent with zero). These companions contribute to the rising planet mass function toward lower masses.Comment: 4 Figure

Simulation assessment of the direct-push permeameter for characterizing vertical variations in hydraulic conductivity

This is the published version. Copyright American Geophysical Union[1] The direct-push permeameter (DPP) is a tool for the in situ characterization of hydraulic conductivity (K) in shallow, unconsolidated formations. This device, which consists of a short screened section with a pair of pressure transducers near the screen, is advanced into the subsurface with direct-push technology. K is determined through a series of injection tests conducted between advancements. Recent field work by Butler et al. (2007) has shown that the DPP holds great potential for describing vertical variations in K at an unprecedented level of detail, accuracy and speed. In this paper, the fundamental efficacy of the DPP is evaluated through a series of numerical simulations. These simulations demonstrate that the DPP can provide accurate K information under conditions commonly faced in the field. A single DPP test provides an effective K for the domain immediately surrounding the interval between the injection screen and the most distant pressure transducer. Features that are thinner than that interval can be quantified by reducing the vertical distance between successive tests and analyzing the data from all tests simultaneously. A particular advantage of the DPP is that, unlike most other single borehole techniques, a low-K skin or a clogged screen has a minimal impact on the K estimate. In addition, the requirement that only steady-shape conditions be attained allows for a dramatic reduction in the time required for each injection test

A Planetary Companion to the Nearby M4 Dwarf, Gliese 876

Doppler measurements of the M4 dwarf star, Gliese 876, taken at both Lick and Keck Observatory reveal periodic, Keplerian velocity variations with a period of 61 days. The orbital fit implies that the companion has a mass of, M = 2.1 MJUP /sin i, an orbital eccentricity of, e = 0.27+-0.03, and a semimajor axis of, a = 0.21 AU. The planet is the first found around an M dwarf, and was drawn from a survey of 24 such stars at Lick Observatory. It is the closest extrasolar planet yet found, providing opportunities for follow--up detection. The presence of a giant planet on a non-circular orbit, 0.2 AU from a 1/3 M_Sun star, presents a challenge to planet formation theory. This planet detection around an M dwarf suggests that giant planets are numerous in the Galaxy.Comment: 13 pages, 3 Figure

Economic Evaluation of Multisystemic Therapy for Young People at Risk for Continuing Criminal Activity in the UK

Abstract Objective: To evaluate whether multisystemic therapy (MST) is more cost-effective than statutory interventions that are currently available for young offenders in England. Method: A cost-offset evaluation of MST based on data from a randomised controlled trial conducted in North London, England, comparing MST with usual services provided by two youth offending teams (YOT). Service costs were compared to cost savings in terms of rates of criminal re-offending. Results: 108 adolescents, aged 11–17 years, were randomly allocated to MST+YOT (n = 56) or YOT alone (n = 52). Reductions in offending were evident in both groups, but were higher in the MST+YOT group. At 18-month follow-up, the MST+YOT group cost less in terms of criminal activity (£9,425 versus £11,715, p = 0.456). The MST+YOT group were significantly cheaper in terms of YOT services than the YOT group (£3,402 versus £4,619, p = 0.006), but more expensive including the cost of MST, although not significantly so (£5,687 versus £4,619, p = 0.195). The net benefit per young person for the 18-month follow-up was estimated to be £1,222 (95% CI 2£5,838 to £8,283). Conclusions: The results reported in this study support the finding that MST+YOT has scope for cost-savings when compared to YOT alone. However, the limitations of the study in terms of method of economic evaluation, outcome measures used and data quality support the need for further research

On the 2:1 Orbital Resonance in the HD 82943 Planetary System

We present an analysis of the HD 82943 planetary system based on a radial velocity data set that combines new measurements obtained with the Keck telescope and the CORALIE measurements published in graphical form. We examine simultaneously the goodness of fit and the dynamical properties of the best-fit double-Keplerian model as a function of the poorly constrained eccentricity and argument of periapse of the outer planet's orbit. The fit with the minimum chi_{nu}^2 is dynamically unstable if the orbits are assumed to be coplanar. However, the minimum is relatively shallow, and there is a wide range of fits outside the minimum with reasonable chi_{nu}^2. For an assumed coplanar inclination i = 30 deg. (sin i = 0.5), only good fits with both of the lowest order, eccentricity-type mean-motion resonance variables at the 2:1 commensurability, theta_1 and theta_2, librating about 0 deg. are stable. For sin i = 1, there are also some good fits with only theta_1 (involving the inner planet's periapse longitude) librating that are stable for at least 10^8 years. The libration semiamplitudes are about 6 deg. for theta_1 and 10 deg. for theta_2 for the stable good fit with the smallest libration amplitudes of both theta_1 and theta_2. We do not find any good fits that are non-resonant and stable. Thus the two planets in the HD 82943 system are almost certainly in 2:1 mean-motion resonance, with at least theta_1 librating, and the observations may even be consistent with small-amplitude librations of both theta_1 and theta_2.Comment: 24 pages, including 10 figures; accepted for publication in Ap

Pumping tests in networks of multilevel sampling wells: Motivation and methodology

This is the published version. Copyright American Geophysical UnionThe identification of spatial variations in hydraulic conductivity (K) on a scale of relevance for transport investigations has proven to be a considerable challenge. Recently, a new field method for the estimation of interwell variations in K has been proposed. This method, hydraulic tomography, essentially consists of a series of short-term pumping tests performed in a tomographic-like arrangement. In order to fully realize the potential of this approach, information about lateral and vertical variations in pumping-induced head changes (drawdown) is required with detail that has previously been unobtainable in the field. Pumping tests performed in networks of multilevel sampling (MLS) wells can provide data of the needed density if drawdown can accurately and rapidly be measured in the small-diameter tubing used in such wells. Field and laboratory experiments show that accurate transient drawdown data can be obtained in the small-diameter MLS tubing either directly with miniature fiber-optic pressure sensors or indirectly using air-pressure transducers. As with data from many types of hydraulic tests, the quality of drawdown measurements from MLS tubing is quite dependent on the effectiveness of well development activities. Since MLS ports of the standard design are prone to clogging and are difficult to develop, alternate designs are necessary to ensure accurate drawdown measurements. Initial field experiments indicate that drawdown measurements obtained from pumping tests performed in MLS networks have considerable potential for providing valuable information about spatial variations in hydraulic conductivity

England and America in the writings of Wilhelm Raabe: A critical study of his knowledge and appreciation of language, literature and people

Raabe's views on England and America, as manifested above all in his characterization of the English and the Americans, are examined in detail, and attention is drawn to various works by his contemporaries in which comparable views are expressed or implied. Certain historical figures, events, and situations - and certain happenings during the author's own lifetime - did little to dispose him favourably towards the English. In some ways he found America attractive; but he did not portray it as a friendly country, and he disapproved of several supposedly American characteristics. There follows an account of Raabe's familiarity with the English language, based largely on the evidence of his published writings and correspondence. He was self-taught, it appears, and the English he wrote is a strange mixture of good and bad: his was primarily a reading knowledge. Raabe reveals much of his knowledge and appreciation of English and American literature through quotations and allusions. Quotations and expressions of literary origin which were popular in his day are treated separately: the more hackneyed the quotation, the more likely it is that he was not aware of its source - or at least did not have the original context in mind at the time of writing. Occasionally the new contexts point to his knowledge of the source in question. In general, however, these tags merely serve to strengthen impressions gained elsewhere - notably from less common quotations (and from other references to English and American writers and their works) which occur in Raabe's novels and Novellen. The relevant passages are considered at some length. Biographical material is also taken into account. Of particular interest are the passages relating to Shakespeare, whom Raabe knew well. Appended is a brief survey of the writer's personal contacts with people who knew England and America from direct experience. <p