Thermodynamics of Neutral Protein Evolution

Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the molecular clock. Here we present a mathematical theory that predicts the number of accumulated mutations, the index of dispersion, and the distribution of stabilities in an evolving protein population from knowledge of the stability effects (ddG values) for single mutations. Our theory quantitatively describes how neutral evolution leads to marginally stable proteins, and provides formulae for calculating how fluctuations in stability cause an overdispersion of the molecular clock. It also shows that the structural influences on the rate of sequence evolution that have been observed in earlier simulations can be calculated using only the single-mutation ddG values. We consider both the case when the product of the population size and mutation rate is small and the case when this product is large, and show that in the latter case proteins evolve excess mutational robustness that is manifested by extra stability and increases the rate of sequence evolution. Our basic method is to treat protein evolution as a Markov process constrained by a minimal requirement for stable folding, enabling an evolutionary description of the proteins solely in terms of the experimentally measureable ddG values. All of our theoretical predictions are confirmed by simulations with model lattice proteins. Our work provides a mathematical foundation for understanding how protein biophysics helps shape the process of evolution

A Multiwavelength Investigation of Unidentified EGRET Sources

Statistical studies indicate that the 271 point sources of high-energy gamma rays belong to two groups: a Galactic population and an isotropic extragalactic population. Many unidentified extragalactic sources are certainly blazars, and it is the intention of this work to uncover gamma-ray blazars missed by previous attempts. Until recently, searches for blazar counterparts to unidentified EGRET sources have focused on finding AGN that have 5-GHz radio flux densities S_5 near or above 1 Jy. However, the recent blazar identification of 3EG J2006-2321 (S_5 = 260 mJy) and other work suggest that careful studies of weaker flat-spectrum sources may be fruitful. In this spirit, error circles of 4 high-latitude unidentified EGRET sources have been searched for 5-GHz sources. The gamma-ray sources are 3EG J1133+0033, 3EG J1212+2304, 3EG J1222+2315, and 3EG J1227+4302. Within the error contours of each of the four sources are found 6 radio candidates; by observing the positions of the radio sources with the 0.81-m Tenagra II telescope it is determined that 14 of these 24 radio sources have optical counterparts with R < 22. Eight of these from two different EGRET sources have been observed in the B, V, and R bands in more than one epoch and the analysis of these data is ongoing. Any sources that are found to be variable will be the objects of multi-epoch polarimetry studies.Comment: 6 pages, 2 tables. To appear in Astrophysics & Space Scienc

What is the best treatment for Osgood-Schlatter disease?

Osgood-Schlatter disease is a common cause of pain and tenderness at the tibial tuberosity in active adolescents. It is typically a self-limited condition that waxes and wanes, but which often takes months to years to resolve entirely. It is best managed with conservative measures (activity modification, ice, anti- inflammatory agents) and time (strength of recommendation [SOR]: B, several case series and retrospective studies). In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks (SOR: C, several case series). Corticosteroid injections are not recommended (SOR: C, case reports and expert opinion)

Mechanical coupling in flashing ratchets

We consider the transport of rigid objects with internal structure in a flashing ratchet potential by investigating the overdamped behavior of a rod-like chain of evenly spaced point particles. In 1D, analytical arguments show that the velocity can reverse direction multiple times in response to changing the size of the chain or the temperature of the heat bath. The physical reason is that the effective potential experienced by the mechanically coupled objects can have a different symmetry than that of individual objects. All analytical predictions are confirmed by Brownian dynamics simulations. These results may provide a route to simple, coarse-grained models of molecular motor transport that incorporate an object's size and rotational degrees of freedom into the mechanism of transport.Comment: 9 pages, 10 figure

Do antioxidants (vitamins C, E) improve outcomes in patients with coronary artery disease?

Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality (grade of recommendation: A, 4 high quality randomized controlled trials [RCTs]). There is no evidence that vitamin C decreases mortality in patients at risk for coronary disease (grade of recommendation: A, meta-analysis of 3 small RCTs). Combination antioxidant regimens (Vitamins E, C, and betacarotene) seem safe, but do not decrease mortality or incidence of major coronary and vascular events (grade recommendation: A, 1 high-quality RCT)

Bloom-Gilman duality of the nucleon structure function and the elastic peak contribution

The occurrence of the Bloom-Gilman duality in the nucleon structure function is investigated by analyzing the Q**2-behavior of low-order moments, both including and excluding the contribution arising from the nucleon elastic peak. The Natchmann definition of the moments has been adopted in order to cancel out target-mass effects. It is shown that the onset of the Bloom-Gilman duality occurs around Q**2 ~ 2 (GeV/c)**2 if only the inelastic part of the nucleon structure function is considered, whereas the inclusion of the nucleon elastic peak contribution leads to remarkable violations of the Bloom-Gilman duality.Comment: in Proc. of the XVI European Conference on Few-body Problems in Physics, Autrans (France), July 199

Unveiling the Origin of Grb 090709A: Lack of Periodicity in a Reddened Cosmological Long-Duration Gamma-Ray Burst

We present broadband (gamma-ray, X-ray, near-infrared, optical, and radio) observations of the Swift gamma-ray burst (GRB) 090709A and its afterglow in an effort to ascertain the origin of this high-energy transient. Previous analyses suggested that GRB 090709A exhibited quasi-periodic oscillations with a period of 8.06 s, a trait unknown in long-duration GRBs but typical of flares from soft gamma-ray repeaters. When properly accounting for the underlying shape of the power-density spectrum of GRB 090709A, we find no conclusive (>3σ) evidence for the reported periodicity. In conjunction with the location of the transient (far from the Galactic plane and absent any nearby host galaxy in the local universe) and the evidence for extinction in excess of the Galactic value, we consider a magnetar origin relatively unlikely. A long-duration GRB, however, can account for the majority of the observed properties of this source. GRB 090709A is distinguished from other long-duration GRBs primarily by the large amount of obscuration from its host galaxy (A_(K,obs) ≳ 2 mag)

The Host Galaxy and Optical Light Curve of the Gamma-Ray Burst GRB 980703

We present deep HST/STIS and ground-based photometry of the host galaxy of the gamma-ray burst GRB 980703 taken 17, 551, 710, and 716 days after the burst. We find that the host is a blue, slightly over-luminous galaxy with V_gal = 23.00 +/- 0.10, (V-R)_gal = 0.43 +/- 0.13, and a centre that is approximately 0.2 mag bluer than the outer regions of the galaxy. The galaxy has a star-formation rate of 8-13 M_sun/yr, assuming no extinction in the host. We find that the galaxy is best fit by a Sersic R^(1/n) profile with n ~= 1.0 and a half-light radius of 0.13 arcsec (= 0.72/h_100 proper kpc). This corresponds to an exponential disk with a scale radius of 0.22 arcsec (= 1.21/h_100 proper kpc). Subtracting a fit with elliptical isophotes leaves large residuals, which suggests that the host galaxy has a somewhat irregular morphology, but we are unable to connect the location of GRB 980703 with any special features in the host. The host galaxy appears to be a typical example of a compact star forming galaxy similar to those found in the Hubble Deep Field North. The R-band light curve of the optical afterglow associated with this gamma-ray burst is consistent with a single power-law decay having a slope of alpha = -1.37 +/- 0.14. Due to the bright underlying host galaxy the late time properties of the light-curve are very poorly constrained. The decay of the optical light curve is consistent with a contribution from an underlying Type Ic supernova like SN1998bw, or a dust echo, but such contributions cannot be securely established.Comment: 9 pages, 5 figures, LaTeX using A&A Document Class v4.05, to appear in A&

The Discovery and Broad-band Follow-up of the Transient Afterglow of GRB 980703

We report on the discovery of the radio, infrared and optical transient coincident with an X-ray transient proposed to be the afterglow of GRB 980703. At later times when the transient has faded below detection, we see an underlying galaxy with R=22.6; this galaxy is the brightest host galaxy (by nearly 2 magnitudes) of any cosmological GRB thus far. In keeping with an established trend, the GRB is not significantly offset from the host galaxy. Interpreting the multi-wavelength data in the framework of the popular fireball model requires that the synchrotron cooling break was between the optical and X-ray bands on July 8.5 UT and that the intrinsic extinction of the transient is Av=0.9. This is somewhat higher than the extinction for the galaxy as a whole, as estimated from spectroscopy.Comment: 5 pages, 3 figures, and 2 tables. Submitted to the Astrophysical Journal Letters on 27 August 199