A Biosilification Fusion Protein for a ‘Self-immobilising’ Sarcosine Oxidase Amperometric Enzyme Biosensor

Monomeric sarcosine oxidase (mSOx) fusion with the silaffin peptide, R5, designed previously for easy protein production in low resource areas, was used in a biosilification process to form an enzyme layer electrode biosensor. mSOx is a low activity enzyme (10-20 U/mg) requiring high amounts of enzyme to obtain an amperometric biosensor signal, in the clinically useful range 10mM. An amperometric biosensor model was fitted to experimental data to investigate dynamic range. mSOx constructs were designed with 6H (6 x histidine) and R5 (silaffin) peptide tags and compared with native mSOx. Glutaraldehyde (GA) cross-linked proteins retained ~5% activity for mSOx and mSOx-6H and only 0.5% for mSOx-R5. In contrast R5 catalysed biosilification on (3-mercaptopropyl) trimethoxysilane (MPTMS) and tetramethyl orthosilicate (TMOS) particles created a ‘self-immobilisation’ matrix retaining 40% and 76% activity respectively. The TMOS matrix produced a thick layer (>500μm) on a glassy carbon electrode with a mediated current due to sarcosine in the clinical range for sarcosinemia (0-1mM). The mSOx-R5 fusion protein was also used to catalyse biosilification in the presence of creatinase and creatininase, entrapping all three enzymes. A mediated GC enzyme linked current was obtained with dynamic range available for creatinine determination of 0.1-2mM for an enzyme layer ~ 800nm.Non

Dependence of X-Ray Burst Models on Nuclear Reaction Rates

X-ray bursts are thermonuclear flashes on the surface of accreting neutron stars and reliable burst models are needed to interpret observations in terms of properties of the neutron star and the binary system. We investigate the dependence of X-ray burst models on uncertainties in (p,$\gamma$), ($\alpha$,$\gamma$), and ($\alpha$,p) nuclear reaction rates using fully self-consistent burst models that account for the feedbacks between changes in nuclear energy generation and changes in astrophysical conditions. A two-step approach first identified sensitive nuclear reaction rates in a single-zone model with ignition conditions chosen to match calculations with a state-of-the-art 1D multi-zone model based on the {\Kepler} stellar evolution code. All relevant reaction rates on neutron deficient isotopes up to mass 106 were individually varied by a factor of 100 up and down. Calculations of the 84 highest impact reaction rate changes were then repeated in the 1D multi-zone model. We find a number of uncertain reaction rates that affect predictions of light curves and burst ashes significantly. The results provide insights into the nuclear processes that shape X-ray burst observables and guidance for future nuclear physics work to reduce nuclear uncertainties in X-ray burst models.Comment: 24 pages, 13 figures, 4 tables, submitte

Discovery of Variability of the Progenitor of SN 2011dh in M51 Using the Large Binocular Telescope

We show that the candidate progenitor of the core-collapse SN 2011dh in M51 (8 Mpc away) was fading by 0.039 +- 0.006 mag/year during the three years prior to the supernova, and that this level of variability is moderately unusual for other similar stars in M 51. While there are uncertainties about whether the true progenitor was a blue companion to this candidate, the result illustrates that there are no technical challenges to obtaining fairly high precision light curves of supernova progenitors using ground based observations of nearby (<10 Mpc) galaxies with wide field cameras on 8m-class telescopes. While other sources of variability may dominate, it is even possible to reach into the range of evolution rates required by the quasi-static evolution of the stellar envelope. For M 81, where we have many more epochs and a slightly longer time baseline, our formal 3 sigma sensitivity to slow changes is presently 3 millimag/year for a M_V ~= -8 mag star. In short, there is no observational barrier to determining whether the variability properties of stars in their last phases of evolution (post Carbon ignition) are different from earlier phases.Comment: 17 pages, 5 figures, submitted to Ap

Late Emission from the Type Ib/c SN 2001em: Overtaking the Hydrogen Envelope

The Type Ib/c supernova SN 2001em was observed to have strong radio, X-ray, and Halpha emission at an age of about 2.5 yr. Although the radio and X-ray emission have been attributed to an off-axis gamma-ray burst, we model the emission as the interaction of normal SN Ib/c ejecta with a dense, massive (3 Msun) circumstellar shell at a distance about 7 x 10^{16} cm. We investigate two models, in which the circumstellar shell has or has not been overtaken by the forward shock at the time of the X-ray observation. The circumstellar shell was presumably formed by vigorous mass loss with a rate (2-10) x 10^{-3} Msun/yr at 1000-2000 yr prior to the supernova explosion. The hydrogen envelope was completely lost, and subsequently was swept up and accelerated by the fast wind of the presupernova star up to a velocity of 30-50 km/s. Although interaction with the shell can explain most of the late emission properties of SN 2001em, we need to invoke clumping of the gas to explain the low absorption at X-ray and radio wavelengths.Comment: 26 pages, 4 figures, ApJ submitte

Low-Mass Relics of Early Star Formation

The earliest stars to form in the Universe were the first sources of light, heat and metals after the Big Bang. The products of their evolution will have had a profound impact on subsequent generations of stars. Recent studies of primordial star formation have shown that, in the absence of metals (elements heavier than helium), the formation of stars with masses 100 times that of the Sun would have been strongly favoured, and that low-mass stars could not have formed before a minimum level of metal enrichment had been reached. The value of this minimum level is very uncertain, but is likely to be between 10^{-6} and 10^{-4} that of the Sun. Here we show that the recent discovery of the most iron-poor star known indicates the presence of dust in extremely low-metallicity gas, and that this dust is crucial for the formation of lower-mass second-generation stars that could survive until today. The dust provides a pathway for cooling the gas that leads to fragmentation of the precursor molecular cloud into smaller clumps, which become the lower-mass stars.Comment: Offprint of Nature 422 (2003), 869-871 (issue 24 April 2003

Prostate tumor attenuation in the nu/nu murine model due to anti-sarcosine antibodies in folate-targeted liposomes

Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa

The Formation of the First Low-Mass Stars From Gas With Low Carbon and Oxygen Abundances

The first stars in the Universe are predicted to have been much more massive than the Sun. Gravitational condensation accompanied by cooling of the primordial gas due to molecular hydrogen, yields a minimum fragmentation scale of a few hundred solar masses. Numerical simulations indicate that once a gas clump acquires this mass, it undergoes a slow, quasi-hydrostatic contraction without further fragmentation. Here we show that as soon as the primordial gas - left over from the Big Bang - is enriched by supernovae to a carbon or oxygen abundance as small as ~0.01-0.1% of that found in the Sun, cooling by singly-ionized carbon or neutral oxygen can lead to the formation of low-mass stars. This mechanism naturally accommodates the discovery of solar mass stars with unusually low (10^{-5.3} of the solar value) iron abundance but with a high (10^{-1.3} solar) carbon abundance. The minimum stellar mass at early epochs is partially regulated by the temperature of the cosmic microwave background. The derived critical abundances can be used to identify those metal-poor stars in our Milky Way galaxy with elemental patterns imprinted by the first supernovae.Comment: 14 pages, 2 figures (appeared today in Nature