Ultrasensitivity in phosphorylation-dephosphorylation cycles with little substrate

Cellular decision-making is driven by dynamic behaviours, such as the preparations for sunrise enabled by circadian rhythms and the choice of cell fates enabled by positive feedback. Such behaviours are often built upon ultrasensitive responses where a linear change in input generates a sigmoidal change in output. Phosphorylation-dephosphorylation cycles are one means to generate ultrasensitivity. Using bioinformatics, we show that in vivo levels of kinases and phosphatases frequently exceed the levels of their corresponding substrates in budding yeast. This result is in contrast to the conditions often required by zero-order ultrasensitivity, perhaps the most well known means for how such cycles become ultrasensitive. We therefore introduce a mechanism to generate ultrasensitivity when numbers of enzymes are higher than numbers of substrates. Our model combines distributive and non-distributive actions of the enzymes with two-stage binding and concerted allosteric transitions of the substrate. We use analytical and numerical methods to calculate the Hill number of the response. For a substrate with [Formula: see text] phosphosites, we find an upper bound of the Hill number of [Formula: see text], and so even systems with a single phosphosite can be ultrasensitive. Two-stage binding, where an enzyme must first bind to a binding site on the substrate before it can access the substrate's phosphosites, allows the enzymes to sequester the substrate. Such sequestration combined with competition for each phosphosite provides an intuitive explanation for the sigmoidal shifts in levels of phosphorylated substrate. Additionally, we find cases for which the response is not monotonic, but shows instead a peak at intermediate levels of input. Given its generality, we expect the mechanism described by our model to often underlay decision-making circuits in eukaryotic cells

Monte Carlo Markov Chain parameter estimation in semi-analytic models of galaxy formation

We present a statistical exploration of the parameter space of the De Lucia and Blaizot version of the Munich semi-analytic (SA) model built upon the Millennium dark matter simulation. This is achieved by applying a Monte Carlo Markov Chain method to constrain the six free parameters that define the stellar and black hole mass functions at redshift zero. The model is tested against three different observational data sets, including the galaxy K-band luminosity function, B - V colours and the black hole-bulge mass relation, separately and combined, to obtain mean values, confidence limits and likelihood contours for the best-fitting model. Using each observational data set independently, we discuss how the SA model parameters affect each galaxy property and find that there are strong correlations between them. We analyse to what extent these are simply reflections of the observational constraints, or whether they can lead to improved understandings of the physics of galaxy formation. When all the observations are combined, we find reasonable agreement between the majority of the previously published parameter values and our confidence limits. However, the need to suppress dwarf galaxy formation requires the strength of the supernova feedback to be significantly higher in our best-fitting solution than in previous work. To balance this, we require the feedback to become ineffective in haloes of lower mass than before, so as to permit the formation of sufficient high-luminosity galaxies: unfortunately, this leads to an excess of galaxies around L*. Although the best fit is formally consistent with the data, there is no region of parameter space that reproduces the shape of galaxy luminosity function across the whole magnitude range. For our best fit, we present the model predictions for the bJ-band luminosity and stellar mass functions. We find a systematic disagreement between the observed mass function and the predictions from the K-band constraint, which we explain in light of recent works that suggest uncertainties of up to 0.3 dex in the mass determination from stellar population synthesis models. We discuss modifications to the SA model that might simultaneously improve the fit to the observed mass function and reduce the reliance on excessive supernova feedback in small haloes

The 2-Dimensional Quantum Euclidean Algebra

The algebra dual to Woronowicz's deformation of the 2-\-di\-men\-sion\-al Euclidean group is constructed. The same algebra is obtained from $SU_{q}(2)$ via contraction on both the group and algebra levels.Comment: 8 pages, LBL-31711 and UCB-PTH-92/0

Iron in galaxy groups and clusters: confronting galaxy evolution models with a newly homogenized data set

We present an analysis of the iron abundance in the hot gas surrounding galaxy groups and clusters. To do this, we first compile and homogenize a large data set of 79 low-redshift (z ̃ = 0.03) systems (159 individual measurements) from the literature. Our analysis accounts for differences in aperture size, solar abundance, and cosmology, and scales all measurements using customized radial profiles for the temperature (T), gas density (ρgas), and iron abundance (ZFe). We then compare this data set to groups and clusters in the L-GALAXIES galaxy evolution model. Our homogenized data set reveals a tight T–ZFe relation for clusters, with a scatter in ZFe of only 0.10 dex and a slight negative gradient. After examining potential measurement biases, we conclude that some of this negative gradient has a physical origin. Our model suggests greater accretion of hydrogen in the hottest systems, via stripping from infalling satellites, as a cause. In groups, L-GALAXIES over-estimates ZFe, indicating that metal-rich gas removal (via e.g. AGN feedback) is required. L-GALAXIES is consistent with the observed ZFe in the intracluster medium (ICM) of the hottest clusters at z = 0, and shows a similar rate of ICM enrichment as that observed from at least z ∼ 1.3 to the present day. This is achieved without needing to modify any of the galactic chemical evolution (GCE) model parameters. However, the ZFe in intermediate-T clusters could be under-estimated in our model. We caution that modifications to the GCE modelling to correct this disrupt the agreement with observations of galaxies’ stellar components

Morphological evolution and galactic sizes in the L-Galaxies SA model

In this work we update theL-Galaxiessemi-analytic model (SAM) to better follow thephysical processes responsible for the growth of bulges via disc instabilities (leading to pseudo-bulges) and mergers (leading to classical bulges). We address the former by considering thecontribution of both stellar and gaseous discs in the stability of the galaxy, and we update thelatter by including dissipation of energy in gas-rich mergers. Furthermore, we introduce angularmomentum losses during cooling and find that an accurate match to the observed correlationbetween stellar disc scale length and mass atz∼0.0requires that the gas loses 20%of its initialspecific angular momentum to the corresponding dark matter halo during the formation of thecold gas disc. We reproduce the observed trends between the stellar mass and specific angularmomentum for both disc- and bulge-dominated galaxies, with the former rotating faster thanthe latter of the same mass. We conclude that a two-component instability recipe provides amorphologically diverse galaxy sample which matches the observed fractional breakdown ofgalaxies into different morphological types. This recipe also enables us to obtain an excellent fitto the morphology-mass relation and stellar mass function of different galactic types. Finally, we find that energy dissipation during mergers reduces the merger remnant sizes and allowsus to match the observed mass-size relation for bulge-dominated system

Preliminary Spectral Analysis of the Type II Supernova 1999em

We have calculated fast direct spectral model fits to two early-time spectra of the Type-II plateau SN 1999em, using the SYNOW synthetic spectrum code. The first is an extremely early blue optical spectrum and the second a combined HST and optical spectrum obtained one week later. Spectroscopically this supernova appears to be a normal Type II and these fits are in excellent agreement with the observed spectra. Our direct analysis suggests the presence of enhanced nitrogen. We have further studied these spectra with the full NLTE general model atmosphere code PHOENIX. While we do not find confirmation for enhanced nitrogen (nor do we rule it out), we do require enhanced helium. An even more intriguing possible line identification is complicated Balmer and He I lines, which we show falls naturally out of the detailed calculations with a shallow density gradient. We also show that very early spectra such as those presented here combined with sophisticated spectral modeling allows an independent estimate of the total reddening to the supernova, since when the spectrum is very blue, dereddening leads to changes in the blue flux that cannot be reproduced by altering the ``temperature'' of the emitted radiation. These results are extremely encouraging since they imply that detailed modeling of early spectra can shed light on both the abundances and total extinction of SNe II, the latter improving their utility and reliability as distance indicators.Comment: to appear in ApJ, 2000, 54