Modeling Networks of Coupled Enzymatic Reactions Using the Total Quasi-Steady State Approximation

In metabolic networks, metabolites are usually present in great excess over the enzymes that catalyze their interconversion, and describing the rates of these reactions by using the Michaelis–Menten rate law is perfectly valid. This rate law assumes that the concentration of enzyme–substrate complex (C) is much less than the free substrate concentration (S (0)). However, in protein interaction networks, the enzymes and substrates are all proteins in comparable concentrations, and neglecting C with respect to S (0) is not valid. Borghans, DeBoer, and Segel developed an alternative description of enzyme kinetics that is valid when C is comparable to S (0). We extend this description, which Borghans et al. call the total quasi-steady state approximation, to networks of coupled enzymatic reactions. First, we analyze an isolated Goldbeter–Koshland switch when enzymes and substrates are present in comparable concentrations. Then, on the basis of a real example of the molecular network governing cell cycle progression, we couple two and three Goldbeter–Koshland switches together to study the effects of feedback in networks of protein kinases and phosphatases. Our analysis shows that the total quasi-steady state approximation provides an excellent kinetic formalism for protein interaction networks, because (1) it unveils the modular structure of the enzymatic reactions, (2) it suggests a simple algorithm to formulate correct kinetic equations, and (3) contrary to classical Michaelis–Menten kinetics, it succeeds in faithfully reproducing the dynamics of the network both qualitatively and quantitatively

Probing The Multiphase Interstellar Medium Of The Dwarf Starburst Galaxy NGC 625 With FUSE Spectroscopy

We present new FUSE spectroscopy of the dwarf starburst galaxy NGC 625. These observations probe multiple phases of the interstellar medium, including the coronal, ionized, neutral and molecular gas. This nearby (D = 3.9 +/- 0.2 Mpc) system shows a clear detection of outflowing coronal gas as traced by OVI 1032 Angstrom absorption. The centroid of the OVI profile is blueshifted with respect to the galaxy systemic velocity by ~ 30 km/sec, suggesting a low-velocity outflow. The implied OVI velocity extent is found to be 100 +/- 20 km/sec, which is fully consistent with the detected HI outflow velocity found in radio synthesis observations. We detect multiple lines of diffuse H2 absorption from the ISM of NGC 625; this is one of only a few extragalactic systems with FUSE detections of H2 lines in the Lyman and Werner bands. We find a potential abundance offset between the neutral and nebular gas that exceeds the errors on the derived column densities. Since such an offset has been found in multiple dwarf galaxies, we discuss the implications of a lower-metallicity halo surrounding the central star forming regions of dwarf galaxies. The apparent offset may be due to saturation of the observed OI line, and higher S/N observations are required to resolve this issue.Comment: ApJ, in press; full-resolution version may be obtained at http://www.astro.umn.edu/~cannon/n625.fuse.p

Sodium content as a predictor of the advanced evolution of globular cluster stars

The asymptotic giant branch (AGB) phase is the final stage of nuclear burning for low-mass stars. Although Milky Way globular clusters are now known to harbour (at least) two generations of stars they still provide relatively homogeneous samples of stars that are used to constrain stellar evolution theory. It is predicted by stellar models that the majority of cluster stars with masses around the current turn-off mass (that is, the mass of the stars that are currently leaving the main sequence phase) will evolve through the AGB phase. Here we report that all of the second-generation stars in the globular cluster NGC 6752 -- 70 per cent of the cluster population -- fail to reach the AGB phase. Through spectroscopic abundance measurements, we found that every AGB star in our sample has a low sodium abundance, indicating that they are exclusively first-generation stars. This implies that many clusters cannot reliably be used for star counts to test stellar evolution timescales if the AGB population is included. We have no clear explanation for this observation.Comment: Published in Nature (online 29 May 2013, hard copy 13 June), 12 pages, 3 figures + supplementary information sectio

Emergence of collective intonation in the musical performance of crowds

To be published in EPLTo be published in EP

Energy demand on dairy farms in Ireland

peer-reviewedReducing electricity consumption in Irish milk production is a topical issue for 2 reasons. First, the introduction of a dynamic electricity pricing system, with peak and off-peak prices, will be a reality for 80% of electricity consumers by 2020. The proposed pricing schedule intends to discourage energy consumption during peak periods (i.e., when electricity demand on the national grid is high) and to incentivize energy consumption during off-peak periods. If farmers, for example, carry out their evening milking during the peak period, energy costs may increase, which would affect farm profitability. Second, electricity consumption is identified in contributing to about 25% of energy use along the life cycle of pasture-based milk. The objectives of this study, therefore, were to document electricity use per kilogram of milk sold and to identify strategies that reduce its overall use while maximizing its use in off-peak periods (currently from 0000 to 0900h). We assessed, therefore, average daily and seasonal trends in electricity consumption on 22 Irish dairy farms, through detailed auditing of electricity-consuming processes. To determine the potential of identified strategies to save energy, we also assessed total energy use of Irish milk, which is the sum of the direct (i.e., energy use on farm) and indirect energy use (i.e., energy needed to produce farm inputs). On average, a total of 31.73 MJ was required to produce 1kg of milk solids, of which 20% was direct and 80% was indirect energy use. Electricity accounted for 60% of the direct energy use, and mainly resulted from milk cooling (31%), water heating (23%), and milking (20%). Analysis of trends in electricity consumption revealed that 62% of daily electricity was used at peak periods. Electricity use on Irish dairy farms, therefore, is substantial and centered around milk harvesting. To improve the competitiveness of milk production in a dynamic electricity pricing environment, therefore, management changes and technologies are required that decouple energy use during milking processes from peak periods

Efficacy of pulmonary artery pressure monitoring in patients with chronic heart failure:a meta-analysis of three randomized controlled trials

Aims Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question. Methods A systematic literature search was performed for randomized clinical trials with PA pressure monitoring devices in patients and results with HF. The primary outcome of interest was the total number of HF hospitalizations. Other outcomes assessed were urgent visits leading to treatment with intravenous diuretics, all-cause mortality, and composites. Treatment effects are expressed as hazard ratios, and pooled effect estimates were obtained applying random effects meta-analyses. Three eligible randomized clinical trials were identified that included 1898 outpatients in New York Heart Association functional classes II–IV, either hospitalized for HF in the prior 12 months or with elevated plasma NT-proBNP concentrations. The mean followup was 14.7 months, 67.8% of the patients were men, and 65.8% had an ejection fraction ≤40%. Compared to patients in the control group, the hazard ratio (95% confidence interval) for total HF hospitalizations in those randomized to PA pressure monitoring was 0.70 (0.58–0.86) (P = .0005). The corresponding hazard ratio for the composite of total HF hospitalizations, urgent visits and all-cause mortality was 0.75 (0.61–0.91; P = .0037) and for all-cause mortality 0.92 (0.73–1.16). Subgroup analyses, including ejection fraction phenotype, revealed no evidence of heterogeneity in the treatment effect. Conclusion The use of remote PA pressure monitoring to guide treatment of patients with HF reduces episodes of worsening HF and subsequent hospitalizations.</p

Strings in AdS_3 and the SL(2,R) WZW Model. Part 2: Euclidean Black Hole

We consider the one-loop partition function for Euclidean BTZ black hole backgrounds or equivalently thermal AdS_3 backgrounds which are quotients of H_3 (Euclidean AdS_3). The one-loop partition function is modular invariant and we can read off the spectrum which is consistent to that found in hep-th/0001053. We see long strings and discrete states in agreement with the expectations.Comment: 23 pages, 3 figure

Predicting Crystal Structures with Data Mining of Quantum Calculations

Predicting and characterizing the crystal structure of materials is a key problem in materials research and development. It is typically addressed with highly accurate quantum mechanical computations on a small set of candidate structures, or with empirical rules that have been extracted from a large amount of experimental information, but have limited predictive power. In this letter, we transfer the concept of heuristic rule extraction to a large library of ab-initio calculated information, and demonstrate that this can be developed into a tool for crystal structure prediction.Comment: 4 pages, 3 pic

The Progenitors of Dwarf Spheroidal Galaxies

Dwarf spheroidal (dSph) galaxies present an evolutionary puzzle that we explore in 40 early- and late-type dwarfs in the Local Group and nearby field. Although dSphs formed stars over extended periods, today all but one are free of detectable interstellar matter (ISM), even in the Fornax dSph, where stars still formed 100 Myr ago. Combining metallicities for red giants with HI data from the literature, we show that the well-known offset in luminosity-metallicity (L-Z) relations for dSphs and dwarf irregular (dIrr) galaxies exists also when comparing only their old stellar populations: dSphs have higher mean stellar metallicities for a fixed luminosity. Evidently younger dSphs experienced more efficient enrichment than young dIrrs. Dwarf galaxies, whose locus in the L-Z diagram is consistent with that of dSphs even for baryonic luminosities, are the ``transition-type dwarfs'' Phoenix, DDO210, LGS3, Antlia, and KKR25. They have mixed dIrr/dSph morphologies, low stellar masses, low angular momentum, and HI contents of less than a few 10^6 solar masses. Unlike dIrrs, many transition-type dwarfs would closely resemble dSphs if their gas were removed; they are likely dSph progenitors. As gas removal is key, we consider the empirical evidence for various gas removal processes. We suggest that internal gas removal mechanisms are inadequate and favor ram pressure stripping to make dSphs. A combination of initial conditions and environment seems to support the formation of dSphs, which appear to form from small galaxies with active early star formation, whose evolution halts due to externally induced gas loss. Transition-type dwarfs then are dSphs that kept their ISM, and therefore should replace dSphs in isolated locations where stripping is ineffective. (Abridged)Comment: 25 pages in AASTeX two-column preprint style, 1 table, 3 figures. Accepted for publication in the Astronomical Journal (April 2003 issue