Macromolecular crowding explains overflow metabolism in cells

Overflow metabolism is a metabolic phenotype of cells characterized by mixed oxidative phosphorylation (OxPhos) and fermentative glycolysis in the presence of oxygen. Recently, it was proposed that a combination of a protein allocation constraint and a higher proteome fraction cost of energy generation by OxPhos relative to fermentation form the basis of overflow metabolism in the bacterium, Escherichia coli. However, we argue that the existence of a maximum or optimal macromolecular density is another essential requirement. Here we re-evaluate our previous theory of overflow metabolism based on molecular crowding following the proteomic fractions formulation. We show that molecular crowding is a key factor in explaining the switch from OxPhos to overflow metabolism

Serine biosynthesis with one carbon catabolism represents a novel pathway for ATP generation in cells using alternative glycolysis with zero net ATP production

Recent experimental evidence indicates that some cancer cells have an alternative glycolysis pathway with net zero ATP production, implying that upregulation of glycolysis in these cells may not be related to the generation of ATP. Here we use a genome-scale model of human cell metabolism to investigate the potential metabolic alterations in cells using net zero ATP glycolysis. We uncover a novel pathway for ATP generation that involves reactions from the serine biosynthesis and one-carbon metabolism pathways. This pathway has a predicted two-fold higher flux rate in cells using net zero ATP glycolysis than those using standard glycolysis and generates twice as much ATP with significantly lower rate of lactate- but higher rate of alanine secretion. Thus, in cells using the standard- or the net zero ATP glycolysis pathways a significant portion of the glycolysis flux is always associated with ATP generation, and the ratio between the flux rates of the two pathways determines the rate of ATP generation and lactate and alanine secretion during glycolysis

Serine biosynthesis with one carbon catabolism represents a novel pathway for ATP generation in cells using alternative glycolysis with zero net ATP production

Recent experimental evidence indicates that some cancer cells have an alternative glycolysis pathway with net zero ATP production, implying that upregulation of glycolysis in these cells may not be related to the generation of ATP. Here we use a genome-scale model of human cell metabolism to investigate the potential metabolic alterations in cells using net zero ATP glycolysis. We uncover a novel pathway for ATP generation that involves reactions from the serine biosynthesis and one-carbon metabolism pathways. This pathway has a predicted two-fold higher flux rate in cells using net zero ATP glycolysis than those using standard glycolysis and generates twice as much ATP with significantly lower rate of lactate- but higher rate of alanine secretion. Thus, in cells using the standard- or the net zero ATP glycolysis pathways a significant portion of the glycolysis flux is always associated with ATP generation, and the ratio between the flux rates of the two pathways determines the rate of ATP generation and lactate and alanine secretion during glycolysis

The relative importance of Term Spread, Policy Inertia and Persistent Monetary Policy Shocks in Monetary Policy Rules

This paper estimates a standard version of the New Keynesian Monetary Model (NKM) augmented with the term structure in order to analyze two types of issue. First we analyse the relative importance of policy inertia, persistent policy shocks and the term spread in the estimated US monetary policy rule. Second, we study the ability of the model to reproduce some stylized facts such as high persistent dynamics and the weak comovement between economic activity and inflation observed in actual US data. The estimation procedure implemented is a classical structural method based on the indirect inference principle. The empirical results show that (i) policy intertia, persistent policy shocks and the term spread are all significant determinants in the estimated US monetary policy rule, (ii) the Fed responds to the information content of the spread about future inflation and real activity, but the Fed does not seem to respond independently to the spread; and (iii) the model augmented with term structure reproduces the weak comovement between economic activity and inflation as well as the strong comovement at medium and long-term forecast horizons between the Fed rate and the 1-yar rate observed in the US datNKM model, term structure, monetary policy rule

Randomness in Competitions

We study the effects of randomness on competitions based on an elementary random process in which there is a finite probability that a weaker team upsets a stronger team. We apply this model to sports leagues and sports tournaments, and compare the theoretical results with empirical data. Our model shows that single-elimination tournaments are efficient but unfair: the number of games is proportional to the number of teams N, but the probability that the weakest team wins decays only algebraically with N. In contrast, leagues, where every team plays every other team, are fair but inefficient: the top $\sqrt{N}$ of teams remain in contention for the championship, while the probability that the weakest team becomes champion is exponentially small. We also propose a gradual elimination schedule that consists of a preliminary round and a championship round. Initially, teams play a small number of preliminary games, and subsequently, a few teams qualify for the championship round. This algorithm is fair and efficient: the best team wins with a high probability and the number of games scales as $N^{9/5}$, whereas traditional leagues require N^3 games to fairly determine a champion.Comment: 10 pages, 8 figures, reviews arXiv:physics/0512144, arXiv:physics/0608007, arXiv:cond-mat/0607694, arXiv:physics/061221

Giant magnon bound states from strongly coupled N=4 SYM

We calculate in a very simple way the spectrum of giant magnon bound states at strong coupling in N=4 SYM, by utilizing the description of the field theory vacuum in terms of a condensate of eigenvalues of commuting matrices. We further show that these calculations can be understood in terms of the central charge extension that permits the calculation of BPS masses in the Coulomb branch of N=4 SYM. This paper shows further evidence that the strong coupling expansion of the maximally supersymmetric Yang-Mills theory in four dimensions can be done systematically from first principles, without the assumption of integrability.Comment: 19 pages, uses revte

Activities of \gamma-ray emitting isotopes in rainwater from Greater Sudbury, Canada following the Fukushima incident

We report the activity measured in rainwater samples collected in the Greater Sudbury area of eastern Canada on 3, 16, 20, and 26 April 2011. The samples were gamma-ray counted in a germanium detector and the isotopes 131I and 137Cs, produced by the fission of 235U, and 134Cs, produced by neutron capture on 133Cs, were observed at elevated levels compared to a reference sample of ice-water. These elevated activities are ascribed to the accident at the Fukushima Dai-ichi nuclear reactor complex in Japan that followed the 11 March earthquake and tsunami. The activity levels observed at no time presented health concerns.Comment: 4 pages, 8 figure

Dynamic Control of Explore/Exploit Trade-Off In Bayesian Optimization

Bayesian optimization offers the possibility of optimizing black-box operations not accessible through traditional techniques. The success of Bayesian optimization methods such as Expected Improvement (EI) are significantly affected by the degree of trade-off between exploration and exploitation. Too much exploration can lead to inefficient optimization protocols, whilst too much exploitation leaves the protocol open to strong initial biases, and a high chance of getting stuck in a local minimum. Typically, a constant margin is used to control this trade-off, which results in yet another hyper-parameter to be optimized. We propose contextual improvement as a simple, yet effective heuristic to counter this - achieving a one-shot optimization strategy. Our proposed heuristic can be swiftly calculated and improves both the speed and robustness of discovery of optimal solutions. We demonstrate its effectiveness on both synthetic and real world problems and explore the unaccounted for uncertainty in the pre-determination of search hyperparameters controlling explore-exploit trade-off.Comment: Accepted for publication in the proceedings of 2018 Computing Conferenc