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

Diffusive behavior and the modeling of characteristic times in limit order executions

We present an empirical study of the first passage time (FPT) of order book prices needed to observe a prescribed price change Delta, the time to fill (TTF) for executed limit orders and the time to cancel (TTC) for canceled ones in a double auction market. We find that the distribution of all three quantities decays asymptotically as a power law, but that of FPT has significantly fatter tails than that of TTF. Thus a simple first passage time model cannot account for the observed TTF of limit orders. We propose that the origin of this difference is the presence of cancellations. We outline a simple model, which assumes that prices are characterized by the empirically observed distribution of the first passage time and orders are canceled randomly with lifetimes that are asymptotically power law distributed with an exponent lambda_LT. In spite of the simplifying assumptions of the model, the inclusion of cancellations is enough to account for the above observations and enables one to estimate characteristics of the cancellation strategies from empirical data.Comment: 17 pages, 9 figures, 6 tables, to appear in Quantitative Financ

Can We Detect the Anisotropic Shapes of Quasar HII Regions During Reionization Through The Small-Scale Redshifted 21cm Power Spectrum?

Light travel time delays distort the apparent shapes of HII regions surrounding bright quasars during early stages of cosmic reionization. Individual HII regions may remain undetectable in forthcoming redshifted 21 cm experiments. However, the systematic deformation along the line of sight may be detectable statistically, either by stacking tomographic 21cm images of quasars identified, for example, by JWST, or as small-scale anisotropy in the three-dimensional 21cm power spectrum. Here we consider the detectability of this effect. The anisotropy is largest when HII regions are large and expand rapidly, and we find that if bright quasars contributed to the early stages of reionization, then they can produce significant anisotropy, on scales comparable to the typical sizes of HII regions of the bright quasars (approx. 30 Mpc and below). The effect therefore cannot be ignored when analyzing future 21cm power spectra on small scales. If 10 percent of the volume of the IGM at redshift z=10 is ionized by quasars with typical ionizing luminosity of S= 5 x 10^{56} photons/second, the distortions can enhance by more than 10 percent the 21cm power spectrum in the radial (redshift) direction, relative to the transverse directions. The level of this anisotropy exceeds that due to redshift-space distortion, and has the opposite sign. We show that on-going experiments such as MWA should be able to detect this effect. A detection would reveal the presence of bright quasars, and shed light on the ionizing yield and age of the ionizing sources, and the distribution and small-scale clumping of neutral intergalactic gas in their vicinity.Comment: Version accepted by ApJ, with new fiducial model and improved discussio

Quantitative assessment of cell fate decision between autophagy and apoptosis

Abstract Autophagy and apoptosis are cellular processes that regulate cell survival and death, the former by eliminating dysfunctional components in the cell, the latter by programmed cell death. Stress signals can induce either process, and it is unclear how cells ‘assess’ cellular damage and make a ‘life’ or ‘death’ decision upon activating autophagy or apoptosis. A computational model of coupled apoptosis and autophagy is built here to analyze the underlying signaling and regulatory network dynamics. The model explains the experimentally observed differential deployment of autophagy and apoptosis in response to various stress signals. Autophagic response dominates at low-to-moderate stress; whereas the response shifts from autophagy (graded activation) to apoptosis (switch-like activation) with increasing stress intensity. The model reveals that cytoplasmic Ca2+ acts as a rheostat that fine-tunes autophagic and apoptotic responses. A G-protein signaling-mediated feedback loop maintains cytoplasmic Ca2+ level, which in turn governs autophagic response through an AMP-activated protein kinase (AMPK)-mediated feedforward loop. Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ) emerges as a determinant of the competing roles of cytoplasmic Ca2+ in autophagy regulation. The study demonstrates that the proposed model can be advantageously used for interrogating cell regulation events and developing pharmacological strategies for modulating cell decisions

Constraints on the Abundance of Highly Ionized Proto-Cluster Regions from the Absence of Large Voids in the Lyman Alpha Forest

Energetic feedback processes during the formation of galaxy clusters may have heated and ionized a large fraction of the intergalactic gas in proto-cluster regions. When such a highly ionized hot ``super-bubble'' falls along the sightline to a background quasar, it would be seen as a large void, with little or no absorption, in the Lyman alpha forest. We examine the spectra of 137 quasars in the Sloan Digital Sky Survey, to search for such voids, and find no clear evidence of their existence. The size distribution of voids in the range 5-70 Angstrom (corresponding to physical sizes of approximately 3-35 comoving Mpc/h) is consistent with the standard model for the Lyman alpha forest without additional hot bubbles. We adapt a physical model for HII bubble growth during cosmological reionization (Furlanetto, Zaldarriaga and Hernquist 2004), to describe the expected size-distribution of hot super-bubbles at redshift around z = 3. This model incorporates the conjoining of bubbles around individual neighboring galaxies. Using the non-detection of voids, we find that models in which the volume filling factor of hot bubbles exceeds approximately 20 percent at z=3 can be ruled out, primarily because they overproduce the number of large (40-50 Angstrom) voids. We conclude that any pre-heating mechanism that explains galaxy cluster observations must avoid heating the low-density gas in the proto-cluster regions, either by operating relatively recently (z<3) or by depositing entropy in the high-density regions.Comment: submitted to ApJ, 9 emulateapj pages with 3 figure

Destruction of Molecular Hydrogen During Cosmological Reionization

We investigate the ability of primordial gas clouds to retain molecular hydrogen (H_2) during the initial phase of the reionization epoch. We find that before the Stromgren spheres of the individual ionizing sources overlap, the UV background below the ionization threshold is able to penetrate large clouds and suppress their H_2 abundance. The consequent lack of H_2 cooling could prevent the collapse and fragmentation of clouds with virial temperatures T_vir < 10^4 K (or masses 10^8 Msun [(1+z_vir)/10]^{-3/2}). This negative feedback on structure-formation arises from the very first ionizing sources, and precedes the feedback due to the photoionization heating.Comment: 14 pages, uuencoded compressed Postscript, 4 figures included. To appear in Ap

Topology with Dynamical Overlap Fermions

We perform dynamical QCD simulations with $n_f=2$ overlap fermions by hybrid Monte-Carlo method on $6^4$ to $8^3\times 16$ lattices. We study the problem of topological sector changing. A new method is proposed which works without topological sector changes. We use this new method to determine the topological susceptibility at various quark masses.Comment: 15 pages, 3 figure