Hybrid modeling and simulation of stochastic effects on progression through the eukaryotic cell cycle

The eukaryotic cell cycle is regulated by a complicated chemical reaction network. Although many deterministic models have been proposed, stochastic models are desired to capture noise in the cell resulting from low numbers of critical species. However, converting a deterministic model into one that accurately captures stochastic effects can result in a complex model that is hard to build and expensive to simulate. In this paper, we first apply a hybrid (mixed deterministic and stochastic) simulation method to such a stochastic model. With proper partitioning of reactions between deterministic and stochastic simulation methods, the hybrid method generates the same primary characteristics and the same level of noise as Gillespie's stochastic simulation algorithm, but with better efficiency. By studying the results generated by various partitionings of reactions, we developed a new strategy for hybrid stochastic modeling of the cell cycle. The new approach is not limited to using mass-action rate laws. Numerical experiments demonstrate that our approach is consistent with characteristics of noisy cell cycle progression, and yields cell cycle statistics in accord with experimental observations.     

The origin of nanopores

Summary The survey covers the methods of producing pores of nanometer width. Features of such nanomaterials differ remarkably from both that of nanoparticles and that of materials with pores in the micrometer range.     

The origin of life

The theory of the evolution of the species, which is today widely accepted, requires a starting point. It is postulated that the biological starting point could have emerged only if chemical evolution had preceded it. Experiments are described which show the formation of organic substances from inorganic gases under conditions which prevailed on earth in the prebiotic era; also demonstrated is the polymerization of such organic substances into biological macromolecules. Hypotheses are discussed whereby these macromolecules could be transformed into dynamic structures which might finally lead to self-reproduction.     

Studies on the origin of the voltammetric response of the PC-3 cell suspension

A novel experimental method was developed to study the origin of the voltammetric response of human prostate cancer (PC-3) cell suspension as a model in consideration of the biological characters of living cells. The presence of guanine and xanthine in the cell eluent secreted by the living cells was verified by HPLC assay with a DAD system and chemometric method. Comparative studies of voltammetric behaviors of the PC-3 cell suspension, the PC-3 cell eluent, and the PC-3 cell sediment re-suspension showed that the voltammetric response of the PC-3 cells was given by xanthine and guanine bases in the PC-3 cell eluent, not by the cells. Linear relationship between the peak currents of guanine and xanthine in the cell eluent and the cell concentrations was found. Other factors, such as the cell secretion time and the immersion time of the multiwalled carbon nanotubes modified glassy carbon electrode (MWCNTs-modified GCE) in the cell eluent, also influenced the intensity of the peak currents. The biochemical mechanisms of the voltammetric behavior for the cell suspension were proposed.     

The origin of the dynamic transition in proteins

Despite extensive efforts in experimental and computational studies, the microscopic understanding of dynamics of biological macromolecules remains a great challenge. It is known that hydrated proteins, DNA and RNA, exhibit a so-called "dynamic transition." It appears as a sharp rise of their mean-squared atomic displacements r2 at temperatures above 200-230 K. Even after a long history of studies, this sudden activation of biomolecular dynamics remains a puzzle and many contradicting models have been proposed. By combining neutron and dielectric spectroscopy data, we were able to follow protein dynamics over an extremely broad frequency range. Our results show that there is no sudden change in the dynamics of the protein at temperatures around approximately 200-230 K. The protein's relaxation time exhibits a smooth temperature variation over the temperature range of 180-300 K. Thus the experimentally observed sharp rise in r2 is just a result of the protein's structural relaxation reaching the limit of the experimental frequency window. The microscopic mechanism of the protein's structural relaxation remains unclear.     

The origin and development of the acidity function

The acidity function is a thermodynamic quantitative measure of acid strength for non-aqueous and concentrated aqueous Brønsted acids, with acid strength being defined as the extent to which the acid protonates a base of known basicity. The acidity function, which was developed, both theoretically and experimentally, by Louis P. Hammett of Columbia University during the 1930s, has proven useful in the area of physical organic chemistry where it has been used to correlate rates of acid-catalyzed reactions and to quantitate the acidity of superacids, acids with protonating abilities greater than pure sulfuric acid. All Brønsted acids can now be compared using a common measure. Karl Popper’s seminal idea of theory falsification does not apply here because of the many successful applications of the acidity function. Likewise, Thomas Kuhn’s idea of a paradigm shift does not apply here, even though the acidity function concept was revolutionary, because the acidity function is commensurate with classical concepts of acidity.     

The origin of the electrode effect in various electrolytes

The problem of the origin of electrode effects in various electrolytes is studied on the ground of Fourier's equation. Thus the electrolysis time elapsed before the occurrence of an electrode effect is shown to be equal to the calculated time which is the time necessary to bring the temperature of the electrolyte surrounding the electrode up to its boiling point. Then we can conclude in all cases investigated that the electrode effects are induced by a Joule effect heating of the electrolyte.     

The rheological similarity of the physical networks of different origin

It has been established that the Newtonian viscosity of solutions of styrene-acrylic acid (4 mol%) copolymers inionomeric form (0–50 mol%) in DMPh is proportional to exp n (n being the degree of neutralization). The principle of temperature-time-concentration superposition is applicable for the dependence of shear modulus on temperature (20–100°), frequency (10^?3–1.5 Hz), decree of neutralization (0–50 mol%) and concentration (15–45 g/dl). These facts can be explained in terms of the rheological similarity of physical networks connected with macromolecular chain entanglements and with salt group interactions. Some details of the model for concentrated polymer solutions are discussed.     

The biosynthesis of broussonetines: origin of the carbon skeleton

Broussonetines are glycosidase-inhibitory alkaloids obtained from Broussonetia kazinoki. Feeding experiments using [1-13C]glucose and 13C-NMR spectroscopic studies showed that broussonetines are biosynthesized through routes similar to those of sphingosine and phytosphingosine.     

The origin of the formation of cavities in galvanized coatings

The role of water‐soluble corrosion products on galvanized wires was examined. The samples used were industrial hot‐dip galvanized wires, which were exposed to the open air under all weather conditions for a relatively short time (6 and 12 months), in an urban environment close to the sea. The samples were studied by different methods, i.e. scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD) and optical microscopy (OM). Several phases were detected because of the galvanization procedure and the steel substrate. Furthermore, phases which were formed as a result of the reaction of zinc with the atmosphere were also detected. These were oxides like ZnO, carbonates like ZnCO₃ and hydrated Zn and Fe sulfates. Their presence influences the corrosion resistance of the wires, which finally, strongly depends on the solubility of the wires in water. The SO₄^2? compounds especially are very soluble and consequently are easily removed from the coating surface, leading to its degradation by the formation of cavities. In any case, their presence, even after a short period of exposure, implies that the coating is highly affected by the atmosphere of the modern city. Copyright © 2006 John Wiley & Sons, Ltd.     

The origin of thermodynamic stability of microemulsions

The adsorption of surfactant and cosurfactant on the surface of the globules decreases the interfacial tension between oil and water to very low values. In addition, the decrease of the bulk concentrations of the surfactant and cosurfactant decreases their chemical potential both in the bulk and at the interface, thus decreasing the free energy of the system (dilution effect). The thermodynamic stability of microemulsions is due to the fact that the total free energy change caused by these effects can become negative. The theory can explain the occurence of stable microemulsions for both non-ionic and ionic surfactants.     

The origin and nature of the π-electron steric effect

The existence of conformational or steric proximity substituent effects involving π-electrons has been demonstrated in a number of recent reports but the question of whether this effect is due simply to the size of the substituent or to lone pair electrons on the substituent has not been investigated. Relative to this question, pK_a's for an extensive series of 2'- and 4'-substituted-4-aminobiphenyls and for a series of 4'-substituted-2-amino-biphenyls have been determined. The results of this study demonstrate that a π-electron steric effect is operative in the 2'-substituted-4-aminobiphenyls and that it occurs primarily (when possible) via lone pair electron-π electron interactions and not simply via a steric size effect. The pK_a data for the 4'-substituted-2-aminobiphenyls reinforce this conclusion and further demonstrate that 2,4'-resonance is possible in appropriately substituted 2,4'-disubstituted biphenyls. In addition, the relativity of the concept of substituent size and of electron withdrawing or donating character of various groups is illustrated.     

The origin of dips for the graphene-based DNA sequencing device

We recently proposed an ultrafast DNA sequencing method that electrically distinguishes different nucleobases on a graphene nanoribbon (GNR), utilizing π-π interaction. Analyzing the molecular orbitals (MOs) and the features of dips in conductance for our GNR-based sequencing device, we prove that the Fano resonance is responsible for the characteristic dips of each nucleobase.     

The biosynthetic origin of fusicoccin hydroxyisopropyl group

The biosynthetic origin of the hydroxyisopropyl group of fusicoccin 1 has been determined. Two out of the eight tritium mevalonoid atoms retained in 1 following incorporation of MVA-[2-³H₂,2-¹⁴C] have been located at C-20; whilst none has been found in the C-19 methylene group.     

The origin of fluorescence from trans-trans diphenylbutadiene

Fluorescence decay time and yield of trans-trans diphenylbutadiene in methylcyclohexane/isohexane and propylene glycol were measured between ?50 and +50°C. The radiative rate parameter is independent of solvent and temperature, with a mean value of 8.2 × 10⁸ s^?1. This is similar to trans-stilbene but unlike longer polyenes, and is consistent with emission from ¹B^*_u rather than the low-lying ¹Ag^*_g state.