Kinetics of the template-directed oligomerization of guanosine 5'-phosphate-2-methylimidazolide: Effect of temperature on individual steps of reactionion

Non-enzymatic, template-directed reactions have been proposed as models for prebiological polynucleotide synthesis. Chemically activated mononucleotides react in the presence of a polynucleotide, acting as the template in a Watson-Crick base-pairing fashing, and form the complementary daughter polynucleotide. Phosphoimidazolide-activated nucleotides have been used successfully as substrates in these reactions. The kinetics of the guanosine 5'-monophosphate-2-methylimidazolide (2-MelmpG) reaction in aqueous pH 8.0 solutions in the presence and in the absence of polycytidylate (poly(C)) were studied, acting as the template at 6, 23, and 37 C. In the absence of the template, the major reaction pathway of 2-MelmpG is hydrolysis of the P-N bond to form the unreactive guanosine 5'-monophosphate (5'-GMP) and 2-methylimidazole. Concentrated solution of 2-MelmpG (greater than 0.02 M) in the absence of the template form only a small amount dinucleotide, (pG)2, but in the presence of poly(C), oligoguanylates, (pG)n with 2 less than or = n less than or = 40, can be detected. We were able to determine the rate constants for individual steps of this reaction. A summary of the conclusions is presented

Homogenization and Scattering Analysis of Second-Harmonic Generation in Nonlinear Metasurfaces

We propose an extensive discussion on the homogenization and scattering analysis of second-order nonlinear metasurfaces. Our developments are based on the generalized sheet transition conditions (GSTCs) which are used to model the electromagnetic responses of nonlinear metasurfaces. The GSTCs are solved both in the frequency domain, assuming an undepleted pump regime, and in the time-domain, assuming dispersionless material properties but a possible depleted pump regime. Based on these two modeling approaches, we derive the general second-harmonic reflectionless and transmissionless conditions as well as the conditions of asymmetric reflection and transmission. We also discuss and clarify the concept of nonreciprocal scattering pertaining to nonlinear metasurfaces

Photoelasticity of sodium silicate glass from first principles

Based on density-functional perturbation theory we have computed the photoelastic tensor of a model of sodium silicate glass of composition (Na$_2$O)$_{0.25}$(SiO$_2$)$_{0.75}$ (NS3). The model (containig 84 atoms) is obtained by quenching from the melt in combined classical and Car-Parrinello molecular dynamics simulations. The calculated photoelastic coefficients are in good agreement with experimental data. In particular, the calculation reproduces quantitatively the decrease of the photoelastic response induced by the insertion of Na, as measured experimentally. The extension to NS3 of a phenomenological model developed in a previous work for pure a-SiO$_2$ indicates that the modulation upon strain of other structural parameters besides the SiOSi angles must be invoked to explain the change in the photoelstic response induced by Na

A 475 years-old founder effect involving IL12RB1: a highly prevalent mutation conferring Mendelian susceptibility to mycobacterial diseases in European descendants

Mutations in IFNGR1, IFNGR2, IL12RB1, IL12B, STAT1 and NEMO result in a common clinical phenotype known as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Interleukin-12 receptor 01 (IL12R beta 1) deficiency is the most common genetic etiology for MSMD. Known mutations affecting IL12RB1 are recessively inherited and are associated with null response to both IL-12 and IL-23. Mutation IL12RB1 1623_1624delinsTT was originally described in 5 families from European origin (2 from Germany: I from Cyprus, France and Belgium). Interestingly, this same mutation was found in an unexpectedly high prevalence among IL-12R beta 1 deficient patients in Argentina: 5-out-of-6 individuals born to unrelated families carried this particular change. To determine whether mutation 1623_1624delinsTT represents a DNA mutational hotspot or a founder effect, 34 polymorphic markers internal or proximal to IL12RB1 were studied in the Argentinean and the Belgian patients. A common haplotype spanning 1.45-3.51 Mb was shared by all chromosomes carrying mutation 1623_1624delinsTT, and was not detected on 100 control chromosomes. Applying a modified likelihood-based method the age of the most recent common ancestor carrying mutation 1623_1624delinsTT was estimated in 475 years (95% CI, 175-1275), which is the time when the Spaniards initiated the colonization of the Americas. Mutation 1623_1624delinsTT represents the first founder effect described on IL-12R beta 1, the most frequently affected gene in MSMD, and affecting patients with European ancestors. The reason(s) behind the persistency of this mutation across multiple generations, its relative high prevalence, and any potential selective advantage are yet to be established

Product and rate determinations with chemically activated nucleotides in the presence of various prebiotic materials, including other mono- and polynucleotides

We are investigating the reactions of ImpN's in the presence of a number of prebiotically plausible materials, such as metal ions, phosphate, amines and other nucleotides and hope to learn more about the stability/reactivity of ImpN's in a prebiotic aqueous environment. We find that, in the presence of phosphate, ImpN's form substantial amounts of diphosphate nucleotides. These diphosphate nucleotides are not very good substrates for template directed reactions, but are chemically activated and are known to revert to the phosphoimidazolides in the presence of imidazole under solid state conditions. With respect to our studies of the oligomerization reaction, the determination of the dimerization rate constant of a specific ImpN (guanosine 5'-phospho 2 methylimidazolide) both in the absence and the presence of the template leads to the conclusion that at 37 C the dimerization is not template directed, although the subsequent polymerization steps are. In other words, this specific polynucleotide synthesizing system favors the elongation of oligonucleotides as compared with the formation of dimers and trimers. This favoring of the synthesis of long as opposed to short oligonucleotides may be regarded as a rudimentary example of natural selection at the molecular level

A Rapid Dynamical Monte Carlo Algorithm for Glassy Systems

In this paper we present a dynamical Monte Carlo algorithm which is applicable to systems satisfying a clustering condition: during the dynamical evolution the system is mostly trapped in deep local minima (as happens in glasses, pinning problems etc.). We compare the algorithm to the usual Monte Carlo algorithm, using as an example the Bernasconi model. In this model, a straightforward implementation of the algorithm gives an improvement of several orders of magnitude in computational speed with respect to a recent, already very efficient, implementation of the algorithm of Bortz, Kalos and Lebowitz.Comment: RevTex 7 pages + 4 figures (uuencoded) appended; LPS preprin