Primer extension reactions as a tool to uncover folding motifs within complex G-rich sequences: analysis of the human KRAS NHE

We employed primer extension reactions to uncover folding motifs in a nuclease hypersensitive element (NHE) with a complex guanine pattern, located in the human KRAS promoter. We also identified and characterized a new G-rich motif of 21 nt capable of forming a parallel G-quadruplex that is disrupted by protein UP1.     

Molecular geometries of H2S···ICF3 and H2O···ICF3 characterised by broadband rotational spectroscopy

The rotational spectra of three isotopologues of H(2)S···ICF(3) and four isotopologues of H(2)O···ICF(3) are measured from 7-18 GHz by chirped-pulse Fourier transform microwave spectroscopy. The rotational constant, B(0), centrifugal distortion constants, D(J) and D(JK), and nuclear quadrupole coupling constant of (127)I, χ(aa)(I), are precisely determined for H(2)S···ICF(3) and H(2)O···ICF(3) by fitting observed transitions to the Hamiltonians appropriate to symmetric tops. The measured rotational constants allow determination of the molecular geometries. The C(2) axis of H(2)O/H(2)S intersects the C(3) axis of the CF(3)I sub-unit at the oxygen atom. The lengths of halogen bonds identified between iodine and sulphur, r(S···I), and iodine and oxygen, r(O···I), are determined to be 3.5589(2) ? and 3.0517(18) ? respectively. The angle, φ, between the local C(2) axis of the H(2)S/H(2)O sub-unit and the C(3) axis of CF(3)I is found to be 93.7(2)° in H(2)S···ICF(3) and 34.4(20)° in H(2)O···ICF(3). The observed symmetric top spectra imply nearly free internal rotation of the C(2) axis of the hydrogen sulphide/water unit about the C(3) axis of CF(3)I in each of these complexes. Additional transitions of H(2)(16)O···ICF(3), D(2)(16)O···ICF(3) and H(2)(18)O···ICF(3) can be assigned only using asymmetric top Hamiltonians, suggesting that the effective rigid-rotor fits employed do not completely represent the internal dynamics of H(2)O···ICF(3).     

Absorption and emission spectra of fluorescent silica nanoparticles from TD-DFT/MM/PCM calculations

A multi-scale computational protocol, which combines Quantum Mechanics and Molecular Mechanics (QM/MM) calculations with the polarisable continuum model (PCM), has been used to study the tetramethylrhodamine isothiocyanate (TRITC) fluorophore, embedded in three different environments, namely in water, on an amorphous silica surface and covalently encapsulated in a silica nanoparticle (C dot). Absorption and emission spectra have been simulated by using TD-B3LYP/PCM calculations, performed on the TRITC ground and excited state geometries, optimized at the QM/MM level. The results are in good agreement with experimental data confirming the caging effect played by the silica shell on the mobility of the TRITC molecule when covalently encapsulated in silica nanoparticles. This could result in a decrease of the nonradiative decay rate and thus an increase of the quantum yield of the molecule.     

Fluorescence spectra of organic dyes in solution: a time dependent multilevel approach

Classical all-atom molecular dynamics (MD) simulations and quantum mechanical (QM) time-dependent density functional theory (TD-DFT) calculations are employed to study the conformational and photophysical properties of the first emitter excited state of tetramethyl-rhodamine iso-thiocyanate fluorophore in aqueous solution. For this purpose, a specific and accurate force field has been parameterised from QM data to model the fluorophore's first bright excited state. During the MD simulations, the consequences of the π→π* electronic transition on the structure and microsolvation sphere of the dye has been analysed in some detail and compared to the ground state behaviour. Thereafter, fluorescence has been calculated at the TD-DFT level on configurations sampled from the simulated MD trajectories, allowing us to include time dependent solvent effects in the computed emission spectrum. The latter, when compared with the absorption spectrum, reproduces well the experimental Stokes shift, further validating the proposed multilevel computational procedure.     

A Dynamic Supplier Selection and Inventory Management Model for a Serial Supply Chain with a Novel Supplier Price Break Scheme and Flexible Time Periods

A new supplier price break and discount scheme taking into account order frequency and lead time is introduced and incorporated into an integrated inventory planning model for a serial supply chain that minimizes the overall incurred cost including procurement, inventory holding, production, and transportation. A mixed-integer linear programming (MILP) formulation is presented addressing this multi-period, multi-supplier, and multi-stage problem with predetermined time-varying demand for the case of a single product. Then, the length of the time period is considered as a variable. A new MILP formulation is derived when each period of the model is split into multiple sub-periods, and under certain conditions, it is proved that the optimal solution and objective value of the original model form a feasible solution and an upper bound for the derived model. In a numerical example, three scenarios of the derived model are solved where the number of sub-period is set to 2, 3, and 4. The results further show the decrease of the optimal objective value as the length of the time period is shortened. Sufficient evidence demonstrates that the length of the time period has a significant influence on supplier selection, lot sizing allocation, and inventory planning decisions. This poses the necessity of the selection of appropriate length of a time period, considering the trade-off between model complexity and cost savings.     

Log‐symmetric regression models: information criteria and application to movie business and industry data with economic implications

This work deals with log‐symmetric regression models, which are particularly useful when the response variable is continuous, strictly positive, and following an asymmetric distribution, with the possibility of modeling atypical observations by means of robust estimation. In these regression models, the distribution of the random errors is a member of the log‐symmetric family, which is composed by the log‐contaminated‐normal, log‐hyperbolic, log‐normal, log‐power‐exponential, log‐slash and log‐Student‐t distributions, among others. One way to select the best family member in log‐symmetric regression models is using information criteria. In this paper, we formulate log‐symmetric regression models and conduct a Monte Carlo simulation study to investigate the accuracy of popular information criteria, as Akaike, Bayesian, and Hannan‐Quinn, and their respective corrected versions to choose adequate log‐symmetric regressions models. As a business application, a movie data set assembled by authors is analyzed to compare and obtain the best possible log‐symmetric regression model for box offices. The results provide relevant information for model selection criteria in log‐symmetric regressions and for the movie industry. Economic implications of our study are discussed after the numerical illustrations.     

A cryogenic underground observatory for rare events: CUORE, an update

CUORE is a proposed tightly packed array of 1000 TeO₂ bolometers, each being a cube 5 cm on a side with a mass of 750 g. The array consists of 25 vertical towers, arranged in a square of 5 towers by 5 towers, each containing ten layers of four crystals. The design of the detector is optimized for ultralow-background searches for neutrinoless double beta decay of ¹³⁰Te (33.8% abundance), cold dark matter, solar axions, and rare nuclear decays. A preliminary experiment involving 20 crystals of various sizes (MIBETA) has been completed, and a single CUORE tower is being constructed as a smaller scale experiment called CUORICINO. The expected performance and sensitivity, based on Monte Carlo simulations and extrapolations of present results, are reported.