Ab initio study of the alternating current impedance of a molecular junction

The small-bias conductance of the C6 molecule, stretched between two metallic leads, is studied using time-dependent density functional theory within the adiabatic local density approximation. The leads are modeled by jellium slabs, the electronic density and the current density are described on a grid, whereas the core electrons and the highly oscillating valence orbitals are approximated using standard norm-conserving pseudopotentials. The jellium leads are supplemented by a complex absorbing potential that serves to absorb charge reaching the edge of the electrodes and hence mimic irreversible flow into the macroscopic metal. The system is rapidly exposed to a ramp potential directed along the C6 axis, which gives rise to the onset of charge and current oscillations. As time progresses, a fast redistribution of the molecular charge is observed, which translates into a direct current response. Accompanying the dc signal, alternating current fluctuations of charge and currents within the molecule and the metallic leads are observed. These form the complex impedance of the molecule and are especially strong at the plasmon frequency of the leads and the lowest excitation peak of C6. We study the molecular conductance in two limits: the strong coupling limit, where the edge atoms of the chain are submerged in the jellium and the weak coupling case, where the carbon atoms and the leads do not overlap spatially.     

Disrupting the MAD2L2-Rev1 Complex Enhances Cell Death upon DNA Damage

DNA-damaging chemotherapy agents such as cisplatin have been the first line of treatment for cancer for decades. While chemotherapy can be very effective, its long-term success is often reduced by intrinsic and acquired drug resistance, accompanied by chemotherapy-resistant secondary malignancies. Although the mechanisms causing drug resistance are quite distinct, they are directly connected to mutagenic translesion synthesis (TLS). The TLS pathway promotes DNA damage tolerance by supporting both replication opposite to a lesion and inaccurate single-strand gap filling. Interestingly, inhibiting TLS reduces both cisplatin resistance and secondary tumor formation. Therefore, TLS targeting is a promising strategy for improving chemotherapy. MAD2L2 (i.e., Rev7) is a central protein in TLS. It is an essential component of the TLS polymerase zeta (ζ), and it forms a regulatory complex with Rev1 polymerase. Here we present the discovery of two small molecules, c#2 and c#3, that directly bind both in vitro and in vivo to MAD2L2 and influence its activity. Both molecules sensitize lung cancer cell lines to cisplatin, disrupt the formation of the MAD2L2-Rev1 complex and increase DNA damage, hence underlining their potential as lead compounds for developing novel TLS inhibitors for improving chemotherapy treatments.     

Aspidosperma Alkaloids. A New Didehydrodimerization Mode of β-Anilinoacrylic Alkaloids by Anodic Oxidation

A regio- and stereoselective didehydrodimerization procedure, whose key step involves the anodic oxidation, allows the conversion of β-anilinoacrylic alkaloids belonging to the Aspidosperma class, typified by tabersonine ( 1 ) and its 3-oxo derivative 2 , into the hitherto unknown 16,10′-didehydro dimers 3 and 7 , respectively.     

Leptogenesis from supersymmetry breaking

We show that soft supersymmetry breaking terms involving the heavy sneutrinos can lead to sneutrino-antisneutrino mixing and to new sources of CP violation, which are present even if a single generation is considered. These terms are naturally present in supersymmetric versions of leptogenesis scenarios, and they induce indirect CP violation in the decays of the heavy sneutrinos, eventually generating a baryon asymmetry. This new contribution can be comparable to or even dominate over the asymmetry produced in traditional leptogenesis scenarios.     

Comparison of biased and unbiased estimators of variances of qualitative and semi-quantitative results of testing

Unbiased estimators of within-laboratory and between-laboratory (or within reference material unit and between-unit) variances of results of qualitative and semi-quantitative testing are formulated and discussed. Qualitative and semi-quantitative test results were treated as binary nominal and ordinal values, respectively, in framework of the newly developed ordinal analysis of variance (ORDANOVA). It is shown that the difference of the unbiased and the biased estimators of a within-laboratory variance does not exceed 5 %, when the number of replicate tests in a laboratory is larger than 20. Such a difference is increasing when the replicate number is decreasing, not depending on the number of laboratories and the between-laboratory variation, since both the unbiased and the biased estimators are based on the averaged within-laboratory variances. The difference of the unbiased and the biased estimators of the between-laboratory variance depends not only on the number of replicates, but also on the number of laboratories and on the ratio of the contributions to the total variance (the between-laboratory variance and the averaged within-laboratory variance). This difference does not exceed 5 %, when the number of replicates and the number of laboratories are larger than 20 and the ratio of the between-laboratory to the averaged within-laboratory variances does not yield 1. For a limited size of experiment (smaller numbers of replicates and laboratories), the difference is increasing with the size decreasing and can be significant.     

Pressure measuring techniques in I.C.E.

Summary A revue of the possible errors affecting pressure measurements in internal combustion engines is presented. A new instrument based on the principle of the Balanced Pressure Indicator and signal multiplexing was developped. Its characteristics used both to obtain an accurate mean pressure diagram and to calibrate pressure transducers in working engines. The overall ability of obtaining meaningful pressure data was shown, even if it is clear that pressure measurements are more an art than a mere technique, given the complexity of the problems involved.

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Sommario L'articolo presenta un'analisi dei possibili errori che possono distorcere la misurazione delle pressioni nella camera di combustione dei motori a combustione interna. Un nuovo strumento, basato sul principio dell'indicatore di pressione a bilanciamento di pressioni e del multiplex a modi di impulsi, è qui anche presentato ed utilizzato sia per ottenere un diagramma medio di pressioni di notevole accuratezza, che per calibrare trasduttori di pressione in condizioni di lavoro, cioè mentre il motore è in funzione. Ne risulta che è possibile ottenere diagrammi di pressione veramente rappresentativi delle condizioni di lavoro del motore, anche se è chiaro che, data la complessità dei problemi relativi a detta misurazione, misurare la pressione nei motori è più un'arte che pura tecnica.

     

The Sequential Occupancy Problem through Group Throwing of Indistinguishable Balls

The occupancy problem is generalized to the case where instead of throwing one ball at a time, a fixed size group of indistinguishable balls are distributed sequentially into cells. Bose-Einstein statistics is used for analyzing the distribution of the waiting time until each cell is occupied by at least one ball. Each trial is classified according to its jump size, i.e. the number of newly occupied cells. We propose an approach to decompose the occupancy and filling processes in terms of the jumps sizes using a multi-dimensional representation. A set of recursive equations is built in order to obtain the joint generating probability function of a series of random variables, each of which denotes the number of trials for a given jump size that occurred during the filling process. As a special case, the joint probability function of these random variables is obtained.     

Structural elucidation of amino amide‐type local anesthetic drugs and their main metabolites in urine by LC‐MS after derivatization and its application for differentiation between positional isomers of prilocaine

The demand for clinical toxicology analytical methods for identifying drugs of abuse and medicinal drugs is steadily increasing. Structural elucidation of amino amide‐type local anesthetic drugs and their main metabolites by GC‐EI‐MS and LC‐ESI‐MS/MS is of great analytical challenge. These compounds exhibit only/mostly fragments/product ions representing the amine‐containing residue, while the aromatic amide moiety remains unidentified. This task becomes even more complicated when discrimination between positional isomers of such compounds is required. Here, we report the development of a derivatization procedure for the differentiation and structural elucidation of a mixture of local anesthetic drugs and their metabolites that possess tertiary and secondary amines in water and urine. A method based on two sequential “in‐vial” instantaneous derivatization processes at ambient temperature followed by LC‐ESI‐MS/MS analysis was developed. 2,2,2‐Trichloro‐1,1‐dimethylethyl chloroformate (TCDMECF) was utilized to selectively convert the secondary amines into their carbamate derivatives, followed by hydrogen peroxide addition to produce the corresponding tertiary amine oxides. The resulting derivatives exhibited rich fragmentation patterns, enabling improved structural elucidation of the original compounds. The developed method was successfully applied to the differentiation and structural elucidation of prilocaine and its four positional isomers, which all possess similar GC and LC retention times and four of them exhibit almost identical EI‐MS and ESI‐MS/MS spectra, enabling their structural elucidation in a single LC‐ESI‐MS/MS analysis. The developed technique is fast and simple and enables discrimination between isomers based on different diagnostic ions/fragmentation patterns.     

Nanostructure changes in protic ionic liquids (PILs) through adding solutes and mixing PILs

The effect of adding primary n-alcohols with aliphatic chains and hexane on the nanostructure of a series of 14 protic ionic liquids (PILs) was explored using small and wide angle X-ray scattering (SAXS and WAXS). PILs were investigated with primary, secondary and tertiary ammonium cations containing different alkyl chain lengths, with and without hydroxyl substitution of the alkyl chain. Formate or nitrate anions were paired with these cations. The PILs which had no identified intermediate range order between 5-16 ? had very low solubilities of the solutes. The other PILs, which had non-polar domains present, were mostly miscible with the primary alcohols of ethanol, propanol and butanol. When the alkyl chain length of the alcohols was similar to the PILs then the alcohols co-partitioned with the alkylammonium cation components of the PILs and caused either an increase or decrease in the size of the non-polar domains, depending on whether the alcohol chain length was longer or shorter than that of the cation in the PIL respectively. For ethylammonium nitrate (EAN) with propanol or butanol and propylammonium nitrate (PAN) with butanol, the difference between the alcohol chain length and the alkyl chain length was too great to lead to a modified nanostructure, and instead large aggregates were present. The solubility of hexane in the alkylammonium nitrate PILs had a very strong correlation to the alkyl chain length. The addition of hexane had very little effect on the non-polar domain sizes, which was attributed to it not being orientated in alignment with the alkylammonium cations in the non-polar domains. Lastly, seven binary PIL-PIL solution series were investigated using SAXS and WAXS to show how the nanostructure of these systems can be fine tuned to control the size and structure of the non-polar domains.     

Magnetization dynamics in arrays of strongly interacting magnetic nanocrystals

Arrays of 6.6 nm iron oxide nanocrystals coated with fatty acid molecules were produced using the Langmuir-Blodgett technique. The arrays had a varying number of layers stacked together, going from two dimensional to three dimensional and two different in-plane interparticle separations. While temperature-dependent ac susceptibility measurements of the isolated nanocrystals obeyed the Neel-Brown relaxation law, the array relaxation deviated significantly from this simple law. This deviation together with the observed dc field influence on the susceptibility-temperature curves, the large shifts in blocking temperatures and reduction in susceptibility-temperature curve widths on going from isolated particles to the arrays indicated collective magnetization dynamics during magnetization freezing. A scaling law analysis of this freezing dynamics yielded different powers for the two different interparticle separations with no dependence on dimensionality. In spite of the spin-glass-like behavior, it is possible that small, magnetically ordered domains of nanocrystals form at low temperature.