Spectral modulation detection as a function of modulation frequency, carrier bandwidth, and carrier frequency region

The present study investigates the nature of spectral envelope perception using a spectral modulation detection task in which sinusoidal spectral modulation is superimposed upon a noise carrier. The principal goal of this study is to characterize spectral envelope perception in terms of the influence of modulation frequency (cycles/octave), carrier bandwidth (octaves), and carrier frequency region (defined by lower and upper cutoff frequencies in Hz). Spectral modulation detection thresholds measured as a function of spectral modulation frequency result in a spectral modulation transfer function (SMTF). The general form of the SMTF is bandpass in nature, with a minimum modulation detection threshold in the region between 2 to 4 cycles/octave. SMTFs are not strongly dependent on carrier bandwidth (ranging from 1 to 6 octaves) or carrier frequency region (ranging from 200 to 12 800 Hz), with the exception of carrier bands restricted to very low audio frequencies (e.g., 200-400 Hz). Spectral modulation detection thresholds do not depend on the presence of random level variations or random modulation phase across intervals. The SMTFs reported here and associated excitation pattern computations are considered in terms of a linear systems approach to spectral envelope perception and potential underlying mechanisms for the perception of spectral features.     

Alkali‐Metal‐Mediated Magnesiations of an N‐Heterocyclic Carbene: Normal,Abnormal, and “Paranormal” Reactivity in a Single Tritopic Molecule

Herein the sodium alkylmagnesium amide [Na₄Mg₂(TMP)₆(nBu)₂] (TMP=2,2,6,6‐tetramethylpiperidide), a template base as its deprotonating action is dictated primarily by its 12 atom ring structure, is studied with the common N‐heterocyclic carbene (NHC) IPr [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene]. Remarkably, magnesiation of IPr occurs at the para‐position of an aryl substituent, sodiation occurs at the abnormal C4 position, and a dative bond occurs between normal C2 and sodium, all within a 20 atom ring structure accommodating two IPr²⁻. Studies with different K/Mg and Na/Mg bimetallic bases led to two other magnesiated NHC structures containing two or three IPr⁻ monoanions bound to Mg through abnormal C4 sites. Synergistic in that magnesiation can only work through alkali‐metal mediation, these reactions add magnesium to the small cartel of metals capable of directly metalating a NHC.     

Dielectrophoretic immobilization of proteins: Quantification by atomic force microscopy

The combination of alternating electric fields with nanometer‐sized electrodes allows the permanent immobilization of proteins by dielectrophoretic force. Here, atomic force microscopy is introduced as a quantification method, and results are compared with fluorescence microscopy. Experimental parameters, for example the applied voltage and duration of field application, are varied systematically, and the influence on the amount of immobilized proteins is investigated. A linear correlation to the duration of field application was found by atomic force microscopy, and both microscopical methods yield a square dependence of the amount of immobilized proteins on the applied voltage. While fluorescence microscopy allows real‐time imaging, atomic force microscopy reveals immobilized proteins obscured in fluorescence images due to low S/N. Furthermore, the higher spatial resolution of the atomic force microscope enables the visualization of the protein distribution on single nanoelectrodes. The electric field distribution is calculated and compared to experimental results with very good agreement to atomic force microscopy measurements.     

Chemometric strategy for untargeted lipidomics: Biomarker detection and identification in stressed human placental cells

A lipidomic study was developed in a human placental choriocarcinoma cell line (JEG-3) exposed to tributyltin (TBT) and to a mixture of perfluorinated chemicals (PFCs). The method was based on the application of multivariate curve resolution-alternating least squares (MCR-ALS) to data sets obtained by ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC–TOF-MS) using an untargeted approach. Lipids from exposed JEG-3 cells were solid–liquid extracted and analyzed by UHPLC–TOF-MS in full scan mode, together with control samples. Raw UHPLC–TOF-MS data of the different cell samples were subdivided into 20 distinct chromatographic windows and each window was further organized in a column-wise augmented data matrix, where data from every sample was in an individual data matrix. Then, the 20 new augmented data matrices were modeled by MCR-ALS. A total number of 86 components were resolved and a statistical comparative study of their elution profiles showed distinct responses for the lipids of exposed versus control cells, evidencing a lipidome disruption attributed to the presence of the xenobiotics. Results from one-way ANOVA followed by a multiple comparisons test and from discriminant partial least squares (PLS-DA) analysis were compared as usual strategies for the determination of potential biomarkers. Identification of 24 out of the 33 proposed biomarkers contributed to the better understanding of the effects of PFCs and TBT in the lipidome of human placental cells. Overall, this study proposes an innovative untargeted LC–MS MCR-ALS approach valid for -omic sciences such as lipidomics.     

A Minimal β‐Lactone Fragment for Selective β5c or β5i Proteasome Inhibitors

Broad‐spectrum proteasome inhibitors are applied as anticancer drugs, whereas selective blockage of the immunoproteasome represents a promising therapeutic rationale for autoimmune diseases. We here aimed at identifying minimal structural elements that confer β5c or β5i selectivity on proteasome inhibitors. Based on the natural product belactosin C, we synthesized two β‐lactones featuring a dimethoxybenzyl moiety and either a methylpropyl (pseudo‐isoleucin) or an isopropyl (pseudo‐valine) P1 side chain. Although the two compounds differ only by one methyl group, the isoleucine analogue is six times more potent for β5i (IC₅₀=14 nM ) than the valine counterpart. Cell culture experiments demonstrate the cell‐permeability of the compounds and X‐ray crystallography data highlight them as minimal fragments that occupy primed and non‐primed pockets of the active sites of the proteasome. Together, these results qualify β‐lactones as a promising lead‐structure motif for potent nonpeptidic proteasome inhibitors with diverse pharmaceutical applications.     

Neighborhood radius estimation for variable-neighborhood random fields

We consider random fields defined by finite-region conditional probabilities depending on a neighborhood of the region which changes with the boundary conditions. To predict the symbols within any finite region, it is necessary to inspect a random number of neighborhood symbols which might change according to the value of them. In analogy with the one-dimensional setting we call these neighborhood symbols the context associated to the region at hand. This framework is a natural extension, to d-dimensional fields, of the notion of variable length Markov chains introduced by Rissanen [24] in his classical paper. We define an algorithm to estimate the radius of the smallest ball containing the context based on a realization of the field. We prove the consistency of this estimator. Our proofs are constructive and yield explicit upper bounds for the probability of wrong estimation of the radius of the context.     

Atomistic details of precipitates in lean Al–Mg–Si alloys with trace additions of Ag and Ge studied by HAADF-STEM and DFT

Abstract

Bonding energies and volume misfits for alloying elements and vacancies in multicomponent Al–Mg–Si alloys have been calculated using density functional theory (DFT). A detailed atomic scale analysis has been done for characteristic precipitate structures, using high-angle annular dark-field scanning transmission electron microscopy. Two new stacking configurations of the important strengthening phase β′′ were discovered in the Ge-added alloy. All three stacking variations were found to be energetically favourable to form from DFT calculations. The second stacking configuration, β₂′′, contains vacated columns in its unit cell, consequently requiring less solute to create the same volume fraction of precipitate needles. DFT suggests a lower formation enthalpy per atom for β₂′′ when Si is exchanged with Ge. In the alloy containing Ag additions, a new Q’/C-like local configuration containing Ag instead of Cu was discovered, also this phase was deemed energetically favourable from DFT.