Compact dielectric particles as a building block for low-loss magnetic metamaterials

We characterize experimentally a compact dielectric particle that can be used to design very low-loss artificial electromagnetic materials (metamaterials). Focusing on magnetic media, we show that the particle can behave almost identically to the well-known split-ring resonators (SRRs) widely used in present designs, without suffering from the Ohmic losses that can limit the applicability of SRRs especially at high frequencies. We experimentally compare qualitatively and quantitatively the dielectric particle with a typical split-ring resonator of the same size built on a low-loss dielectric substrate and show that at GHz frequencies the quality factor of the dielectric particle is more than 3 times bigger than that of its metallic counterpart. Low-loss and simple geometry are significant advantages compared to conventional metal SRRs.     

Real-time animal functional magnetic resonance imaging and its application to neuropharmacological studies

In pharmacological magnetic resonance imaging (phMRI) with anesthetized animals, there is usually only a single time window to observe the dynamic signal change to an acute drug administration since subsequent drug injections are likely to result in altered response properties (e.g., tolerance). Unlike the block-design experiments in which fMRI signal can be elicited with multiple repetitions of a task, these single-event experiments require stable baseline in order to reliably identify drug-induced signal changes. Such factors as subject motion, scanner instability and/or alterations in physiological conditions of the anesthetized animal could confound the baseline signal. The unique feature of such functional MRI (fMRI) studies necessitates a technique that is able to monitor MRI signal in a real-time fashion and to interactively control certain experimental procedures. In the present study, an approach for real-time MRI on a Bruker scanner is presented. The custom software runs on the console computer in parallel with the scanner imaging software, and no additional hardware is required. The utility of this technique is demonstrated in manganese-enhanced MRI (MEMRI) with acute cocaine challenge, in which temporary disruption of the blood-brain barrier (BBB) is a critical step for MEMRI experiments. With the aid of real-time MRI, we were able to assess the outcome of BBB disruption following bolus injection of hyperosmolar mannitol in a near real-time fashion prior to drug administration, improving experimental success rate. It is also shown that this technique can be applied to monitor baseline physiological conditions in conventional fMRI experiments using blood oxygenation level-dependent (BOLD) contrast, further demonstrating the versatility of this technique.     

Sound segregation based on temporal envelope structure and binaural cues

The ability to segregate two spectrally and temporally overlapping signals based on differences in temporal envelope structure and binaural cues was investigated. Signals were a harmonic tone complex (HTC) with 20 Hz fundamental frequency and a bandpass noise (BPN). Both signals had interaural differences of the same absolute value, but with opposite signs to establish lateralization to different sides of the medial plane, such that their combination yielded two different spatial configurations. As an indication for segregation ability, threshold interaural time and level differences were measured for discrimination between these spatial configurations. Discrimination based on interaural level differences was good, although absolute thresholds depended on signal bandwidth and center frequency. Discrimination based on interaural time differences required the signals' temporal envelope structures to be sufficiently different. Long-term interaural cross-correlation patterns or long-term averaged patterns after equalization-cancellation of the combined signals did not provide information for the discrimination. The binaural system must, therefore, have been capable of processing changes in interaural time differences within the period of the harmonic tone complex, suggesting that monaural information from the temporal envelopes influences the use of binaural information in the perceptual organization of signal components.     

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of navitoclax

The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax-d8, was achieved with a Waters Acquity UPLC BEH C₁₈ column using isocratic flow over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5–5,000 ng/ml and proved to be accurate (89.5–104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at −70°C was at least 43 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose.     

5-amino-2-methylpyridinium hydrogen fumarate: An XRD and NMR crystallography analysis

Single-crystal X-ray diffraction structures of the 5-amino-2-methylpyridinium hydrogen fumarate salt have been solved at 150 and 300 K (CCDC 1952142 and 1952143). A base–acid–base–acid ring is formed through pyridinium-carboxylate and amine-carboxylate hydrogen bonds that hold together chains formed from hydrogen-bonded hydrogen fumarate ions. ¹H and ¹³C chemical shifts as well as ¹⁴N shifts that additionally depend on the quadrupolar interaction are determined by experimental magic angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) and gauge-including projector-augmented wave (GIPAW) calculation. Two-dimensional homonuclear ¹H-¹H double-quantum (DQ) MAS and heteronuclear ¹H-¹³C and ¹⁴N-¹H spectra are presented. Only small differences of up to 0.1 and 0.6 ppm for ¹H and ¹³C are observed between GIPAW calculations starting with the two structures solved at 150 and 300 K (after geometry optimisation of atomic positions, but not unit cell parameters). A comparison of GIPAW-calculated ¹H chemical shifts for isolated molecules and the full crystal structures is indicative of hydrogen bonding strength.     

A periodic isoperimetric problem related to the unique games conjecture

We prove the endpoint case of a conjecture of Khot and Moshkovitz related to the unique games conjecture, less a small error. Let n ≥ 2. Suppose a subset Ω of n‐dimensional Euclidean space satisfies ?Ω = Ω^c and Ω + v = Ω^c (up to measure zero sets) for every standard basis vector . For any and for any q ≥ 1, let and let . For any x ∈ ?Ω, let N(x) denote the exterior normal vector at x such that ‖N(x)‖₂ = 1. Let . Our main result shows that B has the smallest Gaussian surface area among all such subsets Ω, less a small error: In particular, Standard arguments extend these results to a corresponding weak inequality for noise stability. Removing the factor 6 × 10^?9 would prove the endpoint case of the Khot‐Moshkovitz conjecture. Lastly, we prove a Euclidean analogue of the Khot and Moshkovitz conjecture. The full conjecture of Khot and Moshkovitz provides strong evidence for the truth of the unique games conjecture, a central conjecture in theoretical computer science that is closely related to the P versus NP problem. So, our results also provide evidence for the truth of the unique games conjecture. Nevertheless, this paper does not prove any case of the unique games conjecture.     

The Fundamental Equations of Change in Statistical Ensembles and Biological Populations

A recent article in Nature Physics unified key results from thermodynamics, statistics, and information theory. The unification arose from a general equation for the rate of change in the information content of a system. The general equation describes the change in the moments of an observable quantity over a probability distribution. One term in the equation describes the change in the probability distribution. The other term describes the change in the observable values for a given state. We show the equivalence of this general equation for moment dynamics with the widely known Price equation from evolutionary theory, named after George Price. We introduce the Price equation from its biological roots, review a mathematically abstract form of the equation, and discuss the potential for this equation to unify diverse mathematical theories from different disciplines. The new work in Nature Physics and many applications in biology show that this equation also provides the basis for deriving many novel theoretical results within each discipline.     

Experimental probes of silver metal nanoparticle formation kinetics: Comparing indirect versus more direct methods

The kinetics of noble metal nanoparticle formation in bottom-up syntheses are important for controlling and optimizing these methods. Hence, experimental probes that are easily accessible to most laboratories are also of interest. We collected kinetic curves for the formation of silver nanoparticles in a modified Turkevich method with citrate acting as the reducing and stabilizing agent by (i) measuring the change in silver nanoparticle surface plasmon resonance by UV-visible spectroscopy, a somewhat indirect method, and then also by (ii) measuring the change in silver ion concentration by ion-selective electrode potentiometry and/or atomic absorption spectroscopy, two more direct methods. The resulting sigmoidal kinetic curves were curvefitted with the Finke-Watzky two-step kinetic model of slow, continuous nucleation and fast autocatalytic growth to extract average rate constants. We found that the kinetic curves obtained by following the change in silver ion concentration were apparent mirror images of those constructed by following the change in nanoparticle surface plasmon resonance, and that their respective curvefits displayed the same sigmoidal characteristics. The resultant values of the rate constants for nucleation and growth overlapped within experimental error between the methods and showed similar trends over the range of citrate concentrations studied. The use of multiple probes in this work to follow the kinetics of nanoparticle formation helps fill a need for the comparison and evaluation of different methods available to scientists, particularly those considered easily accessible.     

Towards the Design of Optically Active Thiophene S-Oxides using Quantum Chemistry

The importance of axially chiral biaryls has risen steeply in the recent decades. This structural motif proved to be successful in catalytic asymmetric synthesis and the configuration of the biaryl axis is decisive for the biological activity. A new approach for the atroposelective synthesis of biaryls would be through a cycloaddition between an enantiopure phenyl-substituted thiophene S-oxide and an alkyne. Importantly, the chiral center of the thiophene S-oxide needs to be stable enough to avoid pyramidal inversion during the cycloaddition. Considering that the racemization of thiophene monoxides has been scarcely investigated so far, we perform a thorough quantum chemical study on the inversion barriers of a large number of chiral thiophene S-oxide derivatives. Our main goal is to identify substitution patterns leading to stable atropisomers at room temperature. Appealingly, the role of stereoelectronic effects and the position of the substituents as well as the importance of aromaticity on the pyramidal inversion barrier are elucidated for the first time.