Dereplication of known pregnane glycosides and structural characterization of novel pregnanes in Marsdenia tenacissima by high-performance liquid chromatography and electrospray ionization-tandem mass spectrometry

In the search for novel natural products in plants, particularly those with potential bioactivity, it is important to efficiently distinguish novel compounds from previously isolated, known compounds, a process known as dereplication. In this study, electrospray ionization-multiple stage tandem mass spectrometry (ESI-MS(n)) was used to study the behaviour of 12 pregnane glycosides and genins previously isolated from Marsdenia tenacissima, a traditional Chinese medicinal plant, as a basis for dereplication of compounds in a plant extract. In addition to [M + Na](+) and [M + NH(4)](+) ions, a characteristic [M-glycosyl + H](+) ion was observed in full-scan mode with in-source fragmentation. Sequential in-trap collision-induced dissociation of [M + Na](+) ions from 11,12-diesters revealed consistent preferred losses of substituents first from C-12, then from C-11, followed by losses of monosaccharide fragments from the C-3 tri- and tetrasaccharide substituents. A crude methanol extract of M. tenacissima stems was analysed using high-performance liquid chromatography coupled to ESI-MS. Several previously isolated pregnane glycosides were dereplicated, and the presence of an additional nine novel pregnane glycosides is predicted on the basis of the primary and fragment ions observed, including two with a previously unreported C(4)H(7)O C-11/C-12 substituent of pregnane glycosides. This study is the first report of prediction of the structures of novel pregnane glycosides in a crude plant extract by a combination of in-source fragmentation and in-trap collision-induced dissociation and supports the usefulness of LC-ESI-MS(n) not only for dereplication of active compounds in extracts of medicinal plants but also for detecting the presence of novel related compounds.     

Small-angle Coulomb collision model for particle-in-cell simulations

We construct and investigate a set of stochastic differential equations that incorporate the physics of velocity-dependent small-angle Coulomb collisions among the plasma particles in a particle-in-cell simulation. Each particle is scattered stochastically from all the other particles in a simulation cell modeled as one or more Maxwellians. Total energy and momentum are conserved by linear transformation of the velocity increments. In two test simulations the proposed “particle-moment” collision algorithm performs well with time steps as large as 10% of the relaxation time – far larger than a particle-pairing collision algorithm, in which pairs of particles are scattered from one another, requires to achieve the same accuracy.     

Perceptually based head-related transfer function database optimization

In the context of binaural audio rendering, choosing the best head-related transfer function (HRTF) for an individual from large databases poses several problems. This study proposes a method to reduce the size of a given HRTF database. Participants, 45 in total, were asked to rate the quality of binaural synthesis for 46 HRTFs. The lack of reciprocity in the ratings was noted. Results were used to create a perceptually optimized HRTF subset which satisfied all participants' judgments. The subset was validated using localization tests on a separate group of subjects with results showing reduced errors when subjects were given their best choice, rather than their worst choice HRTF.     

A self consistent normalized calibration protocol for three dimensional magnetic resonance gel dosimetry

In a clinical setting, mixed and inconsistent results have been reported using Magnetic Resonance Relaxation imaging of irradiated aqueous polymeric gels as a three-dimensional dosimeter, for dose verification of conformal radiation therapy. The problems are attributed to the difficulty of identifying an accurate dose calibration protocol for each delivered gel at the radiation site in a clinical setting. While careful calibration is done at the gel manufacturing site in a controlled laboratory setting, there is no guarantee that the dose sensitivity of the gels remains invariant upon delivery, irradiation, magnetic resonance imaging and storage at the clinical site. In this study, we have compared three different dose calibration protocols on aqueous polymeric gels for a variety of irradiation scenarios done in a clinical setting. After acquiring the three-dimensional proton relaxation maps of the irradiated gels, the dose distributions were generated using the off-site manufacturer provided calibration curve (Cal-1), the on-site external tube gel calibration (Cal-2) and the new on-site internal normalized gel calibration (Cal-3) protocols. These experimental dose distributions were compared with the theoretical dose distributions generated by treatment-planning systems. We observed that the experimental dose distributions generated from the Cal-1 and Cal-2 protocols were off by 10% to 40% and up to 200% above the predicted maximum dose, respectively. On the other hand, the experimental dose distributions generated from the Cal-3 protocol matched reasonably well with the theoretical dose distributions to within 10% difference. Our result suggests that an independent on-site normalized internal calibration must be performed for each batch of gel dosimeters at the time of MR relaxation imaging in order to account for the variations in dose sensitivity caused by various uncontrollable conditions in a clinical setting such as oxygen contamination, temperature changes and shelf life of the delivered gel between manufacturing and MR acquisitions.     

The 't Hooft–Polyakov monopole in the presence of a 't Hooft operator

We present explicit BPS field configurations representing one non-Abelian monopole with one minimal weight 't Hooft operator insertion. We explore the SO(3)$\mathit{SO}(3)$ and SU(2)$\mathit{SU}(2)$ gauge groups. In the case of SU(2)$\mathit{SU}(2)$ gauge group the minimal 't Hooft operator can be completely screened by the monopole. If the gauge group is SO(3)$\mathit{SO}(3)$, however, such screening is impossible. In the latter case we observe a different effect of the gauge symmetry enhancement in the vicinity of the 't Hooft operator.     

MRICOM–MRI COntrast Modelling using 2D T1–T2 correlation spectra and relaxation signatures

Image contrast is calculated by inputting experimental 2D T₁–T₂ relaxation spectra into the ODIN software interface. The method involves characterising a magnetic resonance imaging pulse sequence with a “relaxation signature” which describes the sensitivity of the sequence to relaxation and is independent of sample parameters. Maximising (or minimising) the overlap between the experimental 2D T₁–T₂ relaxation spectra and the relaxation signature can then be used to maximise image contrast. The concept is illustrated using relaxation signatures for the echo planar imaging and Turbo spin-echo imaging sequences, together with in-vitro 2D T₁–T₂ spectra for liver and cartilage.     

Study of Strangeness Photoproduction on the Neutron in the Threshold Region

Photoproduction of the neutral kaon on the deuteron has been investigated at the Research Center for Electron Photon Science, Tohoku University. We constructed the Neutral Kaon Spectrometer-2 for the detection of charged particles from the decay of the neutral kaon and the hyperon. We obtained a momentum distribution of K ⁰ with the inclusive measurement. It was consistent with the previous measurement. The total cross section of γ + d → K ⁰ + Λ + p was estimated from the measured integral cross section of γ + d → Λ + X. The total cross section with respect to the photon energy was compared with the theoretical calculations. It favored the Saclay-Lyon A model calculation with the ratio of the neutral to charged coupling constants of the axial-vector meson, K ₁, as ~ ?1.5. The energy dependence and the magnitude of the total cross section were similar to the total cross section of γ + p → K ⁺ Λ.     

Macroscopic Determinism in Noninteracting Systems Using Large Deviation Theory

We consider a general system of n noninteracting identical particles which evolve under a given dynamical law and whose initial microstates are a priori independent. The time evolution of the n-particle average of a bounded function on the particle microstates is then examined in the large-n limit. Using the theory of large deviations, we show that if the initial macroscopic average is constrained to be near a given value, y, then the macroscopic average at time t converges in probability as n to a value _t(y) given explicitly in terms of a canonical expectation. Some general features of the graph of _t(y) versus t are examined, particularly in regard to continuity, symmetry, and convergence.     

The importance for speech intelligibility of random fluctuations in "steady" background noise

Spectrally shaped steady noise is commonly used as a masker of speech. The effects of inherent random fluctuations in amplitude of such a noise are typically ignored. Here, the importance of these random fluctuations was assessed by comparing two cases. For one, speech was mixed with steady speech-shaped noise and N-channel tone vocoded, a process referred to as signal-domain mixing (SDM); this preserved the random fluctuations of the noise. For the second, the envelope of speech alone was extracted for each vocoder channel and a constant was added corresponding to the root-mean-square value of the noise envelope for that channel. This is referred to as envelope-domain mixing (EDM); it removed the random fluctuations of the noise. Sinusoidally modulated noise and a single talker were also used as backgrounds, with both SDM and EDM. Speech intelligibility was measured for N?=?12, 19, and 30, with the target-to-background ratio fixed at -7 dB. For SDM, performance was best for the speech background and worst for the steady noise. For EDM, this pattern was reversed. Intelligibility with steady noise was consistently very poor for SDM, but near-ceiling for EDM, demonstrating that the random fluctuations in steady noise have a large effect.     

The dynamic range of useful temporal fine structure cues for speech in the presence of a competing talker

Within an auditory channel, the speech waveform contains both temporal envelope (E(O)) and temporal fine structure (TFS) information. Vocoder processing extracts a modified version of the temporal envelope (E') within each channel and uses it to modulate a channel carrier. The resulting signal, E'(Carr), has reduced information content compared to the original "E(O)?+ TFS" signal. The dynamic range over which listeners make additional use of E(O)?+ TFS over E'(Carr) cues was investigated in a competing-speech task. The target-and-background mixture was processed using a 30-channel vocoder. In each channel, E(O)?+ TFS replaced E'(Carr) at either the peaks or the valleys of the signal. The replacement decision was based on comparing the short-term channel level to a parametrically varied "switching threshold," expressed relative to the long-term channel level. Intelligibility was measured as a function of switching threshold, carrier type, target-to-background ratio, and replacement method. Scores showed a dependence on all four parameters. Derived intensity-importance functions (IIFs) showed that E(O)?+ TFS information from 8-13 dB below to 10 dB above the channel long-term level was important. When E(O)?+ TFS information was added at the peaks, IIFs peaked around -2 dB, but when E(O)?+ TFS information was added at the valleys, the peaks lay around +1 dB.