Impurity profiling of acetylspiramycin by liquid chromatography–ion trap mass spectrometry

Investigation of acetylspiramycin (ASPM) and its related substances was carried out using a reversed-phase liquid chromatography/tandem mass spectrometry method. The identification of impurities in the ASPM complex was performed with a quadrupole ion trap mass spectrometer, with an electrospray ionization (ESI) source in the positive ion mode which provides MSⁿ capability. A total of 83 compounds were characterized in commercial samples, among which 31 impurities that had never been reported and 31 partially characterized impurities were deduced using the collision-induced dissociation (CID) spectra of major ASPM components as templates. Most of the major impurities arise from the starting materials and the synthesis process. This work provides very useful information for quality control of ASPM and evaluation of its synthesis process.     

Bidirectional clear speech perception benefit for native and high-proficiency non-native talkers and listeners: intelligibility and accentedness

This study investigated how native language background interacts with speaking style adaptations in determining levels of speech intelligibility. The aim was to explore whether native and high proficiency non-native listeners benefit similarly from native and non-native clear speech adjustments. The sentence-in-noise perception results revealed that fluent non-native listeners gained a large clear speech benefit from native clear speech modifications. Furthermore, proficient non-native talkers in this study implemented conversational-to-clear speaking style modifications in their second language (L2) that resulted in significant intelligibility gain for both native and non-native listeners. The results of the accentedness ratings obtained for native and non-native conversational and clear speech sentences showed that while intelligibility was improved, the presence of foreign accent remained constant in both speaking styles. This suggests that objective intelligibility and subjective accentedness are two independent dimensions of non-native speech. Overall, these results provide strong evidence that greater experience in L2 processing leads to improved intelligibility in both production and perception domains. These results also demonstrated that speaking style adaptations along with less signal distortion can contribute significantly towards successful native and non-native interactions.     

Auditory evoked potentials in two short-finned pilot whales (Globicephala macrorhynchus)

The hearing sensitivities of two short-finned pilot whales (Globicephala macrorhynchus) were investigated by measuring auditory evoked potentials generated in response to clicks and sinusoidal amplitude modulated (SAM) tones. The first whale tested, an adult female, was a long-time resident at SeaWorld San Diego with a known health history. Click-evoked responses in this animal were similar to those measured in other echolocating odontocetes. Auditory thresholds were comparable to dolphins of similar age determined with similar evoked potential methods. The region of best sensitivity was near 40 kHz and the upper limit of functional hearing was between 80 and 100 kHz. The second whale tested, a juvenile male, was recently stranded and deemed non-releasable. Click-evoked potentials were not detected in this animal and testing with SAM tones suggested severe hearing loss above 10 kHz.     

Homonuclear mixing sequences for perdeuterated proteins

We tested the performance of several (13)C homonuclear mixing sequences on perdeuterated microcrystalline ubiquitin. All sequences were applied without (1)H decoupling and at relatively low MAS frequencies. We found that RFDR gave the highest overall transfer efficiency and that DREAM performs surprisingly well under these conditions being twice as efficient in the aliphatic region of the spectrum than the other mixing sequences tested.     

A Deployable In Vivo EPR Tooth Dosimeter for Triage After a Radiation Event Involving Large Populations

In order to meet the potential need for emergency large-scale retrospective radiation biodosimetry following an accident or attack, we have developed instrumentation and methodology for in vivo electron paramagnetic resonance spectroscopy to quantify concentrations of radiation-induced radicals within intact teeth. This technique has several very desirable characteristics for triage, including independence from confounding biologic factors, a non-invasive measurement procedure, the capability to make measurements at any time after the event, suitability for use by non-expert operators at the site of an event, and the ability to provide immediate estimates of individual doses. Throughout development there has been a particular focus on the need for a deployable system, including instrumental requirements for transport and field use, the need for high throughput, and use by minimally trained operators.Numerous measurements have been performed using this system in clinical and other non-laboratory settings, including in vivo measurements with unexposed populations as well as patients undergoing radiation therapies. The collection and analyses of sets of three serially-acquired spectra with independent placements of the resonator, in a data collection process lasting approximately five minutes, provides dose estimates with standard errors of prediction of approximately 1 Gy. As an example, measurements were performed on incisor teeth of subjects who had either received no irradiation or 2 Gy total body irradiation for prior bone marrow transplantation; this exercise provided a direct and challenging test of our capability to identify subjects who would be in need of acute medical care.     

Hydrophobic switching nature of methylcellulose ultra-thin films: thickness and annealing effects

We have studied the thermosensitive property of methylcellulose (MC) thin films supported on Si substrate by static sessile drop contact angle measurements, and their surface properties and thin film structure by x-ray reflectivity (XRR) and atomic force microscopy (AFM) techniques. From the static sessile drop contact angle measurements, the MC thin films showed the characteristic hydrophilic-to-hydrophobic transition at ～70?°C, which is the lower critical solution temperature of the bulk solution volume phase separation transition. For films with thickness d ≤ R(g), the onset of such a transition is affected by the film thickness while very thick films, d ? R(g), yielded higher contact angles. Annealing the MC thin films with thicknesses ～200 ? (near the radius of gyration, R(g), of the polymer) below the bulk glass transition temperature (T(g) ～ 195?° C) would not change the hydrophobic switch nature of the film but annealing 'at' and above the bulk T(g) would change its surface property. From surface topography images by AFM, there were no significant changes in either the roughness or the film texture before and after annealing. With XRR data, we were able to determine that such changes in the surface properties are highly correlated to the film thickness changes after the annealing process. This study, we believe, is the first to examine the thermal annealing affects on the thermal response function of a thermoresponsive polymer and is important for researching how to tailor the hydrophobic switching property of MC thin films for future sensing applications.     

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling

Objective

To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis.

Methods

Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis.

Results

Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity.

Conclusion

Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.     

Using Talent Searches to Identify and Meet the Educational Needs of Mathematically Talented Youngsters

Regional talent searches have been available since Julian Stanley developed the Talent Search model in the early 1970s, and over 200,000 students per year nationwide take advantage of the opportunities these university-based programs offer. The above-level testing offered by regional talent searches is useful in (a) identifying mathematically talented students, (b) tailoring educational recommendations to the abilities of the students, and (c) providing challenging educational opportunities for the students. Important considerations and concerns, as well as a discussion of the benefits, are explored in this article.