Combination of LC/TOF-MS and LC/Ion trap MS/MS for the identification of diphenhydramine in sediment samples

Diphenhydramine (Benadryl) is a popular over-the-counter antihistaminic medication used for the treatment of allergies. After consumption, excretion, and subsequent discharge from wastewater treatment plants, it is possible that diphenhydramine will be found in environmental sediments due to its hydrophobicity (log P = 3.27). This work describes a methodology for the first unequivocal determination of diphenhydramine bound to environmental sediments. The drug is removed from the sediments by accelerated solvent extraction and then analyzed by liquid chromatography with a time-of-flight mass spectrometer and an ion trap mass spectrometer. This combination of techniques provided unequivocal identification and confirmation of diphenhydramine in two sediment samples. The accurate mass measurements of the protonated molecules were m/z 256.1703 and 256.1696 compared to the calculated mass of m/z 256.1701, resulting in errors of 0.8 and 2.3 ppm. This mass accuracy was sufficient to verify the elemental composition of diphenhydramine in each sample. Furthermore, accurate mass measurements of the primary fragment ion were obtained. This work is the first application of time-of-flight mass spectrometry for the identification of diphenhydramine and shows the accumulation of an over-the-counter medication in aquatic sediments at five different locations.     

Impact of Phosphorothioate Chirality on Double-Stranded siRNAs: A Systematic Evaluation of Stereopure siRNA Designs

Oligonucleotides are important therapeutic approaches, as evidenced by recent clinical successes with antisense oligonucleotides (ASOs) and double-stranded short interfering RNAs (siRNAs). Phosphorothioate (PS) modifications are a standard feature in the current generation of oligonucleotide therapeutics, but generate isomeric mixtures, leading to 2ⁿ isomers. All currently marketed therapeutic oligonucleotides (ASOs and siRNAs) are complex isomeric mixtures. Recent chemical methodologies for stereopure PS insertions have resulted in preliminary rules for ASOs, with multiple stereopure ASOs moving into clinical development. Although siRNAs have comparatively fewer PSs, the field has yet to embrace the idea of stereopure siRNAs. Herein, it has been investigated whether the individual isomers contribute equally to the in vivo activity of a representative siRNA. The results of a systematic evaluation of stereopure PS incorporation into antithrombin-3 (AT3) siRNA are reported and demonstrate that individual PS isomers dramatically affect in vivo activity. A standard siRNA design with six PS insertions was investigated and it was found that only about 10 % of the 64 possible isomers were as efficacious as the stereorandom control. Based on this data, it can be concluded that G1R stereochemistry is critical, G2R is important, G21S is preferable, and G22 and P1/P2 tolerate both isomers. Surprisingly, the disproportionate loss of efficacy for most isomers does not translate into significant gain for the productive isomers, and thus, warrants further mechanistic studies.     

Sexual arousal in male pigtailed monkeys (Macaca nemestrina): Effects of serial matings by two males.

Examined male sexual arousal in 4 vasectomized male and 3 intact multiparous female pigtailed monkeys with the postejaculatory interval (PEI) used as the dependent variable. 12 paired trials were conducted in which a male and female copulated, the 1st male was removed and a 2nd male was or was not allowed to copulate with the female, and the 1st male was again permitted to copulate with the female. In male–female pairs, the PEI was shortened by 60% of normal (control) values if the male observed another male copulating with his female partner. Results demonstrate that the normal PEI is not an absolute male refractory period; males are capable of copulating sooner, and they will do so when presented with certain behavioral stimuli. A long PEI may prevent males from disrupting their own plugs prematurely, whereas a short PEI may result from a premature disruption of the plug by another male. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eigenentladung und Zeitkonstante des Hochspannungs-ölpapierkondensators

Zusammenfassung Die untersuchten Kondensatoren sind in HartpapiergehÄusen untergebrachte, ölgetrÄnkte Rundwickel aus Spezialpapier mit Einlagen aus Aluminiumfolie. Die Zeitkonstanten, die gemÄ\ der bekannten Beziehung aus jeweils zwei nahe beieinander liegenden Werten der Entladekurve punktweise berechnet werden, sind in AbhÄngigkeit von der Spannung wiedergegeben. Sie liegen im Bereich von 2·10³ bis 2·10⁵ s und gelten für Spannungen bis zu 250 kV. GrundsÄtzlich nehmen sie zu höheren Spannungen hin ab. Dafür ist zum Teil die SpannungsabhÄngigkeit der IsolationswiderstÄnde ma\gebend. Im übrigen ergibt sich aber auch eine AbhÄngigkeit von der Dauer der elektrischen Einwirkung; die Zeitkonstante wÄchst mit dieser bei vorgegebener Spannung an und strebt bei lÄngerer Beanspruchung schlie\lich einem Grenzwert zu. Dazu kommt ein Einflu\ der Vorbeanspruchung derart, da\ der Kondensator dann besonders günstige Zeitkonstanten aufweist, wenn er vorher einer höheren Spannung unterworfen gewesen war.     

The understanding of relative speeds, distances, and durations of movement.

In an extension of an earlier study by R. S. Siegler and D. D. Richards (see record 1979-28311-001), 102 1st–7th graders judged the relative speeds, distances, and durations of travel in 16 selected displays of 2 toy trains moving in the same direction down parallel tracks. A major variant in the investigation was the use of displays in which speeds, distances, and durations were sometimes equal instead of always unequal. Results further clarify both the order of concept acquisition and the nature of thought during the development of each concept. (5 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuroendocrine influence on attention and memory.

Examined the effects of melanocyte-stimulating hormone (MSH) on attention and memory under conditions of constant darkness and constant illumination in a study with 60 male Holtzman albino rats. After acquiring a brightness discrimination problem, Ss were given either a reversal or memory task. Ss treated with MSH and those tested in the dark performed the reversal task significantly faster than Ss tested under constant illumination. Although differences in memory were detected between groups, these were not statistically significant. Results are interpreted to suggest that increased MSH levels lead to increased awareness of the environment in the rat and that functionally equivalent behavior among other species may derive from similar neuroendocrine substrates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attention, distraction, and cold-pressor pain.

Compared the effects of distracting oneself from, vs attending to, the sensations produced by cold-pressor stimulation. Exp I (35 undergraduates) revealed that distraction was a better coping strategy than attention to sensations when Ss were asked to report pain threshold and tolerance. Exps II and III (75 Ss) examined the hypothesis that distraction is effective because persons hold a commonsense belief in the benefits of distraction as a coping device. Neither experiment supported the commonsense hypothesis as an explanation for Exp I's results. In Exp IV, 39 male Ss were assigned to either distraction, attention, or no-instruction conditions and asked to report their distress during a 4-min cold-pressor trial. Distraction reduced distress early in the trial, but attention to sensations was a superior strategy for the last 2 min. It is proposed that distraction and attention to sensations may be differentially effective depending on the duration of the painful stimulus. Possible mediating processes underlying the 2 strategies are discussed. (10 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Next-Generation Hard X-Ray Nanoprobe Beamline for In Situ Studies of Energy Materials and Devices

The Advanced Photon Source is developing a suite of new X-ray beamlines to study materials and devices across many length scales and under real conditions. One of the flagship beamlines of the APS upgrade is the In Situ Nanoprobe (ISN) beamline, which will provide in situ and operando characterization of advanced energy materials and devices under varying temperatures, gas ambients, and applied fields, at previously unavailable spatial resolution and throughput. Examples of materials systems include inorganic and organic photovoltaic systems, advanced battery systems, fuel cell components, nanoelectronic devices, advanced building materials and other scientifically and technologically relevant systems. To characterize these systems at very high spatial resolution and trace sensitivity, the ISN will use both nanofocusing mirrors and diffractive optics to achieve spots sizes as small as 20 nm. Nanofocusing mirrors in Kirkpatrick–Baez geometry will provide several orders of magnitude increase in photon flux at a spatial resolution of 50 nm. Diffractive optics such as zone plates and/or multilayer Laue lenses will provide a highest spatial resolution of 20 nm. Coherent diffraction methods will be used to study even small specimen features with sub-10 nm relevant length scale. A high-throughput data acquisition system will be employed to significantly increase operations efficiency and usability of the instrument. The ISN will provide full spectroscopy capabilities to study the chemical state of most materials in the periodic table, and enable X-ray fluorescence tomography. In situ electrical characterization will enable operando studies of energy and electronic devices such as photovoltaic systems and batteries. We describe the optical concept for the ISN beamline, the technical design, and the approach for enabling a broad variety of in situ studies. We furthermore discuss the application of hard X-ray microscopy to study defects in multi-crystalline solar cells, one of the lines of inquiries for which the ISN is being developed.