Virtual screening for high affinity guests for synthetic supramolecular receptors

The protein/ligand docking software GOLD, which was originally developed for drug discovery, has been used in a virtual screen to identify small molecules that bind with extremely high affinities (K ≈ 107 M-1) in the cavity of a cubic coordination cage in water. A scoring function was developed using known guests as a training set and modified by introducing an additional term to take account of loss of guest flexibility on binding. This scoring function was then used in GOLD to successfully identify 15 new guests and accurately predict the binding constants. This approach provides a powerful predictive tool for virtual screening of large compound libraries to identify new guests for synthetic hosts, thereby greatly simplifying and accelerating the process of identifying guests by removing the reliance on experimental trial-and-error

The neural correlates of emotion regulation by implementation intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency

A multi-gene phylogeny for species of Mycosphaerella occurring on Eucalyptus leaves

Species of the ascomycete genus Mycosphaerella are regarded as some of the most destructive leaf pathogens of a large number of economically important crop plants. Amongst these, approximately 60 Mycosphaerella spp. have been identified from various Eucalyptus spp. where they cause leaf diseases collectively known as Mycosphaerella Leaf Disease (MLD). Species concepts for this group of fungi remain confused, and hence their species identification is notoriously difficult. Thus, the introduction of DNA sequence comparisons has become the definitive characteristic used to distinguish species of Mycosphaerella. Sequences of the Internal Transcribed Spacer (ITS) region of the ribosomal RNA operon have most commonly been used to consider species boundaries in Mycosphaerella. However, sequences for this gene region do not always provide sufficient resolution for cryptic taxa. The aim of this study was, therefore, to use DNA sequences for three loci, ITS, Elongation factor 1-alpha (EF-1α) and Actin (ACT) to reconsider species boundaries for Mycosphaerella spp. from Eucalyptus. A further aim was to study the anamorph concepts and resolve the deeper nodes of Mycosphaerella, for which part of the Large Subunit (LSU) of the nuclear rRNA operon was sequenced. The ITS and EF-1α gene regions were found to be useful, but the ACT gene region did not provide species-level resolution in Mycosphaerella. A phylogeny of the combined DNA datasets showed that species of Mycosphaerella from Eucalyptus cluster in two distinct groups, which might ultimately represent discrete genera

The neural correlates of regulating another person's emotions: an exploratory fMRI study

Studies investigating the neurophysiological basis of intrapersonal emotion regulation (control of one's own emotional experience) report that the frontal cortex exerts a modulatory effect on limbic structures such as the amygdala and insula. However, no imaging study to date has examined the neurophysiological processes involved in interpersonal emotion regulation, where the goal is explicitly to regulate another person's emotion. Twenty healthy participants (10 males) underwent fMRI while regulating their own or another person's emotions. Intrapersonal and interpersonal emotion regulation tasks recruited an overlapping network of brain regions including bilateral lateral frontal cortex, pre-supplementary motor area, and left temporo-parietal junction. Activations unique to the interpersonal condition suggest that both affective (emotional simulation) and cognitive (mentalizing) aspects of empathy may be involved in the process of interpersonal emotion regulation. These findings provide an initial insight into the neural correlates of regulating another person's emotions and may be relevant to understanding mental health issues that involve problems with social interaction

Psychometric properties of standardized balance confidence, fear of falling, and falls-efficacy measures in people with lower limb amputations

Background: In Canada, \u3e50% of community-dwelling lower limb amputees (LLA) fall at least once each year, a rate that is almost twice that of community-dwelling older adults. While the physical consequences of falls may be readily apparent, psychological sequelae that follow may be just as, if not more, detrimental than an actual fall itself. Current measures of balance confidence show no change in LLA following discharge from rehabilitation. The limited detectable change may be due to content validity challenges of the measures as they were not developed for the unique challenges faced by LLA. Objectives: 1) Review items from standardized scales measuring falls-related concerns with participants to determine the applicability of test items to the LLA population. 2) Solicit novel examples of relevant activities from participants to inform the development of an LLA-specific balance confidence scale. Proposed Methods: This cross-sectional study will include adult unilateral/bilateral LLA (n=60) recruited through the Outpatient Amputee Rehabilitation Program at Parkwood Institute. Falls-related concerns will be evaluated using seven relevant clinical measures of a concern for falling. Participants will be asked to identify inapplicable questions and to provide i) a list of activities they are physically able to do but are avoiding; and ii) a list of activities they currently do but are worried about becoming unsteady or falling when performed. Future Directions/Implications: The results of this project could provide important details for the creation of an amputee-specific measurement tool to better quantify psychological concerns related to falls

The effects of heat stress on neuromuscular activity during endurance exercise

This study analysed the effect of hot (35 C) and cold (15 C) environments on electromyographic (EMG) signal characteristics, skin and rectal temperatures and heart rate during progressive endurance exercise. Eight healthy subjects performed three successive 15-min rides at 30%, 50% and 70% of their peak sustained power output and then cycled at increasing (15 W/min) work rates to exhaustion in both 35 C and 15 C environments. Skin and rectal temperatures, heart rate and EMG data were measured during the trials. The skin temperatures were higher and the subjects felt more uncomfortable in the hot conditions (Bedford scale) (P<0.01). Rectal temperature was slightly, but not significantly, higher under hot conditions. Heart rate was significantly higher in the hot group (between condition P<0.05). Peak power output (267.4€67.7 W vs. 250.1€61.5 W) and time-toexhaustion (55.7€16.7 min vs. 54.5€17.1 min) (COLD vs. HOT) were not different between conditions. There were no differences in integrated EMG (IEMG) or mean power frequency spectrum between conditions. Rating of perceived exertion increased similarly in both conditions over time. Although the hot conditions increased heart rate and skin temperature, there were no differences in muscle recruitment or maximal performance, which suggests that the thermal stress of 35 C, in combination with exercise, did not impair maximal performance in this study

Development of a telescope for medium-energy gamma-ray astronomy

The Advanced Energetic Pair Telescope (AdEPT) is being developed at GSFC as a future NASA MIDEX mission to explore the medium-energy (5–200 MeV) gamma-ray range. The enabling technology for AdEPT is the Three- Dimensional Track Imager (3-DTI), a gaseous time projection chamber. The high spatial resolution 3-D electron tracking of 3-DTI enables AdEPT to achieve high angular resolution gamma-ray imaging via pair production and triplet production (pair production on electrons) in the medium-energy range. The low density and high spatial resolution of 3-DTI allows the electron positron track directions to be measured before they are dominated by Coulomb scattering. Further, the significant reduction of Coulomb scattering allows AdEPT to be the first medium-energy gamma-ray telescope to have high gamma-ray polarization sensitivity. We review the science goals that can be addressed with a medium-energy pair telescope, how these goals drive the telescope design, and the realization of this design with AdEPT. The AdEPT telescope for a future MIDEX mission is envisioned as a 8 m3 active volume filled with argon at 2 atm. The design and performance of the 3-DTI detectors for the AdEPT telescope are described as well as the outstanding instrument challenges that need to be met for the AdEPT mission