Faculty Bibliography

While most processes in biology are highly deterministic, stochastic mechanisms are sometimes used to increase cellular diversity. In human and Drosophila eyes, photoreceptors sensitive to different wavelengths of light are distributed in stochastic patterns, and one such patterning system has been analyzed in detail in the Drosophila retina. Interestingly, some species in the dipteran family Dolichopodidae (the "long legged" flies, or "Doli") instead exhibit highly orderly deterministic eye patterns. In these species, alternating columns of ommatidia (unit eyes) produce corneal lenses of different colors. Occasional perturbations in some individuals disrupt the regular columns in a way that suggests that patterning occurs via a posterior-to-anterior signaling relay during development, and that specification follows a local, cellular-automaton-like rule. We hypothesize that the regulatory mechanisms that pattern the eye are largely conserved among flies and that the difference between unordered Drosophila and ordered dolichopodid eyes can be explained in terms of relative strengths of signaling interactions rather than a rewiring of the regulatory network itself. We present a simple stochastic model that is capable of explaining both the stochastic Drosophila eye and the striped pattern of Dolichopodidae eyes and thereby characterize the least number of underlying developmental rules necessary to produce both stochastic and deterministic patterns. We show that only small changes to model parameters are needed to also reproduce intermediate, semi-random patterns observed in another Doli species, and quantification of ommatidial distributions in these eyes suggests that their patterning follows similar rules.

Common data elements (CDEs) are becoming more common as more areas of preclinical research have generated CDEs. Herein we provide an overview of the progress to date in generating CDEs for preclinical epilepsy research. Currently there are CDEs that have been developed for Physiology (in vivo), Behavior, Pharmacology, and Electroencephalography (EEG). Together the CDEs and methodologic considerations associated with these CDEs are laid out in consecutive manuscripts published in Epilepsia Open, each describing CDEs for their respective topic area. In addition to the overview of progress for the 4 subjects, core characteristics (Core CDEs) are described and explained. Data collection using a case report form (CRF) is described, and considerations that are involved in using the CDEs and CRFs are discussed.

PURPOSE/OBJECTIVE:The ultimate intrinsic signal-to-noise ratio (UISNR) is normally calculated using electrodynamic simulations with a complete basis of modes. Here, we provide an exact solution for the UISNR at the center of a dielectric sphere and assess how accurately this solution approximates UISNR away from the center. METHODS:We performed a mode analysis to determine which modes contribute to central UISNR - ζ(r→0). We then derived an analytic expression to calculate ζ(r→0) and analyzed its dependence on main magnetic field strength, sample geometry, and electrical properties. We validated the proposed solution against an established method based on dyadic Green's function simulations. RESULTS:Only one divergence-free mode contributes to ζ(r→0). The UISNR given by the exact solution matched the full simulation results for various parameter settings, whereas calculation speed was approximately 1000 times faster. We showed that the analytic expression can approximate the UISNR with <5% error at positions as much as 10-20% of the radius away from the center. CONCLUSION/CONCLUSIONS:The proposed formula enables rapid and direct calculation of UISNR in the central region of a sphere. The resulting UISNR value may be used, for example, as an absolute reference to assess the performance of head coils with spherical phantoms.

PURPOSE/OBJECTIVE:-weighted images from a single scan and allows for free-breathing acquisition. THEORY AND METHODS/UNASSIGNED:-weighted gradient-echo (GRE) data. Improved robustness is achieved by extracting a respiratory signal from the GRE data and using it for motion-weighted reconstruction. RESULTS:-weighted Dixon acquisition is possible. CONCLUSION/CONCLUSIONS:-weighted imaging in a single scan. In addition to free-breathing abdominal examination, it promises value for clinical applications that are frequently affected by motion artifacts.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force created the TASK3 working groups to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve standardization of experimental designs. This article concerns the parameters that can be measured to assess the physiologic condition of the animals that are used to study rodent models of epilepsy. Here we discuss CDEs for physiologic parameters measured in adult rats and mice such as general health status, temperature, cardiac and respiratory function, and blood constituents. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript we discuss the monitoring of different aspects of physiology of the animals. The CDEs, CRFs, and companion paper are available to all researchers, and their use will benefit the harmonization and comparability of translational preclinical epilepsy research. The ultimate hope is to facilitate the development of biomarkers and new treatments for epilepsy.

OBJECTIVE:In the context of the current opioid epidemic, there has been a renewed interest in the use of ketamine as an analgesic agent. METHODS:We have reviewed ketamine analgesia. RESULTS:Ketamine is well-known as an antagonist for N-methyl-D-aspartate receptors. In addition, it can regulate the function of opioid receptors and sodium channels. Ketamine also increases signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. These myriad of molecular and cellular mechanisms are responsible for a number of pharmacological functions including pain relief and mood regulation. Clinically, a number of studies have investigated the role of ketamine in the setting of acute and chronic pain, and there is evidence that ketamine can provide analgesia in a variety of pain syndromes. DISCUSSION/CONCLUSIONS:In this review, we have examined basic mechanisms of ketamine and its current clinical use as well as potential novel use in pain management.

PURPOSE/OBJECTIVE:profiles in the longitudinal (z) direction and allow for next-nearest neighbor decoupling. METHODS:Two cylindrical 8-channel arrays having the same length and diameter, 1 of triangular coils and the other of rectangular coils, were constructed and compared in phantom imaging experiments using measures of excitation distribution for a variety of RF shim settings and geometry factor maps for different accelerations on different planes. RESULTS:Coupling between elements was -20 dB or better for all triangular coil pairs, but worse than -12 dB for several of the rectangular coil pairs. Both coils could produce adequate shims on a central transverse plane, but the same shim produced worse results off center for the triangular coil array than for the rectangular coil array. Compared to the rectangular coil array, the maximum geometry factor for the triangular coil array was reduced by a factor of 13.1 when using a 2-fold acceleration in the z-direction. CONCLUSION/CONCLUSIONS:profiles along the z-direction, although this also means that individual slices must be shimmed separately. This design is well suited for parallel transmit applications while also having high receive sensitivity.

Localizing the sources of stimuli is essential. Most organisms cannot eat, mate, or escape without knowing where the relevant stimuli originate. For many, if not most, animals, olfaction plays an essential role in search. While microorganismal chemotaxis is relatively well understood, in larger animals the algorithms and mechanisms of olfactory search remain mysterious. In this symposium, we will present recent advances in our understanding of olfactory search in flies and rodents. Despite their different sizes and behaviors, both species must solve similar problems, including meeting the challenges of turbulent airflow, sampling the environment to optimize olfactory information, and incorporating odor information into broader navigational systems.

The extracellular space occupies approximately one-fifth of brain volume, molding a spider web of gaps filled with interstitial fluid and extracellular matrix where neurons and glial cells perform in concert. Yet, very little is known about the spatial organization and dynamics of the extracellular space, let alone its influence on brain function, owing to a lack of appropriate techniques (and a traditional bias toward the inside of cells, not the spaces in between). At the same time, it is clear that understanding fundamental brain functions, such as synaptic transmission, memory, sleep, and recovery from disease, calls for more focused research on the extracellular space of the brain. This review article highlights several key research areas, covering recent methodological and conceptual progress that illuminates this understudied, yet critically important, brain compartment, providing insights into the opportunities and challenges of this nascent field.