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We demonstrate that the method of characterizing viscoelastic materials with Atomic Force Microscopy (AFM) by fitting analytical models to force-distance (FD) curves often yields conflicting and physically unrealistic results. Because this method involves specifying a constitutive time-dependent viscoelastic model and then fitting said model to the experimental data, we show that the inconsistencies in this method are due to a lack of sensitivity of the model with respect to its parameters. Using approaches from information theory, this lack of sensitivity can be interpreted as a narrowed distribution of information which is obtained from the experiment. Furthermore, the equivalent representation of the problem in the frequency domain, achieved via modified Fourier transformation, offers an enhanced sensitivity through a widening of the information distribution. Using these distributions, we then define restrictions for the timescales which can be reliably accessed in both the time and frequency domains, which leads to the conclusion that the analysis of experiments in the time domain can frequently lead to inaccuracies. Finally, we provide an example where we use these restrictions as a guide to optimally design an experiment to characterize a polydimethylsiloxane (PDMS) polymer sample., 23 pages main paper, 21 pages supporting information document

The anterior hypothalamic area (AHA) is a critical structure for defensive responding. Here, we identified a cluster of parvalbumin-expressing neurons in the AHA (AHAPV) that are glutamatergic with fast-spiking properties and send axonal projections to the dorsal premammillary nucleus (PMD). Using in vivo functional imaging, optogenetics, and behavioral assays, we determined the role of these AHAPV neurons in regulating behaviors essential for survival. We observed that AHAPV neuronal activity significantly increases when mice are exposed to a predator, and in a real-time place preference assay, we found that AHAPV neuron photoactivation is aversive. Moreover, activation of both AHAPV neurons and the AHAPV→PMD pathway triggers escape responding during a predator-looming test. Furthermore, escape responding is impaired after AHAPV neuron ablation, and anxiety-like behavior as measured by the open field and elevated plus maze assays does not seem to be affected by AHAPV neuron ablation. Finally, whole-brain metabolic mapping using positron emission tomography combined with AHAPV neuron photoactivation revealed discrete activation of downstream areas involved in arousal, affective, and defensive behaviors including the amygdala and the substantia nigra. Our results indicate that AHAPV neurons are a functional glutamatergic circuit element mediating defensive behaviors, expanding the identity of genetically defined neurons orchestrating fight-or-flight responses. Together, our work will serve as a foundation for understanding neuropsychiatric disorders such as aggression or fear.

The anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Here, we first examined AHA activity patterns during fear conditioning using in vivo functional imaging. We observed that neuronal activity in the AHA increases during both foot shock delivery and foot-shock associated auditory cues. Moreover, we used a combination of optogenetics and behavioral assays to determine the functional connectivity between the ventromedial hypothalamus (VMH) and the AHA. We found that photoactivation of the VMH→AHA pathway is aversive and triggers compulsive grooming behavior. Furthermore, we observed spatial and temporal changes of grooming behavior during the periods following VMH→AHA photoactivation. Interestingly, whole brain metabolic mapping using positron emission tomography (PET) combined with optogenetic activation of the VMH→AHA pathway in anesthetized mice revealed the amygdala as a downstream area activated by the stimulation of this pathway. Together, our findings show that the AHA responds to threat and that such increases in activity are sufficient to trigger compulsive grooming behavior. Thus, our results may help to understand some neuropsychiatric disorders characterized by repetitive and compulsive behaviors.

Hydrogels have emerged as a crucial class of materials within the field of tissue engineering. There is growing interest in matching the mechanical properties of hydrogel scaffolds to tissues in the human body and optimizing these properties for cell growth and differentiation. Gelatin methacrylate (GelMA) is a well-accepted, biocompatible hydrogel with tunable mechanical properties. However, the effects of various formulation parameters on its mechanical properties are not well understood. In this study, an array of GelMA scaffold fabrication parameters is evaluated by varying GelMA concentration and ultraviolet light exposure time. Our overarching goal is to characterize the mechanical properties through ultrasound and rheological measurements, providing a framework for GelMA scaffold selection. Pulse-echo ultrasound techniques were used to non-invasively determine the sound speed and attenuation of the scaffolds, revealing significant dependence on GelMA concentration. Steady shear rate and strain- and frequency-controlled oscillatory shear tests using a rotational rheometer (Model: DHR-2, TA Instruments) revealed a range in the levels of shear-thinning as well as viscoelasticity and showed moduli-dependence on both GelMA concentration and light exposure time. Together, this acoustic and rheological characterization can be used to inform the selection of GelMA scaffolds in tissue engineering applications.

As a fourth-year graduate student and ASA Student Council representative, I have had access to the opinions of students and gained insight on what they expect from their mentors and advisors. In this talk, I hope to demystify the student perspective by discussing the themes that have emerged from both Blackstock Mentor Award applications and a mentoring survey sent to Biomedical Acoustics students. One question drives the analysis: What kind of mentor/mentee relationship leads to the most successful outcomes and how is that success measured by students?

Cell growth and differentiation rely upon both biochemical and mechanical cues. Though the focus has historically been biochemical, there is an increasing interest on the mechanical properties of scaffold materials within the field of tissue engineering. When the mechanical properties of a scaffold material more closely match with those of the intended native tissue, the functionality of the tissue scaffold is significantly enhanced. This study explores how an acoustic and viscoelastic characterization of a popular hydrogel, gelatin methacrylate (GelMA), can be used to inform the synthesis and fabrication parameters for a variety of tissue engineering applications. GelMA scaffolds exhibiting a range of mechanical properties were produced by varying the concentration of GelMA and by varying the curing time of the scaffolds. Pulse-echo ultrasound techniques were used to determine the sound speed and attenuation, revealing a significant dependence on the GelMA concentration. Compression tests were also performed, showing an increased stiffness with certain preparation parameters. Finally, atomic force microscopy experiments were used to obtain the storage and loss moduli of the hydrogels, revealing an increase in hydrogel stiffness at short time scales for both the GelMA concentration and curing time.

Smoking tobacco products is the leading cause of preventable death worldwide. Coordinated efforts have successfully reduced tobacco cigarette smoking in the United States; however, electronic cigarettes (e-cigarette) and other electronic nicotine delivery systems (ENDS) recently have replaced traditional cigarettes for many users. While the clinical risks associated with long-term ENDS use remain unclear, advancements in preclinical rodent models will enhance our understanding of their overall health effects. This review examines the peripheral and central effects of ENDS-mediated exposure to nicotine and other drugs of abuse in rodents and evaluates current techniques for implementing ENDS in preclinical research.