Graphene quantum dots (GQDs) have gained attention in the bioimaging community due to their biocompatibility and enhanced imaging depth in the near infra-red (NIR). Developing and optimizing a facile synthesis method of biocompatible NIR fluorescent GQDs from a variety of precursors remains, therefore, a critical task. Herein, we synthesized various GQD structures capable of fluorescing in the NIR via facile bottom-up pyrolysis of precursor materials (ascorbic acid, chitosan, citric acid, dextran, glucose, glucosamine hydrochloride, hyaluronic acid, l-glutamic acid, polyethylene glycol (PEG), sodium cholate, or sodium citrate). All synthesized GQD structures exhibit remarkable biocompatibility at concentrations of up to 1 mg/mL evaluated by an MTT assay which makes them suitable for a variety of therapeutic applications. All 11 GQD structures are successfully tracked by their NIR fluorescence in vitro bioimaging while exhibiting effective cellular internalization maximized at 12 hours in HEK293 cell line. This work provides a unique comprehensive study exploring a scalable and cost-effective process to synthesize NIR-emissive highly biocompatible GQDs from 11 precursor materials, while theoretically describing their optical properties. Due to their exceptional biocompatibility and photostable NIR emission, GQD structures developed here are expected to become prominent candidates for future clinical fluorescence imaging applications.

Between the Andromeda (M31) and Triangulum (M33) galaxies lies a population of neutral hydrogen clouds which have velocities in between M31 and M33. The origin of these clouds is unknown, and it is thought that they could represent (1) a tidal bridge that links M31 with one of its satellite galaxies, (2) an inflowing intergalactic medium stream, (3) halo gas condensations, or (4) tidally-stripped material from a population of satellite galaxies. To ascertain the origin(s) of these clouds, we embark on a UV absorption and radio-line study to constrain their chemical composition. We assessed the ionization state of the gas using photoionization modeling with Cloudy that we anchored using HI and ion column densities that we measured from our Green Bank Telescope and HST/COS datasets. Through this work, we resolve the properties of a single gaseous stream of M31 along multiple sightlines, aiding in our understanding of L* galaxy ecosystems.

Modulating the Interferon Response to Enhance Oncolytic Virotherapy in Cancer Treatment
Anushka Velala, Hana Dobrovolny Ph.D
TCU Department of Physics, Fort Worth, TX
Background: Oncolytic viruses (OVs) are a promising immunotherapeutic strategy that can selectively target and lyse cancer cells while stimulating an anti-tumor immune response. However, their efficiency is often limited by the interferon (IFN) response, which acts as a key antiviral defense mechanism in host cells. Understanding the interplay between oncolytic viruses and IFN signaling is crucial for optimizing viral-based cancer therapies that have potential of success.
Hypothesis/Objective: This study aims to investigate how oncolytic viruses interact with the IFN response in a simulated tumor microenvironment. We hypothesize that higher values of variation in the IFN modulation can significantly negatively affect viral replication and therapeutic oncolytic efficacy.
Study Design and Research Methods: An analysis was conducted using a mathematical model with systems of differential equations. This model encompasses factors such as tumor growth, oncolytic infection dynamics, viral production and clearance, and the IFN-mediated immune response. Furthermore, sensitivity analysis was conducted to assess the influence of key parameters, including viral production rate, infection rate, and IFN clearance, on the treatment outcomes.
Results: Various simulations indicate that higher IFN levels correlate with reduced viral spread, leading to diminished oncolytic activity. However, parameter variations suggest that therapeutic efficacy can be optimized by adjusting certain parameters to mitigate excessive IFN responses. For instance, higher values of IFN efficacy are correlated with stronger IFN-mediated suppression of viral production, leading to lower sustained viral loads, while lower IFN efficacy levels allow for prolonged high viral replication. Similarly, IFN clearance rate affects how long IFN-induced killing of infected cells and uninfected cells persists, which can modulate the viral load over time. The most effective interferon response is a low-level response with low IFN clearance and high values of IFN efficacy, coupled with higher values of IFN-induced killing of uninfected cancer cells.
Conclusions: These findings underscore the role of the IFN response in modulating OV therapy and suggest that targeted suppression of IFN signaling could enhance OV efficacy in resistant tumors. This research provides insights for optimizing oncolytic virotherapy and improving clinical outcomes in cancer treatment, given the rising prominence of immunotherapy.

Frustrative nonreward (FNR), an adverse reaction brought on by unexpected reward reductions or omissions, can be induced by a downshift in the quantity or quality of the reward. The consummatory successive negative contrast (cSNC) task is a well-known paradigm for studying FNR. cSNC involves monitoring the behavioral reaction to a lower reward (downshift) after exposure to a larger or better incentive. It supports the idea that an acceptable but less preferred reward will be rejected in a situation that is associated with a better and more desirable reward. The intensity of FNR depends, among other things, on the strength of the expectation of the large reward. We assumed that overtraining would enhance reward expectancy such that a reward downshift would lead to a stronger cSNC effect than that observed under regular training conditions. This would support the hypothesis that behavior (licking for sucrose) was guided by reward expectancies—an action. But overtraining often leads to habitual behavior that depends on eliciting stimuli, rather than reward expectancies. A failure to show the cSNC effect after overtraining would be consistent with the hypothesis that behavior had become automatic—a habit. Our experiment was designed to test whether overtraining in the cSNC task would result in behavior becoming either an action or a habit. In the experiment, 47 rats were exposed to different concentrations of sucrose, 32%, 16%, or 4%, and 2 training periods, overtraining for 30 sessions and regular training for 10 sessions. Animals exposed to 32% and 16% sucrose were randomly assigned to two groups depending on the amount of training they received before the downshift, either 30 (overtraining) or 10 sessions (regular training). These animals were given access to 4% sucrose after their designated training period. An unshifted control group received only access to 4% sucrose throughout training. The data obtained after 10 vs. 30 sessions of training were compared to the unshifted controls. The results showed that overtraining enhanced the cSNC effect relative to regular training, suggesting that licking was an action guided by the expectation of the current reward, rather than a habit. These results suggest that FNR induced by reward downshifts overcomes the development of a habit even after prolonged training.

Humans produce complex and learned behaviors like speech, playing musical instruments, and sports through exceptional motor abilities. These learned actions need specific motor planning and preparation. Researchers use songbirds in part because they produce a stereotyped motor sequence whenever they engage in singing behavior. Further, Zebra Finches learn their song through vocal production learning, similar to human speech acquisition; they mimic their adult male tutor's song and reproduce a similar version in adulthood. This motor learning process leads to the generation and execution of a highly skilled and stereotyped motor program production. Before the song, Zebra finches sing a sequence of introductory notes that are short-duration, non-stereotyped sounds. Previous work has speculated that these introductory notes are a form of motor preparation, but an experimental test of this hypothesis has not been conducted. This study casually examines the role of introductory notes as a motor preparation phase to help transition to executing the main song motor sequence. To distinguish motor preparation from song execution, we reasoned that presenting an external stimulus would delay preparation but not execution. We used air pressure recording to identify introductory notes and triggered white-noise playback during the introductory note performance in six birds and found that the external stimulus led to a delay, which can lead to interruption of the typical song motor pattern (e.g., abnormal pauses). Whereas the same stimulus presented during the song either caused an abnormal early termination of the motor program or did not affect the song (continuation), but it did not delay the execution of the song's motor gestures. Our findings suggest that introductory notes are flexible and modifiable by external stimuli, which is consistent with the hypothesis that they function as a preparatory motor gesture for the upcoming stereotyped song.
Understanding motor planning can provide insight into neurological, behavioral, speech, and motor disorders that are characterized by deficits in neuromuscular preparation.