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Active biological molecules present a powerful, yet largely untapped, opportunity to impart autonomous regulation to materials. Because these systems can function robustly to regulate when and where chemical reactions occur, they have the ability to bring complex, life-like behavior to synthetic materials. Here, we achieve this design feat by using functionalized circadian clock proteins, KaiB and KaiC, to engineer time-dependent crosslinking of colloids. The resulting material self-assembles with programmable kinetics, producing macroscopic changes in material properties, via molecular assembly of KaiB-KaiC complexes. We show that colloid crosslinking depends strictly on the phosphorylation state of KaiC, with kinetics that are synced with KaiB-KaiC complexing. Our microscopic image analyses and computational models indicate that the stability of colloidal super-structures depends sensitively on the number of Kai complexes per colloid connection. Consistent with our model predictions, a high concentration stabilizes the material against dissolution after a robust self-assembly phase, while a low concentration allows circadian oscillation of material structure. This work introduces the concept of harnessing biological timers to control synthetic materials; and, more generally, opens the door to using protein-based reaction networks to endow synthetic systems with life-like functional properties.

Various diffusion MRI (dMRI) preprocessing pipelines are currently available to yield more accurate diffusion parameters. Here, we evaluated accuracy and robustness of the optimized Diffusion parameter EStImation with Gibbs and NoisE Removal (DESIGNER) pipeline in a large clinical dMRI dataset and using ground truth phantoms. DESIGNER has been modified to improve denoising and target Gibbs ringing for partial Fourier acquisitions. We compared the revisited DESIGNER (Dv2) (including denoising, Gibbs removal, correction for motion, EPI distortion, and eddy currents) against the original DESIGNER (Dv1) pipeline, minimal preprocessing (including correction for motion, EPI distortion, and eddy currents only), and no preprocessing on a large clinical dMRI dataset of 524 control subjects with ages between 25 and 75 years old. We evaluated the effect of specific processing steps on age correlations in white matter with DTI and DKI metrics. We also evaluated the added effect of minimal Gaussian smoothing to deal with noise and to reduce outliers in parameter maps compared to DESIGNER (Dv2)'s noise removal method. Moreover, DESIGNER (Dv2)'s updated noise and Gibbs removal methods were assessed using ground truth dMRI phantom to evaluate accuracy. Results show age correlation in white matter with DTI and DKI metrics were affected by the preprocessing pipeline, causing systematic differences in absolute parameter values and loss or gain of statistical significance. Both in clinical dMRI and ground truth phantoms, DESIGNER (Dv2) pipeline resulted in the smallest number of outlier voxels and improved accuracy in DTI and DKI metrics as noise was reduced and Gibbs removal was improved. Thus, DESIGNER (Dv2) provides more accurate and robust DTI and DKI parameter maps as compared to no preprocessing or minimal preprocessing.

There has been renewed interest in understanding the mathematical structure of ecological population models that lead to overcompensation, the process by which a population recovers to a higher level after suffering a permanent increase in predation or harvesting. Here, we apply a recently formulated kinetic population theory to formally construct an age-structured single-species population model that includes a cannibalistic interaction in which older individuals prey on younger ones. Depending on the age-dependent structure of this interaction, our model can exhibit transient or steady-state overcompensation of an increased death rate as well as oscillations of the total population, both phenomena that have been observed in ecological systems. Analytic and numerical analysis of our model reveals sufficient conditions for overcompensation and oscillations. We also show how our structured population partial integrodifferential equation (PIDE) model can be reduced to coupled ODE models representing piecewise constant parameter domains, providing additional mathematical insight into the emergence of overcompensation.

We present a real-time visualization system for Transcranial Magnetic Stimulation (TMS), a non-invasive neuromodulation technique for treating various brain disorders and mental health diseases. Our solution targets the current challenges of slow and labor-intensive practices in treatment planning. Integrating Deep Learning (DL), our system rapidly predicts electric field (E-field) distributions in 0.2 seconds for precise and effective brain stimulation. The core advancement lies in our tool's real-time neuronavigation visualization capabilities, which support clinicians in making more informed decisions quickly and effectively. We assess our system's performance through three studies: First, a real-world use case scenario in a clinical setting, providing concrete feedback on applicability and usability in a practical environment. Second, a comparative analysis with another TMS tool focusing on computational efficiency across various hardware platforms. Lastly, we conducted an expert user study to measure usability and influence in optimizing TMS treatment planning. The system is openly available for community use and further development on GitHub: https://github.com/lorifranke/SlicerTMS.

The site frequency spectrum (SFS) is a widely used summary statistic of genomic data. Motivated by recent evidence for the role of neutral evolution in cancer, we investigate the SFS of neutral mutations in an exponentially growing population. Using branching process techniques, we establish (first-order) almost sure convergence results for the SFS of a Galton-Watson process, evaluated either at a fixed time or at the stochastic time at which the population first reaches a certain size. We finally use our results to construct consistent estimators for the extinction probability and the effective mutation rate of a birth-death process.

Background: FLASH Radiotherapy (RT) is an emergent cancer radiotherapy modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications.

Purpose: A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: 1) large area coverage; 2) a low mass profile; 3) a linear response over a broad dynamic range; 4) radiation hardness; 5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation do-simetry and excellent spatial resolution.

Methods: The FBSM uses a proprietary low mass, less than 0.5 mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ~10 cm. A field programmable gate array (FPGA) data acquisition system (DAQ) generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100-1000 Hz for pulsed electrons and 10-20 kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams (⁸⁶Kr⁺²⁶ and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital radiotherapy clinic with electron beams.

Results: Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. The HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 minutes at a FLASH compatible dose rate of 237 Gy/s. Measurements of the signal amplitude vs beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of > 40 Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35-40 μm. Tests of the firmware beta version show successful operation at 20,000 Hz frame rate or 50 μs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 μs.

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