ArXiv最新文献

Purpose: To theoretically and experimentally study implant lead tip heating caused by radiofrequency (RF) power deposition in different wire configurations that contain loop(s).

Methods: Maximum temperature rise caused by RF heating was measured at 1.5T on 20 insulated, capped wires with various loop and straight segment configurations. The experimental results were compared with predictions from the previously reported simple exponential and the adapted transmission line models, as well as with a long-wavelength approximation.

Results: Both models effectively predicted the trends in lead tip temperature rise for all the wire configurations, with the adapted transmission line model showing superior accuracy. For superior/inferior (S/I)-oriented wires, increasing the number of loops decreased the overall heating. However, when wires were oriented right/left (R/L) where the x-component of the electric field is negligible, additional loops increased the overall heating.

Conclusion: The simple exponential and the adapted transmission line models previously developed for, and tested on, straight wires require no additional terms or further modification to account for RF heating in a variety of loop configurations. These results extend the models' usefulness to manage implanted device lead tip heating and provide theoretical insight regarding the role of loops and electrical lengths in managing RF safety of implanted devices.

Protein phosphorylation involves the reversible modification of a protein (substrate) residue by another protein (kinase). Liquid chromatography-mass spectrometry studies are rapidly generating massive protein phosphorylation datasets across multiple conditions. Researchers then must infer kinases responsible for changes in phosphosites of each substrate. However, tools that infer kinase-substrate interactions (KSIs) are not optimized to interactively explore the resulting large and complex networks, significant phosphosites, and states. There is thus an unmet need for a tool that facilitates user-friendly analysis, interactive exploration, visualization, and communication of phosphoproteomics datasets. We present PhosNetVis, a web-based tool for researchers of all computational skill levels to easily infer, generate and interactively explore KSI networks in 2D or 3D by streamlining phosphoproteomics data analysis steps within a single tool. PhostNetVis lowers barriers for researchers in rapidly generating high-quality visualizations to gain biological insights from their phosphoproteomics datasets. It is available at: https://gumuslab.github.io/PhosNetVis/.

Rare diseases are collectively common, affecting approximately one in twenty individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in DNA sequencing, development of new computational and experimental approaches to prioritize genes and genetic variants, and increased global exchange of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis. The Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) Consortium was initiated to study thousands of challenging rare disease cases and families and apply, standardize, and evaluate emerging genomics technologies and analytics to accelerate their adoption in clinical practice. Further, all data generated, currently representing ~7500 individuals from ~3000 families, is rapidly made available to researchers worldwide via the Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) to catalyze global efforts to develop approaches for genetic diagnoses in rare diseases (https://gregorconsortium.org/data). The majority of these families have undergone prior clinical genetic testing but remained unsolved, with most being exome-negative. Here, we describe the collaborative research framework, datasets, and discoveries comprising GREGoR that will provide foundational resources and substrates for the future of rare disease genomics.

All biological systems are subject to perturbations: due to thermal fluctuations, external environments, or mutations. Yet, while biological systems are composed of thousands of interacting components, recent high-throughput experiments show that their response to perturbations is surprisingly low-dimensional: confined to only a few stereotyped changes out of the many possible. Here, we explore a unifying dynamical systems framework - soft modes - to explain and analyze low-dimensionality in biology, from molecules to eco-systems. We argue that this one framework of soft modes makes non-trivial predictions that generalize classic ideas from developmental biology to disparate systems, namely: phenocopying, dual buffering, and global epistasis. While some of these predictions have been borne out in experiments, we discuss how soft modes allow for a surprisingly far-reaching and unifying framework in which to analyze data from protein biophysics to microbial ecology.

Sound produces surface waves along the cochlea's basilar membrane. To achieve the ear's astonishing frequency resolution and sensitivity to faint sounds, dissipation in the cochlea must be canceled via active processes in hair cells, effectively bringing the cochlea to the edge of instability. But how can the cochlea be globally tuned to the edge of instability with only local feedback? To address this question, we use a discretized version of a standard model of basilar membrane dynamics, but with an explicit contribution from active processes in hair cells. Surprisingly, we find the basilar membrane supports two qualitatively distinct sets of modes: a continuum of localized modes and a small number of collective extended modes. Localized modes sharply peak at their resonant position and are largely uncoupled. As a result, they can be amplified almost independently from each other by local hair cells via feedback reminiscent of self-organized criticality. However, this amplification can destabilize the collective extended modes; avoiding such instabilities places limits on possible molecular mechanisms for active feedback in hair cells. Our work illuminates how and under what conditions individual hair cells can collectively create a critical cochlea.

Action segmentation of behavioral videos is the process of labeling each frame as belonging to one or more discrete classes, and is a crucial component of many studies that investigate animal behavior. A wide range of algorithms exist to automatically parse discrete animal behavior, encompassing supervised, unsupervised, and semi-supervised learning paradigms. These algorithms - which include tree-based models, deep neural networks, and graphical models - differ widely in their structure and assumptions on the data. Using four datasets spanning multiple species - fly, mouse, and human - we systematically study how the outputs of these various algorithms align with manually annotated behaviors of interest. Along the way, we introduce a semi-supervised action segmentation model that bridges the gap between supervised deep neural networks and unsupervised graphical models. We find that fully supervised temporal convolutional networks with the addition of temporal information in the observations perform the best on our supervised metrics across all datasets.

Lens tension is essential for accommodative vision but remains challenging to measure with precision. Here, we present an optical coherence elastography (OCE) technique that quantifies both the tension and elastic modulus of lens tissue and capsule. This method derives mechanical parameters from surface wave dispersion across a critical frequency range of 1-30 kHz. Using isolated lenses from six-month-old pigs, we measured intrinsic anterior capsular tensions of 0-20 kPa and posterior capsular tensions of 40-50 kPa, induced by intra-lenticular pressure at the cortical surface. Young's modulus $\left(E\right)$ was 1.9 MPa for anterior capsules and 1.2 MPa for posterior capsules. Tensions in cortical tissue $(E\sim 10\text{kPa})$ were below 1 kPa. Biaxial zonular stretching (~4% strain) increased anterior capsular tension from near zero to 64 kPa. This acousto-optical method holds significant promise for diagnosing and managing accommodative dysfunctions through lens mechanics assessment in clinical settings.

The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D and 3D immunofluorescence imaging methods. The design of the Knowledge-Base is modeled after efforts in the open-source software community and includes three facets: a development platform (GitHub), static website, and service for data archiving. The Knowledge-Base facilitates the practice of open science throughout the research life cycle by providing validation data for recommended and non-recommended reagents, e.g., primary and secondary antibodies. In addition to reporting negative data, the Knowledge-Base empowers method adoption and evolution by providing a venue for sharing protocols, videos, datasets, software, and publications. A dedicated discussion forum fosters a sense of community among researchers while addressing questions not covered in published manuscripts. Together, scientists from around the world are advancing scientific discovery at a faster pace, reducing wasted time and effort, and instilling greater confidence in the resulting data.

The integration of Large Language Models (LLMs) into healthcare applications offers promising advancements in medical diagnostics, treatment recommendations, and patient care. However, the susceptibility of LLMs to adversarial attacks poses a significant threat, potentially leading to harmful outcomes in delicate medical contexts. This study investigates the vulnerability of LLMs to two types of adversarial attacks in three medical tasks. Utilizing real-world patient data, we demonstrate that both open-source and proprietary LLMs are vulnerable to malicious manipulation across multiple tasks. We discover that while integrating poisoned data does not markedly degrade overall model performance on medical benchmarks, it can lead to noticeable shifts in fine-tuned model weights, suggesting a potential pathway for detecting and countering model attacks. This research highlights the urgent need for robust security measures and the development of defensive mechanisms to safeguard LLMs in medical applications, to ensure their safe and effective deployment in healthcare settings.

The motility of eukaryotic cells is strongly influenced by their environment, with confined cells often developing qualitatively different motility patterns from those migrating on simple two-dimensional substrates. Recent experiments, coupled with data-driven methods to extract a cell's equation of motion, showed that cancerous MDA-MB-231 cells persistently hop in a limit cycle when placed on two-state adhesive micropatterns (two large squares connected by a narrow bridge), while they remain stationary on average in rectangular confinements. In contrast, healthy MCF10A cells migrating on the two-state micropattern are bistable, i.e., they settle into either basin on average with only noise-induced hops between the two states. We can capture all these behaviors with a single computational phase field model of a crawling cell, under the assumption that contact with non-adhesive substrate inhibits the cell front. Our model predicts that larger and softer cells are more likely to persistently hop, while smaller and stiffer cells are more likely to be bistable. Other key factors controlling cell migration are the frequency of protrusions and their magnitude of noise. Our results show that relatively simple assumptions about how cells sense their geometry can explain a wide variety of different cell behaviors, and show the power of data-driven approaches to characterize both experiment and simulation.