bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of ClC‐1 chloride channels in zebrafish: a new model to study myotonia
Authors: Gaitán‐Peñas Héctor , Pérez‐Rius Carla , Muhaisen Ashraf , Castellanos Aida , Errasti‐Murugarren Ekaitz , Barrallo‐Gimeno Alejandro , Alcaraz‐Pérez Francisca , Estévez Raúl 
Published: July 2024

AbstractThe function of the chloride channel ClC‐1 is crucial for the control of muscle excitability. Thus, reduction of ClC‐1 functions by CLCN1 mutations leads to myotonia congenita. Many different animal models have contributed to understanding the myotonia pathophysiology. However, these models do not allow in vivo screening of potentially therapeutic drugs, as the zebrafish model does. In this work, we identified and characterized the two zebrafish orthologues (clc‐1a and clc‐1b) of the ClC‐1 channel. Both channels are mostly expressed in the skeletal muscle as revealed by RT‐PCR, western blot, and electrophysiological recordings of myotubes, and clc‐1a is predominantly expressed in adult stages. Characterization in Xenopus oocytes shows that the zebrafish channels display similar anion selectivity and voltage dependence to their human counterparts. However, they show reduced sensitivity to the inhibitor 9‐anthracenecarboxylic acid (9‐AC), and acidic pH inverts the voltage dependence of activation. Reduction of clc‐1a/b expression hampers spontaneous and mechanically stimulated movement, which could be reverted by expression of human ClC‐1 but not by some ClC‐1 containing myotonia mutations. Treatment of clc‐1‐depleted zebrafish with mexiletine, a typical drug used in human myotonia, improves the motor behaviour. Our work extends the repertoire of ClC channels to evolutionary structure–function studies and proposes the zebrafish clcn1 crispant model as a simple tool to find novel therapies for myotonia.
imageKey points
We have identified two orthologues of ClC‐1 in zebrafish (clc‐1a and clc‐1b) which are mostly expressed in skeletal muscle at different developmental stages.
Functional characterization of the activity of these channels reveals many similitudes with their mammalian counterparts, although they are less sensitive to 9‐AC and acidic pH inverts their voltage dependence of gating.
Reduction of clc‐1a/b expression hampers spontaneous and mechanically stimulated movement which could be reverted by expression of human ClC‐1.
Myotonia‐like symptoms caused by clc‐1a/b depletion can be reverted by mexiletine, suggesting that this model could be used to find novel therapies for myotonia.
Brainstem neuronal responses to transcutaneous auricular and cervical vagus nerve stimulation in rats
Authors: Owens Misty M. , Jacquemet Vincent , Napadow Vitaly , Lewis Nicole , Beaumont Eric 
Published: July 2024

AbstractTranscutaneous auricular vagus nerve stimulation (taVNS) targets subcutaneous axons in the auricular branch of the vagus nerve at the outer ear. Its non‐invasive nature makes it a potential treatment for various disorders. taVNS induces neuromodulatory effects within the nucleus of the solitary tract (NTS), and due to its widespread connectivity, the NTS acts as a gateway to elicit neuromodulation in both higher‐order brain regions and other brainstem nuclei (e.g. spinal trigeminal nucleus; Sp5). Our objective was to examine stimulation parameters on single‐neuron electrophysiological responses in α‐chloralose‐anaesthetized Sprague–Dawley rats within NTS and Sp5. taVNS was also compared to traditional cervical VNS (cVNS) on single neuronal activation. Specifically, electrophysiological extracellular recordings were evaluated for a range of frequency and intensity parameters (20–250 Hz, 0.5–1.0 mA). Neurons were classified as positive, negative or non‐responders based on increased activity, decreased activity or no response during stimulation, respectively. Frequency‐dependent analysis showed that 20 and 100 Hz generated the highest proportion of positive responders in NTS and Sp5 with 1.0 mA intensities eliciting the greatest magnitude of response. Comparisons between taVNS and cVNS revealed similar parameter‐specific activation for caudal NTS neuronal populations; however, individual neurons showed different activation profiles. The latter suggests that cVNS and taVNS send afferent input to NTS via different neuronal pathways. This study demonstrates differential parameter‐specific taVNS responses and begins an investigation of the mechanisms responsible for taVNS modulation. Understanding the neuronal pathways responsible for eliciting neuromodulatory effects will enable more tailored taVNS treatments in various clinical disorders.
imageKey points
Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non‐invasive alternative to invasive cervical vagus nerve stimulation (cVNS) by activating vagal afferents in the ear to induce neuromodulation.
Our study evaluated taVNS effects on neuronal firing patterns in the nucleus of the solitary tract (NTS) and spinal trigeminal nucleus (Sp5) and found that 20 and 100 Hz notably increased neuronal activity during stimulation in both nuclei.
Increasing taVNS intensity not only increased the number of neurons responding in Sp5 but also increased the magnitude of response, suggesting a heightened sensitivity to taVNS compared to NTS.
Comparisons between cVNS and taVNS revealed similar overall activation but different responses on individual neurons, indicating distinct neural pathways.
These results show parameter‐specific and nuclei‐specific responses to taVNS and confirm that taVNS can elicit responses comparable to cVNS at the neuronal level, but it does so through different neuronal pathways.
Transforming Oil Well Drilling: Prediction of Real-Time Rate of Penetration With Novel Machine Learning Approach in Varied Lithological Formations
Authors: Gupta Raunak , Bhui Uttam K. 
Published: July 2024

Abstract
The rate of penetration (ROP) is crucial for efficient and cost-effective oil well drilling. This study introduces a novel prediction method for the rate of penetration that pioneers the use of different types of drill bits and lithologies with traditional drilling parameters. Utilizing a comprehensive dataset from 12 diverse wells, it employs advanced machine learning techniques including an adaptive moment estimation-based artificial neural network for developing the algorithm. By integrating various controllable and uncontrollable drilling parameters, the random forest, decision tree, and K-nearest neighbor models demonstrated superior performance. These models achieved a coefficient of determination of approximately 98% and a mean absolute percentage error of only 3.30%, outperforming traditional models such as Maurer and Bingham, as well as other machine learning models. Using 500 testing and 2000 training data points from real-time measurements reduced the risk of overfitting and enhanced model effectiveness in different drilling environments. The predictions of the developed model can modify the input parameters to increase rate of penetration through various formations. This study highlights the importance of lithology and utilizes feature ablation analysis to transition from a black-to-white box model. Additionally, based on the predictions of this work, post-drilling analysis can reduce costs and time by only requiring surface-measured parameters and eliminates the need for extensive study on geological, laboratory, and drilling data prior to drilling activities. This integrated approach sets new standards for machine learning in drilling, representing a robust and adaptive strategy to enhance operational efficiency.
Concept of Error Compensation for Nonorthogonality in Two-Axis Displacement Measurement System Utilizing Single Grating Scale and Littrow Configuration
Authors: Michihata Masaki , Fujimura Souki , Masui Shuzo , Takahashi Satoru 
Published: July 2024

Abstract
In this study, we proposed a measurement system that compensates for orthogonality in planar stages and demonstrated its principle. The proposed measurement system consists of a single diffraction grating scale placed diagonally across the stage and two interferometers aligned in a Littrow configuration, which are sensitive only to stage displacement in the optical axis direction. The direction of measurement is determined with high accuracy by the pitch of the diffraction grating and optical wavelength of the laser, allowing orthogonality compensation. In the experiments, we demonstrated that the interferometer aligned at Littrow configuration was capable of measuring the stage displacement component in the optical axis direction. In the discussion, our assessment of orthogonality identified two crucial factors: (1) how accurately the Littrow configuration can be aligned and (2) the accuracy of the pitch of the grating scale.
Phenazine-1 carboxylic acid of
Pseudomonas aeruginosa
induces the expression of
Staphylococcus aureus
Tet38 MDR efflux pump and mediates resistance to phenazines and antibiotics
Authors: Truong-Bolduc Q. C. , Wang Y. , Lawton B. G. , Brown Harding H. , Yonker L. M. , Vyas J. M. , Hooper D. C. 
Published: July 2024

ABSTRACT

In this study, we showed that phenazine-1 carboxylic acid (PCA) of
Pseudomonas aeruginosa
induced the expression of Tet38 efflux pump triggering
Staphylococcus aureus
resistance to tetracycline and phenazines. Exposure of
S. aureus
RN6390 to supernatants of
P. aeruginosa
PA14 and its pyocyanin (PYO)-deficient mutants showed that
P. aeruginosa
non-PYO phenazines could induce the expression of Tet38 efflux pump. Direct exposure of RN6390 to PCA compound at 0.25× MIC led to a five-fold increase in
tet38
transcripts. Expression of Tet38 protein was identified through confocal microscopy using RN6390(pRN-
tet38
p-
yfp
) that expressed YFP under control of the
tet38
promoter by PCA at 0.25× MIC. The MICs of PCA of a Tet38-overexpressor and a
Δtet38
mutant showed a three-fold increase and a two-fold decrease, respectively, compared with that of wild-type. Pre-exposure of RN6390 to PCA (0.25× MIC) for 1 hour prior to addition of tetracycline (1× or 10× MIC) improved bacteria viability of 1.5-fold and 2.6-fold, respectively, but addition of NaCl 7% together with tetracycline at 10× MIC reduced the number of viable PCA-exposed RN6390 of a 2.0-log
10
CFU/mL. The transcript levels of
tetR21
, a repressor of
tet38
, decreased and increased two-fold in the presence of PCA and NaCl, respectively, suggesting that the effects of PCA and NaCl on
tet38
production occurred through TetR21 expression. These data suggest that PCA-induced Tet38 protects
S. aureus
against tetracycline during coinfection with
P. aeruginosa
; however, induced
tet38
-mediated
S. aureus
resistance to tetracycline is reversed by NaCl 7%, a nebulized treatment used to enhance sputum mobilization in CF patients.
Accounting for cellular-level variation in lysis: implications for virus–host dynamics
Authors: Dominguez-Mirazo Marian , Harris Jeremy D. , Demory David , Weitz Joshua S. 
Published: July 2024

ABSTRACT

Viral impacts on microbial populations depend on interaction phenotypes—including viral traits spanning the adsorption rate, latent period, and burst size. The latent period is a key viral trait in lytic infections. Deﬁned as the time from viral adsorption to viral progeny release, the latent period of bacteriophage is conventionally inferred via one-step growth curves in which the accumulation of free virus is measured over time in a population of infected cells. Developed more than 80 years ago, one-step growth curves do not account for cellular-level variability in the timing of lysis, potentially biasing inference of viral traits. Here, we use nonlinear dynamical models to understand how individual-level variation of the latent period impacts virus–host dynamics. Our modeling approach shows that inference of the latent period via one-step growth curves is systematically biased—generating estimates of shorter latent periods than the underlying population-level mean. The bias arises because variability in lysis timing at the cellular level leads to a fraction of early burst events, which are interpreted, artefactually, as an earlier mean time of viral release. We develop a computational framework to estimate latent period variability from joint measurements of host and free virus populations. Our computational framework recovers both the mean and variance of the latent period within simulated infections including realistic measurement noise. This work suggests that reframing the latent period as a distribution to account for variability in the population will improve the study of viral traits and their role in shaping microbial populations.

IMPORTANCE
Quantifying viral traits—including the adsorption rate, burst size, and latent period—is critical to characterize viral infection dynamics and develop predictive models of viral impacts across scales from cells to ecosystems. Here, we revisit the gold standard of viral trait estimation—the one-step growth curve—to assess the extent to which assumptions at the core of viral infection dynamics lead to ongoing and systematic biases in inferences of viral traits. We show that latent period estimates obtained via one-step growth curves systematically underestimate the mean latent period and, in turn, overestimate the rate of viral killing at population scales. By explicitly incorporating trait variability into a dynamical inference framework that leverages both virus and host time series, we provide a practical route to improve estimates of the mean and variance of viral traits across diverse virus–microbe systems.
Mud cohesion governs unvegetated meander migration rates and deposit architecture
Authors: Douglas Madison M. , Miller Kimberly Litwin , Lamb Michael P. 
Published: July 2024

Abstract
Vegetation is thought to be a main source of riverbank cohesion, enabling meandering and a deposit architecture characterized by sandy channel belts isolated in mudstone. However, early Earth and Mars had meandering rivers without vegetation, implying that other sources of bank strength can allow meandering with potentially different deposit characteristics. Here we studied the Amargosa River in Death Valley, California, USA, as a modern analog of meandering rivers without vegetation. We monitored flow and erosion at two bends and used radiocarbon dating of strandlines to quantify flood frequency. We also sampled cutbank mud and constrained an erosion theory using flume experiments. Cutbank erosion occurred for floods with &gt;2 yr recurrence intervals, and 18 cm occurred for an ~6 yr reoccurrence, bankfull event. Mud set the rate of meander migration: salt crusts rapidly and completely dissolved during floods, vegetation was absent, and mud entrainment theory matched observed erosion rates. Flood-frequency analysis showed that most bank erosion occurs at flows below bankfull, challenging the threshold channel hypothesis. We used meander migration rates to constrain the time scale of channel-belt formation and compared it to the time scale of avulsion. These calculations, combined with floodplain facies mapping and core sedimentology, indicated a likely deposit architecture of sandy point bar accretion sets intermixed with muddy overbank facies. This deposit architecture is characteristic of vegetated meandering rivers, but due to muddy banks, occurred for the Amargosa River in the absence of plants.
Oceanic anoxic event 3 in Arctic Canada—Arc volcanism and ocean fertilization drove anoxia
Authors: Grasby Stephen E. , Crowley James L. , Mohr Michael T. , Percival Jeanne B. , Ardakani Omid H. , Galloway Jennifer , Bringué Manuel , Smith I. Rod , Yuan Wanju 
Published: July 2024

Abstract
The global extent of the Late Cretaceous oceanic anoxic event 3 (OAE 3) remains uncertain. It is not considered to have extended into the Boreal Realm. To test this, we examined Late Cretaceous organic- and metal-rich black mudstones of the Smoking Hills Formation in Arctic Canada. New high-precision U-Pb zircon ages indicate that deposition of the Smoking Hills Formation (88.535–78.230 Ma) was temporally coincident with OAE 3, indicating a much broader global expression of this event than previously thought. OAE 3 was likely manifest throughout the proto–Arctic Ocean (now Arctic Canada). Abundant bentonite layers and cryptotephra within the Smoking Hills Formation have rare earth element (REE) patterns that are consistent with ashfall derived from Cretaceous arc volcanism. Anomalously high organic matter content in the Smoking Hills Formation, as compared to underlying and overlying units, suggests that ocean fertilization led to enhanced productivity and metal drawdown. A peak in arc volcanism may have been a key driver of the OAE 3 event. We also explored the potential use of cadmium as a geochemical marker of volcanism and show that high volcanogenic metal loading could affect the use of Cd and other proxies for marine productivity (e.g., Zn, Cu).
Healthcare spending for non-fatal falls among older adults, USA
Authors: Haddad Yara K , Miller Gabrielle F , Kakara Ramakrishna , Florence Curtis , Bergen Gwen , Burns Elizabeth Rose , Atherly Adam 
Published: July 2024

BackgroundThe older adult (65+) population in the USA is increasing and with it the number of medically treated falls. In 2015, healthcare spending attributable to older adult falls was approximately US$50 billion. We aim to update the estimated medical expenditures attributable to older adult non-fatal falls.MethodsGeneralised linear models using 2017, 2019 and 2021 Medicare Current Beneficiary Survey and cost supplement files were used to estimate the association of falls with healthcare expenditures while adjusting for demographic characteristics and health conditions in the model. To portion out the share of total healthcare spending attributable to falls versus not, we adjusted for demographic characteristics and health conditions, including self-reported health status and certain comorbidities associated with increased risk of falling or higher healthcare expenditure. We calculated a fall-attributable fraction of expenditure as total expenditures minus total expenditures with no falls divided by total expenditures. We applied the fall-attributable fraction of expenditure from the regression model to the 2020 total expenditures from the National Health Expenditure Data to calculate total healthcare spending attributable to older adult falls.ResultsIn 2020, healthcare expenditure for non-fatal falls was US$80.0 billion, with the majority paid by Medicare.ConclusionHealthcare spending for non-fatal older adult falls was substantially higher than previously reported estimates. This highlights the growing economic burden attributable to older adult falls and these findings can be used to inform policies on fall prevention efforts in the USA.
AFFINE MODELS WITH PATH-DEPENDENCE UNDER PARAMETER UNCERTAINTY AND THEIR APPLICATION IN FINANCE
Authors: GEUCHEN BENEDIKT , OBERPRILLER KATHARINA , SCHMIDT THORSTEN 
Published: July 2024

In this paper, we consider one-dimensional generalized affine processes under the paradigm of Knightian uncertainty (the so-called nonlinear generalized affine models). This extends and generalizes previous results in Fadina et al. ( 2019 ) and Lütkebohmert et al. ( 2022 ). In particular, we study the case when the payoff is allowed to depend on the path, like it is the case for barrier options or Asian options. To this end, we develop the path-dependent setting for the value function relying on functional Itô calculus. We establish a dynamic programming principle which then leads to a functional nonlinear Kolmogorov equation describing the evolution of the value function. While for Asian options, the valuation can be traced back to PDE methods, this is no longer possible for more complicated payoffs like barrier options. To handle such payoffs in an efficient manner, we approximate the functional derivatives with deep neural networks and show that the numerical valuation under parameter uncertainty is highly tractable. Finally, we consider the application to structural modelling of credit and counterparty risk, where both parameter uncertainty and path-dependence are crucial and the approach proposed here opens the door to efficient numerical methods in this field.
Computational Homogenization for Inverse Design of Surface-based Inflatables
Authors: Ren Yingying , Panetta Julian , Suzuki Seiichi , Kusupati Uday , Isvoranu Florin , Pauly Mark 
Published: July 2024

Surface-based inflatables are composed of two thin layers of nearly inextensible sheet material joined together along carefully selected fusing curves. During inflation, pressure forces separate the two sheets to maximize the enclosed volume. The fusing curves restrict this expansion, leading to a spatially varying in-plane contraction and hence metric frustration. The inflated structure settles into a 3D equilibrium that balances pressure forces with the internal elastic forces of the sheets.
We present a computational framework for analyzing and designing surface-based inflatable structures with arbitrary fusing patterns. Our approach employs numerical homogenization to characterize the behavior of parametric families of periodic inflatable patch geometries, which can then be combined to tessellate the sheet with smoothly varying patterns. We propose a novel parametrization of the underlying deformation space that allows accurate, efficient, and systematical analysis of the stretching and bending behavior of inflated patches with potentially open boundaries.
We apply our homogenization algorithm to create a database of geometrically diverse fusing patterns spanning a wide range of material properties and deformation characteristics. This database is employed in an inverse design algorithm that solves for fusing curves to best approximate a given input target surface. Local patches are selected and blended to form a global network of curves based on a geometric flattening algorithm. These fusing curves are then further optimized to minimize the distance of the deployed structure to target surface. We show that this approach offers greater flexibility to approximate given target geometries compared to previous work while significantly improving structural performance.