A new look at TFPI inhibition of factor X activation.

Blood coagulation is a vital physiological process involving a complex network of biochemical reactions, which converge to form a blood clot that repairs vascular injury. This process unfolds in three phases: initiation, amplification, and propagation, ultimately leading to thrombin formation. Coagulation begins when tissue factor (TF) is exposed on an injured vessel's wall.

Percolation transitions in a binary mixture of active Brownian particles with different softness.

Homogeneous active Brownian particle (ABP) systems with purely repulsive interactions are considered to exhibit a simple phase behavior, but various physical attributes of active entities can lead to variation in the collective dynamics. Recent studies have shown that even homogeneous ABPs exhibit complex behavior due to an interplay between particle softness and motility. However, the heterogeneity in the composition of ABPs has not been explored yet.

The value of long-duration energy storage under various grid conditions in a zero-emissions future.

Long-duration energy storage (LDES) is a key resource in enabling zero-emissions electricity grids but its role within different types of grids is not well understood. Using the Switch capacity expansion model, we model a zero-emissions Western Interconnect with high geographical resolution to understand the value of LDES under 39 scenarios with different generation mixes, transmission expansion, storage costs, and storage mandates. We find that a) LDES is particularly valuable in majority wind-powered regions and regions with diminishing hydropower generation, b) seasonal operation of storage becomes cost-effective if storage capital costs fall below US$5 kWh, and c) mandating the installation of enough LDES to enable year-long storage cycles would reduce electricity prices during times of high demand by over 70%.

The language network ages well: Preserved selectivity, lateralization, and within-network functional synchronization in older brains.

Healthy aging is associated with structural and functional brain changes. However, cognitive abilities differ from one another in how they change with age: whereas executive functions, like working memory, show age-related decline, aspects of linguistic processing remain relatively preserved (Hartshorne et al., 2015).

Migration and proliferation drive the emergence of patterns in co-cultures of differentiating vascular progenitor cells.

Vascular cells self-organize into unique structures guided by cell proliferation, migration, and/or differentiation from neighboring cells, mechanical factors, and/or soluble signals. However, the relative contribution of each of these factors remains unclear. Our objective was to develop a computational model to explore the different factors affecting the emerging micropatterns in 2D.

Water, not carbon, drives drought-constraints on stem terpene defense against simulated bark beetle attack in Pinus edulis.

Drought predisposes forest trees to bark beetle-induced mortality, but the physiological mechanisms remain unclear. While drought-induced water and carbon limitations have been implicated in defensive failure and tree susceptibility, evidence demonstrating how these factors interact is scarce. We withheld water from mature, potted Pinus edulis and subsequently applied a double-stem girdle to inhibit carbohydrate transport from the crown and roots.

Coiled Coil Peptide Tiles (CCPTs): Expanding the Peptide Building Block Design with Multivalent Peptide Macrocycles.

Owing to their synthetic accessibility and protein-mimetic features, peptides represent an attractive biomolecular building block for the fabrication of artificial biomimetic materials with emergent properties and functions. Here, we expand the peptide building block design space through unveiling the design, synthesis, and characterization of novel, multivalent peptide macrocycles (96mers), termed coiled coil peptide tiles (CCPTs). CCPTs comprise multiple orthogonal coiled coil peptide domains that are separated by flexible linkers.

The fastest-growing and most destructive fires in the US (2001 to 2020).

The most destructive and deadly wildfires in US history were also fast. Using satellite data, we analyzed the daily growth rates of more than 60,000 fires from 2001 to 2020 across the contiguous US. Nearly half of the ecoregions experienced destructive fast fires that grew more than 1620 hectares in 1 day.

Mathematical modeling identifies clotting factor combinations that modify thrombin generation in normal and factor VIII-, IX-, or XI-deficient blood.

Background: In healthy individuals, plasma levels of clotting proteins naturally vary within a range of 50% to 150% of their mean values. We do not know how these variations modify thrombin generation.

Objectives: To assess the impact of protein level variations on simulated thrombin generation in normal and factor (F)VIII-, FIX-, or FXI-deficient blood.

Ballistic to diffusive transition for swimmers in a periodic vortex array.

We study the transport of rigid ellipsoidal swimmers in a periodic vortex array via numerical simulation and dynamical systems analysis. Via ensemble simulations, we show the counterintuitive result that slower swimming speeds can generate fast ballistic transport, while faster swimming speeds generate chaotic and diffusive transport, which is inherently slower in the long run. To explain this, we use the symmetry of the flow to construct a time-reversible Poincaré return map on a two-dimensional surface of section in phase space.

Tiletamine/Zolazepam and Ketamine with Dexmedetomidine (TKD) Cocktail Is as Effective as Tiletamine/Zolazepam and Ketamine with Xylazine (TKX) in Providing Pig General Anesthesia.

This study aimed to evaluate dexmedetomidine as an alternative to xylazine in pigs. We compared TKD (0.05 mL/kg) to TKX (0.

Underrepresented minority faculty in the USA face a double standard in promotion and tenure decisions.

Underrepresented minority (URM) faculty face challenges in many domains of academia, from university admissions to grant applications. We examine whether this translates to promotion and tenure (P&T) decisions. Data from five US universities on 1,571 faculty members' P&T decisions show that URM faculty received 7% more negative votes and were 44% less likely to receive unanimous votes from P&T committees.

Persistence of Structural Lubricity on Contaminated Graphite: Rejuvenation, Aging, and Friction Switches.

Using atomic force microscopy experiments and molecular dynamics simulations of gold nanoislands on graphite, we investigate why ultralow friction commonly associated with structural lubricity can be observed even under ambient conditions. Measurements conducted within a few days after sample synthesis reveal previously undiscovered phenomena in structurally lubric systems: , a drop in kinetic friction of an order of magnitude shortly after the onset of sliding; , a significant increase in kinetic friction forces after a rest period of 30 min or more; and , spontaneous jumps between distinct friction branches. These three effects are drastically suppressed a few weeks later.

How to scan naked DNA using promiscuous recognition and no clamping: a model for pioneer transcription factors.

Most DNA scanning proteins uniquely recognize their cognate sequence motif and slide on DNA assisted by some sort of clamping interface. The pioneer transcription factors that control cell fate in eukaryotes must forgo both elements to gain access to DNA in naked and chromatin forms; thus, whether or how these factors scan naked DNA is unknown. Here, we use single-molecule techniques to investigate naked DNA scanning by the Engrailed homeodomain (enHD) as paradigm of highly promiscuous recognition and open DNA binding interface.

Charge balanced aggregation: A universal approach to aqueous organic nanocrystals.

Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method.

Exposure to acute ambient temperature extremes and neonatal intensive care unit admissions: A case-crossover study.

Background: Extreme in utero temperatures have been associated with adverse birth outcomes, including preterm birth and low birthweight. However, there is limited evidence on associations with neonatal intensive care unit (NICU) admissions, which reflect a range of poor neonatal health outcomes.

Methods: This case-crossover study assesses the associations between ambient temperature changes during the week of delivery and risk of NICU admission.

Charting Diagnostic Safety: Exploring Patient-Provider Discordance in Medical Record Documentation.

Background: The 21st Century Cures Act enables patients to access their medical records, thus providing a unique opportunity to engage patients in their diagnostic journey.

Objective: To explore the concordance between patients' self-reported diagnostic concerns and clinician-interpreted information in their electronic health records.

Design: We conducted a mixed-methods analysis of a cohort of 467 patients who completed a structured data collection instrument (the Safer Dx Patient) to identify diagnostic concerns while reviewing their clinician's notes.

Coassembly and binning of a twenty-year metagenomic time-series from Lake Mendota.

The North Temperate Lakes Long-Term Ecological Research (NTL-LTER) program has been extensively used to improve understanding of how aquatic ecosystems respond to environmental stressors, climate fluctuations, and human activities. Here, we report on the metagenomes of samples collected between 2000 and 2019 from Lake Mendota, a freshwater eutrophic lake within the NTL-LTER site. We utilized the distributed metagenome assembler MetaHipMer to coassemble over 10 terabases (Tbp) of data from 471 individual Illumina-sequenced metagenomes.

Rational Design of High Affinity Interaction Between CC Chemokine Binding Protein vCCI and CCL17/TARC.

The poxvirus-derived protein vCCI (viral CC chemokine inhibitor) binds almost all members of the CC chemokine family with nanomolar affinity, inhibiting their pro-inflammatory actions. Understanding the affinity and specificity of vCCI could lead to new anti-inflammatory therapeutics. CCL17, also known as TARC, is unusual among CC chemokines by having only micromolar binding to vCCI.

GPU-accelerated on-the-fly nonadiabatic semiclassical dynamics.

GPU-accelerated on-the-fly nonadiabatic dynamics is enabled by interfacing the linearized semiclassical dynamics approach with the TeraChem electronic structure program. We describe the computational workflow of the "PySCES" code interface, a Python code for semiclassical dynamics with on-the-fly electronic structure, including parallelization over multiple GPU nodes. We showcase the abilities of this code and present timings for two benchmark systems: fulvene solvated in acetonitrile and a charge transfer system in which a photoexcited zinc-phthalocyanine donor transfers charge to a fullerene acceptor through multiple electronic states on an ultrafast timescale.

Childhood family socioeconomic status is linked to adult brain electrophysiology.

A large body of research has linked childhood family socioeconomic status (SES) to neurodevelopment in childhood and adolescence. However, it remains unclear to what extent childhood family SES relates to brain functioning in adulthood. To address this gap, the present study investigated the associations between retrospective accounts of objective and subjective childhood family SES and two well-established electrophysiological indices of brain functioning in adulthood-the MMN and P3b event-related potentials (ERP) components, as neural correlates of automatic change detection and cognitive control respectively.

Local carbon reserves are insufficient for phloem terpene induction during drought in Pinus edulis in response to bark beetle-associated fungi.

Stomatal closure during drought inhibits carbon uptake and may reduce a tree's defensive capacity. Limited carbon availability during drought may increase a tree's mortality risk, particularly if drought constrains trees' capacity to rapidly produce defenses during biotic attack. We parameterized a new model of conifer defense using physiological data on carbon reserves and chemical defenses before and after a simulated bark beetle attack in mature Pinus edulis under experimental drought.

Protein surface chemistry encodes an adaptive tolerance to desiccation.

Cellular desiccation - the loss of nearly all water from the cell - is a recurring stress in an increasing number of ecosystems that can drive protein unfolding and aggregation. For cells to survive, at least some of the proteome must resume function upon rehydration. Which proteins tolerate desiccation, and the molecular determinants that underlie this tolerance, are largely unknown.