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Prevalent resistance to inhibitors that target the influenza A M2 proton channel has necessitated a continued drug design effort, supported by a sustained study of the mechanism of channel function and inhibition. Recent high-resolution X-ray crystal structures present the first opportunity to see how the adamantyl amine class of inhibitors bind to M2 and disrupt and interact with the channel's water network, providing insight into the critical properties that enable their effective inhibition in wild-type M2. In this work, we examine the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. MS-RMD, unlike classical molecular dynamics, models the hydrated proton (hydronium-like cation) as a dynamic excess charge defect and allows bonds to break and form, capturing the intricate interactions between the hydrated excess proton, protein atoms, and water. Through this, we show that the ammonium group of the inhibitors is effectively positioned to take advantage of the channel's natural ability to stabilize an excess protonic charge and act as a hydronium mimic. Additionally, we show that the channel is especially stable in the drug binding region, highlighting the importance of this property for binding the adamantane group. Finally, we characterize an additional hinge point near Val27, which dynamically responds to charge and inhibitor binding. Altogether, this work further illuminates a dynamic understanding of the mechanism of drug inhibition in M2, grounded in the fundamental properties that enable the channel to transport and stabilize excess protons, with critical implications for future drug design efforts.

The influenza A M2 protein is an acid-activated proton channel responsible for acidification of the inside of the virus, a critical step in the viral life cycle. This channel has four central histidine residues that form an acid-activated gate, binding protons from the outside until an activated state allows proton transport to the inside. While previous work has focused on proton transport through the channel, the structural and dynamic changes that accompany proton flux and enable activation have yet to be resolved. In this study, extensive Multiscale Reactive Molecular Dynamics simulations with explicit Grotthuss-shuttling hydrated excess protons are used to explore detailed molecular-level interactions that accompany proton transport in the +0, + 1, and +2 histidine charge states. The results demonstrate how the hydrated excess proton strongly influences both the protein and water hydrogen-bonding network throughout the channel, providing further insight into the channel's acid-activation mechanism and rectification behavior. We find that the excess proton dynamically, as a function of location, shifts the protein structure away from its equilibrium distributions uniquely for different pH conditions consistent with acid-activation. The proton distribution in the xy-plane is also shown to be asymmetric about the channel's main axis, which has potentially important implications for the mechanism of proton conduction and future drug design efforts.

Two-year college mathematics teaching has interesting challenges, and it helps to have a national organization representing the profession that provides professional development, issues position statements on relevant topics, and cultivates leaders. This chapter illustrates how the AMATYC organization provides these services.

We present a hierarchical Bayesian pipeline, BP3M, that measures positions, parallaxes, and proper motions (PMs) for cross-matched sources between Hubble Space Telescope (HST) images and Gaia—even for sparse fields (N * < 10 per image)—expanding from the recent GaiaHub tool. This technique uses Gaia-measured astrometry as priors to predict the locations of sources in HST images, and is therefore able to put the HST images onto a global reference frame without the use of background galaxies/QSOs. Testing our publicly available code in the Fornax and Draco dwarf spheroidal galaxies, we measure PMs that are a median of 8–13 times more precise than Gaia DR3 alone for 20.5 < G < 21 mag. We are able to explore the effect of observation strategies on BP3M astrometry using synthetic data, finding an optimal strategy to improve parallax and position precision at no cost to the PM uncertainty. Using 1619 HST images in the sparse COSMOS field (median nine Gaia sources per HST image), we measure BP3M PMs for 2640 unique sources in the 16 < G < 21.5 mag range, 25% of which have no Gaia PMs; the median BP3M PM uncertainty for 20.25 < G < 20.75 mag sources is 0.44 mas yr−1 compared to 1.03 mas yr−1 from Gaia, while the median BP3M PM uncertainty for sources without Gaia-measured PMs (20.75 < G < 21.5 mag) is 1.16 mas yr−1. The statistics that underpin the BP3M pipeline are a generalized way of combining position measurements from different images, epochs, and telescopes, which allows information to be shared between surveys and archives to achieve higher astrometric precision than that from each catalog alone. [ABSTRACT FROM AUTHOR]

Understanding students' readiness for precalculus and calculus at the community college level is critical not only because of the key role community colleges play in higher education but also because calculus remains a gateway course for students in advancing to higher level mathematics. The Algebra and Precalculus Concept Readiness Assessment for Community Colleges (APCR-CC) was designed to investigate community college students' quantitative reasoning abilities and conceptual understanding in algebra. The present study investigates the psychometric properties of the APCR-CC instrument using item response theory based on a sample of intermediate and college algebra students from six community colleges collected in a pretest (N = 1,131) and posttest (N = 772) setting. We examine unidimensionality, item fit, local item independence, measurement invariance, and sensitivity to instruction. Our findings suggest that the APCR-CC instrument is sufficiently characterized by one underlying construct, local dependence does not seem to be an issue, and 80% of the items in the APCR-CC instrument are sensitive to instruction.

We analyze four epochs of Hubble Space Telescope imaging over 18 yr for the Draco dwarf spheroidal galaxy. We measure precise proper motions for hundreds of stars and combine these with existing line-of-sight (LOS) velocities. This provides the first radially resolved 3D velocity dispersion profiles for any dwarf galaxy. These constrain the intrinsic velocity anisotropy and resolve the mass–anisotropy degeneracy. We solve the Jeans equations in oblate axisymmetric geometry to infer the mass profile. We find the velocity dispersion to be radially anisotropic along the symmetry axis and tangentially anisotropic in the equatorial plane, with a globally averaged value β B ¯ = − 0.20 − 0.53 + 0.28 , (where 1 – β B ≡ 〈 v tan 2 〉 / 〈 v rad 2 〉 in 3D). The logarithmic dark matter (DM) density slope over the observed radial range, Γdark, is − 0.83 − 0.37 + 0.32 , consistent with the inner cusp predicted in ΛCDM cosmology. As expected given Draco's low mass and ancient star formation history, it does not appear to have been dissolved by baryonic processes. We rule out cores larger than 487, 717, and 942 pc at 1 σ, 2 σ, and 3 σ confidence, respectively, thus imposing important constraints on the self-interacting DM cross section. Spherical models yield biased estimates for both the velocity anisotropy and the inferred slope. The circular velocity at our outermost data point (900 pc) is 24.19 − 2.97 + 6.31 km s − 1 . We infer a dynamical distance of 75.37 − 4.00 + 4.73 kpc and show that Draco has a modest LOS rotation, with v / σ = 0.22 ± 0.09 . Our results provide a new stringent test of the so-called "cusp–core" problem that can be readily extended to other dwarfs. [ABSTRACT FROM AUTHOR]

We estimate the mass of the Large Magellanic Cloud (LMC) using the kinematics of 30 LMC globular clusters (GCs). We combine proper motions measured with the Hubble Space Telescope, Gaia, or a combination of the two, from a recent study by Bennet et al. with literature line-of-sight velocities (LOSVs) to give three components of motion. With these, we derive a 3D velocity dispersion anisotropy β = − 0.72 − 1.07 + 0.62 , consistent with the GCs forming a flattened system with significant azimuthal motion. We then apply a tracer mass estimator and measure an enclosed mass M (< 13.2 kpc) = 2.66 − 0.36 + 0.42 × 10 10 M ⊙. This is broadly consistent with results from previous studies of the LOSVs of GCs and other luminous tracers. Assuming a cosmologically constrained Navarro–Frenk–White distribution for the dark matter, this implies a virial mass M virial = 1.80 − 0.54 + 1.05 × 10 11 M ⊙. Despite being an extrapolation by almost an order of magnitude in radius, this result is consistent with published estimates from other methods that are directly sensitive to the LMC's total mass. Our results support the conclusion that the LMC is approximately 17 − 6 + 10 % of the Milky Way's mass, making it a significant contributor to the Local Group potential. [ABSTRACT FROM AUTHOR]

In this paper, we examine the relationships between teachers' subject matter preparation and experience in teaching and their performance on an instrument measuring mathematical knowledge for teaching Algebra 1. We administered the same instrument to two different samples of teachers−high school practicing teachers and community college faculty − who teach the same algebra content in different levels of institutions, and we compared the performance of the two different samples and the relationships between the measured knowledge and their educational and teaching background across the samples. The comparison suggested that the community college faculty possess a higher level of mathematical knowledge for teaching Algebra 1 than high school teachers. The subsequent analyses using the Multiple Indicator Multiple Causes (MIMIC) models based on our hypothesis on the factors contributing to the differences in the knowledge between the two teacher samples suggest that experience teaching advanced algebra courses has positive effects on the mathematical knowledge for teaching Algebra 1 in both groups. Highlighting the positive effect of algebra-based teaching experience on test performance, we discuss the implications of the impact of subject specific experience in teaching on teachers' mathematical content knowledge for teaching. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) and posttraumatic stress disorder (PTSD) are costly and highly co-occurring diagnoses, particularly among veterans, suggesting a need to understand this comorbidity and effectively treat both disorders among this population. The current study aimed to examine substance use outcomes among post-9/11 veterans and service members (N = 48) who completed a two-week intensive outpatient program with concurrent treatment for and PTSD using Prolonged Exposure and substance use. Substance use was assessed at two weeks and three months posttreatment. The intensive program had high completion rates and demonstrated decreases in substance use at two weeks and three months posttreatment. Additionally, lower PTSD symptoms at treatment completion were related to less substance use posttreatment. Concurrent intensive treatment of PTSD and SUDs can lead to symptom improvement in a short period of time. Findings support the self-medication model, such that PTSD symptoms at treatment completion were related to substance use at follow-up. [ABSTRACT FROM AUTHOR]

Despite evidence that genetic variation contributes to aggression, few studies have examined how genetic variation contributes to IPA specifically. In the current study, 69 couples from a Midwestern university completed self-report measures of IPA, childhood trauma exposure, and hazardous alcohol use, and were randomly assigned to consume either a placebo or alcohol beverage before participating in an analogue aggression task against their partner. Genetic risk (i.e., association with lower transcriptional efficiency) for aggression was measured with a polygenic risk score (PRS) created from four polymorphisms (HTR1B rs13212041, HTR2B rs6437000, 5-HTTLPR, and MAOA uVNTR). Among individuals with a low PRS, individuals who consumed alcohol (BrAC =0.07%) showed greater unprovoked IPA than individuals who consumed a placebo. Findings contribute to our limited understanding regarding the etiology of IPA and suggest that individuals who have increased transcriptional activity in certain serotonin system genes may be at higher risk of IPA when intoxicated., Author(s): Christa C. Christ [sup.1] , Laura E. Watkins [sup.2] , David DiLillo [sup.3] , Scott F. Stoltenberg [sup.3] [sup.4] Author Affiliations: (1) Department of Psychology, Hamilton College, 0000 0004 [...]

This commentary articulates the need to investigate problems of mathematics instruction at community colleges. The authors briefly describe some features of this often-ignored institution and the current status of research. They also make an argument for how investigations of instruction in this setting can both advance understanding of this particular context and give practitioners tools to deal with pressures from policymakers to show short-term results.

Background: The role of alcohol expectancies and evaluations (i.e., perceived outcomes of drinking and whether these outcomes are desirable) in alcohol-related intimate partner aggression (IPA) has been debated, with some researchers arguing that expectancies fully account for the alcohol-IPA relationship and others suggesting they play a minimal if any role in alcohol-related IPA. In the current study, we examine the impact of expectancies and evaluations on alcohol-related IPA observed in the lab, in order to clarify what impact, if any, alcohol expectancies have on alcohol-related IPA. Consistent with findings from laboratory studies examining general aggression, we expected that individuals who were intoxicated would display greater IPA than individuals who were sober, but that alcohol expectancies and evaluations would be unrelated to in vivo IPA. Method: Participants were 69 dating couples (total N = 138), randomly assigned to consume either an alcohol or placebo beverage. IPA was measured with an in vivo aggression task based on the Taylor Aggression Paradigm. Results: As expected, alcohol intoxication predicted in vivo IPA following provocation (p <.03), whereas alcohol expectancies and evaluations were not related to IPA. Conclusions: These findings provide further support that alcohol expectancies and evaluations play little if any role in alcohol-related IPA. Rather, intoxication likely increases risk for IPA through its physiological effects on perception and thought. Further, treatments targeting alcohol use, rather than beliefs about outcomes of drinking, may have a greater impact on alcohol-related IPA. [ABSTRACT FROM AUTHOR]

Objective: The authors conducted a meta-analysis of empirical studies investigating associations between indices of posttraumatic stress disorder (PTSD) and intimate relationship problems to empirically synthesize this literature. Method: A literature search using PsycINFO, Medline, Published International Literature on Traumatic Stress (PILOTS), and Dissertation Abstracts was performed. The authors identified 31 studies meeting inclusion criteria. Results: True score correlations ([rho]) revealed medium-sized associations between PTSD and intimate relationship discord ([rho] = 0.38, N = 7,973, K = 21), intimate relationship physical aggression perpetration ([rho] = 0.42, N = 4,630, K = 19), and intimate relationship psychological aggression perpetration ([rho] = 0.36, N = 1,501, K = 10). The strength of the association between PTSD and relationship discord was higher in military (vs. civilian) samples, and when the study was conducted in the United States (vs. other country), and the study represented a doctoral dissertation (vs. published article). The strength of the association between PTSD and physical aggression was higher in military (vs. civilian) samples, males (vs. females), community (vs. clinical) samples, studies examining PTSD symptom severity (vs. diagnosis), when the physical aggression measure focused exclusively on severe violence (vs. a more inclusive measure), and the study was published (vs. dissertation). For the PTSD-psychological aggression association, 98% of the variance was accounted for by methodological artifacts such as sampling and measurement error; consequently, no moderators were examined in this relationship. Conclusions: Findings highlight a need for the examination of models explaining the relationship difficulties associated with PTSD symptomatology and interventions designed to treat problems in both areas. (Contains 3 tables, 1 figure and 1 footnote.)

The objective of this study was the quantitative evaluation and comparison of the responses of the Hybrid III 5th percentile female (HIII-05F) and the 5th percentile female Test Device for Human Occupant Restraint (THOR-05F) anthropomorphic test devices (ATDs) subjected to abdominal loading conditions. The HIII-05F and THOR-05F were subjected to 3 different abdominal loading conditions: fixed-back belt pull (low compression), fixed-back belt pull (high compression), and free-back rigid bar impact at 6 m/s. The stroke of the impact was controlled to represent injurious and noninjurious loading conditions as observed in the experiments with postmortem human subjects (PMHS). Quantitative comparisons were made between the ATD abdominal force and compression responses and biofidelity corridors obtained from matched-pair PMHS tests under identical loading conditions, using the most recent version of the NHTSA Biofidelity Ranking System (BRS). The overall THOR-05F BRS scores across all tests (BRS score = 1.84) indicated good biofidelity. For the belt loading test conditions, the average BRS scores for both THOR-05F (BRS scores = 1.45 and 1.34) and HIII-05F (BRS scores = 1.42 and 1.01) showed good biofidelity. For the rigid bar loading condition, the THOR-05F (BRS score = 2.74) showed better biofidelity compared to HIII-05F (BRS score = 10.63), with the HIII-05F exhibiting poor performance in this condition. The average pressures recorded by the abdomen pressure twin sensors (APTS) in the current study ranged from 45 to 130 kPa, increasing proportionally with higher stroke and loading rate. Overall, the THOR-05F BRS scores were better than the HIII-05F BRS scores, which suggests improved biofidelity of the THOR-05F abdomen. The abdominal insert in the HIII-05F did not provide enough room for compression, leading to higher stiffness and occupant motion as observed in the rigid bar tests. Because of practical challenges in measuring abdomen deflection in a soft ATD abdomen component, use of APTS in THOR-05F provides the ability to measure the restraint loading to the abdomen and assess the risk of abdominal injury. With good BRS scores observed in this study for THOR-05F, pressure and other measurements included in the THOR-05F may be used to develop abdominal injury risk functions in the future. [ABSTRACT FROM AUTHOR]

We present the results of a spectroscopic survey of the outskirts of four globular – 1261, NGC 4590, NGC 1904, and NGC 1851 – covering targets within 1° from the cluster centres, with 2dF/AAOmega on the Anglo-Australian Telescope (AAT) and FLAMES on the very large telescope (VLT). We extracted chemo-dynamical information for individual stars, from which we estimated the velocity dispersion profile and the rotation of each cluster. The observations are compared to direct N -body simulations and appropriate limepy / spes models for each cluster to interpret the results. In NGC 1851, the detected internal rotation agrees with existing literature, and NGC  1261 shows some rotation signal beyond the truncation radius, likely coming from the escaped stars. We find that the dispersion profiles for both the observations and the simulations for NGC 1261, NGC 1851, and NGC 1904 do not decrease as the limepy / spes models predict beyond the truncation radius, where the N -body simulations show that escaped stars dominate; the dispersion profile of NGC 4590 follows the predictions of the limepy / spes models, though the data do not effectively extend beyond the truncation radius. The increasing/flat dispersion profiles in the outskirts of NGC 1261, NGC 1851, and NGC 1904, are reproduced by the simulations. Hence, the increasing/flat dispersion profiles of the clusters in question can be explained by the tidal interaction with the galaxy without introducing dark matter. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy of a simulation-based mastery curriculum to train clinicians with limited-to-no sonography experience how to use ultrasound (US) to assess neonatal endotracheal tube (ETT) positioning. Methods: In a single-centered, prospective, educational study, 29 neonatology clinicians participated in a simulation-based mastery curriculum composed of a didactic lecture, followed by a one-on-one simulation session using a newly designed, three-dimensional (3D) printed US phantom model of the neonatal trachea and aorta. After mastery training, clinicians were evaluated with a performance checklist on their skills obtaining US images and assessing ETT positioning in the US phantom model. They also completed pre- and postcurriculum knowledge assessment tests and self-assessment surveys. The data were analyzed using Wilcoxon signed rank tests and repeated measures analysis of variance. Results: The mean checklist score improved significantly during three attempts (mean difference: 2.6552; 95% confidence interval [CI]: 2.2578–3.0525; P < 0.0001). The mean time to perform US decreased significantly from the first to third attempt (mean difference: −1.8276 min; 95% CI: −3.3391 to − 0.3161; P = 0.0196). In addition, there was a significant improvement in median knowledge assessment scores (50% vs. 80%; P < 0.0001) and survey ratings on knowledge and self-efficacy (P < 0.0001). Conclusion: Clinicians with limited-to-no sonography experience demonstrated improved knowledge and skill acquisition in using US to assess ETT positioning through simulation-based mastery training. The use of 3D modeling enhances simulation experiences and optimizes the quality of training during limited opportunities to achieve procedural competency in a controlled environment before further application into the clinical setting. [ABSTRACT FROM AUTHOR]

We examine the degree of energy equipartition in nine Galactic globular clusters using proper motions measured with the Hubble Space Telescope. For most clusters in the sample, this is the first energy equipartition study ever performed. This study is also the largest of its kind, albeit with only nine clusters. We begin by rigorously cleaning the catalogs to remove poor-quality measurements and to ensure high signal to noise for the study. Using the cleaned catalogs, we investigate how velocity dispersion σ changes with stellar mass m. We fit two functional forms: the first, a classic power law of the form σ ∝ m âˆ' η where η is the degree of energy equipartition, and the second from Bianchini et al. parameterized by an equipartition mass m eq where η changes with stellar mass. We find that both functions fit well but cannot distinguish with statistical significance which function provides the best fit. All clusters exhibit varying degrees of partial equipartition; no cluster is at or near full equipartition. We search for correlations of η and m eq with various cluster properties. The most significant correlation is observed with the number of core or median relaxation times ( N core or N half) the cluster has experienced. Finally, we determine the radial equipartition profile for each cluster, that is, how the degree of equipartition changes with projected distance from the cluster center. We do not detect statistically significant trends in the degree of equipartition with radius. Overall, our observational findings are in broad agreement with theoretical predictions from N -body models published in recent years. [ABSTRACT FROM AUTHOR]

Objectives: Point of care ultrasound (POCUS) in adult critical care environments has become the standard of care in many hospitals. A robust literature shows its benefits for both diagnosis and delivery of care. The utility of POCUS in the pediatric intensive care unit (PICU), however, is understudied. This study describes in a series of PICU patients the clinical indications, protocols, findings and impact of pediatric POCUS on clinical management. Design: Retrospective analysis of 200 consecutive POCUS scans performed by a PICU physician. Patients: Pediatric critical care patients who required POCUS scans over a 15-month period. Setting: The pediatric and cardiac ICUs at a tertiary pediatric care center. Interventions: Performance of a POCUS scan by a pediatric critical care attending with advanced training in ultrasonography. Measurement and Main Results: A total of 200 POCUS scans comprised of one or more protocols (lung and pleura, cardiac, abdominal, or vascular diagnostic protocols) were performed on 155 patients over a 15-month period. The protocols used for each scan reflected the clinical question to be answered. These 200 scans included 133 thoracic protocols, 110 cardiac protocols, 77 abdominal protocols, and 4 vascular protocols. In this series, 42% of scans identified pathology that required a change in therapy, 26% confirmed pathology consistent with the ongoing plans for new therapy, and 32% identified pathology that did not result in initiation of a new therapy. Conclusions: POCUS performed by a trained pediatric intensivist provided useful clinical information to guide patient management. [ABSTRACT FROM AUTHOR]

This study examined rates and correlates of intimate partner and general aggression perpetration among 236 male combat veterans seeking services in a Veteran's Affairs posttraumatic stress disorder (PTSD) clinic. Approximately 33% of those in an intimate relationship reported perpetrating partner physical aggression in the previous year, and 91% reported partner psychological aggression. Comparable rates were found for general aggression perpetration among partnered and nonpartnered veterans. PTSD symptoms as well as symptoms of depression were associated with aggression across subgroups and forms of aggression, and PTSD symptoms reflecting arousal and lack of control were generally the strongest predictor of aggression. Findings indicate a need for additional aggression screening and intervention development for this population, and highlight the targeting of heightened arousal and lack of behavioral control in aggression interventions. Keywords: aggression, domestic violence, veterans, posttraumatic stress disorder DOI: 10.1037/a0016657

We present GaiaHub, a publicly available tool that combines Gaia measurements with Hubble Space Telescope (HST) archival images to derive proper motions (PMs). It increases the scientific impact of both observatories beyond their individual capabilities. Gaia provides PMs across the whole sky, but the limited mirror size and time baseline restrict the best PM performance to relatively bright stars. HST can measure accurate PMs for much fainter stars over a small field, but this requires two epochs of observation, which are not always available. GaiaHub yields considerably improved PM accuracy compared to Gaia-only measurements, especially for faint sources (G ≳ 18), requiring only a single epoch of HST data observed more than ∼7 yr ago (before 2012). This provides considerable scientific value, especially for dynamical studies of stellar systems or structures in and beyond the Milky Way (MW) halo, for which the member stars are generally faint. To illustrate the capabilities and demonstrate the accuracy of GaiaHub, we apply it to samples of MW globular clusters (GCs) and classical dwarf spheroidal (dSph) satellite galaxies. This allows us, e.g., to measure the velocity dispersions in the plane of the sky for objects out to and beyond ∼100 kpc. We find, on average, mild radial velocity anisotropy in GCs, consistent with existing results for more nearby samples. We observe a correlation between the internal kinematics of the clusters and their ellipticity, with more isotropic clusters being, on average, more round. Our results also support previous findings that Draco and Sculptor dSph galaxies appear to be radially anisotropic systems. [ABSTRACT FROM AUTHOR]