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Isoform- and ligand-specific modulation of the adhesion GPCR ADGRL3/Latrophilin3 by a synthetic binder
No full textAdhesion G protein-coupled receptors (aGPCRs) are cell-surface proteins with large extracellular regions that bind to multiple ligands to regulate key biological functions including neurodevelopment and organogenesis. Modulating a single function of a specific aGPCR isoform while affecting no other function and no other receptor is not trivial. Here, we engineered an antibody, termed LK30, that binds to the extracellular region of the aGPCR ADGRL3, and specifically acts as an agonist for ADGRL3 but not for its isoform, ADGRL1. The LK30/ADGRL3 complex structure revealed that the LK30 binding site on ADGRL3 overlaps with the binding site for an ADGRL3 ligand – teneurin. In cellular-adhesion assays, LK30 specifically broke the trans-cellular interaction of ADGRL3 with teneurin, but not with another ADGRL3 ligand – FLRT3. Our work provides proof of concept for the modulation of isoform- and ligand-specific aGPCR functions using unique tools, and thus establishes a foundation for the development of fine-tuned aGPCR-targeted therapeutics
Who’s Cheating Whom? Changing the Narrative Around Academic Misconduct
No full textConcerns about academic misconduct are nearly ubiquitous among educators, and are especially prevalent in computer science. However most conversations relating to misconduct focus on how students cheat, how to detect when they do, and how to discipline offenders. This emphasis on "detect and punish" can have severe negative consequences, including toxic classroom cultures, adversarial student-staff relationships, and massive mental and emotional workloads for instructors. In this panel, we examine possible root causes for misconduct in CS courses and advocate for shifting the narrative to focus on designing and delivering courses that discourage misconduct by being inclusive and supportive to all students. We also offer concrete suggestions for approaches to reduce mis-conduct through non-punitive means
Strain Measurement in Coilable Thin Composite Shells with Embedded Fiber Bragg Grating Sensors
No full textProgress towards the use of ultra-thin fiber Bragg grating sensors for the in-situ strain measurement of coilable thin composite shells is presented. The first part of this work presents the manufacturing procedure used in the construction of these composite shells with embedded sensors. The second part of this work investigates how embedded ultra-thin fiber Bragg grating sensors affect the bending stiffness and failure curvature of these laminates through the use of the column bending test. The influence of the embedded sensors on the failure of these laminates is further investigated through μCT imaging after failure
Slew Maneuver Constraints for Agile Flexible Spacecraft
No full textTraditional spacecraft design paradigms rely on stiff bus structures with comparatively flexible appendages. More recent trends, however, trade deployed stiffness for packaging efficiency to stow apertures with larger areas inside existing launch vehicles. By leveraging recent advances in materials and structures, these spacecraft may be up to several orders of magnitude lighter and more flexible than the current state-of-the-art. Motivated by the goal of achieving agility despite structural flexibility, this paper proposes a quantitative method for determining structure-based performance limits for maneuvering flexible spacecraft. It then uses a geometrically nonlinear flexible multibody dynamics model of a representative very flexible spacecraft to verify this method. The results demonstrate that, contrary to common assumptions, other constraints impose more restrictive limits on maneuverability than the dynamics of the structure. In particular, it is shown that the available attitude control system momentum and torque are often significantly more limiting than the compliance of the structure. Consequently, these results suggest that there is an opportunity to design less-conservative, higher-performance space systems that can either be maneuvered faster, assuming suitable actuators are available, or built using lighter-weight, less-stiff architectures that move the structure-based performance limits closer to those of the rest of the system
A practical guide to electromagnetically induced transparency in atomic vapor
No full textThis tutorial introduces the theoretical and experimental basics of electromagnetically induced transparency (EIT) in thermal alkali vapors. We first give a brief phenomenological description of EIT in simple three-level systems of stationary atoms and derive analytical expressions for optical absorption and dispersion under EIT conditions. Then we focus on how the thermal motion of atoms affects various parameters of the EIT system. Specifically, we analyze the Doppler broadening of optical transitions, ballistic versus diffusive atomic motion in a limited-volume interaction region, and collisional depopulation and decoherence. Finally, we discuss the common trade-offs important for optimizing an EIT experiment and give a brief ‘walk-through’ of a typical EIT experimental setup. We conclude with a brief overview of current and potential EIT applications
X-Ray Polarimetry Reveals the Magnetic-field Topology on Sub-parsec Scales in Tycho’s Supernova Remnant
No full textSupernova remnants are commonly considered to produce most of the Galactic cosmic rays via diffusive shock acceleration. However, many questions regarding the physical conditions at shock fronts, such as the magnetic-field morphology close to the particle acceleration sites, remain open. Here we report the detection of a localized polarization signal from some synchrotron X-ray emitting regions of Tycho’s supernova remnant made by the Imaging X-ray Polarimetry Explorer. The derived degree of polarization of the X-ray synchrotron emission is 9% ± 2% averaged over the whole remnant, and 12% ± 2% at the rim, higher than the value of polarization of 7%–8% observed in the radio band. In the west region, the degree of polarization is 23% ± 4%. The degree of X-ray polarization in Tycho is higher than for Cassiopeia A, suggesting a more ordered magnetic field or a larger maximum turbulence scale. The measured tangential direction of polarization corresponds to the radial magnetic field, and is consistent with that observed in the radio band. These results are compatible with the expectation of turbulence produced by an anisotropic cascade of a radial magnetic field near the shock, where we derive a magnetic-field amplification factor of 3.4 ± 0.3. The fact that this value is significantly smaller than those expected from acceleration models is indicative of highly anisotropic magnetic-field turbulence, or that the emitting electrons either favor regions of lower turbulence, or accumulate close to where the orientation of the magnetic field is preferentially radially oriented due to hydrodynamical instabilities
Tailoring Two-Dimensional Matter Using Strong Light–Matter Interactions
No full textThe shaping of matter into desired nanometric structures with on-demand functionalities can enhance the miniaturization of devices in nanotechnology. Herein, strong light–matter interaction was used as an optical lithographic tool to tailor two-dimensional (2D) matter into nanoscale architectures. We transformed 2D black phosphorus (BP) into ultrafine, well-defined, beyond-diffraction-limit nanostructures of ten times smaller size and a hundred times smaller spacing than the incident, femtosecond-pulsed light wavelength. Consequently, nanoribbons and nanocubes/cuboids scaling tens of nanometers were formed by the structured ablation along the extremely confined periodic light fields originating from modulation instability, the tailoring process of which was visualized in real time via light-coupled in situ transmission electron microscopy. The current findings on the controllable nanoscale shaping of BP will enable exotic physical phenomena and further advance the optical lithographic techniques for 2D materials
Grand Canonical Quantum Mechanics with Applications to Mechanisms and Rates for Electrocatalysis
No full textWe outline the recently developed Grand Canonical Potential Kinetics (GCP-K) method to implement Grand Canonical Quantum Mechanics for predicting electrochemical reactions as a function of applied potential rather than with fixed numbers of electrons as in traditional Quantum Mechanics (QM) calculations. We describe here the recent validation of GCP-K for The Co/TiO₂ single atom catalyst for the Oxygen Evolution Reaction (OER) on a single crystal nanoparticle where a single surface facet was present. The basal plane of transition metal dichalcogenides (TMDs) in the 1 T’ phase of WSe₂ and WTe₂, which leads to high-performance for the hydrogen evolution reaction (HER). We find that GCP-K predicts accurate TOF and currents as a function of applied potential and accurate Tafel slopes for both the Co/TiO₂ OER and the chalcogenide HER systems for which we can be confident of the surface structure. Thus we expect that these methods will be useful in the more common situation for which there is much less certainty about the surface structure under experimental conditions
The connection between heart rate variability (HRV), neurological health, and cognition: A literature review
No full textThe heart and brain have bi-directional influences on each other, including autonomic regulation and hemodynamic connections. Heart rate variability (HRV) measures variation in beat-to-beat intervals. New findings about disorganized sinus rhythm (erratic rhythm, quantified as heart rate fragmentation, HRF) are discussed and suggest overestimation of autonomic activities in HRV changes, especially during aging or cardiovascular events. When excluding HRF, HRV is regulated via the central autonomic network (CAN). HRV acts as a proxy of autonomic activity and is associated with executive functions, decision-making, and emotional regulation in our health and wellbeing. Abnormal changes of HRV (e.g., decreased vagal functioning) are observed in various neurological conditions including mild cognitive impairments, dementia, mild traumatic brain injury, migraine, COVID-19, stroke, epilepsy, and psychological conditions (e.g., anxiety, stress, and schizophrenia). Efforts are needed to improve the dynamic and intriguing heart-brain interactions
Quantitative analyses of cytokine profiles reveal hormone-mediated modulation of cytokine profiles in recurrent spontaneous miscarriage
No full textPurpose. Cytokines play important roles in pregnancy complications. Some hormones such as estrogen, progesterone, and dydrogesterone have been shown to alter cytokine profiles. Understanding how cytokine profiles are affected by these hormones is therefore an important step towards immunomodulatory therapies for pregnancy complications. We analyse previously published data on the effects of estrogen, progesterone, and dydrogesterone on cytokine balances in women having recurrent spontaneous miscarriages.
Materials and methods. Levels of eight cytokines (IFN-γ, IL-2, IL-6, IL-10, IL-13, IL-17, IL-23, TNF-α) from n = 22 women presenting unexplained recurrent spontaneous miscarriages were studied. Cytokine values were recorded after in vitro exposure of peripheral blood cells to estrogen, progesterone, and dydrogesterone. We expand on earlier analysis of the dataset by employing different statistical techniques including effect sizes for individual cytokine values, a more powerful statistical test, and adjusting p-values for multiple comparisons. We employ multivariate analysis methods, including to determine the relative magnitude of the effects of the hormone therapies on cytokines. A new statistical method is introduced based on pairwise distances able to accommodate complex relations in cytokine profiles.
Results. We report several statistically significant differences in individual cytokine values between the control group and each hormone treated group, with estrogen affecting the fewest cytokines, and progesterone and dydrogesterone both affecting seven out of eight cytokines. Exposure to estrogen produces no large effects sizes however, while IFN-γ and IL-17 show large effect sizes for both progesterone and dydrogesterone, among other cytokines. Our new method for identifying which collections (i.e. subsets) of cytokines best distinguish contrasting groups identifies IFN-γ, IL-10 and IL-23 as especially noteworthy for both progesterone and dydrogesterone treatments.
Conclusions. While some statistically significant differences in cytokine levels after exposure to estrogen are found, these have small effect sizes and are unlikely to be clinically relevant. Progesterone and dydrogesterone both induce statistically significant and large effect-size differences in cytokine levels, hence therapy with these two progestogens is more likely to be clinically relevant. Univariate and multivariate methods for identifying cytokine importances provide insight into which groups of cytokines are most affected and in what ways by therapies