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Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials

The Cholesterol Lowering Atherosclerosis Study, a randomized angiographic clinical trial, demonstrated the beneficial effect of niacin/colestipol plus diet therapy on coronary atherosclerosis. Outcome was determined by panel-based estimates (viewed in both still and cine modes) of percent stenosis severity and change in native artery and bypass graft lesions. Computer-based quantitative coronary angiography (QCA) was also used to measure lesion and bypass graft stenosis severity and change in individual frames closely matched in orientation, opacification, and cardiac phase. Both methods jointly evaluated 350 nonoccluded lesions. The correlation between QCA and panel estimates of lesion size was 0.70 (p less than 0.0001) and for change in lesion size was 0.28 (p = 0.002). Agreement between the two methods in classifying lesion changes (i.e., regression, unchanged, or progression) occurred for 60% (210 of 350) of the lesions kappa +/- SEM = 0.20 +/- 0.05, p less than 0.001). The panel identified 442 nonoccluded lesions for which QCA stenosis measurements could not be obtained. Lesions not measurable by QCA included those with stenosis greater than 85% that could not be reliably edge tracked, segments with diffuse or ecstatic disease that had no reliable reference diameter, and segments for which matched frames could not be located. Seventy-nine lesions, the majority between 21% and 40% stenosis, were identified and measured by QCA but were not identified by the panel. This comparison study demonstrates the need to consider available angiographic measurement methods in relation to the goals of their use.

NASA Center JPL↗

An Investigation of the Kinematic and Microphysical Control of Lightning Rate, Extent and NOX Production using DC3 Observations and the NASA Lightning Nitrogen Oxides Model (LNOM)

The Deep Convective Clouds and Chemistry (DC3) experiment seeks to quantify the relationship between storm physics, lightning characteristics and the production of nitrogen oxides via lightning (LNOx). The focus of this study is to investigate the kinematic and microphysical control of lightning properties, particularly those that may govern LNOx production, such as flash rate, type and extent across Alabama during DC3. Prior studies have demonstrated that lightning flash rate and type is correlated to kinematic and microphysical properties in the mixed‐phase region of thunderstorms such as updraft volume and graupel mass. More study is required to generalize these relationships in a wide variety of storm modes and meteorological conditions. Less is known about the co‐evolving relationship between storm physics, morphology and three‐dimensional flash extent, despite its importance for LNOx production. To address this conceptual gap, the NASA Lightning Nitrogen Oxides Model (LNOM) is applied to North Alabama Lightning Mapping Array (NALMA) and Vaisala National Lightning Detection NetworkTM (NLDN) observations following ordinary convective cells through their lifecycle. LNOM provides estimates of flash rate, flash type, channel length distributions, lightning segment altitude distributions (SADs) and lightning NOx production profiles. For this study, LNOM is applied in a Lagrangian sense to multicell thunderstorms over Northern Alabama on two days during DC3 (21 May and 11 June 2012) in which aircraft observations of NOx are available for comparison. The LNOM lightning characteristics and LNOX production estimates are compared to the evolution of updraft and precipitation properties inferred from dual‐Doppler and polarimetric radar analyses applied to observations from a nearby radar network, including the UAH Advanced Radar for Meteorological and Operational Research (ARMOR). Given complex multicell evolution, particular attention is paid to storm morphology, cell mergers and possible dynamical, microphysical and electrical interaction of individual cells when testing various hypotheses.

Carey, Lawrence↗

Molecular Structure of Sphingomyelin in Fluid Phase Bilayers Determined by the Joint Analysis of Small-Angle Neutron and X-ray Scattering Data

In this work, we have determined the fluid bilayer structure of palmitoyl sphingomyelin (PSM) and stearoyl sphingomyelin (SSM) by simultaneously analyzing small-angle neutron and X-ray scattering data. Using a newly developed scattering density profile (SDP) model for sphingomyelin lipids, we report structural parameters including the area per lipid, total bilayer thickness, and hydrocarbon thickness, in addition to lipid volumes determined by densitometry. Unconstrained all-atom simulations of PSM bilayers at 55 °C using the C36 CHARMM force field produced a lipid area of 56 Å 2 , a value that is 10% lower than the one determined experimentally by SDP analysis (61.9 Å2). Furthermore, scattering form factors calculated from the unconstrained simulations were in poor agreement with experimental form factors, even though segmental order parameter (S CD ) profiles calculated from the simulations were in relatively good agreement with S CD profiles obtained from NMR experiments. Conversely, constrained area simulations at 61.9 Å 2 resulted in good agreement between the simulation and experimental scattering form factors, but not with S CD profiles from NMR. We discuss possible reasons for the discrepancies between these two types of data that are frequently used as validation metrics for molecular dynamics force fields.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Topological Phases in Cove-Edged and Chevron Graphene Nanoribbons: Geometric Structures, Z 2 Invariants, and Junction States

Graphene nanoribbons (GNRs) have recently been shown by Cao, Zhao, and Louie [Cao, T.; Zhao, F.; Louie, S. G. Phys. Rev. Lett.2017, 119, 076401] to possess distinct topological phases in general, characterized by a 2 invariant. Cove-edged and chevron GNRs moreover are chemically and structurally diverse, quasi-one-dimensional (1D) nanostructures whose structure and electronic properties can be rationally controlled by bottom-up synthesis from precursor molecules. We derive the value of the topological invariant of the different types of cove-edged and chevron GNRs, and we investigate the electronic properties of various junctions formed by these GNRs, as well as such GNRs with the more common armchair or zigzag GNRs. We study the topological junction states at the interface of two topologically distinct segments. For an isolated GNR having two ends of different terminations, topological end states are shown to develop only at the topologically nontrivial end. Our work extends the explicit categorization of topological invariants of GNRs beyond the previously demonstrated armchair GNRs and provides new design rules for novel GNR junctions as well as future GNR-based nanoelectronic devices.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Three-Dimensional Ultrastructure of Arabidopsis Cotyledons Infected with Colletotrichum higginsianum

We used serial block-face scanning electron microscopy (SBF-SEM) to study the host–pathogen interface between Arabidopsis cotyledons and the hemibiotrophic fungus Colletotrichum higginsianum. By combining high-pressure freezing and freeze-substitution with SBF-SEM, followed by segmentation and reconstruction of the imaging volume using the freely accessible software IMOD, we created 3D models of the series of cytological events that occur during the Colletotrichum–Arabidopsis susceptible interaction. We found that the host cell membranes underwent massive expansion to accommodate the rapidly growing intracellular hypha. As the fungal infection proceeded from the biotrophic to the necrotrophic stage, the host cell membranes went through increasing levels of disintegration culminating in host cell death. Intriguingly, we documented autophagosomes in proximity to biotrophic hyphae using transmission electron microscopy (TEM) and a concurrent increase in autophagic flux between early to mid/late biotrophic phase of the infection process. Occasionally, we observed osmiophilic bodies in the vicinity of biotrophic hyphae using TEM only and near necrotrophic hyphae under both TEM and SBF-SEM. Overall, we established a method for obtaining serial SBF-SEM images, each with a lateral ( x-y) pixel resolution of 10 nm and an axial ( z) resolution of 40 nm, that can be reconstructed into interactive 3D models using the IMOD. Application of this method to the Colletotrichum–Arabidopsis pathosystem allowed us to more fully understand the spatial arrangement and morphological architecture of the fungal hyphae after they penetrate epidermal cells of Arabidopsis cotyledons and the cytological changes the host cell undergoes as the infection progresses toward necrotrophy. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Biochemistry & Molecular Biology↗

An Investigation of the Kinematic and Microphysical Control of Lightning Rate, Extent and NOx Production using DC3 Observations and the NASA Lightning Nitrogen Oxides Model (LNOM)

The Deep Convective Clouds and Chemistry (DC3) experiment seeks to quantify the relationship between storm physics, lightning characteristics and the production of nitrogen oxides via lightning (LNOx). The focus of this study is to investigate the kinematic and microphysical control of lightning properties, particularly those that may govern LNOx production, such as flash rate, type and extent across Alabama during DC3. Prior studies have demonstrated that lightning flash rate and type is correlated to kinematic and microphysical properties in the mixed‐phase region of thunderstorms such as updraft volume and graupel mass. More study is required to generalize these relationships in a wide variety of storm modes and meteorological conditions. Less is known about the co‐evolving relationship between storm physics, morphology and three‐dimensional flash extent, despite its importance for LNOx production. To address this conceptual gap, the NASA Lightning Nitrogen Oxides Model (LNOM) is applied to North Alabama Lightning Mapping Array (NALMA) and Vaisala National Lightning Detection Network(TM) (NLDN) observations following ordinary convective cells through their lifecycle. LNOM provides estimates of flash rate, flash type, channel length distributions, lightning segment altitude distributions (SADs) and lightning NOx production profiles. For this study, LNOM is applied in a Lagrangian sense to multicell thunderstorms over Northern Alabama on two days during DC3 (21 May and 11 June 2012) in which aircraft observations of NOx are available for comparison. The LNOM lightning characteristics and LNOX production estimates are compared to the evolution of updraft and precipitation properties inferred from dual‐Doppler and polarimetric radar analyses applied to observations from a nearby radar network, including the UAH Advanced Radar for Meteorological and Operational Research (ARMOR). Given complex multicell evolution, particular attention is paid to storm morphology, cell mergers and possible dynamical, microphysical and electrical interaction of individual cells when testing various hypotheses.

Carey, Lawrence↗

Simulator evaluation of display concepts for pilot monitoring and control of space shuttle approach and landing. Phase 2: Manual flight control

A study of the display requirements for final approach management of the space shuttle orbiter vehicle is presented. An experimental display concept, providing a more direct, pictorial representation of the vehicle's movement relative to the selected approach path and aiming points, was developed and assessed as an aid to manual flight path control. Both head-up, windshield projections and head-down, panel mounted presentations of the experimental display were evaluated in a series of simulated orbiter approach sequence. Data obtained indicate that the experimental display would enable orbiter pilots to exercise greater flexibility in implementing alternative final approach control strategies. Touchdown position and airspeed dispersion criteria were satisfied on 91 percent of the approach sequences, representing various profile and wind effect conditions. Flight path control and airspeed management satisfied operationally-relevant criteria for the two-segment, power-off orbiter approach and were consistently more accurate and less variable when the full set of experimental display elements was available to the pilot. Approach control tended to be more precise when the head-up display was used; however, the data also indicate that the head-down display would provide adequate support for the manual control task.

Gartner, W. B.↗

Advanced UVOIR Mirror Technology Development for Very Large Space Telescopes

The Advanced Mirror Technology Development (AMTD) project is in phase 2 of a multiyear effort, initiated in FY 2012. This effort is to mature, by at least a half Technology Readiness Level step, the critical technologies required to enable 4-meter or larger ultraviolet, optical, and infrared (UVOIR) space telescope primary mirror assemblies for both general astrophysics and ultra-high contrast observations of exoplanets. AMTD continues to achieve all of its goals and has accomplished all of its milestones to date. This has been achieved by assembling an outstanding team from academia, industry, and government with extensive expertise in astrophysics and exoplanet characterization, and in the design/manufacture of monolithic and segmented space telescopes; by deriving engineering specifications for advanced normal-incidence mirror systems needed to make the required science measurements; and by defining and prioritizing the most important technical problems to be solved. Our results have been presented to the CoPAG and Mirror Tech Days 2013, and proceedings papers of the 2013 and 2014 SPIE Optics & Photonics Symposia have been published.

Effinger, Mike↗

Exploring Environmental and Aerosol Impacts on Maritime Tropical Convection using Airborne Radiometer, Radar, Lidar, and Dropsondes

The field deployment phase of NASA’s Cloud, Aerosol and Monsoon Processes Philippines Experiment (CAMP2Ex) took place around the Philippines during August–October 2019, with the primary goal of jointly investigating aerosols and tropical meteorology at the micro-β to meso-β scales. A suite of instruments was deployed on NASA’s P-3B Orion aircraft to accomplish this mission, including: the Advanced Microwave Precipitation Radiometer (AMPR), Airborne Precipitation and cloud Radar 3rd Generation (APR-3), High Spectral Resolution Lidar 2 (HSRL2), and Advanced Vertical Atmospheric Profiling System (AVAPS) dropsondes. To examine potential aerosol influences on maritime tropical convection, P-3 flight segments throughout CAMP2Ex were binned into similar environmental groups using “low,” “medium,” and “high” values of nine AVAPS-derived parameters with known physical connections to convective frequency and/or intensity. Aerosol concentrations in each flight segment were evaluated using three HSRL2 variables at 355 and 532 nm: aerosol backscatter, aerosol extinction, and aerosol optical thickness. A set of radiometer- and radar-derived variables directly related to convective frequency and/or intensity was used to characterize convection, which included: AMPR-derived integrated cloud liquid water; polarization-corrected temperatures at 10.7, 19.35, 37.1, and 85.5 GHz; peak equivalent radar reflectivity factor (ZH); peak height of 30-dBZ ZH; and the number of radar data columns with composite ZH > 30 dBZ. The ZH analyses were performed using both Ku- and Ka-band APR-3 data. For each flight segment, correlation coefficients were calculated between each convective parameter and aerosol concentrations within the “low,” “medium,” and “high” groups for each environmental variable. The environmental stratification thresholds were then varied in a series of sensitivity tests. Several noteworthy correlations were observed between the convective and aerosol parameters within the environmental groups, especially when stratifying the environments based on their 850–500-hPa temperature lapse rate, 700–500-hPa temperature lapse rate, and K-Index. The convective parameters were often correlated most strongly with 355-nm extinction, 532-nm extinction, and 532-nm backscatter, while the presence of precipitation-sized liquid and ice hydrometeors contributed to some unexpected negative correlations. In general, as environmental conditions became more favorable for convection, a stronger correlation was observed between the convective parameters and aerosol concentrations. However, a “Goldilocks” zone of medium aerosol concentration was correlated most strongly with the convective parameters in many cases. These results stress the importance of considering environmental and aerosol conditions together when evaluating their impacts on convection. This presentation will provide a detailed discussion of these results and their implications, a summary of the limitations associated with such an analysis, and suggestions for future work.

Corey G. Amiot↗

Hydrogen Effects on Cladding Performance during Simulated Loss of Coolant Accident Testing

Fresh Zircaloy cladding segments were charged with hydrogen and subjected to simulated Loss of Coolant Accident (LOCA) conditions to assess the impact of hydrogen on the cladding mechanical performance and rupture resistance. The cladding rupture temperature decreased by 10 °C for every 100 wppm H added into the system for two different internal pressurization cases. Post-test analysis showed a loss of ductility with increasing hydrogen content, evident through decreased balloon sizes, smaller rupture openings, and sharper rupture interfaces. Digital image correlation was used to map the cladding strain in situ for two cladding segments. An elevated intermediate temperature uniform strain was visible for the hydride cladding, occurring prior to the decreased ductility during balloon and rupture determined from posttest fractography and microscopy. The thermal stability of Zr alloys as a function of hydrogen concentration and the thermal stability of Zr hydride as a function of temperature are likely responsible for the uniform deformation behavior at intermediate temperatures. The present framework for rapid assessment of hydrogen effects on cladding rupture can be utilized as an initial comparison to high burnup cladding thermomechanical response to a LOCA, where local regions may contain high concentrations of precipitated Zr hydride phase.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Hydrogen Effects on Cladding Performance during Simulated Loss of Coolant Accident Testing

Fresh Zircaloy cladding segments were charged with hydrogen and subjected to simulated Loss of Coolant Accident (LOCA) conditions to assess the impact of hydrogen on the cladding mechanical performance and rupture resistance. The cladding rupture temperature decreased by 10 °C for every 100 wppm H added into the system for two different internal pressurization cases. Post-test analysis showed a loss of ductility with increasing hydrogen content, evident through decreased balloon sizes, smaller rupture openings, and sharper rupture interfaces. Digital image correlation was used to map the cladding strain in situ for two cladding segments. An elevated intermediate temperature uniform strain was visible for the hydride cladding, occurring prior to the decreased ductility during balloon and rupture determined from posttest fractography and microscopy. The thermal stability of Zr alloys as a function of hydrogen concentration and the thermal stability of Zr hydride as a function of temperature are likely responsible for the uniform deformation behavior at intermediate temperatures. The present framework for rapid assessment of hydrogen effects on cladding rupture can be utilized as an initial comparison to high burnup cladding thermomechanical response to a LOCA, where local regions may contain high concentrations of precipitated Zr hydride phase.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Vertical Navigation Control Laws and Logic for the Next Generation Air Transportation System

A vertical navigation (VNAV) outer-loop control system was developed to capture and track the vertical path segments of energy-efficient trajectories that are being developed for high-density operations in the evolving Next Generation Air Transportation System (NextGen). The VNAV control system has a speed-on-elevator control mode to pitch the aircraft for tracking a calibrated airspeed (CAS) or Mach number profile and a path control mode for tracking the VNAV altitude profile. Mode control logic was developed for engagement of either the speed or path control modes. The control system will level the aircraft to prevent it from flying through a constraint altitude. A stability analysis was performed that showed that the gain and phase margins of the VNAV control system significantly exceeded the design gain and phase margins. The system performance was assessed using a six-deg-of-freedom non-linear transport aircraft simulation and the performance is illustrated with time-history plots of recorded simulation data.

Hueschen, Richard M.↗

The Kinematic and Microphysical Control of Lightning Rate, Extent and NOX Production

The Deep Convective Clouds and Chemistry (DC3) experiment seeks to quantify the relationship between storm physics, lightning characteristics and the production of nitrogen oxides via lightning (LNOx). The focus of this study is to investigate the kinematic and microphysical control of lightning properties, particularly those that may govern LNOx production, such as flash rate, type and extent across Alabama during DC3. Prior studies have demonstrated that lightning flash rate and type is correlated to kinematic and microphysical properties in the mixed-phase region of thunderstorms such as updraft volume and graupel mass. More study is required to generalize these relationships in a wide variety of storm modes and meteorological conditions. Less is known about the co-evolving relationship between storm physics, morphology and three-dimensional flash extent, despite its importance for LNOx production. To address this conceptual gap, the NASA Lightning Nitrogen Oxides Model (LNOM) is applied to North Alabama Lightning Mapping Array (NALMA) and Vaisala National Lightning Detection Network(TM) (NLDN) observations following ordinary convective cells through their lifecycle. LNOM provides estimates of flash rate, flash type, channel length distributions, lightning segment altitude distributions (SADs) and lightning NOx production profiles. For this study, LNOM is applied in a Lagrangian sense to multicell thunderstorms over Northern Alabama on two days during DC3 (21 May and 11 June 2012) in which aircraft observations of NOx are available for comparison. The LNOM lightning characteristics and LNOX production estimates are compared to the evolution of updraft and precipitation properties inferred from dual-Doppler and polarimetric radar analyses applied to observations from a nearby radar network, including the UAH Advanced Radar for Meteorological and Operational Research (ARMOR). Given complex multicell evolution, particular attention is paid to storm morphology, cell mergers and possible dynamical, microphysical and electrical interaction of individual cells when testing various hypotheses.

Carey, Lawrence↗

The Nightside Auroral Gap: Implications for Magnetosphere-Ionosphere Coupling in the Midnight Auroral Zone

We present observations of a new synoptic scale feature of the nightside aurora identified by the Polar Ultraviolet Imager (UVI) in which a well defined segment of the pre-midnight auroral oval exhibits significantly reduced auroral luminosity in the atomic oxygen and Lyman-Birge-Hopfield (LBH) emission bands in comparison to adjacent auroral activity. This gap in the nightside aurora is typically observed in the 2200-2400 MLT sector and spans 1.0-1.5 hours in local time (710-1100 km). The energy flux ($\rm erg$ $\rm cm'{-2}$ $\rm s'{-1}$) is shown to be lower by as much as a factor of four in the nightside gap region in comparison to the adjacent auroral activity. The appearance of the nightside gap does not depend on substorm phase. However, substorm intensifications are often observed on either side of the nightside gap which remains relatively inactive. Moreover, auroral breakups sometimes develop within the nightside gap, indicating that this feature may have dynamical implications for substorm onset location.

Chua, D. H.↗

AMTD: Update of Engineering Specifications Derived from Science Requirements for Future UVOIR Space Telescopes

The Advance Mirror Technology Development (AMTD) project is in Phase 2 of a multiyear effort, initiated in FY12, to mature by at least a half TRL step six critical technologies required to enable 4 meter or larger UVOIR space telescope primary mirror assemblies for both general astrophysics and ultra-high contrast observations of exoplanets. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND provide a high-performance low-cost low-risk system. To give the science community options, we are pursuing multiple technology paths. A key task is deriving engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicles and their mass and volume constraints. A key finding of this effort is that the science requires an 8 meter or larger aperture telescope

Stahl, H. Philip↗

Automated Segmentation and Quantification of Drusen in Fundus and Optical Coherence Tomography Images for Detection of ARMD

Age-related macular degeneration (ARMD) is one of the most common retinal syndromes that occurs in elderly people. Different eye testing techniques such as fundus photography and optical coherence tomography (OCT) are used to clinically examine the ARMD-affected patients. Many researchers have worked on detecting ARMD from fundus images, few of them also worked on detecting ARMD from OCT images. However, there are only few systems that establish the correspondence between fundus and OCT images to give an accurate prediction of ARMD pathology. In this paper, we present fully automated decision support system that can automatically detect ARMD by establishing correspondence between OCT and fundus imagery. The proposed system also distinguishes between early, suspect and confirmed ARMD by correlating OCT B-scans with respective region of the fundus image. In first phase, proposed system uses different B-scan based features along with support vector machine (SVM) to detect the presence of drusens and classify it as ARMD or normal case. In case input OCT scan is classified as ARMD, region of interest from corresponding fundus image is considered for further evaluation. The analysis of fundus image is performed using contrast enhancement and adaptive thresholding to detect possible drusens from fundus image and proposed system finally classified it as early stage ARMD or advance stage ARMD. The proposed system is tested on local data set of 100 patients with100 fundus images and 6800 OCT B-scans. Proposed system detects ARMD with the accuracy, sensitivity, and specificity ratings of 98.0, 100, and 97.14%, respectively.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Functional Coordination of a Full-Body Gaze Control Mechanisms Elicited During Locomotion

Control of locomotion requires precise interaction between several sensorimotor subsystems. Exposure to the microgravity environment of spaceflight leads to postflight adaptive alterations in these multiple subsystems leading to postural and gait disturbances. Countermeasures designed to mitigate these postflight gait alterations will need to be assessed with a new generation of functional tests that evaluate the interaction of various elements central to locomotor control. The goal of this study is to determine how the multiple, interdependent, full- body sensorimotor subsystems aiding gaze stabilization during locomotion are functionally coordinated. To explore this question two experiments were performed. In the first study (Study 1) we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects (n=9) performed two discreet gaze stabilization tasks while walking at 6.4 km/hr on a motorized treadmill: 1) focusing on a central point target; 2) reading numeral characters; both presented at 2m in front at eye level. The second study (Study 2) investigated the potential of adaptive remodeling of the full-body gaze control systems following exposure to visual-vestibular conflict. Subjects (n=14) walked (6.4 km/h) on the treadmill before and after they were exposed to 0.5X minifying lenses worn for 30 minutes during self-generated sinusoidal vertical head rotations performed while seated. In both studies we measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. Results from Study 1 showed that while reading numeral characters as compared to the central point target: 1) compensatory head pitch movements were on average 22% greater 2) the peak acceleration measured at the head was significantly reduced by an average of 13% in four of the six subjects 3) the knee joint total movement was on average 11% greater during the period from the heel strike event to the peak knee flexion event in stance phase of the gait cycle. Results from Study 2 indicate that following exposure to visual-vestibular conflict changes in full-body strategies were observed consistent with the requirement to aid gaze stabilization during locomotion.

Bloomberg, Jacob J.↗

Sequence Design of Random Heteropolymers as Protein Mimics

Random heteropolymers (RHPs) have been computationally designed and experimentally shown to recapitulate protein-like phase behavior and function. However, unlike proteins, RHP sequences are only statistically defined and cannot be sequenced. Recent developments in reversible-deactivation radical polymerization allowed simulated polymer sequences based on the well-established Mayo–Lewis equation to more accurately reflect ground-truth sequences that are experimentally synthesized. This led to opportunities to perform bioinformatics-inspired analysis on simulated sequences to guide the design, synthesis, and interpretation of RHPs. We compared batches on the order of 10000 simulated RHP sequences that vary by synthetically controllable and measurable RHP characteristics such as chemical heterogeneity and average degree of polymerization. Our analysis spans across 3 levels: segments along a single chain, sequences within a batch, and batch-averaged statistics. We discuss simulator fidelity and highlight the importance of robust segment definition. Examples are presented that demonstrate the use of simulated sequence analysis for in-silico iterative design to mimic protein hydrophobic/hydrophilic segment distributions in RHPs and compare RHP and protein sequence segments to explain experimental results of RHPs that mimic protein function. To facilitate the community use of this workflow, the simulator and analysis modules have been made available through an open source toolkit, the RHPapp.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗