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234 records · Page 13

Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease

The long interspersed nuclear element-1 (LINE-1 or L1) retrotransposon is the only active autonomously replicating retrotransposon in the human genome. L1 harms the cell by inserting new copies, generating DNA damage, and triggering inflammation. Therefore, L1 inhibition could be used to treat many diseases associated with these processes. Previous research has focused on inhibition of the L1 reverse transcriptase due to the prevalence of well-characterized inhibitors of related viral enzymes. Here we present the L1 endonuclease as another target for reducing L1 activity. We characterize structurally diverse small molecule endonuclease inhibitors using computational, biochemical, and biophysical methods. We also show that these inhibitors reduce L1 retrotransposition, L1-induced DNA damage, and inflammation reinforced by L1 in senescent cells. These inhibitors could be used for further pharmacological development and as tools to better understand the life cycle of this element and its impact on disease processes.

60 APPLIED LIFE SCIENCES↗

Nondestructive geochemical characterization of fossil hominin taphonomy and burial history

To date, only three Homo habilis specimens have been discovered that have associated craniodental and postcranial elements, providing a limited fossil record of the ontogeny and morphology of early members of the genus Homo. Recently, a nearly complete dentition, likely attributable to H. habilis, was discovered and excavated from early Pleistocene-age fluvial-lacustrine sediments of the upper Burgi Member of the Koobi Fora Formation at site F25787 in Area 13, near Ileret, Kenya. On the surface less than 15 m away, at site F25966, postcranial elements were found, which, if from the same individual as the nearby dentition, would represent the fourth associated craniodental and postcranial assemblage of this species. We developed a geochemical taphonomic history of these ca. 2 Ma hominin fossils using nondestructive X-ray based microanalytical tools (synchrotron and benchtop X-ray fluorescence chemical imaging and micro- and nano-computed tomography volumetric reconstruction), bulk analyses of sediments and paleosols at the excavation sites, and sedimentologic and stratigraphic observations. We integrate the chemical and physical taphonomic histories to test whether teeth (excavated in situ) and postcranial bones (eroded onto the outcrop surface) derive from a single individual. Minor differences in taphonomic history are attributable to the different biomineral properties of the dental and osseous components and to differences in physical damage during early post-mortem scavenging, dispersal, and burial in adjacent depositional settings. Microscale geochemical mapping enabled the temporal ordination of chemical and physical events in the specimens’ chemical taphonomic histories. Specifically, authigenic Fe- and K-bearing clays and Y, U, and Sr uptake occurred in post-burial fractures in bones and were also incorporated pervasively throughout dentin in teeth. Barite mineralization occurred along the latest fractures in both materials, and as a coating on tooth roots. The stratigraphic, taphonomic, and geochemical evidence supports the interpretation that the hominin fossils represent a single individual. Finally, successful application of these nondestructive sample characterization methods demonstrates capabilities for thorough interrogation of the taphonomic histories of other potential hominin fossil associations, enabling more robust and accurate palaeontologic constraints using those relationships.

36 MATERIALS SCIENCE↗

Calculation of Compressible Flows past Aerodynamic Shapes by Use of the Streamline Curvature

A simple approximate method is given for the calculation of isentropic irrotational flows past symmetrical airfoils, including mixed subsonic-supersonic flows. The method is based on the choice of suitable values for the streamline curvature in the flow field and the subsequent integration of the equations of motion. The method yields limiting solutions for potential flow. The effect of circulation is considered. A comparison of derived velocity distributions with existing results that are based on calculation to the third order in the thickness ratio indicated satisfactory agreement. The results are also presented in the form of a set of compressibility correction rules that lie between the Prandtl-Glauert rule and the von Karman-Tsien rule (approximately). The different rules correspond to different values of the local shape parameter square root sign YC sub a, in which Y is the ordinate and C sub a is the curvature at a point on an airfoil. Bodies of revolution, completely supersonic flows, and the significance of the limiting solutions for potential flow are also briefly discussed.

Perl, W↗

Solution Irregularity Remediation for Spatial Discretization Error Estimation for S N Transport Solutions

The discrete ordinates linear Boltzmann transport equation is typically solved in its spatially discretized form, incurring spatial discretization error. Quantification of this error for purposes such as adaptive mesh refinement or error analysis requires an a posteriori estimator, which utilizes the numerical solution to the spatially discretized equation to compute an estimate. Because the quality of the numerical solution informs the error estimate, irregularities, present in the true solution for any realistic problem configuration, tend to cause the largest deviation in the error estimate vis-a-vis the true error. In this paper, an analytical partial singular characteristic tracking (pSCT) procedure for reducing the estimator’s error is implemented within our novel residual source estimator for a zeroth-order discontinuous Galerkin scheme, at the additional cost of a single inner iteration. Here, a metric-based evaluation of the pSCT scheme versus the standard residual source estimator is performed over the parameter range of a Method of Manufactured Solutions test suite. The pSCT scheme generates near-ideal accuracy in the estimate in problems where the dominant source of the estimator’s error is the solution irregularity, namely, problems where the true solution is discontinuous and problems where the true solution’s first derivative is discontinuous and the scattering ratio is low. In problems where the scattering ratio is high and the true solution is discontinuous in the first derivative, the error in the scattering source, which is not converged by the pSCT scheme, is greater than the error incurred due to the irregularity. Ultimately, a pSCT scheme is judged to be useful for error estimation in problems where the computational cost of the scheme is justified. In the presence of many irregularities, such a scheme may be intractable for general use, but in benchmarks, as an analytical tool, or in problems that have nondissipative discontinuities, the scheme may prove invaluable.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Approximate hydrodynamic design of a finite span hydrofoil

Previous work on the motion of various bodies under the surface of a heavy fluid is discussed. The solution of the motion of a flat plate by Keldysh and Lavrentiev is applied to the motion of a hydrofoil, making possible the presentation of charts for determining the lift and resistance of an infinite span hydrofoil operating in a heavy frictionless fluid having infinite depth below the free water surface. Consideration is given to the effects of viscosity and a method is suggested to correct for the finite span. The effect of the water surface on the downwash behind the foil is also discussed. A comparison of theoretical results obtained from this work with experimental data indicates that a basis for the approximate hydrodynamic design of a finite span hydrofoil has been achieved.

HYDRODYNAMICS↗

Model certainty in cellular network-driven processes with missing data

Mathematical models are often used to explore network-driven cellular processes from a systems perspective. However, a dearth of quantitative data suitable for model calibration leads to models with parameter unidentifiability and questionable predictive power. Here we introduce a combined Bayesian and Machine Learning Measurement Model approach to explore how quantitative and non-quantitative data constrain models of apoptosis execution within a missing data context. We find model prediction accuracy and certainty strongly depend on rigorous data-driven formulations of the measurement, and the size and make-up of the datasets. For instance, two orders of magnitude more ordinal (e.g., immunoblot) data are necessary to achieve accuracy comparable to quantitative (e.g., fluorescence) data for calibration of an apoptosis execution model. Notably, ordinal and nominal (e.g., cell fate observations) non-quantitative data synergize to reduce model uncertainty and improve accuracy. Finally, we demonstrate the potential of a data-driven Measurement Model approach to identify model features that could lead to informative experimental measurements and improve model predictive power.

59 BASIC BIOLOGICAL SCIENCES↗

Investigation of the Liquid Fluorine-liquid Diborane Propellant Combination in a 100-pound-thrust Rocket Engine

The experimental performance of liquid fluorine and liquid diborane was investigated in a 100-pound-thrust engine at a combustion pressure of 300 pounds per square inch absolute. Methods of handling and transporting liquid fluorine were developed. It was extremely difficult to obtain satisfactory operation because of the high flame speed and high combustion chamber temperatures. The maximum performance obtained was 280 pound seconds per pound, 88 percent of the theoretical maximum. The theoretical performance was recalculated with revised thermodynamic data, indicating a maximum specific impulse of 311 pound seconds per pound as compared with the previously reported value of 323.

COMBUSTION - ROCKET ENGINES↗

Common radiation analysis model for 75,000 pound thrust NERVA engine (1137400E)

The mathematical model and sources of radiation used for the radiation analysis and shielding activities in support of the design of the 1137400E version of the 75,000 lbs thrust NERVA engine are presented. The nuclear subsystem (NSS) and non-nuclear components are discussed. The geometrical model for the NSS is two dimensional as required for the DOT discrete ordinates computer code or for an azimuthally symetrical three dimensional Point Kernel or Monte Carlo code. The geometrical model for the non-nuclear components is three dimensional in the FASTER geometry format. This geometry routine is inherent in the ANSC versions of the QAD and GGG Point Kernal programs and the COHORT Monte Carlo program. Data are included pertaining to a pressure vessel surface radiation source data tape which has been used as the basis for starting ANSC analyses with the DASH code to bridge into the COHORT Monte Carlo code using the WANL supplied DOT angular flux leakage data. In addition to the model descriptions and sources of radiation, the methods of analyses are briefly described.

Warman, E. A.↗

Domain Knowledge Guided Bayesian Optimization For Autonomous Alignment Of Complex Scientific Instruments

Bayesian Optimization (BO) is a powerful tool for optimizing complex non-linear systems. However, its performance degrades in high-dimensional problems with tightly coupled parameters and highly asymmetric objective landscapes, where rewards are sparse. In such needle-in-a-haystack scenarios, even advanced methods like trust-region BO (TurBO) often lead to unsatisfactory results. We propose a domain knowledge guided Bayesian Optimization approach, which leverages physical insight to fundamentally simplify the search problem by transforming coordinates to decouple input features and align the active subspaces with the primary search axes. We demonstrate this approach's efficacy on a challenging 12-dimensional, 6-crystal Split-and-Delay optical system, where conventional approaches, including standard BO, TuRBO and multi-objective BO, consistently led to unsatisfactory results. When combined with an reverse annealing exploration strategy, this approach reliably converges to the global optimum. The coordinate transformation itself is the key to this success, significantly accelerating the search by aligning input co-ordinate axes with the problem's active subspaces. As increasingly complex scientific instruments, from large telescopes to new spectrometers at X-ray Free Electron Lasers are deployed, the demand for robust high-dimensional optimization grows. Our results demonstrate a generalizable paradigm: leveraging physical insight to transform high-dimensional, coupled optimization problems into simpler representations can enable rapid and robust automated tuning for consistent high performance while still retaining current optimization algorithms.

FOS: Computer and information sciences↗

Informing climate adaptation strategies using ecological simulation models and spatial decision support tools

Introduction: Forest landscapes offer resources and ecosystem services that are vital to the social, economic, and cultural well-being of human communities, but managing for these provisions can require socially and ecologically relevant trade-offs. We designed a spatial decision support model to reveal trade-offs and synergies between ecosystem services in a large eastern Cascade Mountain landscape in Washington State, USA. Methods: We used process-based forest landscape (LANDIS-II) and hydrology (DHSVM) models to compare outcomes associated with 100 years of simulated forest and wildfire dynamics for two management scenarios, Wildfire only and Wildfire + Treatments. We then examined the strength and spatial distribution of potential treatment effects and trends in a set of resources and ecosystem services over the simulation period. Results: We found that wildfire area burned increased over time, but some impacts could be mitigated by adaptation treatments. Treatment benefits were not limited to treated areas. Interestingly, we observed neighborhood benefits where fire spread and severity were reduced not only in treated patches but in adjacent patches and landscapes as well, creating potential synergies among some resource benefits and services. Ordinations provided further evidence for two main kinds of outcomes. Positive ecological effects of treatments were greatest in upper elevation moist and cold forests, while positive benefits to human communities were aligned with drier, low- and mid-elevation forests closer to the wildland urban interface. Discussion: Our results contribute to improved understanding of synergies and tradeoffs linked to adaptation and restoration efforts in fire-prone forests and can be used to inform management aimed at rebuilding resilient, climate-adapted landscapes.

54 ENVIRONMENTAL SCIENCES↗

Using Polarized PCRTM-Solar Model to Validate EMIT Surface Reflectance L2A Product

Using the vector linearized discrete ordinate radiative transfer model (VLIDORT), a multiple-scattering multi-layer scattering code, coupled with a fast principal component (PC) radiative transfer model (PCRTM), we can simulate hyperspectral radiation fields from visible to shortwave infrared (VSWIR), i.e., 250 nm to 2500 nm. Since only limited accurate line-by-line calculation using VLIDORT is needed, this coupled PCRTM-VLIDORT approach is very efficient for simulating hyperspectral VSWIR spectra. These simulations incorporate accurately defined optical properties (gas absorptions, molecular and aerosol/cloud particle scattering) and detailed surface reflectance inputs. In this study we used the current L2A products of the Earth Surface Mineral Dust Source Investigation (EMIT) imaging spectrometer as the inputs to PCRTM-VLIDORT to simulate EMIT spectra. Comparing the simulated spectra with EMIT measurements provides an efficient method to validate the current EMIT product.

Xiaozhen Xiong↗

Validation of a Solid Rocket Motor Internal Environment Model

In a prior effort, a thermal/fluid model of the interior of Penn State University's laboratory-scale Insulation Test Motor (ITM) was constructed to predict both the convective and radiative heat transfer to the interior walls of the ITM with a minimum of empiricism. These predictions were then compared to values of total and radiative heat flux measured in a previous series of ITM test firings to assess the capabilities and shortcomings of the chosen modeling approach. Though the calculated fluxes reasonably agreed with those measured during testing, this exercise revealed means of improving the fidelity of the model to, in the case of the thermal radiation, enable direct comparison of the measured and calculated fluxes and, for the total heat flux, compute a value indicative of the average measured condition. By replacing the P1-Approximation with the discrete ordinates (DO) model for the solution of the gray radiative transfer equation, the radiation intensity field in the optically thin region near the radiometer is accurately estimated, allowing the thermal radiation flux to be calculated on the heat-flux sensor itself, which was then compared directly to the measured values. Though the fully coupling the wall thermal response with the flow model was not attempted due to the excessive computational time required, a separate wall thermal response model was used to better estimate the average temperature of the graphite surfaces upstream of the heat flux gauges and improve the accuracy of both the total and radiative heat flux computations. The success of this modeling approach increases confidence in the ability of state-of-the-art thermal and fluid modeling to accurately predict SRM internal environments, offers corrections to older methods, and supplies a tool for further studies of the dynamics of SRM interiors.

Martin, Heath T.↗

Validation of a Solid Rocket Motor Internal Environment Model

In a prior effort, a thermal/fluid model of the interior of Penn State University's laboratory-scale Insulation Test Motor (ITM) was constructed to predict both the convective and radiative heat transfer to the interior walls of the ITM with a minimum of empiricism. These predictions were then compared to values of total and radiative heat flux measured in a previous series of ITM test firings to assess the capabilities and shortcomings of the chosen modeling approach. Though the calculated fluxes reasonably agreed with those measured during testing, this exercise revealed means of improving the fidelity of the model to, in the case of the thermal radiation, enable direct comparison of the measured and calculated fluxes and, for the total heat flux, compute a value indicative of the average measured condition. By replacing the P1-Approximation with the discrete ordinates (DO) model for the solution of the gray radiative transfer equation, the radiation intensity field in the optically thin region near the radiometer is accurately estimated, allowing the thermal radiation flux to be calculated on the heat-flux sensor itself, which was then compared directly to the measured values. Though the fully coupling the wall thermal response with the flow model was not attempted due to the excessive computational time required, a separate wall thermal response model was used to better estimate the average temperature of the graphite surfaces upstream of the heat flux gauges and improve the accuracy of both the total and radiative heat flux computations. The success of this modeling approach increases confidence in the ability of state-of-the-art thermal and fluid modeling to accurately predict SRM internal environments, offers corrections to older methods, and supplies a tool for further studies of the dynamics of SRM interiors.

Martin, Heath T.↗

Evaluation of data collection bias of third molar stages of mineralisation for age estimation in the living

Abstract Age assessment of the living is a fundamental procedure in the process of human identification, in order to guarantee fair treatment of individuals, which has ethical, civil, legal, and medical repercussions. The careful selection of the appropriate methods requires evaluation of several parameters: accuracy, precision of the method, as well as its reproducibility. The approach proposed by Mincer et al. adapted from Demirjian et al. exploring third molar mineralisation, is one of the most frequently considered for age estimation of the living. Thus, this work aims to assess potential bias in the data collection when applying the classification stages for dental mineralisation adapted by Mincer et al. A total of 102 orthopantomographs, of clinical origin, belonging to individuals aged between 12 and 25 years ($ \bar{\textit x} $ = 20.12 years, SD = 3.49 years; 65 females, 37 males, all of Portuguese nationality) were included and a retrospective analysis performed by five observers with different levels of experience (high, average, and basic). The performance and agreement between five observers were evaluated using Weighted Cohen’s Kappa and the Intraclass Correlation Coefficient. To access the influence of impaction on third molar classification, variables were tested using ordinal logistic regression Generalised Linear Model. It was observed that there were variations in the number of teeth identified among the observers, but the agreement levels ranged from moderate to substantial (0.4–0.8). Upon closer examination of the results, it was observed that although there were discernible differences between highly experienced observers and those with less experience, the gap was not as significant as initially hypothesised, and a greater disparity between the classifications of the upper (0.24–0.49) and lower third molars (>0.55) was observed. When bone superimposition is present, the classification process is not significantly influenced; however, variation in teeth angulation affects the assessment. The results suggest that with an efficient preparation, the level of experience as a factor can be overcome. Mincer and colleague's classification system can be replicated with ease and consistency, even though the classification of upper and lower third molars presents distinct challenges.

de Oliveira Santos, Inês (ORCID:0000000267324347)↗

Examination of coal combustion management sites for microbiological and chemical signatures of groundwater impacts

Coal combustion accounts for 40% of the world’s electricity and generates more than a billion tons of coal combustion products (CCP) annually, half of which end up in landfills and impoundments. CCP contain mixtures of chemicals that can be mobile in the environment and impact the quality of surface water and potable groundwater. In this investigation, water samples from 14 coal combustion management sites across 4 physiographic regions in the United States, paired with background and down-gradient groundwater samples, were analyzed for water chemistry and microbiology. The objective was to determine if microbiology data alone, or supported by chemistry data, could reliably differentiate source waters and identify sites where CCP is known or expected to be influencing groundwater. Two percent of the total amplicons showed genus level conservation across CCP management sites, regions, and sample types; corresponding to ubiquitous, facultatively aerobic proteobacterial taxa that are generally recognized for the potential to respire using different terminal electron acceptors. Ordination plots did not reveal significant differences ( p > 0.05) in 16S rRNA gene amplicon diversity by CCP management site, water sample types, or physiographic regions. Contrastingly, chemistry distinguished sample types by standard water quality metrics (total dissolved solids, Ca:SO 4 ratio), alkali earth metals (K, Na, Li), selenium, boron, and fluoride. A focused evaluation of 16S rRNA gene amplicons for a subset of CCP management sites revealed microbiological features and chemical drivers (F, Ca, temperature) that positively identified the single CCP management site confirmed to have groundwater impacted by CCP leachate. At this site, 9 genera (>0.5% relative abundance) were exclusive to CCP porewater and downgradient groundwater. Inferred metabolisms for these taxa indicates potential for N and S biogeochemical transformations and 1-C metabolism that are consistent with a reducing environment, as evidenced by low ORP and depleted SO 4 2− . This research contributes to a growing understanding of conditions where these data types, analyses, and interpretation methods could be applied for distinguishing influence from CCP on the surrounding environment, as well as practical limitations.

01 COAL, LIGNITE, AND PEAT↗

An Optimal-Estimation-Based Aerosol Retrieval Algorithm Using OMI Near-UV Observations

An optimal-estimation(OE)-based aerosol retrieval algorithm using the OMI (Ozone Monitoring Instrument) near-ultraviolet observation was developed in this study. The OE-based algorithm has the merit of providing useful estimates of errors simultaneously with the inversion products. Furthermore, instead of using the traditional lookup tables for inversion, it performs online radiative transfer calculations with the VLIDORT (linearized pseudo-spherical vector discrete ordinate radiative transfer code) to eliminate interpolation errors and improve stability. The measurements and inversion products of the Distributed Regional Aerosol Gridded Observation Network campaign in northeast Asia (DRAGON NE-Asia 2012) were used to validate the retrieved aerosol optical thickness (AOT) and single scattering albedo (SSA). The retrieved AOT and SSA at 388 nm have a correlation with the Aerosol Robotic Network (AERONET) products that is comparable to or better than the correlation with the operational product during the campaign. The OEbased estimated error represented the variance of actual biases of AOT at 388 nm between the retrieval and AERONET measurements better than the operational error estimates. The forward model parameter errors were analyzed separately for both AOT and SSA retrievals. The surface reflectance at 388 nm, the imaginary part of the refractive index at 354 nm, and the number fine-mode fraction (FMF) were found to be the most important parameters affecting the retrieval accuracy of AOT, while FMF was the most important parameter for the SSA retrieval. The additional information provided with the retrievals, including the estimated error and degrees of freedom, is expected to be valuable for relevant studies. Detailed advantages of using the OE method were described and discussed in this paper.

Air Pollution↗

Development of a Griffin model of the advanced test reactor

In the pursuit of a higher fidelity deterministic simulation capability of the Advanced Test Reactor, it is important to have a fast yet accurate deterministic neutronics model. Here, to achieve this, we employed an advanced two-step method. The first step involves generating homogenized cross sections using OpenMC, a cutting-edge Monte Carlo neutron transport code. OpenMC offers excellent modular capabilities, allowing for easy component integration and flexibility in incorporating new designs into the model. The second step involves deterministic transport calculations, which are performed using Griffin, a reactor physics application based on the Multiphysics Object-Oriented Simulation Environment (MOOSE). To ensure the accurate spatial resolution and assignment of material cross sections, a Cubit-generated mesh for the Advanced Test Reactor is utilized as an intermediate step between the OpenMC and Griffin models; Griffin utilizes the mesh for its finite element solution, while OpenMC material identifications are written to the mesh file to be used in Griffin material assignments. Additionally, a Python-based script converts the cross sections generated by OpenMC into the ISOXML format required by Griffin. Initial comparisons using the Griffin diffusion solver indicated good agreement between the neutron multiplication factors obtained from the standalone OpenMC model and the Griffin model, with differences of less than 10 pcm in the 2D geometry configuration; it was later determined that this agreement was likely due to compensating effect and was more likely on the order of –700 pcm relative to the OpenMC solution. However, in three-dimensional calculations, an unacceptably large error (almost 8,000 pcm) was found in the Griffin solution with the diffusion solver. Subsequent calculations using Griffin’s discrete ordinates solver demonstrated substantially improved agreement, within 116 pcm of the OpenMC solution used to generate the cross sections for Griffin. Building on this capability, future work will seek to perform more detailed validation calculations. The ultimate goal is to evaluate both transient and multiphysics simulations of the reactor.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Summary of Airfoil Data

Recent airfoil data for both flight and wind-tunnel tests have been collected and correlated insofar as possible. The flight data consist largely of drag measurements made by the wake-survey method. Most of the data on airfoil section characteristics were obtained in the Langley two-dimensional low-turbulence pressure tunnel. Detail data necessary for the application of NACA 6-serles airfoils to wing design are presented in supplementary figures, together with recent data for the NACA 24-, 44-, and 230-series airfoils. The general methods used to derive the basic thickness forms for NACA 6- and 7-series airfoils and their corresponding pressure distributions are presented. Data and methods are given for rapidly obtaining the approximate pressure distributions for NACA four-digit, five-digit, 6-, and 7-series airfoils. The report includes an analysis of the lift, drag, pitching-moment, and critical-speed characteristics of the airfoils, together with a discussion of the effects of surface conditions. Available data on high-lift devices are presented. Problems associated with lateral-control devices, leading-edge air intakes, and interference are briefly discussed. The data indicate that the effects of surface condition on the lift and drag characteristics are at least as large as the effects of the airfoil shape and must be considered in airfoil selection and the prediction of wing characteristics. Airfoils permitting extensive laminar flow, such as the NACA 6-series airfoils, have much lower drag coefficients at high speed and cruising lift coefficients than earlier types-of airfoils if, and only if, the wing surfaces are sufficiently smooth and fair. The NACA 6-series airfoils also have favorable critical-speed characteristics and do not appear to present unusual problems associated with the application of high-lift and lateral-control devices. Much of the data given in the NACA Advance Confidential Report entitled "Preliminary Low-Drag-Airfoil and Flap Data from Tests at Large Reynolds Number and Low Turbulence," by Eastman N. Jacobs, Ira R. Abbott, and Milton Davidson, March 1942 has been corrected and included in the present paper, which supersedes the previously published paper.

LOW-DRAG↗