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At least 631 records · Page 35

A Comprehensive Scientific Survey of Excipients Used in Currently Marketed, Therapeutic Biological Drug Products

The steady development of biotechnology-derived therapeutic biologics over the last few decades has generated drugs that are now standard medical treatments for a range of indications. While the development of protein products has surged in recent years, the formulation and delivery of these complex molecules have relied on drug-specific studies and, in some instances, data from non-proteinaceous drug products. The commonalities, trends, and gaps in excipient technologies used to support the development of therapeutic proteins largely remain unexplored due to the drug-specific nature of many formulations. Using a comprehensive and relational database approach, we aimed to provide a scientific survey of all approved or licensed biotechnology-derived drug products with the goal of providing evidence-based information on common attributes and trending features in protein product excipients. We examined 665 formulations, and 395 unique formulations based on having unique excipients within them, that supported 211 therapeutic proteins as of June 2020. We report the prevalence of each excipient class and excipient chemical used in eight different drug types including monoclonal antibodies, antibody conjugates, cytokines and growth factors, enzymes, polypeptide hormones, pulmonary surfactants, recombinant fusion proteins, and toxins. We also report the prevalence by excipient type among all therapeutic proteins, in the context of each drug’s recommended pH range, concentration ranges for excipients, and route of administration. The results of our analyses indicate certain excipients common to monoclonal antibodies, cytokines, and polypeptide hormones. We also report on excipients unique to protein drug products, such as amino acids, solubilizers, and lyoprotectants. Overall, our report summarizes the current landscape of excipients used in marketed biotechnology-derived therapeutic biologic products.

60 APPLIED LIFE SCIENCES↗

Instrument design for an inertial confinement fusion ion temperature imager

A mix of contaminant mass is a known, performance-limiting factor for laser-driven inertial confinement fusion (ICF). It has also recently been shown that the contaminant mass is not necessarily in thermal equilibrium with the deuterium–tritium plasma. Contaminant mass temperature is one of the dominant uncertainties in contaminant mass estimates. The MixIT diagnostic is a new and potentially transformative diagnostic, capable of spatially resolving ion temperature. The approach combines principles of neutron time-of-flight and neutron imaging diagnostics. The information from the MixIT diagnostic can be used to optimize ICF target and laser drive designs as well as provide key constraints on ICF radiation-hydrodynamic simulations that are critical to contaminant mass estimates. This work details the design and optimization of the major components of the MixIT diagnostic: the neutron aperture, the neutron detector (scintillator), and the recording system.

47 OTHER INSTRUMENTATION↗

Investigating the possible existence of hyper-heavy nuclei in a neutron-star environment

The synthesis of hyper-heavy elements is investigated under conditions simulating neutron star environment. The constrained molecular dynamics approach is used to simulate low energy collisions of extremely n-rich nuclei. A new type of the fusion barrier due to a “neutron wind” is observed when the effect of neutron star environment (screening of Coulomb interaction) is introduced implicitly. When introducing also a background of surrounding nuclei, the nuclear fusion becomes possible down to temperatures of 10 8 K and synthesis of extremely heavy and n-rich nuclei appears feasible. A possible existence of hyper-heavy nuclei in a neutron star environment could provide a mechanism of extra coherent neutrino scattering or an additional mechanism, resulting in x-ray burst or a gravitational wave signal and, thus, becoming another crucial process adding new information to the suggested models on neutron star evolution.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

The $$\pi f_0(500)$$ decay of the $$a_1(1260)$$

Abstract We evaluate the $$a_1(1260) \rightarrow \pi \sigma (f_0(500))$$ a 1 ( 1260 ) → π σ ( f 0 ( 500 ) ) decay width from the perspective that the $$a_1(1260)$$ a 1 ( 1260 ) resonance is dynamically generated from the pseudoscalar–vector interaction and the $$\sigma $$ σ arises from the pseudoscalar–pseudoscalar interaction. A triangle mechanism with $$a_1(1260) \rightarrow \rho \pi $$ a 1 ( 1260 ) → ρ π followed by $$\rho \rightarrow \pi \pi $$ ρ → π π and a fusion of two pions within the loop to produce the $$\sigma $$ σ provides the mechanism for this decay under these assumptions for the nature of the two resonances. We obtain widths of the order of 13–22 MeV. Present experimental results differ substantially from each other, suggesting that extra efforts should be devoted to the precise extraction of this important partial decay width, which should provide valuable information on the nature of the axial vector and scalar meson resonances and help clarify the role of the $$\pi \sigma $$ π σ channel in recent lattice QCD calculations of the $$a_1$$ a 1 .

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Hot filament technique for measuring the thermal conductivity of molten lithium fluoride

Molten salts, such as lithium fluoride, are attractive candidates for thermal energy storage in solar dynamic space power systems because of their high latent heat of fusion. However, these same salts have poor thermal conductivities which inhibit the transfer of heat into the solid phase and out of the liquid phase. One concept for improving the thermal conductivity of the thermal energy storage system is to add a conductive filler material to the molten salt. High thermal conductivity pitch-based graphite fibers are being considered for this application. Although there is some information available on the thermal conductivity of lithium fluoride solid, there is very little information on lithium fluoride liquid, and no information on molten salt graphite fiber composites. This paper describes a hot filament technique for determining the thermal conductivity of molten salts. The hot filament technique was used to find the thermal conductivity of molten lithium fluoride at 930 C, and the thermal conductivity values ranged from 1.2 to 1.6 W/mK. These values are comparable to the slightly larger value of 5.0 W/mK for lithium fluoride solid. In addition, two molten salt graphite fiber composites were characterized with the hot filament technique and these results are also presented.

Jaworske, Donald A.↗

Representation and Integration of Scientific Information

The objective of this Joint Research Interchange with NASA-Ames was to investigate how the Tsimmis technology could be used to represent and integrate scientific information. The main goal of the Tsimmis project is to allow a decision maker to find information of interest from such sources, fuse it, and process it (e.g., summarize it, visualize it, discover trends). Another important goal is the easy incorporation of new sources, as well the ability to deal with sources whose structure or services evolve. During the Interchange we had research meetings approximately every month or two. The funds provided by NASA supported work that lead to the following two papers: Fusion Queries over Internet Databases; Efficient Query Subscription Processing in a Multicast Environment.

Source record↗

Dynamic and Structural Gas Turbine Engine Modeling

Model the interactions between the structural dynamics and the performance dynamics of a gas turbine engine. Generally these two aspects are considered separate, unrelated phenomena and are studied independently. For diagnostic purposes, it is desirable to bring together as much information as possible, and that involves understanding how performance is affected by structural dynamics (if it is) and vice versa. This can involve the relationship between thrust response and the excitation of structural modes, for instance. The job will involve investigating and characterizing these dynamical relationships, generating a model that incorporates them, and suggesting and/or developing diagnostic and prognostic techniques that can be incorporated in a data fusion system. If no coupling is found, at the least a vibration model should be generated that can be used for diagnostics and prognostics related to blade loss, for instance.

Turso, James A.↗

Spatiotemporal Automatic Calibration of Infrastructure Lidar, Radar, and Camera with a Global Navigation Satellite System: Preprint

Robust and accurate perception is important for modern intelligent transportation systems (ITS), which use sensors of various modalities for data fusion to create a digital twin of an intersection. Sensor calibration is an important process that creates a unified coordinate frame for the sensor output data so that it can be used for data fusion. Classical approaches for sensor calibration are time-consuming, require an overlapping field of view for feature matching, and are not feasible for ITS application as they cause disruptions in the flow of traffic. In this paper, we present a spatiotemporal automatic calibration approach to calibrate multiple infrastructure lidar, radar, and cameras installed at a traffic intersection. The approach uses global navigation satellite system (GNSS) positioning information shared by connected vehicles, and when the vehicle is detected by the sensor, we match the sensor detections with the GNSS coordinates. The proposed algorithm is evaluated with a real-world dataset utilizing detections from two radars, cameras, and lidars with a test vehicle instrumented with a post-processing kinematic (PPK)-corrected GNSS driving past the sensors installed at a four-way traffic intersection. The experimental results show that the proposed automatic calibration approach can achieve the transformation with a root mean squared error of less than 0.5 for radar and lidar and less than 2 for camera detections. The ability to rapidly calibrate sensors not only benefits initial installations, but can also be used for system health monitoring, while utilizing available connected vehicle data to test the real-time sensor fidelity and operational status.

ADVANCED PROPULSION SYSTEMS↗

Recap of DIP Workshop Series: #1 DIP Architecture and Data Integrations Services

This workshop will cover DIP architecture and data integration services to obtain feedback from America for Airlines (A4A) Air Traffic Management Council (ATMC). Participants will get a look at how the DIP architecture is set-up as well as how data integration services are planned to be hosted on the platform. The DIP architecture review is intended to cover how DIP was envisioned and how DIP is being developed to address data needs across the industry. Participants will have a chance to provide feedback on the DIP architecture and gain insight into how one might interface with the DIP to send or receive data. The data integration services portion is intended to cover DIP’s technical approach to data integration. As an example implementation, there will be a first look at possible data fusion on the platform, including utilizing NASA’s Fuser, and tailoring for industry data consumers. Descriptions, at a high-level, of input to and output of the Fuser will also be discussed.

ATM-X↗

Verification of an improved equation-free projective integration method for neoclassical plasma-profile evolution in tokamak geometry

A brute-force, long-time gyrokinetic simulation of plasma profile evolution in magnetic fusion devices is not desirable due to large computational resource requirements and a possible accumulation of numerical error. The equation-free projective integration method of Keverekidis et al. [Commun. Math. Sci. 1(4), 715–762 (2003)] is one of the outstanding candidates in projecting micro-scale simulations to a longer timescale. However, its application to tokamak plasma has not been fruitful due to the appearance of spurious transient oscillations in the lifting process, which are present when the kinetic simulations are initialized with a simplified model distribution function and which make the kinetic simulations to deviate from the desired paths. In this work, a kinetically informed lifting algorithm is added to the equation-free projective integration method, which is then verified in the electrostatic gyrokinetic particle-in-cell code XGCa [R. Hager and C. S. Chang, Phys. Plasmas 23, 042503 (2016)] for a neoclassical ion heat transport problem with adiabatic electrons. This new lifting operator is demonstrated to control spurious transients, enabling an over four-times reduction in the overall computing time in the time-evolution of the ion temperature profile in an axisymmetric toroidal plasma. Further reduction in the computing time is found to be limited due to the stability properties of the linear least squares projective integrator.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Earth Science Technology Office (ESTO) New Observing Strategies (NOS) and NOS-Testbed (NOS-T)

With the advancement of space hardware technologies such as smaller spacecraft, component and instrument miniaturization and high performance space processors, and with the advancement of software technologies in artificial intelligence, big data analysis and autonomous decision making, Earth Science is looking at novel ways to observe phenomena that previously could not have been studied or would have been too expensive to study with traditional missions. In particular, the New Observing Strategies (NOS) component of the NASA Earth Science Technology Office (ESTO) Advanced Information Systems Technology (AIST) Program aims at leveraging these novel technologies as well as low cost and easy access to space to acquire multi-temporal or simultaneous multi-angular, multi-locations, multi-resolution and multi-spectral observations that will provide better multi-source measurements and will build a more dynamic and comprehensive picture of Earth Science phenomena that need to be studied and analyzed. For applications such as water resources management, air quality monitoring, biodiversity studies or disaster management, NOS will integrate the use of small instruments, small spacecraft, constellations of spacecraft and networks of sensors to design new missions that will provide the necessary measurements to improve future forecast and science modeling systems.Measurement acquisition will therefore be approached as a system of systems rather than on a mission basis, and a system of this complexity should not be expected to work without full integration and experimental characterization. Although most of the individual technologies enabling to link and coordinate multi-source observations are more or less mature, a few technologies need to be developed and all of them need to be integrated and tested as a system. In order for this validation to occur, the AIST Program is developing the NOS Testbed that includes 3 main goals:1.Validate novel NOS technologies, independently and as a system2.Demonstrate novel distributed operations concepts3.Socialize new Distributed Spacecraft Mission (DSM) and SensorWeb (SW) technologies and concepts to the science community by significantly retiring the risk of integrating these new technologies.The NOS Testbed will consist of multiple sensing nodes, simulated or actual, representing space, air and/or ground measurements, that are interconnected by a communications fabric (infrastructure that permits nodes to transmit and receive data between one another and interact with each other). Each node will be supported by hardware capabilities required to perform nodes monitoring and command & control, as well as intelligent "onboard" computing. The nodes will work together in a collaborative manner to demonstrate optimal science capabilities. The testbed will enable to validate technologies such as inter-node communication models, techniques and protocols; inter-node coordination; real-time data fusion and understanding; planning; sensor re-targeting; etc. Additionally, the testbed will have the capability to interact with various mission design tools, OSSEs and one or several forecast models. More details about the NOS Testbed will be presented at the confererence.

Earth Science missions; Advanced information Syste↗

Anomalies of coset non-invertible symmetries

Anomalies of global symmetries provide important information on the quantum dynamics. We show the dynamical constraints can be organized into three classes: genuine anomalies, fractional topological responses, and integer responses that can be realized in symmetry-protected topological (SPT) phases. Coset symmetry can be present in many physical systems including quantum spin liquids, and the coset symmetry can be a non-invertible symmetry. We introduce twists in coset symmetries, which modify the fusion rules and the generalized Frobenius-Schur indicators. We call such coset symmetries twisted coset symmetries, and they are labeled by the quadruple (G, K, ω D+1 , α D ) in D spacetime dimensions where G is a group and K ⊂ G is a discrete subgroup, ω D+1 is a (D + 1)-cocycle for group G, and α D is a D-cochain for group K. We present several examples with twisted coset symmetries using lattice models and field theory, including both gapped and gapless systems (such as gapless symmetry-protected topological phases). We investigate the anomalies of general twisted coset symmetry, which presents obstructions to realizing the coset symmetry in (gapped) symmetry-protected topological phases. We show that finite coset symmetry G/K becomes anomalous when G cannot be expressed as the bicrossed product G = H ⋈ K , and such anomalous coset symmetry leads to symmetry-enforced gaplessness in generic spacetime dimensions. We illustrate examples of anomalous coset symmetries with A 5 / \Z 2 symmetry, with realizations in lattice models.

Hsin, Po-Shen [King’s College London (United Kingd↗

How do tradeoffs in satellite spatial and temporal resolution impact snow water equivalent reconstruction?

Given the tradeoffs between spatial and temporal resolution, questions about resolution optimality are fundamental to the study of global snow. Answers to these questions will inform future scientific priorities and mission specifications. Heterogeneity of mountain snowpacks drives a need for daily snow cover mapping at the slope scale (≤30 m) that is unmet for a variety of scientific users, ranging from hydrologists to the military to wildlife biologists. But finer spatial resolution usually requires coarser temporal or spectral resolution. Thus, no single sensor can meet all these needs. Recently, constellations of satellites and fusion techniques have made noteworthy progress. The efficacy of two such recent advances is examined: (1) a fused MODIS–Landsat product with daily 30 m spatial resolution and (2) a harmonized Landsat 8 and Sentinel 2A and B (HLS) product with 3–4 d temporal and 30 m spatial resolution. State-of-the-art spectral unmixing techniques are applied to surface reflectance products from 1 and 2 to create snow cover and albedo maps. Then an energy balance model was run to reconstruct snow water equivalent (SWE). For validation, lidar-based Airborne Snow Observatory SWE estimates were used. Results show that reconstructed SWE forced with 30 m resolution snow cover has lower bias, a measure of basin-wide accuracy, than the baseline case using MODIS (463 m cell size) but greater mean absolute error, a measure of per-pixel accuracy. However, the differences in errors may be within uncertainties from scaling artifacts, e.g., basin boundary delineation. Other explanations are (1) the importance of daily acquisitions and (2) the limitations of downscaled forcings for reconstruction. Conclusions are as follows: (1) spectrally unmixed snow cover and snow albedo from MODIS continue to provide accurate forcings for snow models and (2) finer spatial and temporal resolution through sensor design, fusion techniques, and satellite constellations are the future for Earth observations, but existing moderate-resolution sensors still offer value.

Edward H. Bair↗

Three-dimensional reconstruction of implosion stagnation in laser direct drive on OMEGA

Multidimensional effects on hot-spot formation must be considered to better understand the current limits on the performance of direct-drive inertial confinement fusion experiments on OMEGA with cryogenically layered solid deuterium–tritium targets. A comprehensive reconstruction effort has been established at the Laboratory for Laser Energetics to infer hot-spot and shell conditions at stagnation from a large collection of x-ray, neutron, and particle detectors along multiple lines of sight. Several time-gated and time-integrated x-ray imagers are being used to record the shape of the hot-spot plasma. A 3D hot-spot x-ray emission tomography technique has been developed to infer low-mode drive asymmetries from the hot-spot shape. A suite of neutron diagnostics is used to provide measurements of hot-spot flow velocity, ion temperature, and areal density. Here, the information obtained from the x-ray and neutron detectors will be combined into a coherent model of the shape of the hot spot and shell assembly.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Validation of magnetized gas-jet experiments to investigate the effects of an external magnetic field on laser-plasma instabilities

Laser-plasma instabilities (LPI) play a detrimental role in energy coupling to the target in inertial confinement fusion (ICF). The recent development of applied strong magnetic fields for use in ICF and laboratory astrophysics experiments has opened opportunities to investigate the role of external magnetic fields on LPIs. Recent numerical studies have shown that stimulated Raman scattering (SRS) can be mitigated by external magnetic fields in the kinetic regime of the instability and warrant systematic experimental studies to validate modelling. To this end, we design experiments at the OMEGA-EP laser facility to investigate the effect of an external perpendicular B-field of 5–30 T on the backscattered light spectrum from a gas-jet target. We present measurements from a proof-of-principle experiment, where the backward-SRS (BSRS) is in the kinetic regime, for which the magnetization is expected to produce the greatest effects on instability growth. New simulations motivated by this experiment are used to inform the proposal of an upgraded experimental design. Our simulation predictions show that the new design is suited to experimentally demonstrating BSRS mitigation by an external magnetic field, despite the magnetization effects on the hydrodynamics, as well as the inherent temporal and spatial variations in plasma conditions.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Diagnosing magnetic fields in cylindrical implosions with oblique proton radiography

Two experiments at the OMEGA Laser System used oblique proton radiography to measure magnetic fields in cylindrical implosions with and without an applied axial magnetic field. Although the goal of both experiments was to measure the magnitude of the compressed axial magnetic field in the core of the implosion, this field was obfuscated by two features in the coronal plasma produced by the compression beams: an azimuthal self-generated magnetic field and small length scale, high-amplitude structures attributed to collisionless effects. In order to understand these features, synthetic radiographs are generated using fields produced by 3D HYDRA simulations. These synthetic radiographs reproduce the features of the experimental radiographs with the exception of the small-scale structures. A direct inversion algorithm is successfully applied to a synthetic radiograph but is only partially able to invert the experimental radiographs in part because some protons are blocked by the field coils. The origins of the radiograph features and their dependence on various experimental parameters are explored. Furthermore, the results of this analysis should inform future measurements of compressed axial magnetic fields in cylindrical implosions.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Simultaneous stabilization and control of the n = 1 and n = 2 resistive wall mode

Abstract DIII-D experiments demonstrate simultaneous stability measurements and control of resistive wall modes (RWMs) with toroidal mode numbers n = 1 and n = 2. RWMs with n > 1 are sometimes observed on DIII-D following the successful feedback stabilization of the n = 1 mode, motivating the development of multi- n control. A new model-based multi-mode feedback algorithm based on the VALEN physics code has been implemented on the DIII-D tokamak using a real-time GPU installed directly into the DIII-D plasma control system. In addition to stabilizing RWMs, the feedback seeks to control the stable plasma error field response, enabling compensation of the typically unaddressed DIII-D n = 2 error field component. Experiments recently demonstrated this algorithm’s ability to simultaneously control n = 1 and n = 2 perturbed fields for the first time in a tokamak, using reactor relevant external coils. Control was maintained for hundreds of wall-times above the n = 1 no-wall pressure limit and approaching the n = 1 and n = 2 ideal-wall limits. Furthermore, a rotating non-zero target was set for the feedback, allowing stability to be assessed by monitoring the rotating plasma response (PR) while maintaining control. This novel technique can be viewed as a closed-loop extension of active MHD spectroscopy, which has been used to validate stability models through comparisons of the PR to applied, open-loop perturbations. The closed-loop response measurements are consistent with open-loop MHD spectroscopy data over a wide range of β N approaching the n = 1 ideal-wall limit. These PR measurements were then fit to produce both VALEN and single-mode stability models. These models allowed for important plasma stability information to be determined and have been shown to agree with experimentally observed RWM growth rates.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Resolution Enhancement of MODIS-Derived Water Indices for Studying Persistent Flooding

Monitoring coastal marshes for persistent flooding and salinity stress is a high priority issue in Louisiana. Remote sensing can identify environmental variables that can be indicators of marsh habitat conditions, and offer timely and relatively accurate information for aiding wetland vegetation management. Monitoring activity accuracy is often limited by mixed pixels which occur when areas represented by the pixel encompasses more than one cover type. Mixtures of marsh grasses and open water in 250m Moderate Resolution Imaging Spectroradiometer (MODIS) data can impede flood area estimation. Flood mapping of such mixtures requires finer spatial resolution data to better represent the cover type composition within 250m MODIS pixel. Fusion of MODIS and Landsat can improve both spectral and temporal resolution of time series products to resolve rapid changes from forcing mechanisms like hurricane winds and storm surge. For this study, using a method for estimating sub-pixel values from a MODIS time series of a Normalized Difference Water Index (NDWI), using temporal weighting, was implemented to map persistent flooding in Louisiana coastal marshes. Ordinarily NDWI computed from daily 250m MODIS pixels represents a mixture of fragmented marshes and water. Here, sub-pixel NDWI values were derived for MODIS data using Landsat 30-m data. Each MODIS pixel was disaggregated into a mixture of the eight cover types according to the classified image pixels falling inside the MODIS pixel. The Landsat pixel means for each cover type inside a MODIS pixel were computed for the Landsat data preceding the MODIS image in time and for the Landsat data succeeding the MODIS image. The Landsat data were then weighted exponentially according to closeness in date to the MODIS data. The reconstructed MODIS data were produced by summing the product of fractional cover type with estimated NDWI values within each cover type. A new daily time series was produced using both the reconstructed 250-m MODIS, with enhanced features, and the approximated daily 30-m high-resolution image based on Landsat data. The algorithm was developed and tested over the Calcasieu-Sabine Basin, which was heavily inundated by storm surge from Hurricane Ike to study the extent and duration of flooding following the storm. Time series for 2000-2009, covering flooding events by Hurricane Rita in 2005 and Hurricane Ike in 2008, were derived. High resolution images were formed for all days in 2008 between the first cloud free Landsat scene and the last cloud-free Landsat scene. To refine and validate flooding maps, each time series was compared to Louisiana Coastwide Reference Monitoring System (CRMS) station water levels adjusted to marsh to optimize thresholds for MODIS-derived time series of NDWI. Seasonal fluctuations were adjusted by subtracting ten year average NDWI for marshes, excluding the hurricane events. Results from different NDWI indices and a combination of indices were compared. Flooding persistence that was mapped with higher-resolution data showed some improvement over the original MODIS time series estimates. The advantage of this novel technique is that improved mapping of extent and duration of inundation can be provided.

Underwood, L. W.↗