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Temporal Galactose‐Manganese Feeding in Fed‐Batch and Perfusion Bioreactors Modulates UDP‐Galactose Pools for Enhanced mAb Glycosylation Homogeneity

ABSTRACT Monoclonal antibodies (mAbs) represent a majority of biotherapeutics in the market today. These glycoproteins undergo posttranslational modifications, such as N‐linked glycosylation, that influence the structural & functional characteristics of the antibody. Glycosylation is a heterogenous posttranslational modification that may influence therapeutic glycoprotein stability and clinical efficacy, which is why it is often considered a critical quality attribute (CQA) of the mAb product. While much is known about the glycosylation pathways of Chinese Hamster Ovary (CHO) cells and how cell culture chemical modifiers may influence the N‐glycosylation profile of the final product, this knowledge is often based on the final cumulative glycan profile at the end of the batch process. Building a temporal understanding of N‐glycosylation and how mAb glycoform composition responds to real‐time changes in the biomanufacturing process will help build integrated process models that may allow for glycosylation control to produce a more homogenous product. Here, we look at the effect of specific nutrient feed media additives (e.g., galactose, manganese) and feeding times on the N‐glycosylation pathway to modulate N‐glycosylation of a Herceptin biosimilar mAb (i.e., Trastuzumab). We deploy the N‐GLYcanyzer process analytical technology (PAT) to monitor glycoforms in near real‐time for bench‐scale bioprocesses operated in both fed‐batch and perfusion modes to build an understanding of how temporal changes in mAb N‐glycosylation are dependent on specific media additives. We find that Trastuzumab terminal galactosylation is sensitive to media feeding times and intracellular nucleotide sugar pools. Temporal analysis reveals an increased desirable production of single and double galactose‐occupied glycoforms over time under glucose‐starved fed‐batch cultures. Comparable galactosylation profiles were also observed between fed‐batch (nutrient‐limited) and perfusion (non‐nutrient‐limited) bioprocess conditions. In summary, our results demonstrate the utility of real‐time monitoring of mAb glycoforms and feeding critical cell culture nutrients under fed‐batch and perfusion bioprocessing conditions to produce higher‐quality biologics.

Biotechnology & Applied Microbiology

Temporal relationships among lunar crustal rocks

Temporal relationships among the three most common suites of lunar crustal rocks have been investigated by obtaining new high precision ages on Felsic/Alkali-suite Quartz monzodiorite Clast B from breccia 15405 and Magnesian-suite norite 78235/6/8/55/56 and comparing them to previously dated ferroan anorthosite sample 60025. The weighted average age of 4337.19 ± 0.49 Ma of 15405 Clast B is defined by zircon U-Pb and Pb-Pb ages as well as mineral isochron Sm-Nd and Nd-Nd ages. It is identical to the weighted average age for Apollo 17 norite 78235/6/8/55/56 of 4334.1 ± 3.5 Ma which is defined by Pb-Pb ages measured on baddeleyites in this investigation and less precise Pb-Pb and Sm-Nd ages reported in the literature. Both ages are ∼ 25 Ma younger than the weighted average of Sm-Nd and Pb-Pb ages reported in the literature on ferroan anorthosite 60025 of 4359.3 ± 2.3 Ma. The fact that ages of all three samples are defined by multiple U-Pb, Pb-Pb, Sm-Nd, and 142 Nd- 143 Nd chronometers provide confidence that they record the igneous crystallization history of the samples and do not represent disturbances or mixing lines with no temporal significance. Here, the extent to which these three ages represent broader scale magmatism is difficult to evaluate. Nevertheless, the age defined for 15405 Clast B, 78235/6/8/55/56, and 60025 are contemporaneous with the peak of ages observed in detrital zircons from the Apollo 12, 14, 15, and 17 landing sites (4340 ± 20 Ma), a Mg-suite Sm-Nd whole rock isochron defined by samples from Apollo 14, 15, 16, and 17 landing sites (4348 ± 25 Ma), and a Ferroan Anorthosite-suite Sm-Nd whole rock isochron defined by samples from the Apollo 15 and 16 landing sites (4354 ± 29 Ma). This implies that Ferroan Anorthosite-suite magmatism is temporally distinct and earlier than magmatism associated with the Mg-suite and the Felsic/Alkali-suite, as predicted by the lunar magma ocean model of lunar differentiation. The short 35 ± 10 Ma interval between primary ferroan anorthosite magmatism and secondary magmatism suggests that the lunar crust formed over a limited period of time. Although heat from decay of long-lived isotopes, large impacts, tidal heating associated with interactions between the Earth and Moon, and density driven overturn of the magma ocean have all been invoked to explain production of ancient secondary crustal magmatism, only tidal heating and cumulate overturn are consistent with the apparent short duration of secondary crustal magmatism and the great depth of crystallization implied for some Mg-suite samples. The initial ε 143 Nd values derived from the 15405 Clast B and 78238 Mg-suite norite isochrons, as well as a Mg-suite whole rock isochron are −0.23 ± 0.11, −0.27 ± 0.74, and −0.25 ± 0.09, respectively. They are identical within uncertainty indicating that Mg-suite and Felsic/Alkali-suite magmas were derived from materials that had the same time averaged Sm/Nd ratios since the formation of the solar system. This, combined with the contemporaneous nature of 15405 Clast B and 78235/6/8/55/56 Mg-suite norite, is consistent with evolution of both samples, and likely both magma suites, from a common source through closed system fractional crystallization or partial melting processes.

Chronology

Spatially and Temporally Detailed Water and Carbon Footprints of U.S. Electricity Generation and Use

Electricity generation in the United States entails significant water usage and greenhouse gas emissions. However, accurately estimating these impacts is complex due to the intricate nature of the electric grid and the dynamic electricity mix. Existing methods to estimate the environmental consequences of electricity use often generalize across large regions, neglecting spatial and temporal variations in water usage and emissions. Consequently, electric grid dynamics, such as temporal fluctuations in renewable energy resources, are often overlooked in efforts to mitigate environmental impacts. The U.S. Department of Energy (DOE) has initiated the development of resilient energyshed management systems, requiring detailed information on the local electricity mix and its environmental impacts. This study supports DOE's goal by incorporating geographic and temporal variations in the electricity mix of the local electric grid to better understand the environmental impacts of electricity end users. We offer hourly estimates of the U.S. electricity mix, detailing fuel types, water withdrawal intensity, and water consumption intensity for each grid balancing authority through our publicly accessible tool, the Water Integrated Mapping of Power and Carbon Tracker (Water IMPACT). While our primary focus is on evaluating water intensity factors, our dataset and programming scripts for historical and real-time analysis also include evaluations of carbon dioxide (equivalence) intensity within the same modeling framework. This integrated approach offers a comprehensive understanding of the environmental footprint associated with electricity generation and use, enabling informed decision-making to effectively reduce Scope 2 water usage and emissions.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI

Temporal reflection from short pump pulses inside a dispersive nonlinear medium: the impact of pump parameters

We have studied, through a series of experiments and numerical simulations, how temporal reflection from an intense pump pulse inside a photonic crystal fiber is affected by parameters of the pump pulse used to form a moving high-index boundary. We used femtosecond pump pulses, which slow down inside the fiber as their spectrum red-shifts because of intrapulse Raman scattering. Temporal reflection of probe pulses occurs from such decelerating pump pulses. We changed the width and chirp of our pump pulses with a 4f pulse shaper capable of providing both spectral filtering and frequency chirping. We found that temporal refection exhibited novel features, to our knowledge, when pump pulses were made wider or chirped. In both cases, two or more reflected pulses were produced at different wavelengths in a specific range of the initial pump-probe delays. Furthermore, numerical simulations reveal that the origin of such novel features is related to the complex nonlinear evolution of pump pulses inside optical fibers.

47 OTHER INSTRUMENTATION

Understanding Event Trajectories Across Massive Temporal Datasets with Word Embeddings and Visualization

In collaboration with researchers from Virginia Tech, Savannah River National Laboratory has continued development of a natural language processing pipeline to identify and extract events of interest from massive open data sources in the domain of worldwide state-sponsored civil nuclear energy. The foundation of the pipeline is built on compass aligned temporal word embedding models, whereby contextual shifts are automatically identified by comparing keyword embedding vectors across successive time windows. Within the approach, a contextual shift indicates the occurrence of a potential event of interest. However, in such a broad topical domain that captures events at a global scale, across various life cycle stages, and across numerous different technology types, a user that is monitoring events may have broad interests in capturing many different event types with varying degrees of signal. As such, the quantity of information that may be returned from an automated event extraction pipeline can be substantial, requiring manual effort to sift through the information to identify any relevant bits of information. Therefore, a more streamlined workflow that aids in directing a user toward specific information at different points in time is necessary. The workflow presented here has been developed with this concept in mind, built on top of the initial prototype event extraction pipeline, whereby a user can analyze temporal text-based data sources at multiple different contextual levels to isolate key points in time and key subdomains captured within a data corpus. Using multiple corpuses that consist of approximately 7 million Tweets and 7 million news articles, the team has extended compass aligned temporal word embedding models to establish an interconnected and hierarchical structure that relates known key words of interest to documents, local topics (i.e., within a time window), and global topics across the corpuses. All of this information is packaged into a visual analytics system that is linked to the information extraction pipeline and enables a user to identify contextual information that describes the evolution of a high dimensional embedding space across time to isolate changes of interest and explore associated events. This report demonstrates the use of these analytics and a means to fuse information across multiple datasets.

97 MATHEMATICS AND COMPUTING

Temporal Explosion Source Processes of Declared Nuclear Tests in the Democratic People’s Republic of Korea

In this work we highlight a preliminary temporal source analysis of the six declared Democratic People's Republic of Korea (DPRK) nuclear tests. We use regional seismic data to estimate relative source time functions (RSTFs) via iterative time-domain deconvolution (Ammon, 2006; Pippin, 2022) of vertical-component ground motions recorded within 2000 km of the source region. Since RSTFs are ideally independent of site and propagation effects, their amplitude spectrum is equivalent to the source spectral ratio, but they also retain phase information. We compare observed RSTFs (in the time and frequency domains) with synthetic RSTFs derived from the Mueller & Murphy (1971) explosion source model. The resolution of these time functions varies, however, we generally obtain high-quality results within the limitations of the recording broadband instrumentation. The results indicate that this method effectively preserves source time-history information that can be used for temporal analysis of remote nuclear explosions. This preliminary analysis is intended to assess the viability of using time-domain deconvolution methods for extracting temporal source information.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF

Temporal Coarse Graining for Classical Stochastic Noise in Quantum Systems

Simulations of quantum systems with Hamiltonian classical stochastic noise can be challenging when the noise exhibits temporal correlations over a multitude of time scales, such as for 1/f noise in solid-state quantum information processors. Here we present an approach for simulating Hamiltonian classical stochastic noise that performs temporal coarse-graining by effectively integrating out the high-frequency components of the noise. We focus on the case where the stochastic noise can be expressed as a sum of Ornstein-Uhlenbeck processes. Temporal coarse-graining is then achieved by conditioning the stochastic process on a coarse realization of the noise, expressing the conditioned stochastic process in terms of a sum of smooth, deterministic functions and bridge processes with boundaries fixed at zero, and performing the ensemble average over the bridge processes. For Ornstein-Uhlenbeck processes, the deterministic components capture all dependence on the coarse realization, and the stochastic bridge processes are not only independent but taken from the same distribution with correlators that can be expressed analytically, allowing the associated noise propagators to be precomputed once for all simulations. This combination of noise trajectories on a coarse time grid and ensemble averaging over bridge processes has practical advantages, such as a simple concatenation rule, that we highlight with numerical examples.

Albash, Tameem [Sandia National Lab. (SNL-NM), Alb

Privacy-Preserving Real-Time Action Detection in Intelligent Vehicles Using Federated Learning-Based Temporal Recurrent Network

This study introduces a privacy-preserving approach for the real-time action detection in intelligent vehicles using a federated learning (FL)-based temporal recurrent network (TRN). This approach enables edge devices to independently train models, enhancing data privacy and scalability by eliminating central data consolidation. Our FL-based TRN effectively captures temporal dependencies, anticipating future actions with high precision. Extensive testing on the Honda HDD and TVSeries datasets demonstrated robust performance in centralized and decentralized settings, with competitive mean average precision (mAP) scores. The experimental results highlighted that our FL-based TRN achieved an mAP of 40.0% in decentralized settings, closely matching the 40.1% in centralized configurations. Notably, the model excelled in detecting complex driving maneuvers, with mAPs of 80.7% for intersection passing and 78.1% for right turns. These outcomes affirm the model’s accuracy in action localization and identification. The system showed significant scalability and adaptability, maintaining robust performance across increased client device counts. The integration of a temporal decoder enabled predictions of future actions up to 2 s ahead, enhancing the responsiveness. Our research advances intelligent vehicle technology, promoting safety and efficiency while maintaining strict privacy standards.

33 ADVANCED PROPULSION SYSTEMS

Temporal Properties of Compressible Magnetohydrodynamic Turbulence

Describing the temporal properties of compressible magnetohydrodynamic (MHD) turbulence is a fundamental problem that has important implications for particle acceleration and transport in astrophysical plasmas. Here, by carefully analyzing the spatial and temporal properties of compressible MHD turbulence, we derive a new spectral power density function that is supported by simulations. This new function reveals that the low-frequency fluctuations are dominated by modes with small parallel wavenumbers with respect to the mean background magnetic field. Furthermore, for fluctuations with dynamically significant parallel wavenumbers, broadening around their eigenfrequencies is described by this function, which is in close agreement with simulations. We use this formalism to present the scaling properties of individual MHD modes. Such broadening is a direct consequence of nonlinear processes and is different for the three fundamental MHD modes. Our results provide a new window to investigate the temporal properties of turbulence and will enable further studies on the interaction between compressible MHD turbulence and energetic plasmas.

79 ASTRONOMY AND ASTROPHYSICS

Global Characteristics of the IBEX Ribbon and Its Temporal Variation: Implications for Relationships with Solar Cycle Variability and the Interstellar Magnetic Field

The Interstellar Boundary Explorer (IBEX) has revealed the existence of the energetic neutral atom (ENA) ribbon, a narrow and nearly circular band of enhanced flux that enables probing plasma and magnetic field conditions outside the heliopause (HP). In this study, we investigate the global structure and temporal variation of the IBEX ribbon using 14 yr of IBEX-Hi ENA observations. We derive geometric parameters of the ribbon: center location, angular radius, eccentricity, and major axis orientation. We find that the ribbon exhibits systematic variations tied to the solar cycle. The ribbon center shows a solar cycle–modulated latitudinal motion at low energies. The angular radius increases with ENA energy and displays a pronounced enlargement between 2013 and 2018, coinciding with changes in high-latitude fast solar wind from polar coronal holes. The eccentricity remains consistently around 0.3 with some temporal evolution, while the major axis rotates gradually over time, becoming increasingly perpendicular to the ecliptic meridional plane. A notable hemispheric asymmetry has emerged over time: the ribbon in the northern hemisphere remains remarkably stable in position, whereas the southern ribbon exhibits temporal migration. By combining these results with solar wind observations, global heliosphere, and ribbon modeling, we suggest that this asymmetry is explained by a coupled effect of magnetic field draping and the latitude-dependent timing of fast solar wind from polar coronal holes. These results establish the most detailed long-term geometric characterization of the IBEX ribbon to date and provide observational support for models of secondary ENA production and magnetic field draping outside the HP.

Noh, Sung Jun [New Mexico Consortium, Los Alamos,

Pattern recognition of Landsat data based upon temporal trend analysis

The Delta Classifier defined as an agricultural crop classification scheme employing a temporal trend procedure is applied to more than 100 different Landsat data sets collected during the 1974-1975 growing season throughout the major wheat-producing regions of the United States. The classification approach stresses examination of temporal trends of the Landsat mean vectors of crops in the absence of corresponding ground truth information. It is shown that the resulting classifications compare favorably to ground truth estimates for wheat proportion in those cases where ground truth is available, and that the temporal trend procedure yields estimates of the wheat proportion that are comparable to the best results from maximum likelihood classification with photointerpreter-defined training fields.

Engvall, J. L.

Spatial and temporal filtering technique for processing lidar photocount data

Shot noise places a practical limit on the spatial and temporal resolution of lidar photocount data. A 2-D signal-processing technique that utilizes spatial and temporal filtering to reduce shot noise and increase resolution is described. The technique is applied to sodium lidar data collected during the fall of 1979 over Urbana, Illinois. Temporal filtering is shown to enhance the spatial resolution of the sodium profiles significantly by reducing shot noise by more than 10 dB. The signal-processing technique is applicable to a wide variety of lidar data.

Gardner, C. S.

Temporal development of composition, spectra, and anisotropies during upstream particle events

An analysis is conducted of the temporal development of particle intensity, composition, and anisotropies during diffuse particle events. The observations were made with an ultra-low energy charge analyzer (ULECA) sensor. ULECA basically consists of an electrostatic deflection system and an array of solid state detectors. The simultaneous measurement of energy per charge and total energy makes it possible to determine the charge state of a particle. Spectra are derived by an iterative technique involving the numerical integration of particle spectra with the energy response functions of the individual detectors. The presented data are explained in terms of temporal and spatial structures in the upstream region. The temporal structures during the event onset are consistent with a time-dependent first-order Fermi acceleration model, as discussed by Scholer et al. (1980).

Ipavich, F. M.

An interval logic for higher-level temporal reasoning

Prior work explored temporal logics, based on classical modal logics, as a framework for specifying and reasoning about concurrent programs, distributed systems, and communications protocols, and reported on efforts using temporal reasoning primitives to express very high level abstract requirements that a program or system is to satisfy. Based on experience with those primitives, this report describes an Interval Logic that is more suitable for expressing such higher level temporal properties. The report provides a formal semantics for the Interval Logic, and several examples of its use. A description of decision procedures for the logic is also included.

Schwartz, R. L.

Differences in the temporal variations of solar UV flux, 10.7-cm solar radio flux, sunspot number, and Ca-K plage data caused by solar rotation and active region evolution

Attention is given to two types of temporal variations in the solar UV spectral irradiance caused by solar rotation and active region evolution. It is noted that the first type of dissimilar temporal behavior occurs when concentrations of solar active regions evolve at solar longitudes nearly 180 deg apart. Both the UV observations and modeled UV fluxes based on Ca-K plage data then exhibit pronounced 13-day periodicity, whereas the 10.7-cm solar radio flux and sunspot number exhibit quite dissimilar temporal variations. This type of dissimilarity is related to the modeled UV flux and has a dependence on the solar central meridian distance that is narrower than that for the 10.7-cm radio flux or for sunspot numbers. A second case of marked dissimilarity is seen when major new solar active regions arise and dominate the full-disk fluxes for several rotations. It is found that the strongest peaks in 10.7 cm and sunspot numbers tend to occur on their first rotation, for example, during major dips in the total solar irradiance, whereas the Ca-K plages and UV enhancements peak on the next rotation and then decay more slowly on subsequent rotations.

Donnelly, R. F.

Development of algorithms for understanding the temporal and spatial variability of the earth's radiation balance

A brief description is given of how temporal and spatial variability in the earth's radiative behavior influences the goals of satellite radiation monitoring systems and how some previous systems have addressed the existing problems. Then, results of some simulations of radiation budget monitoring missions are presented. These studies led to the design of the Earth Radiation Budget Experiment (ERBE). A description is given of the temporal and spatial averaging algorithms developed for the ERBE data analysis. These algorithms are intended primarily to produce monthly averages of the net radiant exitance on regional, zonal, and global scales and to provide insight into the regional diurnal variability of radiative parameters such as albedo and long-wave radiant exitance. The algorithms are applied to scanner and nonscanner data for up to three satellites. Modeling of dialy shortwave albedo and radiant exitance with satellite samling that is insufficient to fully account for changing meteorology is discussed in detail. Studies performed during the ERBE mission and software design are reviewed. These studies provide quantitative estimates of the effects of temporally sparse and biased sampling on inferred diurnal and regional radiative parameters. Other topics covered include long-wave diurnal modeling, extraction of a regional monthly net clear-sky radiation budget, the statistical significance of observed diurnal variability, quality control of the analysis, and proposals for validating the results of ERBE time and space averaging.

Brooks, D. R.

Loss factors associated with spatial and temporal tracking errors in intersatellite PPM communication links

The performance of an optical PPM intersatellite link in the presence of spatial and temporal tracking errors is investigated. It is shown that for a given rms spatial tracking error, an optimal transmitter beamwidth exists which minimizes the probability of bit error. The power penalty associated with the spatial tracking error when the transmitter beamwidth is adjusted to achieve optimal performance is shown to be large (greater than 9 dB) when the rms pointing jitter becomes a significant fraction (greater than 30 percent) of the diffraction limited beamwidth. The power penalty due to temporal tracking error, on the other hand, is relatively small (less than 0.1 dB) when the tracking loop bandwidth is less than 0.1 percent of the slot frequency. By properly allocating losses to spatial and temporal tracking errors, it is seen that a 10 to the -9th error rate can be achieved for a realistic link design with an approximately 3 dB signal power margin.

Chen, C. C.

Very high elevation water ice clouds on Mars: Their morphology and temporal behavior

Quantitative analysis of Viking images of the martian planetary limb has uncovered the existence and temporal behavior of water ice clouds that form between 50 and 90 km elevation. These clouds show a seasonal behavior that may be correlated with lower atmosphere dynamics. Enhanced vertical mixing of the atmosphere as Mars nears perihelion is hypothesized as the cause of the seasonal dependence, and the diurnal dependence is explained by the temporal behavior of the martian diurnal thermal tide. Viking images also provide a data set of the vertical distribution of aerosols in the martian atmosphere. The temporal and spatial distribution of aerosols are characterized.

Jaquin, Fred