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In support of the power requirements for the Space Station Alpha (SSA), a joint program by the U.S. and Russia for a permanently manned space station to be launched into orbit by 1998, a robust control scheme is needed to assure the stability of the rotating machines that will be integrated into the power subsystem. A framework design and systems studies for modeling and analysis is presented. It employs classical d-q axes machine model with voltage/frequency dependent loads. To guarantee that design requirements and necessary trade studies are done, a functional analysis tool CORE is used for the study. This provides us with different control options for stability assessment. Initial studies and recommendations using advanced simulation tools are also presented. The benefits of the stability/control scheme for evaluating future designs and power management are discussed.
Medium-resolution gamma-ray spectrometer (MRGS) detectors such as the LaBr 3 and CZT detectors present a more practical and less expensive alternative to high-resolution gamma-ray spectrometers because they operate at room temperature, are more compact and reliable, and are easy to use and maintain. Making them capable of isotopic analysis of uranium and plutonium samples is a desirable feature, which is useful in various safeguards applications. That feature is provided by the upgraded Fixed-Energy Response-Function Analysis with Multiple Efficiency (FRAM) code, which can analyze the isotopic compositions of uranium and plutonium from spectra obtained by a LaBr 3 or CZT detector system. This upgraded code is FRAM version 6.1, to be released soon. It is a major upgrade from the current version 5.2, which was released in 2013. In addition to the capability to analyze the LaBr 3 and CZT spectra, FRAM v.6.1 will implement various new features to improve usability, sustainability, compatibility, and maintainability.
Three clinically relevant ebolaviruses – Ebola (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) viruses, are responsible for severe disease and occasional deadly outbreaks in Africa. The largest Ebola virus disease (EVD) epidemic to date in 2013-2016 in West Africa highlighted the urgent need for countermeasures, leading to the development and FDA approval of the Ebola virus vaccine rVSV-ZEBOV (Ervebo ® ) in 2020 and two monoclonal antibody (mAb)-based therapeutics (Inmazeb ® [atoltivimab, maftivimab, and odesivimab-ebgn] and Ebanga ® (ansuvimab-zykl) in 2020. The humoral response plays an indispensable role in ebolavirus immunity, based on studies of mAbs isolated from the antibody genes in peripheral blood circulating ebolavirus-specific human memory B cells. However, antibodies in the body are not secreted by circulating memory B cells in the blood but rather principally by plasma cells in the bone marrow. Little is known about the protective polyclonal antibody responses in convalescent plasma. Here we exploited both single-cell antibody gene sequencing and proteomic sequencing approaches to assess the composition of the ebolavirus glycoprotein (GP)-reactive antibody repertoire in the plasma of an EVD survivor. We first identified 1,512 GP-specific mAb variable gene sequences from single cells in the memory B cell compartment. Using mass spectrometric analysis of the corresponding GP-specific plasma IgG, we found that only a portion of the large B cell antibody repertoire was represented in the plasma. Molecular and functional analysis of proteomics-identified mAbs revealed recognition of epitopes in three major antigenic sites - the GP head domain, the glycan cap, and the base region, with a high prevalence of neutralizing and protective mAb specificities that targeted the base and glycan cap regions on the GP. Polyclonal plasma antibodies from the survivor reacted broadly to EBOV, BDBV, and SUDV GP, while reactivity of the potently neutralizing mAbs we identified was limited mostly to the homologous EBOV GP. Together these results reveal a restricted diversity of neutralizing humoral response in which mAbs targeting two antigenic sites on GP – glycan cap and base – play a principal role in plasma-antibody-mediated protective immunity against EVD.
The Integrated Microbial Genomes & Microbiomes system at the Department of Energy (DOE) Joint Genome Institute (JGI) continues to provide support for users to perform comparative analysis of isolate and single cell genomes, metagenomes, and metatranscriptomes. In addition to datasets produced by the JGI, IMG v.7 also includes datasets imported from public sources such as NCBI Genbank, SRA, and the DOE National Microbiome Data Collaborative (NMDC), or submitted by external users. In the past couple years, we have continued our effort to help the user community by improving the annotation pipeline, upgrading the contents with new reference database versions, and adding new analysis functionalities such as advanced scaffold search, Average Nucleotide Identity (ANI) for high-quality metagenome bins, new cassette search, improved gene neighborhood display, and improvements to metatranscriptome data display and analysis. Here, we also extended the collaboration and integration efforts with other DOE-funded projects such as NMDC and DOE Biology Knowledgebase (KBase).
It is pointed out that a controversy exists concerning the required role of man, and his attendant skills and levels of skills, for Sortie Lab operations. As a result, a study was conducted to generate a taxonomy of candidate crew roles which would: (1) be applicable across all experiments, and (2) be usable for Sortie scientists and engineers in determination of level of skill as well as type of skill. Nine basic roles were identified in the study, and the tasks associated with each were developed from a functional description of a generalized in-flight experiment. The functional analysis comprised the baseline for establishment of crew roles, with roles being defined as combinations of tasks, associated skills, and knowledges. A role classification scheme was developed in which the functions and tasks identified were allocated to each of the nine role types. This classification scheme is presented together with the significant results of the study.
Production function analysis used to estimate the cost effectiveness of three alternative technologies in higher education: traditional instruction, instructional television, and computer-assisted instruction is presented. Criteria and selection of a functional form are outlined and a general discussion of variable selection and measurement is presented.
The objective of this task is analytical support of the NASA Satellite Laser Ranging (SLR) program in the areas of SLR data analysis, software development, assessment of SLR station performance, development of improved models for atmospheric propagation and interpretation of station calibration techniques, and science coordination and analysis functions for the NASA led Central Bureau of the International Laser Ranging Service (ILRS). The contractor shall in each year of the five year contract: (1) Provide software development and analysis support to the NASA SLR program and the ILRS. Attend and make analysis reports at the monthly meetings of the Central Bureau of the ILRS covering data received during the previous period. Provide support to the Analysis Working Group of the ILRS including special tiger teams that are established to handle unique analysis problems. Support the updating of the SLR Bibliography contained on the ILRS web site; (2) Perform special assessments of SLR station performance from available data to determine unique biases and technical problems at the station; (3) Develop improvements to models of atmospheric propagation and for handling pre- and post-pass calibration data provided by global network stations; (4) Provide review presentation of overall ILRS network data results at one major scientific meeting per year; (5) Contribute to and support the publication of NASA SLR and ILRS reports highlighting the results of SLR analysis activity.
Discoidin Domain Receptor 2 (DDR2) is a collagen-binding receptor tyrosine kinase that initiates delayed and sustained tyrosine phosphorylation signalling. To understand the molecular basis of this unique phosphorylation profile, here we utilise fluorescence microscopy to map the spatiotemporal localisation of DDR2 and tyrosine phosphorylated proteins upon stimulation with collagen. We show that cellular phosphorylated proteins are localised to the interface where DDR2 is in contact with collagen and not in the early endosomes or lysosomes. We find that DDR2 localisation is independent of integrin activation and the key DDR2 signalling effector SHC1. Structure-function analysis reveals that DDR2 mutants defective for collagen binding or kinase activity are unable to localise to the cell surface, demonstrating for the first time that both collagen binding and kinase functions are required for spatial localisation of DDR2. This study provides new insights into the underlying structural features that control DDR2 activation in space and time.
SUMMARY Infrasonic waves are influenced by variations in the density, pressure and temperature as well as the ambient winds. Modelling infrasonic propagation can be challenging due to the dynamic nature of the atmosphere as well as the sparseness of measurements which result in variability and notable uncertainty. A framework is presented to quantify spatial and seasonal trends in atmospheric structure via analysis of the effective sound speed profile and identification of temporal trends in the middle atmospheric waveguide produced by the circumpolar vortex winds. Seasonal definitions identifying typical atmospheric structures during the summer, winter and spring/fall transition periods are identified using atmospheric data from 2010 through 2020. Seasonal trend analysis is conducted for a number of locations across the contiguous United States to quantify spatial variations in atmospheric structure that impact infrasonic propagation. For each season and location, empirical orthogonal function analysis is used to reduce the historical archive of atmospheric data into a smaller representative set that can be analysed using numerical tools more efficiently. Infrasonic ray tracing and finite-frequency modal propagation analyses are applied to construct propagation path geometry and transmission loss statistics which are useful in localization and yield estimation for infrasonic sources, respectively. An example application is detailed in which transmission loss statistics are combined with an explosive source model and noise statistics to quantify the capability of a network to detect nearby sources.
This document is the final report for the project entitled 'Thermal Structure Analyses for CSM Testbed (COMET),' for the period of May 16, 1992 - August 15, 1994. The project was focused on the investigation and development of finite element analysis capability of the computational structural mechanics (CSM) testbed (COMET) software system in the field of thermal structural responses. The stages of this project consisted of investigating present capabilities, developing new functions, analysis demonstrations, and research topics. The appendices of this report list the detailed documents of major accomplishments and demonstration runstreams for future references.
Peptide nucleic acids (PNAs) have gained considerable attention due to their remarkable potential in gene editing and targeting-based strategies. However, cellular delivery of PNAs remains a challenge in developing their broader therapeutic applications. Here, we investigated a novel complex made of lipid bicelles and PNA-based carriers for the efficient delivery of PNAs. For proof of concept, PNAs targeting microRNA (miR) 210 and 155 were tested. Comprehensive evaluation of positive as well as negative charge-containing bicelles with PNA : lipid ratios of 1 : 100, 1 : 1000, and 1 : 2500 was performed. The negatively charged bicelles with a PNA : lipid molar ratio of 1 : 2500 yielded a discoidal shape with a uniform diameter of ~30 nm and a bilayer thickness of 5 nm, while the positively charged bicellar system contained irregular vesicles after the incorporation of PNA. Small-angle X-ray scattering (SAXS) analysis was performed to provide insight into how the hydrophobic PNAs interact with bicelles. Further, flow cytometry followed by confocal microscopy analyses substantiate the superior transfection efficiency of bicelles containing dyeconjugated antimiR PNAs. Functional analysis also confirmed miR inhibition by PNA oligomers delivered by bicelles. The nanodiscoidal complex opens a new pathway to deliver PNAs, which, on their own, are a great challenge to be endocytosed into cells.
We present a fictional scenario that, while undeniably whimsical, provides the foundation for a unique exercise in extended problem solving, physics analysis, and quantitative model development. Starting with the foundational premise of the Wild Cards shared-world superhero universe, we demonstrate how a variety of concepts appropriate to the advanced undergraduate level—ergodicity, functional analysis, Lagrangian mechanics, and the ever-important simplifying approximation—can be combined into a rich, coherent mathematical model. The goal of this case study is to develop a useful pedagogical exercise in exploring an open-ended research question that presents, at first glance, no clear path forward. Being both eclectic and lengthy, this exercise offers a unique way for students to apply their core physics and mathematics education. It is perhaps best used within a senior honors seminar or within a brief (e.g., January term) elective class.
What You Will Learn: The focus is on payload imaging performance due to pointing motion. Some historical background on pointing performance analysis is given. The Optical Transfer Function (OTF) and Modulation Transfer Function (MTF) are defined. The imaging performance due to pointing motion is measured by image motion optical transfer functions (IM OTF). IM OTFs are defined for displacement, smear, and jitter motions, which are all rigorously defined. Deterministic and Statistical IM OTFs are briefly derived and graphically illustrated and compared. The IM OTFs are parameterized by pointing error metrics(PEM), which are means and covariances of displacement, smear, and jitter. Emphasis is on procedures and algorithms to evaluate the image motion optical transfer functions and pointing error metrics. Three procedures are covered, which depend on whether the pointing error data is from time-domain simulation, frequency-domain analysis, or stochastic modeling. A method to evaluate the relative contribution of disturbance sources and to identify the most significant contributors is presented. The presentation includes pertinent discussion of flexible structures and control-structure interaction. No single book can adequately cover this subject, so a book is not required for the course. A list of selected articles, reports, documents, and books is provided for reference and further study. Mathis kept to the minimum necessary to convey principles; lengthy derivations are left to the reference material. Graphics are used to illustrate concepts. As with any such learning endeavor, the knowledge gained will be retained and strengthened through actual practice.c©2019–2021 Mark E. Pittelkau— 5
The functional architecture for an integrated command, control, communications, and computation system applicable to the command and control portion of the NASA End-to-End Data. System is described including the downlink data processing and analysis functions required to support the uplink processes. The functional architecture is composed of four elements: (1) the functional hierarchy which provides the decomposition and allocation of the command and control functions to the system elements; (2) the key system features which summarize the major system capabilities; (3) the operational activity threads which illustrate the interrelationahip between the system elements; and (4) the interfaces which illustrate those elements that originate or generate data and those elements that use the data. The interfaces also provide a description of the data and the data utilization and access techniques.
Project Title: Immunophilins in the assembly and maintenance of photosynthetic electron transport chain in Arabidopsis Applicant: The Regents of the University of California PI: Sheng Luan, University of California at Berkeley Photosynthetic light energy conversion entails coordinated function of complex molecular machines that capture and convert light energy into chemical forms through photosynthetic electron transport chain. Each molecular machine, such as photosystem II (PSII), may consist of dozens of protein subunits and small molecule cofactors. Despite advanced understanding of the structure and function of these complexes, little is known about “How individual proteins and cofactors assemble into a functional machine and how do these molecular machines maintain their structure and function under a highly hazardous lumenal environment.” Our studies on immunophilins have unexpectedly contributed to the understanding of this question. Originally defined as cellular receptors for immunosuppressants, immunophilins have been discovered in a wide range of organisms from bacteria, fungi, plants, to animals. Immunophilins function in protein folding processes as chaperones and foldases. Arabidopsis genome encodes ca. 50 immunophilins. The most striking finding is that 16 immunophilin members are targeted to chloroplast thylakoid lumen, by far the largest group in the lumenal proteome. What is the function of immunophilins in the thylakoid lumen? Our studies have demonstrated critical roles for several immunophilins in the biogenesis and maintenance of photosynthetic complexes such as PSII. These studies have made a critical link between immunophilins and the assembly of photosynthetic machines and thus opened up a new area of research in photosynthesis. Our goal is to dissect the roles of immunophilins and their partners in the assembly and maintenance of the photosynthetic electron transport chain. The specific objectives for this funding period will be: 1. To dissect the mechanism of action for CYP38. Our studies suggest an “autoinhibitory” model for CYP38 action. We plan to test this model and determine the mechanistic details for CYP38 function by biochemical and genetic procedures. 2. To determine the mechanism of action of FKBP20-2/FKBP16-3. Studies on FBKP16-3 and FKBP20-2 suggest that they may work together as a redox-dependent duo in PSII assembly. We will test this hypothesis using biochemical and genetic tools. 3. To determine the function of lumenal FKBPs by multi-gene mutagenesis approach. Using new genetic knockout (KO) procedures especially CRISPR/CAS9 system, we plan to generate multi-gene KO models that will likely provide vital information on those FKBPs with functional redundancy. 4. Functional analysis of thylakoid lumen network. We will focus our effort on objectives 1-3. Objective 4 represents a long-term goal to establish a more comprehensive network of proteins in the thylakoid lumen and their function in the assembly and maintenance of photosynthetic complexes. I hypothesize that the 16 immunophilin-type chaperones and foldases in the thylakoid lumen constitute an “assembly line” for the various components in the photosynthetic electron transport chain. Understanding this assembly line will enable further engineering of more efficient photosynthetic machines to capture more light energy and enhance plant productivity. Furthermore, it is envisioned that such molecular “assembly line” may be rebuilt to produce artificial photosynthesis in vitro or in non-photosynthetic organisms. These are highly relevant to the mission of “Photosynthetic Systems” and “Physical Biosciences” programs to “enhance our understanding of energy capture, conversion, and/or storage.” During the funding period, we have performed a number of experiments under the proposed objectives and obtained several new results. We have found in Objective 1 that CYP38 is associated to the thylokoid membrane with a larger complex that might be PSII supercomplex. Under objective 2, we have found that FKBP16-2 interacted with PSB27 that was further pursuited and published a research article in PNAS (attached). Under Objective 3, we have identified several mutants of other FKBPs in the thyalkoid lumen that should be further studied if future funding is available. Under Objective 4, we have started to build a network of lumenal proteins that play a number of roles in photosynthesis. For example, the CYP37 and CYP28 are linked to chloroplast signaling to nucleus, critical for controlling plant response to high light and adaptation to climate change. Unfortunately these studies have been terminated due to funding shortage.
Analysis of space vehicle structures using transfer function concept
This communication extends a statistical analysis of forced-descent decompression sickness at altitude in exercising subjects (J Appl Physiol 1994; 76:2726-2734) with a data subset having an additional explanatory variable, rate of ascent. The original explanatory variables for risk-function analysis were environmental pressure of the altitude, duration of exposure, and duration of pure-O2 breathing before exposure; the best fit was consistent with the idea that instantaneous risk increases linearly as altitude exposure continues. Use of the new explanatory variable improved the fit of the smaller data subset, as indicated by log likelihood. Also, with ascent rate accounted for, replacement of the term for linear accrual of instantaneous risk by a term for rise and then decay made a highly significant improvement upon the original model (log likelihood increased by 37 log units). The authors conclude that a more representative data set and removal of the variability attributable to ascent rate allowed the rise-and-decay mechanism, which is expected from theory and observations, to become manifest.