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At least 55 records · Page 3

Reconstructing Ancient Forms of Life

Progress in the past three months has occurred in two areas, reconstruction of ancestral proteins and improved understanding of chemical features that are likely to be universal in generic matter regardless of its genesis. Ancestral ribonucleases have been reconstructed, and an example has been developed that shows how physiological function can be assigned to in vitro behaviors observed in biological systems. Sequence data have been collected to permit the reconstruction of src homology 2 domains that underwent radiative divergence at the time of the radiative divergence of chordates. New studies have been completed that show how genetic matter (or its remnants) might be detected on Mars (or other non-terrean locations.) Last, the first in vitro selection experiments have been completed using a nucleoside library carrying positively charged functionality, illustrating the importance of non-standard nucleotides to those attempting to obtain evidence for an "RNA world" as an early episode of life on earth.

Benner, Steven A.↗

RNA language models predict mutations that improve RNA function

Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. RNA structure prediction is not yet possible due to a lack of high-quality reference data associated with organismal phenotypes that could inform RNA function. We present GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB). GARNET links RNA sequences to experimental and predicted optimal growth temperatures of GTDB reference organisms. Using GARNET, we develop sequence- and structure-aware RNA generative models, with overlapping triplet tokenization providing optimal encoding for a GPT-like model. Leveraging hyperthermophilic RNAs in GARNET and these RNA generative models, we identify mutations in ribosomal RNA that confer increased thermostability to the Escherichia coli ribosome. The GTDB-derived data and deep learning models presented here provide a foundation for understanding the connections between RNA sequence, structure, and function.

59 BASIC BIOLOGICAL SCIENCES↗

Simplifying operations with an uplink/downlink integration toolkit

The Operations Engineering Lab (OEL) at JPL has developed a simple, generic toolkit to integrate the uplink/downlink processes, (often called closing the loop), in JPL's Multimission Ground Data System. This toolkit provides capabilities for integrating telemetry verification points with predicted spacecraft commands and ground events in the Mission Sequence Of Events (SOE) document. In the JPL ground data system, the uplink processing functions and the downlink processing functions are separate subsystems that are not well integrated because of the nature of planetary missions with large one-way light times for spacecraft-to-ground communication. Our new closed-loop monitoring tool allows an analyst or mission controller to view and save uplink commands and ground events with their corresponding downlinked telemetry values regardless of the delay in downlink telemetry and without requiring real-time intervention by the user. An SOE document is a time-ordered list of all the planned ground and spacecraft events, including all commands, sequence loads, ground events, significant mission activities, spacecraft status, and resource allocations. The SOE document is generated by expansion and integration of spacecraft sequence files, ground station allocations, navigation files, and other ground event files. This SOE generation process has been automated within the OEL and includes a graphical, object-oriented SOE editor and real-time viewing tool running under X/Motif. The SOE toolkit was used as the framework for the integrated implementation. The SOE is used by flight engineers to coordinate their operations tasks, serving as a predict data set in ground operations and mission control. The closed-loop SOE toolkit allows simple, automated integration of predicted uplink events with correlated telemetry points in a single SOE document for on-screen viewing and archiving. It automatically interfaces with existing real-time or non real-time sources of information, to display actual values from the telemetry data stream. This toolkit was designed to greatly simplify the user's ability to access and view telemetry data, and also provide a means to view this data in the context of the commands and ground events that are used to interpret it. A closed-loop system can prove especially useful in small missions with limited resources requiring automated monitoring tools. This paper will discuss the toolkit implementation, including design trade-offs and future plans for enhancing the automated capabilities.

Murphy, Susan C.↗

Metagenomic clustering links specific metabolic functions to globally relevant ecosystems

ABSTRACT Metagenomic sequencing has advanced our understanding of biogeochemical processes by providing an unprecedented view into the microbial composition of different ecosystems. While the amount of metagenomic data has grown rapidly, simple-to-use methods to analyze and compare across studies have lagged behind. Thus, tools expressing the metabolic traits of a community are needed to broaden the utility of existing data. Gene abundance profiles are a relatively low-dimensional embedding of a metagenome’s functional potential and are, thus, tractable for comparison across many samples. Here, we compare the abundance of KEGG Ortholog Groups (KOs) from 6,539 metagenomes from the Joint Genome Institute’s Integrated Microbial Genomes and Metagenomes (JGI IMG/M) database. We find that samples cluster into terrestrial, aquatic, and anaerobic ecosystems with marker KOs reflecting adaptations to these environments. For instance, functional clusters were differentiated by the metabolism of antibiotics, photosynthesis, methanogenesis, and surprisingly GC content. Using this functional gene approach, we reveal the broad-scale patterns shaping microbial communities and demonstrate the utility of ortholog abundance profiles for representing a rapidly expanding body of metagenomic data. IMPORTANCE Metagenomics, or the sequencing of DNA from complex microbiomes, provides a view into the microbial composition of different environments. Metagenome databases were created to compile sequencing data across studies, but it remains challenging to compare and gain insight from these large data sets. Consequently, there is a need to develop accessible approaches to extract knowledge across metagenomes. The abundance of different orthologs (i.e., genes that perform a similar function across species) provides a simplified representation of a metagenome’s metabolic potential that can easily be compared with others. In this study, we cluster the ortholog abundance profiles of thousands of metagenomes from diverse environments and uncover the traits that distinguish them. This work provides a simple to use framework for functional comparison and advances our understanding of how the environment shapes microbial communities.

54 ENVIRONMENTAL SCIENCES↗

A dynamic integrated test for the Space Shuttle

The dynamic integrated test (DIT) has been designed to perform a final checkout of the assembled Space Shuttle vehicle at Kennedy Space Center. The fact that the vehicle is not in a laboratory environment for the test represents a significant constraint in that the use of test equipment is extremely limited, and environment models cannot be used. In essence, the DIT causes the vehicle to believe that it is flying, so that hardware and software systems are exercised much as they would be for a real flight. This technique provides a tool for verifying such items as data bus activity patterns, critical timing sequences, software and hardware moding as a function of flight parameters, absence of EMI problems and other systems interactions which cannot be tested fully in the laboratory.

Brody, S.↗

Halogen occultation experiment (HALOE) performance verification test procedure

The Performance Verification Test Procedure is given for the Halogen Occultation Experiment (HALOE) instrument, which is being developed in house at the Langley Research Center for the Upper Atmosphere Research Satellite (UARS). This procedure is used for comprehensive performance testing of the HALOE instrument which occurs before, during, and after flight environmental tests. The radiometric performance tests include noise, drift, linearity, instantaneous field-of-view, cal wheel gas cell characterization, and self thermal emissions. Pointer/tracker performance tests include sun sensor performance, gimbal performance, control system performance, and boresight alignment. In addition, the instrument is tested functionally in simulated orbit sequences and all command operating modes are exercised. The data analysis required for each test is specified and pass/fail criteria are given where applicable. This test will fully demonstrate the HALOE instrument's ability to achieve science mission requirements. The HALOE instrument is a gas correlation radiometer that measures vertical distribution of eight upper atmospheric constituents: O3, HCl, HF, NO, CH4, H2O, NO2, and CO2.

Mauldin, L. E., III↗

Biological Information Signal Processor

Biological Information Signal Processor (BISP) is computing system analyzing data on deoxyribonucleic acid (DNA) sequences for molecular genetic analysis. Includes coprocessors, specialized microprocessors complementing present and future computers by performing rapidly most-time-consuming DNA-sequence-analyzing functions, establishing relationships (alignments) between both global sequences and defining patterns in multiple sequences. Also includes state-of-art software and data-base systems on both conventional and parallel computer systems to augment analytical abilities of developmental coprocessors.

Chow, Edward T.↗

Distributed integrated instrumentation and control system

The operation and capabilities of a new integrated instrumentation and control system are described. The system will, under one main program, both acquire data from a conducted test and automatically control the test sequence. The system layout has a multiplexer front end and control-function electronics at the test area, while the system control computer, recording devices, and monitors are located remotely. The system's data, control, and communication signals are transmitted via fiber-optic lines. Diagrams are presented illustrating the control and data displays.

Hagood, Don↗

A Route to Design Novel Functional Peptides by Applying a Denoising Diffusional Model to mRNA Display Libraries

In vitro directed evolution techniques, such as mRNA display, enable peptide ligand discovery and optimization. However, physical libraries that rely on a genetic code can only search a small fraction of sequence space due to inherent biases in the genetic code and experimental limitations. To address this challenge, denoising diffusion implicit models (DDIMs) are applied to generate novel peptide ligands against B‐cell lymphoma extra‐large (Bcl‐x L ), a key cancer target. Starting with high‐throughput sequencing data from previous selections, a DDIM is trained to produce novel sequences with high affinity binding. Experimental validation confirms that most generated sequences are functionally equivalent to the original library members for Bcl‐x L binding and demonstrated comparable binding kinetics and affinity relative to the wildtype and nearest original neighbors. Importantly, this approach generated rare sequences not easily accessible via mutation and directed evolution. These results indicate that DDIMs can complement and expand directed evolution data, efficiently exploring underrepresented regions of sequence space. This approach provides a broadly applicable framework for accelerating ligand discovery and optimizing molecular properties across diverse targets.

Qi, Pearl [Mork Family Department of Chemical Engi↗

Autonomous Real Time Requirements Tracing

One of the more challenging aspects of software development is the ability to verify and validate the functional software requirements dictated by the Software Requirements Specification (SRS) and the Software Detail Design (SDD). Insuring the software has achieved the intended requirements is the responsibility of the Software Quality team and the Software Test team. The utilization of Timeliner-TLX(sup TM) Auto- Procedures for relocating ground operations positions to ISS automated on-board operations has begun the transition that would be required for manned deep space missions with minimal crew requirements. This transition also moves the auto-procedures from the procedure realm into the flight software arena and as such the operational requirements and testing will be more structured and rigorous. The autoprocedures would be required to meet NASA software standards as specified in the Software Safety Standard (NASASTD- 8719), the Software Engineering Requirements (NPR 7150), the Software Assurance Standard (NASA-STD-8739) and also the Human Rating Requirements (NPR-8705). The Autonomous Fluid Transfer System (AFTS) test-bed utilizes the Timeliner-TLX(sup TM) Language for development of autonomous command and control software. The Timeliner-TLX(sup TM) system has the unique feature of providing the current line of the statement in execution during real-time execution of the software. The feature of execution line number internal reporting unlocks the capability of monitoring the execution autonomously by use of a companion Timeliner-TLX(sup TM) sequence as the line number reporting is embedded inside the Timeliner-TLX(sup TM) execution engine. This negates I/O processing of this type data as the line number status of executing sequences is built-in as a function reference. This paper will outline the design and capabilities of the AFTS Autonomous Requirements Tracker, which traces and logs SRS requirements as they are being met during real-time execution of the targeted system. It is envisioned that real time requirements tracing will greatly assist the movement of autoprocedures to flight software enhancing the software assurance of auto-procedures and also their acceptance as reliable commanders.

Plattsmier, George↗

Autonomous Real Time Requirements Tracing

One of the more challenging aspects of software development is the ability to verify and validate the functional software requirements dictated by the Software Requirements Specification (SRS) and the Software Detail Design (SDD). Insuring the software has achieved the intended requirements is the responsibility of the Software Quality team and the Software Test team. The utilization of Timeliner-TLX(sup TM) Auto-Procedures for relocating ground operations positions to ISS automated on-board operations has begun the transition that would be required for manned deep space missions with minimal crew requirements. This transition also moves the auto-procedures from the procedure realm into the flight software arena and as such the operational requirements and testing will be more structured and rigorous. The autoprocedures would be required to meet NASA software standards as specified in the Software Safety Standard (NASASTD- 8719), the Software Engineering Requirements (NPR 7150), the Software Assurance Standard (NASA-STD-8739) and also the Human Rating Requirements (NPR-8705). The Autonomous Fluid Transfer System (AFTS) test-bed utilizes the Timeliner-TLX(sup TM) Language for development of autonomous command and control software. The Timeliner- TLX(sup TM) system has the unique feature of providing the current line of the statement in execution during real-time execution of the software. The feature of execution line number internal reporting unlocks the capability of monitoring the execution autonomously by use of a companion Timeliner-TLX(sup TM) sequence as the line number reporting is embedded inside the Timeliner-TLX(sup TM) execution engine. This negates I/O processing of this type data as the line number status of executing sequences is built-in as a function reference. This paper will outline the design and capabilities of the AFTS Autonomous Requirements Tracker, which traces and logs SRS requirements as they are being met during real-time execution of the targeted system. It is envisioned that real time requirements tracing will greatly assist the movement of autoprocedures to flight software enhancing the software assurance of auto-procedures and also their acceptance as reliable commanders

Plattsmier, George I.↗

An object-oriented data reduction system in Fortran

A data reduction system for the AAO two-degree field project is being developed using an object-oriented approach. Rather than use an object-oriented language (such as C++) the system is written in Fortran and makes extensive use of existing subroutine libraries provided by the UK Starlink project. Objects are created using the extensible N-dimensional Data Format (NDF) which itself is based on the Hierarchical Data System (HDS). The software consists of a class library, with each class corresponding to a Fortran subroutine with a standard calling sequence. The methods of the classes provide operations on NDF objects at a similar level of functionality to the applications of conventional data reduction systems. However, because they are provided as callable subroutines, they can be used as building blocks for more specialist applications. The class library is not dependent on a particular software environment thought it can be used effectively in ADAM applications. It can also be used from standalone Fortran programs. It is intended to develop a graphical user interface for use with the class library to form the 2dF data reduction system.

Bailey, J.↗

ISSYS: An integrated synergistic Synthesis System

Integrated Synergistic Synthesis System (ISSYS), an integrated system of computer codes in which the sequence of program execution and data flow is controlled by the user, is discussed. The commands available to exert such control, the ISSYS major function and rules, and the computer codes currently available in the system are described. Computational sequences frequently used in the aircraft structural analysis and synthesis are defined. External computer codes utilized by the ISSYS system are documented. A bibliography on the programs is included.

Dovi, A. R.↗

Microelectronics Instrument Products Shock and Vibration Electro-Optics: Acceptance Data Package - Section B

The motor/encoder (henceforth referred to as the UUT) test sequence began with a baseline functional evaluation, which demonstrated that the motor satisfied the operating torque, cogging torque, winding resistance, and mechanical requirements of SOW. In addition, the encoder electrical requirements were verified, as well as the alignment of the encoder outputs relative to the motor shaft position. There were no discrepancies observed in this portion of the test. The UUT was then exposed to a number of environments, including thermal vacuum, thermal cycling, random and sine vibration, and mechanical shock. During the thermal environments, the performance of the UUT under load was verified at specified points in the cycles, as described in ATP 20049. In addition, the UUT was bench tested between the two thermal environments. No anomalies were observed during the thermal tests. The vibration and shock tests were performed by East-West Technology Corporation, West Babylon, New York. The UUT was delivered to the lab in a sealed vibration fixture in order to maintain the cleanliness levels required by the SOW. In addition, a three ounce load was attached to the motor shaft. The attachment method of this load caused damage to the shaft and bearing during random vibration of S/N 0003 on April 28, 1995, and is described further in NCR 00168.

Source record↗

RB-TnSeq elucidates dicarboxylic-acid-specific catabolism in β-proteobacteria for improved plastic monomer upcycling

Dicarboxylic acids are key components of many polymers and plastics, making them a target for both engineered microbial degradation and sustainable bioproduction. In this study, we generated a comprehensive data set of functional evidence for the genetic basis of dicarboxylic and fatty acid metabolism using randomly barcoded transposon sequencing (RB-TnSeq). We identified four β-proteobacteria that displayed robust growth with dicarboxylic acid sole carbon source and cultured their mutant libraries with dicarboxylic and fatty acids with carbon chain lengths from C3 to C12. The resulting fitness data suggested that dicarboxylic and fatty acid metabolisms are largely distinct, and different sets of β-oxidation genes are required for catabolizing dicarboxylic versus fatty acids of the same carbon chain lengths. In addition, we identified transcriptional regulators and transporters with strong fitness phenotypes related to dicarboxylic acid utilization. In Ralstonia sp. UNC404CL21Col (R. CL21), we deleted two transcriptional repressors to improve its utilization of short-chain dicarboxylic acids. We exploited the diacid-utilizing catabolism of R. CL21 to upcycle a mock mixture of the dicarboxylic acids produced when polyethylene is oxidized. After introducing a heterologous indigoidine production pathway, this engineered Ralstonia produced 0.56 ± 0.02 g/L indigoidine from a mixture of dicarboxylic acids as a carbon source, demonstrating the potential of R. CL21 to upcycle plastic wastes to products derived from tricarboxylic acid (TCA) cycle intermediates. IMPORTANCE: Upcycling the carbon in plastic wastes to value-added products is a promising approach to address the plastic waste and climate crises, and dicarboxylic acid metabolism is an important facet of several approaches. Improving our understanding of the genetic basis of this metabolism has the potential to uncover new enzymes and genetic parts for engineered pathways involving dicarboxylic acids. Our data set is the most comprehensive interrogation of dicarboxylic acid catabolism to date, and this work will be of utility to researchers interested in both plastics bioproduction and upcycling applications.

Pearson, Allison N↗

Lunar Impact Basins: Stratigraphy, Sequence and Ages from Superposed Impact Crater Populations Measured from Lunar Orbiter Laser Altimeter (LOLA) Data

Impact basin formation is a fundamental process in the evolution of the Moon and records the history of impactors in the early solar system. In order to assess the stratigraphy, sequence, and ages of impact basins and the impactor population as a function of time, we have used topography from the Lunar Orbiter Laser Altimeter (LOLA) on the Lunar Reconnaissance Orbiter (LRO) to measure the superposed impact crater size-frequency distributions for 30 lunar basins (D ≥ 300 km). These data generally support the widely used Wilhelms sequence of lunar basins, although we find significantly higher densities of superposed craters on many lunar basins than derived by Wilhelms (50% higher densities). Our data also provide new insight into the timing of the transition between distinct crater populations characteristic of ancient and young lunar terrains. The transition from a lunar impact flux dominated by Population 1 to Population 2 occurred before the mid-Nectarian. This is before the end of the period of rapid cratering, and potentially before the end of the hypothesized Late Heavy Bombardment. LOLA-derived crater densities also suggest that many Pre-Nectarian basins, such as South Pole-Aitken, have been cratered to saturation equilibrium. Finally, both crater counts and stratigraphic observations based on LOLA data are applicable to specific basin stratigraphic problems of interest; for example, using these data, we suggest that Serenitatis is older than Nectaris, and Humboldtianum is younger than Crisium. Sample return missions to specific basins can anchor these measurements to a Pre-Imbrian absolute chronology.

Fassett, C. I.↗

Combinatorial transcription factor binding encodes cis -regulatory wiring of mouse forebrain GABAergic neurogenesis

Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as in vivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.

59 BASIC BIOLOGICAL SCIENCES↗