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18 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Identification of potent inhibitors of JUN N-terminal kinases for treatment of endometriosis and associated pain

Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibitors with increased potency and specificity are needed to address the inflammatory pathology of endometriosis and to prevent disease progression. Leveraging a DNA-encoded chemical library collection of ~4 billion compounds, we identified lead inhibitor CDD-2428 and optimized derivatives, CDD-2728 and CDD-3013, with excellent binding affinity to JNK1-3 (K d = 0.12 to 3.7 nM), enhanced selectivity, metabolic stability, and cellular permeability. Crystallographic and biochemical studies confirmed that CDD-3013 exhibited superior kinase selectivity with improved efficacy compared to existing JNK inhibitors. In primary endometriosis cell models, CDD-2728 and CDD-3013 suppressed JNK-dependent inflammatory signaling, dampening pathways linked to pain, invasion, angiogenesis, and macrophage recruitment. In an endometriosis mouse model, both CDD-2728 and CDD-3013 reduced endometriotic lesion size, macrophage infiltration, and cellular proliferation, showing in vivo efficacy. When tested in a lipopolysaccharide-induced hyperalgesia model, CDD-2728 and CDD-3013 decreased markers of induced pain, as measured by changes in a dynamic weight bearing test and Grimace scores. These findings nominate CDD-2728 and CDD-3013 as potent, nonhormonal therapeutic candidates for endometriosis with broad anti-inflammatory and analgesic activity, addressing a critical unmet clinical need.

Madasu, Chandrashekhar [Department of Pathology an↗
DOE OSTI2024

Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse DNA-encoded chemical libraries (DECLs) against the kinase domain of ALK2. Off-DNA synthesis of DECL hits and biochemical validation revealed nanomolar potent ALK2 inhibitors. Further structure-activity relationship studies yielded center for drug discovery (CDD)-2789, a potent [NanoBRET (NB) cell IC50: 0.54 μM] and metabolically stable analog with good pharmacological profile. Crystal structures of ALK2 bound with CDD-2281, CDD-2282, or CDD-2789 show that these inhibitors bind the active site through Van der Waals interactions and solvent-mediated hydrogen bonds. CDD-2789 exhibits high selectivity toward ALK2/ALK1 in KINOMEscan analysis and NB K192 assay. In cell-based studies, ALK2 inhibitors effectively attenuated activin A and BMP-induced Phosphorylated SMAD1/5 activation in fibroblasts from individuals with FOP in a dose-dependent manner. Thus, CDD-2789 is a valuable tool compound for further investigation of the biological functions of ALK2 and ALK1 and the therapeutic potential of specific inhibition of ALK2.

Jimmidi, Ravikumar↗
NASA NTRS1984

Nutritional models for space travel from chemically defined diets

Human nutritional requirements are summarized, including recommended daily intake and maximum safe chronic intake of nutrients. The biomedical literature on various types of chemically defined diets (CDD's), which are liquid, formulated diets for enteral and total parenteral nutrition, is reviewed. The chemical forms of the nutrients in CDD's are detailed, and the compositions and sources of representative commercial CDD's are tabulated. Reported effects of CDD's in medical patients, healthy volunteers, and laboratory animals are discussed. The effects include gastrointestinal side effects, metabolic imbalances, nutrient deficiencies and excesses, and psychological problems. Dietary factors contributing to the side effects are examined. Certain human nutrient requirements have been specified more precisely as a result of long-term use of CDD's, and related studies are included. CDD's are the most restricted yet nutritionally complete diets available.

Dufour, P. A.↗
NASA NTRS1992

Candidate Mission from Planet Earth control and data delivery system architecture

Using a structured, experienced-based approach, Goddard Space Flight Center (GSFC) has assessed the generic functional requirements for a lunar mission control and data delivery (CDD) system. This analysis was based on lunar mission requirements outlined in GSFC-developed user traffic models. The CDD system will facilitate data transportation among user elements, element operations, and user teams by providing functions such as data management, fault isolation, fault correction, and link acquisition. The CDD system for the lunar missions must not only satisfy lunar requirements but also facilitate and provide early development of data system technologies for Mars. Reuse and evolution of existing data systems can help to maximize system reliability and minimize cost. This paper presents a set of existing and currently planned NASA data systems that provide the basic functionality. Reuse of such systems can have an impact on mission design and significantly reduce CDD and other system development costs.

Shapiro, Phillip↗
NASA NTRS2009

Using XML Configuration-Driven Development to Create a Customizable Ground Data System

The Mission data Processing and Control Subsystem (MPCS) is being developed as a multi-mission Ground Data System with the Mars Science Laboratory (MSL) as the first fully supported mission. MPCS is a fully featured, Java-based Ground Data System (GDS) for telecommand and telemetry processing based on Configuration-Driven Development (CDD). The eXtensible Markup Language (XML) is the ideal language for CDD because it is easily readable and editable by all levels of users and is also backed by a World Wide Web Consortium (W3C) standard and numerous powerful processing tools that make it uniquely flexible. The CDD approach adopted by MPCS minimizes changes to compiled code by using XML to create a series of configuration files that provide both coarse and fine grained control over all aspects of GDS operation.

Nash, Brent↗
NASA NTRS2018

Using the cFS Command and Data Dictionary (CCDD) to Automate Software Development on Habulous

Final paper is attached. The NASA developed Core Flight System (cFS) is a reusable software architecture that has been used on multiple spaceflight missions. By using this framework, missions are able to reuse code from other missions, as well as leverage deployment onto similar computer architectures (i.e. not "reinvent the wheel" on each new mission). The success in the cFS concept can be seen in the large number of projects using cFS at FSW-2018. The Habulous project is an Earth-based testbed, used for hardware and software that may one day be used on a future space habitat unit, with many participating groups from various NASA centers and aerospace organizations around the country. The distributed nature of the various teams mean that defining (and following) an interface definition is critical on the project. Additionally, since various groups use various types of computer hardware (32/64-bit, big/little endian, Linux/VxWorks/Windows) many additional complications exist in interfacing all the various components into a final integrated system. cFS is used on the majority the flight software (FSW) in running in Habulous. But some subsystems have elected to not use cFS, and use a software bridge (called SBN_lib) to interact with the other cFS nodes in Habulous. In order to most efficiently develop the FSW, a central database is used to define and store each message sent by cFS. A Command and Data Dictionary (CDD) is something nearly universal on spacecraft, but as a team we worked to develop the CDD before the SW development was complete, and not treat it like "as built" documentation. To manage the CDD, the cFS Command and Data Dictionary (CCDD) tool was chosen (available from NASA as open source software). The CCDD tool has successfully been used to automate/autocode a large amount of software used on Habulous, as we are hoping to use it to define even more items in the future (time-triggered Ethernet (TTE) network maps, CPU scheduling). Additionally, Habulous has been exploring the use of cFS on wildly heterogeneous CPUs, and how to coordinate all those various machines using/extending the software bus – network (SBN) application in cFS, as well as TTE to coordinate message passing between various synchronized machines. The major topics to be covered in the presentation are: (1) Updating to the CCSDS_v2 extended headers (and using CPU# as subsystem ID). (2) Managing all the message identification numbers for each cFS message sent/received on any of the various CPUs. (3) Using the CCDD information to automatically generate the C-header files that define the structure for all software bus (SB) commands/telemetry messages. (4) Using the CCDD to automatically generate XML Telemetry and Command Exchange (XTCE) files, which streams display production/integration/testing in a web based display architecture (5) Extending/customizing SBN to pass messages among computers on multiple networks. (6) Using "Protobetter" inside SBN to manage different endian-ness/architectures. (7) Using SBN_lib to allow non-cFS node to communicate with cFS nodes. (8) Developing TTE network and schedule tables for all the various CPUs to use.

Hirsh, Robert L.↗
NASA NTRSDate not supplied

Estimating Future Changes of Energy Demand for Heating and Cooling Buildings at NASA Centers GC23J-1198

With its unique and trusted earth observations, NASA is a critical source in informing decisions that will help achieve the U.S. goal of Net-Zero Greenhouse Gas (GHG) Emissions by 2050. NASA’s Prediction of Worldwide Energy Resource (POWER) project facilitates the use of NASA Earth Science data holdings within the energy, agricultural, and building heating/cooling design industries. POWER packages solar and meteorological data from several NASA projects in a user friendly GIS-enabled web services system (https://power.larc.nasa.gov). As part of the development of new data products to support the energy and building heating/cooling design communities, we estimate the changes in energy required to heat and cool buildings in the future climate at 14 different NASA site locations spread throughout the continental United States, as projected by CMIP6 climate models under different emissions scenarios. Bias-corrected downscaled time series of meteorological variables are taken from NASA Earth Exchange (NEX) Global Daily Downscaled Projections (GDDP-CMIP6) downscaled climate model data. The spread between the different model projections is accounted for by analyzing both the ensemble average of 22 CMIP6 models and 6 representative models with different climate sensitivities and different interannual variability. Changes in energy use are estimated in two ways. First, changes in the total annual heating and cooling degree days (HDD and CDD, respectively) are calculated relative to the current climate. This is done at all 14 sites. Second, the downscaled time series are used as inputs into RETScreen(R), a clean energy management decision tool, to give an estimate of heating/cooling energy use for a typical office building. We use this estimation method with model data at Langley Research Center. In the next 50 years, the annual total of HDD (CDD) is projected to decrease by 8-38% (increase by 5-28%) at all sites, with the increase in CDD typically a larger magnitude the decrease in HDD. For a typical small office building at Langley Research Center, the amount of energy needed to cool increases by 33-54% and the amount of energy to heat decreases by 29-40%. POWER is working to develop long term climate data services based on these results to include in future data products to provide to users.

Bradley M. Hegyi↗
DOE OSTI2024

Who will be making wave energy? A community-driven design approach toward just and sustainable energy futures in Alaska

Renewable energy transition, once thought of as a singular, large-scale switch in industrial energy generating technologies from fossil fuels to renewables, have gained a broader set of requirements, including the need for justice and environmental protection. While discourse around policy and process has grown to consider these requirements, the focus of design of new renewable energy projects and technologies remains dominantly fixed on maximizing energy production, and renewables are falling short of meeting the requirements of just energy transitions. Meanwhile, in design studies, participatory and co-design approaches which explicitly consider justice in both process and outcomes have long been theorized and applied. However, applications of these approaches to renewable energy project design are under-theorized. In this paper, we explore the effectiveness of the adoption and adaptation of a co-design approach called Community-Driven Design (CDD) in enabling meaningful participation prior to technological maturity and bringing the attention of designers to a more diverse set of energy futures focused on justice and sustainability. Here, we do so by developing and testing the approach with community members in Sitka, AK, USA. We conclude that the approach has the potential to increase meaningful participation. Furthermore, we conclude that through diverse understandings of energy and the emergence of design narratives that engage with the complexity of vulnerability, accountability, and resilience, CDD led designers to consider justice, sustainability, and a diverse set of possible energy futures both within and beyond Sitka.

16 TIDAL AND WAVE POWER↗
DOE OSTI2024

Increasing extreme hourly precipitation risk for New York City after Hurricane Ida

The remnants of Hurricane Ida caused major damage and death in the United States on September 1st, 2021, and 11 people drowned in flooded basement apartments within New York City (NYC). It was catastrophic because the maximum hourly precipitation intensity, recorded as 3.47 inches (88.1 mm) per hour at Central Park, was unprecedentedly high for the NYC region. The stormwater infrastructure in NYC is built for 1.75 inches (44.5 mm) per hour, and so understanding the dynamic risk associated with Ida can inform city planning efforts for climate change’s impact on short duration extreme precipitation events. We contextualize this storm’s record-breaking hourly intensity within the historical record as well as project its risk in the near- to medium-term future using nonstationary stochastic models. These models are conditioned on average temperature (T avg ) and cooling degree day (CDD) projections from three climate models as a covariate, each with a SSP 126 and SSP 370 scenario. The likelihood of such a storm was slowly increasing even before Ida happened, but the projected aggregate reoccurrence risk of an event of Ida’s magnitude over time from the non-stationary models ranges from 4 to 52 times higher than the risk given by the stationary model. Using CDD as a covariate resulted in risks that were more than twice the magnitude than when using T avg . Presenting both covariates provides a broader envelope of uncertainty, which highlights the importance and nuances in the choice of a regionally appropriate covariate for non-stationary risk analysis.

Mossel, Carolien↗
NASA NTRS1993

Methods and means used in programming intelligent searches of technical documents

In order to meet the data research requirements of the Safety, Reliability & Quality Assurance activities at Kennedy Space Center (KSC), a new computer search method for technical data documents was developed. By their very nature, technical documents are partially encrypted because of the author's use of acronyms, abbreviations, and shortcut notations. This problem of computerized searching is compounded at KSC by the volume of documentation that is produced during normal Space Shuttle operations. The Centralized Document Database (CDD) is designed to solve this problem. It provides a common interface to an unlimited number of files of various sizes, with the capability to perform any diversified types and levels of data searches. The heart of the CDD is the nature and capability of its search algorithms. The most complex form of search that the program uses is with the use of a domain-specific database of acronyms, abbreviations, synonyms, and word frequency tables. This database, along with basic sentence parsing, is used to convert a request for information into a relational network. This network is used as a filter on the original document file to determine the most likely locations for the data requested. This type of search will locate information that traditional techniques, (i.e., Boolean structured key-word searching), would not find.

Gross, David L.↗
DOE OSTI2025

Implications of Changes in Water Stress and Precipitation Extremes for Cocoa Production in Côte D'ivoire and Ghana

ABSTRACT Climate change induces high variability in drought patterns and extreme precipitation indices in rainfed cocoa farming, impacting cocoa production. This study evaluated water stress, meteorological and agricultural drought conditions, and critical extreme precipitation indices in the world's two largest cocoa‐producing nations from 1981 to 2022. The results revealed a significant reduction in total annual precipitation (PRCPTOT), in the last three decades, with the greatest decline in the 1991–2000 and 2011–2022 periods. Ghana experienced the most significant reduction up to 15% (200 mm/year) in the last decade, attributed to a substantial decrease in wet days number (RR1) up to 25 days per year, a reduction in maximum consecutive wet days (CWD) up to 6 days per year, and an increase in maximum consecutive dry days (CDD) up to 15 days per year. Moreover, there was a notable decline in the Simple Daily Intensity Index (SDII), with reductions of up to 4 mm/day in certain areas, contributing to increased drought frequency, severity, and duration. In the most recent decade (2011–2022), particularly during the extremely dry years of 2013 and 2015, cocoa‐growing regions in Ghana (GHA) and eastern Côte d'Ivoire (CIV) experienced prolonged agricultural drought expressed by soil moisture deficit, typically extending from May to September. Additionally, large portions of central and eastern Ghana, as well as northeastern Côte d'Ivoire experienced sustained water stress, with over three consecutive months of total monthly precipitation falling below 100 mm, negatively impacting cocoa productivity. The decrease in the yield in the range of 2.5% to 37% was noted in the dry years and the following years, varying according to the country depending on the severity of the drought. Sensitivity analysis highlights cocoa yield's responsiveness to drought and water stress, particularly in specific years when water stress occurred, such as 1984,1985, 1989, 1995, 1999, 2000, and 2008. Considering the observed trends in precipitation patterns and their impact on cocoa production, it is crucial to acknowledge the inherent uncertainty of future precipitation patterns due to climate change. To address this challenge effectively, our study underscores the importance of identifying and closely monitoring regions currently facing water stress, as determined by precipitation and drought indicators. Over the analysed period (1981–2022), we have noted shifts in the distribution of water‐stressed areas, highlighting the dynamic nature of this issue. Consequently, we advocate for a targeted approach to implement cocoa supplementary irrigation in consistently water‐stressed regions.

Obahoundje, Salomon [International Water Managemen↗
NASA NTRS1979

Large area CCD image sensors for space astronomy

The Defense Advanced Research Projects Agency (DARPA) has a substantial program to develop a 2200 x 2200 pixel CCD (Charge Coupled Device) mosaic array made up of 400 individual CCD's, 110 x 110 pixels square. This type of image sensor appeared to have application in space and ground-based astronomy. Under this grant a CCD television camera system was built which was capable of operating an array of 4 CCD's to explore the suitability of the CCD's to explore the suitability of the CCD for astronomical applications. Two individual packaged CCD's were received and evaluated. Evaluation of the basic characteristics of the best individual chips was encouraging, but the manufacturer found that their yield in manufacturing this design is two low to supply sufficient CDD's for the DARPA mosaic array. The potential utility of large mosaic arrays in astronomy is still substantial and continued monitoring of the manufacturers progress in the coming year is recommended.

Schwarzschild, M.↗
NASA NTRS1980

Numerical solution of the Navier-Stokes equations for a family of three-dimensional corner geometries

Three-dimensional corners occur in many aerodynamic engineering situations. Supersonic flow about such geometries is characterized by strong inviscid-viscid interactions which are analyzed adequately only through the solution of the Navier-Stokes equations. In this paper numerical solution for the laminar compressible Navier-Stokes equations are presented for a family of three-dimensional corners consisting of wedge-plate and wedge-cylinder intersecting boundaries. The equations of motion are transformed to a uniform rectangular computational domain. The computational technique is the MacCormack time-split algorithm vectorized and programmed to run on the CDD CYBER 203 computer. The metric data for the transformation is obtained from the 'two-boundary technique.'

Smith, R. E.↗
NASA NTRS1986

Intensified-CCD focal plane detector for space applications A second generation

An intensified-CCD detector system developed for space applications from commercially available components is described. This detector uses components which are readily available and are mechanically, thermally, and optically coupled to produce the final compact system. The CCD is cooled using a Peltier-effect thermoelectric cooler to reduce thermal noise. The image is formed on the photocathode of a proximity-focused image intensifier and is transferred fiber-optically from the intensifier to the CDD. Various photocathode and window materials are used to optimize the system for use within the wavelength range extending from the far UV to the near IR. The basic design, including the image intensifier, intensifier-CCD interface, CCD array, cooling, electronics, and mounting, and the detector performance are described in detail.

Torr, M. R.↗
NASA NTRS1995

COMET Progresses Toward First Mission

The COMmercial Experiment Transporter (COMET) is a set of hardware and related infrastructure used to support orbital experiments of the CDD's and their industrial partners. During this year major support contracts were signed, preliminary design reviews conducted, experiments selected for the first mission, and long lead items place on order. The Program Office and CCDS Monitors took an active role in guiding COMET through the activation maze. Launch and recovery sites were selected and licenses for the launch vehicle, recovery system, and recovery operations were filed by the contractors with the Department of Transportation. As the period closed, COMET was preparing for Critical Design Reviews on all major systems and a target launch data was selected. This report deals primarily with the programmatic issues which were resolved as the program matured. At times is is impossible to disassociate the technical from the programmatic and, in such cases the technical material is presented to provide insight into the paths selected by both CCDS and Contractor Management.

Pawlick, J.↗
NASA NTRS2013

Navigation Performance of Global Navigation Satellite Systems in the Space Service Volume

This paper extends the results I reported at this year's ION International Technical Meeting on multi-constellation GNSS coverage by showing how the use of multi-constellation GNSS improves Geometric Dilution of Precision (GDOP). Originally developed to provide position, navigation, and timing for terrestrial users, GPS has found increasing use for in space for precision orbit determination, precise time synchronization, real-time spacecraft navigation, and three-axis attitude control of Earth orbiting satellites. With additional Global Navigation Satellite Systems (GNSS) coming into service (GLONASS, Galileo, and Beidou) and the development of Satellite Based Augmentation Services, it is possible to obtain improved precision by using evolving multi-constellation receiver. The Space Service Volume formally defined as the volume of space between three thousand kilometers altitude and geosynchronous altitude ((is) approximately 36,500 km), with the volume below three thousand kilometers defined as the Terrestrial Service Volume (TSV). The USA has established signal requirements for the Space Service Volume (SSV) as part of the GPS Capability Development Documentation (CDD). Diplomatic efforts are underway to extend Space service Volume commitments to the other Position, Navigation, and Timing (PNT) service providers in an effort to assure that all space users will benefit from the enhanced capabilities of interoperating GNSS services in the space domain.

Force, Dale A.↗
NASA NTRS2015

Combined Global Navigation Satellite Systems in the Space Service Volume

Besides providing position, navigation, and timing (PNT) services to traditional terrestrial and airborne users, GPS is also being increasingly used as a tool to enable precision orbit determination, precise time synchronization, real-time spacecraft navigation, and three-axis attitude control of Earth orbiting satellites. With additional Global Navigation Satellite System (GNSS) constellations being replenished and coming into service (GLONASS, Beidou, and Galileo), it will become possible to benefit from greater signal availability and robustness by using evolving multi-constellation receivers. The paper, "GPS in the Space Service Volume," presented at the ION GNSS 19th International Technical Meeting in 2006 (Ref. 1), defined the Space Service Volume, and analyzed the performance of GPS out to seventy thousand kilometers. This paper will report a similar analysis of the signal coverage of GPS in the space domain; however, the analyses will also consider signal coverage from each of the additional GNSS constellations noted earlier to specifically demonstrate the expected benefits to be derived from using GPS in conjunction with other foreign systems. The Space Service Volume is formally defined as the volume of space between three thousand kilometers altitude and geosynchronous altitude circa 36,000 km, as compared with the Terrestrial Service Volume between 3,000 km and the surface of the Earth. In the Terrestrial Service Volume, GNSS performance is the same as on or near the Earth's surface due to satellite vehicle availability and geometry similarities. The core GPS system has thereby established signal requirements for the Space Service Volume as part of technical Capability Development Documentation (CDD) that specifies system performance. Besides the technical discussion, we also present diplomatic efforts to extend the GPS Space Service Volume concept to other PNT service providers in an effort to assure that all space users will benefit from the enhanced interoperability of GNSS services in the space domain. A separate paper presented at the conference covers the individual GNSS performance parameters for respective Space Service Volumes.

navigation satellites↗
NASA NTRSDate not supplied

Data Definition Management for Orion Backup Flight Software

The NASA developed Core Flight System (cFS) is a reusable software architecture that has been used on multiple spaceflight missions. Missions using cFS can reuse code from other missions, as well as leverage deployment to similar computer architectures. The Orion Backup Flight Software (BFS) team selected cFS as the architecture to be used on the program, and this presentation will describe some design choices we made, and the consequences of those decisions.

CFS↗