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NASA NTRS2011

Designing a Distributed Space Systems Simulation in Accordance with the Simulation Interoperability Standards Organization (SISO)

Simulations are essential for engineering design. These virtual realities provide characteristic data to scientists and engineers in order to understand the details and complications of the desired mission. A standard development simulation package known as Trick is used in developing a source code to model a component (federate in HLA terms). The runtime executive is integrated into an HLA based distributed simulation. TrickHLA is used to extend a Trick simulation for a federation execution, develop a source code for communication between federates, as well as foster data input and output. The project incorporates international cooperation along with team collaboration. Interactions among federates occur throughout the simulation, thereby relying on simulation interoperability. Communication through the semester went on between participants to figure out how to create this data exchange. The NASA intern team is designing a Lunar Rover federate and a Lunar Shuttle federate. The Lunar Rover federate supports transportation across the lunar surface and is essential for fostering interactions with other federates on the lunar surface (Lunar Shuttle, Lunar Base Supply Depot and Mobile ISRU Plant) as well as transporting materials to the desired locations. The Lunar Shuttle federate transports materials to and from lunar orbit. Materials that it takes to the supply depot include fuel and cargo necessary to continue moon-base operations. This project analyzes modeling and simulation technologies as well as simulation interoperability. Each team from participating universities will work on and engineer their own federate(s) to participate in the SISO Spring 2011 Workshop SIW Smackdown in Boston, Massachusetts. This paper will focus on the Lunar Rover federate.

Cowen, Benjamin↗

NASA NTRS2012

Design and Implementation of a Lunar Communications Satellite and Server for the 2012 SISO Smackdown

Last year, the Simulation Interoperability Standards Organization (SISO) inaugurated the now annual High Level Architecture (HLA) Smackdown at the Spring Simulation Interoperability Workshop (SIW). A primary objective of the Smackdown event is to provide college students with hands-on experience in the High Level Architecture (HLA). The University of Alabama in Huntsville (UAHuntsville) fielded teams in 2011 and 2012. Both the 2011 and 2012 smackdown scenarios were a lunar resupply mission. The 2012 UAHuntsville fielded four federates: a communications network Federate called Lunar Communications and Navigation Satellite Service (LCANServ) for sending and receiving messages, a Lunar Satellite Constellation (LCANSat) to put in place radios needed by the communications network for Line-Of-Sight communication calculations, and 3D graphical displays of the orbiting satellites and a 3D visualization of the lunar surface activities. This paper concentrates on the first two federates by describing the functions, algorithms, the modular FOM, experiences, lessons learned and recommendations for future Smackdown events.

Bulgatz, Dennis↗

NASA NTRS2012

Three Dimensional Computer Graphics Federates for the 2012 Smackdown Simulation

The Simulation Interoperability Standards Organization (SISO) Smackdown is a two-year old annual event held at the 2012 Spring Simulation Interoperability Workshop (SIW). A primary objective of the Smackdown event is to provide college students with hands-on experience in developing distributed simulations using High Level Architecture (HLA). Participating for the second time, the University of Alabama in Huntsville (UAHuntsville) deployed four federates, two federates simulated a communications server and a lunar communications satellite with a radio. The other two federates generated 3D computer graphics displays for the communication satellite constellation and for the surface based lunar resupply mission. Using the Light-Weight Java Graphics Library, the satellite display federate presented a lunar-texture mapped sphere of the moon and four Telemetry Data Relay Satellites (TDRS), which received object attributes from the lunar communications satellite federate to drive their motion. The surface mission display federate was an enhanced version of the federate developed by ForwardSim, Inc. for the 2011 Smackdown simulation. Enhancements included a dead-reckoning algorithm and a visual indication of which communication satellite was in line of sight of Hadley Rille. This paper concentrates on these two federates by describing the functions, algorithms, HLA object attributes received from other federates, development experiences and recommendations for future, participating Smackdown teams.

Fordyce, Crystal↗

NASA NTRS2015

Integrated Mission Simulation (IMSim): Multiphase Initialization Design with Late Joiners, Rejoiners and Federation Save & Restore

This document describes the design of the Integrated Mission Simulation (IMSim) federate multiphase initialization process. The main goal of multiphase initialization is to allow for data interdependencies during the federate initialization process. IMSim uses the High Level Architecture (HLA) IEEE 1516 [1] to provide the communication and coordination between the distributed parts of the simulation. They are implemented using the Runtime Infrastructure (RTI) from Pitch Technologies AB. This document assumes a basic understanding of IEEE 1516 HLA, and C++ programming. In addition, there are several subtle points in working with IEEE 1516 and the Pitch RTI that need to be understood, which are covered in Appendix A. Please note the C++ code samples shown in this document are for the IEEE 1516-2000 standard.

Dexter, Daniel E.↗

NASA NTRS2016

A First Look at the Upcoming SISO Space Reference FOM

Spaceflight is difficult, dangerous and expensive; human spaceflight even more so. In order to mitigate some of the danger and expense, professionals in the space domain have relied, and continue to rely, on computer simulation. Simulation is used at every level including concept, design, analysis, construction, testing, training and ultimately flight. As space systems have grown more complex, new simulation technologies have been developed, adopted and applied. Distributed simulation is one those technologies. Distributed simulation provides a base technology for segmenting these complex space systems into smaller, and usually simpler, component systems or subsystems. This segmentation also supports the separation of responsibilities between participating organizations. This segmentation is particularly useful for complex space systems like the International Space Station (ISS), which is composed of many elements from many nations along with visiting vehicles from many nations. This is likely to be the case for future human space exploration activities. Over the years, a number of distributed simulations have been built within the space domain. While many use the High Level Architecture (HLA) to provide the infrastructure for interoperability, HLA without a Federation Object Model (FOM) is insufficient by itself to insure interoperability. As a result, the Simulation Interoperability Standards Organization (SISO) is developing a Space Reference FOM. The Space Reference FOM Product Development Group is composed of members from several countries. They contribute experiences from projects within NASA, ESA and other organizations and represent government, academia and industry. The initial version of the Space Reference FOM is focusing on time and space and will provide the following: (i) a flexible positioning system using reference frames for arbitrary bodies in space, (ii) a naming conventions for well-known reference frames, (iii) definitions of common time scales, (iv) federation agreements for common types of time management with focus on time stepped simulation, and (v) support for physical entities, such as space vehicles and astronauts. The Space Reference FOM is expected to make collaboration politically, contractually and technically easier. It is also expected to make collaboration easier to manage and extend.

Mueller, Bjorn↗

NASA NTRSDate not supplied

Enabling Simulation Interoperability between International Standards in the Space Domain

Today, the design and development of space systems are conducted cooperatively by historical space agencies in this area such as NASA, ESA, Roscosmos, and JAXA together with their industrial partners. The space system lifecycle is characterized by high costs, uncertain conditions, and dangerous scenarios. To mitigate these issues, space agencies rely heavily on Modelling and Simulation as a key technology to support the analysis, design, and operation of space systems. To support large-scale distributed simulations, the scientific community has developed several standards to support the reuse and interoperability of simulation models such as IEEE 1516 High-Level Architecture (HLA), Real-time Platform Reference Federation Object Model (RPR FOM), Simulation Model Portability (SMP), and the novel Space Reference Federation Object Model (SpaceFOM). While the SpaceFOM standard has been specifically conceptualized for handling space systems, the other ones are more general-purpose and can be used to design and simulate generic complex systems. As a consequence, there is a lake of rules and guidelines to enable interoperability among these standards. The paper presents solutions and experiences for enabling interoperability and transferability of HLA, RPR FOM, and SMP simulation models with SpaceFOM.

Simulation↗

DOE OSTI2022

Quarterly Management Document – FY22, 3rd Quarter, Multi-pass Hybrid Laser Arc Welding of Alloy 740H

During the 3rd quarter of FY22, progress was made on modeling and simulation of deep penetration laser welding of Alloy 740H. Advances in the modeling of residual stress development arising from the calculated temperature field of the solidifying weld pool were made to understand the development of solidification cracking. Additionally, preliminary modeling of the temperature field within the weld pool of a wobbling laser heat source was performed. The maximum temperature of the weld pool was found to vary with time. These result will allow modeling of deep penetration laser welding using a wobbling laser to mitigate weld defects and cracking. Also, additional characterization of hybrid laser arc welds indicated that these welds were not defect-free as originally thought and the current HLA welds would not be acceptable under criteria outlined in the ASME Boiler and Pressure Vessel Code, Section IX. Therefore, additional welding trails with variation of the welding parameters and HLA welding configurations are required to produce welds acceptable under the Section IX criteria. It was shown that considerable reduction of HLAW defects had been achieved with each successive welding campaign. Therefore additional variation of HLAW parameters may still yield the desired defect-free welds, however, options for alternate HLAW configurations as well as plate preheating are outlined as contingency plans to obtain suitable welds. These additional (unplanned) HLAW trial may prevent subsequent milestones from being achieved within the original budget.

36 MATERIALS SCIENCE↗

NASA NTRS2008

Interfacing Space Communications and Navigation Network Simulation with Distributed System Integration Laboratories (DSIL)

NASA's planned Lunar missions will involve multiple NASA centers where each participating center has a specific role and specialization. In this vision, the Constellation program (CxP)'s Distributed System Integration Laboratories (DSIL) architecture consist of multiple System Integration Labs (SILs), with simulators, emulators, testlabs and control centers interacting with each other over a broadband network to perform test and verification for mission scenarios. To support the end-to-end simulation and emulation effort of NASA' exploration initiatives, different NASA centers are interconnected to participate in distributed simulations. Currently, DSIL has interconnections among the following NASA centers: Johnson Space Center (JSC), Kennedy Space Center (KSC), Marshall Space Flight Center (MSFC) and Jet Propulsion Laboratory (JPL). Through interconnections and interactions among different NASA centers, critical resources and data can be shared, while independent simulations can be performed simultaneously at different NASA locations, to effectively utilize the simulation and emulation capabilities at each center. Furthermore, the development of DSIL can maximally leverage the existing project simulation and testing plans. In this work, we describe the specific role and development activities at JPL for Space Communications and Navigation Network (SCaN) simulator using the Multi-mission Advanced Communications Hybrid Environment for Test and Evaluation (MACHETE) tool to simulate communications effects among mission assets. Using MACHETE, different space network configurations among spacecrafts and ground systems of various parameter sets can be simulated. Data that is necessary for tracking, navigation, and guidance of spacecrafts such as Crew Exploration Vehicle (CEV), Crew Launch Vehicle (CLV), and Lunar Relay Satellite (LRS) and orbit calculation data are disseminated to different NASA centers and updated periodically using the High Level Architecture (HLA). In addition, the performance of DSIL under different traffic loads with different mix of data and priorities are evaluated.

Traffic Measuring and Monitoring↗

DOE OSTI2014

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Immunological responses against hepatitis B virus in human peripheral blood mononuclear cell-engrafted mice

Highlights: • DKO-NOG mice, which were NOG mice deficient in both MHC class I and II, were established. • Liver damage was reduced, and survival time was prolonged in human PBMC-engrafted DKO-NOG mice. • HBV-specific immune responses were observed in the established DKO-NOG mice. It is well known that immune-mediated virus elimination is necessary for the treatment of HBV infection. Reconstitution of human immune cells in liver chimeric mice is warranted to understand the immunopathogenesis of HBV infection. Here, we report a new immunologically humanized mouse model with a human immune system via reconstitution of immunodeficient NOG-Iaβ/β2 m double KO mice, which are NOG mice that are deficient in both MHC class I and II (DKO-NOG mice), with human HLA-A2-positive peripheral blood mononuclear cells (PBMCs). After injection of PBMCs, the xenogeneic graft-versus-host disease observed in PBMC-engrafted NOG mice was prevented in PBMC-engrafted DKO-NOG mice. Liver damage was reduced, and the survival time was prolonged in human PBMC-engrafted DKO-NOG mice compared to those in the NOG mice. The expression levels of PD-1 and Tim-3 on human T cells from PBMC-engrafted DKO-NOG mice were lower than those from NOG mice. By induction of HBV-specific T cell responses, such as vaccination with HBc-derived, peptide-pulsed DCs, hydrodynamic injection of HBV vector and intrasplenic injection of HepG2.2.15, the number of HBc-derived, peptide-specific CTLs increased in PBMC-engrafted DKO-NOG mice. Moreover, the recombinant HBV vaccine resulted in the production of hepatitis B surface antibody in 50% of the vaccinated mice. The induction of HBV-specific immune responses could be established in the immunologically humanized mice.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Expression profile analysis of differentially expressed genes in ruptured intracranial aneurysms: In search of biomarkers

Highlights: • Bioinformatics can identify potential biomarkers of ruptured intracranial aneurysm. • BASP1, CD74, CEBPB, ECHDC2, GZMK, HLA-DRB3, KLHL3, SLC2A3 & SOCS3 affect IA rupture. • DEGs are involved in antigen processing and presentation and immune response. • Vascular brain injury affects gene expression in IA tissue. Intracranial aneurysms (IAs) result from the bulging of arterial walls secondary to several factors such as flow, vessel morphology, and genetics. Subarachnoid hemorrhage occurs when such walls rupture, leading to high disability and mortality. Despite numerous investigations pertaining to the relationship between geometric characteristics and IA rupture, only a few have obtained consistent results. This study aimed to further identify the potential genes associated with the pathogenesis of IAs, which may provide novel molecular biomarkers. We downloaded and reanalyzed six datasets, which were divided into four groups. IA walls and blood samples were screened for differentially expressed genes (DEGs); then, functional and pathway enrichment analyses were conducted. In total, 158 common DEGs were identified from Groups 1–3 and 396 genes (187 upregulated and 209 downregulated genes) were differentially expressed in Group 4. The functional analysis revealed that the DEGs were mainly associated with the major histocompatibility complex class II protein complex and antigen processing and presentation. Finally, we identified nine key genes, both in aneurysm tissue samples and blood samples, of which three were mostly associated with the progression and rupture of IAs. Bioinformatics was used to analyze the datasets of the ruptured IAs and identify potential biomarkers, which may provide information for the early detection and treatment of IAs.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Up-regulated lncRNA-MSX2P1 promotes the growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7

Highlights: • High expression of MSX2P1 and S100A7 in psoriatic lesion tissues. • MSX2P1, functions as miR-6731-5p sponge, modulates S100A7 expression. • miR-6731-5p inhibits the progression of IL-22-stimulated keratinocytes by S100A7. Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for shared miRNAs and play critical roles in disease development. Psoriasis is a long-lasting, recurring chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. The keratinocyte response is triggered by the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT) cells treated with or without IL-22. We used hematoxylin and eosin (H&E) staining to determine the pathological changes in skin cells and immunohistochemistry to evaluate the expression of S100A7. We used qRT-PCR and Western blotting to detect the expression levels of MSX2P1 and S100A7. We down-regulated the expression of MSX2P1 by infecting with lentiviral-vector shRNA. We measured cell proliferation, cell cycle status, and apoptosis by the CCK-8 assay, flow cytometry, and Annexin Ⅴ-FITC/PI staining, respectively. In addition, we used the luciferase reporter gene assay to determine the relationships between MSX2P1 or miR-6731-5p and S100A7, respectively. LncRNA array analysis revealed that 103 lncRNAs were up-regulated and 51 were down-regulated. Furthermore, qRT-PCR showed that the mRNAs levels of MSX2P1 was significantly altered in HaCaT cells treated with IL-22, compared with control cells; and MSX2P1 was mainly in the cytoplasm. Based on the IL-22-stimulated lncRNA-associated ceRNA network, we selected MSX2P1-miR-6731-5p-S100A7 for further study. H&E staining exhibited characteristic features specific to psoriatic lesions. Immunohistochemistry demonstrated significantly increased expression levels of S100A7 in psoriatic lesions, compared with normal skin tissue. We observed a positive correlation between lncRNA-MSX2P1 expression and S100A7 expression. In addition, miR-6731-5p suppressed proliferation, accelerated apoptosis in IL-22-stimulated keratinocytes, and decreased the expressions of S100A7, IL-12β, IL-23, HLA-C, CCHCR1, TNF-α, and NF-κB proteins. Our data demonstrated that MSX2P1 facilitate the progression and growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7. We speculate that the biological network of MSX2P1-miR-6731-5p-S100A7 is a potential novel therapeutic target for the future treatment of psoriasis.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Human myoblasts differentiate in various mesenchymal lineages and inhibit allogeneic T cell proliferation through an indolamine 2,3 dioxygenase dependent pathway

Muscle stem cells (MuSC) are considered as a reliable source of therapeutic cells to restore diseased muscles. However in most cases, injected MuSC-derived myoblasts are rapidly destroyed by the host immune response, which impairs the beneficial effect. By contrast, human mesenchymal stromal cells (MSC), have been reported to exhibit potent immune regulatory functions. Thus, we investigated, in vitro, the multipotent differentiation- and immunosuppressive capacities of human myoblasts and compared these features with those of human MSC. Myoblasts shared numerous cell surface markers with MSC, including CD73, CD90, CD105 and CD146. Both cell type were negative for HLA-DR and CD45, CD34 and CD31. CD56, a myogenic marker, was expressed by myoblasts exclusively. Myoblasts displayed multipotent potential capabilities with differentiation in chondrocytes, adipocytes and osteoblasts in vitro. Myoblasts also inhibited allogenic T cell proliferation in vitro in a dose dependent manner, very similarly to MSC. This effect was partly mediated via the activation of indolamine 2,3 dioxygenase enzyme (IDO) after IFNγ exposure. Altogether, these data demonstrate that human myoblasts can differentiate in various mesenchymal linages and exhibit powerful immunosuppressive properties in vitro. Such features may open new therapeutic strategies for MuSC-derived myoblasts.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Optimized simple and affordable procedure for differentiation of monocyte-derived dendritic cells from LRF: An accessible and valid alternative biological source

Dendritic cells are one of the most popular immune cells, which plays a remarkable role in both immunotherapy and tolerance induction. Due to unwanted side effects of leukocyte presence in donated blood, the policy of blood service is the pre-storage reduction of leukocytes, which today, filtration is the most common method for this purpose. The filtration method has led to diminished access to Buffy coat as a generally used conventional source of biological cells. We developed a simple, affordable, and reproducible method for dendritic cell differentiation from filter-derived monocytes and, the results of the filter study were compared with differentiated DCs from the conventional buffy coat-derived monocytes. The Monocytes were recovered from leukoreduction filter using an optimized protocol with supplemented PBS buffer. Following the adhesion method, CD14{sup +} Monocyte-enriched population with the purity of 94 % was obtained. After cytokine stimulation over a 6-day period and maturation induction by LPS, differentiated DCs were evaluated for morphology, surface markers (CD86, CD40, CD83 and, HLA-DR), antigen uptake potency and IL-12 secretion. Analysis and comparison of the results represented no significant difference between the two groups. Accordingly, we conclude that leukoreduction filters could be introduced as a reliable and research-grade source of monocyte for DC generation in biological research.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Dynamics-Based Peptide–MHC Binding Optimization by a Convolutional Variational Autoencoder: A Use-Case Model for CASTELO

An unsolved challenge in the development of antigen-specific immunotherapies is determining the optimal antigens to target. Comprehension of antigen–major histocompatibility complex (MHC) binding is paramount toward achieving this goal. Here, we apply CASTELO, a combined machine learning-molecular dynamics (ML-MD) approach, to identify per-residue antigen binding contributions and then design novel antigens of increased MHC-II binding affinity for a type 1 diabetes-implicated system. We build upon a small-molecule lead optimization algorithm by training a convolutional variational autoencoder (CVAE) on MD trajectories of 48 different systems across four antigens and four HLA serotypes. We develop several new machine learning metrics including a structure-based anchor residue classification model as well as cluster comparison scores. ML-MD predictions agree well with experimental binding results and free energy perturbation-predicted binding affinities. Moreover, ML-MD metrics are independent of traditional MD stability metrics such as contact area and root-mean-square fluctuations (RMSF), which do not reflect binding affinity data. Finally, our work supports the role of structure-based deep learning techniques in antigen-specific immunotherapy design.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2020

An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells

Proinflammatory cytokines are important mediators of pancreatic beta cell dysfunction and demise in the early stages of type 1 diabetes (T1D). Interferon-a (IFNa), a type I interferon member, is expressed in the islets of T1D individuals and it is expression and signaling is regulated by both genetic (T1D risk variants) and environmental factors (viral infections) associated to T1D. We presently characterized human beta cells responses to IFNa by combining ATAC-seq, RNA-seq and proteomics assays. The initial beta cell response to IFNa was characterized by major chromatin remodeling, followed by marked changes in transcriptional and translational regulation. IFNa-induced changes in alternative splicing (AS) and first exon usage increased the diversity of transcripts expressed by beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may significantly expand the peptide repertoire presented by beta cells to the immune system. On the other hand, beta cells up-regulated checkpoint proteins, such as PDL1 and HLA-E, that may protect them against the autoimmune assault. Data mining of the present multi-omics analysis led to the identification of two compound classes that revert IFNa effects on human beta cells and may be translated to clinical trials.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Molecular mechanism of phosphopeptide neoantigen immunogenicity

Abstract often leads to surface presentation of phosphopeptide neoantigens. However, their role in cancer immunogenicity remains unclear. Here we describe a mechanism by which an HLA-B*0702-specific acute myeloid leukemia phosphoneoantigen, pMLL 747–755 (EPR(pS)PSHSM), is recognized by a cognate T cell receptor named TCR27, a candidate for cancer immunotherapy. We show that the replacement of phosphoserine P 4 with serine or phosphomimetics does not affect pMHC conformation or peptide-MHC affinity but abrogates TCR27-dependent T cell activation and weakens binding between TCR27 and pMHC. Here we describe the crystal structures for TCR27 and cognate pMHC, map of the interface produced by nuclear magnetic resonance, and a ternary complex generated using information-driven protein docking. Our data show that non-covalent interactions between the epitope phosphate group and TCR27 are crucial for TCR specificity. This study supports development of new treatment options for cancer patients through target expansion and TCR optimization.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

A genomic data archive from the Network for Pancreatic Organ donors with Diabetes

The Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, islet autoantibody positivity (AAb+), and without diabetes. nPOD recovers, processes, analyzes, and distributes high-quality biospecimens, collected using optimized standard operating procedures, and associated de-identified data/metadata to researchers around the world. Herein describes the release of high-parameter genotyping data from this collection. 372 donors were genotyped using a custom precision medicine single nucleotide polymorphism (SNP) microarray. Data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 donors were assessed for rare known and novel coding region variants via whole exome sequencing (WES). These data are publicly-available to enable genotype-specific sample requests and the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis to promote the development of novel therapies.

59 BASIC BIOLOGICAL SCIENCES↗