Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “MESSENGER”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7

Waning immunity and IgG4 responses following bivalent mRNA boosting

Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) responses against XBB variants and isotype switching to immunoglobulin G4 (IgG4) responses following bivalent mRNA boosting. Bivalent mRNA boosting elicited modest XBB.1-, XBB.1.5-, and XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, bivalent mRNA boosting induced more robust and sustained NAbs against the ancestral WA1/2020 strain, suggesting immune imprinting. Following bivalent mRNA boosting, serum antibody responses were primarily IgG2 and IgG4 responses with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosted all isotypes including IgG1 and IgG3 with robust Fc functional activity. These data show substantial immune imprinting for the ancestral spike and isotype switching to IgG4 responses following bivalent mRNA boosting, with important implications for future booster designs and boosting strategies.

Science & Technology - Other Topics↗

Multimessenger constraints on the neutron-star equation of state and the Hubble constant

Observations of neutron-star mergers with distinct messengers, including gravitational waves and electromagnetic signals, can be used to study the behavior of matter denser than an atomic nucleus and to measure the expansion rate of the Universe as quantified by the Hubble constant. We performed a joint analysis of the gravitational-wave event GW170817 with its electromagnetic counterparts AT2017gfo and GRB170817A, and the gravitational-wave event GW190425, both originating from neutron-star mergers. We combined these with previous measurements of pulsars using x-ray and radio observations, and nuclear-theory computations using chiral effective field theory, to constrain the neutron-star equation of state. We found that the radius of a 1.4–solar mass neutron star is 11.75 − 0.81 + 0.86 km at 90% confidence and the Hubble constant is 66.2 − 4.2 + 4.4 at 1σ uncertainty.

Dietrich, Tim↗

Rapid assessment of SARS-CoV-2–evolved variants using virus-like particles

Efforts to determine why new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants demonstrate improved fitness have been limited to analyzing mutations in the spike (S) protein with the use of S-pseudotyped particles. In this study, we show that SARS-CoV-2 virus-like particles (SC2-VLPs) can package and deliver exogenous transcripts, enabling analysis of mutations within all structural proteins and at multiple steps in the viral life cycle. In SC2-VLPs, four nucleocapsid (N) mutations found universally in more-transmissible variants independently increased messenger RNA delivery and expression ~10-fold, and in a reverse genetics model, the serine-202→arginine (S202R) and arginine-203→methionine (R203M) mutations each produced >50 times as much virus. SC2-VLPs provide a platform for rapid testing of viral variants outside of a biosafety level 3 setting and demonstrate N mutations and particle assembly to be mechanisms that could explain the increased spread of variants, including B.1.617.2 (Delta, which contains the R203M mutation).

60 APPLIED LIFE SCIENCES↗

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody–induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan–targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.

Science & Technology - Other Topics↗

Antibiotic that inhibits trans -translation blocks binding of EF-Tu to tmRNA but not to tRNA

trans-Translation is conserved throughout bacteria and is essential in many species. High-throughput screening identified a tetrazole-based trans-translation inhibitor, KKL-55, that has broad-spectrum antibiotic activity. A biotinylated version of KKL-55 pulled down elongation factor thermo-unstable (EF-Tu) from bacterial lysates. Purified EF-Tu bound KKL-55 in vitro with a K d = 2 µM, confirming a high-affinity interaction. An X-ray crystal structure showed that KKL-55 binds in domain 3 of EF-Tu, and mutation of residues in the binding pocket abolished KKL-55 binding. RNA-binding assays in vitro showed that KKL-55 inhibits binding between EF-Tu and transfer-messenger RNA (tmRNA) but not between EF-Tu and tRNA. These data demonstrate a new mechanism for the inhibition of EF-Tu function and suggest that this specific inhibition of EF-Tu•tmRNA binding is a viable target for antibiotic development.

59 BASIC BIOLOGICAL SCIENCES↗

Bacteria export alarmone synthetases that produce (p)ppApp and (p)ppGpp

Guanosine penta- and tetraphosphate [(p)ppGpp] and their adenosine analogs [(p)ppApp] are bacterial second messengers known as alarmones. Members of the RelA-SpoT homolog (RSH) family synthesize (p)ppGpp to mediate the stringent response during nutrient starvation, whereas (p)ppApp synthetases have been identified as bactericidal toxins in diverse contexts including type VI secretion systems, toxin-antitoxin modules, and phages. Although alarmone synthesis has traditionally been viewed as a cytoplasmic process, early studies in Streptomyces suggested the existence of secreted alarmone synthetases. Here, we identify SaEAS, an exported alarmone synthetase (EAS) from Streptomyces albidoflavus, as the long-mysterious source of extracellular alarmone synthetase activity in Streptomyces. SaEAS produces both (p)ppGpp and (p)ppApp at rates exceeding 100,000 molecules per minute and has kinetic properties adapted to low substrate environments. A broader bioinformatic survey reveals ~600 EASs linked to a range of specialized bacterial secretion systems. Characterization of two additional EASs, VpEAS from Vibrio parahaemolyticus and AaEAS from Amycolatopsis azurea, shows that both produce (p)ppGpp exclusively and inhibit bacterial growth when localized to the cytoplasm. These findings challenge the longstanding view of (p)ppGpp as strictly pro-survival and unveil a diverse family of secreted RSH enzymes with potential roles in interbacterial antagonism and environmental signaling.

Ahmad, Shehryar↗

Fecal microbiota transplantation ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota in db/db mice

Gut microbiome (GM) deregulation has been implicated in major conditions such as obesity and type 2 diabetes (T2DM). Our previous prospective study indicated that fecal microbiota transplantation (FMT) successfully improved patients with T2DM. We hypothesized that FMT may be a potential therapeutic method for T2DM, but its precise mechanisms in T2DM remains to be elucidated. Eight db/m mice were FMT donors and control mice, and 16 genetically diabetic db/db mice were equally divided into two groups (db/db+phosphate-buffered saline (PBS) group, db/db+FMT group). The db/db+FMT group was administered fresh fecal suspension (0.2 mL/mice) daily for 4 weeks. Analysis of the GM and serum metabolome was carried out by 16S ribosomal RNA sequencing and liquid chromatogram-mass spectrometry, respectively. Effects of FMT on the gut barrier and pancreas were assessed using protein assays, messenger RNA, immunohistology and clinical indicators testing. Our results showed that FMT treatment of db/db mice relieves a series of clinical indicators, including fasting plasma glucose, serum insulin and oral glucose tolerance test among others. Compared with non-diabetic control mice, db/db+PBS mice exhibited decreased abundance of Ruminococaceae, Porphyromonadaceae and increased abundance of Rikenellaceae and Lactobacillaceae. FMT treatment reversed this effect on the microbiome. Eleven metabolites were changed between the db/db+PBS and db/db+FMT groups. Correlation analysis showed that the structural changes of the GM were correlated with host metabolite levels. We further showed that FMT treatment of db/db mice improved intestinal barrier function, reduced inflammation and caused an alteration in the number of circulating immune cells. FMT-mediated changes in the GM, serum metabolites, intestinal epithelial barrier, inflammation and circulating immune cells play an important role in the efficacy of FMT on T2DM disease progression.

60 APPLIED LIFE SCIENCES↗

Snowmass white paper: beyond the standard model effects on neutrino flavor

Neutrinos are one of the most promising messengers for signals of new physics Beyond the Standard Model (BSM). On the theoretical side, their elusive nature, combined with their unknown mass mechanism, seems to indicate that the neutrino sector is indeed opening a window to new physics. On the experimental side, several long-standing anomalies have been reported in the past decades, providing a strong motivation to thoroughly test the standard three-neutrino oscillation paradigm. In this Snowmass21 white paper, we explore the potential of current and future neutrino experiments to explore BSM effects on neutrino flavor during the next decade.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Cold freeze out of superheavy dark matter and Hubble tension

We present a unified framework, the "X miracle", in which dark matter consists of superheavy, nonthermal X particles whose relic abundance is determined not by the conventional weak-scale, semi-relativistic ("hot") freeze-out of WIMPs, but by annihilation or decay occurring within the smallest and earliest gravitationally bound objects. Unlike thermal WIMPs, which decouple at velocities of order 0.3c with relic abundance ρ∞ set by weak-scale interactions, X particles are produced nonthermally with an initial overabun dance ρ ini >> ρ ∞ . They become nonrelativistic extremely early, redshift to ultra-cold velocities, allowing collapse into compact bound structures characterized by a novel quantum gravitational scale, r X = 4$\hbar$ 2 $/Gm^3_X$ = 10 −13 m $\hbar$$/m_Xc$, much larger than the Compton wavelength. The framework predicts a particle mass of 10 12 GeV and an enhanced cross section of 10 −21 m 3 /s. Overlapping particle wavefunctions in these compact structures drive annihilation or decay into additional radiation, leading to a "cold" freeze-out that converts most of ρ ini into radiation while leaving a relic density ρ ∞ . Solutions to the Boltzmann equation indicate that an extreme ("big") depletion, with only one particle in a billion surviving, yields an additional radiation contribution $ΔN_{eff}$ ≈ 0.4, which could help alleviate the Hubble tension. For particles of 10 12 GeV, the scenario predicts a dark coupling constant α X = 0.09 that is responsible for an instanton-induced decay process, consistent with current UHECR bounds. Early collapse at 10 −6 s may release binding energy as high-frequency (100kHz) gravitational waves or ultralight GUT-scale axions (10 −9 eV). Superheavy sterile neutrinos provide a natural particle realization, linking dark matter to neutrino mass and baryogenesis. If gravitationally produced, this framework favors high-scale inflation and effi cient reheating. The "X miracle" thus demonstrates that dark matter need not be weak-scale: gravitational dynamics can control freeze-out and evolution, producing multi-messenger observational signatures in UHECRs, axions, gravitational waves, and small-scale structures.

Xu, Zhijie Jay [Pacific Northwest National Laborat↗

Neutrinos in Stellar Astrophysics (in The Encyclopedia of Cosmology)

The physics of the mysterious and stealthy neutrino is at the heart of many phenomena in the cosmos. These particles interact with matter and with each other through the aptly named weak interaction. At typical astrophysical energies the weak interaction is some twenty orders of magnitude weaker than the electromagnetic interaction. However, in the early universe and in collapsing stars neutrinos can more than make up for their feeble interaction strength with huge numbers. Neutrinos can dominate the dynamics in these sites and set the conditions that govern the synthesis of the elements. Here we journey through the history of the discovery of these particles and describe their role in stellar evolution and collapse, the big bang, and multi-messenger astrophysics. Neutrino physics is at the frontier of elementary particle physics, nuclear physics, astrophysics and cosmology. All of these fields overlap in the neutrino story.

Haxton, Wick↗

DoCeph: DPU-Offloaded Messaging in Ceph for Reduced Host CPU Utilization

Ceph is a widely used distributed object store, but its messenger layer imposes substantial CPU overhead on the host. To address this limitation, we propose DoCeph, a DPU-offloaded storage architecture for Ceph that disaggregates the system by offloading the communication-intensive messaging component to the DPU while retaining the storage backend on the host. The DPU efficiently manages communication, using lightweight RPC for metadata operations and DMA for data transfer. Moreover, DoCeph introduces a pipelining technique that overlaps data transmission with buffer preparation, mitigating hardware-imposed transfer size limitations. We implemented DoCeph on a Ceph cluster with NVIDIA BlueField-3 DPUs. Evaluation results indicate that DoCeph cuts host CPU usage by up to 92% while sustaining stable throughput and providing larger performance benefits for object writes over 1 MB.

Park, Kuri [Sogang University]↗

A robust method of nuclei isolation for single-cell RNA sequencing of solid tissues from the plant genus Populus

Single-cell transcriptome analysis has been extensively applied in humans and animal models to uncover gene expression heterogeneity between the different cell types of a tissue or an organ. It demonstrated its capability to discover key regulatory elements that determine cell fate during developmental programs. Single-cell analysis requires the isolation and labeling of the messenger RNA (mRNA) derived from each cell. These challenges were primarily addressed in mammals by developing microfluidic-based approaches. For plant species whose cells contain cell walls, these approaches have generally required the generation of isolated protoplasts. Many plant tissues’ secondary cell wall hinders enzymatic digestion required for individual protoplast isolation, resulting in an unequal representation of cell types in a protoplast population. This limitation is especially critical for cell types located in the inner layers of a tissue or the inner tissues of an organ. Consequently, single-cell RNA sequencing (scRNA-seq) studies using microfluidic approaches in plants have mainly been restricted to Arabidopsis roots, for which well-established procedures of protoplast isolation are available. Here we present a simple alternative approach to generating high-quality protoplasts from plant tissue by characterizing the mRNA extracted from individual nuclei instead of whole cells. We developed the protocol using two different plant materials with varying cellular complexity levels and cell wall structure, Populus shoot apices, and more lignified stems. Using the 10× Genomics Chromium technology, we show that this procedure results in intact mRNA isolation and limited leakage, with a broad representation of individual cell transcriptomes.

54 ENVIRONMENTAL SCIENCES↗

Correlating transcription and protein expression profiles of immune biomarkers following lipopolysaccharide exposure in lung epithelial cells

Universal and early recognition of pathogens occurs through recognition of evolutionarily conserved pathogen associated molecular patterns (PAMPs) by innate immune receptors and the consequent secretion of cytokines and chemokines. The intrinsic complexity of innate immune signaling and associated signal transduction challenges our ability to obtain physiologically relevant, reproducible and accurate data from experimental systems. One of the reasons for the discrepancy in observed data is the choice of measurement strategy. Immune signaling is regulated by the interplay between pathogen-derived molecules with host cells resulting in cellular expression changes. However, these cellular processes are often studied by the independent assessment of either the transcriptome or the proteome. Correlation between transcription and protein analysis is lacking in a variety of studies. In order to methodically evaluate the correlation between transcription and protein expression profiles associated with innate immune signaling, we measured cytokine and chemokine levels following exposure of human cells to the PAMP lipopolysaccharide (LPS) from the Gram-negative pathogen Pseudomonas aeruginosa . Expression of 84 messenger RNA (mRNA) transcripts and 69 proteins, including 35 overlapping targets, were measured in human lung epithelial cells. We evaluated 50 biological replicates to determine reproducibility of outcomes. Following pairwise normalization, 16 mRNA transcripts and 6 proteins were significantly upregulated following LPS exposure, while only five (CCL2, CSF3, CXCL5, CXCL8/IL8, and IL6) were upregulated in both transcriptomic and proteomic analysis. This lack of correlation between transcription and protein expression data may contribute to the discrepancy in the immune profiles reported in various studies. The use of multiomic assessments to achieve a systems-level understanding of immune signaling processes can result in the identification of host biomarker profiles for a variety of infectious diseases and facilitate countermeasure design and development.

59 BASIC BIOLOGICAL SCIENCES↗

A Microbe Associated with Sleep Revealed by a Novel Systems Genetic Analysis of the Microbiome in Collaborative Cross Mice

The microbiome influences health and disease through complex networks of host genetics, genomics, microbes, and environment. Identifying the mechanisms of these interactions has remained challenging. Systems genetics in laboratory mice (Mus musculus) enables data-driven discovery of biological network components and mechanisms of host–microbial interactions underlying disease phenotypes. To examine the interplay among the whole host genome, transcriptome, and microbiome, we mapped QTL and correlated the abundance of cecal messenger RNA, luminal microflora, physiology, and behavior in a highly diverse Collaborative Cross breeding population. One such relationship, regulated by a variant on chromosome 7, was the association of Odoribacter (Bacteroidales) abundance and sleep phenotypes. In a test of this association in the BKS.Cg-Dock7 m +/+ Lepr db /J mouse model of obesity and diabetes, known to have abnormal sleep and colonization by Odoribacter, treatment with antibiotics altered sleep in a genotype-dependent fashion. The many other relationships extracted from this study can be used to interrogate other diseases, microbes, and mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗

VERITAS highlights of observations and results

Located in southern Arizona, VERITAS is amongst the most sensitive detectors for astrophysical very high energy (VHE; E>100 GeV) gamma rays and has been operational since April 2007. We highlight some recent results from VERITAS observations. These include the long-term observations of the gamma-ray binaries HESS J0632+057 and LS I +61° 303, the observations of the Galactic Center region, and of the supernova remnant Cas A. We discuss the results from a decade of multi-wavelength observations of the blazar 1ES 1215+303, the EHT 2017 campaign on the M87 galaxy, the discovery of 3C 264 in VHE, and the observation of three flaring quasars. Brief highlights of the indirect dark matter searches and targets-of-opportunity (ToO) observations are also discussed. The ToO observations allow for rapid follow-up of multi-messenger alerts and astrophysical transients.

Patel, Sonal Ramesh↗

Determination of Solar System R-Process Abundances using ENDF/B-VIII.0 and TENDL-2015 libraries

Recent multi-messenger detection of the binary neutron star merger (GW170817) energized the astrophysical community and encouraged further research for determination of nuclear physics observables. Comprehensive studies of atomic nuclei in the cosmos provide an opportunity for investigating these astrophysical phenomena and acquiring complementary information on stellar nucleosynthesis processes that can be verified using the latest nuclear data. Evaluated Nuclear Data File (ENDF) libraries contain complete collections of reaction cross sections over the energy range relevant to astrophysics, fission yields and decay data. These data collections have been used worldwide in nuclear science, industry and national security applications. There is great interest in exploring the ENDF/B-VIII.0 and TALYS Evaluated Nuclear Data Library (TENDL-2015) for nuclear astrophysics purposes and comparing findings with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS). The Maxwellian-averaged cross sections (MACS) and astrophysical reaction rates have been calculated using the ENDF/B-VIII.0 and TENDL-2015 evaluated data sets. The calculated cross sections were combined with the solar system abundances and fitted using the classical model of stellar nucleosynthesis. Astrophysical rapid- and slow-neutron capture, r- and s-process, respectively, abundances were obtained from present data and compared with available values. Further analysis of MACS reveals potential evaluated libraries data deficiencies and a strong need for new measurements. The current results demonstrate a large nuclear astrophysics potential of evaluated libraries and mutually beneficial relations between nuclear industry and research e orts.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Dust Formation and Growth in Supernovae Explosions

Dust is a multi-messenger probe able to explore the dynamics of the Supernova Engine. The yield and composition of grains formed in the supernova explosion are dependent on the initial explosion characteristics of the progenitor and on the explosion mechanism. Using dust as a prove, the dynamics of dust formation and growth is modeled in a diverse set of Core-Collapse Supernovae Explosions (CCSNe). The progenitor mass, explosion energy engine type, and composition are varied across 72 models. The explosion is evolved using a 1-D Lagrangian Hydro-dynamical code (hydrocodes) to roughly 3 years. A multigrain nucleation and dust growth model is used to post process the hydrocode results and model grain formation and growth. The results show an earlier onset of grain formation, a larger silicate grain abundance, and smaller grain sizes in high explosion energy models.

79 ASTRONOMY AND ASTROPHYSICS↗

Next-Generation Simulations of the Remarkable Deaths Of Massive Stars [Slides]

3D models of stellar convection are necessary for accurate description of state of model near collapse. Convection is occurring at many scales with the large dominant mode near collapse. 3D instabilities can affect flow properties and mass entrainment. Mach number profiles show favorable conditions for explosion. 3D rotating progenitor models are ALSO necessary. The redistribution of AM diverges from the MESA model, with implications for remnant. There is turbulent transport of AM in convective shell regions. Multi-D models can provide input for successful CCSN models. Larger non-radial kinetic energy exists when using multi-D progenitor input. The 3D CCSN model showed prompt convection and asymmetric shock runaway. Explosion properties suggest robust impact on multi-messenger signals.

79 ASTRONOMY AND ASTROPHYSICS↗