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At least 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia

The molecular and cellular origin of the primary neurons of the inner ear, the vestibular and spiral neurons, is reviewed including how they connect to the specific sensory epithelia and what the molecular nature of their survival is. Primary neurons of the ear depend on a single basic Helix-Loop-Helix (bHLH) protein for their formation, neurogenin 1 (ngn1). An immediate downstream gene is the bHLH gene neuronal differentiation (NeuroD). Targeted null mutations of ngn1 results in absence of primary neuron formation; targeted null mutation of NeuroD results in loss of almost all spiral and many vestibular neurons. NeuroD and a later expressed gene, Brn3a, play a role in pathfinding to and within sensory epithelia. The molecular nature of this pathfinding property is unknown. Reduction of hair cells in ngn1 null mutations suggests a clonal relationship with primary neurons. This relationship may play some role in specifying the identity of hair cells and the primary neurons that connect with them. Primary neuron neurites growth to sensory epithelia is initially independent of trophic factors released from developing sensory epithelia, but becomes rapidly dependent on those factors. Null mutations of specific neurotrophic factors lose distinct primary neuron populations which undergo rapid embryonic cell death.

Review↗
NASA NTRS2003

Expression and function of FGF10 in mammalian inner ear development

We have investigated the expression of FGF10 during ear development and the effect of an FGF10 null mutation on ear development. Our in situ hybridization data reveal expression of FGF10 in all three canal crista sensory epithelia and the cochlea anlage as well as all sensory neurons at embryonic day 11.5 (E11.5). Older embryos (E18.5) displayed strong graded expression in all sensory epithelia. FGF10 null mutants show complete agenesis of the posterior canal crista and the posterior canal. The posterior canal sensory neurons form initially and project rather normally by E11.5, but they disappear within 2 days. FGF10 null mutants have no posterior canal system at E18.5. In addition, these mutants have deformations of the anterior and horizontal cristae, reduced formation of the anterior and horizontal canals, as well as altered position of the remaining sensory epithelia with respect to the utricle. Hair cells form but some have defects in their cilia formation. No defects were detected in the organ of Corti at the cellular level. Together these data suggest that FGF10 plays a major role in ear morphogenesis. Most of these data are consistent with earlier findings on a null mutation in FGFR2b, one of FGF10's main receptors. Copyright 2003 Wiley-Liss, Inc.

NASA Discipline Developmental Biology↗
NASA NTRS2006

Terrestrial Planet Finder Interferometer Technology Status and Plans

A viewgraph presentation on the technology status and plans for Terrestrial Planet Finder Interferometer is shown. The topics include: 1) The Navigator Program; 2) TPF-I Project Overview; 3) Project Organization; 4) Technology Plan for TPF-I; 5) TPF-I Testbeds; 6) Nulling Error Budget; 7) Nulling Testbeds; 8) Nulling Requirements; 9) Achromatic Nulling Testbed; 10) Single Mode Spatial Filter Technology; 11) Adaptive Nuller Testbed; 12) TPF-I: Planet Detection Testbed (PDT); 13) Planet Detection Testbed Phase Modulation Experiment; and 14) Formation Control Testbed.

Terrestrial Planet Finder (TPF)↗
NASA NTRS2007

High-Resolution N-Band Observations of the Nova RS Ophiuchi with the Keck Interferometer Nuller

We report new observations of the nova RS Ophiuchi (RS Oph) using the Keck Interferometer Nulling Instrument, approximately 3.8 days following the most recent outburst that occurred on 2006 February 12. The Keck Interferometer Nuller (KIN) operates in K-band from 8 to 12.5 pm in a nulling mode, which means that the central broad-band interference fringe is a dark fringe - with an angular width of 25 mas at mid band - rather than the bright fringe used ill a conventional optical interferometer. In this mode the stellar light itself is suppressed by the destructive fringe, effectively enhancing the contrast of the circumstellar material located near the star. By subsequently shifting the neighboring bright fringe onto the center of the source brightness distribution and integrating, a second spatial regime dominated by light from the central portion of the source is almost simultaneously sampled. The nulling technique is the sparse aperture equivalent of the conventional corongraphic technique used in filled aperture telescopes. By fitting the unique KIK inner and outer spatial regime data, we have obtained an angular size of the mid-infrared continuum of 6.2, 4.0. or 5.4 mas for a disk profile, gaussian profile (fwhm), and shell profile respectively. The data show evidence of enhanced neutral atomic hydrogen emission located in the inner spatial regime relative to the outer regime. There is also evidence of a 9.7 micron silicate feature seen outside of this region. Importantly, we see spectral lines excited by the nova flash in the outer region before the blast wave reaches these regions. These lines are from neutral, weakly excited atoms which support the following interpretation. We discuss the present results in terms of a unifying model of the system that includes an increase in density in the plane of the orbit of the two stars created by a spiral shock wave caused by the motion of the stars through the cool wind of the red giant star. These data show the power and potential of the nulling technique which has been developed for the detection of Earth-like planets around nearby stars for the Terrestrial Planet Finder Mission and Darwin missions.

Barry, R. K.↗
NASA NTRS2024

Large-scale Coronal Dimming Foreshadowing a Solar Eruption on 2011 October 1

Understanding large-scale solar eruptions requires detailed investigation of the entire system's evolution, including the magnetic environment enveloping the source region and searches for precursor activity prior to event onset. We combine stereoscopic observations from the Solar Dynamics Observatory (SDO) and STEREO-B spacecraft for several hours before a filament ejection, M1.2-class eruptive flare, and coronal mass ejection (CME) originating in NOAA active region (AR) 11305 on 2011 October 1. Two episodes of significant preeruption coronal dimming that occurred well to the southeast of the ejected filament are identified. The CME subsequently took off with a substantial component of velocity toward the dimming, which became very pronounced during eruption. We used SDO/Helioseismic and Magnetic Imager (HMI) data to reconstruct the magnetic environment of the system and found that it contains a null point near the dimming region. AR 11305 had quite complex connections to nearby ARs 11302 and 11306, as well as to other regions of decayed AR flux. The intensifying and spatially expanding precursor dimming was accompanied by southeastward rising motions of loops toward the null point and northeastward and southwestward motions of loops retracting away. These motions and the dimming are consistent with persistent magnetic reconnection occurring at the null point as it moved upward and southeastward, thereby removing a strapping magnetic field high above AR 11305. Eventually, the filament was ejected explosively toward the null point. We conclude that the breakout model for solar eruptions provides a compelling account of this event. Furthermore, we conjecture that preeruption dimmings may be much more frequent than currently recognized.

solar flares↗
DOE OSTI2021

The light-ray OPE and conformal colliders

We derive a nonperturbative, convergent operator product expansion (OPE) for null-integrated operators on the same null plane in a CFT. The objects appearing in the expansion are light-ray operators, whose matrix elements can be computed by the generalized Lorentzian inversion formula. For example, a product of average null energy (ANEC) operators has an expansion in the light-ray operators that appear in the stress-tensor OPE. An important application is to collider event shapes. The light-ray OPE gives a nonperturbative expansion for event shapes in special functions that we call celestial blocks. As an example, we apply the celestial block expansion to energy-energy correlators in N = 4 Super Yang-Mills theory. Using known OPE data, we find perfect agreement with previous results both at weak and strong coupling, and make new predictions at weak coupling through 4 loops (NNNLO).

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2018

Evolution of the mean jet shape and dijet asymmetry distribution of an ensemble of holographic jets in strongly coupled plasma

Some of the most important experimentally accessible probes of the quark- gluon plasma (QGP) produced in heavy ion collisions come from the analysis of how the shape and energy of sprays of energetic particles produced within a cone with a specified opening angle (jets) in a hard scattering are modified by their passage through the strongly coupled, liquid, QGP. We model an ensemble of back-to-back dijets for the purpose of gaining a qualitative understanding of how the shapes of the individual jets and the asymmetry in the energy of the pairs of jets in the ensemble are modified by their passage through an expanding cooling droplet of strongly coupled plasma, in the model in a holographic gauge theory that is dual to a 4+1-dimensional black-hole spacetime that is asymptotically anti-de Sitter (AdS). We build our model by constructing an ensemble of strings in the dual gravitational description of the gauge theory. We model QCD jets in vacuum using strings whose endpoints are moving “downward” into the gravitational bulk spacetime with some fixed small angle, an angle that represents the opening angle (ratio of jet mass to jet energy) that the QCD jet would have in vacuum. Such strings must be moving through the gravitational bulk at (close to) the speed of light; they must be (close to) null. This condition does not specify the energy distribution along the string, meaning that it does not specify the shape of the jet being modeled. We study the dynamics of strings that are initially not null and show that strings with a wide range of initial conditions rapidly accelerate and become null and, as they do, develop a similar distribution of their energy density. We use this distribution of the energy density along the string, choose an ensemble of strings whose opening angles and energies are distributed as in perturbative QCD, and show that we can then fix one of the two model parameters such that the mean jet shape for the jets in the ensemble that we have built matches that measured in proton-proton collisions reasonably well. This is a novel way for hybridizing relevant inputs from perturbative QCD and a strongly coupled holographic gauge theory in the service of modeling jets in QGP. We send our ensemble of strings through an expanding cooling droplet of strongly coupled plasma, choosing the second model parameter so as to get a reasonable value for $R$ $^{AA}_{jet}$, the suppression in the number of jets, and study how the mean jet shape and the dijet asymmetry are modified, comparing both to measurements from heavy ion collisions at the LHC.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2024

Chaotic LLM billiards

Abstract We study null geodesics of the ten-dimensional LLM geometries. In particular, we show that there are a subset of these null geodesics that are confined to the LLM plane. The effective dynamics of these in-plane geodesics is that of a Hamiltonian system with two degrees of freedom (a phase space of dimension 4). We show that these are chaotic. In the two-coloring of the LLM plane, if they start in the empty region, they cannot penetrate the filled region and viceversa. The dynamical problem is therefore very similar to that of a billiards problem with fixed obstacles. We study to what extent LLM geometries with many droplets may be treated as an incipient black hole and draw analogies with the fuzzball proposal. We argue that for in-plane null geodesics deep in the interior of a region with a lot of droplets, in order to exit towards theAdSboundary they will need to undergo a process that resembles diffusion. This mechanism can account for signals getting lost in the putative black hole for a very long time.

Physics↗
DOE OSTI2018

A conformal collider for holographic CFTs

We develop a formalism to study the implications of causality on OPE coefficients in conformal field theories with large central charge and a sparse spectrum of higher spin operators. The formalism has the interpretation of a new conformal collider-type experiment for these class of CFTs and hence it has the advantage of requiring knowledge only about CFT three-point functions. This is accomplished by considering the holographic null energy operator which was introduced in [ 1 ] as a generalization of the averaged null energy operator. Analyticity properties of correlators in the Regge limit imply that the holographic null energy operator is a positive operator in a subspace of the total CFT Hilbert space. Utilizing this positivity condition, we derive bounds on three-point functions $\langle$ TO 1 O 2 $\rangle$of the stress tensor with various operators for CFTs with large central charge and a sparse spectrum. After imposing these constraints, we also find that the operator product expansions of all primary operators in the Regge limit have certain universal properties. All of these results are consistent with the expectation that CFTs in this class, irrespective of their microscopic details, admit universal gravity-like holographic dual descriptions. Furthermore, this connection enables us to constrain various inflationary observables such as the amplitude of chiral gravity waves, non-gaussanity of gravity waves and tensor-to-scalar ratio.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2018

Light-ray operators in conformal field theory

We argue that every CFT contains light-ray operators labeled by a continuous spin J. When J is a positive integer, light-ray operators become integrals of local operators over a null line. However for non-integer J , light-ray operators are genuinely nonlocal and give the analytic continuation of CFT data in spin described by Caron-Huot. A key role in our construction is played by a novel set of intrinsically Lorentzian integral transforms that generalize the shadow transform. Matrix elements of light-ray operators can be computed via the integral of a double-commutator against a conformal block. This gives a simple derivation of Caron-Huot’s Lorentzian OPE inversion formula and lets us generalize it to arbitrary four-point functions. Furthermore, we show that light-ray operators enter the Regge limit of CFT correlators, and generalize conformal Regge theory to arbitrary four-point functions. The average null energy operator is an important example of a light-ray operator. Using our construction, we find a new proof of the average null energy condition (ANEC), and furthermore generalize the ANEC to continuous spin.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2020

Modification to the Hawking temperature of a dynamical black hole by a flow-induced supertranslation

One interesting proposal to solve the black hole information loss paradox without modifying either general relativity or quantum field theory, is the soft hair, a diffeomorphism charge that records the anisotropic radiation in the asymptotic region. This proposal, however, has been challenged, given that away from the source the soft hair behaves as a coordinate transformation that forms an Abelian group, thus unable to store any information. To maintain the spirit of the soft hair but circumvent these obstacles, we consider Hawking radiation as a probe sensitive to the entire history of the black hole evaporation, where the soft hairs on the horizon are induced by the absorption of a null anisotropic flow, generalizing the shock wave considered in [1, 2]. To do so we introduce two different time-dependent extensions of the diffeomorphism associated with the soft hair, where one is the backreaction of the anisotropic null flow, and the other is a coordinate transformation that produces the Unruh effect and a Doppler shift to the Hawking spectrum. Together, they form an exact BMS charge generator on the entire manifold that allows the nonperturbative analysis of the black hole horizon, whose surface gravity, i.e. the Hawking temperature, is found to be modified. The modification depends on an exponential average of the anisotropy of the null flow with a decay rate of 4M, suggesting the emergence of a new 2-D degree of freedom on the horizon, which could be a way out of the information loss paradox.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2020

Recovering the QNEC from the ANEC

We study the relative entropy in QFT comparing the vacuum state to a special family of purifications determined by an input state and constructed using relative modular flow. We use this to prove a conjecture by Wall that relates the shape derivative of relative entropy to a variational expression over the averaged null energy (ANE) of possible purifications. Furthermore, this variational expression can be used to easily prove the quantum null energy condition (QNEC). We formulate Wall’s conjecture as a theorem pertaining to operator algebras satisfying the properties of a half-sided modular inclusion, with the additional assumption that the input state has finite averaged null energy. We also give a new derivation of the strong superadditivity property of relative entropy in this con- text. We speculate about possible connections to the recent methods used to strengthen monotonicity of relative entropy with recovery maps.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2014

The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice

Highlights: • Ethanol administration increased GPD1 mRNA expression. • Ethanol administration increased glucose incorporation into TG glycerol moieties. • No increase in hepatic TG levels was observed in ethanol-injected GPD1 null mice. • We propose that GPD1 is required for ethanol-induced TG accumulation in the liver. - Abstract: Acute ethanol consumption leads to the accumulation of triglycerides (TGs) in hepatocytes. The increase in lipogenesis and reduction of fatty acid oxidation are implicated as the mechanisms underlying ethanol-induced hepatic TG accumulation. Although glycerol-3-phosphate (Gro3P), formed by glycerol kinase (GYK) or glycerol-3-phosphate dehydrogenase 1 (GPD1), is also required for TG synthesis, the roles of GYK and GPD1 have been the subject of some debate. In this study, we examine (1) the expression of genes involved in Gro3P production in the liver of C57BL/6J mice in the context of hepatic TG accumulation after acute ethanol intake, and (2) the role of GPD1 in the progression of ethanol-induced fatty liver using GPD1 null mice. As a result, in C57BL/6J mice, ethanol-induced hepatic TG accumulation began within 2 h and was 1.7-fold greater than that observed in the control group after 6 h. The up-regulation of GPD1 began 2 h after administering ethanol, and significantly increased 6 h later with the concomitant escalation in the glycolytic gene expression. The incorporation of {sup 14}C-labelled glucose into TG glycerol moieties increased during the same period. On the other hand, in GPD1 null mice carrying normal GYK activity, no significant increase in hepatic TG level was observed after acute ethanol intake. In conclusion, GPD1 and glycolytic gene expression is up-regulated by ethanol, and GPD1-mediated incorporation of glucose into TG glycerol moieties together with increased lipogenesis, is suggested to play an important role in ethanol-induced hepatic TG accumulation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. - Highlights: • Fgl1 knockout mice (Fgl1KO) are more prone to carcinogen-induced liver cancer compared to wild type (WT) mates. • Tumors from the Fgl1KO are molecularly distinct with enhanced Akt and mTOR activity in comparison with Fgl1WT tumors. • Tumors from the Fgl1KO have enhanced expression of Trim35 and Tnfrsf10b, putative HCC tumor suppressors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Aldose reductase mediates retinal microglia activation

Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1{sup GFP} mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migration in vivo. When tested on an AR{sup WT} background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Validation of NSFsim as a Grad-Shafranov equilibrium solver at DIII-D

Plasma shape is a significant factor that must be considered for any Fusion Pilot Plant (FPP) as it has significant consequences for plasma stability and core confinement. A new simulator, NSFsim, has been developed based on a historically successful code, DINA [1], offering tools to simulate both transport and plasma shape. Specifically, NSFsim is a free boundary equilibrium and transport solver and has been configured to match the properties of the DIII-D tokamak. This paper is focused on validating the Grad-Shafranov (GS) solver of NSFsim by analyzing its ability to recreate the plasma shape, the poloidal flux distribution, and the measurements of the simulated diagnostic signals originating from flux loops and magnetic probes in DIII-D. Five different plasma shapes are simulated to show the robustness of NSFsim to different plasma conditions; these shapes are Lower Single Null (LSN), Upper Single Null (USN), Double Null (DN), Inner Wall Limited (IWL), and Negative Triangularity (NT). The NSFsim results are compared against real measured signals, magnetic profile fits from EFIT [2], and another plasma equilibrium simulator, GSevolve [3]. EFIT reconstructions of shots are readily available at DIII-D, but GSevolve was manually ran by us to provide simulation data to compare against.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗