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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.

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At least 325 records · Page 18
All sourcesNASA NTRSDOE OSTI
NASA NTRS1984

Regulation of hematopoiesis in the suspended rat as a model for space flight

A series of studies was completed in which a variety of routine hematological and other parameters were obtained from sequential sampling of control and suspended rats. These data showed that, during suspension, the rats failed to gain weight at the same rate as the controls, ate and drank significantly less, demonstrated a transient increase in peripheral hematocrit and RBC count, a transient decrease in MCH, suppressed reticulocyte counts and a progressive decrease in MCV but no change in RBC shape. Leukocyte counts were variably decreased but no significant changes in platelet numbers were noted. Post-suspension, evidence of anemia was present from a reduced RBC count, hemoglobin, hematocrit, and MCV. A leukocytosis was also noted. Efforts directed to the collection of data aimed at understanding changes in blood volume during suspension are also discussed. As part of these studies the following parameters were investigated; RBC survival, in vitro leukocyte reactivity to PHA, bone marrow and spleen cellularity and morphology, ferrokinetics, and the hematopoietic inductive microenvironment.

Dunn, C. D. R.↗
DOE OSTI2014

In silico assessment of interaction of sea anemone toxin APETx2 and acid sensing ion channel 3

Highlights: • We have made a reasonable model of rat ASIC3 using published structure of chicken ASIC1. • We have docked sea anemone toxin APETx2 on the model. • We have identified two putative sites for toxin binding. • We have argued for plausibility one site over the other. • We have identified the residues that are likely to be critical for APETx2–ASIC3 interaction. - Abstract: Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed throughout the nervous system and have been implicated in mediating sensory perception of noxious stimuli. Amongst the six ASIC isoforms, ASIC1a, 1b, 2a and 3 form proton-gated homomers, which differ in their activation and inactivation kinetics, expression profiles and pharmacological modulation; protons do not gate ASIC2b and ASIC4. As with many other ion channels, structure-function studies of ASICs have been greatly aided by the discovery of some toxins that act in isoform-specific ways. ASIC3 is predominantly expressed by sensory neurons of the peripheral nervous system where it acts to detect acid as a noxious stimulus and thus plays an important role in nociception. ASIC3 is the only ASIC subunit that is inhibited by the sea anemone (Anthopleura elegantissima)-derived toxin APETx2. However, the molecular mechanism by which APETx2 interacts with ASIC3 remains largely unknown. In this study, we made a homology model of ASIC3 and used extensive protein–protein docking to predict for the first time, the probable sites of APETx2 interaction on ASIC3. Additionally, using computational alanine scanning, we also suggest the ‘hot-spots’ that are likely to be critical for ASIC3–APETx2 interaction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Preface to Special Topic: Advances in Radio Frequency Physics in Fusion Plasmas

It has long been recognized that auxiliary plasma heating will be required to achieve the high temperature, high density conditions within a magnetically confined plasma in which a fusion “burn” may be sustained by copious fusion reactions. Consequently, the application of radio and microwave frequency electromagnetic waves to magnetically confined plasma, commonly referred to as RF, has been a major part of the program almost since its inception in the 1950s. These RF waves provide heating, current drive, plasma profile control, and Magnetohydrodynamics (MHD) stabilization. Fusion experiments employ electromagnetic radiation in a wide range of frequencies, from tens of MHz to hundreds of GHz. The fusion devices containing the plasma are typically tori, axisymmetric or non, in which the equilibrium magnetic fields are composed of a strong toroidal magnetic field generated by external coils, and a poloidal field created, at least in the symmetric configurations, by currents flowing in the plasma. The waves are excited in the peripheral regions of the plasma, by specially designed launching structures, and subsequently propagate into the core regions, where resonant wave-plasma interactions produce localized heating or other modification of the local equilibrium profiles. Experimental studies coupled with the development of theoretical models and advanced simulation codes over the past 40+ years have led to an unprecedented understanding of the physics of RF heating and current drive in the core of magnetic fusion devices. Nevertheless, there are serious gaps in our knowledge base that continue to have a negative impact on the success of ongoing experiments and that must be resolved as the program progresses to the next generation devices and ultimately to “demo” and “fusion power plant.” A serious gap, at least in the ion cyclotron (IC) range of frequencies and partially in the lower hybrid frequency ranges, is the difficulty in coupling large amount of power to the plasma while minimizing the interaction between the plasma and launching structures. These potentially harmful interactions between the plasma and the vessel and launching structures are challenging: (i) significant and variable loss of power in the edge regions of confined plasmas and surrounding vessel structures adversely affect the core plasma performance and lifetime of a device; (ii) the launcher design is partly “trial and error,” with the consequence that launchers may have to be reconfigured after initial tests in a given device, at an additional cost. Over the broader frequency range, another serious gap is a quantitative lack of understanding of the combined effects of nonlinear wave-plasma processes, energetic particle interactions and non-axisymmetric equilibrium effects on determining the overall efficiency of plasma equilibrium and stability profile control techniques using RF waves. This is complicated by a corresponding lack of predictive understanding of the time evolution of transport and stability processes in fusion plasmas.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
NASA NTRS1987

Lake Bonneville - Constraints on lithospheric thickness and upper mantle viscosity from isostatic warping of Bonneville, Provo, and Gilbert stage shorelines

Data collected from three deformed shorelines of Lake Bonneville (the Bonneville, Provo, and Gilbert shorelines) are used to constrain the effective elastic lithospheric thickness to 23 + or - 2 km, the mantle viscosity to (1.2 + or - 0.2) x 10 to the 20th Pa sec, and the depth to a significant viscosity increase to no less than 300 km. A modification of the earth model of Nakiboglu and Lambeck (1982, 1983) is used for the calculations, and the water load is computed at each time step from a digital terrain model and a specified lake elevation. Differences noted between the observed and computed shoreline elevations indicate a regional tilt down to the NE of about 6 x 10 to the -5th, which is suggested to be due to collapse of the peripheral bulge formed by the Laurentide ice sheet.

Bills, Bruce G.↗
NASA NTRS1992

Inheritance of silicate differentiation during lunar origin by giant impact

It is pointed out that the implication of the popular giant impact model of lunar origin (e.g., Hartmann and Davis, 1975; Cameron and Ward, 1976; Stevenson, 1987) is that any depth-related silicate differentiation within the impactor (and/or the earth) at the time of the impact must be partly inherited by the preferentially peripheral matter that forms the moon. This paper presents calculations of the magnitude of the net differentiation of the protolunar matter for a variety of elements and scenarios, with different assumptions regarding the geometries of the 'sampled' peripheral zones, the relative proportions of the earth-derived to impactor-derived matter in the final moon, and the degree to which the impactor mantle had crystallized prior to the giant impact. It is shown that these differention effects constrain the overall plausibility of the giant impact hypothesis.

Warren, Paul H.↗
NASA NTRS1999

The Evolution of Dust in the Multiphase ISM: Grain Destruction Processes

This proposal covered year one of a long term project in which we acquired the necessary hardware and softwaxe needed to calculate grain destruction processes in the interstellar medium (ISM). The long term goal of this research is to develop a model for the dust evolution in the ISM capable of explaining observations of elemental depletions, the grain size distribution, and the emission characteristics of the ISM from the X-ray through the FIR. We purchased a SUN Ultra 10 workstation and peripheral devices including an Exabyte Tape drive, HP Laser Printer, and Seagate External Hard Disk. The PI installed the hardware and Solaris operating system on the workstation and integrated the hardware into the network. Software was also purchased to enable connections to the workstation from a PC (Hummingbird Exceed). Additional freeware required to carry out the proposed program was installed on the system including compilers (g77, gcc, g++), editors (emacs), a markup language (LaTeX), and display programs (WIP, XV, SAOtng). We have also successfully modified the required plot files to work with our system which display the results of grain processing.

Wolfire, Mark↗
NASA NTRS1999

Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether this contributes to cardiovascular alterations. In these studies, we focus on the basic physiologic mechanisms responsible for the alterations in cardiovascular regulation and function during the simulated microgravity in order to formulate hypotheses regarding what countermeasures are likely to be most effective. Compared to our original proposal, the protocol we are using has been slightly modified to lengthen the bed rest period to 16 days and streamline the data collection. These modifications provide us data on a longer bed rest period and have enabled us to increase our subject throughput. Based on review of our preliminary data we have decided to test a countermeasure which is applied the very end of the bed rest period. We will use the same bed rest protocol to test this countermeasure. We anticipate completing the baseline data collection in our first protocol plus testing of the countermeasure in an additional eight subjects, at which time we plan to initiate the second protocol which includes sleep deprivation. In future studies, we plan to apply CSI to test other potential countermeasures in conjunction with the same bed rest, sleep deprivation and acute stressor models. We also anticipate applying CSI for studying astronauts before and after space flight and ultimately, during space flight. The application of CSI is providing information relevant to the development and evaluation of effective countermeasures allowing humans to adapt appropriately upon re-exposure to a gravity field, and to live and work for longer periods of time in microgravity.

Cohen, Richard↗
DOE OSTI2017

Adverse Health Effects of Thirdhand Smoke: From Cell to Animal Models

The newly identified smoke hazard, thirdhand smoke (THS), has gained public attention in recent years but its health impact and biological effects are largely unknown. THS may be defined by “the four Rs”: tobacco chemicals that remain, react, re-emit, and/or are resuspended long after active smoking has ceased. This review summarizes recent research progress in the effects of THS on genotoxicity, metabolism and early life development using cellular and animal models. We first reported that THS generated in laboratory systems caused significant DNA damage in human cell lines. Our finding that THS significantly induces oxidative base lesions has been confirmed in skin wounds of mice models exposed to THS. THS also induced metabolomic changes in human reproductive cell lines. Furthermore, we demonstrated that early exposure to THS not only negatively impacts body weight in both male and female mice, but also induces persistent changes to immunological parameters in peripheral blood in these mice. These results indicate that THS is genotoxic at realistic experimental doses and that there may be a window of susceptibility for some forms of cellular damage induced by THS.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Measurements of photo-nuclear jet production in Pb + Pb collisions with ATLAS

Ultra-peripheral heavy ion collisions provide a unique opportunity to study the parton distributions in the colliding nuclei via the measurement of photo-nuclear jet production. An analysis of jet production in ultra-peripheral Pb+Pb collisions at √ s NN = 5.02 TeV performed using data collected with the ATLAS detector in 2015 is described. The data set corresponds to a total Pb+Pb integrated luminosity of 0.38 nb -1 . The ultra-peripheral collisions are selected using a combination of forward neutron and rapidity gap requirements. The cross-sections, not unfolded for detector response, are compared to results from Pythia Monte Carlo simulations re-weighted to match a photon spectrum obtained from the STARlight model. As a result, qualitative agreement between data and these simulations is observed over a broad kinematic range suggesting that using these collisions to measure nuclear parton distributions is experimentally realisable.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2024

Reaction plane correlated triangular flow in Au + Au collisions at $\sqrt{s_{NN}}$ = 3 GeV

Here, we measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au + Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v 3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at midrapidity, dv 3 /dy| (y=0) , opposite in sign compared to the slope for directed flow. No significant v 3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
NASA NTRS1994

Mobile Computing for Aerospace Applications

The use of commercial computer technology in specific aerospace mission applications can reduce the cost and project cycle time required for the development of special-purpose computer systems. Additionally, the pace of technological innovation in the commercial market has made new computer capabilities available for demonstrations and flight tests. Three areas of research and development being explored by the Portable Computer Technology Project at NASA Ames Research Center are the application of commercial client/server network computing solutions to crew support and payload operations, the analysis of requirements for portable computing devices, and testing of wireless data communication links as extensions to the wired network. This paper will present computer architectural solutions to portable workstation design including the use of standard interfaces, advanced flat-panel displays and network configurations incorporating both wired and wireless transmission media. It will describe the design tradeoffs used in selecting high-performance processors and memories, interfaces for communication and peripheral control, and high resolution displays. The packaging issues for safe and reliable operation aboard spacecraft and aircraft are presented. The current status of wireless data links for portable computers is discussed from a system design perspective. An end-to-end data flow model for payload science operations from the experiment flight rack to the principal investigator is analyzed using capabilities provided by the new generation of computer products. A future flight experiment on-board the Russian MIR space station will be described in detail including system configuration and function, the characteristics of the spacecraft operating environment, the flight qualification measures needed for safety review, and the specifications of the computing devices to be used in the experiment. The software architecture chosen shall be presented. An analysis of the performance characteristics of wireless data links in the spacecraft environment will be discussed. Network performance and operation will be modeled and preliminary test results presented. A crew support application will be demonstrated in conjunction with the network metrics experiment.

Alena, Richard↗
NASA NTRSDate not supplied

BLOOD-BASED MULTI-SCALE MODEL FOR CANCER RISK FROM GCR IN GENETICALLY DIVERSE POPULATIONS

OBJECTIVES AND METHODS This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2). QUANTIFICATION OF 53BP1+ FOCI IN VITRO AND ASSOCIATIONS TO IN VIVO RADIATION SUSCEPTIBILITY IN 15 MOUSE STRAINS We reported in vitro repair kinetic and repairable fractions of RIF for the 15 mouse strains and introduced a mathematical model for RIF as a function of time, dose and LET. We noted that the metabolic activity of cells modulates the RIF response, and we introduced the open access tool terRIFic (Tool for Enhanced Results of RIF In Cells, https://radbiolab.shinyapps.io/terrific/) to correct for such bias using confluence level. Notably, at 4h post-irradiation, RIF/Gy decreased with dose or LET: as the dose or LET increases, so does the proximity of DNA double-strand-breaks (DSB) and our data suggest that proximal DSBs are brought together inside isolated RIF for repair. The RIF/Gy trend was inverted at 24h, suggesting RIF with high DSB content are more difficult to repair. We showed that in vitro metrics correlate with in vivo measurements in the same 15 mouse strains, such as survival levels of immune cells or spontaneous cancer incidence, suggesting a relationship between the efficiency of DSB repair and cancer risk or radiation toxicity. In addition to the efficiency of repair and persistent RIF, the amount of spontaneous foci before irradiation was also found to be strain dependent. Finally, we performed genome-wide association study in the same 15 mouse strains using all RIF phenotypes measured in vitro, identifying genes of interest and validating RIF as an ideal biomarker for individual radiation sensitivity. BASELINE 53BP1+ FOCI PREDICTS INDIVIDUAL HUMAN RESPONSE TO GCR COMPONENTS Based on the analysis of radiation responses of 576 donor PBMCs (using quantification of 53BP1+ foci, oxidative stress and cell death), we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We identified a relationship between few spontaneous DNA foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, only latent cytomegalovirus infection and age were predictive of high baseline foci formation. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in the process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

53BP1↗
DOE OSTI2021

Solvothermal Synthesis of [Cr 7 S 8 (en) 8 Cl 2 ]Cl 3 ⋅ 2H 2 O with Magnetically Frustrated [Cr 7 S 8 ] 5+ Double‐Cubes**

Abstract A novel transition metal chalcohalide [Cr 7 S 8 (en) 8 Cl 2 ]Cl 3 ⋅ 2H 2 O, with [Cr 7 S 8 ] 5+ dicubane cationic clusters, has been synthesized by a low temperature solvothermal method, using dimethyl sulfoxide (DMSO) and ethylenediamine ( en ) solvents. Ethylenediamine ligand exhibits bi‐ and monodentate coordination modes; in the latter case ethylenediamine coordinates to Cr atoms of adjacent clusters, giving rise to a 2D polymeric structure. Although magnetic susceptibility shows no magnetic ordering down to 1.8 K, a highly negative Weiss constant, θ =−224(2) K, obtained from Curie‐Weiss fit of inverse susceptibility, suggests strong antiferromagnetic (AFM) interactions between S =3/2 Cr(III) centers. Due to the complexity of the system with (2 S +1) 7 =16384 microstates from seven Cr 3+ centers, a simplified model with only two exchange constants was used for simulations. Density‐functional theory (DFT) calculations yielded the two exchange constants to be J 1 =−21.4 cm −1 and J 2 =−30.2 cm −1 , confirming competing AFM coupling between the shared Cr 3+ center and the peripheral Cr 3+ ions of the dicubane cluster. The best simulation of the experimental data was obtained with J 1 =−20.0 cm −1 and J 2 =−21.0 cm −1 , in agreement with the slightly stronger AFM exchange within the triangles of the peripheral Cr 3+ ions as compared to the AFM exchange between the central and peripheral Cr 3+ ions. This compound is proposed as a synthon towards magnetically frustrated systems assembled by linking dicubane transition metal‐chalcogenide clusters into polymeric networks.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1984

Experimental investigation of lateral forces induced by flow through model labyrinth glands

The lateral forces induced by flow through model labyrinth glands were investigated. Circumferential pressure distributions, lateral forces and stiffness coefficients data obtained are discussed. The force system is represented as a negative spring and a tangential force orthogonal to eccentricity. The magnitude of these forces are dependent on eccentricity, entry swirl, rotor peripheral velocity and seal size. A pressure equalization chamber at midgland tests should in significantly reduced forces and stiffness coefficients.

Leong, Y. M. M. S.↗
NASA NTRS2000

Mechanical forces in plant growth and development

Plant cells perceive forces that arise from the environment and from the biophysics of plant growth. These forces provide meaningful cues that can affect the development of the plant. Seedlings of Arabidopsis thaliana were used to examine the cytoplasmic tensile character of cells that have been implicated in the gravitropic response. Laser-trapping technology revealed that the starch-containing statoliths of the central columella cells in root caps are held loosely within the cytoplasm. In contrast, the peripheral cells have starch granules that are relatively resistant to movement. The role of the actin cytoskeleton in affecting the tensile character of these cells is discussed. To explore the role that biophysical forces might play in generating developmental cues, we have developed an experimental model system in which protoplasts, embedded in a synthetic agarose matrix, are subjected to stretching or compression. We have found that protoplasts subjected to these forces from five minutes to two hours will subsequently elongate either at right angles or parallel to the tensive or compressive force vector. Moreover, the cortical microtubules are found to be organized either at right angles or parallel to the tensive or compressive force vector. We discuss these results in terms of an interplay of information between the extracellular matrix and the underlying cytoskeleton.

Non-NASA Center↗
DOE OSTI2015

The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina

The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP. - Highlights: • We systemically explored the neural activities and visual signal pathways of MNU administrated retinas. • The focal photoreceptors had different vulnerabilities to the MNU administration. • Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. • The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models. • The MEA information would enrich our knowledge about the pathology of MNU induced RP models.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Fat Composition Changes in Bone Marrow During Chemotherapy and Radiation Therapy

Purpose: To quantify changes in bone marrow fat fraction and determine associations with peripheral blood cell counts. Methods and Materials: In this prospective study, 19 patients received either highly myelotoxic treatment (radiation therapy plus cisplatin, 5-fluorouracil mitomycin C [FU/MMC], or cisplatin/5-FU/cetuximab) or less myelotoxic treatment (capecitabine-radiation therapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, midtreatment, and posttreatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF[%]) by linear time, treatment, and vertebral column region (lumbar [L]4-sacral [S]2 vs thoracic [T]10-L3 vs cervical[C]3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by white blood cell (WBC) counts versus the differences in PDFF(%) before and after treatment. Results: Cumulative mean dose was associated with a 0.43% per Gy (P=.004) increase in PDFF(%). In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (10.1%, P<.001) and within T10-L3 (3.93%, P=.01), relative to the reference C3-T9. In the less myelotoxic group, we did not observe significant changes in PDFF(%) per visit according to region. Within L4-S2, we observed a significant difference between treatment groups in the change in PDFF(%) per visit (5.36%, P=.04). Rank correlations of the inverse log differences in WBC versus the differences in PDFF(%) overall and within T10-S2 ranged from 0.69 to 0.78 (P<.05). Rank correlations of the inverse log differences in absolute neutrophil counts versus the differences in PDFF(%) overall and within L4-S2 ranged from 0.79 to 0.81 (P<.05). Conclusions: Magnetic resonance imaging fat quantification is sensitive to marrow composition changes that result from chemoradiation therapy. These changes are associated with peripheral blood cell counts. This study supports a rationale for bone marrow-sparing treatment planning to reduce the risk of hematologic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗