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At least 505 records · Page 28

T cell activation responses are differentially regulated during clinorotation and in spaceflight

Studies of T lymphocyte activation with mitogenic lectins during spaceflight have shown a dramatic inhibition of activation as measured by DNA synthesis at 72 h, but the mechanism of this inhibition is unknown. We have investigated the progression of cellular events during the first 24 h of activation using both spaceflight microgravity culture and a ground-based model system that relies on the low shear culture environment of a rotating clinostat (clinorotation). Stimulation of human peripheral blood mononuclear cells (PBMCs) with soluble anti-CD3 (Leu4) in clinorotation and in microgravity culture shows a dramatic reduction in surface expression of the receptor for IL-2 (CD25) and CD69. An absence of bulk RNA synthesis in clinorotation indicates that stimulation with soluble Leu4 does not induce transition of T cells from G0 to the G1 stage of the cell cycle. However, internalization of the TCR by T cells and normal levels of IL-1 synthesis by monocytes indicate that intercellular interactions that are required for activation occur during clinorotation. Complementation of TCR-mediated signaling by phorbol ester restores the ability of PBMCs to express CD25 in clinorotation, indicating that a PKC-associated pathway may be compromised under these conditions. Bypassing the TCR by direct activation of intracellular pathways with a combination of phorbol ester and calcium ionophore in clinorotation resulted in full expression of CD25; however, only partial expression of CD25 occurred in microgravity culture. Though stimulation of purified T cells with Bead-Leu4 in microgravity culture resulted in the engagement and internalization of the TCR, the cells still failed to express CD25. When T cells were stimulated with Bead-Leu4 in microgravity culture, they were able to partially express CD69, a receptor that is constitutively stored in intracellular pools and can be expressed in the absence of new gene expression. Our results suggest that the inhibition of T cell proliferative response in microgravity culture is a result of alterations in signaling events within the first few hours of activation, which are required for the expression of important regulatory molecules.

NASA Experiment Number 9403079 1/2↗

Estimation in nonlinear systems with transport delay.

The problem of estimation of state in nonlinear dynamical systems containing time delays is studied. The plant is specified by a set of nonlinear differential-difference equations. Observations are a nonlinear function of current and/or delayed states. Both contain additive disturbances. The criterion used for the optimal estimates is the integral of the weighted squared error. Using the theory of the calculus of variations, equations are developed for the estimation. They are first expressed in the form of a split boundary value problem, which is then converted to an initial value problem for on-line estimation. The result yields a sequential estimation scheme in which filtered and smoothed estimates are computed in a sequential manner. The applicability of the procedure is demonstrated by a practical example.

Stoller, R. L.↗

Complex symmetric matrices with strongly stable iterates

Complex-valued symmetric matrices are studied. A simple expression for the spectral norm of such matrices is obtained, by utilizing a unitarily congruent invariant form. A sharp criterion is provided for identifying those symmetric matrices whose spectral norm is not exceeding one: such strongly stable matrices are usually sought in connection with convergent difference approximations to partial differential equations. As an example, the derived criterion is applied to conclude the strong stability of a Lax-Wendroff scheme.

Tadmor, E.↗

Vibrational Power Flow Analysis of Rods and Beams

A new method to model vibrational power flow and predict the resulting energy density levels in uniform rods and beams is investigated. This method models the flow of vibrational power in a manner analogous to the flow of thermal power in a heat conduction problem. The classical displacement solutions for harmonically excited, hysteretically damped rods and beams are used to derive expressions for the vibrational power flow and energy density in the rod and beam. Under certain conditions, the power flow in these two structural elements will be shown to be proportional to the energy density gradient. Using the relationship between power flow and energy density, an energy balance on differential control volumes in the rod and beam leads to a Poisson's equation which models the energy density distribution in the rod and beam. Coupling the energy density and power flow solutions for rods and beams is also discussed. It is shown that the resonant behavior of finite structures complicates the coupling of solutions, especially when the excitations are single frequency inputs. Two coupling formulations are discussed, the first based on the receptance method, and the second on the travelling wave approach used in Statistical Energy Analysis. The receptance method is the more computationally intensive but is capable of analyzing single frequency excitation cases. The traveling wave approach gives a good approximation of the frequency average of energy density and power flow in coupled systems, and thus, is an efficient technique for use with broadband frequency excitation.

Wohlever, James Christopher↗

Calculation of the Full Scattering Amplitude without Partial Wave Decomposition II: Inclusion of Exchange

As is well known, the full scattering amplitude can be expressed as an integral involving the complete scattering wave function. We have shown that the integral can be simplified and used in a practical way. Initial application to electron-hydrogen scattering without exchange was highly successful. The Schrodinger equation (SE), which can be reduced to a 2d partial differential equation (pde), was solved using the finite element method. We have now included exchange by solving the resultant SE, in the static exchange approximation, which is reducible to a pair of coupled pde's. The resultant scattering amplitudes, both singlet and triplet, calculated as a function of energy are in excellent agreement with converged partial wave results.

Shertzer, Janine↗

Automated Fluidics Device for Extraction and Quantification of miRNA Biomarkers From Blood

Radiation Assessment DuRing Exposure And long-Duration Spaceflight (RADREADS) demonstrates space-compatible point-of-care technology for quantitative biological monitoring of blood miRNA biomarkers in response to long-term low dose radiation exposure. This individualized monitoring approach will inform targeted treatment strategies to maximize medical resource utilization by accounting for individual susceptibility to radiation-related illnesses. As human spaceflight progresses beyond Earth’s magnetic shielding, radiation exposure poses a significant risk to astronaut health and safety. Extended operation in this environment comes with an increased risk of radiation exposure, leading to higher risks of radiation sickness, cancer, central nervous system effects, and degenerative diseases. While conventional physical dosimetry techniques capture radiation dose, individualistic susceptibility to radiation damage is varied. Multiple characteristics, including age, body weight, sex, genetics, and immune status, have been found to influence radiosensitivity (Liu et al. 2011, and Bouffler 2016). This differential response necessitates individualized monitoring and targeted treatment strategies to maximize medical resource utilization; however, a practical diagnostic platform for quantifying long-term, low dose radiation-induced tissue damage does not currently exist. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression by mediating the degradation of messenger RNA. The levels of particular miRNAs are influenced by biological processes such as inflammation and serve as biomarkers for a variety of conditions including cancer (Singh et al. 2017). MicroRNAs are found in various bodily fluids and are amenable to collection via liquid biopsies, providing a minimally invasive and easily quantifiable readout for a variety of radiosensitive reporters. A preliminary signature of 15 spaceflight sensitive miRNA has been identified in rodent and human studies, including miR-21-5p, miR-24-3p, miR-92a-3p, miR-17-5p, miR-16a-3p, miR-34a-3p, and miR-223-3p. These targets generally increased expression with radiation dose and linear energy transfer, though variation between individuals is not yet described. Current gaps in the field include a lack of understanding of longitudinal biological responses to long-term, low dose radiation exposure and the absence of space-compatible point-of-care technology for quantitative biological monitoring. In this body of work, we aim to develop an automated bleed-to-read system to process whole blood for the detection of miRNA biomarkers in order to monitor individualistic responses to radiation exposure. This will be achieved via separating serum (or plasma) from whole blood, followed by extraction, amplification, and quantification of the miRNA using a RT-qPCR reaction. Previously, the WetLab-2 hardware enabled execution of a RT-qPCR reaction aboard ISS; however, it is a manual system that requires crew manipulation and bulky components (Parra et al. 2017). To address these issues, automated fluid handling hardware was developed for each stage of sample preparation. Extraction of total RNA is achieved by sequentially pumping reagents through an off-the-shelf nucleic acid binding column (miRNeasy Serum/Plasma Advanced Kit, Qiagen). This approach eliminates several manual pipetting and centrifuging steps and limits the use of toxic chemicals commonly found in other sample processing techniques. The resulting elution will then be automatically dispensed for RT-qPCR analysis using a compact rotary qPCR (Mic qPCR Cycler, Bio Molecular Systems) that will improve spaceflight compatibility by removing bubbles from the detection region, another challenge highlighted by WetLab-2 (Parra et al. 2017). Efforts are also being made to simplify the RT-qPCR reaction to a 1-step air-dryable mix to improve long-term reagent stability at room temperature and reduce system complexity. By automating the RT-qPCR processes via microfluidic manipulation, RADREADS will reduce crewmember hands-on time and enable the personalized detection of radiation-induced tissue damage during long duration missions. Minimally invasive, longitudinal monitoring of individual’s response to radiation exposure will inform how the physiological system responds to long-term low dose space radiation and enables development of targeted countermeasures by the medical team. Ultimately, this portable technology will require minimal technical expertise and can also be used to monitor miRNA biomarkers associated with other diseases.

Tristen Head↗

Asymptotic form of the longitudinal correlation function for isotropic homogeneous turbulence

An asymptotic form is derived for the longitudinal correlation function for isotropic homogeneous turbulence in an incompressible fluid governed by the Navier-Stokes equation. The result is obtained from an analysis of the algebraic-differential structure of the two-point correlation tensor contained in the complex-valued Fourier transform of the probability measure over the turbulence ensemble, which reveals that the Hopf characteristic functional (the complex-valued Fourier transform of the probability measure) satisfies the Fourier interference inequality. Consequences of the expression obtained, in which the correlation function is a positive definite function of the inverse cube of the spatial coordinate as it approaches infinity, are shown to include the nonexistence of the Loitsianskii invariant, and the solution is shown to be consistent with empirical formulas.

Rosen, G.↗

Sloshing dynamics modulated angular momentum fluctuations actuated by gravity gradient acceleration associated with spacecraft slew motion

The mathematical formulation of orbital spacecraft sloshing dynamics for a partially filled cryogenic superfluid liquid helium II in a dewar container actuated by the gravity gradient acceleration associated with slew motion is studied. The Advanced X-Ray Astrophysics Facility-Spectroscopy (AXAF-S) spacecraft is chosen as a practical example in this study. Explicit mathematical expressions which manage orbital galaxy gradient acceleration with slew motion which is acting on the spacecraft fluid systems are derived. The numerical computation of sloshing dynamics is based on the non-inertia frame spacecraft bound coordinates and the solution of time-dependent, three-dimensional formulations of partial differential equations subject to initial and boundary conditions. This study discloses the capillary effect of sloshing dynamics governed liquid-vapor interface fluctuations, angular momentum and moment fluctuations of fluid system, and also buble mass center fluctuations driven by the gravity gradient acceleration associated with slew motion which affects the stability of the orbital spacecraft fluid system in a microgravity environment.

Hung, R. J.↗

Diversity and regulation of plant Ca2+ pumps: insights from expression in yeast

The spatial and temporal regulation of calcium concentration in plant cells depends on the coordinate activities of channels and active transporters located on different organelles and membranes. Several Ca2+ pumps have been identified and characterized by functional expression of plant genes in a yeast mutant (K616). This expression system has opened the way to a genetic and biochemical characterization of the regulatory and catalytic features of diverse Ca2+ pumps. Plant Ca(2+)-ATPases fall into two major types: AtECA1 represents one of four or more members of the type IIA (ER-type) Ca(2+)-ATPases in Arabidopsis, and AtACA2 is one of seven or more members of the type IIB (PM-type) Ca(2+)-ATPases that are regulated by a novel amino terminal domain. Type IIB pumps are widely distributed on membranes, including the PM (plasma membrane), vacuole, and ER (endoplasmic reticulum). The regulatory domain serves multiple functions, including autoinhibition, calmodulin binding, and sites for modification by phosphorylation. This domain, however, is considerably diverse among several type IIB ATPases, suggesting that the pumps are differentially regulated. Understanding of Ca2+ transporters at the molecular level is providing insights into their roles in signaling networks and in regulating fundamental processes of cell biology.

Review, Academic↗

Performance evaluation of a Doppler radar system for wind shear detection

Nonlinear stochastic differential equations are used to model wind shear, and extended Kalman filters are used to generate state estimates from measurements received from a Doppler radar onboard an aircraft. Likelihood-ratio tests are then used to detect the presence of wind shear. The performance of the system is evaluated by deriving theoretical expressions for the false alarm and miss error probabiilties. The approach uses a Fokker-Planck equation. The overall methodology is general and should be of interest in other applications.

Khalaf, Camille S.↗

Plasma Dispersion Function for the Kappa Distribution

The plasma dispersion function is computed for a homogeneous isotropic plasma in which the particle velocities are distributed according to a Kappa distribution. An ordinary differential equation is derived for the plasma dispersion function and it is shown that the solution can be written in terms of Gauss' hypergeometric function. Using the extensive theory of the hypergeometric function, various mathematical properties of the plasma dispersion function are derived including symmetry relations, series expansions, integral representations, and closed form expressions for integer and half-integer values of K.

Podesta, John J.↗

Numerical calculations of high-altitude differential charging: Preliminary results

A two dimensional simulation program was constructed in order to obtain theoretical predictions of floating potential distributions on geostationary spacecraft. The geometry was infinite-cylindrical with angle dependence. Effects of finite spacecraft length on sheath potential profiles can be included in an approximate way. The program can treat either steady-state conditions or slowly time-varying situations, involving external time scales much larger than particle transit times. Approximate, locally dependent expressions were used to provide space charge, density profiles, but numerical orbit-following is used to calculate surface currents. Ambient velocity distributions were assumed to be isotropic, beam-like, or some superposition of these.

Laframboise, J. G.↗

Magnetic Field Effect on Convective Fluid Flow in a Vertical Bridgman System

We studied the magnetic field effects on convective fluid flow in a differentially heated HgCdTe Bridgman growth system with linearly stratified vertical HgTe concentration. We followed J. E. Hart's system set-up, boundary conditions, and formulation. We obtained analytical steady parallel flow solutions for fluid flow's velocity and solutal concentration. These solutions depend only on solutal Rayleigh number. Our analytical solutions had different expressions from that of Hart's, but had similar numerical simulation results for the mean fluid velocity and solutal concentration gradient as a function of solutal Rayleigh number. We studied the effects of a transverse magnetic field on the fluid flow of the Bridgman growth systems both on the ground and in the space. The simulation results and comparison with experimental results will be presented.

Wang, J. C.↗

Modulation of Bone Marrow Primary Cell Osteoblastogenesis and Cell Senescence by Mechanical Stimulation

Cell and animal studies conducted onboard the International Space Station and formerly the Shuttle flights have provided groundbreaking data illuminating the deleterious biological response of bone to mechanical unloading. Specifically CDKN1A/p-21 a cell senescence protein, was found to be upregulated in osteoprecursor cells of the femur during 15-day spaceflight, leading to the working hypothesis that CDKN1A/p-21 plays a role in inhibition of bone formation via mechanical regulation. To evaluate this hypothesis, utilizing a p-21 knockout mouse-line and relevant wildtype control, we cultured femoral bone marrow primary cells under unloaded (static) and cyclically stretched loading through a 30 day osteoblastogenesis protocol. Morphologic evaluation of the cultures demonstrated that mechanical stretching aligned the cells and increased the presence of defined focal adhesion expressing talin, integrin αvβ3, and PTK2 protein tyrosine kinase 2, also known as focal adhesion kinase (FAK) in both mouse strains. In corroboration with previous investigations of cell survival signals relation to FAK, our study found that with greater concentration of focal adhesions via stretch stimulation the live cell percentage was significantly higher than the unloaded controls (p-21 knockout line: +49.70%, p*=0.009, wildtype control: +18.14%, p*=.01). Also evaluated was the mineralization and ECM secretion capability of the differentiating cells. Von Kossa staining has shown that in the p-21 knockout cells unloaded cells produce more matrix that the stretch stimulated, however the matrix is unorganized presenting in sporadic nodules covering approximately 30% of the culture area at day 14 (n=6 wells) while the stretch stimulated cultures have less mineralization content the surface area containing mineralized matrix is greater (~68% at day 14). Q-PCR evaluation of the p-21 knockout cells revealed that canonical (β-catenin cascade) and non-canonical wnt11 and downstream planar cell polarity (wnt/PCP) pathway molecule RAC1 are prevalently upregulated with mechanical stimulation. Immunofluorescence for β-catenin and RAC1 showed co-localization at the nuclear membrane of the p-21 knockout cells but not the wildtype (n=1) suggesting that molecular communication via the canonical and wnt/PCP pathway are initiated by mechanical loading and experience regulation along the signaling cascade by CDKN1A/p-21. Future investigations will further elucidate this relationship and provide causal data demonstrating mechanical loading’s modulatory effect on p-21 expression change.

Juran, Cassandra M.↗

Nonlinear behavior of acoustic waves in combustion chambers

The nonlinear growth and limiting amplitude of acoustic waves in a combustion chamber are considered. A formal framework is provided within which practical problems can be treated with a minimum of effort and expense. The general conservation equations were expanded in two small parameters, one characterizing the mean flow field and one measuring the amplitude of oscillations, and then combined to yield a nonlinear inhomogeneous wave equation. The unsteady pressure and velocity fields were expressed as syntheses of the normal modes of the chamber, but with unknown time-varying amplitudes. This procedure yielded a representation of a general unsteady field as a system of coupled nonlinear oscillators. The system of nonlinear equations was treated by the method of averaging to produce a set of coupled nonlinear first order differential equations for the amplitudes and phases of the modes. The analysis is applicable to any combustion chamber. The most interesting applications are probably to solid rockets, liquid rockets, or thrust augmentors on jet engines.

Culick, F. E. C.↗

Photon escape probabilities in a semi-infinite plane-parallel medium

It is shown in this work how to obtain the probabilities of photons escaping from a cold electron plasma environment after having undergone an arbitrary number of scatterings. This is done by retaining the exact differential cross section for Thomson scattering as opposed to using its polarization and angle averaged form. The results are given in the form of recursion relations. The geometry used is the semi-infinite plane-parallel geometry witlh a photon source located on a plane at an arbitrary optical depth below the surface. Analytical expressions are given for the probabilities which are accurate over a wide range of initial optical depth. These results can be used to model compact X-ray galactic sources which are surrounded by an electron-rich plasma.

Williams, A. C.↗

On the fundamental frequency of rectangular simply-supported symmetric laminated plates

A new closed-form approximate solution for the fundamental frequency of symmetric rectangular laminates which are simply supported on all four edges is derived. The solution, obtained from eigensensitivity analysis, is expressed as a truncated Maclaurin series in the coupling stiffnesses D16 and D26. Results show that the predicted fundamental frequency is remarkably accurate. A comparison of the fundamental frequencies of four-ply symmetric angle-ply laminates calculated from the new formula with those determined from a Rayleigh-Ritz procedure yielded a maximum differential of 0.6 percent over a wide range of principal stiffness ratios, plate aspect ratios, and design angles.

Reiss, Robert↗

A Logical Account of Diagnosis with Multiple Theories

Model-based diagnosis is a powerful, first-principles approach to diagnosis. The primary drawback with model-based diagnosis is that it is based on a system model, and this model might be inappropriate. The inappropriateness of models usually stems from the fundamental tradeoff between completeness and efficiency. Recently, Struss has developed an elegant proposal for diagnosis with multiple models. Struss characterizes models as relations and develops a precise notion of abstraction. He defines relations between models and analyzes the effect of a model switch on the space of possible diagnoses. In this paper we extend Struss's proposal in three ways. First, our account of diagnosis with multiple models is based on representing models as more expressive first-order theories, rather than as relations. A key technical contribution is the use of a general notion of abstraction based on interpretations between theories. Second, Struss conflates component modes with models, requiring him to define models relations such as choices which result in non-relational models. We avoid this problem by differentiating component modes from models. Third, we present a more general account of simplifications that correctly handles situations where the simplification contradicts the base theory.

Pandurang, P.↗