311 research outputs found
George C. Marshall Space Flight Center Research and Technology Report 2014
Many of NASA's missions would not be possible if it were not for the investments made in research advancements and technology development efforts. The technologies developed at Marshall Space Flight Center contribute to NASA's strategic array of missions through technology development and accomplishments. The scientists, researchers, and technologists of Marshall Space Flight Center who are working these enabling technology efforts are facilitating NASA's ability to fulfill the ambitious goals of innovation, exploration, and discovery
Thermodynamic metrics and optimal paths
A fundamental problem in modern thermodynamics is how a molecular-scale
machine performs useful work, while operating away from thermal equilibrium
without excessive dissipation. To this end, we derive a friction tensor that
induces a Riemannian manifold on the space of thermodynamic states. Within the
linear-response regime, this metric structure controls the dissipation of
finite-time transformations, and bestows optimal protocols with many useful
properties. We discuss the connection to the existing thermodynamic length
formalism, and demonstrate the utility of this metric by solving for optimal
control parameter protocols in a simple nonequilibrium model.Comment: 5 page
Marshall Space Flight Center Research and Technology Report 2015
The investments in technology development we made in 2015 not only support the Agency's current missions, but they will also enable new missions. Some of these projects will allow us to develop an in-space architecture for human space exploration; Marshall employees are developing and testing cutting-edge propulsion solutions that will propel humans in-space and land them on Mars. Others are working on technologies that could support a deep space habitat, which will be critical to enable humans to live and work in deep space and on other worlds. Still others are maturing technologies that will help new scientific instruments study the outer edge of the universe-instruments that will provide valuable information as we seek to explore the outer planets and search for life
Absence of dissipation in trajectory ensembles biased by currents
We consider biased ensembles of trajectories associated with large deviations of currents in equilibrium systems. The biased ensembles are characterised by non-zero currents and lack the time-reversal symmetry of the equilibrium state. In cases where the equilibrium system has an inversion symmetry which is broken by the bias, we show that the biased ensembles retain a generalised time-reversal symmetry, involving a spatial transformation that inverts the current. This means that these ensembles lack dissipation. Hence, they differ significantly from non-equilibrium steady states where currents are induced by external forces. One consequence of this result is that maximum entropy assumptions (MaxEnt/MaxCal), widely used for modelling thermal systems away from equilibrium, have quite unexpected implications, including apparent superfluid behaviour in a classical model of shear flow
Engineered swift equilibration of a Brownian particle
A fundamental and intrinsic property of any device or natural system is its
relaxation time relax, which is the time it takes to return to equilibrium
after the sudden change of a control parameter [1]. Reducing relax , is
frequently necessary, and is often obtained by a complex feedback process. To
overcome the limitations of such an approach, alternative methods based on
driving have been recently demonstrated [2, 3], for isolated quantum and
classical systems [4--9]. Their extension to open systems in contact with a
thermostat is a stumbling block for applications. Here, we design a
protocol,named Engineered Swift Equilibration (ESE), that shortcuts
time-consuming relaxations, and we apply it to a Brownian particle trapped in
an optical potential whose properties can be controlled in time. We implement
the process experimentally, showing that it allows the system to reach
equilibrium times faster than the natural equilibration rate. We also estimate
the increase of the dissipated energy needed to get such a time reduction. The
method paves the way for applications in micro and nano devices, where the
reduction of operation time represents as substantial a challenge as
miniaturization [10]. The concepts of equilibrium and of transformations from
an equilibrium state to another, are cornerstones of thermodynamics. A textbook
illustration is provided by the expansion of a gas, starting at equilibrium and
expanding to reach a new equilibrium in a larger vessel. This operation can be
performed either very slowly by a piston, without dissipating energy into the
environment, or alternatively quickly, letting the piston freely move to reach
the new volume
Quark Potential in a Quark-Meson Plasma
We investigate quark potential by considering meson exchanges in the two
flavor Nambu--Jona-Lasinio model at finite temperature and density. There are
two kinds of oscillations in the chiral restoration phase, one is the Friedel
oscillation due to the sharp quark Fermi surface at high density, and the other
is the Yukawa oscillation driven by the complex meson poles at high
temperature. The quark-meson plasma is strongly coupled in the temperature
region with being the critical temperature of
chiral phase transition. The maximum coupling in this region is located at the
critical point.Comment: 8 pages and 8 figure
Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms
Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability
Facilitating Adolescent Well-Being: A Review of the Challenges and Opportunities and the Beneficial Roles of Parents, Schools, Neighborhoods, and Policymakers
Adolescents face exceptional challenges and opportunities that may have a lifelong impact on their consumption and personal and societal well-being. Parents, community members (schools and neighborhoods), and policymakers play major roles in shaping adolescents and influencing their engagement in consumption behaviors that are either developmentally problematic (e.g., drug use and unhealthy eating) or developmentally constructive (e.g., academic pursuits and extracurricular activities). In this article, we discuss two main topics: (a) the challenges and opportunities that characterize adolescence, based primarily on research in epidemiology and neuroscience, and (b) the ways that parents, community members, and policymakers can facilitate positive adolescent development, based on research from many disciplines including marketing, psychology, sociology, communications, public health, and education. Our goal is to summarize the latest scientific findings that can be used by various stakeholders to help adolescents navigate this turbulent period and become well-adjusted, thriving adults
Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles
There are very few drug delivery
systems that target key organs
via the oral route, as oral delivery advances normally address gastrointestinal
drug dissolution, permeation, and stability. Here we introduce a nanomedicine
in which nanoparticles, while also protecting the drug from gastric
degradation, are taken up by the gastrointestinal epithelia and transported
to the lung, liver, and spleen, thus selectively enhancing drug bioavailability
in these target organs and diminishing kidney exposure (relevant to
nephrotoxic drugs). Our work demonstrates, for the first time, that
oral particle uptake and translocation to specific organs may be used
to achieve a beneficial therapeutic response. We have illustrated
this using amphotericin B, a nephrotoxic drug encapsulated within <i>N</i>-palmitoyl-<i>N</i>-methyl-<i>N</i>,<i>N</i>-dimethyl-<i>N</i>,<i>N</i>,<i>N</i>-trimethyl-6-<i>O</i>-glycol chitosan
(GCPQ) nanoparticles, and have evidenced our approach in three separate
disease states (visceral leishmaniasis, candidiasis, and aspergillosis)
using industry standard models of the disease in small animals. The
oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease
models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral
liposomal AmB (AmBisome). Our work thus paves the way for others to
use nanoparticles to achieve a specific targeted delivery of drug
to key organs via the oral route. This is especially important for
drugs with a narrow therapeutic index
Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases
Abstract. Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually. Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury. Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome. Inflammatory shock as a consequence of LPS release remains a serious clinical concern. In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death. A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS. Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4. This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction. KEY WORDS: drug discovery; LPS; sepsis; toll-like receptor antagonists
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