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At least 199 records · Page 11

Lipophilic bisphosphonates reduced cyst burden and ameliorated hyperactivity of mice chronically infected with Toxoplasma gondii

ABSTRACT The current treatments for toxoplasmosis are only active against fast-growing tachyzoites, present in acute infections, with little effect on slow-growing bradyzoites within tissue cysts, present in latent chronic infections. The mitochondrion ofToxoplasma gondiiis essential for its survival, and one of the major anti-parasitic drugs, atovaquone, inhibits the mitochondrial electron transport chain at the coenzyme Q:cytochrome c oxidoreductase site. Coenzyme Q (also known as ubiquinone [UQ]) consists of a quinone head and a lipophilic, isoprenoid tail that anchors UQ to membranes. The synthesis of the isoprenoid unit is essential for cell growth and is inhibited by lipophilic bisphosphonates, which inhibit the parasite growth. In this work, we investigated the effect of lipophilic bisphosphonates on the chronic stages ofT. gondii. We discovered that three lipophilic bisphosphonates (BPH-1218, BPH-1236, and BPH-1238), effective for the acute infection, were also effective in controlling the development of chronic stages. We showed effectiveness by testing them againstin vitrocysts andin vivoderived tissue cysts and, most importantly, these compounds reduced the cyst burden in the brains of chronically infected mice. We monitored the activity of infected mice non-invasively and continuously with a novel device termed the CageDot. A decrease in activity accompanied the acute phase, but mice recovered to normal activity and showed signs of hyperactivity when the chronic infection was established. Moreover, treatment with atovaquone or BPH-1218 ameliorated the hyperactivity observed during the chronic infection. IMPORTANCE Treatment for toxoplasmosis is challenged by a lack of effective drugs to eradicate the chronic stages. Most of the drugs currently used are poorly distributed to the central nervous system, and they trigger allergic reactions in a large number of patients. There is a compelling need for safe and effective treatments for toxoplasmosis. Bisphosphonates (BPs) are analogs of inorganic pyrophosphate and are used for the treatment of bone disorders. BPs target the isoprenoid pathway and are effective against several experimental parasitic infections. Some lipophilic BPs can specifically inhibit the mitochondrial activity ofToxoplasma gondiiby interfering with the mechanism by which ubiquinone is inserted into the inner mitochondrial membrane. In this work, we present the effect of three lipophilic BPs againstT. gondiichronic stages. We also present a new strategy for the monitoring of animal activity during disease and treatment that is non-invasive and continuous.

Microbiology↗

Assessing Electrolyte Fluorination Impact on Calendar Aging of Blended Silicon-Graphite Lithium-Ion Cells Using Potentiostatic Holds

Silicon-based lithium-ion batteries have started to meet cycle life metrics, but they exhibit poor calendar life. Here, electrolyte fluorination impact on calendar fade of blended silicon-graphite anodes is explored using a LiPF 6 in EC:EMC:FEC electrolyte vs LiBOB in EC:EMC electrolyte. We utilize a combined experimental-modeling approach applying potentiostatic voltage holds (V-hold) to evaluate electrolyte suitability for calendar life in a shortened testing timeframe (~2 months). Our theoretical framework deconvolutes the irreversible parasitic capacity losses (lithium lost to the solid electrolyte interphase) from the V-hold electrochemical data. Unfluorinated electrolyte (dominant LiBOB reduction) exhibits higher cell resistance as compared to fluorinated electrolyte (dominant FEC reduction). Both systems have similar irreversible capacities during the voltage hold duration with slower rate of parasitic capacity loss for the LiBOB system. Extrapolation of the parasitic losses to end of life capacity fade of 20% shows LiBOB electrolyte outperforming LiPF 6 electrolyte in calendar life. The results demonstrate the applicability of the V-hold protocol as a rapid material screening tool providing semi-quantitative calendar lifetime estimates.

25 ENERGY STORAGE↗

Quantifying SEI Reaction Rate in the Presence and Absence of Mn 2+

In this work, a methodology utilizing potentiostatic holds is developed for measuring side-reaction rates at graphite (Gr) electrodes. The influence of Mn 2+ on parasitic reactions is evaluated in the presence of various preformed solid-electrolyte interphases (SEI). Gr SEI preformation was carried out using vinylene carbonate (VC) or lithium difluoro(oxalato)borate (LiDFOB) as an additive. In addition, a highly fluorinated electrolyte, free of traditional non-fluorinated organic carbonates, was used. Parasitic current increases were observed for all preformed Gr SEIs when Mn 2+ was present. Of the preforming electrolytes, the VC-derived SEI showed the lowest parasitic currents both with and without Mn 2+ .

Tornheim, Adam [Argonne National Laboratory (ANL),↗

Survival, healing, and swim performance of juvenile migratory sea lamprey ( Petromyzon marinus ) implanted with a new acoustic microtransmitter designed for small eel-like fishes

Background: Little is known about the transformer stage of the parasitic lampreys, a brief but critical period that encompasses juvenile out-migration from rivers to lakes or oceans to begin parasitic feeding. Information about this life stage could have significant conservation implications for both imperiled and invasive lampreys. We investigated tag retention, survival, wound healing, and swim performance of newly transformed sea lamprey (Petromyzon marinus) implanted with a new micro-acoustic transmitter, the eel–lamprey acoustic transmitter (ELAT), in a controlled laboratory environment. Results: The 61-day survival of our tagged subjects was 71%, within the range reported in similar studies of juvenile lampreys. However, survival was significantly lower in the tagged animals (vs control), with no effect statistically attributable to measures of animal length, mass, condition, or population of origin (Great Lakes vs. Atlantic drainage). Mortality in tagged fish was concentrated in the first four days post-surgery, suggesting injury from the surgical process. An unusually long recovery time from anesthesia may have contributed to the increased mortality. In a simple burst swim assay, tagged animals swam significantly slower (– 22.5%) than untagged animals, but were not significantly different in endurance swim tests. A composite wound healing score at day four was a significant predictor of maximum burst swim speed at day 20, and wound condition was related to animal mass, but not length, at the time of tagging. Conclusions: Impairments to survival and swim performance of juvenile sea lamprey implanted with the ELAT transmitter were within currently reported ranges for telemetry studies with small, difficult to observe fishes. Our results could be improved with more refined anesthesia and surgical techniques. The ability to track migratory movements of imperiled and pest populations of parasitic lampreys will improve our ability to estimate vital rates that underlie recruitment to the adult population (growth, survival) and to investigate the environmental factors that regulate the timing and rates of movement, in wild populations.

59 BASIC BIOLOGICAL SCIENCES↗

A non-traditional crystal-based compound screening method targeting the ATP binding site of Plasmodium falciparum GRP78 for identification of novel nucleoside analogues

Drug resistance to front-line malarial treatments represents an ongoing threat to control malaria, a vector borne infectious disease. The malarial parasite, Plasmodium falciparum has developed genetic variants, conferring resistance to the current standard therapeutic artemisinin and its derivatives commonly referred to as artemisinin-combination therapies (ACTs). Emergence of multi-drug resistance parasite genotypes is a warning of potential treatment failure, reaffirming the urgent and critical need to find and validate alternate drug targets to prevent the spread of disease. An attractive and novel drug target includes glucose-regulated protein 78 kDa (GRP78, or BiP), an essential molecular chaperone protein involved in the unfolded protein response that is upregulated in ACT treated P. falciparum parasites. We have shown that both sequence and structure are closely related to human GRP78 (hGRP78), a chaperone belonging to the HSP70 class of ATPase proteins, which is often upregulated in cellular stress responses and cancer. By screening a library of nucleoside analogues, we identified eight ‘hit’ compounds binding at the active site of the ATP binding domain of P. falciparum GRP78 using a high-throughput ligand soaking screen using x-ray crystallography. These compounds were further evaluated using protein thermal shift assays to assess target binding activity. The nucleoside analogues identified from our screen provide a starting point for the development of more potent and selective antimalarial inhibitors. In addition, we have established a well-defined, high-throughput crystal-based screening approach that can be applied to many crystallizable P. falciparum proteins for generating anti-Plasmodium specific compounds.

59 BASIC BIOLOGICAL SCIENCES↗

Structural evolution of Arsia Mons, Pavonis Mons, and Ascreus Mons Tharsis region of Mars

Analysis of Viking Orbiter data suggests that Arsia Mons, Pavonis Mons, and Ascreus Mons, three large shield volcanoes of the Tharsis volcanoes of Mars, have had similar evolutionary trends. Arsia Mons appears to have developed in the following sequence: (1) construction of a main shield volcano, (2) outbreak of parasitic eruption centers on the northeast and southwest flanks, (3) volcano-tectonic subsidence of the summit and formation of concentric fractures and grabens, possibly by evacuation of an underlying magma chamber during eruption of copious lavas from parasitic eruption centers on the northeast and southwest flanks, and (4) continued volcanism along a fissure or rift bisecting the main shield, resulting in flooding of the floor of the volcano-tectonic depression and inundation of the northeast and southwest flanks by voluminous lavas locally forming parasitic shields. In terms of this sequence Pavonis Mons has developed to stage (3) and Ascreus Mons has evolved to stage (2). This interpretation is supported by crater frequency-diameter distributions in the 0.1- to 3.0-km diameter range.

Crumpler, L. S.↗

An adaptive array antenna for mobile satellite communications

The adaptive array is linearly polarized and consists essentially of a driven lambda/4 monopole surrounded by an array of parasitic elements all mounted on a ground plane of finite size. The parasitic elements are all connected to ground via pin diodes. By applying suitable bias voltages, the desired parasitic elements can be activated and made highly reflective. The directivity and pointing of the antenna beam can be controlled in both the azimuth and elevation planes using high speed digital switching techniques. The antenna RF losses are neglible and the maximum gain is close to the theoretical value determined by the effective aperture size. The antenna is compact, has a low profile, is inexpensive to manufacture and can handle high transmitter power.

Milne, Robert↗

CFD analysis to optimize a design modification of BSMT

The Bearings, Seals and Materials Tester (BSMT) is a test article being used at MSFC to evaluate the performance of conventional rolling contact bearings. Pressure differentials between the BSMT inlet and exit cavities are found to cause large parasitic axial loads on the bearing-carrier walls. These parasitic loads, besides being detrimental to the life of bearings, make the testing and evaluation of bearing performance very difficult, and need to be eliminated if at all possible. The objectives of this study are to estimate the hydrodynamic loads on the bearings and to recommend feasible design modifications for BSMT to eliminate the parasitic loads. Three-dimensional computational analyses of inlet and exit cavities in their baseline configuration were performed with REFLEQS which is an advanced finite-volume Navier-Stokes code. Computations were performed with and without a 1/4 inch diameter temperature probe included in each of the cavities. The results of the analyses indicate that the temperature probes substantially alter the flow field and reduce the pressure drop/rise in the cavities. The overall pressure drop across the tester compares quite well with the measurements.

Ratcliff, Mark↗

Mechanical cooler-to-Dewar interfacing in a long-lifetime, hybrid stored cryogen system

The means for making efficient use of mechanical coolers to limit the parasitic heating into the Dewar are addressed. Thermal efficiency is achieved by minimizing the parasitic heating and thermal impedance of the cooler-to-Dewar interface within the mechanical constraints. The important issues related to compatibility with the instrument system are also briefly discussed. Parasitic heating from the nonoperating (reserved or failed) cooler pair can be reduced with an active thermal switch that isolates the cooler cold tips from the cold finger. An analysis was performed to determine the optimal switch-operating characteristics for this application. Requirements associated with the use of the coolers, analyses performed, and the interface design concept are discussed.

Hopkins, R. A.↗

A generalized vortex theory of the screw propeller and its application

The vortex theory as presented by the author in earlier papers has been extended to permit the solution of the following problems: (1) the investigation of the relation between thrusts and torque distribution and energy loss as given by the induction of helical vortex sheets and by the parasite drag; (2) the checking of the theorem of Betz of the rigidly behaving helical vortex sheet of minimum induced energy loss; (3) the extension of the theory of the screw propeller of minimum energy loss for the inclusion of parasite-drag distribution along the blades. A simple system of diagrams has been developed to systematize the design of airplane propellers for a wide range of parasite-drag distribution along the blades.

Reissner, Hans↗

Natural frequency of uniform and optimized tetrahedral truss platforms

Qualitative and quantitative estimates for the fundamental frequency of uniform and optimized tetrahedral truss platforms are determined. A semiempirical equation is developed for the frequency of free-free uniform trusses as a function of member material properties, truss dimensions, and parasitic (nonstructural) mass fraction Mp/Mt. Optimized trusses with frequencies approximately two times those of uniform trusses are determined by varying the cross-sectional areas of member groups. Trusses with 3 to 8 rings, no parasitic mass, and member areas up to 25 times the minimum area are optimized. Frequencies computed for ranges of both Mp/Mt and the ratio of maximum area to minimum area are normalized to the frequency of a uniform truss with no parasitic mass. The normalized frequency increases with the number of rings, and both frequency and the ratio of maximum area to minimum area decrease with increasing Mp/Mt. Frequency improvements that are achievable with a limited number of member areas are estimated for a 3-ring truss by using Taguchi methods. Joint stiffness knockdown effects are also considered. Comparison of optimized and baseline uniform truss frequencies indicates that tailoring can significantly increase structural frequency; maximum gains occur for trusses with low values of Mp/Mt. This study examines frequency trends for ranges of structural parameters and may be used as a preliminary design guide.

Wu, K. Chauncey↗

Telescience operations with the solar array module plasma interaction experiment

The Solar Array Module Plasma Interactions Experiment (SAMPIE) is a flight experiment that flew on the Space Shuttle Columbia (STS-62) in March 1994, as part of the OAST-2 mission. The overall objective of SAMPIE was to determine the adverse environmental interactions within the space plasma of low earth orbit (LEO) on modern solar cells and space power system materials which are artificially biased to high positive and negative direct current (DC) voltages. The two environmental interactions of interest included high voltage arcing from the samples to the space plasma and parasitic current losses. High voltage arcing can cause physical damage to power system materials and shorten expected hardware life. parasitic current losses can reduce power system efficiency because electric currents generated in a power system drain into the surrounding plasma via parasitic resistance. The flight electronics included two programmable high voltage DC power supplies to bias the experiment samples, instruments to measure the surrounding plasma environment in the STS cargo bay, and the on-board data acquisition system (DAS). The DAS provided in-flight experiment control, data storage, and communications through the Goddard Space Flight Center (GSFC) Hitchhiker flight avionics to the GSFC Payload Operations Control Center (POCC). The DAS and the SAMPIE POCC computer systems were designed for telescience operations; this paper will focus on the experiences of the SAMPIE team regarding telescience development and operations from the GSFC POCC during STS-62. The SAMPIE conceptual development, hardware design, and system verification testing were accomplished at the NASA Lewis Research Center (LeRC). SAMPIE was developed under the In-Space Technology Experiment Program (IN-STEP), which sponsors NASA, industry, and university flight experiments designed to enable and enhance space flight technology. The IN-STEP Program is sponsored by the Office of Space Access and Technology (OSAT).

Wald, Lawrence W.↗

An Active Substrate Driver for Enabling Mixed-Voltage SOI Systems-On-A-Chip

The current trend for space application systems is towards fully integrated systems-on-a-chip. To facilitate this drive, high-voltage transistors must reside on the same substrate as low-voltage transistors. These systems must also be radiation tolerant, particularly for space missions such as the Europa Lander and Titan Explorer. SOI CMOS technology offers high levels of radiation hardness. As a result, a high-voltage lateral MOSFET has been developed in a partially-depleted (PD) SOI technology. Utilizing high voltages causes a parasitic transistor to have non-negligible effects on a circuit. Several circuit architectures have been used to compensate for the radiation induced threshold voltage shift of the parasitic back-channel transistor. However, a new architecture for high-voltage systems must be employed to bias the substrate to voltage levels insuring all parasitic transistors remain off. An active substrate driver has been developed to accomplish task. Additional information is contained in the original extended abstract.

Jackson, S. A.↗

Development of Electronic Load Controllers for Free-Piston Stirling Convertors Aided by Stirling Simulation Model

The free-piston Stirling convertor end-to-end modeling effort at the NASA Glenn Research Center has produced a software-based test bed in which free-piston Stirling convertors can be simulated and evaluated. The simulation model includes all the components of the convertor: the Stirling cycle engine, heat source, linear alternator, controller, and load. So far, it has been used in evaluating the performance of electronic controller designs. Three different controller design concepts were simulated using the model: 1) Controllers with parasitic direct current loading. 2) Controllers with parasitic alternating current loading. 3) Controllers that maintain a reference current. The free-piston Stirling convertor is an electromechanical device that operates at resonance. It is the function of the electronic load controller to ensure that the electrical load seen by the machine is always great enough to keep the amplitude of the piston and alternator oscillation at the rated value. This is done by regulating the load on the output bus. The controller monitors the instantaneous voltage, regulating it by switching loads called parasitic loads onto the bus whenever the bus voltage is too high and removing them whenever the voltage is too low. In the first type of controller, the monitor-ing and switching are done on the direct-current (dc) bus. In the second type, the alternating current bus is used. The model allows designers to test a controller concept before investing time in hardware. The simulation code used to develop the model also offers detailed models of digital and analog electronic components so that the resulting designs are realistic enough to translate directly into hardware circuits.

Regan, Timothy F.↗

Identifying Geographic Areas at Risk of Soil-transmitted Helminthes Infection Using Remote Sensing and Geographical Information Systems: Boaco, Nicaragua as a Case Study

Several types of intestinal nematodes, that can infect humans and specially school-age children living in poverty, develop part of their life cycle in soil. Presence and survival of these parasites in the soil depend on given environmental characteristics like temperature and moisture that can be inferred with remote sensing (RS) technology. Prevalence of diseases caused by these parasitic worms can be controlled and even eradicated with anthelmintic drug treatments and sanitation improvement. Reliable and updated identification of geographic areas at risk is required to implement effective public health programs; to calculate amount of drug required and to distribute funding for sanitation projects. RS technology and geographical information systems (GIS) will be used to analyze for associations between in situ prevalence and remotely sensed data in order to establish RS proxies of environmental parameters that indicate the presence of these parasits. In situ data on helminthisasis will be overlaid over an ecological map derived from RS data using ARC Map 9.3 (ESRI). Temperature, vegetation, and distance to bodies of water will be inferred using data from Moderate-Resolution Imaging Spectroradiometer (MODIS) and Landsat TM and ETM+. Elevation will be estimated with data from The Shuttle Radar Topography Mission (SRTM). Prevalence and intensity of infections are determined by parasitological survey (Kato Katz) of children enrolled in rural schools in Boaco, Nicaragua, in the communities of El Roblar, Cumaica Norte, Malacatoya 1, and Malacatoya 2). This study will demonstrate the importance of an integrated GIS/RS approach to define clusters and areas at risk. Such information will help to the implementation of time and cost efficient control programs and sanitation efforts.

Moreno, Max J.↗

Electrochemical Ultracapacitors Using Graphitic Nanostacks

Electrochemical ultracapacitors (ECs) have been developed using graphitic nanostacks as the electrode material. The advantages of this technology will be the reduction of device size due to superior power densities and relative powers compared to traditional activated carbon electrodes. External testing showed that these materials display reduced discharge response times compared to state-of-the-art materials. Such applications are advantageous for pulsed power applications such as burst communications (satellites, cell phones), electromechanical actuators, and battery load leveling in electric vehicles. These carbon nanostructures are highly conductive and offer an ordered mesopore network. These attributes will provide more complete electrolyte wetting, and faster release of stored charge compared to activated carbon. Electrochemical capacitor (EC) electrode materials were developed using commercially available nanomaterials and modifying them to exploit their energy storage properties. These materials would be an improvement over current ECs that employ activated carbon as the electrode material. Commercially available graphite nanofibers (GNFs) are used as precursor materials for the synthesis of graphitic nanostacks (GNSs). These materials offer much greater surface area than graphite flakes. Additionally, these materials offer a superior electrical conductivity and a greater average pore size compared to activated carbon electrodes. The state of the art in EC development uses activated carbon (AC) as the electrode material. AC has a high surface area, but its small average pore size inhibits electrolyte ingress/egress. Additionally, AC has a higher resistivity, which generates parasitic heating in high-power applications. This work focuses on fabricating EC from carbon that has a very different structure by increasing the surface area of the GNF by intercalation or exfoliation of the graphitic basal planes. Additionally, various functionalities to the GNS surface will be added that can exhibit pseudocapacitance. This pseudocapacitance exhibits faradaic (charge transfer) properties that can further increase the overall relative and volumetric capacitance of the material. A process is also proposed to use GNF as a precursor material to fabricate GNS that will be used as EC electrodes. This results in much better electrical conductivity than activated carbon. This is advantageous for high-pulsed-power applications to reduce parasitic heating. Larger average pore size allows more complete electrolyte wetting (faster charge transfer kinetics). These properties contribute to a lowered equivalent series resistance (ESR), increased specific power, shorter charging times, and decreased parasitic heating. The high density of basal plane edges provides nucleation sites for activation (addition of hydrophilic functional groups) that facilitate electrolyte wetting, and will contribute to pseudocapacitance.

Marotta, Christopher↗

Two Dimensional Heat Transfer around Penetrations in Multilayer Insulation

The objective of this task was to quantify thermal losses involving integrating MLI into real life situations. Testing specifically focused on the effects of penetrations (including structural attachments, electrical conduit/feedthroughs, and fluid lines) through MLI. While there have been attempts at quantifying these losses both analytically and experimentally, none have included a thorough investigation of the methods and materials that could be used in such applications. To attempt to quantify the excess heat load coming into the system due to the integration losses, a calorimeter was designed to study two dimensional heat transfer through penetrated MLI. The test matrix was designed to take as many variables into account as was possible with the limited test duration and system size. The parameters varied were the attachment mechanism, the buffer material (for buffer attachment mechanisms only), the thickness of the buffer, and the penetration material. The work done under this task is an attempt to measure the parasitic heat loads and affected insulation areas produced by system integration, to model the parasitic loads, and from the model produce engineering equations to allow for the determination of parasitic heat loads in future applications. The methods of integration investigated were no integration, using a buffer to thermally isolate the strut from the MLI, and temperature matching the MLI on the strut. Several materials were investigated as a buffer material including aerogel blankets, aerogel bead packages, cryolite, and even an evacuated vacuum space (in essence a no buffer condition).

Johnson, Wesley L.↗

Self-powered Heating: Efficiency Analysis

Conventional fuel-fired heating devices such as furnaces, boilers, and water heaters have fuel efficiency less than 100% on the basis of higher heating value. They also require electricity from the electric grid to power parasitic loads such as blowers, pumps, fans, and ignitors. The primary energy efficiency of the device accounts for both fuel used on-site and primary energy used off-site to produce electric power used by the device. This work compares conventional fuel-fired heating devices to two types of self-powered devices. A self-powered device (SPD) integrates a power cycle onboard to eliminate consumption of grid electricity. We assume that all heat rejected by the onboard power cycle is added to the process fluid, so that, compared with a conventional device, the same amount of heat is provided to the process fluid and the same amount of fuel is consumed, but grid electricity consumption is eliminated. The first SPD type is the basic one: exactly the electricity required is generated. The second type considered is the SPD with heat pump (SPD-HP), in which the power cycle generates more electricity than needed for parasitic loads, and the excess electricity is used to power a heat pump. The heat pump extracts additional heat from the ambient to boost efficiency. Both SPD and SPD-HP self-consume all the generated electricity, in contrast to combined heat and power (CHP) systems that export electricity. In this work, equations are derived to express the efficiency of three classes of heating devices: conventional (consuming grid electricity), self-powered (consuming no grid electricity), and self-powered with heat pump. The efficiency of each is derived as a function of up to six factors: (1) the fraction of combustion heat captured, (2) the rate of parasitic power consumption, (3) the fraction of electric energy dissipated as useful heat, (4) the power cycle conversion efficiency, (5) the grid efficiency, when applicable, and (6) the heat pump COP, when applicable. Scenarios are identified in which it is possible to achieve efficiency greater than 100% on a higher heating value basis. Plausible configurations using existing technology options are outlined.

Gluesenkamp, Kyle↗