Fault tree safety analysis of a large Li/SOCl(sub)2 spacecraft battery

The results of the safety fault tree analysis on the eight module, 576 F cell Li/SOCl2 battery on the spacecraft and in the integration and test environment prior to launch on the ground are presented. The analysis showed that with the right combination of blocking diodes, electrical fuses, thermal fuses, thermal switches, cell balance, cell vents, and battery module vents the probability of a single cell or a 72 cell module exploding can be reduced to .000001, essentially the probability due to explosion for unexplained reasons

A I-V analysis of irradiated Gallium Arsenide solar cells

A computer program was used to analyze the illuminated I-V characteristics of four sets of gallium arsenide (GaAs) solar cells irradiated with 1-MeV electrons and 10-MeV protons. It was concluded that junction regions (J sub r) dominate nearly all GaAs cells tested, except for irradiated Mitsubishi cells, which appear to have a different doping profile. Irradiation maintains or increases the dominance by J sub r. Proton irradiation increases J sub r more than does electron irradiation. The U.S. cells were optimized for beginning of life (BOL) and the Japanese for end of life (EOL). I-V analysis indicates ways of improving both the BOL and EOL performance of GaAs solar cells

Gallium Arsenide solar cell radiation damage experiment

Gallium arsenide (GaAs) solar cells for space applications from three different manufactures were irradiated with 10 MeV protons or 1 MeV electrons. The electrical performance of the cells was measured at several fluence levels and compared. Silicon cells were included for reference and comparison. All the GaAs cell types performed similarly throughout the testing and showed a 36 to 56 percent power areal density advantage over the silicon cells. Thinner (8-mil versus 12-mil) GaAs cells provide a significant weight reduction. The use of germanium (Ge) substrates to improve mechanical integrity can be implemented with little impact on end of life performance in a radiation environment

Optimal Contracts for Outsourced Computation

While expensive cryptographically verifiable computation aims at defeating malicious agents, many civil purposes of outsourced computation tolerate a weaker notion of security, i.e., “lazy-but-honest” contractors. Targeting this type of agents, we develop optimal contracts for outsourcing of computational tasks via appropriate use of rewards, punishments, auditing rate, and “redundancy”. Our contracts provably minimize the expense of the outsourcer (principal) while guaranteeing correct computation. Furthermore, we incorporate practical restrictions of the maximum enforceable fine, limited and/or costly auditing, and bounded budget of the outsourcer. By examining the optimal contracts, we provide insights on how resources should be utilized when auditing capacity and enforceability are limited. Finally, we present a light-weight cryptographic implementation of the contracts and discuss a comparison across different implementations of auditing in outsourced computation

Follicle and Oocyte Relationships During Superovulation in the Heifer

As the female cow matures, the majority of her follicles become atretic and are lost as a store house of the female gamete (oocyte). Emphasis on in vitro fertilization to maximize the utilization of superior animals for transplant of frozen embryos is considerably limited by the number of viable mature oocytes that can be collected. Understanding the biochemical environment required to produce maximum numbers of mature, fertilizable oocytes is a prime requirement to utilize this technology in increasing meat animal production and efficiency. The goal of these studies was to characterize the endocrine and biochemical events associated with follicle and oocyte maturation to establish the best environment for follicle development and maximize numbers

Advances in three-dimensional geoelectric forward solver techniques

Modern geoelectrical data acquisition systems allow large amounts of data to be collected in a short time. Inversions of such data sets require powerful forward solvers for predicting the electrical potentials. State-of-the-art solvers are typically based on finite elements. Recent developments in numerical mathematics led to direct matrix solvers that allow the equation systems arising from such finite element problems to be solved very efficiently. They are particularly useful for 3-D geoelectrical problems, where many electrodes are involved. Although modern direct matrix solvers include optimized memory saving strategies, their application to realistic, large-scale 3-D problems is still somewhat limited. Therefore, we present two novel techniques that allow the number of gridpoints to be reduced considerably, while maintaining a high solution accuracy. In the areas surrounding an electrode array we attach infinite elements that continue the electrical potentials to infinity. This does not only reduce the number of gridpoints, but also avoids the artificial Dirichlet or mixed boundary conditions that are well known to be the cause of numerical inaccuracies. Our second development concerns the singularity removal in the presence of significant surface topography. We employ a fast multipole boundary element method for computing the singular potentials. This renders unnecessary mesh refinements near the electrodes, which results in substantial savings of gridpoints of up to more than 50 per cent. By means of extensive numerical tests we demonstrate that combined application of infinite elements and singularity removal allows the number of gridpoints to be reduced by a factor of ≈6-10 compared with traditional finite element methods. This will be key for applying finite elements and direct matrix solver techniques to realistic 3-D inversion problem

Discrete tomography and joint inversion for loosely connected or unconnected physical properties: application to crosshole seismic and georadar data sets

Tomographic inversions of geophysical data generally include an underdetermined component. To compensate for this shortcoming, assumptions or a priori knowledge need to be incorporated in the inversion process. A possible option for a broad class of problems is to restrict the range of values within which the unknown model parameters must lie. Typical examples of such problems include cavity detection or the delineation of isolated ore bodies in the subsurface. In cavity detection, the physical properties of the cavity can be narrowed down to those of air and/or water, and the physical properties of the host rock either are known to within a narrow band of values or can be established from simple experiments. Discrete tomography techniques allow such information to be included as constraints on the inversions. We have developed a discrete tomography method that is based on mixed-integer linear programming. An important feature of our method is the ability to invert jointly different types of data, for which the key physical properties are only loosely connected or unconnected. Joint inversions reduce the ambiguity in tomographic studies. The performance of our new algorithm is demonstrated on several synthetic data sets. In particular, we show how the complementary nature of seismic and georadar data can be exploited to locate air- or water-filled cavitie

Inhibition and stimulation of the human breast cancer resistance protein as in vitro predictor of drug–drug interactions of drugs of abuse

Transporter-mediated drug–drug interactions (DDI) may induce adverse clinical events. As drugs of abuse (DOA) are marketed without preclinical safety studies, only very limited information about interplay with membrane transporters are available. Therefore, 13 DOA of various classes were tested for their in vitro affinity to the human breast cancer resistance protein (hBCRP), an important efflux transporter. As adenosine 5′-triphosphate (ATP) hydrolysis is crucial for hBCRP activity, adenosine 5′-diphosphate (ADP) formation was measured and used as in vitro marker for hBCRP ATPase activity. ADP quantification was performed by hydrophilic interaction liquid chromatography coupled to high-resolution tandem mass spectrometry and its amount in test compound incubations was compared to that in reference incubations using the hBCRP substrate sulfasalazine or the hBCRP inhibitor orthovanadate. If DOA caused stimulation or inhibition, further investigations such as Michaelis–Menten kinetic modeling or IC50 value determination were conducted. Among the tested DOA, seven compounds showed statistically significant hBCRP ATPase stimulation. The entactogen 3,4-BDB and the plant alkaloid mitragynine were identified as strongest stimulators. Their affinity to the hBCRP ATPase was lower than that of sulfasalazine but comparable to that of rosuvastatin, another hBCRP model substrate. Five DOA showed statistically significant hBCRP ATPase inhibition. Determination of IC50 values identified the synthetic cannabinoid receptor agonists JWH-200 and WIN 55,212-2 as the strongest inhibitors comparable to orthovanadate. The present study clearly demonstrated that tested DOA show in part high affinities to the hBCRP within the range of model substrates or inhibitors. Thus, there is a risk of hBCRP-mediated DDI, which needs to be considered in clinical settings

What is the contribution of human FMO3 in the N-oxygenation of selected therapeutic drugs and drugs of abuse?

Little is known about the role of flavin-containing monooxygenases (FMOs) in the metabolism of xenobiotics. FMO3 is the isoform in adult human liver with the highest impact on drug metabolism. The aim of the presented study was to elucidate the contribution of human FMO3 to the N-oxygenation of selected therapeutic drugs and drugs of abuse (DOAs). Its contribution to the in vivo hepatic net clearance of the N-oxygenation products was calculated by application of an extended relative activity factor (RAF) approach to differentiate from contribution of cytochrome P450 (CYP) isoforms. FMO3 and CYP substrates were identified using pooled human liver microsomes after heat inactivation and chemical inhibition, or single enzyme incubations. Kinetic parameters were subsequently determined using recombinant human enzymes and mass spectrometric analysis via authentic reference standards or simple peak areas of the products divided by those of the internal standard. FMO3 was identified as enzyme mainly responsible for the formation of N,N-diallyltryptamine N-oxide and methamphetamine hydroxylamine (>80% contribution for both). A contribution of 50 and 30% was calculated for the formation of N,N-dimethyltryptamine N-oxide and methoxypiperamide N-oxide, respectively. However, FMO3 contributed with less than 5% to the formation of 3-bromomethcathinone hydroxylamine, amitriptyline N-oxide, and clozapine N-oxide. There was no significant difference in the contributions when using calibrations with reference metabolite standards or peak area ratio calculations. The successful application of a modified RAF approach including FMO3 proved the importance of FMO3 in the N-oxygenation of DOAs in human metabolism

An easy and fast adenosine 5'-diphosphate quantification procedure based on hydrophilic interaction liquid chromatography-high resolution tandem mass spectrometry for determination of the in vitro adenosine 5'-triphosphatase activity of the human breast cancer resistance protein ABCG2

Interactions with the human breast cancer resistance protein (hBCRP) significantly influence the pharmacokinetic properties of a drug and can even lead to drug-drug interactions. As efflux pump from the ABC superfamily, hBCRP utilized energy gained by adenosine 5′-triphosphate (ATP) hydrolysis for the transmembrane movement of its substrates, while adenosine 5′-diphosphate (ADP) and inorganic phosphate were released. The ADP liberation can be used to detect interactions with the hBCRP ATPase. An ADP quantification method based on hydrophilic interaction liquid chromatography (HILIC) coupled to high resolution tandem mass spectrometry (HR-MS/MS) was developed and successfully validated in accordance to the criteria of the guideline on bioanalytical method validation by the European Medicines Agency. ATP and adenosine 5′-monophosphate were qualitatively included to prevent interferences. Furthermore, a setup consisting of six sample sets was evolved that allowed detection of hBCRP substrate or inhibitor properties of the test compound. The hBCRP substrate sulfasalazine and the hBCRP inhibitor orthovanadate were used as controls. To prove the applicability of the procedure, the effect of amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir on the hBCRP ATPase activity was tested. Nelfinavir, ritonavir, and saquinavir were identified as hBCRP ATPase inhibitors and none of the five HIV protease inhibitors turned out to be an hBCRP substrate. These findings were in line with a pervious publication