Experiences using lightweight formal methods for requirementsmodeling

The paper describes three case studies in the lightweight application of formal methods to requirements modeling for spacecraft fault protection systems. The case studies differ from previously reported applications of formal methods in that formal methods were applied very early in the requirements engineering process to validate the evolving requirements. The results were fed back into the projects to improve the informal specifications. For each case study, we describe what methods were applied, how they were applied, how much effort was involved, and what the findings were. In all three cases, formal methods enhanced the existing verification and validation processes by testing key properties of the evolving requirements and helping to identify weaknesses. We conclude that the benefits gained from early modeling of unstable requirements more than outweigh the effort needed to maintain multiple representations     

Effect of dissolved tungsten on the deformation of 70Ni-30Fe alloys

A series of Ni-Fe alloys containing various levels of tungsten in solid solution have been prepared as a means to assess the influence of solid solution strengthening on the mechanical behavior of monolithic 70Ni-30Fe. In particular, 70Ni-30Fe alloys plus equilibrium concentrations of tungsten in solid solution nominally correspond to the compositions associated with the matrix-only portion of certain tungsten heavy alloys, that is, alloys comprised of a high volume fraction of nominally pure tungsten particles embedded within a minority Ni-Fe-W based matrix. The study shows that the working solubility of tungsten within the 70Ni-30Fe base composition increases slightly with temperature, from approximately 21 wt pct at room temperature to approximately 23 wt pct at 1400 °C. Increasing the level of tungsten in solid solution leads to increases in room-temperature yield strength, tensile strength, and ductility. In contrast, the deformation characteristics of the alloys, as quantified by the power-law work-hardening exponent, n, and the strain-rate-sensitivity exponent, m, show little variation with tungsten solute concentration.     

Updating Situation Models: Reply to Zwaan and Madden (2004).

E. J. O'Brien, M. L. Rizzella, J. E. Albrecht, and J. G. Halleran (1998) demonstrated that, consistent with the memory-based text processing view, outdated or incorrect information can be reactivated through a passive resonance process. Once reactivated, this outdated information can still influence comprehension. R. A. Zwaan and C. J. Madden (2004) suggested that the O'Brien et al. findings resulted from problems with the materials used. The present authors show that the possible "problems" identified by Zwaan and Madden do not adequately explain the findings of O'Brien et al. and that Zwaan and Madden's Experiment 3 lacks sufficient control or power to support their alternative interpretation of O'Brien et al. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Calorimetric and thermodynamic analysis of palladium-deuterium electrochemical cells

An analysis is made of the chemical heats liberated from a palladium-deuterium electrochemical cell operating inside a calorimeter. It is important, in such an analysis, to carefully identify the chemical and electrochemical sources of heat, before any “excess heats” can be ascribed to non-chemical reactions.⁽¹⁾ The calorimeter measures the enthalpy (ΔH _r ) of the reaction; whereas, the electrochemical voltage of the cell reflects the free energy (ΔG _r ) of the reaction within the Pd-D electrolysis cell. The heat energy from the calorimeter cell therefore doesnot equal the electrical energy supplied to the cell, as might initially be expected. The magnitudes of the differing calorimetric and electrochemical energies were found to be related through the “thermoneutral potential” (ξ_H) of the electrochemical reaction. The chemical heat theoretically expected from the calorimeter is given by (1) I(ξ_L-ξ_H), the cell current (I), multiplied by the difference between the operating cell voltage (ξ_L) and the thermoneutral potential (ξ_H), rather than (2) Iξ_L, the electrical input power. This was verified empirically using a freon vaporization calorimeter, which operates on the principle of accurate measurement of the vaporization rate of liquid freon which completely surrounds the electrochemical cell. The calorimetrically-measured heats observed from a Pt/D₂O, 0.1M LiOD/Pd electrochemical cell were within 2% of the thermoneutral potential predicted value, I(ξ_L-ξ_H); but were found to be 15–30% less than the electrical work supplied to the cell, Iξ_L. Measurements of D₂O consumed by the cell reactions also verified that essentially no significant recombination of D₂ and O₂ gases occurred within the cell. No “excess heats” were observed from this Pd cell during the 36 days of its electrolytic operation. Likewise, no increase in the neutron flux around the cell was found, using three³He radiation detectors.     

Trans-Reduction of Cerebral Small Vessel Disease Proteins by Notch-Derived EGF-like Sequences

Cysteine oxidation states of extracellular proteins participate in functional regulation and in disease pathophysiology. In the most common inherited dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), mutations in NOTCH3 that alter extracellular cysteine number have implicated NOTCH3 cysteine states as potential triggers of cerebral vascular smooth muscle cytopathology. In this report, we describe a novel property of the second EGF-like domain of NOTCH3: its capacity to alter the cysteine redox state of the NOTCH3 ectodomain. Synthetic peptides corresponding to this sequence (NOTCH3 N-terminal fragment 2, NTF2) readily reduce NOTCH3 N-terminal ectodomain polypeptides in a dose- and time-dependent fashion. Furthermore, NTF2 preferentially reduces regional domains of NOTCH3 with the highest intensity against EGF-like domains 12–15. This process requires cysteine residues of NTF2 and is also capable of targeting selected extracellular proteins that include TSP2 and CTSH. CADASIL mutations in NOTCH3 increase susceptibility to NTF2-facilitated reduction and to trans-reduction by NOTCH3 produced in cells. Moreover, NTF2 forms complexes with the NOTCH3 ectodomain, and cleaved NOTCH3 co-localizes with the NOTCH3 ectodomain in cerebral arteries of CADASIL patients. The potential for NTF2 to reduce vascular proteins and the enhanced preference for it to trans-reduce mutant NOTCH3 implicate a role for protein trans-reduction in cerebrovascular pathological states such as CADASIL.     

Quantification of protein phosphorylation by liquid chromatography-mass spectrometry

The identification and quantification of specific phosphorylation sites within a protein by mass spectrometry has proved challenging when measured from peptides after protein digestion because each peptide has a unique ionization efficiency that alters with modification, such as phosphorylation, and because phosphorylation can alter cleavage by trypsin, shifting peptide distribution. In addition, some phosphorylated peptides generated by tryptic digest are small and hydrophilic and, thus, are not retained well on commonly used C18 columns. We have developed a novel C-terminal peptide (2)H-labeling derivatization strategy and a mass balance approach to quantify phosphorylation. We illustrate the application of our method using electrospray ionization liquid chromatography-mass spectrometry by quantifying phosphorylation of troponin I with protein kinase A and protein kinase C. The method also improves the retention and elution of hydrophilic peptides. The method defines phosphorylation without having to measure the phosphorylated peptides directly or being affected by variable miscleavage. Measurement of phosphorylation is shown to be linear (relative standard error <5%) with a detection limit of <10%.     

Carbon isotopes profiles of human whole blood, plasma, red blood cells, urine and feces for biological/biomedical 14C-accelerator mass spectrometry applications

Radiocarbon ((14)C) is an ideal tracer for in vivo human ADME (absorption, distribution, metabolism, elimination) and PBPK (physiological-based pharmacokinetic) studies. Living plants peferentially incorporate atmospheric (14)CO(2) versus (13)CO(2) versus (12)CO(2), which result in unique signature. Furthermore, plants and the food chains they support also have unique carbon isotope signatures. Humans, at the top of the food chain, consequently acquire isotopic concentrations in the tissues and body fluids depending on their dietary habits. In preparation of ADME and PBPK studies, 12 healthy subjects were recruited. The human baseline (specific to each individual and their diet) total carbon (TC) and carbon isotope (13)C (δ(13)C) and (14)C (F(m)) were quantified in whole blood (WB), plasma, washed red blood cell (RBC), urine, and feces. TC (mg of C/100 μL) in WB, plasma, RBC, urine, and feces were 11.0, 4.37, 7.57, 0.53, and 1.90, respectively. TC in WB, RBC, and feces was higher in men over women, P < 0.05. Mean δ(13)C were ranked low to high as follows: feces < WB = plasma = RBC = urine, P < 0.0001. δ(13)C was not affected by gender. Our analytic method shifted δ(13)C by only ±1.0 ‰ ensuring our F(m) measurements were accurate and precise. Mean F(m) were ranked low to high as follows: plasma = urine < WB = RBC = feces, P < 0.05. F(m) in feces was higher for men over women, P < 0.05. Only in WB, (14)C levels (F(m)) and TC were correlated with one another (r = 0.746, P < 0.01). Considering the lag time to incorporate atmospheric (14)C into plant foods (vegetarian) and or then into animal foods (nonvegetarian), the measured F(m) of WB in our population (recruited April 2009) was 1.0468 ± 0.0022 (mean ± SD), and the F(m) of WB matched the (extrapolated) atmospheric F(m) of 1.0477 in 2008. This study is important in presenting a procedure to determine a baseline for a study group for human ADME and PBPK studies using (14)C as a tracer.     

Analytical characterization of the electrospray ion source in the nanoflow regime

A detailed characterization of a conventional low-flow electrospray ionization (ESI) source for mass spectrometry (MS) using solution compositions typical of reversed-phase liquid chromatography is reported. Contrary to conventional wisdom, the pulsating regime consistently provided better ESI-MS performance than the cone-jet regime for the interface and experimental conditions studied. This observation is supported by additional measurements showing that a conventional heated capillary interface affords more efficient sampling and transmission for the charged aerosol generated by a pulsating electrospray. The pulsating electrospray provided relatively constant MS signal intensities over a wide range of voltages, while the signal decreased slightly with increasing voltage for the cone-jet electrospray. The MS signal also decreased with increasing emitter-interface distance for both pulsating and cone-jet electrosprays due to the expansion of the charged aerosol plume. At flow rates below 100 nL/min, the MS signal increased with increasing flow rate due to increased number of gas-phase ions produced. At flow rates greater than 100 nL/min, the signal reached a plateau due to decreasing ionization efficiency at larger flow rates. These results suggest approaches for improving MS interface performance for low-flow (nano- to micro-) electrosprays.     

Surface alloying of Mg alloys after surface nanocrystallization

Surface nanocrystallization using a surface mechanical attrition treatment effectively activates the surface of magnesium alloys due to the increase in grain boundary diffusion channels. As a result, the temperature of subsequent surface alloying treatment of pure Mg and AZ91 alloy can be reduced from 430 degrees C to 380 degrees C. Thus, it is possible to combine the surface alloying process with the solution treatment for this type of alloy. After surface alloying, the hardness of the alloyed layer is 3 to 4 times higher than that of the substrate and this may significantly improve the wear resistance of magnesium alloys.