Model Checking with Program Slicing Based on Variable Dependence Graphs

In embedded control systems, the potential risks of software defects have been increasing because of software complexity which leads to, for example, timing related problems. These defects are rarely found by tests or simulations. To detect such defects, we propose a modeling method which can generate software models for model checking with a program slicing technique based on a variable dependence graph. We have applied the proposed method to one case in automotive control software and demonstrated the effectiveness of the method. Furthermore, we developed a software tool to automate model generation and achieved a 35% decrease in total verification time on model checking.Comment: In Proceedings FTSCS 2012, arXiv:1212.657

Reduction of formaldehyde emission from plywood using composite resin composed of resorcinol–formaldehyde and urea-modified scallop shell nanoparticles

More than 200,000 tons of scallop shells are disposed annually 1 alone in Japan. Nanoparticles derived from scallop shells have the potential to adsorb gaseous formaldehyde; therefore such discarded shells have now been tested as additive filler in plywood adhesive by mixing high specific surface area, urea-modified shell nanoparticles with a resorcinol?formaldehyde resin; with this procedure it was found that the emission of formaldehyde from the resulting plywood could be substantially reduced. The urea-modified scallop shell nanoparticles were prepared by two different methods: (i) by a dry method in which the shells were treated with planetary ball-grinding under ambient conditions ? a completely dried powder was obtained after addition of the surface-modifying urea solution; (ii) by a moist method by treating dry-ground shell particles in a wet grinding process with the urea solution, followed by the use of centrifugation to obtain a paste. The specific surface area of the nanoparticles obtained by both treatments was 42 ± 3 m213 /g. Measurement of the subsequent formaldehyde emission showed that the addition of the modified scallop shell nanoparticles substantially reduced the formaldehyde emission from plywood; the reduction depends from the specific mass uptake of urea on the nanoparticles which especially was the case when resins containing nanoparticles processed by the moist method were used

A proximity biotinylation-based approach to identify protein-E3 ligase interactions induced by PROTACs and molecular glues

Proteolysis-targeting chimaeras (PROTACs) as well as molecular glues such as immunomodulatory drugs (IMiDs) and indisulam are drugs that induce interactions between substrate proteins and an E3 ubiquitin ligases for targeted protein degradation. Here, we develop a workflow based on proximity-dependent biotinylation by AirID to identify drug-induced neo-substrates of the E3 ligase cereblon (CRBN). Using AirID-CRBN, we detect IMiD-dependent biotinylation of CRBN neo-substrates in vitro and identify biotinylated peptides of well-known neo-substrates by mass spectrometry with high specificity and selectivity. Additional analyses reveal ZMYM2 and ZMYM2-FGFR1 fusion protein—responsible for the 8p11 syndrome involved in acute myeloid leukaemia—as CRBN neo-substrates. Furthermore, AirID-DCAF15 and AirID-CRBN biotinylate neo-substrates targeted by indisulam and PROTACs, respectively, suggesting that this approach has the potential to serve as a general strategy for characterizing drug-inducible protein–protein interactions in cells

PHOSPHATEMIC INDEX EVALUATES PHOSPHORUS LOAD

Objective: Dietary phosphorus (P) restriction is crucial to treat hyperphosphatemia and reduce cardiovascular disease risk and mortality in patients with chronic kidney disease (CKD) and the wider population. Various methods for dietary P restriction exist, but the bioavailability of P in food should also be considered when making appropriate food choices to maintain patients’ quality of life. Here, we propose the ‘‘Phosphatemic Index’’ (PI) as a novel tool for evaluating dietary P load based on P bioavailability; we also evaluated the effect of continuous intake of different PI foods in mixed meals on serum intact fibroblast growth factor 23 concentration. Design and Methods: A 2-stage crossover study was conducted: Study 1: 20 healthy participants consumed 10 different foods containing 200 mg of P, and the PI was calculated from the area under the curve of a time versus serum P concentration curve; Study 2: 10 healthy participants consumed 4 different test meals (low, medium, or high PI meals or a control) over a 5-day period. Results: Study 1 showed milk and dairy products had high PI values, pork and ham had medium PI values, and soy and tofu had low PI values. In Study 2, ingestion of high PI test meals showed higher fasting serum intact fibroblast growth factor 23 levels and lower serum 1,25-dihydroxyvitamin D levels compared with ingestion of low PI test meals. Conclusion: These findings suggest that the PI can usefully evaluate the dietary P load of various foods and may help to make appropriate food choices for dietary P restriction in CKD patients

Modeling Retinal Degeneration Using Patient-Specific Induced Pluripotent Stem Cells

Retinitis pigmentosa (RP) is the most common inherited human eye disease resulting in night blindness and visual defects. It is well known that the disease is caused by rod photoreceptor degeneration; however, it remains incurable, due to the unavailability of disease-specific human photoreceptor cells for use in mechanistic studies and drug screening. We obtained fibroblast cells from five RP patients with distinct mutations in the RP1, RP9, PRPH2 or RHO gene, and generated patient-specific induced pluripotent stem (iPS) cells by ectopic expression of four key reprogramming factors. We differentiated the iPS cells into rod photoreceptor cells, which had been lost in the patients, and found that they exhibited suitable immunocytochemical features and electrophysiological properties. Interestingly, the number of the patient-derived rod cells with distinct mutations decreased in vitro; cells derived from patients with a specific mutation expressed markers for oxidation or endoplasmic reticulum stress, and exhibited different responses to vitamin E than had been observed in clinical trials. Overall, patient-derived rod cells recapitulated the disease phenotype and expressed markers of cellular stresses. Our results demonstrate that the use of patient-derived iPS cells will help to elucidate the pathogenic mechanisms caused by genetic mutations in RP

Multicolor and multi-spot observations of Starlink's Visorsat

This study provides the results of simultaneous multicolor observations for the first Visorsat (STARLINK-1436) and the ordinary Starlink satellite, STARLINK-1113 in the $U$, $B$, $V$, $g'$, $r$, $i$, $R_{\rm C}$, $I_{\rm C}$, $z$, $J$, $H$, and $K_s$ bands to quantitatively investigate the extent to which Visorsat reduces its reflected light. Our results are as follows: (1) in most cases, Virorsat is fainter than STARLINK-1113, and the sunshade on Visorsat, therefore, contributes to the reduction of the reflected sunlight; (2) the magnitude at 550 km altitude (normalized magnitude) of both satellites often reaches the naked-eye limiting magnitude ($<$ 6.0); (3) from a blackbody radiation model of the reflected flux, the peak of the reflected components of both satellites is around the $z$ band; and (4) the albedo of the near infrared range is larger than that of the optical range. Under the assumption that Visorsat and STARLINK-1113 have the same reflectivity, we estimate the covering factor, $C_{\rm f}$, of the sunshade on Visorsat, using the blackbody radiation model: the covering factor ranges from $0.18 \leq C_{\rm f} \leq 0.92$. From the multivariable analysis of the solar phase angle (Sun-target-observer), the normalized magnitude, and the covering factor, the phase angle versus covering factor distribution presents a moderate anti-correlation between them, suggesting that the magnitudes of Visorsat depend not only on the phase angle but also on the orientation of the sunshade along our line of sight. However, the impact on astronomical observations from Visorsat-designed satellites remains serious. Thus, new countermeasures are necessary for the Starlink satellites to further reduce reflected sunlight.Comment: 31 pages, 9 figures, published in PAS

Optical transmittance investigation of 1-keV ion-irradiated sapphire crystals as potential VUV to NIR window materials of fusion reactors

We investigate the optical transmittances of ion-irradiated sapphire crystals as potential vacuum ultraviolet (VUV) to near-infrared (NIR) window materials of fusion reactors. Under potential conditions in fusion reactors, sapphire crystals are irradiated with hydrogen (H), deuterium (D), and helium (He) ions with 1-keV energy and ∼ 1020-m-2 s-1 flux. Ion irradiation decreases the transmittances from 140 to 260 nm but hardly affects the transmittances from 300 to 1500 nm. H-ion and D-ion irradiation causes optical absorptions near 210 and 260 nm associated with an F-center and an F+-center, respectively. These F-type centers are classified as Schottky defects that can be removed through annealing above 1000 K. In contrast, He-ion irradiation does not cause optical absorptions above 200 nm because He-ions cannot be incorporated in the crystal lattice due to the large ionic radius of He-ions. Moreover, the significant decrease in transmittance of the ion-irradiated sapphire crystals from 140 to 180 nm is related to the light scattering on the crystal surface. Similar to diamond polishing, ion irradiation modifies the crystal surface thereby affecting the optical properties especially at shorter wavelengths. Although the transmittances in the VUV wavelengths decrease after ion irradiation, the transmittances can be improved through annealing above 1000 K. With an optical transmittance in the VUV region that can recover through simple annealing and with a high transparency from the ultraviolet (UV) to the NIR region, sapphire crystals can therefore be used as good optical windows inside modern fusion power reactors in terms of light particle loadings of hydrogen isotopes and helium.Iwano K., Yamanoi K., Iwasa Y., et al. Optical transmittance investigation of 1-keV ion-irradiated sapphire crystals as potential VUV to NIR window materials of fusion reactors. AIP Advances 6, 105108 (2016); https://doi.org/10.1063/1.4965927