Mitsubishi Space Software (Japan)

Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

Precision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing‐based panel tests, including 160 cancer‐related genes (PleSSision‐160), on 88 malignant ovarian tumors (high‐grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. Actionable BRCA1 and BRCA2 variants were found in 4.5% of each of the cases. ERBB2 amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high‐grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high‐grade serous carcinoma (P < .005) than in other histologic subtypes; some clear cell carcinoma showed high copy number alterations that were correlated with advanced stage (P < .05) and worse survival (P < .01). A high count of copy number alteration was associated with worse survival in all malignant ovarian tumors (P < .05). Our study shows that targeted agents can be detected in approximately 40% of malignant ovarian tumors via multigene panel testing, and copy number alteration count can be a useful marker to help assess risks in malignant ovarian tumor patients.

This paper presents the revised domain engineering process to develop product lines of automotive body parts in Aisin Seiki Co., Ltd. In the process, feature analysis is conducted by a limited number of engineers with talent of abstraction and separation and other work including specifications and architecture design is conducted by average engineers who know the products. Feature analysis defines a hierarchy of abstraction, achieves separation of concerns, and disciplines other artifacts to follow the structure of abstraction and separation. Requirements and specifications are refined by the use case, use case scenario, and hierarchical tabular description (USDM) in a step-wise manner. The specification in USDM is refined to a system decomposition in a quantitative and accountable manner using the robustness diagram and design structure matrix. The revised domain engineering process reduced the issues pointed out in software reviews concerning errors on specifications and architecture design. Moreover, it reduced lead time for architecture design and produced the architecture tolerant to changes.

Outputs from ocean general circulation models driven by different wind data sets, i.e., from satellite measurements (QSCAT) and numerical reanalysis (NCEP/NCAR), are used to examine the dependence of oceanic internal structures in simulated fields on the surface wind input. Comparison between the two simulated fields reveals large differences in the subsurface layers corresponding to the thermocline depth near 100 m along 10°N in the western tropical North Pacific Ocean. These differences, characterized by a 50-m shallower thermocline in this region when simulated using NCEP winds than when simulated using QSCAT, produce discrepancies in the surface current fields of the tropical gyre. Simulated fields are compared to observational ones, including gridded Argo products, sea surface heights from satellite altimetry, and hydrographic measurements along 137°E. Results show that fields simulated using the QSCAT winds are consistent with observed ones in our study area, while those simulated using the NCEP winds exhibit significant differences from the observed fields. A reliable wind product is key to simulating realistic fields at the ocean surface and in the subsurface. Further, the results obtained using a reliable wind product suggest that the Sverdrup relation is applicable to the tropical North Pacific.

A laser microphone that uses the self-coupling effect of a semiconductor laser is an optical microphone. It has excellent characteristics, such as a wide and flat frequency characteristic. However, as a laser microphone has a large noise component in its output, the signal-to-noise ratio is low. Therefore, the sensitivity of a laser microphone is not sufficiently high for practical use. In this work, two methods to improve the sensitivity of a laser microphone are proposed. The first method uses a sound collector that collects widespread sound waves on a laser beam. The second method uses a right-angle prism that extends the light path. By using a sound collector, the sensitivity can increase up to nine times and the signal-to-noise ratio increases up to six times. However, the sensitivity decreases for frequencies below 10 kHz, and the directivity has a sharp peak. By using a right-angle prism, the sensitivity increases up to three times and the signal-to-noise ratio increases up to six times. In addition, the sensitivity can be improved while maintaining the wide and flat frequency characteristics and the wide directivity.

e13115 Background: The development of clinical sequence systems in hospitals is a critical issue in Japan, especially for medical oncology, as multiplex gene profiling enables precision medicine for cancer. We have launched an in-house clinical sequencing system,“CLHURC” to perform exhaustive targeted exome sequencing for patients with all types of cancer, as an outpatient service. We have analyzed the clinical utility of this system. Methods: Genomic DNA was extracted from tumor tissues and peripheral blood sera of 81 patients with different stages of cancer, during April-December 2016. The top five types of primary cancer were pancreas (16%), colorectal (16%), breast (10%), stomach (9%), and lung (6%). We performed a targeted amplicon exome sequencing for 160 cancer-related genes. The sequencing data was analyzed using an original bioinformatics pipeline within three days, and we identified cancer-specific somatic gene alterations such as SNV (Single Nucleotide Variation), Ins (Insertion)/Del (Deletion), and CNV (Copy Number Variation). The primary endpoints were the detection rates of potential actionable and druggable genes. The secondary endpoints were the detection rates of incidental germline variants and the period from initial visit to elucidation of the results to the patients. Results: Actionable and druggable gene alterations were detected in 90% (73/81) and 51% (41/81) of the subjects, respectively. Druggable gene alterations were frequently detected in BRCA1/2 (11/41), PIK3CA (9/41), AKT1/2 (6/41), TSC1 (5/41), and PTEN (5/41). Surprisingly, incidental germline variants were detected in 31% (25/81) of the patients, and were found in BRCA1/2 (5/25), APC (5/25), and TSC1(3/25), among others. The median period of examination was 21 days (10-66 days). Twelve out of the 81 patients (15%) were treated with therapeutic agents, based on the results of our clinical sequencing. Conclusions: We have established a robust in-house clinical sequencing system, “CLHURC,” and have initiated the development of precision medicine for cancer in Japan. Our novel clinical sequencing system could improve individualized medicine against cancer throughout Japan and Asia.

In a conventional microphone, the diaphragm limits the detectable sound frequency range. To overcome this limitation, a laser microphone was developed using the self-coupling effect of a semiconductor laser. In this paper, the supersonic band characteristics of the laser microphone were investigated using a super tweeter. From the experiment results, it was observed that the optimum reflectivity of a reflector is almost 25% when the laser power is 25 mW. Moreover, a flat frequency response is achieved between 40 Hz and 150 kHz when the long diameter of the laser beam is 1.0 mm, and the upper limit of the detectable frequency relates to the long diameter of the laser beam.

Scattering component decomposition techniques for POLSAR data are powerful tool for the POLSAR data analysis. The three component decomposition technique is the one of the major technique among them. However, the algorithm requires several assumptions to solve the problem because of the lack of independent observables. To overcome this difficulty, we have proposed the multi-baseline POLSAR scattering component decomposition technique which utilizes the concept of the MUSIC algorithm with spatial smoothing preprocessing (SSP) scheme. However resolution performance depends on the decorrelation performance by the SSP. In this report, we propose several enhanced schemes for the SSP, and show some experimental results to show their performance.

The Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E) had been operated in special slow rotation mode to obtain continuous brightness temperatures for the inter-comparison with those of AMSR2 on the Global Change Observation Mission-Water (GCOM-W) for three years. Although its observation coverage is sparse and some calibration uncertainties exist, the data are still very useful for straightforward inter-comparison.