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The implementation of automation will enable Advanced Air Mobility (AAM), which could alter the human's responsibilities from those of an active controller to a passive monitor of vehicles. Mature AAM operations will likely rely on both experienced and novice operators to supervise multiple aircraft. As AAM constitutes a complex and increasingly autonomous system, the human operator's set of responsibilities will transition from those of a controller, to a manager, and eventually to an assistant to highly automated systems. The development of AAM will require system designers to characterize these three sets of human responsibilities. The present work proposes different human responsibilities across various roles (i.e., pilot in command, system operator, system assistant) in the context of AAM along with pertinent attention-related constructs that could contribute to each of the three identified roles of AAM operators including situation awareness, workload, complacency, and vigilance.

Pathfinder networks are a method to represent mental models from empirically generated pairwise relatedness ratings. This study examined the effects of training exposure on mental model structures based on relatedness ratings collected using the Target Rating method. Forty-eight participants read instruction slides with or without explicit information on the functionality of an autopilot system (Advanced Mental Model or Basic Mental Model groups, respectively). Participants provided relatedness ratings and completed a comprehension test. The Advanced Mental Model group had more common links with the expected model, higher within-group network similarity scores, and higher mental model assessment questionnaire scores than the Basic Mental Model group. Both groups had coherence scores above the minimum threshold for internal consistency. Pathfinder network analysis was sensitive to changes produced by a simple exposure training intervention. In practice, a simple training program may effectively influence operator mental models in novel technological environments such as Advanced Air Mobility.

Background The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. Methods The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. Results Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). Conclusions This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

PDF file, 87KB, Tissue section stained with hematoxylin and eosin before (left) and after (right) laser microdissection in six representative samples of colorectal cancer. (Part II)

Purpose: Cancer stroma plays an important role in the progression of cancer. Although alterations in miRNA expression have been explored in various kinds of cancers, the expression of miRNAs in cancer stroma has not been explored in detail.Experimental Design: Using a laser microdissection technique, we collected RNA samples specific for epithelium or stroma from 13 colorectal cancer tissues and four normal tissues, and miRNA microarray and gene expression microarray were carried out. The expression status of miRNAs was confirmed by reverse transcriptase PCR. Furthermore, we investigated whether miRNA expression status in stromal tissue could influence the clinicopathologic factors.Results: Oncogenic miRNAs, including two miRNA clusters, miR-17-92a and miR-106b-25 cluster, were upregulated in cancer stromal tissues compared with normal stroma. Gene expression profiles from cDNA microarray analyses of the same stromal tissue samples revealed that putative targets of these miRNA clusters, predicted by Target Scan, such as TGFBR2, SMAD2, and BMP family genes, were significantly downregulated in cancer stromal tissue. Downregulated putative targets were also found to be involved in cytokine interaction and cellular adhesion. Importantly, expression of miR-25 and miR-92a in stromal tissues was associated with a variety of clinicopathologic factors.Conclusions: Oncogenic miRNAs were highly expressed in cancer stroma. Although further validation is required, the finding that stromal miRNA expression levels were associated with clinicopathologic factors suggests the possibility that miRNAs in cancer stroma are crucially involved in cancer progression. Clin Cancer Res; 18(11); 3054–70. ©2012 AACR.

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PDF file, 69KB, Two-dimensional hierarchical cluster analysis of upregulated miRNAs and samples was performed to generate a heatmap. The distance between every pair of miRNAs was calculated as 1.0 - (Pearson's correlation coefficient in expression signal between these two miRNAs). The heatmaps indicate a high (red) or low (green) level of expression. The Ward's linkage algorithm was used for cluster analysis. A: Results of unsupervised hierarchical clustering of four normal and thirteen cancer stromal samples based on expression of miRNAs. Each column represents a sample and each row a probe set.

PDF file, 69KB, Supplementary Table S: Correlation coefficient of array signals in the components of the miR-17-92a and miR-25-106b clusters; Supplementary Table S2; Supplementary Table. S3: Downregulated microRNAs in colorectal cancer stromal tissue compared with normal stromal tissue; Supplementary Table. S4A: Upregulated microRNAs in colorectal cancer stromal tissue compared with cancer epithelial tissue; Supplementary Table. S4B: Downregulated microRNAs in colorectal cancer stromal tissue compared with cancer epithelial tissue.

Supplementary Figures S1-S9 PDF file - 984K, Representative photomicrographs of tissue sections immunostained for PLS3 (S1); The clinical significance of PLS3 expression in a second independent set of 110 primary colorectal cancer samples (S2); PLS3 expression profiles in various tissues, including peripheral blood-derived cells (S3); EMT induction in CaR-1 cells by TGF-beta1 (S4); PLS3 mRNA expression in LoVo cells expressing stem cell makers (S5); Immunocytochemical staining of PLS3 in rectal cancer cell line CaR-1 and peripheral blood mononuclear cells (S6); Validation of PLS3 expression in PB after recurrence (S7); Survival curves of Dukes stage B CRC patients based on the level of CK19/CK20 mRNA expression in PB (S8); PLS3 expression profiles in several cancer cell lines (S9)

Supplementary Tables S1-S2 PDF file - 41K, CRC Patient characteristics in training set (2000-2004) and validation set (2005-2008) (S1); Gene list of GSEA analysis (S2).

Supplementary Figure Legends PDF file - 49K, Legend for Supplementary Figures S1-S9

Circulating tumor cells (CTC) in blood have attracted attention both as potential seeds for metastasis and as biomarkers. However, most CTC detection systems might miss epithelial–mesenchymal transition (EMT)-induced metastatic cells because detection is based on epithelial markers. First, to discover novel markers capable of detecting CTCs in which EMT has not been repressed, microarray analysis of 132 colorectal cancers (CRC) from Japanese patients was conducted, and 2,969 genes were detected that were overexpressed relative to normal colon mucosa. From the detected genes, we selected those that were overexpressed CRC with distant metastasis. Then, we analyzed the CRC metastasis-specific genes (n = 22) to determine whether they were expressed in normal circulation. As a result, PLS3 was discovered as a CTC marker that was expressed in metastatic CRC cells but not in normal circulation. Using fluorescent immunocytochemistry, we validated that PLS3 was expressed in EMT-induced CTC in peripheral blood from patients with CRC with distant metastasis. PLS3-expressing cells were detected in the peripheral blood of approximately one-third of an independent set of 711 Japanese patients with CRC. Multivariate analysis showed that PLS3-positive CTC was independently associated with prognosis in the training set (n = 381) and the validation set [n = 330; HR = 2.17; 95% confidence interval (CI) = 1.38–3.40 and HR = 3.92; 95% CI = 2.27–6.85]. The association between PLS3-positive CTC and prognosis was particularly strong in patients with Dukes B (HR = 4.07; 95% CI = 1.50–11.57) and Dukes C (HR = 2.57; 95% CI = 1.42–4.63). PLS3 is a novel marker for metastatic CRC cells, and it possesses significant prognostic value. Cancer Res; 73(7); 2059–69. ©2012 AACR.

A model that introduces surface tension as a pressure boundary condition, named the surface tension as pressure (STP) model, was developed for free surface flow analyses by the moving particle simulation (MPS) method. The STP model assigns to surface particles the liquid pressure of Laplace’s formula. The model is an alternative to previous models that apply surface tension as volume force such as the continuum surface force model. Problems that appeared when using the volume force models, such as the dependencies of calculation results on particle resolution and pressure gradient accuracy, were solved by using the STP model. Calculations predicted the theoretical values of the internal pressure of a 3D spherical droplet and the oscillation period of a 2D elliptic droplet over a wide range of surface tension coefficients and droplet sizes with errors less than 10%. Since the STP model is easy to implement, does not increase computation cost from previous models, and does not require surface reconstruction or additional marker particles, the model is suitable for practical and large-scale free surface flow problems that involve violent deformation of the liquid surface such as liquid atomization.

In this study, several nanometer-thick transition metal overlayers (M) were formed on an Fe–Cr–Al metal (SUS) foil by pulsed cathodic arc-plasma deposition. The thin-film materials prepared, exhibiting a full-coverage M overlayer (M/SUS), were applied as catalysts for NH3 oxidation in the presence of excess O2 (300 ppm NH3, 8% O2, and He balance). Under dry conditions (0% H2O in the gas feed), the observed NH3 oxidation activity decreased in the order of Ir > Pt > Co > Pd > Cu > Rh when the product selectivity was not taken into consideration. The activities of the materials composed of Co and Cu decreased significantly in the presence of 10% H2O, while those of the catalysts containing Pt and Ir remained nearly unchanged. Based on the kinetic analyses and X-ray photoelectron spectrometry experiments conducted, it was determined that the contrasting effect of H2O on the activity of M/SUS was related to the ease of oxidation of the non-precious metals studied. The resulting hydrophilic oxide surface was more susceptible to the competitive adsorption of H2O and thus inhibited the NH3 reaction than a metallic surface. The negative effect of H2O was evident by the decrease in the NH3 concentration in the gas feed. Notably, the metallic surface of the Pt overlayer was stable even under oxidizing reaction conditions; therefore, the oxidation of NH3 was less susceptible to the effects of high H2O concentrations.

Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is the most widely used method for analyzing genome-wide DNA-protein interactions. Because there is considerable variation in the modes and strengths of DNA-protein interactions, chromatin immunoprecipitation (ChIP) protocols have been diversified and optimized for different needs. Here, we describe protocols for detecting histone modifications and modifiers using various crosslinking and immunoprecipitation conditions. We provide a complete ChIP-seq workflow covering sample preparation, immunoprecipitation, next-generation sequencing (NGS) library preparation, and data analyses.

The CCAAT motif-binding factor NF-Y consists of three different subunits, NF-YA, NF-YB, and NF-YC. Although it is suggested that NF-Y activity is essential for normal tissue homeostasis, survival, and metabolic function, its precise role in lipid metabolism is not clarified yet. In Drosophila, eye disc specific knockdown of Drosophila NF-YA (dNF-YA) induced aberrant morphology of the compound eye, the rough eye phenotype in adults and mutation of the lipase 4 (lip4) gene suppressed the rough eye phenotype. RNA-seq analyses with dNF-YA knockdown third instar larvae identified the lip4 gene as one of the genes that are up-regulated by the dNF-YA knockdown. We identified three dNF-Y-binding consensuses in the 5'flanking region of the lip4 gene, and a chromatin immunoprecipitation assay with the specific anti-dNF-YA IgG demonstrated dNF-Y binding to this genomic region. The luciferase transient expression assay with cultured Drosophila S2 cells and the lip4 promoter-luciferase fusion genes with and without mutations in the dNF-Y-binding consensuses showed that each of the three dNF-Y consensus sequences negatively regulated lip4 gene promoter activity. Consistent with these results, qRT-PCR analysis with the dNF-YA knockdown third instar larvae revealed that endogenous lip4 mRNA levels were increased by the knockdown of dNF-YA in vivo. The specific knockdown of dNF-YA in the fat body with the collagen-GAL4 driver resulted in smaller oil droplets in the fat body cells. Collectively, these results suggest that dNF-Y is involved in lipid storage through its negative regulation of lip4 gene transcription.