The Recruitment Model of Metabolic Evolution: Jasmonate-Responsive Transcription Factors and a Conceptual Model for the Evolution of Metabolic Pathways

Plants produce a vast array of structurally diverse specialized metabolites with various biological activities, including medicinal alkaloids and terpenoids, from relatively simple precursors through a series of enzymatic steps. Massive metabolic flow through these pathways usually depends on the transcriptional coordination of a large set of metabolic, transport, and regulatory genes known as a regulon. The coexpression of genes involved in certain metabolic pathways in a wide range of developmental and environmental contexts has been investigated through transcriptomic analysis, which has been successfully exploited to mine the genes involved in various metabolic processes. Transcription factors are DNA-binding proteins that recognize relatively short sequences known as cis-regulatory elements residing in the promoter regions of target genes. Transcription factors have positive or negative effects on gene transcription mediated by RNA polymerase II. Evolutionarily conserved transcription factors of the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) and basic helix-loop-helix (bHLH) families have been identified as jasmonate (JA)-responsive transcriptional regulators of unrelated specialized pathways in distinct plant lineages. Here, I review the current knowledge and propose a conceptual model for the evolution of metabolic pathways, termed “recruitment model of metabolic evolution.” According to this model, structural genes are repeatedly recruited into regulons under the control of conserved transcription factors through the generation of cognate cis-regulatory elements in the promoters of these genes. This leads to the adjustment of catalytic activities that improve metabolic flow through newly established passages

Neural network-based virtual microphone estimation with virtual microphone and beamformer-level multi-task loss

Array processing performance depends on the number of microphones available. Virtual microphone estimation (VME) has been proposed to increase the number of microphone signals artificially. Neural network-based VME (NN-VME) trains an NN with a VM-level loss to predict a signal at a microphone location that is available during training but not at inference. However, this training objective may not be optimal for a specific array processing back-end, such as beamforming. An alternative approach is to use a training objective considering the array-processing back-end, such as a loss on the beamformer output. This approach may generate signals optimal for beamforming but not physically grounded. To combine the advantages of both approaches, this paper proposes a multi-task loss for NN-VME that combines both VM-level and beamformer-level losses. We evaluate the proposed multi-task NN-VME on multi-talker underdetermined conditions and show that it achieves a 33.1 % relative WER improvement compared to using only real microphones and 10.8 % compared to using a prior NN-VME approach.Comment: 5 pages, 2 figures, 1 tabl

一人の保健師が地域包括支援センターの保健師として 職業的アイデンティティを形成するまでのプロセス －複線径路等至性モデリング（TEM）による分析－

目的： 複線径路等至性モデリング（TEM）の手法を用いて，地域包括支援センターの保健師が職業的アイデンティティ（以下，職業的ID）を形成していくプロセスを分析する．方法： 地域包括支援センターの保健師A 氏に半構造化面接を2 回実施した．逐語録化した音声データを切片化し，職業的ID の形成に関連すると考えられる事象を時系列に配置し，経験の径路を可視化した図（TEM 図）を作成し，そのプロセスを分析した．結果： A 氏の径路は，「保健師を夢見て仲間と歩んだ学修期」，「疑問と失意の新人期」，「看護師としての再生期」，「保健師としての覚醒期」，「地域包括保健師としての発展期」の5 つの時期に区分された．産業保健師に挫折したA 氏は地域包括支援センターで地域の人々の実態に触れ，その体感を関係機関や他職種と共有しながら意欲的に活動を積み重ね，成長を遂げていた．考察： A 氏は社会福祉士としての確固たる信念を持つ「師匠」の下で「保健師とは何か」を自問しながら活動を重ねた. これにより，実体験に裏打ちされた確固たる職業的ID を形成していったと考えられる．結論： A 氏の径路から保健と福祉の視点を併せ持った地域包括保健師の独自の職業的ID が示された

Intraoperative diagnosis of lymph node metastasis during segmentectomy for non-small cell lung cancer by rapid immunohistochemistry using noncontact alternating current electric field mixing

Background: Although lobectomy is considered the standard surgery for any non-small cell lung cancer (NSCLC), recent evidence indicates that for early NSCLCs segmentectomy may be equally effective. For segmentectomy to be oncologically safe, however, adequate intraoperative lymph node staging is essential. The aim of this study was to compare the results of a new rapid-IHC system to the HE analysis for intraoperative nodal diagnosis in lung cancer patients considered for segmentectomy. Methods: This retrospective study analyzed the pathological reports from NSCLC resections over a six-year period between 2014 and 2020. Using a new device for rapid-IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the antipancytokeratin antibody as the voltage is switched on/off. Rapid-IHC can provide a nodal diagnosis within 20 minutes. Results: Frozen sections from 106 resected lymph nodes from 70 patients were intraoperatively evaluated for metastasis. Of those, five nodes were deemed positive based on both HE staining and rapid-IHC. In addition, rapid-IHC alone detected isolated tumor cells in one hilar lymph node. Three cStage IA patients with nodal metastasis detected with HE staining and rapid-IHC received complete lobectomies. Five-year relapse-free survival and overall survival among patients receiving segmentectomy with rapid-IHC were 88.77% and 88.79%, respectively. Conclusions: Rapid-IHC driven by AC mixing is simple, highly accurate, and preserves nodal tissue for subsequent tests. This system can be used effectively for intraoperative nodal diagnosis. Rapid immunohistochemistry based on alternating-current field mixing (completed within 20 minutes) is simple and highly accurate. This system will assist clinicians when making intraoperative diagnoses of lymph node metastasis and deciding upon the appropriate surgical procedure in segmentectomy for lung cancer

Harmonization across programmed death ligand 1 (PD-L1) assays for lung cancer by immunohistochemistry using noncontact alternating current electric field mixing

Background Immune checkpoint inhibitors (ICIs) are a promising advance in the treatment of patients with lung cancer. However, each ICI has been tested with an independently designed companion diagnostic assay that is based on a unique antibody. Consequently, the different trial-validated programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays should not be considered interchangeable. Our aim was to compare the performance of each available PD-L1 antibody for its ability to accurately measure PD-L1 expression and to investigate the possibility of harmonization across antibodies through the use of a new rapid IHC system, which uses noncontact alternating current (AC) mixing to achieve more stable staining. Methods First, 58 resected non-small cell lung cancer (NSCLC) specimens were stained using three PD-L1 IHC assays (28-8, SP142, and SP263) to assess the harmonization achieved with AC mixing IHC. Second, specimens from 27 patients receiving ICIs for postoperative recurrent NSCLC were stained using the same IHC method to compare the clinical performance of ICIs to PD-L1 scores. All patients received a tumor proportion score (TPS) with the 22C3 companion diagnostic test. Results Better staining was achieved with the new AC mixing IHC method than the conventional IHC in PD-L1-positive cases, and the interchangeability of some combinations of assays was increased in PD-L1-positive. In addition, AC mixing IHC provided more appropriate overall response rates for ICIs in all assays. Conclusions Stable PD-L1 IHC driven by AC mixing helped to improve TPS scoring and patient selection for ICIs through interchangeable assays

Candidate Brown-dwarf Microlensing Events with Very Short Timescales and Small Angular Einstein Radii

Short-timescale microlensing events are likely to be produced by substellar brown dwarfs (BDs), but it is difficult to securely identify BD lenses based on only event timescales t_E because short-timescale events can also be produced by stellar lenses with high relative lens-source proper motions. In this paper, we report three strong candidate BD-lens events found from the search for lensing events not only with short timescales (t_E ≲ 6 days) but also with very small angular Einstein radii (θ_E ≲ 0.05 mas) among the events that have been found in the 2016–2019 observing seasons. These events include MOA-2017-BLG-147, MOA-2017-BLG-241, and MOA-2019-BLG-256, in which the first two events are produced by single lenses and the last event is produced by a binary lens. From the Monte Carlo simulations of Galactic events conducted with the combined t_E and θ_E constraint, it is estimated that the lens masses of the individual events are 0.051^(+0.100)_(−0.027) M⊙, 0.044^(+0.090)_(−0.023) M⊙, and 0.046^(+0.067)_(−0.023) M⊙/0.038^(+0.056)_(−0.019) M⊙ and the probability of the lens mass smaller than the lower limit of stars is ~80% for all events. We point out that routine lens mass measurements of short-timescale lensing events require survey-mode space-based observations

A Gas Giant Planet in the OGLE-2006-BLG-284L Stellar Binary System

We present the analysis of microlensing event OGLE-2006-BLG-284, which has a lens system that consists of two stars and a gas giant planet with a mass ratio of $q_p = (1.26\pm 0.19) \times 10^{-3}$ to the primary. The mass ratio of the two stars is $q_s = 0.289\pm 0.011$, and their projected separation is $s_s = 2.1\pm 0.7\,$AU, while the projected separation of the planet from the primary is $s_p = 2.2\pm 0.8\,$AU. For this lens system to have stable orbits, the three-dimensional separation of either the primary and secondary stars or the planet and primary star must be much larger than that these projected separations. Since we do not know which is the case, the system could include either a circumbinary or a circumstellar planet. Because there is no measurement of the microlensing parallax effect or lens system brightness, we can only make a rough Bayesian estimate of the lens system masses and brightness. We find host star and planet masses of $M_{L1} = 0.35^{+0.30}_{-0.20}\,M_\odot$, $M_{L2} = 0.10^{+0.09}_{-0.06}\,M_\odot$, and $m_p = 144^{+126}_{-82}\,M_\oplus$, and the $K$-band magnitude of the combined brightness of the host stars is $K_L = 19.7^{+0.7}_{-1.0}$. The separation between the lens and source system will be $\sim 90\,$mas in mid-2020, so it should be possible to detect the host system with follow-up adaptive optics or Hubble Space Telescope observations

A Gas Giant Planet in the OGLE-2006-BLG-284L Stellar Binary System

We present the analysis of microlensing event OGLE-2006-BLG-284, which has a lens system that consists of two stars and a gas giant planet with a mass ratio of q_p = (1.26 ± 0.19) × 10⁻³ to the primary. The mass ratio of the two stars is q_s = 0.289 ± 0.011, and their projected separation is s_s = 2.1 ± 0.7 au, while the projected separation of the planet from the primary is s_p = 2.2 ± 0.8 au. For this lens system to have stable orbits, the three-dimensional separation of either the primary and secondary stars or the planet and primary star must be much larger than the projected separations. Since we do not know which is the case, the system could include either a circumbinary or a circumstellar planet. Because there is no measurement of the microlensing parallax effect or lens system brightness, we can only make a rough Bayesian estimate of the lens system masses and brightness. We find host star and planet masses of, M_(L1) = 0.35^(+0.30)_(−0.20) M⊙, M_(L2) = 0.10^(+0.09)_(−0.06) M⊙, and m_p = 144^(+126)_(−82) M⊕, and the K-band magnitude of the combined brightness of the host stars is K_L = 19.7^(+0.7)_(−1.0). The separation between the lens and source system will be ~90 mas in mid-2020, so it should be possible to detect the host system with follow-up adaptive optics or Hubble Space Telescope observations