This article reports the measurement of the neutron background flux accidentally induced by the neutrino beam at the J-PARC facility in Japan. In particular, neutrino-nucleus neutral-current quasi-elastic (NCQE) scattering events, ν(ν̄)+N→ν(ν̄)+N′, can be obscured by a massive background of neutron-nucleus scattering events. The neutrons are produced within the materials (such as sand and concrete) located between the beam dump and the experimental area where the detectors are placed. We measured the accidental neutron events at the J-PARC neutrino facility using BGO and liquid scintillation detectors, with a plastic scintillation detector serving as an active veto counter. Based on a neutrino-mode data set of 2.972×1020 POT, we observed 88 neutron-induced recoil proton events within an electron-equivalent recoil energy range of 0.98–11.60 MeVee, selected via pulse-shape discrimination in the liquid scintillation detector. Accounting for the detection efficiency and resolution, and through comparison with simulations, the neutron flux was determined to be[1.45−0.24+0.22(stat.)±0.55(sys.)]×10−7cm−2s−1POT−1, assuming an exponential neutron energy spectrum. This result will contribute to the evaluation of neutron backgrounds for neutrino experiments at the J-PARC facility.
This study examined whether counterarguments generated by large language models (LLMs) influence the moral judgments of younger and older adults, and whether these effects vary by dilemma type, cognitive functioning, trust in AI, and prior LLM experience. Using the switch and footbridge trolley dilemmas, 130 participants (56 younger adults and 74 older adults) were presented with ChatGPT-generated counterarguments that opposed their initial judgments. More than 30% of participants reversed their judgments in both dilemmas (32.31% in the switch dilemma and 36.92% in the footbridge dilemma). Older adults tended to be more likely than younger adults to reverse their judgments and showed a significantly greater degree of judgment change in the switch dilemma. In the emotionally aversive footbridge dilemma, older adults with lower cognitive functioning were significantly more likely to align with the LLM-generated counterargument. General trust in AI and prior LLM experience did not predict judgment reversal, whereas lower initial confidence and higher perceived task difficulty were associated with greater susceptibility to LLM influence. These findings suggest that LLMs may support cognitive offloading but increase susceptibility among individuals with limited cognitive resources. The ecological generalizability of these findings to everyday dilemma situations remains to be examined in future research.
Stress-related experiences alter glutamatergic signaling and neuronal excitability, but the mechanisms that couple experience to dentate granule cell function remain incompletely understood. Here, we examined how protein kinase N1a (PKN1a), a protein kinase C-like serine/threonine kinase, and repeated swim exposure regulate mouse hippocampal dentate granule cell excitability, with a focus on the neuronal glutamate transporter excitatory amino acid transporter 3 (EAAT3) and group I metabotropic glutamate receptors (mGluRs). Five days of repeated swim exposure increased spike firing in mature dentate granule cells from wild-type mice. PKN1a knockout produced a similar increase, and repeated swim did not further enhance firing in knockout mice. The enhanced firing observed after repeated swim exposure and in PKN1a knockout mice was reduced by co-application of an mGluR1 antagonist (LY367385) and an mGluR5 antagonist (MPEP). Inhibition of glutamate transporters with DL-TBOA increased granule cell firing in control wild-type mice but did not further increase firing in repeated-swim wild-type or PKN1a knockout mice, suggesting occlusion of transporter-dependent regulation of excitability. Repeated swim exposure and PKN1a knockout also reduced total and surface expression of EAAT3 in the hippocampus, whereas expression of the glial glutamate transporter EAAT2 was not significantly altered. Finally, PKN1a knockout and repeated swim exposure reduced anxiety-related behavior in the elevated plus maze test. Thus, PKN1a-dependent regulation of EAAT3 may restrain group I mGluR-dependent excitability in dentate granule cells, whereas repeated swim exposure and PKN1a knockout shift this system toward a lower-EAAT3, higher-excitability state accompanied by reduced anxiety-related behavior.
Engineering of nonribosomal peptide synthetases (NRPSs) is frequently limited by loss of biosynthetic productivity following domain recombination, particularly within the initiation module, where interdomain compatibility plays a critical yet underexplored role. Although substrate selectivity can often be reprogrammed by replacing the starter condensation (Cs) domain, such modifications are typically accompanied by severe reductions in productivity, imposing a major bottleneck in NRPS engineering. To produce long-chain surfactin homologs, we replaced the native Cs domain of the surfactin synthetase SrfAA with a homologous Cs domain from a long-chain lipopeptide-producing NRPS. This enabled incorporation of long-chain fatty acyl substrates but resulted in a substantial decrease in production titer. Systematic analyses suggested that this productivity loss is primarily associated with suboptimal interdomain compatibility within the engineered initiation module rather than intrinsic deficiencies of the substituted Cs domain. By combining targeted mutagenesis of the Cs domain with interdomain engineering and fine-tuning of the carrier (T1) domain, we achieved recovery of production through combinatorial optimization. Notably, improved productivity was largely achieved without altering acyl-chain specificity, supporting the view that catalytic efficiency can be enhanced independently of substrate selection. These findings suggest that productive reprogramming of NRPS initiation modules requires coordinated optimization of both domain-specific properties and interdomain compatibility.
Human brain organoids (HBOs) are three-dimensional structures derived from human stem cells that model aspects of brain development and function, offering potentially unprecedented opportunities for studying neurological disorders and for developing treatments. This consensus paper presents recommendations from the Asia Pacific Neuroethics Working Group, developed through interdisciplinary collaboration among scientists, bioethicists, philosophers, and legal scholars who convened in Singapore in November 2024. We provide a comprehensive analysis of the ethical, legal, and sociocultural dimensions of HBO research, addressing both current realities and future possibilities. The paper examines key ethical considerations, including the potential moral status of HBOs, particularly regarding sentience and consciousness, while identifying and dispelling common misconceptions and “ethical red herrings” arising from sensationalized portrayals. We analyze consent frameworks for cell donation, privacy concerns, dual-use risks, and questions of distributive justice. Legal challenges are explored, including the categorical ambiguity of HBOs within existing regulatory frameworks, intellectual property issues, and cross-border inconsistencies in standards. Sociocultural perspectives emphasize the importance of public understanding, cross-cultural engagement, and empirical research on diverse community attitudes toward HBO research. In our recommendations, we advocate for evidence-based ethical discussions, anticipatory frameworks addressing potential future developments, contextualized analysis comparing HBOs to related experimental models, robust informed consent processes, proportionate responses to consciousness concerns, development of adaptive regulatory frameworks, responsible science communication to manage public expectations, and sustained interdisciplinary collaboration. We emphasize a balanced approach that promotes scientific innovation while maintaining rigorous ethical oversight, recognizing HBOs’ significant potential for advancing neuroscience and medicine. This represents the first comprehensive ethical framework for HBO research from the Asia Pacific region, helping to establish foundational principles for responsible development of this rapidly advancing field.
