The full repertoire of Drosophila gustatory receptors for detecting an aversive compound.

The ability to detect toxic compounds in foods is essential for animal survival. However, the minimal subunit composition of gustatory receptors required for sensing aversive chemicals in Drosophila is unknown. Here we report that three gustatory receptors, GR8a, GR66a and GR98b function together in the detection of L-canavanine, a plant-derived insecticide. Ectopic co-expression of Gr8a and Gr98b in Gr66a-expressing, bitter-sensing gustatory receptor neurons (GRNs) confers responsiveness to L-canavanine. Furthermore, misexpression of all three Grs enables salt- or sweet-sensing GRNs to respond to L-canavanine. Introduction of these Grs in sweet-sensing GRNs switches L-canavanine from an aversive to an attractive compound. Co-expression of GR8a, GR66a and GR98b in Drosophila S2 cells induces an L-canavanine-activated nonselective cation conductance. We conclude that three GRs collaborate to produce a functional L-canavanine receptor. Thus, our results clarify the full set of GRs underlying the detection of a toxic tastant that drives avoidance behaviour in an insect

The association between prescription drugs and colorectal cancer prognosis: a nationwide cohort study using a medication-wide association study

Background With the availability of health insurance claim data, pharmacovigilance for various drugs has been suggested; however, it is necessary to establish an appropriate analysis method. To detect unintended drug effects and to generate new hypotheses, we conducted a hypothesis-free study to systematically examine the relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients. Methods We used the Korean National Health Insurance Service-National Sample Cohort database. A total of 2,618 colorectal cancer patients diagnosed between 2004 and 2015 were divided into drug discovery and drug validation sets (1:1) through random sampling. Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification system: 76 drugs classified as ATC level 2 and 332 drugs classified as ATC level 4 were included in the analysis. We used a Cox proportional hazard model adjusted for sex, age, colorectal cancer treatment, and comorbidities. The relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients was analyzed, controlling for multiple comparisons with the false discovery rate. Results We found that one ATC level-2 drug (drugs that act on the nervous system, including parasympathomimetics, addictive disorder drugs, and antivertigo drugs) showed a protective effect related to colorectal cancer prognosis. At the ATC level 4 classification, 4 drugs were significant: two had a protective effect (anticholinesterases and opioid anesthetics), and the other two had a detrimental effect (magnesium compounds and Pregnen [4] derivatives). Conclusions In this hypothesis-free study, we identified four drugs linked to colorectal cancer prognosis. The MWAS method can be useful in real-world data analysis. Keywords Colorectal cancer, Medication-wide association study, Pharmacovigilance, Hypothesis free, Agnostic, Korean populationThis work was supported by the Bisa Research Grant of Keimyung University in 2022 and the National Research Foundation of Korea (2017R1A2B4009233). The funding organizations had no role in the design or conduct of this research

Squeezing Limit of the Josephson Ring Modulator as a Non-Degenerate Parametric Amplifier

Two-mode squeezed vacuum states are a crucial component of quantum technologies. In the microwave domain, they can be produced by Josephson ring modulator which acts as a three-wave mixing non-degenerate parametric amplifier. Here, we solve the master equation of three bosonic modes describing the Josephson ring modulator with a novel numerical method to compute squeezing of output fields and gain at low signal power. We show that the third-order interaction from the three-wave mixing process intrinsically limits squeezing and reduces gain. Since our results are related to other general cavity-based three-wave mixing processes, these imply that any non-degenerate parametric amplifier will have an intrinsic squeezing limit in the output fields.Comment: 6+6 pages, 4 figure

Bound for Gaussian-state Quantum illumination using direct photon measurement

We present bound for quantum illumination with Gaussian state when using on-off detector or photon number resolving detector, where its performance is evaluated with signal-to-noise ratio. First, in the case of coincidence counting, the best performance is given by two-mode squeezed vacuum (TMSV) state which outperforms coherent state and classically correlated thermal (CCT) state. However coherent state can beat the TMSV state with increasing signal mean photon number when using the on-off detector. Second, the performance is enhanced by taking Fisher information approach of all counting probabilities including non-detection events. In the Fisher information approach, the TMSV state still presents the best performance but the CCT state can beat the TMSV state with increasing signal mean photon number when using the on-off detector. We also show that displaced squeezed state exhibits the best performance in the single-mode Gaussian state.Comment: 5 pages, 2 figures, comments welcom

Geomagnetic field influences probabilistic abstract decision-making in humans

To resolve disputes or determine the order of things, people commonly use binary choices such as tossing a coin, even though it is obscure whether the empirical probability equals to the theoretical probability. The geomagnetic field (GMF) is broadly applied as a sensory cue for various movements in many organisms including humans, although our understanding is limited. Here we reveal a GMF-modulated probabilistic abstract decision-making in humans and the underlying mechanism, exploiting the zero-sum binary stone choice of Go game as a proof-of-principle. The large-scale data analyses of professional Go matches and in situ stone choice games showed that the empirical probabilities of the stone selections were remarkably different from the theoretical probability. In laboratory experiments, experimental probability in the decision-making was significantly influenced by GMF conditions and specific magnetic resonance frequency. Time series and stepwise systematic analyses pinpointed the intentionally uncontrollable decision-making as a primary modulating target. Notably, the continuum of GMF lines and anisotropic magnetic interplay between players were crucial to influence the magnetic field resonance-mediated abstract decision-making. Our findings provide unique insights into the impact of sensing GMF in decision-makings at tipping points and the quantum mechanical mechanism for manifesting the gap between theoretical and empirical probability in 3-dimensional living space.Comment: 32 pages, 5 figures, 4 supplementary figures, 2 supplementary tables, and separate 15 ancillary file

A Study of Micronucleus Induction with Methyl Formate and 2-Methylbutane in Bone Marrow Cells of Male ICR Mice

Objectives: We investigated the genotoxicity of two chemicals, methyl formate and 2-methylbutane, using male ICR mice bone marrow cells for the screening of micronucleus induction. Although these two chemicals have already been tested numerous times, a micronucleus test has not been conducted and the amounts used have recently been increased.Methods: 7 week male ICR mice were tested at dosages of 250, 500, and 1,000mg/kg for methyl formate and 500, 1,000, and 2,000mg/kg for 2-methlybutane, respectively. After 24 hours of oral administration with the two chemicals, the mice were sacrificed and their bone marrow cells were prepared for smearing slides.Results: As a result of counting the micronucleated polychromatic erythrocyte (MNPCE) of 2,000 polychromatic erythrocytes (PCE), all treated groups expressed no statistically significant increase of MNPCE compared to the negative control group. There were no clinical signs related with the oral exposure of these two chemicals.Conclusion: It was concluded that the two chemicals did not induce micronucleus in the bone marrow cells of ICR mice, and there was no direct proportion with dosage. These results indicate that the two chemicals have no mutagenic potential under each study condition

Gaussian Quantum Illumination via Monotone Metrics

Quantum illumination is to discern the presence or absence of a low reflectivity target, where the error probability decays exponentially in the number of copies used. When the target reflectivity is small so that it is hard to distinguish target presence or absence, the exponential decay constant falls into a class of objects called monotone metrics. We evaluate monotone metrics restricted to Gaussian states in terms of first-order moments and covariance matrix. Under the assumption of a low reflectivity target, we explicitly derive analytic formulae for decay constant of an arbitrary Gaussian input state. Especially, in the limit of large background noise and low reflectivity, there is no need of symplectic diagonalization which usually complicates the computation of decay constants. First, we show that two-mode squeezed vacuum (TMSV) states are the optimal probe among pure Gaussian states with fixed signal mean photon number. Second, as an alternative to preparing TMSV states with high mean photon number, we show that preparing a TMSV state with low mean photon number and displacing the signal mode is a more experimentally feasible setup without degrading the performance that much. Third, we show that it is of utmost importance to prepare an efficient idler memory to beat coherent states and provide analytic bounds on the idler memory transmittivity in terms of signal power, background noise, and idler memory noise. Finally, we identify the region of physically possible correlations between the signal and idler modes that can beat coherent states.Comment: 16 pages, 6 figure