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The impact of resolving western boundary currents and mesoscale eddies on a carbon circulation simulation for the North Pacific Ocean is investigated to evaluate the merits of using high‐resolution ocean biogeochemical models for climate projections. Simulations by a 100‐km resolution global ocean biogeochemical model with and without embedding a 10‐km resolution model in the North Pacific Ocean are compared. The major improvement in the high‐resolution simulation is the representation of the Kuroshio, its extension current, and the recirculation gyres formed to its south and north, resulting in a proper representation of the North Pacific subtropical mode water (STMW) and an increase in storage of the anthropogenic CO2 (Canth) in STMW by about two‐thirds. The larger storage rate in STMW is caused by supply of a larger amount of warm surface water containing rich Canth to the formation region by the intensified Kuroshio. A huge buoyancy loss from this warm water results in the increased formation of STMW that occupies a vast area in the western subtropical gyre. The surface uptake of Canth in the formation region of STMW is slightly increased but is largely comparable to that of the low‐resolution model. Moreover, there is no structural difference in Canth uptake in other parts of the subtropical region. Thus, the improvement of Canth distribution can be understood as a redistribution of water mass in the subtropical gyre by the improved circulation. The present assessment motivates the use of a high horizontal resolution ocean model in next‐generation projection experiments with carbon cycles. Plain Language Summary: Accurately representing absorption and accumulation of anthropogenic CO2 (Canth) by the ocean in Earth system models is important to reliably project future climate change. This study investigates the impact of realistically expressing the Kuroshio, which is not expressed adequately in the majority of current Earth system models, on a carbon circulation simulation for the North Pacific Ocean. Two simulations differing in the horizontal grid spacing, about 100 and 10 km, are compared. The intensified Kuroshio in the fine resolution model results in an improved oceanic structure for the upper 500‐m depths in the western North Pacific Ocean, and more Canth is accumulated there, which is closer to observations. Budget analysis suggests that source for the increased Canth accumulation is not local surface flux but a supply of Canth‐rich surface water from low latitudes by the intensified Kuroshio. Such improvements would give more fidelity to projections of regional subsurface water acidification rate. Overall, the use of a fine horizontal resolution ocean model can be recommended in next‐generation projection experiments with carbon cycles for the North Pacific Ocean. Key Points: Storage of anthropogenic carbon in the western North Pacific Ocean is improved by using a 10‐km horizontal resolution ocean modelImprovement in the formation and distribution of the North Pacific subtropical mode water is a keyUse of 10‐km class high horizontal resolution ocean models is recommended as part of Earth system models with carbon cycles [ABSTRACT FROM AUTHOR]

Spatiotemporal variations in air‐sea CO2 fluxes in the Kuroshio region were evaluated using measurements made by voluntary cargo ships and research vessels. The data were re‐gridded to produce a 1° × 1° horizontal grid and 0.1‐year timesteps. Spatial clustering showed that the area north of approximately 30°N was the strongest atmospheric CO2 sink. The spatial differences were largest in winter and insignificant in summer. The oceanic CO2 uptake in the Kuroshio region increased from 2000 to 2019. Changes in the wind speed and total alkalinity affected the decadal increase in CO2 absorption. The spatial distributions of the air‐sea CO2 fluxes were affected by the Kuroshio large meander (KLM). This effect was likely caused by the change in seawater fCO2 via the change in the Kuroshio Extension Path during the KLM period. The Fourier regression technique used in the data analysis was expected to facilitate analyses of the carbonate system in coastal waters, where comprehensive on‐site measurements and satellite analyses are difficult. Plain Language Summary: We analyzed oceanic CO2 uptake in the Kuroshio region using measurements from cargo ships and research vessels. The regression technique used in this study improved the spatiotemporal resolution of the data and is expected to be widely applicable for the analysis of other seawater carbonate systems, especially in coastal areas where comprehensive measurements and satellite analysis are difficult. CO2 absorption was particularly high in the area north of approximately 30°N. The differences between CO2 absorption in that area and other areas were largest in winter and small in summer. The CO2 absorption increased between 2000 and 2019. Changes in wind speed and alkalinity affected the increase in CO2 absorption. The areal differences in CO2 absorption were affected by the Kuroshio large meander. This effect was probably the result of the change of the Kuroshio path during the Kuroshio large meander. Key Points: Spatiotemporal variations in carbonate parameters and air‐sea CO2 fluxes in the Kuroshio region were analyzed by Fourier regressionOceanic CO2 uptake increased between 2000 and 2019. Changes in wind speed and total alkalinity affected the increase rate in CO2 uptakeThe Kuroshio large meander affects the spatial distribution of air‐sea CO2 fluxes by change in the Kuroshio Extension path [ABSTRACT FROM AUTHOR]

Models of artificial intelligence (AI) that have billions of parameters can achieve high accuracy across a range of tasks1,2, but they exacerbate the poor energy efficiency of conventional general-purpose processors, such as graphics processing units or central processing units. Analog in-memory computing (analog-AI)3–7 can provide better energy efficiency by performing matrix–vector multiplications in parallel on ‘memory tiles’. However, analog-AI has yet to demonstrate software-equivalent (SWeq) accuracy on models that require many such tiles and efficient communication of neural-network activations between the tiles. Here we present an analog-AI chip that combines 35 million phase-change memory devices across 34 tiles, massively parallel inter-tile communication and analog, low-power peripheral circuitry that can achieve up to 12.4 tera-operations per second per watt (TOPS/W) chip-sustained performance. We demonstrate fully end-to-end SWeq accuracy for a small keyword-spotting network and near-SWeq accuracy on the much larger MLPerf8 recurrent neural-network transducer (RNNT), with more than 45 million weights mapped onto more than 140 million phase-change memory devices across five chips.A low-power chip that runs AI models using analog rather than digital computation shows comparable accuracy on speech-recognition tasks but is more than 14 times as energy efficient. [ABSTRACT FROM AUTHOR]

Hardware acceleration of deep learning using analog non-volatile memory (NVM) requires large arrays with high device yield, high accuracy Multiply-ACcumulate (MAC) operations, and routing frameworks for implementing arbitrary deep neural network (DNN) topologies. In this article, we present a 14-nm test-chip for Analog AI inference—it contains multiple arrays of phase change memory (PCM)-devices, each array capable of storing 512 $\times $ 512 unique DNN weights and executing massively parallel MAC operations at the location of the data. DNN excitations are transported across the chip using a duration representation on a parallel and reconfigurable 2-D mesh. To accurately transfer inference models to the chip, we describe a closed-loop tuning (CLT) algorithm that programs the four PCM conductances in each weight, achieving <3% average weight-error. A row-wise programming scheme and associated circuitry allow us to execute CLT on up to 512 weights concurrently. We show that the test chip can achieve near-software-equivalent accuracy on two different DNNs. We demonstrate tile-to-tile transport with a fully-on-chip two-layer network for MNIST (accuracy degradation ~0.6%) and show resilience to error propagation across long sequences (up to 10 000 characters) with a recurrent long short-term memory (LSTM) network, implementing off-chip activation and vector-vector operations to generate recurrent inputs used in the next on- chip MAC. [ABSTRACT FROM AUTHOR]

Japanese space weather research and operation began in 1896 with research on radio propagation. LF, MF, and HF radio communication used to be important before the era of communication satellites; however, they are affected by ionospheric conditions and solar activity. A center for the research and development of radio systems was established at Hiraiso, which is now also a space weather observatory for measuring solar activity, geomagnetic fields, and ionospheric conditions. The need for space weather information initially decreased in the communication satellite age, but since the beginning of the 21st century it has been increasing again with the growing use of positioning satellite systems. The role of Southeast Asian countries in space weather research has become important and the range of activities is also growing. The contribution of these countries to space weather research and operation is expected to grow in future. [ABSTRACT FROM AUTHOR]

Japanese space weather research and operation began in 1896 with research on radio propagation. LF, MF, and HF radio communication used to be important before the era of communication satellites; however, they are affected by ionospheric conditions and solar activity. A center for the research and development of radio systems was established at Hiraiso, which is now also a space weather observatory for measuring solar activity, geomagnetic fields, and ionospheric conditions. The need for space weather information initially decreased in the communication satellite age, but since the beginning of the 21st century it has been increasing again with the growing use of positioning satellite systems. The role of Southeast Asian countries in space weather research has become important and the range of activities is also growing. The contribution of these countries to space weather research and operation is expected to grow in future. Key Points: The origin of Japanese space weather forecast began in 1896 with radio propagation researchGlobal space weather research and operation are now widespreadThe importance of Southeast Asian countries in space weather research and operation will increase significantly [ABSTRACT FROM AUTHOR]

It is well established that the ocean plays an important role in absorbing anthropogenic carbonCant from the atmosphere. Under global warming, Earth system model simulations and theoretical arguments indicate that the capacity of the ocean to absorb Cant will be reduced, with this constituting a positive carbon-climate feedback. Here we apply a suite of sensitivity simulations with a comprehensive Earth system model to demonstrate that the surface waters of the shallow overturning structures (spanning 458S-458N) sustain nearly half of the global ocean carbon-climate feedback. The main results reveal a feedback that is initially triggered by warming but that amplifies over time as Cant invasion enhances the sensitivity of surface pCO2 to further warming, particularly in the warmer season. Importantly, this ''heat-carbon feedback'' mechanism is distinct from (and significantly weaker than) what one would expect from temperature-controlled solubility perturbations to pCO2 alone. It finds independent confirmation in an additional perturbation experiment with the same Earth system model. There mechanism denial is applied by disallowing the secular trend in the physical state of the ocean under climate change, while simultaneously allowing the effects of heating to impact sea surface pCO2 and thereby CO2 uptake. Reemergence of Cant along the equator within the shallow overturning circulation plays an important role in the heat-carbon feedback, with the decadal renewal time scale for thermocline waters modulating the feedback response. The results here for 458S-458N stand in contrast to what is found in the high latitudes, where a clear signature of a broader range of driving mechanisms is present. [ABSTRACT FROM AUTHOR]

A positive marine chemistry‐climate feedback was originally proposed by Revelle and Suess (1957, https://doi.org/10.3402/tellusa.v9i1.9075), whereby the invasion flux of anthropogenic carbon into the ocean serves to inhibit future marine CO2 uptake through reductions to the buffering capacity of surface seawater. Here we use an ocean circulation‐carbon cycle model to identify an upper limit on the impact of reemergence of anthropogenic carbon into the ocean's mixed layer on the cumulative airborne fraction of CO2 in the atmosphere. We find under an RCP8.5 emissions pathway (with steady circulation) that the cumulative airborne fraction of CO2 has a sevenfold reduction by 2100 when the CO2 buffering capacity of surface seawater is maintained at preindustrial levels. Our results indicate that the effect of reemergence of anthropogenic carbon into the mixed layer on the buffering capacity of CO2 amplifies the transient climate sensitivity of the Earth system. Key Points: Marine chemistry‐climate feedbacks plan an important role in determining climate sensitivityThe rate of reemergence of anthropogenic carbon plays an important role in determining climate sensitivityThe sensitivity identified here to perturbations to the buffering capacity of CO2 in seawater is larger than that emphasized in IPCC AR5 [ABSTRACT FROM AUTHOR]

The interaction of water and carbon dioxide with nanostructured epitaxial (Ba,Sr)TiO3(001) thin film and bulk single crystal SrTiO3(001) surfaces was studied using x-ray photoemission spectroscopy (XPS), thermal desorption spectroscopy (TDS), and density functional theory (DFT). On both surfaces, XPS and TDS indicate D2O and CO2 chemisorb at room temperature with broad thermal desorption peaks (423–723 K) and a peak desorption temperature near 573 K. A comparison of thermal desorption Redhead activation energies to adsorption energies calculated using DFT indicates that defect surface sites are important for the observed strong adsorbate-surface reactivity. Numerical calculations of the competetive adsorption/desorption equilibria for H2O and CO2 on SrTiO3(001) surfaces show that for typical atmospheric concentrations of 0.038% carbon dioxide and 0.247% water vapor the surfaces are covered to a large extent with both adsorbates. The high desorption temperature indicates that these adsorbates have the potential to impact measurements of the electronic structure of BaTiO3–SrTiO3(001) surfaces exposed to air, or prepared in high vacuum deposition systems, as well as the electrical properties of thin film ATiO3-based devices. [ABSTRACT FROM AUTHOR]

The effect of Nb codoping on the optical properties of the PbWO[sub 4]:Mo scintillator is investigated by radio- and thermoluminescence, scintillation decay, and light yield measurements. Steady-state radioluminescence efficiency of PbWO[sub 4]:Mo,Nb with optimized doping concentrations (2750 and 350 molar ppm, respectively) becomes up to 20 times higher with respect to that of undoped PbWO[sub 4] and is comparable to that of Bi[sub 3]Ge[sub 4]O[sub 12]. However, slow components down to several tens of microseconds appear in the time decay. Their existence may be related to the presence of traps monitored by thermoluminescence. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

X-ray excited luminescence spectra, wavelength-resolved thermoluminescence glow curves, ultraviolet and [sup 22]Na excited emission decays, and [sup 60]Co excited light yield were measured on a set of high purity (99.9999%) PbWO[sub 4]:X (X=Lu[sup 3+], Y[sup 3+], Gd[sup 3+], Sc[sup 3+], Nb[sup 5+], Pb[sup 2+]) samples grown in an equivalent way. Positive influence of trivalent doping (Lu, Gd, Y) was noted, which consists in suppressing the deeper trapping states in the PbWO[sub 4] structure. Such states are related to the radiative recombination processes in the green and red part of the spectra. The presence of the green emission centers also results in the increase of the slow recombination decay components in the microsecond time scale. High concentration of the dopant ions (670 atomic ppm for PbWO[sub 4]:Nb) results in the creation of new nonradiative recombination sites, which suppress the recombination decay components and the light yield as well. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A near‐future, 2‐K warming climate simulation comprising over 3,000 years of ensemble simulations was performed using 60‐km global and 20‐km regional atmospheric models. Even in the +2‐K climate, indices of extreme precipitation and dryness increased significantly in the extratropics compared with the historical climate. Mean precipitation increases in the rainy season and decreases in the dry season, indicating that the seasonal precipitation range becomes amplified with global warming. The intensification of precipitation and dryness from +2 to +4 K was also robust in the mean for climatological wet and arid regions. Around Japan, which was classified as a wet region, the regional atmospheric model predicts that the extreme hourly precipitation in the future climate becomes more extreme on hot days, but slightly weaker on cold days. This extreme precipitation has a high sensitivity to air temperature exceeding 7%/K. Plain Language Summary: Our study shows the precipitation changes in the near‐future around the 2040s, +2‐K climate. Even in the +2‐K climate, both extreme precipitation and dryness in the extratropics increase significantly. These results urge to plan for adaptation to extreme weather in the near future. The 2‐K warming climate simulation was performed with over 3,000 years of ensemble member using 60‐km global and 20‐km regional atmospheric models. A large number of ensemble data elucidated statistically significant increment of the precipitation extremes, moreover the amplifying of the seasonal precipitation range. The data are helpful to investigate the climate in the near‐future containing mixed uncertainty both internal variation and effects of future scenario. It would provide valuable information for policy‐making, planning of mitigation, and adaptation for extreme weather events, such as flooding or droughts in the near‐future climate. Key Points: High‐resolution large‐ensemble simulations are performed to assess precipitation change under the +2‐K climateEven in the +2‐K climate, both extreme precipitation and dryness in the extratropics increase significantly compared with the historical climateThe tendency for the seasonal precipitation range to amplify becomes robust with global warming from the +2‐K to +4‐K climate [ABSTRACT FROM AUTHOR]

Electron slowing-down processes in molecular oxygen gas in the subexcitation domain (below the ionization threshold) are studied by using the Spencer–Fano (SF) equation and its simplification, the continuous-slowing-down approximation (CSDA), both in time-dependent and time-independent representations. Compared to the previously studied cases of N2 and CO2, O2 has the special features in its inelastic cross sections of (i) strong delta-function-like peaks in the vibrational excitation cross section below 1.3 eV and (ii) very low energy thresholds of electronic excitation channels. These features provide a stringent test for the CSDA. Indeed, our results clearly show for the first time that the CSDA fails even qualitatively to reproduce the electron degradation spectrum given by the exact SF method over the whole energy regime studied. [ABSTRACT FROM AUTHOR]

Studies the changes in the absorption spectra induced by Co60 irradiation and temperature annealing for selected PbWO4 crystals. Shaping of the absorption spectrum by four color centers; Thermoluminescence (TSL) glow curves above room temperature; Determination of trap levels resulting from irradiation; Correlation between results obtained by TSL and Co60 irradiation induced absorption changes.

Presents a study which evaluated the localized electronic density of states at the hydrogenated amorphous silicon/silicon nitride interfaces. Experimental details on the use of transient voltage spectroscopy technique; Deposition of plasma-enhanced chemical vapor deposition; Measurements of the signal amplitude.

Presents information on a study which investigated deep electron traps in n-aluminum gallium arsenide grown by molecular-beam epitaxy using deep-level transient capacitance spectroscopy. Methodology of the study; Results and discussion; Conclusion.

Demonstrates laser emission by photopumping at room temperature from a distributed feedback (DFB) structure for a surface-emitting laser constructed by alternating growths of gallium arsenide and aluminum gallium arsenide multiquantum well. Preparation of the DFB structure; Measurement of the reflectivity spectra of the DFB structure; Results.

Presents information on a study which examined the magnesium doping in molecular-beam epitaxy of gallium-arsenic using ionized magnesium beams. Experimental procedures; Results and discussion.

SUMMARY The Si resonator is applied for measuring the voltage in a highly isolated manner. The working principle is based on the resonant frequency shift caused by the electrical field from the electrode connected to the high-voltage source (supposing the battery). Here, the resonator is electrically floated, and its potential is decided by the relative position against the electrodes which are connected to the high voltage and the driving voltage. The induced voltage on the resonator is analyzed against the driving frequency. The resonance is found by the paired peaks in the amplitude curve. The setup for the electrical measurement can make the sensor system compact. A new sensor design for avoiding the electrical field concentration realizes the measurement over 400 V without the breakdown. This will match with the high-voltage dc power supply system. [ABSTRACT FROM AUTHOR]

SUMMARY In fruit farming, the appropriate time of harvesting high-quality and high-value fruits is determined by comparing the surface color of tree's fruit and a fruit color chart defined for each fruit cultivar. This comparative examination comprises visual inspection by the farmer and a sensory inspection based on sensibility information. Thus, the decision varies across individuals because the decision criterion is not defined quantitatively and is not unified. This study aims to develop a system to determine the appropriate time for harvesting fruit from the tree. In this paper, we used apples to develop a quantitative method for appropriate harvest time. We focused on the HSV and L*a*b* color spaces used by image processing. Consequently, it was found that using the value of H and a* in deciding on the proper harvest time was useful. We also conducted a comparative analysis of apple growth and color and color differences to investigate our quantitative method for determining appropriate harvest time. These results of the procedure show that quantitatively determining the proper harvesting time of fruit is possible. [ABSTRACT FROM AUTHOR]

The reaction characteristics, including hydration reaction rate and performance over repeated reaction cycles, of CaO extracted from different local limestone samples in Japan were examined to identify the optimal material to be used in chemical heat storage and pumps. The factors influencing the chemical reaction, including the chemical composition, crystal grain structure, collapse due to hydration/dehydration reactions of CaO/Ca(OH), specific surface area, and mean pore diameter, were compared and discussed. Based on the results, it was observed that CaO derived from limestone from Hiroshima, previously utilized by our research group, and Kawara CaO with a high purity exhibit similar reaction characteristics. Garou CaO, which has more impurities than that in the others tested, exhibits a lower initial hydration reaction rate and conversion change than those of Hiroshima/Okayama and Kawara CaO due to the presence of magnesium in Garou CaO as dolomite, which initially fills the pores. However, it was shown that Garou CaO can be used as a practical material for chemical heat storage and pumps with relatively high strength and reactivity compared with the other limestone samples because of its columnar joint texture and larger pore size following activation by four water vapor reaction cycles. [ABSTRACT FROM AUTHOR]

Presents a study that reported the results of photoluminescence measurements on gallium arsenide (GaAs)/Al[sub0.22]Ga[sub0.78]As single quantum wells (QW) inhomogeneously doped with silicon (Si). Low-temperature photoluminescence (PL) due to exciton bound to Si donors; Binding energies of the exciton; Factors which the PL spectra related to impurities in QW depend on.

The article focuses on the aspects of the ocean heat content. Topics discussed include the role ocean heat storage and transport on the concept of climate which include tropical cyclones, sea levels, and El Niño-Southern Oscillation (ENSO), the statistical presentation of the ocean heat content anomaly (OHCA) from 1993-2015, and the implication of El Niño pattern on sea surface temperatures (SSTs).

Recent decades have seen significant developments in seasonal-to-interannual timescale climate prediction capabilities. However, until recently the potential of such systems to predict Arctic climate had not been assessed. This paper describes a multimodel predictability experiment which was run as part of the Arctic Predictability and Prediction On Seasonal to Inter-annual Timescales (APPOSITE) project. The main goal of APPOSITE was to quantify the timescales on which Arctic climate is predictable. In order to achieve this, a coordinated set of idealised initial-value predictability experiments, with seven general circulation models, was conducted. This was the first model intercomparison project designed to quantify the predictability of Arctic climate on seasonal to inter-annual timescales. Here we present a description of the archived data set (which is available at the British Atmospheric Data Centre) and an update of the project's results. Although designed to address Arctic predictability, this data set could also be used to assess the predictability of other regions and modes of climate variability on these timescales, such as the El Niño Southern Oscillation. [ABSTRACT FROM AUTHOR]

Using an ocean carbon cycle model embedded in an ocean general circulation model, we examine how the budget of anthropogenic CO2 (Cant) is controlled by ocean dynamics. To complement recent studies showing only vertically integrated budgets, we provide a step-by-step description by making use of three different coarse grainings of the full vertical resolution of the ocean model in our budget analysis. For the 11 subdomains of the global ocean, these coarse grainings are (1) a one-layer (vertically integrated) budget, (2) a three-layer budget, and (3) an 11-layer budget. We largely focus on the Pacific circulation. We identify and quantify substantial carbon transport associated with the subtropical cells (STCs), which are dominant contributors to the meridional overturning circulation in the upper ocean in the tropics and subtropics, as playing a fundamental role in governing the ocean interior distribution of Cant. The upper branch of the STCs transports Cant-rich water from the tropics to the subtropics, contributing to the precondition for the high Cant inventory in mode waters. The lower branch of the STCs carries about two thirds of the transported Cant back to the tropics, while it largely excludes Subtropical Mode Waters. This work implies that the reemergence of Cant through recirculation within the STCs may lead to a reduced capacity for further Cant uptake via gas exchange into the surface ocean, potentially contributing to a positive carbon-climate feedback. [ABSTRACT FROM AUTHOR]

Taller pipe-framed greenhouses (pipe houses hereafter) are required to maintain a buffer zone for an improved thermal environment or to install devices for controlling the thermal environment, such as movable curtains. This study investigates the effect of ridge height on the distributions of the wind pressure coefficient (Cp) on pipe houses based on a wind tunnel experiment using 1:20 scale models. The width and length of a standard pipe house in full scale were 6 and 50 m, respectively, while the ridge height was varied from 3.16 to 5.16 m. The results indicate that the Cp distribution on the windward roof was strongly affected by the ridge height when the wind direction was normal to the ridge line. The windward roof was generally subjected to negative wind pressure (suction). The suction had a maximum value behind the windward eave, which increased in magnitude with an increase in ridge height. This effect may be related to the flow separation at the windward eave and reattachment on the windward roof. As a result, the drag and lift coefficients (CD and CL) obtained from the Cp distribution were also affected by the ridge height. High suctions were induced locally at the ridge corner of the leeward roof with an oblique wind. [ABSTRACT FROM AUTHOR]

Zizina emelina (de l'Orza) is listed on Japan's Red Data List as an endangered species because of loss of its principal food plant and habitat. We compared parts of the mitochondrial and nuclear genes of this species to investigate the level of genetic differentiation among the 14 extant populations. We also examined infection of the butterfly with the bacterium Wolbachia to clarify the bacterium's effects on the host population's genetic structure. Mitochondrial and nuclear DNA analyses revealed that haplotype composition differed significantly among most of the populations, and the fixation index FST was positively correlated with geographic distance. In addition, we found three strains of Wolbachia, one of which was a male killer; these strains were prevalent in several populations. There was linkage between some host mitochondrial haplotypes and the three Wolbachia strains, although no significant differences were found in a comparison of host mitochondrial genetic diversity with nuclear genetic diversity in Wolbachia-infected or -uninfected populations. These genetic analyses and Wolbachia infection findings show that Z. emelina has little migratory activity and that little gene flow occurs among the current populations. [ABSTRACT FROM PUBLISHER]

Background Serotonin type 3 receptor (5- HT3R) antagonists are potentially useful therapeutic agents for diarrhea-predominant irritable bowel syndrome ( IBS-D). To identify biomarkers predicting effectiveness of the 5- HT3R antagonist (ramosetron) in IBS-D. Methods Irritable bowel syndrome-D Japanese subjects received 2.5 or 5 μg of ramosetron once daily for 4 weeks. Colonic mucosal S100A and tryptophan hydroxylase ( TPH) mRNA expression levels were measured before treatment. Genomic DNA was extracted from blood and polymorphisms of TPH1 and TPH2 were analyzed. Key Results Forty-two patients (27 men and 15 women, mean age 42 years) with IBS-D were included for analysis. Improvement of IBS symptoms was seen in 26 (61.9%). Baseline S100A10 ( p = 0.02) and TPH1 ( p = 0.02) expression were significantly higher in the ramosetron responders than in the non-responders. The frequencies of the TPH1 rs4537731G allele in linkage disequilibrium with the TPH1 rs7130929 T allele (11.5% vs 50%, p = 0.003; OR: 12; 95% CI: 2.1-69) along with TPH1 rs211105 C allele (3.8% vs 43.8%, p = 0.0003; OR: 19; 95% CI: 2.1-181) were significantly lower in the responders than in the non-responders. The mean scores of diarrhea at baseline were significantly higher (5.2 vs 3.7, p = 0.005) in patients with TPH1 rs211105 T/T than those with the G allele. Conclusions & Inferences TPH1 gene polymorphisms and S100A10 expression, which correlate with 5- HT signaling were associated with ramosetron effectiveness in IBS-D, and may possibly lead to prospective identification of the resistance to treatment. [ABSTRACT FROM AUTHOR]