In this work, we study the application of multimodal analogical reasoning to image retrieval. Multimodal analogy questions are given in a form of tuples of words and images, e.g., “cat”:“dog”::an ...image of a cat sitting on a bench:?, to search for an image of a dog sitting on a bench. Retrieving desired images given these tuples can be seen as a task of finding images whose relation between the query image is close to that of query words. One way to achieve the task is building a common vector space that exhibits analogical regularities. To learn such an embedding, we propose a quadruple neural network called multimodal siamese network. The network consists of recurrent neural networks and convolutional neural networks based on the siamese architecture. We also introduce an effective procedure to generate analogy examples from an image-caption dataset for training of our network. In our experiments, we test our model on analogy-based image retrieval tasks. The results show that our method outperforms the previous work in qualitative evaluation.
We propose a lead-free silver paste as a replacement for a high-temperature lead-rich solder used for electronics. The pastes tested here contain a small amount of solvent, but primarily consist of ...silver powder and alkoxide-passivated silver nanoparticles that undergo nanosintering when heated. The pastes were used to connect silicon diode chips to copper bases at 350°C in nitrogen ambient without external pressure. The resulting diode packages had electrical and thermal properties about equal to those with lead-solder joints. The mechanical strengths also were comparable to the lead joint. These properties make this nanosilver paste the first viable lead-free alternative to a lead solder.
Highlights • GPR52 KO mice were hypersensitive to an adenosine A2A receptor antagonist. • GPR52 KO mice had reduced striatal expression of enkephalin mRNA. • GPR52 may be involved in modulating the ...function of striatopallidal neurons.
In color image processing based on mathematical optimization, a color-line image feature has been considered and many methods that give good results have been proposed. A color-line is a linear color ...distribution (correlation line) observed in a local image region, and is numerically represented by the sparsity of a data matrix generated from the neighboring pixel values. However, the calculation requires a lot of processing time because each data matrix is processed by inverse calculation or singular value decomposition (SVD) with some operations on the decomposed singular values. In this paper, in order to address this problem, we propose a method that can effectively compute SVD for each data matrix. Using the experimental knowledge that matrices obtained from neighboring regions (each centered at an adjacent pixel) are similar to each other, we intentionally design the SVD by using an iterative method (Arnoldi iteration), and propagate the converged singular vectors at a pixel to the next pixel as the initial vectors of the iteration. This propagation can drastically reduce the number of iterations required for convergence. Additionally, the singular values and vectors are obtained in descending order, which is advantageous when a matrix is reconstructed after reducing small singular values, so we can truncate the calculation when a singular value becomes lower than a threshold value. To show the effectiveness, we apply the proposed method to a denoising method, arranged structure-tensor total variation (ASTV), and show that the processing time is shortened by 95% compared to the naive method without losing numerical accuracy.
GPR40/FFAR1 is a Gq protein-coupled receptor expressed in pancreatic β cells and enteroendocrine cells, and mediates insulin and incretin secretion to regulate feeding behavior. Several GPR40 full ...agonists have been reported to reduce food intake in rodents by regulating gut hormone secretion in addition to their potent glucose-lowering effects; however, detailed mechanisms of feeding suppression are still unknown. In the present study, we characterized T-3601386, a novel compound with potent full agonistic activity for GPR40, by using in vitro Ca2+ mobilization assay in Chinese hamster ovary (CHO) cells expressing FFAR1 and in vivo hormone secretion assay. We also evaluated feeding suppression and weight loss after the administration of T-3601386 and investigated the involvement of the vagal nerve in these effects. T-3601386, but not a partial agonist fasiglifam, increased intracellular Ca2+ levels in CHO cells with low FFAR1 expression, and single dosing of T-3601386 in diet-induced obese (DIO) rats elevated plasma incretin levels, suggesting full agonistic properties of T-3601386 against GPR40. Multiple doses of T-3601386, but not fasiglifam, in DIO rats showed dose-dependent weight loss accompanied by feeding suppression and durable glucagon-like peptide-1 elevation, all of which were completely abolished in Ffar1-/- mice. Immunohistochemical analysis in the nuclei of the solitary tract demonstrated that T-3601386 increased the number of c-Fos positive cells, which also disappeared in Ffar1-/- mice. Surgical vagotomy and drug-induced deafferentation counteracted the feeding suppression and weight loss induced by the administration of T-3601386. These results suggest that T-3601386 exerts incretin release and weight loss in a GPR40-dependent manner, and that afferent vagal nerves are important for the feeding suppression induced by GPR40 full agonism. Our novel findings raise the possibility that GPR40 full agonist can induce periphery-derived weight reduction, which may provide benefits such as less adverse effects in central nervous system compared to centrally-acting anti-obesity drugs.
Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically ...effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R) activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs), raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP) profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR). Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist), olanzapine (antagonist), and aripiprazole (partial agonist) all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP) exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP) displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development.
Many drugs of abuse and most neuropharmacological agents regulate G protein-coupled receptors (GPCRs) in the central nervous system (CNS)_ENREF_1. The striatum, in which dopamine D1 and D2 receptors ...are enriched, is strongly innervated by the ventral tegmental area (VTA), which is the origin of dopaminergic cell bodies of the mesocorticolimbic dopamine system_ENREF_3 and plays a central role in the development of psychiatric disorders_ENREF_4. Here we report the comprehensive and anatomical transcript profiling of 322 non-odorant GPCRs in mouse tissue by quantitative real-time PCR (qPCR), leading to the identification of neurotherapeutic receptors exclusively expressed in the CNS, especially in the striatum. Among them, GPR6, GPR52, and GPR88, known as orphan GPCRs, were shown to co-localize either with a D2 receptor alone or with both D1 and D2 receptors in neurons of the basal ganglia. Intriguingly, we found that GPR52 was well conserved among vertebrates, is Gs-coupled and responsive to the antipsychotic drug, reserpine. We used three types of transgenic (Tg) mice employing a Cre-lox system under the control of the GPR52 promoter, namely, GPR52-LacZ Tg, human GPR52 (hGPR52) Tg, and hGPR52-GFP Tg mice. Detailed histological investigation suggests that GPR52 may modulate dopaminergic and glutamatergic transmission in neuronal circuits responsible for cognitive function and emotion. In support of our prediction, GPR52 knockout and transgenic mice exhibited psychosis-related and antipsychotic-like behaviors, respectively. Therefore, we propose that GPR52 has the potential of being a therapeutic psychiatric receptor. This approach may help identify potential therapeutic targets for CNS diseases.
An indirect enzyme-linked immunosorbent assay (ELISA) using lipopolysaccharide extract as antigen was evaluated for detection of antibodies to Actinobacillus pleuropneumoniae serovar 15. The serovar ...15 ELISA had a higher sensitivity and specificity than latex agglutination test for 63 and 80 sera from pigs experimentally infected and not infected with A. pleuropneumoniae, respectively. When the serovar 15 ELISA was applied to 454 field sera, high rates of seropositivity were found in pigs from farms infected with A. pleuropneumoniae serovar 15, but not in those from farms free of A. pleuropneumoniae serovar 15. The results suggest that the serovar 15 ELISA may be useful for the serological surveillance of infection with A. pleuropneumoniae serovar 15.
We searched for peptidic ligands for orphan G protein-coupled receptors utilizing a human genome data base and identified a new gene encoding a preproprotein that could generate a peptide. This ...peptide consisted of 43 amino acid residues starting from N-terminal pyroglutamic acid and ending at C-terminal arginine-phenylalanine-amide. We therefore named it QRFP after pyroglutamylated arginine-phenylalanine-amide peptide. We subsequently searched for its receptor and found that Chinese hamster ovary cells expressing an orphan G protein-coupled receptor, AQ27, specifically responded to QRFP. We analyzed tissue distributions of QRFP and its receptor mRNAs in rats utilizing quantitative reverse transcription-polymerase chain reaction and in situ hybridization. QRFP mRNA was highly expressed in the hypothalamus, whereas its receptor mRNA was highly expressed in the adrenal gland. The intravenous administration of QRFP caused the release of aldosterone, suggesting that QRFP and its receptor have a regulatory function in the rat adrenal gland.
By observing the crystal shapes and kinetics of ice Ih growing at high pressures from the melt, it was found that the prism
{
1
0
1
¯
0
}
faces undergo a roughening transition at approximately
-
16
∘
...C
and 160
MPa (1600
bar) in
H
2
O
ice, and
-
14
∘
C
and 180
MPa (1800
bar) in
D
2
O
ice. At temperatures above the roughening transition, the prism facets completely vanished and the curves of growth rate versus growth drive were linear. In contrast, below the roughening temperature, regions of prism facets existed and the growth rate curves were approximately quadratic. The basal
{
0
0
0
1
}
faces persisted up to
0
∘
C
and gave approximately quadratic growth rate curves. The melting curves of ice Ih for
H
2
O
and
D
2
O
were accurately measured by direct observations of the solid–liquid coexistence equilibrium and found to agree with previous results obtained with other methods.