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Aberrant DNA methylation is associated with oncogenesis of various human cancers, including pancreatic cancer (PC). PC is the seventh most common cancer, and obesity is a known high-risk factor. However, whether obesity influences DNA methylation in pancreatic exocrine cells and if this influences PC development remain unclear. Here, we performed an epigenome-wide analysis of isolated pancreatic exocrine cells obtained from mice with high-fat-diet-induced obesity (DIO). Using the Illumina Mouse Methylation BeadChip array (280K), we identified 316 differentially methylated regions (DMRs) that were enriched for cellular processes, such as DNA repair, transcription regulation, and cell proliferation, which confirmed obesity-related dysregulation of certain metabolic processes in the pancreatic cells in DIO mice. Comparing the DMRs with those in stage IB PC helped identify 82 overlapping DMRs. Three pathways including the cell hypertrophy pathway involving PLC, PKC, SMAD2/3, and TRKA; the metabolic control pathway involving CREB and AMPK; and the potassium regulation pathway involving K

Living-donor kidney transplantation (LDKT) is the most realistic option for patients with end-stage kidney disease because of a severe shortage of deceased donors. Hand-assisted laparoscopic donor nephrectomy (HALDN) and hand-assisted retroperitoneoscopic donor nephrectomy (HARDN) have been undertaken at our institute. We compared these 2 surgical procedures with respect to donor outcome and the graft function of recipients.We reviewed data from 840 consecutive live-donor kidney transplants from October 2003 to April 2019. Propensity scores were calculated for each patient using bivariate logistic regression.After propensity-score matching, the 2 groups each contained 205 patients. Donors in the HALDN group had a longer procedure time (217 minutes, P .0001), less estimated blood loss (51 mL, P .0001), lower serum levels of C-reactive protein at postoperative day (POD) 1 (7.9 mg/dL, P .0001) than those in the HARDN group. There were 22 modified Clavien-classifiable complications among the study groups. A significantly higher conversion to open surgery was noted in the HARDN group (P = .0181) than in the HALDN group, but there was no significant difference in the prevalence of complications in either group. There was no significant difference in the estimated glomerular filtration rate of recipients at POD14 between the 2 groups.Safety and early graft function of HALDN in LDKT are comparable to or even better than that of HARDN.

Neuronal plasma membrane has been thought to retain a lot of lipid raft components which play important roles in the neural function. Although the biochemical analyses of lipid raft using brain tissues have been extensively carried out in the past 20 years, many of their experimental conditions do not coincide with those of standard neuroscience researches such as neurophysiology and neuropharmacology. Hence, the physiological methods for lipid raft analysis that can be compatible with general neuroscience have been required. Herein, we developed a system to physiologically analyze ganglioside GM1-enriched lipid rafts in brain tissues using the “Enzyme-Mediated Activation of Radical Sources (EMARS)” method that we reported (Kotani N. et al. Proc. Natl. Acad. Sci. U S A 105, 7405–7409 (2008)). The EMARS method was applied to acute brain slices prepared from mouse brains in aCSF solution using the EMARS probe, HRP-conjugated cholera toxin subunit B, which recognizes ganglioside GM1. The membrane molecules present in the GM1-enriched lipid rafts were then labeled with fluorescein under the physiological condition. The fluorescein-tagged lipid raft molecules called “EMARS products” distributed differentially among various parts of the brain. On the other hand, appreciable differences were not detected among segments along the longitudinal axis of the hippocampus. We further developed a device to label the lipid raft molecules in acute hippocampal slices under two different physiological conditions to detect dynamics of the lipid raft molecules during neural excitation. Using this device, several cell membrane molecules including Thy1, known as a lipid raft resident molecule in neurons, were confirmed by the EMARS method in living hippocampal slices.

It is unclear whether local anesthetics, such as tetracaine, and antipsychotics, such as phenothiazines, act on lipids or proteins. In Saccharomyces cerevisiae, these drugs inhibit growth, translation initiation, and actin polarization, and induce cell lysis at high concentrations. These activities are likely due to the cationic amphiphilic structure common to these agents. Although drug-induced translational inhibition is conserved in mammalian cells, other mechanisms, including the phosphorylation of eIF2α, a eukaryotic translational initiation factor, remain poorly understood. At a concentration of 10 mM, tetracaine rapidly inhibited translation initiation and lysed cells, whereas, at 2.5 mM, it slowly induced inhibition without lysis. The pat1 disruptant defective in mRNA decapping and the xrn1 disruptant defective in 5'-3' exoribonuclease were partially resistant to translational inhibition by tetracaine at each concentration, but the gcn2 disruptant defective in the eIF2α kinase was not. Phosphorylation of eIF2α was induced by 10 mM but not by 2.5 mM tetracaine, whereas processing bodies (P-bodies) were formed at 2.5 mM in Pat1-dependent and -independent manners. Therefore, administration of tetracaine inhibits translation initiation with P-body formation at both concentrations but acts via the Gcn2-eIF2α system only at the higher concentration. Because other local anesthetics and phenothiazines induced Pat1-dependent P-body formation, the mechanisms involved in translational inhibition by these cationic amphiphiles are similar. These results suggest that this dose-dependent biphasic translational inhibition by tetracaine results from an increase in membrane proteins that are indirectly inhibited by nonspecific interactions of cationic amphiphiles with membrane lipids.

Action mechanisms of anesthetics remain unclear because of difficulty in explaining how structurally different anesthetics cause similar effects. In Saccharomyces cerevisiae, local anesthetics and antipsychotic phenothiazines induced responses similar to those caused by glucose starvation, and they eventually inhibited cell growth. These drugs inhibited glucose uptake, but additional glucose conferred resistance to their effects; hence, the primary action of the drugs is to cause glucose starvation. In hxt0 strains with all hexose transporter (HXT) genes deleted, a strain harboring a single copy of HXT1 (HXT1s) was more sensitive to tetracaine than a strain harboring multiple copies (HXT1m), which indicates that quantitative reduction of HXT1 increases tetracaine sensitivity. However, additional glucose rather than the overexpression of HXT1/2 conferred tetracaine resistance to wild-type yeast; therefore, Hxts that actively transport hexoses apparently confer tetracaine resistance. Additional glucose alleviated sensitivity to local anesthetics and phenothiazines in the HXT1m strain but not the HXT1s strain; thus, the glucose-induced effects required a certain amount of Hxt1. At low concentrations, fluorescent phenothiazines were distributed in various membranes. At higher concentrations, they destroyed the membranes and thereby delocalized Hxt1-GFP from the plasma membrane, similar to local anesthetics. These results suggest that the aforementioned drugs affect various membrane targets via nonspecific interactions with membranes. However, the drugs preferentially inhibit the function of abundant Hxts, resulting in glucose starvation. When Hxts are scarce, this preference is lost, thereby mitigating the alleviation by additional glucose. These results provide a mechanism that explains how different compounds induce similar effects based on lipid theory.

We examined a novel rice mutant, Fukei 71 (Oryza sativa L.), for alterations in the levels of hydroxycinnamoyl esters that are linked to cell wall polysaccharides and lignin units. In this mutant, a recessive mutation at a single locus caused the collapse of parenchyma cells in the internodes. Light microscopy revealed that the abnormal walls of internode parenchyma cells of Fukei 71 were stained by the Mäule reaction, which is specific for syringyl units in phenolic compounds. These walls were not stained by Wiesner's reagent (phloroglucinol-HCl), which reacts cinnamaldehyde in lignin. Levels of p-coumaric acid (PCA) and ferulic acid (FA) were apparently elevated in the abnormal tissue of the mutant. Western blotting analysis with antibodies specific for phenylalanine ammonia-lyase (PAL) revealed higher levels of PAL in the abnormal parenchyma tissue of Fukei 71 than in the parenchyma tissue of the parent cultivar Fujiminori. These results and the observation that PAL was produced at a greatly elevated level indicated that the phenylpropanoid pathway that leads to the biosynthesis of polysaccharide-linked FA and PCA was abnormally activated in the irregularly shaped and collapsed internode parenchyma cells, in which the biosynthesis of lignin is normally repressed.

This paper proposes a Haptic Learning-Science Simulator (HALS) which provides a possible method of higher education in science and mathematics for visually impaired students. When we understand the physics of a phenomenon, we usually try to visualize a phenomenon with the help of our own mental image formed by visual experiences. Owing to the lack of such experiences, it is quite hard for them to have a mental image, and so they have serious difficulties in learning science. Taking advantage of the haptic device, HALS aims at supplying them with some haptic (virtual) experiences of three-dimensional objects and dynamical phenomena. We first give an idea how to build mathematical models in HALS focussing on visualization of graphs of multivariable functions. Further, we discuss a physical model to be put in HALS which helps visually impaired students to perceive a moving body and to understand its physics.

We have built an arm-navigation assisting system for a visually impaired person (user) to reach an object on the table, where optical tracking of marks attacked both on the objects and on his arm is used in order to augment his sight. The system helps him with giving spacial information of the workspace so that he creates a cognitive map of the workspace. For this purpose degrees of congestion on the workspace must be conveyed to the user. Starting from the description of the assisting system, we propose in this paper a method of judging the degrees of congestion of the workspace around arm. There are five of them: from “narrow” to “broad,” which are determined by using well-established Neural Network techniques on the basis of the spacial data obtained by the Distance Field Model (DFM) representation of the workspace. Defining spaciousness by entropy-like measure based on the DFM data is also proposed separately.

Disposable diaper is heavy used in care home or hospital. It's often the case that helper doesn't notice that the patient eliminated. This is very discomfort for patient, and bad for the health. They are problem which should be solved. There are conventional incontinence sensor using gas sensor or capped electrode etc. Most of them are large size. So the patient feels something is wrong when he gets on them. It takes a lot of trouble to use because they are not disposable. These sensors are unfamiliar because of those problems. We developed device which make patient's quality of life better. We are writing to suggest that Ultra Small Disposable Defecation Sensor to solve those problem. This sensor is low cost, very small, and comfortable for patient and helper because of disposable. It enables using RFID.

CD1d-restricted invariant NKT (iNKT) cells play crucial roles in various types of immune responses, including autoimmune diseases, infectious diseases and tumor surveillance. The mechanisms underlying their adjuvant functions are well understood. Nevertheless, although IL-4 and IL-10 production characterize iNKT cells able to prevent or ameliorate some autoimmune diseases and inflammatory conditions, the precise mechanisms by which iNKT cells exert immune regulatory function remain elusive. This study demonstrates that the activation of human iNKT cells by their specific ligand α-galactosylceramide enhances IL-12p70 while inhibiting the IL-23 production by monocyte-derived dendritic cells, and in turn down-regulating the IL-17 production by memory CD4+ Th cells. The ability of the iNKT cells to regulate the differential production of IL-12p70/IL-23 is mainly mediated by a remarkable hallmark of their function to produce both Th1 and Th2 cytokines. In particular, the down-regulation of IL-23 is markedly associated with a production of IL-4 and IL-10 from iNKT cells. Moreover, Th2 cytokines, such as IL-4 and IL-13 play a crucial role in defining the biased production of IL-12p70/IL-23 by enhancement of IL-12p70 in synergy with IFN-γ, whereas inhibition of the IFN-γ-promoted IL-23 production. Collectively, the results suggest that iNKT cells modify the IL-12p70/IL-23 balance to enhance the IL-12p70-induced cell-mediated immunity and suppress the IL-23-dependent inflammatory pathologies. These results may account for the long-appreciated contrasting beneficial and adverse consequence of ligand activation of iNKT cells.

Disposable diaper is in heavy usage. It’s often the case that helper doesn’t notice that the patient eliminated. This is very discomfort for patient, and bad for the health. They are problem which should be solved. There are conventional incontinence sensor using gas sensor or capped electrode etc. Most of them are large size. So the patient feels something is wrong when he gets on them. It takes a lot of trouble to use because they are not disposable. These sensors are unfamiliar because of those problems. We developed device which make patient’s quality of life better. We are writing to suggest that Ultra Small Disposable Defecation Sensor to solve those problem. This sensor is low cost, very small, and comfortable for patient and helper because of disposable. It enables using RFID.

High osmolarity and glucose deprivation cause rapid shutdowns of both actin polarization and translation initiation in yeast. Like these stresses, administration of local anesthetics and of antipsychotic phenothiazines caused similar responses. All these drugs have amphiphilic structures and formed emulsions and permeabilized the cell membrane, indicating that they have the same features as a surfactant. Consistently with this, surfactants induced responses similar to those of local anesthetics and phenothiazines. Benzethonium chloride, a cationic surfactant, showed a more potent shutdown activity than phenothiazines, whereas SDS, an anionic surfactant, transiently depolarized actin without inhibiting translation initiation, suggesting that a cationic charge in the amphiphile is important to the shutdown of both reactions. The clinical drugs and the cationic surfactants at low concentrations caused shutdown without membrane permeabilization, suggesting that these compounds and stresses activate shutdown, via perturbation rather than disruption of the cell membrane.

Recently many studies on ubiquitous computing have been done. In the studies, ubiquitous ID architecture is one of the most important ones. In this study, we propose a new method for connecting to objects with RFTDs through the Internet. At first, we introduce a simple application called "Portable Environment Communicator". We try to apply the proposed method to it. Second, we propose a new name resolver architecture for portable objects, and a new method for selecting the most appropriate wireless base station around the objects, which is connected to the Internet. In the paper, the selection method is carried out using the supper arrangement method, distance field space model, and fuzzy measure theory.

It is well known that quantum mechanics is explained in quantum logic and orthomodular lattices. However, these logic and algebraic structure have not always succeeded in explaining behavior of quantum information systems. A qubit |/spl Psi/>=/spl alpha/|0>+/spl beta/|1> in quantum information systems is extension of classical concept "bit", where |0> and |1> are basis of a two dimensional quantum system, /spl alpha/ and /spl beta/ are probabilistic amplitudes in C (complex numbers). Then, one qubit can have infinite number of values in contrast with classical one bit. In this paper, to analyze various infinite number of quantum states, we establish a discrete algebraic structure as a model of qubit space, which is isomorphic to Kleene algebra 3= . Furthermore, we propose weak Kleenean non-additive measures and weak Kleene-Choquet integrals. Then, we show that we can analyze quantum communication channels effectively by the proposed framework.

It is known that some local anesthetics inhibit the growth of budding yeast cells. To investigate the pathway of local anesthetics’ action, we isolated and characterized mutants that were hyper-sensitive to tetracaine, and at the same time, temperature-sensitive for growth. They were collectively called las (local anesthetic sensitive) mutants. One of the LAS genes, LAS24, was found to be identical to KOG1, which had been independently discovered as a member of the TOR complex 1 (TORC1). Las24p/Kog1p is a widely conserved TOR binding protein containing the NRC domain, HEAT repeats and WD-40 repeats, but its function remains unknown. Like the tor mutants, the las24 mutants were found to have a defect in cell wall integrity and to show sensitivity to rapamycin. Furthermore, Las24p is required not only in TORC1-mediated (rapamycin-sensitive) pathways such as translation initiation control and phosphorylation of Npr1p and Gln3p, but also for the normal distribution of the actin cytoskeleton, which has been regarded as a TORC2-mediated event. Intriguingly, the temperature-sensitivity of the las24 mutant was suppressed by either activation of Tap42/PPase or by down-regulation of the RAS/cAMP pathway. Suppressors of the temperature-sensitivity of the las24-1 mutant were found not to be effective for suppression of the tetracaine-sensitivity of the same mutant. These observations along with the facts that tetracaine and high temperature differentially affected the las24-1 mutant suggest that Las24p/Kog1p is not a target of tetracaine and that the tetracaine-sensitive step may be one of downstream branches of the TORC1 pathway. Consistent with the broad cellular functions exerted by the TOR pathway, we found that Las24p was associated with membranes and was localized at vacuoles, the plasma membrane and small vesicles.

The theory of non-additive measures and integral calculus with respect to them is rich and has been developed in many streams. In this paper, the authors focus on and extend one special non-additive measure, which is called fuzzy measure. Then they focus on and extend an item from the integral calculus, called the Sugeno integral. This expansion enables us to treat concepts such as "negation" and "unknown" in the field of fuzzy measures--these concepts have never been treated well in the field. To achieve it, the authors attempt to translate the vagueness of fuzzy set theory and fuzzy logic to the ambiguity of fuzzy measure by considering the fact that the Sugeno integral in fuzzy measure theory can be represented using fuzzy switching functions with constants in fuzzy logic. Then, we attempt to apply the facts clarified in fuzzy logic to fuzzy measure. Consequently, two new concepts: "Ternary Kleenean Nonadditive Measure" and "Kleene-Sugeno integral" are proposed.

Authors attempts to translate the vagueness of fuzzy set theory and fuzzy logic to the ambiguity of fuzzy measure by considering the fact that the Sugeno integral in fuzzy measure theory can be represented in fuzzy switching functions with constants in fuzzy logic. Then, we attempt to apply the facts clarified in fuzzy logic to fuzzy measure. We propose two new concepts: “Extended fuzzy measure” and “Kleene-Sugeno integral”.