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The synthesis of TaSe3 ring‐shaped crystals displaying the coffee ring effect is investigated. By recrystallizing TaSe3 microcrystals dissolved in droplets of condensed Se gas, ring‐shaped crystals were successfully grown. This novel method for ring formation effectively addressed the issue of connecting the edges of the crystal. Consequently, the synthesis method has the capability to grow MX3 ring‐shaped crystals in any location where droplets can condense, can now be grown in specific locations, thus creating opportunities for advancements in electronic component development. [ABSTRACT FROM AUTHOR]

Estimating governing equations from observed time-series data is crucial for understanding dynamical systems. From the perspective of system comprehension, the demand for accurate estimation and interpretable results has been particularly emphasized. Herein, we propose a novel data-driven method for estimating the governing equations of dynamical systems based on machine learning with high accuracy and interpretability. The proposed method enhances the estimation accuracy for dynamical systems using sparse modeling by incorporating physical constraints derived from Hamiltonian mechanics. Unlike conventional approaches used for estimating governing equations for dynamical systems, we employ a sparse representation of Hamiltonian, allowing for the estimation. Using noisy observational data, the proposed method demonstrates a capability to achieve accurate parameter estimation and extraction of essential nonlinear terms. In addition, it is shown that estimations based on energy conservation principles exhibit superior accuracy in long-term predictions. These results collectively indicate that the proposed method accurately estimates dynamical systems while maintaining interpretability. [ABSTRACT FROM AUTHOR]

Patients with urea cycle disorders intermittently develop episodes of decompensation with hyperammonemia. Although such an episode is often associated with starvation and catabolism, its molecular basis is not fully understood. First, we attempted to elucidate the mechanism of such starvation‐associated hyperammonemia. Using a mouse embryonic fibroblast (MEF) culture system, we found that glucose starvation increases ammonia production, and that this increase is associated with enhanced glutaminolysis. These results led us to focus on α‐ketoglutarate (AKG), a glutamate dehydrogenase inhibitor, and a major anaplerotic metabolite. Hence, we sought to determine the effect of dimethyl α‐ketoglutarate (DKG), a cell‐permeable AKG analog, on MEFs and found that DKG mitigates ammonia production primarily by reducing flux through glutamate dehydrogenase. We also verified that DKG reduces ammonia in an NH4Cl‐challenged hyperammonemia mouse model and observed that DKG administration reduces plasma ammonia concentration to 22.8% of the mean value for control mice that received only NH4Cl. In addition, we detected increases in ornithine concentration and in the ratio of ornithine to arginine following DKG treatment. We subsequently administered DKG intravenously to a newborn pig with hyperammonemia due to ornithine transcarbamylase deficiency and found that blood ammonia concentration declined significantly over time. We determined that this effect is associated with facilitated reductive amination and glutamine synthesis. Our present data indicate that energy starvation triggers hyperammonemia through enhanced glutaminolysis and that DKG reduces ammonia accumulation via pleiotropic mechanisms both in vitro and in vivo. Thus, cell‐permeable forms of AKG are feasible candidates for a novel hyperammonemia treatment. [ABSTRACT FROM AUTHOR]

After producing triple (Gal, H-D and Sda)-KO pigs, hyperacute rejection appeared to no longer be a problem. However, the origin of xeno-rejection continues to be a controversial topic, including small amounts of antibodies and subsequent activation of the graft endothelium, the complement recognition system and the coagulation systems. The complement is activated via the classical pathway by non-Gal/H-D/Sda antigens and by ischemia-reperfusion injury (IRI), via the alternative pathway, especially on islets, and via the lectin pathway. The complement system therefore is still an important recognition and effector mechanism in xeno-rejection. All complement regulatory proteins (CRPs) regulate complement activation in different manners. Therefore, to effectively protect xenografts against xeno-rejection, it would appear reasonable to employ not only one but several CRPs including anti-complement drugs. The further assessment of antigens continues to be an important issue in the area of clinical xenotransplantation. The above conclusions suggest that the expression of sufficient levels of human CRPs on Triple-KO grafts is necessary. Moreover, multilateral inhibition on local complement activation in the graft, together with the control of signals between macrophages and lymphocytes is required. [ABSTRACT FROM AUTHOR]

Xenotransplantation is very attractive strategy for addressing the shortage of donors. While hyper acute rejection (HAR) caused by natural antibodies and complement has been well defined, this is not the case for innate cellular xenogeneic rejection. An increasing body of evidence suggests that innate cellular immune responses contribute to xenogeneic rejection. Various molecular incompatibilities between receptors and their ligands across different species typically have an impact on graft outcome. NK cells are activated by direct interaction as well as by antigen dependent cellular cytotoxicity (ADCC) mechanisms. Macrophages are activated through various mechanisms in xenogeneic conditions. Macrophages recognize CD47 as a "marker of self" through binding to SIRPα. A number of studies have shown that incompatibility of porcine CD47 against human SIRPα contributes to the rejection of xenogeneic target cells by macrophages. Neutrophils are an early responder cell that infiltrates xenogeneic grafts. It has also been reported that neutrophil extracellular traps (NETs) activate macrophages as damage-associated pattern molecules (DAMPs). In this review, we summarize recent insights into innate cellular xenogeneic rejection. [ABSTRACT FROM AUTHOR]

In order to investigate the influence of the surface-active element on the interfacial phenomena between molten iron and molten Al2O3-CaO-SiO2 slag, a mildly surface-active element, nitrogen, was introduced, and the interfacial phenomena were directly observed using an X-ray sessile drop method. The multiphysics model was employed to calculate the velocity of the Marangoni convection caused by the surface/interfacial tension gradient along with the contour of the sessile drop. Movement of the sessile drop was observed in the experiment, and the driving force of the movement was discussed from the distribution of surface tension active element viewpoint. The calculated velocity of the Marangoni convection in the droplet was reasonably agreed with the literature data for the metal-gas system, and thus, the same model was applied for the metal-slag system. The velocity of the Marangoni convection for the metal-slag system becomes ten times lower compared to that of metal-gas system. [ABSTRACT FROM AUTHOR]

The effect of oxygen content on the glass‐forming ability of binary Cu–Zr alloys is investigated by the in situ observation of the cooling process during the containerless solidification using an aerodynamic levitation technique. The oxygen content of ≈0.72 at% induces the crystallization of undercooled liquid Cu47Zr53 alloy, whereas that of ≈0.33 at% enhances the glass‐forming ability and leads to the formation of bulk metallic glass when compared with the alloy containing ≈0.20 at% of oxygen. The differential thermal analysis of the bulk metallic glass samples shows the extension of the undercooled liquid region with an increase in the oxygen content from 0.20 to 0.33 at% in the Cu47Zr53 alloy. Time‐resolved synchrotron X‐ray diffraction experiments reveal structure evolution of the Cu47Zr53 alloy from the undercooled liquid to glass or crystal. The effect of oxygen on the glass‐forming ability is qualitatively described in terms of reducing the critical cooling rate of the alloy. [ABSTRACT FROM AUTHOR]

Management of advanced hormone‐naïve prostate cancer (HNPC) is a critical public health issue. Useful prognostic markers are thus needed to select patients who will benefit from recently introduced upfront therapies. p16 expression is an adverse prognostic marker in prostate cancer. The present study aimed to determine whether p16 expression would serve as an adverse prognostic marker in advanced HNPC. A total of 79 patients diagnosed by needle biopsy with adenocarcinoma Gleason score ≥8 between 2010 and 2013 at Aichi Medical University were included in this study. The median patient age was 73 (range 52–87) years. The median follow‐up was 62 months (range 2–98). Fourteen patients had p16‐positive samples. Fifteen patients died from prostate cancer, 10 of whom were in the p16‐positive group. p16 positivity was associated with clinical T stage (P < 0.001), presence of IDC‐P (P < 0.001), distant metastasis (P < 0.001) and lymph node metastasis (P < 0.001). These results indicate that p16 expression is associated with adverse prognostic factor of prostate cancer and suggest that p16 expression may provide useful information for treatment planning and identifying suitable candidates for upfront chemotherapy or androgen receptor axis‐targeted therapy. [ABSTRACT FROM AUTHOR]

A class of the magnetostrictive iron-cobalt/nickel clad plate cantilever is prepared in this study. The relevant ability for harvesting vibration energy is systematically investigated in comparison with the single iron-cobalt cantilever. In addition, the effects of the magnitude of bias magnetic field (i.e., external magnetic field) and the magnetization angle on the energy-harvesting performance are considered. The results indicated that the iron-cobalt/nickel clad plate cantilever exhibits far greater power generation compared with that of the single iron-cobalt cantilever. Besides, the iron-cobalt/nickel clad plate cantilever displayed high sensitivity to the magnitude of bias magnetic field and the magnetization angle. In more detail, the output voltage of the iron-cobalt/nickel clad plate cantilever peaks at a point even while the bias magnetic field constantly increases. A theory of dynamic balance can explain this phenomenon. Meanwhile, the resonance frequency of the iron-cobalt/nickel clad plate cantilever is proportional to the bias magnetic field due to the influence of the elastic modulus variation. This work provides insights into the exploration and design, not only of the vibration-energy-harvesting components but also of the sensitive detectors. [ABSTRACT FROM AUTHOR]

A two-step plasma arc melting process, comprising a first step under Ar-30 pct H2 gas flow and the second step under Ar gas flow, has been newly developed for the deoxidation of Ti melts. The oxygen content after this process depended on the depth probed in the Ti melt. Decrease in the oxygen content from 1.5 to 0.7 mass pct in the surface region of the Ti melt occurred in the second step. [ABSTRACT FROM AUTHOR]

Background: Pancreatic islet xenotransplantation is a potential treatment for diabetes mellitus, and porcine pancreas may provide a readily available source of islets. Islets in juvenile pigs are smaller than those in young adult pigs, but the insulin content is very similar. In addition, as juvenile pigs are more easily reared in uncontaminated conditions, many researchers have conducted studies using pancreatic islets from juvenile pigs. We aimed to analyze the distributions of endocrine cell clusters by comprehensively evaluating juvenile porcine pancreatic development and to propose an appropriate age at which islets could be isolated from the juvenile porcine pancreas. Methods: Splenic (SL) and duodenal lobe (DL) samples were collected from the pancreases of pigs aged 0–180 days (n = 3/day after birth). The chronological changes in endocrine cell clustering were analyzed in relation to morphological changes, cell characterization, numbers, islet areas, and gene expression. Results: In juvenile pigs aged 0–21 days, the pancreas contained numerous endocrine cells, and compact islets appeared from 21 days of age. Well-defined small islets were seen at 28 days of age, and the clusters were denser in the SL than in the DL. At 35 days of age, the islets were morphologically similar to those observed at 180 days of age, and the greater number of islets was similar to that seen at 90 days of age. The differences in the islets’ cytoarchitecture between the lobes were negligible. The expression of β-cell-related genes was higher in the juvenile pancreas than in the adult pancreas, and the expression of neurogenin-3 decreased dramatically over time. Conclusions: These findings may have implications for attempts to refine the most appropriate age for islet isolation from porcine donors. Focusing on porcine pancreatic islets isolated at around 35 days after birth may offer benefits regarding their xenotransplantation potential. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of a novel biopsy instrument that extends the length of the side‐notch on the detection of prostate cancer in transrectal needle biopsy. Methods: We collaborated with a biopsy needle manufacturer and developed a novel biopsy instrument (PRIMECUT II long‐notch type) with a 25‐mm side‐notch length and 28‐mm stroke length to take longer tissue cores. The sampled core length, cancer detection rate, pain and complications of 489 patients who underwent transrectal biopsy using the long‐notch needle were compared with those of 469 patients who underwent biopsy using a normal instrument with a 19‐mm side‐notch length and 22‐mm stroke length. Results: The mean length of tissue taken by the long‐notch needle was significantly longer than that of tissue taken by the normal‐notch needle (16.3 vs 22.4 mm, P < 0.001). The overall cancer detection rate was 42.0% for the normal‐notch needle and 51.1% for the long‐notch needle (P = 0.005). In patients with a prostate volume of 20–40 mL, the cancer detection rate for the long‐notch needle was especially higher than that for the normal‐notch needle (74.2% vs 47.5%, P < 0.001). Multivariate analysis showed that the long‐notch needle improved cancer detection significantly (odds ratio 1.702, P < 0.001). There were no differences of pain during biopsy and complication between the two groups. Conclusions: The novel biopsy instrument with a 25‐mm side‐notch can take longer tissue samples safely and has a significantly higher rate of prostate cancer detection in transrectal biopsy. [ABSTRACT FROM AUTHOR]

Abstract: A chiral ligand for the rhodium‐catalyzed asymmetric 1,4‐addition of an arylboronic acid to a coumarin substrate that could markedly reduce catalyst loading was developed using interplay between theoretical and experimental approaches. Evaluation of the transition states for insertion and for hydrolysis of intermediate complexes (which were emphasized in response to the experimental results) using DFT calculations at the B97D/6‐31G(d) level with the LANL2DZ basis set for rhodium revealed that: (i) the electron‐poor nature of the ligands and (ii) CH–π interactions between the ligand and coumarin substrates played significant roles in both acceleration of insertion and inhibition of ArB(OH)2 decomposition (protodeboronation). The computationally‐designed ligand, incorporating the above information, enabled a decrease in the catalyst loading to 0.025 mol% (S/C=4,000), which is less than one one‐hundredth relative to past catalyst loadings of typically 3 mol%, with almost complete enantioselectivity. Furthermore, the gram‐scale synthesis of the urological drug, (R)‐tolterodine ( l)‐tartrate, was demonstrated without the need of intermediate purification. [ABSTRACT FROM AUTHOR]

Objectives To compare various methods for measuring tumor extent in prostate biopsy specimens to identify small-volume prostate cancer. Methods A total of 100 radical prostatectomy specimens were retrospectively analyzed. Receiver operating characteristic analysis was used to compare the abilities of prostate-specific antigen density, and four measures of tumor extent in prostate biopsy specimens - positive core number, greatest percentage of cancer in a single core, greatest length of cancer in cores and total length of cancer in cores - to identify small volume prostate cancer. Four definitions of insignificant cancer volume were used in this analysis: index and total tumor volume <0.5 mL, index tumor volume <1.3 mL and total tumor volume <2.5 mL. Multivariate analysis was also used to evaluate variables for predicting small-volume prostate cancer. Results Total length of cancer in cores had the highest areas under the curve of all the measures defining small-volume prostate cancer: index tumor volume <0.5 mL (0.855), total tumor volume <0.5 mL (0.877), index tumor volume <1.3 mL (0.784) and total tumor volume <2.5 mL (0.818). On multivariate analysis total length of cancer in cores was an independent predictive factor for prostate cancers with index tumor volume <0.5 mL ( P < 0.001), <1.3 mL ( P < 0.001) and total tumor volume <0.5 mL ( P < 0.001), respectively. Conclusion Our data suggest that total length of cancer in cores is the optimal measure of tumor extent in prostate biopsy specimens for identifying small-volume prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives To compare perioperative, oncological and functional outcomes of robot-assisted radical prostatectomy between experienced and novice open radical prostatectomy surgeons in a laparoscopically naïve center with a limited caseload. Methods Six surgeons carried out robot-assisted radical prostatectomy in 154 patients, which were divided into the following three groups: group 1 ( n = 90), including patients operated on by a surgeon with experience in both open radical prostatectomy and robot-assisted radical prostatectomy; group 2 ( n = 36), including patients operated on by two surgeons with experience in open radical prostatectomy only; and group 3 ( n = 28), including patients operated on by three surgeons with limited experience in both open radical prostatectomy or robot-assisted radical prostatectomy. Results Groups 2 and 3 did not differ significantly in their median values of external blood loss ( P = 0.165) or console time ( P = 0.103). Positive surgical margin rates for pT2 patients were also similar in these two groups: 21.2% (7/33) in group 2 and 22.7% (5/22) in group 3 ( P = 0.894). Kaplan-Meier analysis showed that 12 months after robot-assisted radical prostatectomy the prostate-specific antigen-free rate for pT2 patients was 96.0% in group 2 and 100% in group 3, but the pad-free continence rate was just 91.0% in group 1, 88.0% in group 2 and 75.5% in group 3 (group 1 vs group 3, P = 0.037; group 2 vs group 3, P = 0.239). The major complication rate after robot-assisted radical prostatectomy was 3.3% (3/90) in group 1, 11.1% (4/36) in group 2 and 17.9% (5/28) in group 3 (group 1 vs group 3, P = 0.008; group 2 vs group 3; P = 0.441). Conclusions Robot-assisted radical prostatectomy offers satisfactory postoperative outcomes even when carried out by surgeons with limited experience in open radical prostatectomy. [ABSTRACT FROM AUTHOR]

Embryonic stem cell research has facilitated the generation of many cell types for the production of tissues and organs for both humans and companion animals. Because ≥30% of pet cats suffer from chronic kidney disease (CKD), xenotransplantation between pigs and cats has been studied. For a successful pig to cat xenotransplant, the immune reaction must be overcome, especially hyperacute rejection. In this study, we isolated the gene for feline decay-accelerating factor (fDAF), an inhibitor of complement proteins, and transfected a swine endothelial cell line with fDAF to “felinize” the pig cells. These fDAF-expressing cells were resistant to feline serum containing anti-pig antibodies, suggesting that felinized pig cells were resistant to hyperacute rejection. Our results suggest that a “felinized” pig kidney can be generated for the treatment of CKD in cats in the future. [ABSTRACT FROM AUTHOR]

Zinc finger nuclease (ZFN) is a powerful tool for genome editing. ZFN-encoding plasmid DNA expression systems have been recently employed for the generation of gene knockout (KO) pigs, although one major limitation of this technology is the use of potentially harmful genome-integrating plasmid DNAs. Here we describe a simple, non-integrating strategy for generating KO pigs using ZFN-encoding mRNA. The interleukin-2 receptor gamma (IL2RG) gene was knocked out in porcine fetal fibroblasts using ZFN-encoding mRNAs, and IL2RG KO pigs were subsequently generated using these KO cells through somatic cell nuclear transfer (SCNT). The resulting IL2RG KO pigs completely lacked a thymus and were deficient in T and NK cells, similar to human X-linked SCID patients. Our findings demonstrate that the combination of ZFN-encoding mRNAs and SCNT provides a simple robust method for producing KO pigs without genomic integration. [ABSTRACT FROM AUTHOR]

Background: The development and validation of stem cell therapies using induced pluripotent stem (iPS) cells can be optimized through translational research using pigs as large animal models, because pigs have the closest characteristics to humans among non-primate animals. As the recent investigations have been heading for establishment of the human iPS cells with naïve type characteristics, it is an indispensable challenge to develop naïve type porcine iPS cells. The pluripotency of the porcine iPS cells can be evaluated using their abilities to form chimeras. Here, we describe a simple aggregation method using parthenogenetic host embryos that offers a reliable and effective means of determining the chimera formation ability of pluripotent porcine cells. Methodology/Significant Principal Findings: In this study, we show that a high yield of chimeric blastocysts can be achieved by aggregating the inner cell mass (ICM) from porcine blastocysts with parthenogenetic porcine embryos. ICMs cultured with morulae or 4–8 cell-stage parthenogenetic embryos derived from in vitro-matured (IVM) oocytes can aggregate to form chimeric blastocysts that can develop into chimeric fetuses after transfer. The rate of production of chimeric blastocysts after aggregation with host morulae (20/24, 83.3%) was similar to that after the injection of ICMs into morulae (24/29, 82.8%). We also found that 4–8 cell-stage embryos could be used; chimeric blastocysts were produced with a similar efficiency (17/26, 65.4%). After transfer into recipients, these blastocysts yielded chimeric fetuses at frequencies of 36.0% and 13.6%, respectively. Conclusion/Significance: Our findings indicate that the aggregation method using parthenogenetic morulae or 4–8 cell-stage embryos offers a highly reproducible approach for producing chimeric fetuses from porcine pluripotent cells. This method provides a practical and highly accurate system for evaluating pluripotency of undifferentiated cells, such as iPS cells, based on their ability to form chimeras. [ABSTRACT FROM AUTHOR]

In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals. [ABSTRACT FROM AUTHOR]

In most transgenic (Tg) animals created to date, a transgene consisting of the minimum promoter region linked to a cDNA has been used. However, transgenes on small plasmids are susceptible to the position effect, increasing the difficulty of controlling transgene expression. In this study, we attempted to create Tg pigs by intracytoplasmic sperm injection-mediated gene transfer (ICSI-MGT) using two large genomic transgenes derived from a bacterial artificial chromosome (BAC) containing the full genomic region encoding two human proteins, type I collagen and albumin. The production efficiencies (Tg piglets/live offspring) of type I collagen and albumin Tg pigs were 11.8% (6/51) and 18.2% (2/11), respectively. In all of the Tg pigs examined by real-time PCR analysis, tissue-specific expression of the transgene was confirmed (type I collagen: skin, tendon, vessels, genitalia; albumin: liver). The production of human proteins derived from BAC transgenes was also confirmed. Fluorescence in situ hybridization analysis indicated that the BAC transgenes transferred into porcine oocytes by ICSI-MGT were integrated into single or multiple sites on the host chromosomes. These data demonstrate that Tg pigs expressing human proteins in a tissue-specific manner can be created using a BAC transgenic construct and the ICSI-MGT method. [ABSTRACT FROM AUTHOR]

Surface segregation is very important for understanding the surface tension of binary systems. In case of a regular solution, the surface segregation is calculated using the Butler model. However, in the case of a complex system, like those forming intermetallic compounds, it is difficult to express the surface segregation. In order to discuss surface segregation in systems forming intermetallic compounds, we measured the density and surface tension of a Si–Cu binary system. We found the effect of clusters in both density and surface tension experimental data. The composition dependence of surface tension was expressed by a modified ideal solution model. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients’ oral temperature was elevated to about 38°C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9–23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium. [ABSTRACT FROM AUTHOR]

We examined the effect of the cytosolic Ca2+ concentration ([Ca2+]c) in marginal cells on the asphyxia- or furosemide-induced decrease in the endocochlear potential (EP) by perfusing the endolymph with or without a Ca2+ chelator or inhibitors of Ca2+-permeable channels or Ca2+-pump during transient asphyxia or intravenous administration of furosemide. We obtained the following results. (1) Endolymphatic administration of SKF96365 (an inhibitor of TRPC and L-type Ca2+ channels) or EGTA-acetoxymethyl ester (EGTA-AM) significantly inhibited both the transient asphyxia-induced decrease in EP (TAID) and the furosemide-induced decrease in EP (FUID). (2) Endolymphatic perfusion with nifedipine significantly inhibited the TAID but not the FUID. (3) The recovery from the FUID was significantly suppressed by perfusing the endolymph with EGTA-AM, nifedipine, or SKF96365. (4) Endolymphatic administration of thapsigargin inhibited both the FUID and TAID. (5) The recovery rate from the FUID was much slower than that from the TAID, indicating that furosemide may inhibit the Ca2+-pump. (6) A strong reaction in immunohistochemical staining for TRPC channels was observed in the luminal and basolateral membranes of marginal cells. (7) A positive staining reaction for the γ subunit of epithelial Na+ channels was observed in the luminal and basolateral membranes of marginal cells. (8) Positive EP was diminished toward 0 mV by the endolymphatic perfusion with 10 μM amiloride or 10 μM phenamil. Taken together, these findings suggest that [Ca2+]c regulated by endoplasmic Ca2+-pump and Ca2+-permeable channels in marginal cells may regulate the positive EP, which is partly produced by the diffusion potential of Na+ across the basolateral membrane in marginal cells. [ABSTRACT FROM AUTHOR]

Background and Aim: γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult mammalian brain. However, GABA is found not only in peripheral neuronal tissue, but also in many peripheral non-neuronal tissues, and is thought to have important physiological functions in addition to neurotransmission. We previously reported that GABA participates in chondrocyte proliferation. In the present study, we investigated the effects of GABA on the proliferation of a gastric cancer cell line, KATO III. Methods: Reverse transcription polymerase chain reaction and immunohistochemical analyses were performed to examine the expression of the GABA synthesis enzyme, glutamate decarboxylase (GAD), and that of the GABAA and GABAB receptor subunits. The production of GABA was confirmed by immunohistochemistry. The proliferative effect of GABA on KATO III cells was analyzed by bromodeoxyuridine incorporation assay, and the activation status of mitogen-activated protein (MAP) kinases (extracellular signal-regulated kinase [ERK]-1/2, Jun-N-terminal kinase, and p38) and the expression of cyclin D1 were analyzed by western blotting. Results: KATO III cells expressed GAD and GABA. More than five GABAA receptor subunits, including the π subunit, were expressed in KATO III cells; however, GABAB receptor subunits were not seen. The addition of GABA to the medium promoted KATO III proliferation, and maximum proliferative effects were observed in the presence of 10 or 1 µM GABA. The addition of 1 µM GABA predominantly activated ERK-1/2 among the three MAP kinases in addition to increasing cyclin D1 expression. Conclusion: GABA is able to promote KATO III cell proliferation in an autocrine or a paracrine fashion through GABAA receptors followed by MAP kinase activation. [ABSTRACT FROM AUTHOR]

Fe–Co alloys are attracting attention as magnetostrictive materials for energy harvesting and sensor applications. This work investigated the magnetostriction characteristics and crystal structure of additive-manufactured Fe–Co alloys using directed energy deposition. The additive-manufactured Fe–Co parts tended to exhibit better magnetostrictive performance than the hot-rolled Fe–Co alloy. The anisotropy energy ΔK1 for the Fe–Co bulk, prepared under a power of 300 W (referred to as bulk−300 W), was larger than for the rolled sample. For the bulk−300 W sample in a particular plane, the piezomagnetic constant d was large, irrespective of the direction of the magnetic field. Elongated voids that formed during additive manufacturing changed the magnetostrictive behavior in a direction perpendicular to these voids. Magnetic property measurements showed that the coercivity decreased. Since sensors should be highly responsive, Fe–Co three-dimensional parts produced via additive manufacturing can be applied as force sensors. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain, is also located in many peripheral nonneuronal tissues. The glutamate decarboxylase 67-green fl uorescent protein (GAD67-GFP) knock-in mouse is a useful model for studying the distribution of GABAergic cells in many tissues and organs. The lungs of these mice contain cells with an intense GFP signal exclusively in the airway epithelium. We aimed to characterize the GFP-positive cells and to clarify their relationship with the GABAergic system. We identified the GFPpositive cells as pulmonary neuroendocrine cells (PNECs) by immunohistochemistry for the protein gene product 9.5 and calcitonin gene-related peptide and by ultrastructural analysis. Immunohistochemistry for GADs and GABA revealed GAD65/67 and GABA in GFP-positive PNECs. Reverse transcription-polymerase chain reaction analyses revealed mRNAs encoding the GABAB receptor subunits necessary for the assembly of functional receptors, R1 and R2, in the lung. GABAB receptor subunit R1 and R2 proteins were expressed in many airway epithelial cells including alveolar epithelial cells other than GFP-positive PNECs. The present findings demonstrated that PNECs in the airway epithelium have a GABA production system and indicated that GABA plays functional roles in airway epithelial cells through GABAB receptors. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA) was first discovered as an inhibitory neurotransmitter in the central nervous system (CNS) and has been reported to have a variety of functions, including regulation of cell division, cell differentiation and maturation, and to be involved in the development of certain cancers outside the CNS. In the present study, using the human renal cell carcinoma cell line Caki-2, we demonstrated that GABA stimulation significantly increased the expression of MMP-2 and -9 and subsequently increased the invasive activity of the cancer cells. Because MAPK signaling is one of the key regulators of MMP expression, we further evaluated MAPK signaling after stimulation with GABA. It was found that GABA stimulation promoted the phosphorylation of MAPKs, including ERK1/2, JNK, and p38. ERK1/2 phosphorylation was sustained for up to 12 h, while phosphorylation of JNK and p38 returned to the endogenous level by 30 min. It was noteworthy that the ras/raf/MEK/ERK pathway inhibitor PD98059 attenuated GABA-induced MMP-9 expression and that both PD98059 and MMP inhibitors attenuated the GABA-induced invasive activity of Caki-2 cells. Moreover, data obtained by depletion of the MEK/ERK pathway using interfering RNA transfection of Caki-2 cells clearly corroborated the above results, as both MMP-9 expression and GABA-induced invasive ability were decreased significantly. We also demonstrated that the GABA-induced increase in invasive ability via ERK1/2 up-regulation was mediated mainly through the GABA-B receptor. These results indicate that GABA stimulation promotes cancer cell invasion and that the effect is partly due to ERK1/2-dependent up-regulation of MMPs. [ABSTRACT FROM AUTHOR]

It is well-known that oxide melts easily form a glass state from a supercooled state; however, it is difficult for some oxides to transform to the glass state from the corresponding supercooled state. β-BaB2O4 (β-BBO) crystals are important materials for laser applications. The β-BBO crystal easily grows from the supercooled melt, and it is therefore difficult to form the BBO glass state. We attempted to make BBO glass by a containerless technique using the conical nozzle gas-jet levitation (CNL) method. We were successful in making BBO glass with a diameter of 2 mm from a highly supercooled melt without rapid quenching. In order to clarify the phase selection mechanism of the BBO melt, we performed high-energy X-ray (113.6 keV) diffraction experiments on the glassy and supercooled liquid BBO using the CNL technique at the BL04B2 beamline of SPring-8. From these experiments, the structure factor S( Q) of BBO glasses and supercooled melts were found to have almost the same features. From these S( Q), we obtained the radial distribution function T( r)=4π rg( r). The analysis also showed that BBO glass and the BBO-supercooled melt have the same short-range distances. For phase selection between crystalline and glassy phases, we discuss a structure model of the BBO melt, including medium range structure based on the short-range structure obtained in this experiment. [ABSTRACT FROM AUTHOR]

High-energy synchrotron X-ray diffraction experiments were performed for clathrate-forming barium–germanium (Ba–Ge) alloys in the liquid state near the eutectic composition. The accurate structure information of highly reactive melts has been obtained by applying electrostatic levitation technique as a containerless method. The structure information obtained from the reverse Monte Carlo simulation suggests that the short-range ordering between the Ge atoms occurs with the addition of Ba atoms in the liquid Ba–Ge alloys. This can be associated with the formation of the cage-like structure composed of the Ge atoms in the liquid alloys near the eutectic composition. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim: The level of γ-amino-butyric acid (GABA) is reported to be increased in colon cancer. Moreover, data suggests that GABA plays a role in the proliferation or maturation of some types of cells. We examined the expression of GABA in intramucosal colonic tumors to clarify the relation between GABA and the degree of atypia. Methods: Paraffin sections were prepared from 56 protruded-type colonic neoplasms, which were classified as intramucosal adenocarcinoma (AC), adenoma with severe atypia (ASA), or adenoma with mild to moderate atypia (AMA). Expression of GABA was investigated immunohistochemically, and GABA immunoreactivity was compared to the staining patterns of carcinoembryonic antigen (CEA) and cancer-associated antigen (CA19-9) which were classified into three categories. Results: Intense GABA immunoreactivity was observed in 73.7%, 54.6%, 13.3%, and 5.4% of AC, ASA, AMA, and normal mucosa specimens, respectively. Kendall's correlation coefficient between GABA immunoreactivity and the degree of atypia was 0.447. Strong, positive CEA staining (pattern 3) was observed in 57.9%, 36.3%, and 13.3% of AC, ASA, and AMA specimens, respectively. Strong, positive CA19-9 staining was observed: 26.3%, 9.1% and 0%, respectively. In AC and ASA, the proportion of glands with strong GABA immunoreactivity was greater than the proportion of glands that were strongly positive for CA19-9. Conclusion: GABA may be useful as a tumor marker in combination with other tumor markers such as CEA and CA19-9. [ABSTRACT FROM AUTHOR]