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The GABA-synthesizing enzymes glutamate decarboxylase (GAD)1 and GAD2 are universally contained in GABAergic neurons in the central nervous system of the mouse and rat. The two isoforms are almost identically expressed throughout the brain and spinal cord. By using in situ hybridization, we found that the mouse lateral striatum concentrates medium-sized projection neurons with high-level expression of GAD1, but not of GAD2, mRNA. This was confirmed with several types of riboprobe, including those directed to the 5'-noncoding, 3'-noncoding and coding regions. Immunohistochemical localization of GAD1 also revealed predominant localization of the enzyme in the same striatal region. The lateral region of the mouse striatum, harboring such neurons, is ovoid in shape and extends between interaural +4.8 and +2.8, and at lateral 2.8 and dorsoventral 2.0. This intriguing region corresponds to the area that receives afferent inputs from the primary motor and sensory cortex that are presumably related to mouth and forelimb representations. The lateral striatum is included in the basal ganglia-thalamocortical loop, and is most vulnerable to various noxious stimuli in the neurodegeneration processes involving the basal ganglia. We have confirmed elevated expression of GAD1 mRNA, but not of GAD2 mRNA, also in the rat lateral striatum. Image analysis favored the view that the regional increase is caused by elevated cellular expression, and that the greatest number of medium-sized spiny neurons were positive for GAD1 mRNA. The GAD1 mRNA distribution in the mouse lateral striatum partially resembled those of GPR155 and cannabinoid receptor type 1 mRNAs, suggesting functional cooperation in some neurons.

CO2-EOR is one of the proven enhanced oil recovery (EOR) techniques and has been used commercially. However, in field applications, unfavorable sweep efficiency is often reported. In order to improve the sweep efficiency of CO2 flooding, we investigated an applicability of CO2 micro bubbles. To evaluate the applicability of CO2 micro bubbles for CO2-EOR, we conducted core flooding experiments using CO2 micro bubbles and the results were compared with the normal CO2 flooding. Previous study confirmed the generation of CO2 micro bubbles by using a specially developed porous filter. Using this filter, core flooding experiments were conducted. During the experiment, flooding behavior was monitored by a medical X ray CT system, and recovered oil and water were collected to make a quantitative comparison with normal CO2 flooding. From the images taken by the medical X ray CT, we observed that CO2 micro bubbles flowed over both upper and lower parts of core samples, while normal CO2 flowed only upper part of core samples. As a result, a delay of CO2 break-through was confirmed in CO2 micro bubble flooding case. The time series of medical X ray CT images indicates improvement in sweep efficiency by using the CO2 micro bubbles. In addition to this, the material balance calculation during the core floodings revealed 3% of additional oil recovery compared to the normal CO2 flooding. From the experiments, differences in flooding behavior were clearly observed between the normal CO2 and the CO2 micro bubbles injection. We consider the differences would lead to the improvement of both vertical and areal sweep efficiencies. Although this technique is still in a stage of fundamental research, since the technique only requires the special filter and it is considered that it can be easily installed at the down hole, it may provide a novel option to improve the CO2-EOR performance.

Nanoparticle albumin–bound paclitaxel (nab-paclitaxel) is delivered to tumors and increases antitumor activity compared with solvent-based paclitaxel. However, in a clinical trial, higher and lower rates of peripheral neuropathy and neutropenia were observed. In this study, we compared the effects of nab-paclitaxel and standard paclitaxel on pain behaviors in rats. Repeated administration of nab-paclitaxel dose-dependently induced both mechanical and cold allodynia, and the effects of nab-paclitaxel on pain behaviors tended to be stronger than that of standard paclitaxel at the doses used clinically. These results suggest that closer attention must be paid to the neuropathy when administering nab-paclitaxel in clinical settings. Keywords:: nanoparticle albumin–bound paclitaxel, paclitaxel, peripheral neuropathy

The stability and support effects of large-scale underground caverns located in jointed rock masses are principally ruled by the mechanical behavior of discontinuities. The major deformations of the host rock masses containing underground caverns originate from the normal and shear movements among the walls of discontinuities. Therefore, in the numerical simulations of the deformation behavior of underground structures, how to accurately model the discontinuities becomes a key problem. In this study, a 2-D distinct element code, UDEC, was used to analyze the deformation behavior of an underground cavern of a pumped storage power plant, based on in-situ geological data. The validity of numerical simulation was evaluated by comparing the numerical results with the site measurement data at two cross-sections of the cavern. Some local deformation behavior of the cavern affected by the characteristics of discontinuity distributions was discussed. The influences of cross-sectional shape of the cavern and the orientation of initial ground stress on the performance of cavern were evaluated. The simulation results revealed that the orientation, position and density of discontinuities as well as the cross-sectional shape of a carven influences its deformation behavior and stability significantly., SOILS AND FOUNDATIONS, 50(5), pp.609-621; 2010

Although the dosage of cationic flocculants used for water treatment is well known to increase in the presence of natural organic matter (NOM), the underlying reasons for this increase are not properly understood. Herein, we studied the flocculation behavior of polystyrene latex (PSL) particles in the presence and absence of polyacrylic acid (PAA5K) as an NOM analogue using an end-over-end rotation apparatus for standardized flow mixing. In the absence of PAA5K, the initial rate of cationic flocculant (PAM5M)-induced flocculation was enhanced, as reflected by the size of flocculant in solution. Additionally, flocculation experiments were performed in the presence of 0.5 mg/L PAA5K for five concentrations of PAM5M and two ionic strengths, and the increase of the initial rate of PAM5M-induced flocculation was suppressed by PAA5K immediately after mixing, with the most pronounced suppression obtained at a PAM5M concentration similar to PAA5K. Based on the above insights and the results of viscosity measurements, the inhibitory effect of PAA on flocculation was ascribed to (1) the reduction of PAM charge and the concomitant shrinkage via electrostatic association with PAA and (2) the termination of polycation adsorption on PSL caused by polyion complex formation when the charge ratio of PAM:PAA is close to unity.

The tribological properties of a new and unique thermoreversible gel lubricant (TR gel lube) were investigated. TR gel lube, which includes 10–40% of amide-type gelling agent in base fluid, is able to repeatedly alter or convert phase from gel state to liquid state at the melting point of the gelling agent. High-pressure rheological tests were performed in order to characterize the behavior of base oil and TR gel lube as a function of pressure and temperature. The effect of TR gel lube on ball bearing fatigue life was carried out by systematic tests using thrust ball bearings. The results of L 10 life tests of TR gel lube showed a longer life than the conventional greases. This result was investigated from the oil film formation. It was found that the gelling agent played a key role in the lubricating properties. Some mechanisms such as adsorbed film formation and solid-like formation are proposed.

Supplemental Digital Content is available in the text, In young children, infrequent antigen exposure, which is partly characterized by fewer vaccinations, may be a factor impairing the immunogenicity of inactivated influenza vaccine. We assessed the effects of prior vaccinations on age-specific immune responses in Japanese children aged 6 months to 3 years, using data from a cohort study with 266 children who had received 2 doses (0.25 mL/dose for < 3 years old, 0.5 mL/dose for 3 years old) in the 2006/2007 season. Serological measures, primarily seroprotection rates, between previously vaccinated and vaccine-naïve children were compared within 1-year age strata. The seroprotection rate was defined in 2 ways as the proportion of subjects who achieved an antibody titer of 1:40 or 1:160. Multivariate logistic regression was also performed to estimate the independent effect of prior vaccination on seroprotection rate. After the first dose, seroprotection rates with the threshold of 1:40 in vaccine-naïve 1-year-olds remained low (28% for AH1, 26% for AH3, 2% for B), similar to those of 0-year-olds. In contrast, seroprotection rates in previously vaccinated 1-year-olds (77% for AH1, 86% for AH3, 18% for B) were significantly higher than those in vaccine-naïve 1-year-olds. These seroprotection rates for AH1 and AH3 were comparable with those in previously vaccinated 2- and 3-year-olds. Although seroprotection rates for B remained low in every age stratum even after the second dose, seroprotection rate in previously vaccinated 1-year-olds (50%) was similar to that in 3-year-olds. After adjustment for age, baseline antibody titer and experience of acute febrile respiratory illness in the preceding season, odds ratios showed a significant independent positive effect of prior vaccination on seroprotection rate for every strain. After the seroprotection threshold was changed from 1:40 to 1:160, the results of the effects of prior vaccinations on immunogenicity were similar or became more evident, which demonstrate the robustness of our findings. Our study found that prior vaccinations improved poor immunogenicity among young children, especially in 1-year-olds.

The rock masses in a construction site of underground cavern are generally not continuum due to the presence of discontinuities, such as bedding, joints, faults and fractures. The performance of an underground cavern is principally ruled by the mechanical behaviors of the discontinuities in the vicinity of the cavern. A number of experimental and numerical investigations have demonstrated the significant influences of discontinuities on the mechanical, thermal and hydraulic behaviors of discontinuous rock masses, indicating that the deformation mechanism and stability of rock structures in the discontinuous rock masses depend not only on the existing discontinuities but also the new cracks generated and thereafter keep propagating due mainly to the stress redistribution induced by excavation. In this study, an Expanded Distinct Element Method (EDEM) was developed for simulating the crack generation and propagation due to the shear and tension failures in the matrix rock blocks. Using this method, excavation simulations of deep underground caverns have been carried out on the models with differing depths of cavern and differing geometrical distributions of the existing discontinuities. Model experiments by using the base friction test apparatus were conducted to verify the proposed numerical approach. Furthermore, the support effects of rock bolts on controlling the deformations of the rock mass surrounding a cavern and movements of key blocks were evaluated by means of the EDEM approach., International Journal of Rock Mechanics and Mining Sciences, 46(1), pp.97-106; 2009

大規模地下空洞掘削時の岩盤変形挙動と安定性を評価するにあたっては，節理，断層などの不連続面の影響を適切にモデル化することが重要である．不連続性岩盤内での空洞掘削を考えた場合，周辺岩盤の変形や破壊の大部分は不連続面に沿うせん断破壊やダイレーションに起因することが多いと認識されていながらも，設計の現状は連続体解析に基づくのが主流である． 本論文では，小丸川発電所の地下空洞掘削における情報化設計施工で得られた調査・計測データを分析し，不連続性岩盤内に掘削された大規模地下空洞の特徴的挙動について整理する．さらに，不連続体解析手法である個別要素法を用いて解析を行い，実計測との比較により解析手法の有用性を検証する．

The phase behavior in the brine/sodium N-dodecanoyl sarcosinate (Sar)/isopropyl N-dodecanoyl sarcosinate (SLIP) system has been investigated by means of phase study, static light scattering, and small-angle X-ray scattering. The liquid crystal phases, hexagonal (H(1)) and discontinuous cubic (I(1)), melt upon the addition of NaCl, which shows the similar effect to the increasing of temperature. The addition of SLIP to the brine/Sar solution at high Sar concentration induces the phase transition from H(1) to I(1) via the isotropic micellar solution (W(m2)). The micellar structure in the W(m2) phase also changes from the wormlike to the globular micelle with SLIP concentration. Adding NaCl reduces the repulsive force between the Sar head groups and simultaneously the space of the solubilized SLIP in the palisade layer, leading SLIP to shift their location further into the micelle core. As a consequence, the hexagonal symmetry breaks into the micelle solution and the liquid crystal order is destabilized entropically.

The phase sequence of the N-dodecyl-N-octyl-N-methylamine oxide (C12C8MAO)/HCl/water system with increasing apparent degree of protonation, X, defined as [HCl]/[C12C8MAO], has been studied. For a 100 mM concentration of C12C8MAO the following sequence of phases has been observed: L1/L2, L1/Lalpha/L2, L1/Lalpha, Lalpha, Lalpha/L2. The single-phase Lalpha region begins at X = 0.007 and ends at X = 0.35. The upper phase boundary, X*, depends strongly on the acid that is used for the protonation of the surfactant. It is shifted for increasing hydrophilicity of the acid to higher X values. For formic acid X* = 0.95, and for HBr X* = 0.05. A weakly protonated 1% solution of the surfactant is an iridescent Lalpha phase. Both unilamellar vesicles and multilamellar vesicles are observed in cryo transmission electron microscopy and freeze fracture transmission electron microscopy images in the Lalpha phase. The phase sequence with protonation differs from that of single-chain amine oxide surfactants. The synergism between the protonated and the nonprotonated species is very weak in the range X < X*, while the transition from the Lalpha phase to the Lalpha/L2 two-phase region is considered to be due to synergism. Little or no synergism is observed regarding the surface tension, but synergism does appear in the interfacial tension between decane and the aqueous solution. The viscoelastic properties of the vesicle/Lalpha phase resemble those of densely packed hard spheres. The effects of electric charge on the elastic property of the vesicles could be understood in terms of the osmotic pressure of the solutions. The interlamellar spacing evaluated by small-angle X-ray scattering showed a minimum around X approximately 0.1, which is interpreted as a result of two opposing contributions. One contribution is the suppression of undulation of bilayer membranes by introduction of electric charges, and the other comes from the increasing total bilayer thickness due to the increasing hydrogen bond formation with increasing X.

The surface tension of aqueous solutions of cationic, nonionic, and anionic surfactants was measured as a function of the size of drop formed under the tip of a glass capillary and the time for whi...

Ryo Fujiki,1,2 Kiichiro Morita,1,2 Mamoru Sato,1,2 Yuji Yamashita,1,2 Yusuke Kato,1,2 Yohei Ishii,2 Yoshihisa Shoji,1,2 Naohisa Uchimura1 1Department of Neuropsychiatry, Kurume University, 2Cognitive and Molecular Research Institute of Brain Diseases, Kurume University School of Medicine, Kurume-City, Japan Abstract: Neuroimaging studies have been conducted using word generation tasks and have shown greater hypofrontality in patients with schizophrenia compared with healthy subjects. In this study, we compared the characteristics of oxygenated hemoglobin changes involved in both phonological and categorical verbal fluency between 35 outpatients with schizophrenia and 35 healthy subjects during a Japanese “shiritori” task using single-event-related near-infrared spectroscopy. During this task, the schizophrenic patients showed significantly smaller activation in the prefrontal cortex area than the controls. In addition, a significant positive correlation was obtained between oxygenated hemoglobin changes (prefrontal cortex area, inferior parietal area) and the severity of positive psychiatric symptoms. It is possible that hypofrontality of patients may be a diagnostic assistance tool for schizophrenia, and that the relationship between activation and positive syndrome scores may be of help in predicting functional outcome in patients. Keywords: word production task, single-event-related near-infrared spectroscopy, schizophrenia, hypofrontality, biological marker

A novel emulsion and its preparation route were established in a quasi-ternary system with a nonionic surfactant, water, glycerol, and squalane. This emulsion is simply obtained by diluting a disco...

It is shown that the hydrophilicity of the alkyldimethylaminoxide surfactants passes with increasing protonation through a minimum. Both the unprotonated species and the completely protonated species are less surface active than the mixture of the species. The properties of the micellar solutions depend also very much on the acid that is used for the protonation. For strong hydrophilic acids like HCl or formic acid the micellar solutions remain in the L1-phase. For acids the counter-ions of which can shield ionic charges very well like HClO4 the micellar solutions pass with increasing protonation from the L1 to the Lα-phase and back to the L1-phase.

Four pediatric clinics in Fukuoka, Japan, collected 822 cases of nasopharyngeal specimens from patients with influenza-like symptoms from 1 October 2002 to 31 March 2003. Age distribution of these cases was 6 months to 15 years old and mean age was 5.98 years old. Two hundred seventy-eight cases were positive for influenza type A(H3N2) and 176 cases for type B. When compared with virus culture, the sensitivity of the rapid detection kits for type A(H3N2) was 89.4% by nasal swab and 78.8% by throat swab, while type B testing revealed 75.7% positive by nasal swab and 78.3% by throat swab. Comparison of sensitivity of rapid detection kits to virus culture from the onset of influenza-like illness showed testing at 6 h from onset yielded the highest sensitivity (89.3%) in A(H3N2) (p

Antigenicity of all the A(H3) viruses which we isolated from specimens collected in Sendai and Fukuoka, Japan in 2002–2003 influenza season was examined by hemagglutination inhibition test (HI) using the ferret antiserum against A/Panama/2007/99 (H3N2), the vaccine strain for the past three influenza seasons, provided by WHO Influenza Collaborating Center, Japan. All the viruses were isolated in MDCK cell system. From the beginning of the epidemic, we found that many isolated virus strains reacted with the standard antiserum more than 4- to 16-fold less than its homologous titer, in both cities. The number of isolation of such antigenic drifted viruses increased and dominated the isolates in this season. We show here the chronological appearance of such variants in this season. Furthermore, we performed genetic analyses on the HA genes of the isolates along with those of previous two consecutive seasons. Thus it was revealed that the isolates of this season make a clear cluster different from the cluster in the previous seasons, and the variants of 2002–2003 season make a different cluster from those of previous two seasons. Moreover, no difference was found in clusters which could explain the difference between these variants and nonvariants, and among variants isolated in four cities.

A series of studies were performed to investigate the ability of rapid antigen-detection kits in diagnosis of influenza. Clinical specimens were collected from a total of more than 3000 cases of influenza-like illness who visited out-patient clinics in Sendai and Fukuoka, Japan, during the 2001–2002 and 2002–2003 influenza seasons. Each clinical specimen was examined with a kit and virus isolation, and results were analyzed retrospectively by several points of interest: sensitivity of the kits based on the virus isolation and the sensitivity by type and subtype of influenza, kinds of specimens, the time course of influenza, and variation of sources of the specimens. Thus, the sensitivities of a kit were 83%, 52% and 58% in general for influenza A(H3N2), A(H1N1), and B, respectively, and those of another kit were 76%, 71%, and 62%, respectively, in 2001–2002 influenza season. The sensitivity using nasal swabs was better than that using throat swab, though only 5% up. Specimens tended to be less sensitive when collected shortly after the onset of illness, and the sensitivity seemed quite varied (17–92%) by source of specimens: staff who collect the specimens, and/or by population of the patients.

In general, spherical or rod micelles in aqueous micellar solution (Wm) or hexagonal liquid crystalline (H1) phases of hydrophilic ionic surfactant change to a bilayer structure of lamellar liquid crystal (Lα) upon addition of amphiphilic oil such as higher alcohol, because such an amphiphilic molecule penetrates in the surfactant palisade layer and the surfactant layer curvature becomes less positive. When an N-acylamino acid derivative oil (N-acylamino acid ester, AAE) such as isopropyl N-dodecanoylsarcosinate (sarcosine N-lauroyl isopropyl, SLIP) is added to sodium dodecyl sulfate (SDS) aqueous solution, a similar phase transition takes place. It was found, however, that the surfactant layer curvature changes in an opposite way from H1 to a discontinuous cubic phase (I1) upon addition of SLIP in the N-acylamino acid based surfactant sodium N-dodecanoylsarcosinate (Sar) instead of SDS. The I1 phase consists of discrete micelles, and its structure is indexed to the Fm3m or F23 space group and confirmed b...

The Krafft temperature and solubilization power of ionic and nonionic surfactants in aqueous solutions are strongly affected by added polar oils such as amino‐acid‐based oils (e.g., N‐acylamino acid esters, AAE), because they tend to be solubilized in the surfactant palisade layer. The Krafft temperatures of 5 wt.% sodium dodecyl sulfate (SDS)‐water and octaoxyethylene octadecyl ether (C18EO8)‐water systems largely decreases upon addition of AAE and 1‐hexanol, whereas it decreases very slightly in isopropyl myristate (IPM) and n‐dodecane. The lowering of the Krafft temperature can be explained by the same mechanism as the melting‐temperature reduction of mixing two ordinary substances. Namely, the polar oils are solubilized in the surfactant palisade layer of micelles and reduce the melting temperature of hydrated solid‐surfactant (Krafft temperature). On the other hand, non‐polar oil such as dodecane is solubilized deep inside micelles and makes an oil pool. The solubilization of non‐polar oil i...

アルツハイマー病では中枢聴覚系の機能障害を示唆する症状を合併する場合が少なくない．また細胞変性等の病変が疾病脳の聴覚上行路各部位にも確認されている．本研究ではマウス脳のこれらの部位におけるコリン線維とムスカリン性受容体（m2，m3タイプ）の発現分布密度を測定した．聴覚上行路諸核で，これらコリン線維・受容体を介する情報伝達・変換が聴覚の伝達に一定の意義を有することが，本研究から強く示唆された．

A-B-type silicone copolymer (or surfactant), Me3SiO(Me2SiO)12-Me2SiCH2CH2CH2-O-(CH2CH2O)33.1H(Si14C3EO33.1), forms lamellar liquid crystal (Lα) in a pure state. In a binary water-Si14C3EO33.1 system, the Lα phase coexists with excess water in a dilute region, whereas the Lα phase changes to an isotropic solution (Wm) by replacing water with ethylene glycol. Although water enhances the segregation between hydrophilic and lipophilic chains of copolymer, it does not change the layer curvature of long lipophilic-chain copolymer to be positive. Since ethylene glycol is more soluble in the hydrophilic chain than water, it changes the curvature from zero to positive, where positive curvature means the copolymer-layer curvature is convex toward water or polar solvent. When ethylene glycol is replaced with PEG 300 (polyethylene glycol, Mn ca=300), the Lα-H1(normal hexagonal phase)-Wm transition takes place. With the further increase in the molecular weight of PEG, the Lα phase coexists with an excess PEG as well as the water-copolymer system and the solubilization of PEG in the Lα phase decreases. This change in the phase behavior may be attributed to the solubilization part of PEG in the hydrophilic chain of the silicone copolymer. On the other hand, non-polar solvent, octamethylcyclotetrasiloxane, D4, is soluble in the lipophilic chain, and the Lα phase changes to a reverse micellar solution (Om) via reverse hexagonal (H2) phase. With the increase in the molecular weight of oil, the Lα phase retreats to the concentrated region and the solubilization of oil (poly(dimethylsiloxane)) in the Lα phase becomes very low. As a result, PEG and silicone oil change the surfactant (or copolymer) layer curvature in the opposite way, but, the swelling of high-molecular-weight solvents or homopolymers in the Lα phase is very restricted. In ternary water/ Si14C3EO33.1/D4, ethylene glycol/ Si14C3EO33.1/D4, and PEG/Si14C3EO33.1/poly (dimethylsiloxane) systems, isotropic microemulsions are formed at an equal polar/non-polar solvent ratio. The relationship between microemulsions with water and oil or with hydrophilic and lipophilic homopolymers is also discussed.

In Japan, the routine immunization program with oral polio vaccine (OPV) has been suspended since September 2012, when a program with 4 doses of inactivated monovalent polio vaccine (IPV) or quadrivalent vaccine against diphtheria, pertussis, and tetanus with IPV (DTaP-IPV) was introduced. The aim of this study was to examine the interchangeability among these 3 types of polio vaccines.We conducted a prospective cohort study at 5 pediatric clinics in Japan. A total of 153 infants were assigned to 1 of the 4 groups by considering the vaccination history of OPV and trivalent vaccine against DTaP. Eleven infants with a history of OPV received 3 doses of DTaP-IPV; 49 infants with a history of OPV and DTaP received 3 doses of IPV; 50 polio vaccine-naive infants received 2 doses of IPV followed by 2 doses of DTaP-IPV; and 43 polio vaccine-naive infants received 2 doses of DTaP-IPV followed by IPV. The immunogenicity after polio vaccination was evaluated among these 4 groups.After 2 doses of polio vaccination, more than 80% of the infants exhibited a neutralization antibody titer ≥1:8 for all Sabin strains and wild strains in all groups. After the third dose, the seroprotection proportion (i.e., a neutralization antibody titer ≥1:8) reached about 100%. After the fourth dose, a neutralization antibody titer exceeded the required protective levels (i.e., a neutralization antibody titer ≥1:8) considerably in all groups.Four doses of polio vaccines induced a sufficient level of immunity in Japanese infants, irrespective of vaccine combinations or order.

Background GABA has important functions in brain plasticity related processes like memory, learning, locomotion and during the development of the nervous system. It is synthesized by the glutamic acid decarboxylase (GAD). There are two isoforms of GAD, GAD1 and GAD2, which are encoded by different genes. During embryonic development the transcription of GAD1 mRNA is regulated by alternative splicing and several alternative transcripts were distinguished in human, mouse and rat. Despite the fact that the structure of GAD1 gene has been extensively studied, knowledge of its exact structural organization, alternative promoter usage and splicing have remained incomplete. Results In the present study we report the identification and characterization of novel GAD1 splicing isoforms (GenBank: KM102984, KM102985) by analyzing genomic and mRNA sequence data using bioinformatics, cloning and sequencing. Ten mRNA isoforms are generated from GAD1 gene locus by the combined actions of utilizing different promoters and alternative splicing of the coding exons. Using RT-PCR we found that GAD1 isoforms share similar pattern of expression in different mouse tissues and are expressed early during development. Quantitative RT-PCR was used to investigate the expression of GAD1 isoforms and GAD2 in olfactory bulb, cortex, medial and lateral striatum, hippocampus and cerebellum of adult mouse. Olfactory bulb showed the highest expression of GAD1 transcripts. Isoforms 1/2 are the most abundant forms. Their expression is significantly higher in the lateral compared to the medial striatum. Isoforms 3/4, 5/6, 7/8 and 9/10 are barely detectable in all investigated regions except of the high expression in olfactory bulb. When comparing GAD1 expression with GAD2 we found that Isoforms 1/2 are the predominant isoforms. In situ hybridization confirmed the predominant expression of Isoforms 7/8 and 9/10 in the olfactory bulb and revealed their weak expression in hippocampus, cerebellum and some other areas known to express GAD1. Conclusions Generation of ten splicing isoforms of GAD1 was described including two so far uncharacterized transcripts. GAD1 splicing isoforms producing the shorter, enzymatically inactive GAD25 protein are expressed at very low level in adult mouse brain except in the olfactory bulb that is associated with neurogenesis and synaptic plasticity even during adulthood. Electronic supplementary material The online version of this article (doi:10.1186/1471-2202-15-114) contains supplementary material, which is available to authorized users.

Surface tension is difficult to measure with high accuracy. This parameter was measured for pure water to determine conditions that would permit high accuracy. Sources of error in assessing stability, variance, reproducibility and time-dependency of surface tension were sought. The glass syringe, differences in inner and outer temperatures of the cell and its inner pressure, etc. were found to affect this parameter. With attention to these factors, greater accuracy was achieved. Use of a glass syringe and holder with exact control of temperature led to maximum elimination of error. The surface tension of pure water, surfactant solutions and volatile organic liquids were measured and compared with previous values. There was less variation and the results were much more reproducible. High accuracy is thus possible with elimination of sources of error. Significant interfacial phenomena such as phase transition in adsorbed film, not observed by usual surface tension measurement apparatus, may thus be effectively studied through use of surface tension obtained with the present apparatus.

To clarify the frictional characteristics and the seizure resistance of radical nitrided stainless steel SUS 440 C rollers, a two-roller test was carried out under forced lubrication using Amusler machine. From the tests, the following results were obtained. The coefficient of friction with the roller pairs RA/RB, RA/NB and RA/RC was in the range of 0.063 to 0.077 at the final load range at which seizuring did not occur. The seizure resistance of the radical nitrided roller pair was at least five times as large as that of the untreated roller pair. The critical surface temperature at the incipient stage of seizure for the case of the radical nitrided roller pair was at least 2∼3 times as large as that for the case of the untreated roller pair. A significant effect of the surface treatment due to the radical nitriding on the seizure resistance of the roller pair was recognized for the case of the roller pairs in which both the slower and the faster rollers were nitrided, and/or only the slower roller was nitrided.

Automatic interfacial tension measurement apparatus based on the drop volume method was developed so as to determine interfacial tension between two liquid phases rapidly and accurately. By this apparatus, for pure water and oil, constant values of equilibrium interfacial tension were obtained. Interfacial tension between aqueous solutions of surfactant and oil, and oil solutions of surfactant and water was measured. In all cases, the equilibrium tension values were determined with high reproducibility and reliability of their absolute values was confirmed. Interfacial tension between two liquid phases could be determined rapidly and automatically with high accuracy, and thus the present apparatus should prove quite using for examining various interfacial phenomena.

We have recently proposed a new general concept regarding amphiphilic materials that have been named as "active interfacial modifier (AIM)." In emulsion systems, an AIM is essentially insoluble in both water and organic solvents; however, it possesses moieties that are attracted to each of these immiscible liquid phases. Hence, an AIM practically stays just at the interface between the two phases and makes the resulting emulsion stable. In this study, the effects of silicone oil species on the dispersion stability of water-in-oil (W/O) emulsions in the presence of an AIM sample were evaluated in order to understand the destabilization mechanism in such emulsion systems. The AIM sample used in this study is an amphiphilic polymer consisting of a silicone backbone modified with hydrocarbon chains and hydrolyzed silk peptides. The Stokes equation predicts that the sedimentation velocity of water droplets dispersed in a continuous silicone oil phase simply depends on the expression (ρ - ρ₀)/η assuming that the droplet size is constant (where ρ is the density of the dispersed water phase, ρ₀ is the density of the continuous silicone oil phase, and η is the viscosity of the oil phase). The experimental results shown in this paper are consistent with the Stokes prediction: i.e., in the low-viscous genuine or quasi-Newtonian fluid region, the dispersion stability increases in the following order: dodecamethylpentasiloxane (DPS)decamethylcyclopentasiloxane (D₅) ≤ dodecamethylcyclohexasiloxane (D₆). This order agrees well with the order obtained by using the expression (ρ - ρ₀)/η as DPSD₅D₆. This indicates that our emulsion system experiences destabilization through sedimentation, but hardly any coalescence occurs owing to the presence of an additional third phase consisting of the AIM that stabilizes the silicone oil/water interface in the emulsions.

Background/aimsTreatment with antiviral neuraminidase inhibitors suppresses influenza viral replication and antigen production, resulting in marked attenuation of mucosal immunity and mild suppression of systemic immunity in mice. This study investigated the effects of immunomodulator clarithromycin (CAM) supplementation on mucosal and systemic immunity in pediatric patients with influenza treated with neuraminidase inhibitors.MethodsA retrospective, non-randomized case series study was conducted among five treatment groups of 195 children aged 5.9±3.3 years infected with influenza A in 2008/2009 season. The five treatment groups were oseltamivir (OSV), zanamivir (ZNV), OSV+CAM, ZNV+CAM and untreated groups. Anti-viral secretory IgA (S-IgA) levels in nasal washes and IgG levels in sera were measured. The re-infection rate was analyzed among the same five treatment groups in the 2009/2010 season.ResultsTreatment of influenza with OSV and ZNV for 5 days attenuated the induction of anti-viral S-IgA in nasal washes and anti-viral IgG in serum, compared with the untreated group. The combination of CAM plus OSV or ZNV boosted and restored the production of mucosal S-IgA and systemic IgG. The re-infection rates in the subsequent season were significantly higher in the OSV and ZNV groups than the untreated, while CAM+OSV and CAM+ZNV tended to reduce such rate.ConclusionsCAM restored the attenuated anti-viral mucosal and systemic immunity and reduced the re-infection rate in the subsequent year in pediatric patients with influenza treated with OSV and ZNV.

Since induced pluripotent stem (iPS) cells have differentiation potential into all three germ layer-derived tissues, efficient purification of target cells is required in many fields of iPS research. One useful strategy is isolation of desired cells from differentiated iPS cells by lineage-specific expression of a drug-resistance gene, followed by drug selection. With this strategy, we purified neural stem/progenitor cells (NSCs), a good candidate source for regenerative therapy, from differentiated mouse iPS cells. We constructed a bicistronic expression vector simultaneously expressing blasticidin S resistance gene and DsRed under the control of tandem enhancer of a 257-base pair region of nestin second intron, an NSC-specific enhancer. This construct was efficiently inserted into the iPS genome by piggyBac transposon-mediated gene transfer, and the established subclone was differentiated into NSCs in the presence or absence of blasticidin S. Consequently, incubation with blasticidin S led to purification of NSCs from differentiated iPS cells. Our results suggest that a lineage-specific drug selection strategy is useful for purification of NSCs from differentiated iPS cells and that this strategy can be applied for the purification of other cell types.

The GABA-synthesizing enzymes glutamate decarboxylase (GAD)1 and GAD2 are universally contained in GABAergic neurons in the central nervous system of the mouse and rat. The two isoforms are almost identically expressed throughout the brain and spinal cord. By using in situ hybridization, we found that the mouse lateral striatum concentrates medium-sized projection neurons with high-level expression of GAD1, but not of GAD2, mRNA. This was confirmed with several types of riboprobe, including those directed to the 5'-noncoding, 3'-noncoding and coding regions. Immunohistochemical localization of GAD1 also revealed predominant localization of the enzyme in the same striatal region. The lateral region of the mouse striatum, harboring such neurons, is ovoid in shape and extends between interaural +4.8 and +2.8, and at lateral 2.8 and dorsoventral 2.0. This intriguing region corresponds to the area that receives afferent inputs from the primary motor and sensory cortex that are presumably related to mouth and forelimb representations. The lateral striatum is included in the basal ganglia-thalamocortical loop, and is most vulnerable to various noxious stimuli in the neurodegeneration processes involving the basal ganglia. We have confirmed elevated expression of GAD1 mRNA, but not of GAD2 mRNA, also in the rat lateral striatum. Image analysis favored the view that the regional increase is caused by elevated cellular expression, and that the greatest number of medium-sized spiny neurons were positive for GAD1 mRNA. The GAD1 mRNA distribution in the mouse lateral striatum partially resembled those of GPR155 and cannabinoid receptor type 1 mRNAs, suggesting functional cooperation in some neurons.

Background: Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the cold hyperalgesia. In the present study, we examined the effects of Ca2+ channel blockers on oxaliplatin-induced cold hyperalgesia in rats. Methods: Cold hyperalgesia was assessed by the acetone test. Oxaliplatin (4 mg/kg), sodium oxalate (1.3 mg/kg) or vehicle was injected i.p. on days 1 and 2. Ca2+ (diltiazem, nifedipine and ethosuximide) and Na+ (mexiletine) channel blockers were administered p.o. simultaneously with oxaliplatin or oxalate on days 1 and 2. Results: Oxaliplatin (4 mg/kg) induced cold hyperalgesia and increased in the transient receptor potential melastatin 8 (TRPM8) mRNA levels in the dorsal root ganglia (DRG). Furthermore, oxalate (1.3 mg/kg) significantly induced the increase in TRPM8 protein in the DRG. Treatment with oxaliplatin and oxalate (500 μM for each) also increased the TRPM8 mRNA levels and induced Ca2+ influx and nuclear factor of activated T-cell (NFAT) nuclear translocation in cultured DRG cells. These changes induced by oxalate were inhibited by nifedipine, diltiazem and mexiletine. Interestingly, co-administration with nifedipine, diltiazem or mexiletine prevented the oxaliplatin-induced cold hyperalgesia and increase in the TRPM8 mRNA levels in the DRG. Conclusions: These data suggest that the L type Ca2+ channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced cold hyperalgesia, and that Ca2+ channel blockers have prophylactic potential for acute neuropathy.

Mast cells (MC) and peripheral blood basophils (PBB) are well known for their role in the allergic response mediated through high affinity IgE receptors (FceRI). However, these cells can also be stimulated by other non-allergic secretagogues to release their inflammatory mediators. Certain fullerene derivatives (FD) have already been shown to stabilize FceRI-mediated MC/PBB responses, but it is not know if they also stabilize these cells through non-IgEmediated mechanisms. A panel of FD was synthesized and tested for their ability to inhibit non-FceRI mediated release from human MC and PBB. It was found that specifically engineered FD could significantly inhibit calcium ionophore, compound 48/80, somatostatin, and poly L-lysine induced MC degranulation and cytokine production, as well as blunt degranulation and cytokine production from N-formyl-methionine-leucine-phenylalanine (fMLP), poly L-lysine, and calcium ionophore stimulated PBB. The mechanism of inhibition was due in part to the prevention of secretagogueinduced increases in cellular reactive oxygen species (ROS) and calcium levels as well as the reduced activation of the MAPK signaling intermediates ERK1/ERK2 and LAT. Additionally, preincubation of MC with FD blunted the prostaglandin D2 (PGD2) production upon exposure to inflammatory stimuli. In both cell types, the extent of inhibition of mediator release in response to each secretagogue was dependent on the moieties/side chains attached to the carbon cage. These results further extend the utility of fullerene nanomaterials to control mediator release through non-IgE mediated pathways in MC/PBB.

エリブリンはクロイソカイメンから発見された抗がん物質ハリコンドリンBの誘導体である．微小管阻害薬であるが従来の類薬とは異なり，微小管の重合部位に選択的に高親和性に結合し微小管を阻害する．細胞周期のG2/M期でがん細胞の増殖を停止させアポトーシスを誘導する．エリブリンのin vitroの検討では，様々ながん細胞の増殖を阻害し，in vivoにおける検討では，乳がん，大腸がん，黒色腫，卵巣がんのモデルにおいて，腫瘍の進展を抑制し縮小させることが確認されている．エリブリンは，国内第II相試験において化学療法治療歴のある転移乳がん患者に対し奏効率21.3%の有効性が確認された．有害事象で発現率が高かったのは，白血球減少症，好中球減少症，脱毛症，リンパ球減少症などであった．海外の第III相試験（EMBRACE試験）では，既存の薬剤からなる主治医選択治療群との比較において，全生存期間の有意な延長が確認された．また末梢神経障害の発現が少ないという特徴も，臨床試験と基礎研究を通じて明らかになった．エリブリンの排泄は主に糞便中であり78.6%が未変化体であった．CYP3A4などの代謝酵素の影響を受けにくいため，他剤との併用のリスクは少ないと思われた．エリブリン投与では，過敏症に対する抗アレルギー薬等の前投与が不要である．水溶液のバイアルにて医療機関に提供され，必要量をそのまま投与または希釈後に点滴投与が可能である．投与時間が2～5分と非常に短いこととあわせ，患者，医療従事者への負担が極めて少ない，製剤上の優れた性質を有した薬剤と言える．エリブリンは抗がん剤の前治療の少ない患者において，有効性だけでなく延命にもより貢献できることが示され，今後はより早期の乳がんに対する効果の検証が進められるであろう．

The results of γ analyses of soil samples obtained from 50 locations in Fukushima prefecture on April 20, 2011, revealed the presence of a spectrum of radionuclides resulted from the accident of the Fukushima Dai-ichi nuclear power plant (FDNPP). The sum γ radioactivity concentration ranged in more than 3 orders of magnitude, depending on the sampling locations. The contamination of soils in the northwest of the FDNPP was considerable. The (131)I/(137)Cs activity ratios of the soil samples plotted as a function of the distance from the F1 NPPs exhibited three distinctive patterns. Such patterns would reflect not only the different deposition behaviors of these radionuclides, but also on the conditions of associated release events such as temperature and compositions and physicochemical forms of released radionuclides. The (136)Cs/(137)Cs activity ratio, on the other hand, was considered to only reflect the difference in isotopic compositions of source materials. Two locations close to the NPP in the northwest direction were found to be depleted in short-lived (136)Cs. This likely suggested the presence of distinct sources with different (136)Cs/(137)Cs isotopic ratios, although their details were unknown at present. Vertical γ activity profiles of (131)I and (137)Cs were also investigated, using 20-30 cm soil cores in several locations. About 70% or more of the radionuclides were present in the uppermost 2-cm regions. It was found that the profiles of (131)I/(137)Cs activity ratios showed maxima in the 2-4 cm regions, suggesting slightly larger migration of the former nuclide.

From fiscal 2010, Japan's listed companies are obliged to disclose Comprehensive Income (CI). In Japan, CI is disclosed in Statements of Comprehensive Income, which are attracting considerable attention. In the United States, Other Comprehensive Income, including gains/losses on Available-for-Sale securities, is said to have become a focus of attention since 1998, when CI was introduced. Therefore, the perspective of financial markets in valuing Japanese financial institutions is likely to change to attach more importance to CI. CI of Japanese banks is more volatile than Net Income by far, reflecting the significant price volatility in equities held. Thus, once financial markets start to pay more attention to CI, the risk recognition of Japanese banks' profits can heighten. This can affect Japanese banks in terms of funding costs and so on. In this situation, Japanese banks are required to evaluate more prudently the balance between risks and returns in holding equities, and to make efforts to reduce risks when judged as being excessive.

Clinical, radiological and surgical studies have been made of 57 farmers who were operated upon for degenerative lumbar canal stenosis (Group A) and degenerative spondylolisthesis (Group B). The improvement rate was excellent in both groups.(Group A: 75.6%, Group B: 71.7%). The improvement rate in abdominal and back muscle strength was lower in cases with postoperative kyphosis than in those with postoperative lordosis. Cases with a slip angle of less than 0 degrees postoperatively showed less improvement and a lower abdomminal and back muscle strength than those with an angle of 0 degrees or more. Disappearance of lumbar lordosis, local kyphotic alignment, low strength of abdominal and back muscles are unfavourable factors influencing return to farm work.

The aim of the present study was to investigate the influenza vaccine effectiveness among young children in Japan. Study subjects were recruited from 43 pediatric clinics. Influenza-like illness (ILI) was defined as an acute febrile illness with respiratory symptoms; ILI with a fever of > or =39 degrees C was considered to be severe ILI (SILI). The adjusted OR of vaccination significantly decreased to 0.75 for SILI. Influenza vaccination for young children had a protective effect on the occurrences of SILI. This study also indicated that three key tools (case surveillance with equal scrutiny, confining observation to the peak epidemic period, and adoption of strict criteria for ILI) could minimize outcome misclassification and thus provide adequate methodology for monitoring vaccine effectiveness without laboratory confirmation.

The tribological properties of a new unique thermo-reversible Gel-Lubricant (TR Gel-Lube) were investigated. TR Gel-Lube which includes 10–40% of amide type gel agent in base fluid, is repeatedly able to change from gel-state to liquid-state at the melting point of its gel agent. High-pressure rheological tests were performed in order to characterize the behavior of base oil and TR Gel-Lube as a function of pressure and temperature. The effect of TR Gel-Lube on ball bearings fatigue life was carried out by systematic tests using thrust ball bearings. The results of L10 life tests of TR Gel-Lube showed a longer life than the conventional greases. This result was investigated from oil film formation. It was found that gel agent played a key role in the lubricating properties. Some mechanisms such as adsorbed film formation and solid like formation are proposed.Copyright © 2009 by ASME