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Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure.

Acanthocytosis gets its name from the presence of acanthocytes, abnormal red blood cells with spiny projections on the cell membrane. The condition is often associated with abetalipoproteinemia (a rare genetic disease resulting from defective synthesis of apoprotein B), and some investigators have suggested that the condition results from a defect in membrane lipids. However, in many cases of acanthocytosis, no defect in the membrane lipids can be detected. Acanthocytosis associated with abetalipoproteinemia is sometimes called Bassen-Kornzweig syndrome, and may involve neurological symptoms. When acanthocytosis occurs with neurological symptoms but no deficiency in lipoprotein can be demonstrated, the condition is called neuroacanthocytosis. The authors discuss in great detail the clinical and biochemical aspects of 19 cases of neuroacanthocytosis. These cases include 12 familial cases representing three families, and seven cases in which family members appear uninvolved. The neurological symptoms varied among the patients. Most, but not all, patients had chorea (complex, coordinated but purposeless involuntary movements); the condition is often mistaken at first for Huntington's disease. About half the patients had some psychiatric symptoms or personality change, and one third had seizures. Autopsy examination was performed on one patient that revealed extensive neuronal loss in the caudate nucleus (mass of gray matter deep with the cerebral hemisphere), explaining the resemblance of the symptoms to those of Huntington's disease, as well as in the substantia nigra (located in the mesencephalon, or the midbrain) and other parts of the brain. Seven of the cases were normal on computed tomography, and in six cases both atrophy in the caudate nucleus and general atrophy of the cortex of the brain were observed. The investigation of the mode of inheritance in the three families did not reveal any conclusive pattern. In one family, however, it was observed that two neuroacanthocytosis patients had the McLeod phenotype, which is an X-linked absence of a red blood cell antigen. About 25 percent of McLeod phenotype patients also have acanthocytosis and the authors speculate that in some cases neuroacanthocytosis may be X-linked. However, some relatives of these two patients showed motor abnormalities resembling neuroacanthocytosis without having the McLeod phenotype. (Consumer Summary produced by Reliance Medical Information, Inc.)

Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men.

The integration of phase-field (PF) simulations and in situ observations is a promising approach for understanding dendrite growth. In this study, a preliminary data assimilation system is developed to integrate PF simulations and in situ real-time X-ray radiography during the directional solidification of a binary alloy. In this system, only the region around the tip of a primary arm is used for data assimilation. The validity of the developed system is confirmed through twin experiments for columnar dendrite growth with different inclined angles of preferred growth direction.

We prepared sub-micron olivine (Fo92) particles of different shapes and different degrees of crystal lattice distortion, and studied both effects on the infrared absorption spectra experimentally. We found that the peak positions of the spectra shifted to short wavelength when the number fraction of spherical grains became large, consistent with spectral calculations using the continuous distributions of ellipsoids (CDE) model. We also found for the first time that the spectral features become broader by crystal lattice distortion. The peak intensities are affected by both effects. The peak intensity decreases with lattice distortion in general, but some peaks are largely affected by particle shape. The spectral difference of olivine measured in different laboratories can be explained by both the shape and lattice distortion effects through sample preparation methods. Broadening features in the infrared spectra of forsterite ejecta from comet Tempel 1 obtained in the Deep Impact mission, and forsterite crystals in circumstellar regions, suggest that forsterite crystals undergo lattice distortion.

This paper presents a method for estimating the condition for the brittle fracture limit of a welded joint with an embedded flaw in the heat-affected zone (HAZ) based on the Weibull stress criterion. A welded joint with an embedded flaw generated by cold cracking was subjected to a wide plate (WP) tension test, and a welded joint with a fatigue crack was subjected to three-point bending (3PB) tests; both tests were conducted at −30 °C. Brittle fractures occurred in all specimens, and the microstructure of the fracture initiation point for the WP specimen in the coarse-grained HAZ (CGHAZ) was upper bainite with M-A constituents. The critical Weibull stress distribution of the CGHAZ was calculated by finite element analyses for the 3PB specimens. The predicted fracture load and global displacement of the WP specimen at the brittle fracture obtained by the critical Weibull stress distribution were in agreement with experimental results from the WP tensile test. This confirmed that the brittle fracture limit of a welded joint with an embedded flaw could be predicted from the Weibull stress criterion.

ZFP521was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK, BTKand BANK1were positively regulated by the ZFP521gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-mycand c-junwere upregulated following activation of ZFP521. Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-mycand c-junand of Ccnd3, which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTKand BANK1, targets of ZFP521, suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521, the homolog of ZFP521in humans, was upregulated. In conclusion, our data showed that the ZFP521gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

Transmission-type terahertz time-domain spectroscopy (THz-TDS) using dipole-antennas on LT-GaAs layers as THzemitter and detector with fs-fiber laser as the excitation light source was applied to determine the stereoisomer of sugars in carefully controlled environment with low humidity below 5% at 20°C. Commercially available -D-lactose including about 4% anomer and -D-lactose including below 30% anomer were used as stereoisomer samples. The absorption spectra of compounds by the -D- and -D-lactose powders with various ratios were successively deconvoluted to four spectra by Lorentzian and dependent on the composition ratio. Integrated absorptions due to -D-lactose and -D-lactose determined the decreasing rate (r) and the increasing rate (r) for the composition ratio of the -D-lactose powder, because the intensities were linearly dependent on the composition ratio. The net-composition ratio of -lactose and -lactose in the compounds was precisely evaluated by the ratio of the integrated intensities and the value of r/ r, for example, the anomer-contents in commercially available -D-lactose and -D-lactose powders were disclosed as 3.9% and 29.1%, respectively. The demonstrated results indicate that THz-TDS is so useful not only for precise qualitativeanalysis but also for precise quantitative-analysis of stereoisomer in sugars with partially different molecular structure such as lactose.

A novel method for measuring nonlinear refractive index coefficient of an optical fiber using input-output characteristics in nonlinear dynamics generated in an optical fiber ring resonator is proposed and demonstrated for a pure silica core fiber. The nonlinear refractive index coefficient n2=1.03×10-22[m2/V2] is obtained in the experimental demonstration.

AbstractPlasmas with high ion-temperature of several keV have been produced by using ion-cyclotron range of frequency (ICRF) heating in the GAMMA 10 tandem mirror. In such high performance plasmas, high and low-frequency fluctuations are excited and ions trapped in the magnetic field interact with such fluctuations. Three types of wave-particle interactions have been observed in the GAMMA 10 tandem mirror. The turning point diffusion near the ion cyclotron resonance layer has been observed in minimum-B configuration on the anchor cell. Pitch angle scattering of high-energy ions due to the AIC modes and low-frequency waves which have differential frequencies between discrete peaks of the AIC modes are clearly detected. The drift-type fluctuations are clearly observed in the central cell. By using a semiconductor detector, high-energy ions are detected at the radial location far from the plasma edge. The fluctuation, of which frequency is the same as that of drift-type fluctuation, is observed in the signal of high-energy ions. From the pitch angle distribution of the phase differences between both fluctuations, radial transport of high-energy ions caused by drift-type fluctuations near their turning points in the confining mirror field is suggested in the experiments.

AbstractRecent progress and near future plan of GAMMA 10 efforts are presented. With high power plug electron cyclotron heating (ECH)up to ~400 kW, the ion confining potential of more than 2 kV was confirmed. The drift type low frequency fluctuations were suppressed by the positive radial electric field produced by plug ECH. It is found that the efficient EC heating on mirror devices from a strong B field side requires the minimization of the stray microwave in addition to the 100% X-mode excitation to avoid the enhancement of the ion loss. The development of a gyrotron, the key tool of these ECH experiments, has been made in collaboration with NIFS (National Institute for Fusion Science), More than 1.5 MW for more than 1s has been demonstrated at 77GHz. The plan of the boundary plasma research program with modification of GAMMA 10 is in progress. The new program includes the physics and technology studies of the divertor and SOL plasmas and PWI relevant to torus plasmas like ITER. The high heat flux experiments using the open end mirror throat has been started and we have obtained successful preliminary data, which include the heat flux of 8 MW/m2.

The occurrence of small scale plasticity can be modeled physically by force doublets embedded in an elastic medium and therefore the plasticity problem can be treated by the superposition of elastic solutions. This idea for the treatment of an inelastic strain is reviewed and generalized to develop a versatile program for two-dimensional elastic-plastic problems based on Body Force Method. In the present study, a treatment of an elastic-perfect plastic body is discussed in detail. The increment of the density of force doublets, which has one to one correspondence to the increment of plastic strain, can be determined from Prandtl-Reuss equation. It was also found the Delaunay triangulation is useful and convenient for the automated elastic-plastic analysis.

This paper describes a study on the application of smart mechanoluminescence (ML) sensor to structures for the visualization of stress distribution. Smart thin film sensor of ML material SrAl2O4:Eu/polyme is coated on the surface of structure. The sensor will emit visual light when the structure is subjected to deformation. The light intensity is proportional to the strain energy density and the equivalent strain of the stressed material based on the energy viewpoint and experimental facts. The distribution of visual light intensity is recorded using CCD camera or ordinary camera. Then the stress distribution can be evaluated from the distribution of visual light intensity based on solid mechanics and the relationship between light intensity and equivalent strain. Compression test of a disk with coated SrAl2O4:Eu/epoxy film sensor is conducted to compare the visual light distribution with the stress distribution obtained from finite element analysis. Furthermore, tensile test of a rectangular specimen with a coated SrAl2O4:Eu/polymer film sensor is performed to demonstrate the relationship between visual light intensity and strain. Experimental and numerical results show that the smart sensor of ML material SrAl2O4:Eu/polymer is an effective strain sensor to directly visualize the stress distribution in real time.

This article evaluates the hydrodynamic interactions between two swimming bacteria precisely. We assume that each bacterium is force free and torque free, with a Stokes flow field around it. The geometry of each bacterium is modeled as a spherical or spheroidal body with a single helical flagellum. The movements of two interacting bacteria in an infinite fluid otherwise at rest are computed using a boundary element method, and the trajectories of the two interacting bacteria and the stresslet are investigated. The results show that as the two bacteria approach each other, they change their orientations considerably in the near field. The bacteria always avoided each other; no stable pairwise swimming motion was observed in this study. The effects of the hydrodynamic interactions between two bacteria on the rheology and diffusivity of a semidilute bacterial suspension are discussed.

The influence of surface roughness in crack face on the behavior of crack growth is studied. Numerical results derived from two kinds of mechanical models representing the macroscopic and microscopic asperity supposed to exist in the face of an initial crack are compared. In macro-asperity model, the influence of location and size of single-triangular asperity on the stress intensity factor is evaluated. In this model, it is found that the mode-I stress singularity appears in certain circumstances even under overall compression. In micro-asperity model, influence of friction coefficient on the trajectory of crack path is discussed. There exists a tendency that a path of wing crack growth becomes more straight and parallel to axis of compression as the friction coefficient increases.

Recently we have proposed that stress distribution of a subject can be visualized by utilizing a novel mechanoluminescence phenomenon that can give intense visible light emission by application of mechanical stress. As the luminescence intensity is proportional to the time-variation of strain energy in the elastic region, we call it elastico-luminescence. In order to realize a high space resolution in such visualization for stress distribution, we aim to develop strong elastico-luminescent nanoparticles, such as a controlled structure of α-SrAl2O4:Eu (monoclinic phase). The processing of the nanoparticles, the property and the applications will be reported in the present work.

Six perylene diimide-appended hexaazatriphenylene, HAT-PDI6, was self-assembled in both solution and film state to form a highly stabilized dimer aggregate, in which an efficient energy transfer occurs from the hexaazatriphenylene core to the perylene-diimide moiety.

An expedition across the Asian part of the Black Sea coast and national parks of Northern Turkey was organized in the summer of 2001 to investigate the presence of Borrelia burgdorferi sensu lato (s.l.), Lyme borreliosis agent, and Anaplasma phagocytophilum, human granulocytic ehrlichiosis agent, in wild mice. A total of 65 Apodemus flavicollis, Apodemus sylvaticus, Microtus epiroticus, Crocidura suaveolens and Mus macedonicus, were captured. Two out of 22 Apodemus sylvaticus specimens were seropositive for B. afzelii by enzyme-linked immunosorbent assay as confirmed by Western blotting, however cultures of skin and bladder samples from all small mammals in Barbour–Stoenner–Kelly's medium-II remained negative for B. burgdorferi s.l. All sera tested were negative for Anaplasma phagocytophilum by indirect immunofluorescent assay. The prevalence of B. burgdorferi s.l. and Anaplasma phagocytophilum is low in wild mice of the Asian part of Northern Turkey.

TSC-22 (Transforming growth factor-β stimulated clone-22) was originally isolated as a TGF-β- inducible gene in mouse osteoblastic cells. TSC-22 encodes a putative transcriptional regulator containing a leucine zipper-like structure. Several differentiation-inducing stimuli up-regulate the TSC-22 gene. Furthermore, TSC-22 acts as an effector that integrates multiple extracellular signals during embryogenesis of Drosophila and mouse. Separately, we identified TSC-22 cDNA as an anti-cancer drug (vesnarinone)-inducible gene in a human salivary gland cancer cell line, TYS. Vesnarinone is known to have a differentiation-inducing activity in several cell types. We showed that TSC-22 negatively regulated the growth of TYS cells, and that down-regulation of TSC-22 played a major role in the salivary gland tumorigenesis. Subsequently, we found that artificial overexpression of TSC-22 enhanced chemosensitivity and radiation-sensitivity by inducing apoptosis in TYS cells. Recently, we isolated TSC-22 genomic DNA and analyzed the transcriptional and posttranscriptional regulation of the TSC-22 gene. Then, we confirmed by the luciferase reporter assay that several differentiation-inducing stimuli directly activated the promoter region of TSC-22 gene. Now we are investigating the chemical compounds, which could enhance the transcription of the TSC-22 gene. Thus, because TSC-22 is a key molecule for differentiation of several cells, it can be used as a molecular target for cancer differentiation therapy in salivary gland cancer.

Summary The compatibilized PET/expandable fluorine mica (ME) hybrid nanocomposite (CN) prepared by in situ polymerization technique showed a partially exfoliated structure of ME in PET matrix by XRD analysis, owing to its broad crystalline peak accompanied by an increase of d-spacing as compared to PET/ME uncompatibilized composite (UC). The analysis by TEM revealed a better dispersion of ME in PET for CN as compared to aggregates of ME in case of UC. Further, the isothermal crystallization behaviour studied using DSC for the same at different crystallization temperature ( T c,) revealed a significant decrease of crystallization half time and remarkable increase of crystallization rates (almost 2 times than pure PET) for CN in contrast to UC. The Avrami exponent n lowered to 2.3 for CN as compared to 3.1-3.4 for pure PET at various T c. The activation energy ( E a) determined from Arrhenius equation reduced dramatically for CN. These various observations could be explained based on the nucleation efficiency by ME accompanied by different crystallization/growth process occurring in case of hybrid nanocomposite.

We investigated the alterations of dopamine transporter (DAT)-immunopositive cells against MPTP neurotoxicity, in comparison with tyrosine hydroxylase (TH)- immunopositive neurons and glial fibrillary acidic protein (GFAP)-immunopositive cells. This study showed that DAT and TH immunoreactivity was decreased gradually in the striatum and substantia nigra of mice after MPTP treatment. The patterns of the intense TH-immunoreactive fibers and cell bodies were similar to those of DAT-immunoreactive fibers and cell bodies in the striatum and substantia nigra of mice after MPTP treatment. In contrast, GFAP immunoreactivity was increased gradually in the striatum and substantia nigra after MPTP treatment. In our double-labeled immunostaining with anti-DAT and anti-GFAP antibodies, DAT immunoreactivity was observed only in the nigral dopaminergic neurons, but not in the reactive astrocytes. The present results provide further evidence that the functional damage of DAT may precede dopaminergic neuronal death after MPTP treatment, although the decrease in the number of TH-immunopositive neurons was more pronounced than that in the number of DAT-immunopositive neurons. Furthermore, our findings demonstrate that MPTP can selectively injure the dopaminergic neurons which DAT proteins are predominantly distributed on the striatum and substantia nigra. The results provide beneficial information for MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.

Pathologic and immunohistochemical changes caused by group I of the fowl adenovirus (FAV) serotype-1 99ZH strain, isolated from broiler chickens exhibiting gizzard erosion, were investigated in commercial broiler chickens. One hundred twenty-two chickens were inoculated with the strain by both oral and ocular routes at 1, 3, or 5 weeks of age and euthanatized for necropsy within 4–18 days of inoculation. Focal gizzard erosions were observed in the inoculated chickens of each age group. A histologically degenerative koilin layer, necrotic mucosa, intranuclear inclusion bodies in the glandular epithelial cells, inflammatory cell infiltrations in the lamina propria, submucosa, and a muscle layer were seen in the gizzards. Immunohistochemical staining showed evidence of FAV antigens in the intranuclear inclusion bodies. These findings were recognized regardless of their maternal antibody levels for FAV serotype-1. Gizzard lesions appeared later in the lower-dose-inoculated chickens than in the higher-dose–inoculated chickens. Numerous CD3-positive cells and IgY-positive plasma cells were seen in the gizzard lesions. In 5-week-old chickens the heterophil infiltrations in the lesions were milder than in younger chickens. Intranuclear inclusion bodies also were observed in the epithelial cells of the ileum or cecal tonsils of some chickens. Thus, this study shows that FAV-99ZH causes adenoviral gizzard erosion in broiler chickens without hepatic or pancreatic lesions and that cell infiltration is more severe than in dietary gizzard erosions.

Different spectroscopic and photoelectrochemical behaviors were observed when racemic and enantiomeric [Ru(bpy)3]²⁺ complexes were intercalated in the interlayer of K4Nb6O17, even for the same intercalation amount. The results are interpreted in terms of the stronger interaction between racemic [Ru(bpy)3]²⁺ molecules in the interlayer spaces of K4Nb6O17. The faster emission decay and lower photocurrent of the racemic [Ru(bpy)3]²⁺−K4Nb6O17 compound compared to the enantiomeric ones suggest that stronger concentration quenching exists between the racemic [Ru(bpy)3]²⁺ ions in the interlayer of K4Nb6O17. Combining the spectroscopic and photoelectrochemical results, the racemic [Ru(bpy)3]²⁺ ions are considered to intercalate more densely than the enantiomeric [Ru(bpy)3]²⁺ ions in the interlayer of K4Nb6O17, even for the same intercalation amount. Two cationic dyes were also directly intercalated into K4Nb6O17. The spectroscopic and photoelectrochemical behaviors of the dye−K4Nb6O17 compounds were investigated.

Effects of neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole), nonselective NOS inhibitor (NG-nitro-L-arginine methyl ester; L-NAME), and monoamine oxidase inhibitor (pargyline) were studied on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The mice received four intraperitoneal injections of MPTP at 1-h intervals. A significant depletion in dopamine and DOPAC concentration was observed in the striatum from 1 day after MPTP treatment. The pretreatment of 7-nitroindazole and pargyline, but not L-NAME, dose-dependently protected against MPTP-induced depletion in dopamine content 3 days after MPTP treatment. Our histochemical study also showed that 7-nitroindazole and pargyline can prevent a marked decrease in the nigral cells and a marked increase in astrocytes in striatum 7 days after MPTP treatment. The protective effect of 7-nitroindazole against MPTP-induced dopamine and DOPAC depletion in the striatum was not attenuated by intraperitoneal pretreatment with L-arginine. Furthermore, the posttreatment of 7-nitroindazole or pargyline protected against MPTP-induced depletion of dopamine content. These results demonstrate that the protective mechanism by which 7-nitroindazole counteracts MPTP neurotoxicity in mice may be due not only to inhibition of nNOS, but also to MAO-B inhibition. Furthermore, our study suggests that the posttreatment of 7-nitroindazole and pargyline can prevent a significant decrease in dopamine levels in the striatum of MPTP-treated mice. These findings have important implications for the therapeutic time window and choice of nNOS or MAO inhibitors in patients with Parkinson's disease.

To develop a new therapeutic agent for sleep disorders, we synthesized a novel series of tricyclic indan derivatives and evaluated them for their binding affinity to melatonin receptors. In our previous paper, we proposed a conformation of the methoxy group favorable for the binding of the MT1 receptor. To fix the methoxy group in an active conformation, we decided to synthesize conformationally restricted tricyclic indan analogues with the oxygen atom in the 6-position incorporated into a furan, 1,3-dioxane, oxazole, pyran, morpholine, or 1,4-dioxane ring system. Among these compounds, indeno[5,4-b]furan analogues were found to be the most potent and selective MT1 receptor ligands and to have superior metabolic stability. The optimization of substituents led to (S)-(−)-22b, which showed very strong affinity for human MT1 (Ki = 0.014 nM), but no significant affinity for hamster MT3 (Ki = 2600 nM) or other neurotransmitter receptors. The pharmacological effects of (S)-(−)-22b were studied in experimental animals, and it was found that a dose of 0.1 mg/kg, po promoted a sleep in freely moving cats, as demonstrated by a decrease in wakefulness and increases in slow wave sleep and rapid eye movement sleep, which lasted for 6 h after administration. Melatonin (1 mg/kg, po) also had a sleep-promoting effect, though it lasted only 2 h. A new chiral method for the synthesis of (S)-(−)-22b starting from 60, which was prepared from 59 employing asymmetric hydrogenation with the (S)-2,2‘-bis(diphenylphosphino)-1,1‘-binaphthyl−Ru complex, was developed. (S)-(−)-22b (TAK-375) is currently under clinical trial for the treatment of insomnia and circadian rhythm disorders.

Summary: A series of PET/expandable fluorine mica (ME) nanocomposites with different proportions of compatibilizer, 10-[3,5-bis(methoxycarbonyl)phenoxy]decyltriphenylphosphonium bromide (IP10TP) were prepared by in situ polymerization process. The crystallite size, nucleation and the effect of content of compatibilizer on the dispersibility of ME in PET matrix were investigated by XRD and DSC techniques. The XRD results showed a decrease in the crystallite size of ME giving rise to partially exfoliated structure and the crystallite size of PET reduced considerably as compared to pure PET at low content of IP10TP. The DSC results revealed a dramatic increase in crystallization temperature (T c) and also showed enhancement in glass transition (T g) and melting point (T m) at low content of IP10TP. These various findings have been explained based on the miscibility of IP10TP/ME with PET.

An atomic force microscope with a colloid probe technique was used to measure forces interacting between smectites, that is, saponite and hectorite. The measured forces fit well to the forces calculated by the Derjaguin−Landau−Verwey−Overbeek (DLVO) theory at separations larger than 4 nm over concentrations of 10^-5−10^-2 M NaCl and the pH range of 4−10. There is also a good agreement between zeta potential and the electrical double-layer (EDL) potential extracted from the best fit to the DLVO force curve. According to the analysis on the pH dependence of the EDL potential using the Gouy−Chapman−Stern−Graham model, the inner Helmholtz layer capacitance for the good fit of the outer Helmholtz plane potential to the EDL potential required a much lower value for hectorite (~5 μF/cm²) than that for saponite (~500 μF/cm²), reflecting the difference in the location of the lattice charge between saponite and hectorite. This provided evidence for the fact that the EDL force for smectites is dominated by the location of the charges as well as the density of the charges. Extra short-range repulsion was observed at separations below ~3 nm with increasing NaCl concentration and pH and then disappeared with decreasing pH or the NaCl concentration. The short-range repulsion was extracted as a double-exponential function, that is, F/R = A1 exp(−D/D1) + A2 exp(−D/D2), by subtracting the DLVO forces from the measured forces in the same way as the study with a surface force apparatus (Pashley, R. M. J. Colloid Interface Sci. 1981, 83, 531). The values of two decay lengths (D1 and D2) for smectites showed a very similar result to those for muscovite mica rather than silica. It was also found that the sum of the force constants (A1 + A2) was closely related to the density and structure of the lattice charge.

ζ potentials of synthetic smectites with different locations of lattice charges, i.e., saponite and hectorite, were investigated as functions of pH and NaCl concentration by a flat plate streaming potential technique where two smectite-coated plates were separated by a Teflon gasket to form a slit channel. The lattice charge of saponite originates from the isomorphous substitution of Si⁴⁺ by Al³⁺ ions in tetrahedral silica sheets, whereas the lattice charge of hectorite is caused by the isomorphous substitution of Mg²⁺ by Li⁺ ions in octahedral magnesia sheets. The ζ potential for saponite was more sensitive to the pH of electrolyte solution than that for hectorite in acidic solution. Such a difference in pH dependence of the ζ potential could be explained by the difference in the location of the lattice charges between saponite and hectorite as a result of an analysis of the inner Helmholtz layer capacitance by using the Gouy−Chapman−Stern−Graham (GCSG) model with a single-site dissociation of surface groups. On the other hand, the dependence of the ζ potential on NaCl concentrations could not be fully interpreted by the GCSG model with a single value of the outer Helmholtz layer capacitance, which suggests a shift of the shear plane and/or a change in the dielectric constant of the outer Helmholtz layer with changing NaCl concentration.

Female hypothyroid (hyt) mice are infertile, but the reason for this infertility is not yet known. The present study was conducted to determine whether hypothyroidism induced infertility in immature and mature hyt mice. Furthermore, animals were treated with thyroxine and gonadotrophins at different times to determine whether infertility was due to failure of follicular development, implantation or pregnancy. There were no significant differences in the numbers of ovulated eggs induced by gonadotrophin treatment or the percentages of eggs developed in vitro among immature normal controls, hyt and thyroxine-treated hyt mice. Mature hyt mice showed continuous dioestrus, and ovulated significantly fewer eggs after gonadotrophin treatment and failed to establish pregnancy after mating compared with mature control mice. Mature hyt mice had significantly fewer corpora lutea > 500 microm in diameter and significantly lower progesterone concentrations. Thyroxine treatment before mating in hyt mice resulted in well-developed corpora lutea, an increase in progesterone and normal pregnancy, regardless of subsequent thyroxine administration. In conclusion, infertility occurs in mature rather than immature hyt mice, is due to the failure of follicular development and pregnancy, and can be reversed by thyroxine treatment before mating.

This prospective study was undertaken to evaluate the efficacy and safety of midazolam as a sedative agent in 14 critically ill patients without coma admitted to the intensive care unit at Nihon University Itabashi Hospital, Japan. Adequate sedation (sedation score [SS] 4–6) was induced with 0.058–0.372 mg/kg midazolam and maintained with a dose range of 0.03–0.4 mg/kg per h. Most burn or trauma patients required higher midazolam doses than patients with cardiovascular disease. The most frequent adverse events observed were hypotension, heart-rate fluctuation and electrocardiogram abnormalities. Pharmacokinetic analysis of the population suggested that lower drug clearance rates correlated with presence of complications. Plasma concentrations (EC50) of SS 5, estimated by logistic regression analysis, varied among patients (mean 194 ng/ml). Midazolam infusion achieved successful sedation in this critical care setting, but the optimum dose differed by patient and was influenced by the presence of complications.

This prospective, phase II study was carried out to evaluate the efficacy and safety of midazolam as a sedative agent in nine critically ill Japanese patients without coma who had been admitted to an intensive care unit. An adequate level of sedation (sedative score [SS] 4–6) was induced by midazolam 0.14–0.39 mg/kg and maintained with a dose range of 0.08–0.24 mg/kg per h. One patient was excluded from the efficacy analysis since optimum sedation was not maintained by continuous infusion. The percentage of time during which SS 5 was achieved varied among the patients. The most frequent adverse events were hypotension, partial pressure of carbon dioxide elevation and premature ventricular contraction. Population pharmacokinetic analysis suggested that lower drug clearance rates were correlated with the presence of complications. The 50% of effective concentration values of SS 5, estimated by logistic regression analysis, varied greatly (mean, 251 ng/ml). In conclusion, midazolam infusion achieved successful sedation in this critical care setting. The optimum dose differed among the patients, however, and was influenced by the presence of complications.

Ventralizing transcriptional repressors in the Vox/Vent family have been proposed to be important regulators of dorsoventral patterning in the early embryo. While the zebrafish genes vox (vega1) and vent (vega2) both have ventralizing activity in overexpression assays, loss-of-function studies are needed to determine whether these genes have distinct or redundant functions in dorsoventral patterning and to provide critical tests of the proposed regulatory interactions among vox, vent and other genes that act to establish the dorsoventral axis. We show that vox and vent are redundant repressors of dorsal fates in zebrafish. Mutants that lack vox function have little or no dorsoventral patterning defect, and inactivation of either vox or vent by injection of antisense morpholino oligonucleotides has little or no effect on the embryo. In contrast, embryos that lack both vox and vent function have a dorsalized phenotype. Expression of dorsal mesodermal genes, including chordin, goosecoid and bozozok, is strongly expanded in embryos that lack vox and vent function, indicating that the redundant action of vox and vent is required to restrict dorsal genes to their appropriate territories. Our genetic analysis indicates that the dorsalizing transcription factor Bozozok promotes dorsal fates indirectly, by antagonizing the expression of vox and vent. In turn, vox and vent repress chordin expression, restricting its function as an antagonist of ventral fates to the dorsal side of the embryo. Our results support a model in which BMP signaling induces the expression of ventral genes, while vox and vent act redundantly to prevent the expression of chordin, goosecoid and other dorsal genes in the lateral and ventral mesendoderm.