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The physiologies of cells depend on electrochemical signals carried by ion channels and receptors. Venomous animals produce an enormous variety of peptide toxins with high affinity for specific ion channels and receptors. The mammalian prototoxin lynx1 shares with α-bungarotoxin the ability to bind and modulate nicotinic receptors (nAChRs); however, lynx1 is tethered to the membrane via a GPI anchor. We show here that several classes of neurotoxins, including bungarotoxins and cobratoxins, retain their selective antagonistic properties when tethered to the membrane. Targeted elimination of nAChR function in zebrafish can be achieved with tethered α-bungarotoxin, silencing synaptic transmission without perturbing synapse formation. These studies harness the pharmacological properties of peptide toxins for use in genetic experiments. When combined with specific methods of cell and temporal expression, the extension of this approach to hundreds of naturally occurring peptide toxins opens a new landscape for cell-autonomous regulation of cellular physiology in vivo.

A new two-dimensional adaptive meshing technique for the analysis of rotating machines is presented. The method preserves the symmetry and periodicity of the meshes during adaptive refinement. This allows for a more accurate calculation of the cogging torque than the standard adaptive meshing scheme. The advantages of this method are demonstrated by results for a surface permanent magnet motor and a permanent magnet motor with pitted teeth.

In this study, we measured damping characteristics and frequency characteristics of magnetic fluid bearing spindles using a high-frequency vibration base by a piezo actuator. Using the high-frequency vibration base, high frequency excitation was added to magnetic fluid bearing spindles mounted on the vibration base, and we proved that magnetic fluid bearing spindles have effective damping. Also the damping effect became larger with higher spindle rotational speed.

Glycosylphosphatidylinositol-anchored neurotoxin-like receptor binding proteins, such as lynx modulators, are topologically positioned to exert pharmacological effects by binding to the extracellular portion of nAChRs. These actions are generally thought to proceed when both lynx and the nAChRs are on the plasma membrane. Here, we demonstrate that lynx1 also exerts effects on α4β2 nAChRs within the endoplasmic reticulum. Lynx1 affects assembly of nascent α4 and β2 subunits and alters the stoichiometry of the receptor population that reaches the plasma membrane. Additionally, these data suggest that lynx1 shifts nAChR stoichiometry to low sensitivity (α4)3(β2)2 pentamers primarily through this interaction in the endoplasmic reticulum, rather than solely via direct modulation of activity on the plasma membrane. To our knowledge, these data represent the first test of the hypothesis that a lynx family member, or indeed any glycosylphosphatidylinositol-anchored protein, could act within the cell to alter assembly of a multisubunit protein.

Nicotinic acetylcholine receptors have been shown to participate in neuroprotection in the aging brain. Lynx protein modulators dampen the activity of the cholinergic system through direct interaction with nicotinic receptors. Although lynx1 null mutant mice exhibit augmented learning and plasticity, they also exhibit macroscopic vacuolation in the dorsal striatum as they age, detectable at the optical microscope level. Despite the relevance of the lynx1 gene to brain function, little is known about the cellular ultrastructure of these age-related changes. In this study, we assessed degeneration in the dorsal striatum in 1-, 3-, 7-, and 13-month-old mice, using optical and transmission electron microscopy. We observed a loss of nerve fibers, a breakdown in nerve fiber bundles, and a loss of neuronal nuclei in the 13-month-old lynx1 null striatum. At higher magnification, these nerve fibers displayed intracellular vacuoles and disordered myelin sheaths. Few or none of these morphological alterations were present in younger lynx1 null mutant mice or in heterozygous lynx1 null mutant mice at any age. These data indicate that neuronal health can be maintained by titrating lynx1 dosage and that the lynx1 gene may participate in a trade-off between neuroprotection and augmented learning.

The clonal structure of Melaleuca cajuputi growing in Thailand was investigated using ten polymorphic microsatellite markers and excavation of root connections. A large-scale test plot (25×45 m) and a small-scale one (10×12 m) within it were established in an M. cajuputi population at a barren sandy location in Narathiwat, southern Thailand (6° 30′ N, 101° 45′ E). Eleven clonal groups were identified from 31 ramets in the small-scale test plot based on root connections between ramets. To evaluate the effectiveness of microsatellite markers for genet analysis of M. cajuputi, clonal groups in the small-scale test plot identified by root connection were compared with genets determined by analysis of ten microsatellite markers. Most of the clonal groups identified by root connection completely matched the genets determined by the microsatellite markers. This indicates that microsatellite markers are very useful for genet analysis of M. cajuputi. Eleven genets were identified from 53 ramets in the large- and small-scale test plots using the ten microsatellite markers; the largest genet was about 23 m wide. This suggests that vegetative reproduction, i.e., shoot sprouting from roots, plays an important role in the establishment of M. cajuputi populations at this barren sandy site.

• Gene flow within and between two populations of the ectomycorrhizal fungus Suillus grevillei is shown here using co-dominant simple sequence repeat (SSR) markers. • Co-dominant SSR markers were developed for S. grevillei. Distribution and frequency of alleles at the three codominant SSR markers were analysed within two S. grevillei populations in two Larix Kaempteri stands located 700 m apart. • Among eight SSR loci isolated from S. grevillei, five loci (designated SG1-5) were polymorphic and SG1-3 were co-dominant. Genets (73) previously identified by inter-simple sequence repeat markers at the Larix stands were divided by the combination of SG1-3 into 22 genotypes. Most of the SSR genotypes were spatially clustered, indicating that the dispersal distance of S. grevillei spores was relatively short. • There was no conspicuous genetic differentiation within or between the two S. grevillei populations, indicating extensive gene flow. The spread of alleles within or between populations might be by repeats of short-distance spore dispersal rather than long-distance spore dispersal.

The possibility of recovering useful hydrocarbons from oil palm waste derived lignocellulose (palm shell oil) using steam tolerant catalysts was investigated. The examined catalysts were rare earth metal exchanged Y-type (REY) zeolites, nickel supporting REY zeolites and FeOOH catalysts. It was found that palm shell oil could be converted to a mixture which mainly contains phenol, acetone and butanone without hardly generating solid residues when a FeOOH catalyst was used. Therefore, by catalytic reaction, this waste-derived material may become a new and abundant chemical source. The catalytic activity of this FeOOH catalyst can be enhanced by supporting ZrO 2 on it. It was found that oxygen transfer during reaction occurs mainly from H 2 O to the products, not from the oxygen of the catalyst. It is assumed that the supported ZrO 2 plays a role of the decomposition of H 2 O adsorbed on the catalyst, yielding active hydrogen and oxygen species, which is also supported by the results of thermal desorption spectra and Mossbauer spectroscopy analysis of the catalyst.

Soluble polymers (PQE and PSE) with each constant π-conjugation length, containing thiophene tetramers and hexamers in the main chains, were prepared by reductive condensation, respectively. The obtained polymers were soluble in common organic solvents. Cast films could be obtained from their solutions. The PQE and PSE films doped with FeCl 3 showed considerable conductivities, 9-7×10 −3 and 0.4-0.2 S(cm, respectively. The polymer solutions and films were oxidized (doped) by stepwise addition of FeCl 3 and characterized by electronic absorption spectra. The spectral change of the PQE solutions and films showed one-step oxidation to produce cation radicals, whereas that of the PSE solutions and films did two-step oxidation to yield cation radicals in the first step and plural-electron-oxidized species such as dications in the second step. In atmosphere, the plural-electron-oxidized species of the PSE films are extremely labile. The spectra of the oxidized PSE films in atmosphere were almost similar to that of doped polythiophene films, indicating that oxidized species existing in doped polythiophenes are mainly cation radicals.

Elapid snake venom neurotoxins exert their effects through high-affinity interactions with specific neurotransmitter receptors. A novel murine gene, lynx1, is highly expressed in the brain and contains the cysteine-rich motif characteristic of this class of neurotoxins. Primary sequence and gene structure analyses reveal an evolutionary relationship between lynx1 and the Ly-6/neurotoxin gene family. lynx1 is expressed in large projection neurons in the hippocampus, cortex, and cerebellum. In cerebellar neurons, lynx1 protein is localized to a specific subdomain including the soma and proximal dendrites. lynx1 binding to brain sections correlates with the distribution of nAChRs, and application of lynx1 to Xenopus oocytes expressing nAChRs results in an increase in acetylcholine-evoked macroscopic currents. These results identify lynx1 as a novel protein modulator for nAChRs in vitro, which could have important implications in the regulation of cholinergic function in vivo.

We built and tested a double-loop thermoacoustic cooler consisting of an engine-loop, a branch resonator, and a cooler-loop. The cooling power of 6.4 W was obtained at the cooling temperature of 0 °C, when the input heat power of 416 W was supplied to the engine-loop. We measured the acoustic power and found that the output power emitted from the engine-loop was 12 W, and that the input acoustic power entering the cooler-loop was 6 W.

Summary Autosomal dominant cerebellar ataxia is a group of clinically and genetically heterogeneous disorders. We carried out genomewide linkage analysis in 15 families with autosomal dominant pure cerebellar ataxia (ADPCA). Evidence for linkage to chromosome 19p markers was found in nine families, and combined multipoint analysis refined the candidate region to a 13.3-cM interval in 19p13.1-p13.2. The remaining six families were excluded for this region. Analysis of CAG-repeat expansion in the alpha1A-voltage-dependent calcium channel (CACNL1A4) gene lying in 19p13.1, recently identified among 8 small American kindreds with ADPCA (spinocerebellar ataxia type 6 [SCA6]), revealed that 8 of the 15 families studied had similar, very small expansion in this gene: all affected individuals had larger alleles (range of CAG repeats 21–25), compared with alleles observed in neurologically normal Japanese (range 5–20 repeats). Inverse correlation between the CAG-repeat number and the age at onset was found in affected individuals with expansion. The number of CAG repeats in expanded chromosomes was completely stable within each family, which was consistent with the fact that anticipation was not statistically proved in the SCA6 families that we studied. We conclude that more than half of Japanese cases of ADPCA map to 19p13.1-p13.2 and are strongly associated with the mild CAG expansion in the SCA6/CACNL1A4 gene.

The level of expression of transgenes in transgenic animals varies among lines, and is often much lower than that of endogenous genes (position effects). In order to surmount position effects and establish a more efficient production system of transgenic animals producing pharmaceutical proteins in their milk, transgenic rats carrying 210-kb YAC DNA containing the human alpha-lactalbumin gene were produced. Three transgenic lines transmitted the transgene to the next generation. They had one copy of the alpha-lactalbumin gene and secreted human alpha-lactalbumin in their milk at concentrations of 2.0-4.3 mg/ml. No position effect was seen. The transgene was expressed specifically in the mammary gland of the transgenic rats. The 210-kb region is thought to contain all the DNA elements required for proper expression of the human alpha-lactalbumin gene. The YAC carrying the human alpha-lactalbumin gene is a potential vector for the expression of foreign genes in the mammary gland.

The classical targets for antipsychotic and antidepressant drugs are G protein-coupled receptors and neurotransmitter transporters, respectively. Full therapeutic actions of these drugs require several weeks. We show how therapeutic effects may eventually accrue after existing therapeutic ligands bind to these classical targets, not on the plasma membrane but rather within endoplasmic reticulum (ER) and cis-Golgi. Consequences of such binding may include pharmacological chaperoning: the nascent drug targets are stabilized against degradation and can therefore exit the ER more readily. Another effect may be matchmaking: heterodimers and homodimers of the target form and can more readily exit the ER. Summarizing recent data for nicotinic receptors, we explain how such effects could lead to reduced ER stress and to a decreased unfolded protein response, including changes in gene activation and protein synthesis. In effects not directly related to cellular stress, escorting would allow increased ER exit and trafficking of known associated proteins, as well as other proteins such as growth factors and their receptors, producing both cell-autonomous and non-cell-autonomous effects. Axonal transport of relevant proteins may underlie the several weeks required for full therapy. In contrast, the antidepressant effects of ketamine and other N-methyl-D-aspartate receptor ligands, which occur within

On October 4, 1994, an earthquake with magnitude Mw8.3 occurred in the western part of Kurile Islands at 43.42°N, 146.81°E and 33 km in depth. The hypocenter parameters were determined by Hokkaido University in Japan. Aftershocks following this remarkable event were located using data from a local seismic network operated by Hokkaido University. We found that most of the aftershocks occurred (1) on the fault plane of the mainshock, (2) in the subducting plate around the fault plane of the mainshock, and (3) in the focal area of the largest aftershock, which occurred on October 9 with Mw7.3. Both (2) and (3) were not active immediately after the mainshock. Considering the time sequence of the aftershock activity, we identified one of the nodal planes of the Harvard quick CMT solutions as the fault plane of the mainshock; the strike is almost parallel to the trench axis and the dip angle is near vertical. It is obvious that this event is different from a low-angle thrust-type interplate earthquake. The distribution of aftershocks strongly suggests that it is an intraplate event.

The cholinergic system underlies both adaptive (learning and memory) and nonadaptive (addiction and dependency) behavioral changes through its ability to shape and regulate plasticity. Protein modulators such as lynx family members can fine tune the activity of the cholinergic system and contribute to the graded response of the cholinergic system, stabilizing neural circuitry through direct interaction with nicotinic receptors. Release of this molecular brake can unmask cholinergic-dependent mechanisms in the brain. Lynx proteins have the potential to provide top-down control over plasticity mechanisms, including addictive propensity. If this is indeed the case, then, what regulates the regulator? Transcriptional changes of lynx genes in response to pharmacological, physiological, and pathological alterations are explored in this review.

A simple method for detecting the 1-alkyl-2-[ 3 H]acetyl- sn -glycero-3-phosphocholine ([ 3 H]acetyl-PAF)-hydrolyzing activity of serum proteins is described. These were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride (PVDF) membranes. The assay involves measurement of the β-radioluminescence of [ 3 H]acetyl-PAF on the PVDF membranes with an ultra-high-sensitivity TV camera system. Enzyme activity is detected as a decrease in β-radioluminescence of [ 3 H]acetyl-PAF on the blotted membranes, since of [ 3 H]acetyl-PAF remains on the membrane but the [ 3 H]acetate released by the enzyme reaction detaches from the membrane. This method has been used to identify PAF acetylhydrolase and phospholipase A 2 .

We employed a pH-sensitive GFP analog, superecliptic phluorin, to observe aspects of nicotinic acetylcholine receptor (nAChR) trafficking to the plasma membrane (PM) in cultured mouse cortical neurons. The experiments exploit differences in the pH among endoplasmic reticulum (ER), trafficking vesicles, and the extracellular solution. The data confirm that few α4β4 nAChRs, but many α4β2 nAChRs, remain in neutral intracellular compartments, mostly the ER. We observed fusion events between nAChR-containing vesicles and PM; these could be quantified in the dendritic processes. We also studied the β4R348C polymorphism, linked to amyotrophic lateral sclerosis (ALS). This mutation depressed fusion rates of α4β4 receptor-containing vesicles with the PM by ∼2-fold, with only a small decrease in the number of nAChRs per vesicle. The mutation also decreased the number of ER exit sites, showing that the reduced receptor insertion results from a change at an early stage in trafficking. We confirm the previous report that the mutation leads to reduced agonist-induced currents; in the cortical neurons studied, the reduction amounts to 2–3-fold. Therefore, the reduced agonist-induced currents are caused by the reduced number of α4β4-containing vesicles reaching the membrane. Chronic nicotine exposure (0.2 μm) did not alter the PM insertion frequency or trafficking behavior of α4β4-laden vesicles. In contrast, chronic nicotine substantially increased the number of α4β2-containing vesicle fusions at the PM; this stage in α4β2 nAChR up-regulation is presumably downstream from increased ER exit. Superecliptic phluorin provides a tool to monitor trafficking dynamics of nAChRs in disease and addiction.

We employed a pH-sensitive GFP analog, superecliptic phluorin, to observe aspects of nicotinic acetylcholine receptor (nAChR) trafficking to the plasma membrane (PM) in cultured mouse cortical neurons. The experiments exploit differences in the pH among endoplasmic reticulum (ER), trafficking vesicles, and the extracellular solution. The data confirm that few α4β4 nAChRs, but many α4β2 nAChRs, remain in neutral intracellular compartments, mostly the ER. We observed fusion events between nAChR-containing vesicles and PM; these could be quantified in the dendritic processes. We also studied the β4R348C polymorphism, linked to amyotrophic lateral sclerosis (ALS). This mutation depressed fusion rates of α4β4 receptor-containing vesicles with the PM by ∼2-fold, with only a small decrease in the number of nAChRs per vesicle. The mutation also decreased the number of ER exit sites, showing that the reduced receptor insertion results from a change at an early stage in trafficking. We confirm the previous report that the mutation leads to reduced agonist-induced currents; in the cortical neurons studied, the reduction amounts to 2–3-fold. Therefore, the reduced agonist-induced currents are caused by the reduced number of α4β4-containing vesicles reaching the membrane. Chronic nicotine exposure (0.2 μm) did not alter the PM insertion frequency or trafficking behavior of α4β4-laden vesicles. In contrast, chronic nicotine substantially increased the number of α4β2-containing vesicle fusions at the PM; this stage in α4β2 nAChR up-regulation is presumably downstream from increased ER exit. Superecliptic phluorin provides a tool to monitor trafficking dynamics of nAChRs in disease and addiction.

Cholinergic neurons and nicotinic acetylcholine receptors (nAChRs) in the brain participate in diverse functions: reward, learning and memory, mood, sensory processing, pain, and neuroprotection. Nicotinic systems also have well-known roles in drug abuse. Here, we review recent insights into nicotinic function, linking exogenous and endogenous manipulations of nAChRs to alterations in synapses, circuits, and behavior. We also discuss how these contemporary advances can motivate attempts to exploit nicotinic systems therapeutically in Parkinson's disease, cognitive decline, epilepsy, and schizophrenia.

The up-regulation of α4β2* nicotinic acetylcholine receptors (nAChRs) by chronic nicotine is a cell-delimited process and may be necessary and sufficient for the initial events of nicotine dependence. Clinical literature documents an inverse relationship between a person’s history of tobacco use and his or her susceptibility to Parkinson’s disease; this may also result from up-regulation. This study visualizes and quantifies the subcellular mechanisms involved in nicotine-induced nAChR up-regulation by using transfected fluorescent protein (FP)-tagged α4 nAChR subunits and an FP-tagged Sec24D endoplasmic reticulum (ER) exit site marker. Total internal reflection fluorescence microscopy shows that nicotine (0.1 µM for 48 h) up-regulates α4β2 nAChRs at the plasma membrane (PM), despite increasing the fraction of α4β2 nAChRs that remain in near-PM ER. Pixel-resolved normalized Förster resonance energy transfer microscopy between α4-FP subunits shows that nicotine stabilizes the (α4)2(β2)3 stoichiometry before the nAChRs reach the trans-Golgi apparatus. Nicotine also induces the formation of additional ER exit sites (ERES). To aid in the mechanistic analysis of these phenomena, we generated a β2enhanced-ER-export mutant subunit that mimics two regions of the β4 subunit sequence: the presence of an ER export motif and the absence of an ER retention/retrieval motif. The α4β2enhanced-ER-export nAChR resembles nicotine-exposed nAChRs with regard to stoichiometry, intracellular mobility, ERES enhancement, and PM localization. Nicotine produces only small additional PM up-regulation of α4β2enhanced-ER-export receptors. The experimental data are simulated with a model incorporating two mechanisms: (1) nicotine acts as a stabilizing pharmacological chaperone for nascent α4β2 nAChRs in the ER, eventually increasing PM receptors despite a bottleneck(s) in ER export; and (2) removal of the bottleneck (e.g., by expression of the β2enhanced-ER-export subunit) is sufficient to increase PM nAChR numbers, even without nicotine. The data also suggest that pharmacological chaperoning of nAChRs by nicotine can alter the physiology of ER processes.

Light propagation is measured through a multiple-scattering medium, and the scattering mean-free path is measured for different densities of scatterers. We analyze the effect of detector orientation relative to the light source, an effect of the anisotropy of the photon current. We compare light propagation in an infinite geometry to reflectance in a backscattering experiment. We compare to models for the boundary conditions applicable at the interface between the scattering medium and the adjacent free medium. These consist of linear combinations of absorbing and reflecting boundary conditions.

Lynx Vision Early in development, correct visual experiences during the so-called “critical period” build the foundations for visual function in adulthood. Hence, when one eye is not working together with the other, an adult may be left with imperfect vision. The plasticity characteristic of the critical period does not persist into adulthood, and later readjustments to visual function may not be fully successful. Morishita et al. (p. 1238 , published online 11 November; see the Perspective by Higley and Strittmatter ) have identified a gene in mice called Lynx1 , which shows increased expression after the critical period. The Lynx1 protein binds to and reduces the sensitivity of acetylcholine receptors, but if mice were treated to enhanced cholinergic signaling, their adult visual plasticity was improved and if mice lacked the Lynx1 gene altogether, they were able to recover visual function even in adulthood.

Dopamine (DA) release in striatum is governed by firing rates of midbrain DA neurons, striatal cholinergic tone, and nicotinic ACh receptors (nAChRs) on DA presynaptic terminals. DA neurons selectively express alpha6* nAChRs, which show high ACh and nicotine sensitivity. To help identify nAChR subtypes that control DA transmission, we studied transgenic mice expressing hypersensitive alpha6(L9'S)* receptors. alpha6(L9'S) mice are hyperactive, travel greater distance, exhibit increased ambulatory behaviors such as walking, turning, and rearing, and show decreased pausing, hanging, drinking, and grooming. These effects were mediated by alpha6alpha4* pentamers, as alpha6(L9'S) mice lacking alpha4 subunits displayed essentially normal behavior. In alpha6(L9'S) mice, receptor numbers are normal, but loss of alpha4 subunits leads to fewer and less sensitive alpha6* receptors. Gain-of-function nicotine-stimulated DA release from striatal synaptosomes requires alpha4 subunits, implicating alpha6alpha4beta2* nAChRs in alpha6(L9'S) mouse behaviors. In brain slices, we applied electrochemical measurements to study control of DA release by alpha6(L9'S) nAChRs. Burst stimulation of DA fibers elicited increased DA release relative to single action potentials selectively in alpha6(L9'S), but not WT or alpha4KO/alpha6(L9'S), mice. Thus, increased nAChR activity, like decreased activity, leads to enhanced extracellular DA release during phasic firing. Bursts may directly enhance DA release from alpha6(L9'S) presynaptic terminals, as there was no difference in striatal DA receptor numbers or DA transporter levels or function in vitro. These results implicate alpha6alpha4beta2* nAChRs in cholinergic control of DA transmission, and strongly suggest that these receptors are candidate drug targets for disorders involving the DA system.

In Japan, Cryptomeria japonica pollen are scattered during each spring season. Daughter allergenic particles are released, which are smaller in size than their parent pollen grain and are abundant in a particle size below 1.1 μm in the atmosphere; nevertheless, Cryptomeria japonica pollen size is about 30 μm. Therefore, daughter allergenic particles of pollen are transported in the urban atmosphere for a long time after their release. In particular, the daily variation delays in the peaks of allergenic Cry j 1 concentrations of Cryptomeria japonica pollen compared with the peaks of airborne pollen counts were observed in high levels during one or two sunny days after rainfall. In addition, long range transportation of Asian dust from the East Asian continent, called yellow sand, was also found during the pollen scattering seasons in Japan, due to global warming. Therefore, the interaction between pollen and air pollutants, including yellow sand, should be of concern. Thus, in this study, the morphological change of Cryptomeria japonica pollen and the elution behavior of its allergenic contents (Cry j 1) were also investigated when in contact with simulated air polluted rain containing various crustal particles and/or secondary formed inorganic particles. As a result, pollen might burst at high humidity before

The behavior of platelet-activating factor (PAF) produced in stimulated human polymorphonuclear leukocytes (PMN) was investigated in the presence of serum under conditions close to those existing in vivo. When the cells were stimulated in the presence of the serum obtained from a PAF acetylhydrolase (PAF-AH)-deficient Japanese subject, over 60% of synthesized PAF was detected in the extracellular medium by bioassay, scintillation proximity RIA and selected ion monitoring/gas chromatography/mass spectrography analysis. The release of PAF from PMN after stimulation with FMLP and A23187 was also observed in the presence of normal serum treated with acid to inactivate PAF-AH. The heterogeneity of the molecular species of extracellular PAF was similar to that of intracellular PAF produced in stimulated PMN in the presence of PAF-AH-deficient serum, ruling out the possibility that a specific molecular species of PAF was preferentially released from the cells in the presence of the serum. As these data suggested the occurrence of PAF-releasing factor(s) in the serum, an attempt was made to partially purify this factor from PAF-AH-deficient serum and acid-treated normal serum by ammonium sulfate fractionation and column chromatography with DEAE-Cellulofine and Sepharose CL-6B. The molecular mass of PAF-releasing factor revealed on a TSK gel G3000 SW HPLC column was 240 kDa, which was different from that of albumin. The binding assay, newly developed for this study, revealed that the PAF-binding activity of PAF-releasing factor is stronger than that of albumin, and that the PAF-releasing factor forms a complex with PAF at low concentration (10(-9) M). PAF bound to this factor was difficult to be hydrolyzed by serum PAF-AH. On the other hand, the PAF/PAF-releasing factor complex had aggregatory activity toward washed rabbit platelets. These observations suggest that certain protein(s) releases and carries the PAF newly synthesized by PMN in blood plasma/serum. Thus it appears that PAF functions as an autacoid in vivo, along with other mediators.

Musty-odorous compounds, metabolites of some species of blue-green algae, are usually contained in both the water and algal cell bodies. The compounds in the latter solid phase were found to be easily removed by coagulation and sedimentation without breakpoint prechlorination (intermediate chlorination used instead). Chlorination of the algae results in an artificial release of the metabolite content into the surrounding water. When a large fraction of the compounds was present in the algal cell bodies, more than 60% of these compounds were removed in the intermediate-chlorination treatment. Powdered activated carbon treatment is effective in removing the compounds in the aqueous phase. However, the effectivness was usually limited in practical treatment to high concentrations of musty odor. On the other hand, the ozonation and granular activated carbon (GAC) treatment was found to be an effective method for removal. It was observed that the musty-odorous compounds were completely removed through the ozonation and GAC treatment system, which included coagulation and sedimentation without prechlorination.

Morbidity due to Cryptomeria japonica pollinosis is increasing, especially in the urban areas of Japan. It represents a major health problem for most modern societies. The reasons for this increase might be the association of pollen with air pollutants. Hyper-reactivity tests are being conducted on mice and rats for allergic immune response. However, such tests cannot evaluate the deposition of pollen to the respiratory tract, because they force the animals to be immunized to pollen allergen mixed with air pollutants separately. The purpose of this study is to investigate how air pollutants deposit onto airborne Cryptomeria japonica pollen grains during the pollen-flying season between urban and mountainous areas, and to aid further bioreactivity and hypersensitive research. Suspended particulate matter (SPM), Cryptomeria japonica perigonium and pollen grains were collected to identify the deposition of air pollutants in an urban area, Saitama City, and in a mountainous area, Okuchichibu, during the pollen flying seasons. Ionic and metallic components of SPM and perigonium and pollen grains were analyzed. We found that crustal components (Al, Fe and Ti) tended to deposit on pollen perigonium. The amount of ionic components of particles (NO3, SO4 and NH4) and gaseous pollutants (NO2, SO2 and NH3) deposited on the perigonium and pollen grains were higher in the urban than in the mountainous areas, the results of which was proven by determination of gaseous Environmental Health Risk V 77 © 2009 WIT Press WIT Transactions on Biomedicine and Health, Vol 14, www.witpress.com, ISSN 1743-3525 (on-line) doi:10.2495/EHR090081 pollutants exposed to Cryptomeria japonica pollen. It is suggested that these phenomena may affect the pollinosis and therefore it is necessary to investigate implications on further bioreactivity and hypersensitive research.

Anxiety disorders are the most prevalent mental disorders in developed societies. Although roles for the prefrontal cortex, amygdala, hippocampus and mediodorsal thalamus in anxiety disorders are well documented, molecular mechanisms contributing to the functions of these structures are poorly understood. Here we report that deletion of Lynx2 , a mammalian prototoxin gene that is expressed at high levels in anxiety associated brain areas, results in elevated anxiety-like behaviors. We show that LYNX2 can bind to and modulate neuronal nicotinic receptors, and that loss of Lynx2 alters the actions of nicotine on glutamatergic signaling in the prefrontal cortex. Our data identify Lynx2 as an important component of the molecular mechanisms that control anxiety, and suggest that altered glutamatergic signaling in the prefrontal cortex of Lynx2 mutant mice contributes to increased anxiety-related behaviors.

The acronym SePhaChARNS, for "selective pharmacological chaperoning of acetylcholine receptor number and stoichiometry," is introduced. We hypothesize that SePhaChARNS underlies classical observations that chronic exposure to nicotine causes "upregulation" of nicotinic receptors (nAChRs). If the hypothesis is proven, (1) SePhaChARNS is the molecular mechanism of the first step in neuroadaptation to chronic nicotine; and (2) nicotine addiction is partially a disease of excessive chaperoning. The chaperone is a pharmacological one, nicotine; and the chaperoned molecules are alpha4beta2* nAChRs. SePhaChARNS may also underlie two inadvertent therapeutic effects of tobacco use: (1) the inverse correlation between tobacco use and Parkinson's disease; and (2) the suppression of seizures by nicotine in autosomal dominant nocturnal frontal lobe epilepsy. SePhaChARNS arises from the thermodynamics of pharmacological chaperoning: ligand binding, especially at subunit interfaces, stabilizes AChRs during assembly and maturation, and this stabilization is most pronounced for the highest-affinity subunit compositions, stoichiometries, and functional states of receptors. Several chemical and pharmacokinetic characteristics render exogenous nicotine a more potent pharmacological chaperone than endogenous acetylcholine. SePhaChARNS is modified by desensitized states of nAChRs, by acid trapping of nicotine in organelles, and by other aspects of proteostasis. SePhaChARNS is selective at the cellular, and possibly subcellular, levels because of variations in the detailed nAChR subunit composition, as well as in expression of auxiliary proteins such as lynx. One important implication of the SePhaChARNS hypothesis is that therapeutically relevant nicotinic receptor drugs could be discovered by studying events in intracellular compartments rather than exclusively at the surface membrane.

This paper describes how dynamic wheel load variation is one of the major causes of railway track deterioration and ground vibration. Lightening of vehicle unsprung-mass is more effective on reducing dynamic wheel load than that of sprung or intermediate mass. This paper estimates and discusses this effect by combining the following three methods; (1) field tests and measurements with a special equipped train, (2) an experimental method with a unique test facility and real track, and (3) a computer simulation which can calculate dynamic interaction between vehicle and track.

This paper presents the achievements for the deeper understanding of the vehicle-track dynamic interactions. First, the paper developed the Track & Structural Dynamics Simulator (TRADYS), which is the testing instrument to excite a certain fixed point on the test track to produce the vehicle-track dynamic interaction similar to that actually produced by the passing trains on the commercial lines. The paper also established the numerical simulation model of the vehicle-track dynamics of TRADYS. Through the combination of the above two experimental and theoretical approaches, the paper analyzed the influence of the track conditions on the wheel load variation. This study took into account the four example track conditions for the test and the simulation, where the assumptions were as follows: (1) Standard track condition of Tokaido Shinkansen, (2) Installment of less elastic rail pads instead of standard rail pads, (3) Installment of resilient sleepers instead of standard sleepers (4) Both above replacements (2) and (3). The vehicle specifications of the Series 700 of Tokaido Shinkansen with the speed at 270km/h were chosen and used in this analysis. As a result, the paper obtained the following outcomes: (1) In the frequency ranges of up to 50 Hz, the replacement of both/either the rail pads and/or the sleepers resulted in no reductive influence on the wheel load variation. (2) On the other hand, in the frequency ranges of over 50 Hz, the replacement of both/either the rail pads and/or the sleepers contributed to the reduction of wheel load variation. (3) In the frequency ranges of over 50Hz, the lower track support spring led to the weaker transmissibility ratio of a track (irregularity) to wheel load variation.

In this paper, an idea of the cutting plane method is employed to improve the fractional distance of a given binary parity check matrix. The fractional distance is the minimum weight (with respect to l1-distance) of vertices of the fundamental polytope. The cutting polytope is defined based on redundant rows of the parity check matrix and it plays a key role to eliminate unnecessary fractional vertices in the fundamental polytope. We propose a greedy algorithm and its efficient implementation for improving the fractional distance based on the cutting plane method., Comment: 8 pages, To be presented at Turbo Coding 2008

The recognition of double-stranded DNA breaks and single-stranded nicks by human poly(ADP-ribose) polymerase and the consequent enzymic activation were examined using derivatives of the enzyme expressed in Escherichia coli. The N-terminal 162 residues encompass two zinc fingers. Deletion or mutation of the first finger results in a loss of activation by DNA with either single-stranded or double-stranded damage. Destruction of the second finger reduces activation by double-stranded DNA breaks only slightly, but eliminates activation by single-stranded DNA nicks. These data suggest that activation by single-stranded DNA nicks requires two zinc fingers, but activation by double-stranded DNA breaks requires only the finger closer to the N terminus. Variant proteins that lack both zinc fingers are enzymically inactive but still exhibit weak DNA binding, which is independent of DNA damage. Thus, other regions are also capable of binding intact DNA, but the recognition of a strand nick or break which occasions the synthesis of poly(ADP-ribose) specifically requires the zinc fingers.

Although a magnesium (Mg)-deficient diet is generally known to induce nephrocalcinosis, our previous study observed that despite the administration of a Mg-deficient diet, the kidney calcium (Ca) and phosphorus (P) concentrations were not increased in male rats. We speculated that this result was due to the P concentration of the experimental diet based on the AIN-93G formula used in the previous study. In the present study, male rats were fed modified AIN-93G diets containing the two different Mg concentrations [0.5 g per kg diet (normal-Mg) or Mg-free (Mg-deficient)] and three different P concentrations [3 (3-P), 5 (5-P) or 7 (7-P) g per kg diet]. By histological examination of the kidney, nephrocalcinosis was not observed in rats fed on the Mg-deficient diet containing 3-P While nephrocalcinosis appeared in rats fed on the Mg-deficient diet containing 5-P and 7-P The degree of nephrocalcinosis was severe in rats fed on the Mg-deficient diet containing 7-P compared with rats fed on the Mg-deficient diet containing 5-P These results demonstrated that the Mg-deficient diet based on AIN-93G formula dose not induce nephrocalcinosis and that the Mg-deficient diet based on AIN-93G formula with increased dietary P concentrations induces nephrocalcinosis in male rats. We suggest that the onset of nephrocalcinosis could depend on the dietary P concentration in male rats fed on a Mg-deficient diet.

The panda mutant in Japanese quail (Coturnix japonica) displays spots of wild-type plumage on a white background and is controlled by an autosomal recessive allele (s). The dotted white is controlled by a third allele (s(dw)) of the s locus with s(dw)/s(dw) quail having less pigmentation than s/s quail. We mapped the s locus to the Japanese quail chromosome 4 (CJA04) in a previous study. The orthologous region of the chicken (Gallus gallus) genome includes endothelin receptor B2 (EDNRB2), an avian-specific paralog of endothelin receptor B (EDNRB). EDNRB mutations in mammals retard the migration of neural crest cells (NCCs), which results in a spotted coat colour and an enteric nervous defect. In the present study, we investigated the association between the s locus and EDNRB2 in Japanese quail. Sequence comparison among transcripts from livers of wild-type, panda and dotted white quail revealed a nucleotide substitution (c.995GA) leading to a p.R332H amino acid change that was specific to panda, whereas no amino acid substitution was found in dotted white birds. The amino acid position 332 is located in the sixth transmembrane domain and is highly conserved in both avian and mammalian endothelin receptors. The A allele at nucleotide position 995 was specific to panda (s/s) birds among 10 strains, and was mapped to the same chromosomal region as the s locus. Quantitative RT-PCR revealed that EDNRB2 transcripts were reduced in both panda and dotted white mutants compared with wild-type. However, there was no difference between the early embryos of wild-type and panda with respect to the migration of NCCs. The genetic association of EDNRB2 with plumage colour in birds was found for the first time in this study.

This paper describes how it is important when studying vehicle-track dynamic interactions to make clear the characteristics of many physical and/or structural parameters of a track. However, it is difficult to estimate them with accuracy only through measurements under a real train load on site. This paper describes an approach using two tools of a test facility and computer simulation. The Track and Structural Dynamics Simulator (TRADYS) is a unique mechanical vibration exciter equipped with hydraulic actuators between a train and a track. The train has the same masses and suspensions as the latest Japanese high speed railway vehicle. We can control arbitrarily the vertical relative displacements between rails and wheels through the directions inputted to the actuator. These relative displacements are supposed to represent a railway track irregularity. In the experiments, dynamic wheel loads, displacements and accelerations of each part of a track are measured as the outputs. In addition to the experiments, computer simulation is carried out. A theoretical model for this special test facility including the actuator is constructed. In this paper the measured physical values and computed solutions are compared, and the accuracy of the parameter values of the track structure components is also discussed.

Two first-order forested watersheds (WS 80 and WS 77) on poorly drained pine-hardwood stands in the South Carolina Coastal Plain have been monitored since mid-1960s to characterize the hydrology, water quality and vegetation dynamics. This study examines the flow and nutrient dynamics of these two watersheds using 13 years (1969-76 and 1977-81) of data prior to Hurricane Hugo (1989) and nearly 10 years (1990-1992, 1996-99, and 2003-06) immediately after Hugo. WS 80 remained as a control throughout the study period, whereas WS 77 underwent several treatments including prescribed burning, partial harvest, salvage logging and prescribed fire for red-cockaded woodpecker habitat management. Depending upon the antecedent moisture conditions, both the watersheds were highly responsive of rainfall events throughout the periods. Accordingly, annual outflows varied from 5% in 1981 to 59% in 1998 with an average of 22% of the annual precipitation for the control (WS 80) and from 9% in 2004 to 44% in 1991, with an average of 27% for the treatment watershed (WS 77). The coefficient of variation (COV) on WS 80 was higher (55%) compared to 36% for the WS 77. Annual rainfall variation was much lower (COV = 14%) than the variation in stream outflows. Post Hugo average outflow from WS 77 increased relative to WS 80 until 1992. By the regeneration period of 1996 reversal in outflow was noticed with the higher outflows on WS 80 than on the WS 77. While prescribed burning of WS 77 in a course of five years (1977-81) did not affect on stream outflows and chemistry, mastication in course of nine months in 2001 followed by another prescribed burning of 84% of WS 77 on May 10, 2003 seemed to have increased the outflows on WS 77 both in 2004 (64%) and 2005 (70%). Average nutrient concentrations were similar on both watersheds although there was a wide variability in NH4-N on the treatment watershed (WS 77) compared to WS 80. pH was slightly lower on the WS 77 (5.4) than on WS 80 (6.8). Both NO3-N and NH4-N concentrations were very low for both the watersheds, before and after Hugo, with organic nitrogen as the dominant factor on both watersheds. Phosphate was also very low (0.02 mg L-1, on average) on both the watersheds during both the periods. Hurricane Hugo substantially increased the nutrient loads primarily due to increase in outflows. Although data presented herein may serve as baseline information for assessing impacts of both the developments and natural disturbance in the region, further studies and analysis with additional data should be conducted to verify some results such as the reversal of flow pattern after the hurricane Hugo that may have changed the dynamics of regenerated vegetation after Hugo possibly affecting stream outflows via evapotranspiration (ET) on these humid coastal plain watersheds.

The objective of this work was to map classical markers (plumage colours and blood proteins) on the microsatellite linkage map of the Japanese quail (Coturnix japonica). The segregation data on two plumage colours and three blood proteins were obtained from 25 three-generation families (193 F2 birds). Linkage analysis was carried out for these five classical markers and 80 microsatellite markers. A total of 15 linkage groups that included the five classical loci and 69 of the 80 microsatellite markers were constructed. Using the BLAST homology search against the chicken genome sequence, three quail linkage groups, QL8, QL10 and QL13, were suggested to be homologous to chicken chromosomes GGA9, GGA20 and GGA24, respectively. Two plumage colour loci, black at hatch (Bh) and yellow (Y), and the three blood protein loci, transferrin (Tf), haemoglobin (Hb-1) and prealbumin-1 (Pa-1), were assigned to CJA01, QL10, QL8, CJA14 and QL13, respectively.

Nurse scheduling problem is one of combinatorial optimisation problems, and it is difficult to search for optimal solutions. This paper describes how bacterial evolutionary algorithm (BEA), which is one of evolutionary algorithms, is applied to search for the optimal solutions of nurse schedules. It takes a large amount of computation time for the scheduling. The nurses scheduling system is implemented on a hardware executed BEA for acceleration, and the system performs in real time.

A novel wholly aromatic polyester poly[oxy-1,4-phenylene(1-methylethylidene)-1,4-phenyleneoxycarbonyl(9,10-dihydr o-2,7-phenanthrenediyl)-carbonyl] (I) was synthesized by palladium catalyzed carbonylation-polycondensation with 2,7-dibromo-9,10-dihydrophenanthrene and bisphenol-A. Polyarylate (I) obtained in 95% yield with high molecular weight (polystyrene equivalent M/sub w/=102,600) under optimum conditions, and was highly heat-resistant and soluble in organic solvent such as chlorobenzene, dichloromethane, and chloroform. The initial thermal degradation temperatures of poly arylate (I) are 332-420/spl deg/C in the air atmosphere and 420-483/spl deg/C under a nitrogen stream. Activation energy of oxidizing degradation reaction in the air atmosphere was 89 KJ/mol. The intrinsic viscosity of polyarylate (I) was 0.46, and their viscosities under the steady shear flow were 22, 250 and 7200 mPa.s at the concentration of 5, 10 and 20 g/dl, respectively. The tensile strength at break and tensile modulus were 44.5 MPa and 1.23 GPa, respectively: these properties are roughly in the same level as those of conventional unsaturated polyester resin. Polyarylate (I) exhibits the dynamic viscoelastic behavior for like typical amorphous polymer. Dynamic viscoelastic curve showed that the glass transition temperature was about 270/spl deg/C.

Evolutionary algorithms (EAs) have been applied to various combinatorial optimization problems. The Bacterial Evolutionary Algorithm (BEA) is an optimization method that incorporates special mechanisms inspired by natural phenomena of microbial evolution. The BEA has been applied to fuzzy modeling of nonlinear systems for efficient discovery of appropriate rules and parameter tunings. Cerebellar Model Arithmetic Computer (CMAC) is a neural network that imitates the human cerebellum. One of the advantages of CMAC is its fast learning capability. It is, however, difficult to find the proper partition of input space of CMAC. The paper proposes an approach to the determination of input space division of CMAC using BEA. Hardware implementation of CMAC using BEA is also done to accelerate the computation time. The CMAC/BEA hardware is 108 times faster in computation than the software run on a conventional processor.

Increased network capabilities and the prevalence of wireless networks have provided an environment where data and compute intensive surveillance applications can be realized as part of existing infrastructures. Nevertheless, careful consideration must be given to how such systems are designed an implemented. In our efforts to consider pervasive surveillance applications, this paper highlights some of the primarily issues related to the transmission, analysis, storage and retrieval of surveillance video and briefly describes our framework for video surveillance from mobile devices.

A cerebellar model arithmetic computer (CMAC) is a neural network whose advantage is fast learning. It is, however, difficult to decide on the various parameters of a CMAC in advance. The pseudo-bacterial genetic algorithm (PBGA) is an evolutionary algorithm that is efficient in local searching. This paper proposes a "PBGA/CMAC" system that decides the positions of partitions, which are the main parameters of a CMAC, using the PBGA. The PBGA/CMAC hardware is implemented for acceleration, because PBGA/CMAC needs a large amount of computation time. An efficient learning method using pipelining is also presented. It is found that the accuracy with the proposed learning method is almost the same as that of the conventional CMAC's learning. The PBGA/CMAC hardware is 140 times faster than that of the equivalent PBGA software.

Evolutionary algorithms (EAs) have been applied to various combinatorial optimization problems. Bacterial evolutionary algorithm (BEA) is an optimization method that incorporates special mechanisms inspired by natural phenomena of microbial evolution. The BEA has been applied to fuzzy modeling of nonlinear systems for efficient discovery of appropriate rules and parameter tunings. CMAC is a neural network that imitates human cerebellum. One of the advantages of CMAC is its fast learning capability. It is, however, difficult to identify appropriate parameters of CMAC. This paper proposes a new approach to determination of input space division of CMAC using BEA. CMAC learning using BEA needs a large amount of computation time. This paper presents a pipelined BEA/CMAC hardware that is about 96 times faster than that by the software executed on the conventional processor. This paper also presents a new approach to CMAC modeling by encoding granule cells of CMAC into chromosomes of BEA for identification of more accurate model.