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Tolosa-Hunt syndrome (THS) is a type of painful ophthalmoplegia characterized by unilateral orbital pain and oculomotor paresis. This report describes a case of painful ophthalmoplegia considered to be THS. The patient was a 72-year-old woman. After dental implant placement in the left maxillary first molar site, she was referred to our hospital for persistent left periorbital and facial pain, diplopia, and taste disorder. With an initial diagnosis of trigeminal neuralgia, diplopia, and taste disorder, we began administration of carbamazepine and polaprezinc, and asked the department of ophthalmology in our hospital to examine her diplopia. With the increase in serum zinc levels, the taste disorder resolved, but her periorbital pain and diplopia were aggravated, and she had to be hospitalized. As a result of extensive examinations, we suspected her painful ophthalmoplegia was due to cavernous sinus abnormalities; finally, THS was diagnosed. There was significant improvement in the periorbital pain within 48 h after the start of corticosteroid therapy. Since then, she has never suffered from painful ophthalmoplegia. This case indicates that careful evaluation and accurate diagnosis are critical in cases of painful ophthalmoplegia, and the possibility of THS should always be kept in mind.

Fifth-generation (5G) mobile communication is expected to provide a suitable network for all service requirements. Automation of network slicing is required to respond to the dynamically changing service requirements. This paper proposes a method to allocate the radio resources that satisfy the service requirements irrespective of the number of slices utilizing reinforcement learning. From the evaluation of the proposed method using a scenario, in which the number of slices fluctuates with the passage of time, it is clarified that this method allocates the radio resources to fulfill the requirements of the service following the change in the number of slices.

The demand for mobile data communication has been increasing owing to the diversification of its purposes and the increase in the number of mobile devices accessing mobile networks. Users are experiencing a degradation in communication quality due to mobile network congestion. Therefore, improving the bandwidth utilization efficiency of cellular infrastructure is crucial. We previously proposed a mobile data offloading protocol (MDOP) for improving the bandwidth utilization efficiency. Although this method balances a load of evolved node B by taking into consideration the content delay tolerance, accurately balancing the load is challenging. In this paper, we apply deep reinforcement learning to MDOP to solve the temporal locality of a traffic. Moreover, we examine and evaluate the concrete processing while considering a delay tolerance. A comparison of the proposed method and bandwidth utilization efficiency of MDOP showed that the proposed method reduced the network traffic in excess of the control target value by 35% as compared with the MDOP. Furthermore, the proposed method improved the data transmission ratio by the delay tolerance range. Consequently, the proposed method improved the bandwidth utilization efficiency by learning how to provide the bandwidth to the user equipment when MDOP cannot be used to appropriately balance a load.

The demand for mobile data communication is increasing due to diversification and the increase in the number of mobile devices accessing mobile networks. This demand is likely to increase further. In a mobile network, communication quality deteriorates due to the congestion of the cellular infrastructure because of the concentration of demand for mobile data communication. Therefore, improving the cellular infrastructure bandwidth utilization efficiency is crucial. To improve the cellular infrastructure bandwidth utilization efficiency, we previously proposed the mobile data offloading protocol. Although this method balances the load by focusing on the delay tolerance of contents in the uplink, accurately balancing the load is challenging. In this paper, we propose a mobile data offloading method using deep reinforcement learning for increasing offloading performance of the uplink. The proposed method can balance the load appropriately by learning what the bandwidth and transmission timing provide to the user equipment when the previous method does not work properly.

The proteins responsible for radiation sensitive disorders, NBS1, kinase ataxia-telangiectasia-(A-T)-mutated (ATM) and MRE11, interact through the C-terminus of NBS1 in response to the generation of DNA double-strand breaks (DSBs) and are all implicated in checkpoint regulation and DSB repair, such as homologous recombination (HR). We measured the ability of several NBS1 mutant clones and A-T cells to regulate HR repair using the DR-GFP or SCneo systems. ATM deficiency did not reduce the HR repair frequency of an induced DSB, and it was confirmed by findings that HR frequencies are only slightly affected by deletion of ATM-binding site at the extreme C-terminus of NBS1. In contrast, The HR-regulating ability is dramatically reduced by deletion of the MRE11-binding domain at the C-terminus of NBS1 and markedly inhibited by mutations in the FHA/BRCT domains at the N-terminus. This impaired capability in HR is consistent with a failure to observe MRE11 foci formation. Furthermore, normal HR using sister chromatid was completely inhibited by the absence of FHA/BRCT domains. These results suggested that the N- and C-terminal domains of NBS1 are the major regulatory domains for HR pathways, very likely through the recruitment and retention of the MRE11 nuclease to DSB sites in an ATM-independent fashion.

Template matching using the silhouette shapes of pedestrians as features is widely used as a method for detecting pedestrians in images taken from an in-vehicle camera. Because of the need to detect a variety of pedestrian shapes, the template matching involves scanning the entire image for a very large number of templates. A large number of computations are needed to utilize multiple templates, and so it is difficult to implement the processing at the video frame rate. Furthermore, because images of outdoor street scenes that are captured by an in-vehicle camera consist of problematic backgrounds, false detections occur easily in the background area. A method is therefore proposed to perform highly efficient, high-speed matching by removing the background region, as this region has a negative impact on the detection capabilities in template matching. The background removal is achieved by using difference calculations that use information about the motion of the observation measured by sensors. Furthermore, an active search is carried out on the images after removing the background to give an efficient search, and a broad reduction in the number of computations is achieved. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(10): 115–126, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20393

The effects of the repeated administration of milnacipran, a serotonin (5-HT)-noradrenaline reuptake inhibitor (SNRI), on the functional status of somatodendritic 5-HT1A receptors, and postsynaptic 5-HT1A receptors were explored using electrophysiological approaches in rats. In-vitro electrophysiological recordings in the dorsal raphe nucleus showed that 5-HT inhibited the firing of serotonergic neurones, and the selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635), reversed the inhibitory effect of 5-HT. The potency of 5-HT to inhibit the firing of serotonergic neurones was slightly attenuated after 3 days of treatment with milnacipran (30 mg/kg, p.o., twice daily), and significantly attenuated after 7 or 14 days treatment at the same dose. The tricyclic antidepressant, imipramine, did not significantly modify the inhibitory effect of 5-HT. After 7 days treatment at 30 mg/kg, p.o., once daily, milnacipran reduced the potency of 5-HT to inhibit the firing of serotonergic neurones, whereas the selective serotonin reuptake inhibitors, fluvoxamine and fluoxetine (60 and 30 mg/kg, p.o., once daily, respectively), did not modify it under these conditions. Treatment with milnacipran (30 mg/kg, p.o., twice daily) for 14 days did not change the inhibition of the CA1 field potential in rat hippocampal slices by 5-HT. These data suggest that somatodendritic 5-HT1A receptors, but not postsynaptic 5-HT1A receptors, rapidly desensitize in response to the repeated administration of milnacipran.

(1S,2R)-1-Phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (2b), which is a conformationally restricted analog of the antidepressant milnacipran [(±)-1], is a new class of potent NMDA (N-methyl-D-aspartic acid) receptor antagonists. A series of analogs of 2b modified at the 1′-position were designed and synthesized starting from (R)-epichlorohydrin via the key intermediate an optically active cyclopropanecarbaldehyde derivative 8 with a (1S,2R)-configuration. Among these analogs, (1S,2R)-1-phenyl-2-[(S)-1-aminobut-3-enyl]-N,N-diethylcyclopropanecarboxamide (2i) and (1S,2R)-1-phenyl-2-[(S)-1-aminobut-3-ynyl]-N,N-diethylcyclopropanecarboxamide (2j) were identified as more potent NMDA receptor antagonists than 2b. The subtype selectivity of 2i and 2j together with 2b was investigated to show that 2i inhibited the GluRe3/ζl and GluRe4/ζl subtypes four times more strongly than GluRe1/ζl and GluRe2/ζl subtypes. Compound 2i is the first GluRe3/ζl and GluRe4/ζl subtype-selective antagonist, while the selectivity is not so high.

High-energy resolution and good charge collection properties have been achieved with CdTe detectors in a new M–π–n design, where a thin iodine-doped n-CdTe epilayer is grown on the high resistivity p-type (π-type) CdTe crystal wafer at a low substrate temperature of 150°C to form the n-layer of the device. The improved spectroscopic performance is obtained due to the use of high-quality crystal wafer and the effective junction fabrication technique that resulted very low leakage currents. The low leakage current enabled us to apply high electric field on the detector, which results in complete charge collection, and the measured spectra show symmetric full-energy peaks with no peak tailing. Energy resolutions of 1.4, 1.7, and 4.2 keV FWHM were obtained at room temperature with a 2 mm×2 mm×0.5 mm detector at the 59.5, 122, and 662 keV gamma-peaks, respectively, without the use of any kinds of pulse correction electronics. Their room-temperature stability was also improved considerably by applying high bias voltages, while they were fully stable on a slight cooling. Performance of detectors at and below room temperatures and their stability issues will be presented.

p–i–n CdTe strip detectors were fabricated in a new and simple technique for their probable applications in astrophysics and medical imaging. The detector has an iodine-doped n-CdTe epitaxial layer followed by aluminum metallization on the Te-face of (1 1 1) oriented CdTe crystal, as an anode. The cathode consists of the p-type segmented regions formed on the crystal by the diffusion of dopant atoms from an alkaline metal compound through a patterned shadow mask using the excimer laser radiation. Afterward, the gold electrode is evaporated through the same shadow mask to make the strip cathodes. In a different way, we also studied the laser ablation process for the selective area etching by irradiating the laser through a mask. Details of these fabrication processes for making strip detectors and results on laser-assisted etching process will be presented.

Heteroepitaxial layers of CdTe were grown on (1 0 0) semi-insulating GaAs substrates at low temperatures (150–250°C) and at a low pressure of 27 Pa using the remote-plasma-assisted metalorganic chemical vapor deposition (RPA-MOCVD) method. Dimethylcadmium and diethyltelluride were used as the source materials. Hydrogen-plasma radicals produced in a remote source were employed to assist the decomposition of organic source and hence low-temperature growth was achieved. The grown epilayers were single crystalline with resistivity in the order of 105 Ω cm for the entire growth range and had smooth surfaces. n-type doping of the layers was then studied. Heavily iodine-doped CdTe layers with carrier concentration in the range of 1016–1018 cm−3 could be obtained at a substrate temperature of 150°C using n-butyliodine as a dopant source. These various results on growth, surface morphology and doping studies will be presented.

CdTe radiation detectors have been fabricated in a new M–π–n structure that provides very effective blocking for the leakage current and, as a result, excellent spectral responses are achieved. An iodine-doped n-CdTe layer was grown on the Te-faces of the (1 1 1)-oriented high-resistivity (∼10 9 Ω cm) ρ-type CdTe wafers at the low substrate temperature of 150°C. An aluminum electrode was evaporated on the n-CdTe side, while a gold electrode was evaporated on the other side. Low leakage current around 60 pA/mm 2 was typically attained for a 0.5 mm thick detector at room-temperature (25°C) for an applied reverse bias of 250 V. Improved charge collection efficiency and spectral responses for different radioisotopes in the energy range of a few tens of keV to several hundreds of keV were obtained due to the application of very large electric fields on the detectors. The performance of the detectors thus fabricated is presented.

An impurity diffusion technique using an excimer laser was studied for the p-type doping of CdTe. A thin layer of Na 2 Te was evaporated on the CdTe crystal, and laser irradiation decomposed the Na 2 Te and diffused Na atoms into the Cd site. The resistivity of the top layer of the crystal decreased to below 1 Ωcm and showed p-type conductivity. This technique is applied for fine-patterned p-type doping on the crystal by laser irradiation through a shadow mask. Furthermore, p-i-n CdTe diodes were fabricated for an X-ray imaging device by growing an iodine-doped n-CdTe layer on one side of the crystal and fine-patterned p-type doping on the other side. This device showed good diode properties with a well-saturated reverse bias current and good imaging properties.

CdTe is an attractive semiconductor material for applications in solid-state high-energy X-ray and γ-ray imaging systems because of its high absorption coefficient, large band gap, good mobility lifetime product of holes and stability at normal atmospheric conditions. We propose a new concept for fabricating an integrated CdTe with monolithic circuit configuration for two-dimensional imaging systems suitable for medical, research or industrial applications and operation at room temperature. A new doping technique has been recently developed that employs excimer laser radiation to diffuse impurity atoms into the semiconductor. Accordingly, heavily doped n- and p-type layers with resistivities less than 1 Ω cm can be formed on the high resistive CdTe crystals. We have further extended this technique for doping with spatial pattern. We will present the laser doping technique and various results thus obtained. Spatially patterned doping is demonstrated and we propose the use of these doping techniques for the fabrication of integrated CdTe two-dimensional imaging systems.

We report on the fabrication and performance of CdTe radiation detectors in a new p–i–n structure which helps to reduce the leakage current to a minimum level. Chlorine-doped single-crystal CdTe substrates having resistivity in the order of 109 Ω cm were used in this study. Iodine-doped n-type CdTe layers were grown homoepitaxially on one face of each crystals using the hydrogen plasma-radical-assisted metalorganic chemical vapor deposition technique at low substrate temperature of 150°C. Indium electrode was evaporated on the n-CdTe side while a gold electrode on the opposite side acted as a p-type contact. Detectors thus fabricated exhibited low leakage current (below 0.4 nA/mm2 at 250 V applied reverse bias for the best one) and good performance at room temperature. Spectral response of the detectors showed improved energy resolution for Am-241, Co-57, and Cs-137 radioisotopes. Detectors were further tested with X-ray photons of different intensities for their potential application in imaging systems and promising responses were obtained.

The authors have developed M-/spl pi/-n (metal high-resistivity p-type crystal, highly n-type epilayer) CdTe detectors in a new design that are suitable for X-ray and /spl gamma/-ray spectrometry in the range of a few tens to several hundred kilo-electron volts. Using high-resistivity single crystal CdTe substrates (resistivity /spl sim/10/sup 9/ /spl Omega//spl middot/cm), an iodine-doped n-CdTe layer was grown homoepitaxially on one face of each wafer at a low substrate temperature of 150/spl deg/C using the hydrogen plasma radical assisted metalorganic chemical vapor deposition technique. An indium electrode was deposited on the n-CdTe side as an ohmic contact by evaporation without heating the crystals, while a gold electrode was deposited on the opposite side for metallic contact. The leakage current was decreased to around 0.5 nA for a 2/spl times/2 mm/sup 2/ detector of thickness 1 mm at room-temperature (18/spl deg/C) and around 10 pA at -15/spl deg/C for an applied negative bias of 350 V. Low leakage currents in the detector enabled the authors to apply higher bias voltages resulting in better charge collection efficiency and improved spectral responses for different radioisotopes.

Novel 3-(ω-(cycloalkyl)-alkyl-1,8,8-trimethyl-3-azabicyclo[3.2.1]octanes that had no aromatic rings were synthesized. Binding studies showed that these compounds were potent sigma ligands. Due to their simple structures without extra functional groups, they are suitable tools with which to identify pharmacophores capable of binding strongly to sigma binding sites.

(+/-)-(Z)-2-(Aminomethyl)-1-phenylcyclopropane-N,N-diethylcarbo xamide (milnacipran, 1), a clinically useful antidepressant, and its derivatives were prepared by an improved method and were evaluated as NMDA receptor antagonists. Of these, milnacipran (1), its N-methyl and N,N-dimethyl derivatives, 7 and 8, respectively, and its homologue 12 at the aminomethyl moiety had binding affinity for the receptor in vitro (IC50: 1, 6.3 +/- 0.3 microM; 7, 13 +/- 2.1 microM; 8, 88 +/- 1.4 microM; 12, 10 +/- 1.2 microM). These also protected mice from NMDA-induced lethality. These compounds would be important as anovel prototype for designing potent NMDA-receptor antagonists because of their characteristic structure, which clearly differentiated them from known competitive and noncompetitive antagonists to the receptor.

A cDNA copy of the carboxymethylcellulase (CMCase 1) gene, CMC1 , of the yeast Cryptococcus flavus was expressed in Saccharomyces cerevisiae under the control of the glyceraldehyde-3-phosphate dehydrogenase gene ( GAP ) promoter derived from S. cerevisiae . In glucose medium, extracellular production of a large amount of CMCase 1 was achieved by S. cerevisiae cells transformed with YEp-plasmid carrying CMC1 . Two major proteins (36 kDa and 34 kDa) secreted in the medium both had CMCase activity and immuno-responsibility to anti-CMCase 1-antibody. From an analysis of amino acid sequences, it was found that the 36 kDa protein is a pro-CMCase 1 having an N-terminal residue, Ala, the 19th amino acid of the peptide deduced from the nucleotide sequence of CMC1 on the cDNA, and that the 34 kDa protein is a mature CMCase 1. Alteration of the cell morphology of S. cerevisiae was induced by transformation with YEp-plasmid carrying CMC1 .

Saccharomyces cerevisiae transformants which secrete high levels of cellulolytic enzymes, with chromosome-integrated multicopies of heterologous DNA sequences encoding the cellulolytic enzymes were constructed. An expression construct of β-glucosidase and carboxymethyl cellulase directed by the GAP promoter was integrated into the chromosomes of the haploid S. cerevisiae using the δ sequence-mediated integration system. Southern blot analysis of the chromosomes prepared from various integrants and separated by pulse-field gel electrophoresis demonstrated that the integration occurred mainly in a particular chromosome and the copy number of the integration was variable. The amount of enzymes secreted by the transformants correlated with the copy number of integration. For each enzyme, the highest activity was about 1.4-fold that produced by the transformant harboring the same expression cassette on a YEp-type plasmid. The δ-integrated exogenous DNA was mitotically stable in rich medium. A haploid double transformant which coexpresses and secretes β-glucosidase and carboxymethyl cellulase was further constructed by genetic crossing of the haploid transformant that produces a high level of the enzyme, followed by meiotic segregation of the resulting diploid strain. The haploid double transformant, but neither of the single transformant, could grow on a plate containing carboxymethyl cellulose as a sole carbon source. It is suggested that the δ-sequence-mediated integration system is a very useful means for the genetic engineering of yeast, especially when overproduction and secretion of multiple heterologous enzymes are desired.

(R)-1,2,3,4-Tetrahydro[1]benzothieno[2,3-c]pyridine derivatives (60-114) were synthesized. The (R)-isomers have affinity for the 5-HT 1A receptor while the (S)-isomers have no such ability. The affinity of the (R)-isomers was discussed on the basis of structure-activity relationships between the affinity and hydrophobicity of the (R)-isomers. Compounds 71 and 107, which are representative derivative compounds, have anticonflict activity and lessening of memory impairment. In particular, compound 107 cannot bind to receptors other than the 5-HT 1A receptor, demonstrating that it is a unique compound with a different mechanism of action from that of conventional anxiolytics

(+/-)-(Z)-2-(Aminomethyl)-1-phenylcyclopropane-N,N-diethylcarbo xamide (milnacipran, 1), a clinically useful antidepressant, and its derivatives were prepared by an improved method and were evaluated as NMDA receptor antagonists. Of these, milnacipran (1), its N-methyl and N,N-dimethyl derivatives, 7 and 8, respectively, and its homologue 12 at the aminomethyl moiety had binding affinity for the receptor in vitro (IC50: 1, 6.3 +/- 0.3 microM; 7, 13 +/- 2.1 microM; 8, 88 +/- 1.4 microM; 12, 10 +/- 1.2 microM). These also protected mice from NMDA-induced lethality. These compounds would be important as anovel prototype for designing potent NMDA-receptor antagonists because of their characteristic structure, which clearly differentiated them from known competitive and noncompetitive antagonists to the receptor.

We report the cloning and expression of a novel 5-HT receptor gene from human genomic DNA. This clone, HGCR1, contains an apparently intronless open reading frame of 390 amino acids with the seven hydrophobic regions, typical of G-protein coupled receptors. The deduced amino acid sequence of HGCR1 is 39%, 55% and 87% identical to that for the human 5-HT1A, the human 5-HT1D and the rat 5-HT1B receptor, respectively. [3H]5-HT binding to transfected COS-7 cell membranes yields a pharmacological profile similar to that of 5-HT1B receptor. Thus these findings indicate the presence of 5-HT1B-type receptor in the human.

This paper presents a method for active background subtraction in sequential images taken from a moving camera on the vehicle. The active subtraction is carried out by estimating camera motion using a gyrosensor. Applying the proposed method to contour matching, we present a fast and robust system for detecting moving pedestrians.

This paper presents a method of frame subtraction for eliminating a background of sequential images taken from moving camera. The subtraction is carried out by finding the difference among frame images using a gyrosensor. Applying the proposed method for contour matching, we present a fast and less erroneous pedestrian detection system.

DNA double strand break (DSB) causes many cytotoxic effects such as cellular lethality, somatic mutation, and carcinogenesis. Fidelity of DSB repair is a important factor that determines the quality of genomic stability. It is known that the most of DSBs are properly repaired on the earth, however, little is known whether those are rejoined at the same fidelity even under the space environment. One of the DSB repair pathway, homologous recombination (HR), allows the cells to repair their DSBs with error free. Therefore, the efficiency of HR is a good index to assess the fidelity of DSB repair. In order to clarify the effect of gravity stress on HR pathway, we established a cell line that can detect a site-specific DNA repair via HR. The cells carrying a reporter construct for HR were incubated under hypergravity condition after induction of site specific DSB. Our preliminary results suggest that the gravity stress may affect the HR efficiency.

Rationale. The prefrontal cortex is implicated in the pathophysiology of depression, and hypoactivity of this brain area has been found in depressed patients. Reduced function of the serotonergic and noradrenergic systems is another feature of depression. Objectives. The present study was aimed at characterizing neurochemically and behaviorally the serotonin and noradrenaline reuptake inhibitor (SNRI), milnacipran, in the prefrontal cortex in comparison with tricyclic antidepressants and selective serotonin reuptake inhibitors. Methods. Sodium-dependent monoamine uptake measurement, radioligand binding assays, microdialysis procedure, forced swimming test and conditioned fear stress test were carried out in rats. Results. Milnacipran selectively inhibited sodium-dependent [3H]serotonin (5-hydroxytryptamine, 5-HT) and [3H]noradrenaline (NA) uptake into the synaptosomes from rat cerebral cortex (IC50=28.0 and 29.6 nM, respectively) without any affinities for various neuroreceptors. In the medial prefrontal cortex, milnacipran (10 and 30 mg/kg, PO) caused a dose-related increase in the extracellular levels of 5-HT and NA with similar potency, whereas imipramine (10 and 30 mg/kg, PO) caused a dominant increase in the output of NA compared to 5-HT. Milnacipran (30 and 60 mg/kg, PO) significantly reduced the duration of both the immobility time in the forced swimming test and the freezing time in the conditioned fear stress test in rats, which are animal behavioral models for depression and anxiety, respectively. Imipramine and maprotiline were active in the former test, but not in the latter. Fluoxetine and fluvoxamine on the other hand were more active in the conditioned fear test. Conclusion. These findings show that milnacipran acts as a SNRI in vitro and in vivo and may be useful for the treatment of anxiety as well as depression.

CdTe and related compound semiconductors are useful for high energy flux detection at room temperature. We propose a new fabrication technique for CdTe detectors in p-i-n design that is suitable for hard x-ray and gamma-ray spectroscopy. Using a high resistivity single crystal CdTe substrate, an iodine doped n-CdTe layer is grown homoepitaxially on one face of the crystal using the hydrogen plasma-radicals- assisted metalorganic chemical vapor deposition method working at a low substrate temperature of 150 degrees C. An indium electrode is evaporated on the n-CdTe side for an ohmic contact, while a gold electrode is placed on the opposite side which acts as a p-type contact. The p-i-n detector thus fabricated exhibited low leakage current at room temperature operation, below 0.5 nA at an applied bias of 350 V for a 2 X 2 mm2 detector of thickness of 1 mm. Leakage current further decreased to 16 pA at 350 V while cooling the detector down to -15 degrees C. Spectral responses of the detector showed improved energy resolution for different radioisotopes of energies in the range form few tens of keV to several hundred keV and stable operation when operated at high applied biases or slightly cooling the detector. Performance of the different detectors thus fabricated will be presented.

(R)-1,2,3,4-Tetrahydro[1]benzothieno[2,3-c]pyridine derivatives (60-114) were synthesized. The (R)-isomers have affinity for the 5-HT 1A receptor while the (S)-isomers have no such ability. The affinity of the (R)-isomers was discussed on the basis of structure-activity relationships between the affinity and hydrophobicity of the (R)-isomers. Compounds 71 and 107, which are representative derivative compounds, have anticonflict activity and lessening of memory impairment. In particular, compound 107 cannot bind to receptors other than the 5-HT 1A receptor, demonstrating that it is a unique compound with a different mechanism of action from that of conventional anxiolytics

A cDNA copy for carboxymethylcellulase (CMCase 1) of the yeast Cryptococcus flavus was cloned by screening an expression cDNA library with anti-CMCase 1 antibody. The sequence of the cDNA had an open reading frame of 1023 bp that encoded a preprotein of 341 amino acids with a molecular weight of 35,698. The putative precursor begins with a hydrophobic segment that possibly acts as a signal sequence for secretion, which is followed by a presumed prosequence and a sequence consistent with the N-terminal amino acid sequence of secreted CMCase 1. No potential N-glycosylation site was found in the sequence of putative pro-CMCase 1. Comparison of the deduced protein sequence shows that the C. flavus CMCase 1 is partially homologous to the Trichoderma reesei endoglucanase EGIII. Alignment of the cDNA copy and the chromosomal DNA showed seven putative introns of 45 to 134 bp. When introduced into E. coli, the cDNA directed the synthesis of CMCase 1 as seen by CMCase activity and Western blotting using anti-CMCase 1 antibody.

Effects of oxiracetam on cholinergic neurons were investigated by biochemical methods. 1) Oxiracetam did not inhibit 3H-QNB binding in the cerebral cortex and hippocampus. 2) In the 3H-QNB binding study, oxiracetam did not change the inhibition-concentration curve for the muscarinic agonist carbachol and had no effect on GppNHp-induced inhibition of oxotremorine binding. 3) Oxiracetam (10-100 microM) enhanced K(+)-induced ACh release from slices of rat hippocampus. 4) In the in vitro perfusion studies, oxiracetam (10-100 microM), but not aniracetam and piracetam, enhanced choline-acetyltransferase (ChAT) activity in the hippocampal slices. 5) Repeated administration of oxiracetam (100 or 500 mg/kg, p.o., once daily) to old rats significantly enhanced ChAT activities in the cerebral cortex, hippocampus and striatum, while it did not influence the Bmax and Kd for 3H-QNB binding in the hippocampus. 6) Oxiracetam did not affect the acetylcholinesterase activity in mouse brain homogenate. These results suggest that oxiracetam enhances precholinergic functions.

1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal neurones in the hippocampus of the Mongolian gerbil brain occurred 7 days after transient bilateral occlusion of the common carotid arteries. 2. A single injection of HA1077 (1 and 3 mg kg-1, i.p.) 5 min after the occlusion led to a dose-dependent protection of the CA1 neurones. Repeated administrations of HA1077 (1 and 3 mg kg-1, i.p., twice daily for 7 days post-ischaemia) revealed an increase in the number of normal cells, compared to findings with a single administration. 3. In contrast to HA1077, nicardipine (0.3 and 1 mg kg-1, i.p.) did not reduce neuronal degeneration. 4. HA1077 did not interact with the ion channel within which MK-801 binds, as determined by receptor binding. 5. The calcium ionophore, A23187, caused a tonic contraction in canine cerebral arterial strips. HA1077, but not nicardipine, relaxed the A23187-induced contraction, concentration-dependently. 6. These results suggest that blockade of the intracellular actions of calcium may provide protection against ischaemic damage in the brain.