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We presented a control strategy for tablet manufacturing processes based on continuous direct compression. The work was conducted by the experts of pharmaceutical companies, machine suppliers, academia, and regulatory authority in Japan. Among different items in the process, the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing. The control and management of the Loss in Weight (LIW) feeder were deemed the most important, and the Residence Time Distribution (RTD) model were regarded effective for setting the control range and for controlling of the LIW feeder. Based on these ideas, the concept of process control using RTD was summarized. The presented contents can serve as a solid fundament for adopting a new control method of continuous direct compression processes in and beyond the Japanese market.

BACKGROUND The effectiveness of sofosbuvir/ribavirin (SOF/RBV) combination therapy, which is one of the 1st-choice therapeutic options for patients with hepatitis C virus (HCV) genotype 2 (HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is unknown. CASE SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2a who could not achieve a sustained virological response (SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with Vogt-Koyanagi-Harada (VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment (SVR12). Regarding adverse events (AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid arthralgia. CONCLUSION SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.

As a result of the research activities of the Japan Agency for Medical Research and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology transfer, process control, and quality control used in the current commercial batch manufacturing would be effective also in continuous manufacturing, while there are differences in the process development using continuous manufacturing and batch manufacturing. This document introduces an example of the way of thinking for establishing a control strategy for continuous manufacturing processes.

Because workers flexibly manipulate various types of products, multi-process handling tasks have been introduced in many factories for high-mix low-volume production. When the high-mix low-volume production is enhanced in a factory, operational errors of workers increase during the manufacturing process of similar products, and the productivity of the production line will decrease owing to the various operation times applied depending on the skill level of the workers. In this study, we develop information system to promote the productivity of the line and to reduce the operational errors of workers in multi-process handling tasks. The developed system consists of two subsystems: a work instruction system and an operation verification system. In the former subsystem, a digital manual is used for operational instructions. In the latter sub-system, images of the semi-finished products are evaluate to judge the completion of the products and to avoid errors. We describe the characteristics of the developed system and evaluate the performance of the system through an assembly experiment.

Continuous manufacturing plays a key role in enabling the modernization of pharmaceutical manufacturing. The fate of this emerging technology will rely, in large part, on the regulatory implementation of this novel technology. This paper, which is based on the 2nd International Symposium on the Continuous Manufacturing of Pharmaceuticals, describes not only the advances that have taken place since the first International Symposium on Continuous Manufacturing of Pharmaceuticals in 2014, but the regulatory landscape that exists today. Key regulatory concepts including quality risk management, batch definition, control strategy, process monitoring and control, real-time release testing, data processing and management, and process validation/verification are outlined. Support from regulatory agencies, particularly in the form of the harmonization of regulatory expectations, will be crucial to the successful implementation of continuous manufacturing. Collaborative efforts, among academia, industry, and regulatory agencies, are the optimal solution for ensuring a solid future for this promising manufacturing technology.

Block copolymer micelles are nanoparticles formed from block copolymers that comprise a hydrophilic polymer such as poly(ethylene glycol) and a poorly soluble polymer such as poly(amino acids). The design of block copolymer micelles is intended to regulate the in vivo pharmacokinetics, stability, and distribution profiles of an entrapped or block copolymer-linked active substance. Several block copolymer micelle products are currently undergoing clinical development; however, a major challenge in the development and evaluation of such products is identification of the physicochemical properties that affect the properties of the drug product in vivo. Here we review the overall in vitro and in vivo characteristics of block copolymer micelle products with a focus on the products currently under clinical investigation. We present examples of methods suitable for the evaluation of the physicochemical properties, non-clinical pharmacokinetics, and safety of block copolymer micelle products.

We have proposed a human detection system using UHF band TV wave. In recent years, a smart meter using 920 MHz band radio wave has attracted attention for developing HEMS. In this study, in order to detect human motion around a house, we proposed housing-site human detection system using the 920 MHz band radio. We investigated the characteristics of radio waves, confirmed the variation of RSSI (Received Signal Strength Indicator) and the appropriate installation location of the receiver. Furthermore, from the difference in RSSI fluctuation of the radio wave, we verified whether human detection is possible based on actual measurements. From the measurement results, we confirmed that the RSSI of 920 MHz band was fluctuated by the movement of human in the housing-site, and also confirmed that there were differences in the RSSI variation characteristics if the location of human movement and the place of receiver installation was different.

The timely breakdown of the extracellular matrix by proteolytic enzymes is essential for development, morphogenesis and cell proliferation in plant and animal cells. Sporangin of the unicellular green alga Chlamydomonas reinhardtii that mediates breakdown of the sporangial cell wall to liberate the daughter cells after cell division is characterized as a subtilase-like serine protease. The sporangin gene is specifically transcribed during S/M phase in a synchronized vegetative cell cycle. In immunoblot analyses using a polyclonal antibody raised against the sporangin polypeptide, the enzyme is synthesized after mitotic cell division and accumulated in the daughter cells before hatching. Immunofluorescence analyses showed that sporangin is localized to the flagella of the daughter cells within the sporangial cell wall, and released into the culture medium. The data suggest that sporangin is released from flagella concurrently with the digestion of sporangial cell wall, and then the daughter cells are hatched from the sporangia in the Chlamydomonas vegetative cell cycle.

When mating type plus and minus gametes of Chlamydomonas are mixed, they agglutinate with each other via their flagella, fuse, then initiate the zygote formation program which includes synthesis of the zygote cell wall, fusion of nuclei and chloroplasts, and the digestion of chloroplast DNA from the minus parent. The mRNAs from gamete and zygote cells was isolated and hybridized to cDNA-macroarray filters both to identify new genes expressed during the mating reaction and the early zygote formation process and to analyze the gene expression programs that underlie these sexual processes. Twenty-one novel genes were identified in this screen, designated as EZY (early zygote expressed) genes. The EZY genes included genes encoding proteins whose function is unknown, and genes encoding proteins that appear to be involved in processes such as cell wall synthesis, gene expression, intracellular trafficking or secretion, and vesicular transport in zygotic cells. All of the EZY genes were strongly induced within 1 h during the mating process, including early zygote formation. The transcriptional characteristics of EZY genes were analyzed by using the fusion-defective mutant fus mt(+). Among the EZY genes, 12 genes were not activated in fusion-defective conditions, suggesting that cell fusion is required for their expression. The remaining nine that were transcribed in fusion-defective fus matings were also inducible by cell wall removal in either vegetative or gametic cells, indicating that these genes were induced only indirectly by the cAMP signaling pathway initiated by flagellar agglutination as a result of mating-induced cell wall loss.

This paper presents the stable isotope data of the snow pack and summer precipitation collected at the July 1 Glacier, Qilian Mountains in northwest China and analyses their relationships with meteorological factors. On an event scale, there is no temperature effect on the δ 18O values in the summer precipitation, whereas the amount effect is shown to be clear. By tracing the moisture transport history and comparing the precipitation with its isotopic composition, it is shown that this amount effect not only reflects the change in moisture trajectory, which is related to the monsoon activities, but is also associated with the cooling degree of vapor in the cloud, the evaporation of falling raindrops and the isotopic exchange between the falling drops and the atmospheric vapor. As very little precipitation occurs in winter, the snow pack profile mainly represents the precipitation in the other three seasons. There are low precipitation δ 18O ratios in summer and high ratios in spring and autumn. The Meteoric Water Line (MLW) for the summer precipitation is δD = 7.6 δ 18O + 13.3, which is similar to that at Delingha, located in the south rim of the Qilian Mountains. The MWL for the snow pack is δD = 10.4 δ 18O + 41.4, showing a large slope and intercept. The deuterium excess (d) of the snow pack is positively correlated with δ 18O, indicating that both d and δ 18O decrease from spring to summer and increase from early autumn to early spring. This then results in the high slope and intercept of the MWL. Seasonal fluctuations of d in the snow pack indicate the change of moisture source and trajectory. During spring and autumn, the moisture originates from continental recycling or rapid evaporation over relatively warm water bodies like Black, Caspian and Aral Seas when the dry westerly air masses pass over them, hence very high d values in precipitation are formed. During summer, the monsoon is responsible for the low d values. This indicates that the monsoon can reach the western part of the Qilian Mountains.

Spinocerebellar ataxia type 6 (SCA6) is caused by polyglutamine expansion in P/Q-type Ca2+ channels (Ca(v)2.1) and is characterized by predominant degeneration of cerebellar Purkinje cells. To characterize the Ca(v)2.1 channel with an SCA6 mutation in cerebellar Purkinje cells, we have generated knock-in mouse models that express human Ca(v)2.1 with 28 polyglutamine repeats (disease range) and with 13 polyglutamine repeats (normal range). Patch-clamp recordings of the Purkinje cells from homozygous control or SCA6 knock-in mice revealed a non-inactivating current that is highly sensitive to a spider toxin omega-Agatoxin IVA, indicating that the human Ca(v)2.1 expressed in Purkinje cells exhibits typical P-type properties in contrast to the previous data showing Q-type properties, when it was expressed in cultured cell lines. Furthermore, the voltage dependence of activation and inactivation and current density were not different between SCA6 and control, though these properties were altered in previous reports using non-neuronal cells as expression systems. Therefore, our results do not support the notion that the alteration of the channel properties may underlie the pathogenic mechanism of SCA6.

Though solar radiation is important for glacier mass-balance simulation, solar radiation data are not always available. As a result of analyzing meteorological data measured in the Himalaya and the Tibetan Plateau, a favorable correlation between precipitation and atmospheric transmissivity of solar radiation is found in terms of monthly values. Monthly mean solar radiation is derived from the relationship between atmospheric transmissivity of solar radiation and precipitation with input of monthly precipitation, latitude, skyline and time. The differences between estimated and observed monthly mean solar radiation are −2 in most cases. However, the differences at some sites are significantly large. The error in the estimated solar radiation during the monsoon season can be large when the monthly mean precipitation rate is about 5 mm d−1. Though the error in the estimated solar radiation during the non-monsoon season is generally small due to low precipitation in the Himalaya and the Tibetan Plateau during this season, it can exceed 100 W m−2.

Porous particles of oxides of transitional metals, such as copper, nickel, cobalt, iron, manganese, and chromium, were prepared in single and binary mixtures by the freeze-drying process to serve as combustion catalysts. Aqueous metal sulfate solutions of the above metals were utilized as raw material for freeze-drying. Spherical drops of the solutions were instantly frozen in a cooled bath. The frozen particles were dried in a vacuum chamber. These were then calcined into particles of single and double oxides, as well as oxide mixtures. The open porosity within the freeze-dried particles induced by sublimation of ice crystals was retained during calcination and the subsequent firing. Methane/air was combusted in an adiabatic tubular reactor in the presence of the porous oxide particles to determine the particles' catalytic activity. The feed gas equivalence ratio and residence time were kept constant while methane conversions were measured as a function of gas temperature. The activity of the catalysts was assessed based on the temperature during the surface-kinetics-controlled regime. Among the catalysts examined, the strongest were binary oxides of cobalt and nickel.

To investigate the functional role of Ca(v)2.3 channel in glucose homeostasis, we performed in vivo glucose tolerance and insulin tolerance tests together with stress-induced glucose release tests using mice deficient in Ca(v)2.3 channel (Ca(v)2.3-/-). The Ca(v)2.3-/- mice were significantly heavier than wild-type mice. In glucose tolerance and insulin tolerance tests, Ca(v)2.3-/- mice showed a significantly higher blood glucose level compared to wild-type mice. However, stress-induced blood glucose changes in Ca(v)2.3-/- mice were similar to those in wild-type mice. These results suggest that Ca(v)2.3 channel plays a role in glucose homeostasis by reducing insulin sensitivity and that Ca(v)2.3-/- mice exhibit symptoms resembling non-insulin-dependent diabetes mellitus.

A new technique for preparing magnesia ceramics of high porosity and high temperature resistance has been developed. Spray freeze drying of magnesium sulfate aqueous solution produced fine salt particles having open pores due to sublimation of ice crystals. The particles were calcined to porous magnesium oxide and formed a green body. Highly porous magnesia was produced by firing the green body. The porous magnesia exhibited a bimodal pore size distribution of macro-pores of micron order and meso-pores smaller than 100 nm. Porosity was 87–90%. After addition of an aluminum additive with an amount 3–5 mol%, the magnesia exhibited high heat resistance; surface area was greater than 20 m 2 g −1 after 20 h exposure in a 1573 K oven. Thus, the porous magnesia is expected to be very suitable for combustion catalyst support used in a high temperature environment.

The importance of voltage-dependent Ca2+ channels (VDCCs) in pain transmission has been noticed gradually, as several VDCC blockers have been shown to be effective in inhibiting this process. In particular, the N-type VDCC has attracted attention, because inhibitors of this channel are effective in various aspects of pain-related phenomena. To understand the genuine contribution of the N-type VDCC to the pain transmission system, we generated mice deficient in this channel by gene targeting. We report here that mice lacking N-type VDCCs show suppressed responses to a painful stimulus that induces inflammation and show markedly reduced symptoms of neuropathic pain, which is caused by nerve injury and is known to be difficult to treat by currently available therapeutic methods. This finding clearly demonstrates that the N-type VDCC is essential for development of neuropathic pain and, therefore, controlling the activity of this channel can be of great importance for the management of neuropathic pain.

BUF/Mna rats spontaneously develop thymomas and cause muscle weakness of hind legs at an advanced age. This rat strain has been recognized as a suitable animal model for human myasthenia gravis or related myopathies. To characterize the structural changes of neuromuscular junctions (NMJs) in BUF/Mna rats, subneural apparatuses (SNAs) of extensor digitorum longus muscles of young-adult (4-month-old) and aged (22- to 25-month-old) male rats were examined using scanning and transmission electron microscopy. The SNAs of NMJs in young rats consist of complex labyrinthine gutters with numerous slit-like junctional folds. SNAs in aged BUF/Mna rats, however, are characterized by: (1) a group of cup-like depressions with very wide slit-like junctional folds in relatively large muscle fibers (the major type), (2) the presence of slit-like folds on the flat sarcoplasm outside the cup-like depressions or on the protruded sarcoplasm, and (3) winding gutters or a small number of round depressions with poorly developed synaptic folds in small and medium-sized muscle fibers (the minor type). Since similar structural changes have been reported in dystrophic mice or normally aged rats, it is suggested that both the slowly progressing muscle atrophy and age-dependent turnover of muscle fibers may occur in the aged BUF/Mna rats.

In rats splenic natural killer (NK) cell activity was found to be significantly higher following chronic uncontrollable electrical stimulation of the lateral hypothalamus in fully conscious rats, compared to sham-operated rats. In a pre-test study, all rats had demonstrated that the electrode site had self-stimulating properties, which supports the possibility that the experience of reward may be implicated in NK cell activity augmentation.

We present population data on percentage body fat (%BF) by bioelectrical impedance analysis (BIA) in 12,287 men and 6657 women aged 30-69 y. In addition, we examined relationships among BMI, %BF and serum lipids (total-cholesterol (TC), HDL-cholesterol (HDLC), TC/HDLC ratio, LDL-cholesterol (LDLC) and triglycerides (TG)) in order to determine whether body mass index (BMI, kg/m2) or %BF by BIA better reflected lipid metabolism. Women had larger %BF than men in all age groups. On the other hand, women aged < 60 y had smaller BMI than corresponding men. Regardless of age, BMI was obviously correlated with %BF (r = 0.743-0.924). As previously reported, high BMI and high %BF were strongly associated with high serum TC/HDLC ratio and TG, and low serum HDLC rather than high serum TC and LDLC. Compared with BMI, %BF by BIA was better correlated with the serum indices except for serum HDLC. These results were found in both sexes, and there was a trend in which younger subjects had stronger correlations among BMI, %BF and serum lipids. Consequently, %BF by BIA (an index of body composition) better reflects serum lipid profile than BMI.

Alcohol intake per Japanese adult has been increasing year by year. To show biological effects of drinking, the dose-response relationships between alcohol use and serum indices were analyzed in 5919 Japanese men aged 40-59 years. The subjects were classified into nine groups: a nondrinking (ND, n = 1827) group and eight drinking (1D-8D) groups, by self-reported drinking habit. The 1D (the lightest drinking, n = 699), 5D (n = 942), and 8D (the heaviest drinking, n = 46) groups consumed alcohol less than 30 g per week, 25-30 g alcohol per day, and 100 g alcohol per day or more, respectively. Ten serum indices, total cholesterol, HDL cholesterol, triglyceride, total/HDL cholesterol ratio, LDL cholesterol, gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, glucose, and uric acid, were used. The dose-response analysis was statistically controlled for age, body mass index, smoking, and habitual exercise, and showed that drinking, even a small amount of alcohol, always had both beneficial and adverse effects on humans. However, alcohol less than 30 g per day may be tolerable for middle-aged Japanese men, because it improved serum lipids profile but did not induce apparent liver cell damage, hyperglycemia, or hyperuricemia.

Laboratory strains of Chlamydomonas reinhardtii, which are descendants of a 1945 isolate by G.M. Smith (Harris 1989), were divided into two groups depending upon whether the vegetative cells require light to differentiate into gametes under ammonium ion-starved conditions. Light-dependent (LD) strains were unable to become gametes in the dark, while light-independent (LI) strains could do so. All the wild-type strains isolated recently from the field showed light-dependency, suggesting that the LDphenotype is the wild-type. The LD-cells failed to acquire flagellar agglutinability, to accumulate cell body agglutinins, or to form mating structures in the dark, but did so rapidly after transfer to light. Moreover, the lightinduced LD-gametes, but not the Li-gametes, lost their mating ability, cell body agglutinins, and mating structures after transfer to darkness, indicating that the LD-cells require light not only for gametic differentiation but also for maintenance of gametic activity.

The role of neurons on expression of myelin-associated glycoprotein (MAG) in oligodendrocytes and oligodendroglial differentiation was examined. Primary cultures of oligodendrocytes prepared from neonatal mouse brains were co-cultured with neuronal cells derived from embryonal carcinoma P19 cells. The levels of MAG mRNAs following this co-culture were determined by reverse transcription (RT)-PCR. In oligodendrocytes co-cultured in direct contact with P19-derived neurons, the levels of MAG mRNAs, particularly that of the L-type isoform, were markedly higher than those in cultures without any neuronal cells. On the other hand, when the P19-derived neurons were present, but not in direct contact, no significant induction of MAG expression was found, though oligodendrocytes appeared to mature morphologically. The L-MAG expression was also stimulated when just the neuronal cell membrane fraction was added, which implies that there might be some effecter(s) in the cell membrane which are possibly exerting a signal transduction for myelin formation. These results suggest that morphological differentiation and functional maturation of oligodendrocytes are due to independent factors. The former is caused by some humoral factor(s) liberated from neuronal cells, while the latter resulted from cellular contact with neuronal cells.

Using an Alzet osmotic minipump, we examined the effect of continuous infusion of O‐conotoxin, a N‐type voltage‐sensitive calcium channel blocker, into the third cerebral ventricle above the suprachiasmatic nucleus (SCN) of the hypothalamus on the circadian drinking rhythm of rats maintained under a 12‐h light and 12‐h dark cycle and constant darkness. O‐Conotoxin (10‐6 mol/h) infusion disrupted the rhythm in both conditions. In contrast, infusions of nifedipine (104 mol/h), a dihydropyridine sensitive L‐type calcium channel blocker, did not eliminate the rhythm. These findings suggest that N‐type voltage‐sensitive calcium channels are involved in the mechanism of generation of the circadian rhythm driven by the circadian oscillator in the SCN.

The study was made on the adsorption of oxygen and nitrogen on natural zeolite (Itaya zeolite) products calcined at 500-700°C. The adsorption measurement was carried out at 5-25°C and under the pressure of 0-5atm.Natural zeolite calcined at 500°C adsorbed more nitrogen than oxygen. Oxygen enriched air (oxygen about 53 volume %) was obtained when natural zeolite was used in the PSA (pressure swing adsorption) process. Natural zeolite is useful to obtain oxygen less than 50 volume % in product gas. Natural zeolite needs to be improved for the supply of oxygen more than 50 volume % in product gas.

ELSEVIER, Shimizu-Okabe, C; Matsuda, Y; Koito, H; Yoshida, S, NEUROSCIENCE LETTERS, 331(3), 203-205, 2001. author, Myelin associated glycoprotein (MAG) has growth promoting effect on mouse cerebellar neurons. In the present study, we examined which isoform of MAG has the effect. cDNA for L-MAG and S-MAG was stably transfected into BALB/c 3T3 cells, on which cerebellar neurons were cultured. The neurons were stained with antibody against microtubule-associated protein-2 (MAP-2). Neurites of the neurons cultured on cells expressing L-MAG extended significantly further than those cultured on cells expressing S-MAG or on control cells. Therefore, intracellular domain of MAG may have the potential to affect MAG-neurite interaction.

Action of habenular efferents on neurons of the ventral tegmental area (VTA) was studied with a slice preparation that preserved the habenula (Hb) and the VTA together with the interconnecting fiber bundle, the fasciculus retroflexus (FR). In the VTA, two types of neurons, presumably corresponding to the dopaminergic and nondopaminergic neurons, were discerned on the basis of the electrophysiological properties. Of 52 VTA neurons sampled, 42 [with the mean resting membrane potential of 56 ± 7 mV (mean ± SD)] responded with excitatory postsynaptic potentials (EPSPs) to FR stimulation. The EPSPs were monosynaptic in nature and rather weak in effect in the sense that they rarely triggered spikes. No significant differences in latency, duration and time to peak were noted between the EPSPs generated in different types of neurons. FR stimulation evoked inhibitory postsynaptic potentials (IPSPs) in only six neurons, their resting membrane potential being 51 ± 4 mV. The IPSPs frequently showed a fluctuation in latency. FR stimulation also produced antidromic responses in a few VTA neurons, but their long latencies precluded the possibility that the VTA-Hb projections contributed to the FR-evoked orthodromic responses in the VTA. EPSPs evoked by FR stimulation could be suppressed by kynurenic acid (1 mM). The findings indicate that the efferents of the Hb primarily have an excitatory effect on VTA neurons of any type and that the excitation may be mediated by amino acid receptors.

The activities of phytase and alkaline phosphatase in the intestine gradually increased in parallel during development of rats, but the 70K and 90K subunits were expressed differentially; only the 70K subunit was detected at birth, whereas the 90K subunit appeared at the weaning period (3 weeks after birth). When rats were forced to wean at 18 days old and fed laboratory chow, the enzyme activity increased markedly and the 90K subunit appeared within 1 day. These findings suggest that weaning is involved in the change in the subunit composition. Increases in the enzyme activity and amount of the 90K subunit were significantly delayed by feeding weanling animals on casein diet, but induced significantly by feeding them on casein diet supplemented with phytate. Thus induction of the 90K subunit seems to be accelerated by intake of phytic acid in the diet. The Km value of the enzyme from suckling rats for phytate was 5.25 mM, while that of adult rats was 0.213 mM. In contrast, the Km value for p-nitrophenyl phosphate (PNPP) was constant during development. The phytase activity of suckling rats did not show a distinct pH-dependence. These findings suggest that the 90K subunit may play some important roles in expressing an efficient phytase activity.

Two conditional mutants of Chlamydomonas reinhardtii, dif-1 and dif-2, affecting gametic differentiation under conditions of nitrogen (N)-starvation, have been isolated. These mutant cell remain "vegetative" at the restrictive temperature (35 degrees C) in -N medium, as defined by assays of cell body-agglutinin and cell wall lytic enzyme activities in the soluble fractions of cell homogenates. Moreover, the mutants fail to form mating structures at the restrictive temperature, but do so at the permissive temperature (25 degrees C). Temperature-shift experiments show that mutant cells which have differentiated into gametes at 25 degrees C dedifferentiate into "vegetative" cells under N-starvation conditions after transfer to 35 degrees C, but differentiate again into gametes at 25 degrees C. Genetic analyses indicate that the dif-1 and dif-2 genes are recessive and unlinked to each other or to the mating-type locus; the dif-1 phenotype cosegregates with a conditional flagellaless phenotype expressed in both +N and -N medium at the restrictive temperature.

The specific surface area of several kinds of zeolite, ie., Moleculite 515, Moleculite 4P-30S, Zeoharb 501, Zeoharb 502 and Itaya zeolite was estimated on the basis of the PSA (Pressure Swing Adsorption) method. PSA is accompanied by the evolution of heat and its adsorption in the zeolite bed with a corresponding recorder deflection.The results were compared with the data obtained by other adsorption methods utilizing nitrogen. This PSA method seems useful for estimation of specific surface area of zeolite as well as life estimation of zeolite adsorbent in a dynamic adsorption process.

わが国の代表的天然ゼオライトである板谷産ゼオライトによる陽イオン(Zn2+, pb2+, Ni2+, Hg2+, ca2+, mg2+, cr6+, NH4+ and H+)の吸着現象(イオン交換を含む)について研究した。15および25℃において,初濃度約100,75,50,25,10,5,2ppmの各陽イオン溶液100鵬Zに試料19を投入すると約24時間でほぼ吸着平衡に達する0吸着等温線は近似的にFreundlich型である。板谷ゼオライトのZn2+肝の吸着性能は,ノ1源子産ゼオライトOMS5Aおよび活性炭よりも良好であった。他の陽イオンについても同様なことが推定できる。したがって,板谷産ゼオライトは排水中などからの陽イオンの吸着除去剤として有望である。

Hybrid SiC f /SiC with 3-D woven preform consisting of orthogonal XYZ bundles using SiC fibers of Tyranno ZMI, Tyranno ZE and Hi-Nicalon Type S were manufactured by polymer-impregnation and pyrolysis(PIP) combined with chemical vapor infiltration(CVI) and glass seal techniques. In order to evaluate mechanical properties and durability of the 3-D woven hybrid SiC f /SiC, tensile tests and 4-point bending tests were carried out. Effects of time and temperature on mechanical properties were also investigated using exposed specimens at elevated temperatures of 1400°C and 1500°C and maximum 6000-hours. Hybrid SiC f /SiC with combined of Tyranno ZMI and Tyranno ZE showed an excellent high temperature durability.

Natural Itaya and Nakano zeolites were treated with hydrochloric acid for 1hr at 100°C. The original zeolites and the treated ones were characterized by X-ray diffraction, chemical analysis, thermo-gravimetric analysis and adsorption. The X-ray diffraction patterns of the zeolite treated with 1mol·dm-3 acid and those of the untreated zeolite were almost identical, but the ratio of SiO2 to Al2O3 was different. The zeolite treated with acid rapidly increased its inner adsorption volume. The monolayer capacity of nitrogen gas rapidly increased as the amount of cations in the zeolite decreased.The effect of hydrochloric acid treatment on gas separation properties of natural Itaya and Nakano zeolites was investigated. Hydrogen, oxygen, nitrogen, methane and carbon monoxide were completely separated on the acid treated Itaya zeolite column, but not on the natural Nakano or its acid treated zeolite column.

Itaya natural zeolite and its cation-treated zeolite were characterized by X-ray diffraction, thermo-gravimetric analysis, adsorption and chemical analysis. No change of X-ray diffraction pattern was found for Itaya zeolites treated with 1mol·dm-3 hydrochloric acid but a slight change of SiO2/Al2O3 ratio was found.The surface of Itaya zeolite seem to contain both meso- or macropores, but its heterogeneous surface became homogeneous with hydrochloric acid treatment, being predominantly composed of micropores. The monolayer adsorption capacity of zeolite for nitrogen gas decreased as the amount of cations in the Itaya zeolite increased. The cation (Na+, K+, NH+4, Ca2+) exchanged Itaya zeolite samples had less nitrogen adsorbing power than the hydrochloric acid-treated zeolite.The gas separation behaviour of Itaya zeolite was compared with that of the cation-treated zeolite. Separation of hydrogen, oxygen, nitrogen, methane and carbon monoxide from the surface of zeolites was investigated at 30-100°C by using Itaya zeolite and its cation-treated zeolite as column packings. Hydrogen, oxygen, nitrogen, carbon monoxide and methane were found to be separatable completely from the mixture gases by using Itaya zeolite, hydrochloric acid treated zeolite and its K+ exchange zeolites. A methane-oxygen mixture could not be separated by Na+, NH+4 and Ca2+ exchanged Itaya zeolites.

Molecular structure of the T-type Ca(2+) channel was first clarified by the cloning of Ca(V)3.1 (alpha(1G)) as an authentic component of the T-type channel. Since then, much progress has been made in understanding functions of the T-type Ca(2+) channels, because it has become possible to study structure-function relationship for the T-type channel using mutagenesis techniques and to examine abnormal phenotypes of T-type channel knock-out mice. Here we will review briefly the recent progress in studies on structure and function of T-type Ca(2+) channels.

Cells of Chlamydomonas reinhardtii differentiate into gametes under conditions of nitrogen (N) starvation, expressing the genes for the N-adaptation program and the gamete program. To investigate the regulatory networks of transcription among the N-starvation-inducible genes, we examined the gene expression in dif mutants, affecting gametic differentiation. In a conditional mutant, dif2, the cells remained ‘vegetative’ at the restrictive temperature, and the induction of 20 out of 21 genes related to the two programs was impaired. They were expressed soon after transfer of the cells to the permissive temperature, in parallel with the acquisition of mating ability. In an unconditional mutant, dif3, the cells could not differentiate into gametes at all, but the induction of only four genes (FUS1, NSG3, NSG6 and NSG7) related to the gamete program was impaired. The results suggest that Dif3 regulates putative N-starvation signal transduction pathways downstream of a master regulator, Dif2. We also examined a light-dependent laboratory strain that was unable to become gametes in the dark. The ‘pre-gametes’ placed in the dark, however, could induce normally all of the 21 genes, suggesting that light is required for the gametic differentiation at the translational and/or post-translational levels.