A 400 K-transistor CMOS sea-of-gates array with continuous track allocation

A 0.8- mu m CMOS sea-of-gates (SOG) array with first-level wiring channels perpendicular to transistor rows and 40 0K transistors is integrated on a 6*7-mm/sup 2/ chip. Implementation of a 64-bit multiplier shows 60-percent gate utilization and density of 1410 G/mm/sup 2/. The wiring length of the multiplier is 70 percent of that in a conventional SOG.<>     

Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast

Autophagy is a bulk protein degradation process that is induced by starvation. The control mechanism for induction of autophagy is not well understood. We found that Tor, a phosphatidylinositol kinase homologue, is involved in the control of autophagy in the yeast, Saccharomyces cerevisiae. When rapamycin, an inhibitor of Tor function, is added, autophagy is induced even in cells growing in nutrient-rich medium. A temperature-sensitive tor mutant also leads to induction of autophagy at a nonpermissive temperature. These results indicate that Tor negatively regulates the induction of autophagy. Tor is the first molecule that is identified as a pivotal player in the starvation-signaling pathway of autophagy. Furthermore, we found that a high concentration of cAMP is inhibitory for induction of autophagy. APG gene products are involved in autophagy induced by starvation. Autophagy was not induced in apg mutants in the presence of rapamycin, indicating that the site of action of Tor is upstream of those of Apg proteins. In nutrient-rich medium, Apg proteins are involved also in the transport of aminopeptidase I from the cytosol to the vacuole. Tor may act to switch Apg function between autophagy and transport of aminopeptidase I.     

Fluorescent estimation of H2O2-induced changes in cell viability and cellular nonprotein thiol level of dissociated rat thymocytes

Vector control and the detection (followed by treatment) of infected individual are the two methods currently available for the control of sleeping sickness. The basic reproduction rate of a compartmental model (Kermack and McKendrick) is used to analyze and compare the two strategies. The model shows that when there is a long first stage characteristic of an endemic situation, the detection of sick individuals is more efficient than vector control. This higher efficiency of detection decreases in a epidemic situation. In this case vector control in the form of a decrease in vector density and/or an increase in vector mortality is relatively more efficient than detection. Because it is squared in the basic reproduction rate, the probability of a tsetse blood meal on humans is an important and sensitive parameter in the study of control strategies. This sensitivity has been observed previously and empirically by field workers. When the probability of a tsetse blood meal on humans is above a certain value, vector control becomes warranted or even necessary.     

Cleavage of single- and double-stranded DNAs containing an abasic residue by Escherichia coli exonuclease III (AP endonuclease VI)

The Escherichia coli exonuclease III (AP endonuclease VI) is a DNA-repair enzyme that hydrolyzes the phosphodiester bond 5' to an abasic site in DNA. To study how the enzyme recognizes the abasic site, we used oligonucleotides containing a synthetic abasic site at any desired position in the sequence. We prepared oligonucleotides containing an abasic residue such as 2'-deoxyribosylformamide, 2'-deoxyribose, 1',2'-dideoxy ribofuranose or propanediol. Duplex oligonucleotides containing an abasic residue used in this study were cleaved on the 5' side of the abasic site by exonuclease III in spite of the varieties of the bases opposite and adjacent to the abasic site. In addition, we observed that the enzyme cleaved single-stranded oligonucleotides containing an abasic site on the 5' side of the abasic site. These findings suggest that the enzyme may principally recognize the DNA-pocket formed at an abasic site. The indole ring of the tryptophan 212 residue of the exonuclease III is probably intercalated to the abasic site. The tryptophan in the vicinity of the catalytic site is conserved in the type II AP endonuclease from various organisms.     

Extremely low noise InGaAs/InAlAs HEMT grown by MOCVD

MOCVD-grown InGaAs/InAlAs HEMTs with excellent noise performance comparable to that of MBE-grown devices have been successfully fabricated. A minimum noise figure lower than 0.30 dB has been obtained with an associated gain of approximately 15 dB at 12 GHz. Furthermore, devices in ceramic packages have exhibited a minimum noise figure of 0.42 dB.<>     

Thermal link for cartridge-type cryostat

We have developed a simple and small thermal link for cooling a cylindrical cartridge, on which device under test is mounted. It consists of a crown-like ring with an inner diameter of 170 or 140 mm and a clamping belt, which is a metal spring or nylon. A thermal conduction of the thermal link is achieved as the crown-like ring clamps the disk-like stage of the cartridge with external force of the clamping belt. This link can be applied at various temperature ranges from 2 to 100 K. The measured thermal conductance of the 170 mm link is 1.7, 5.6 and 3.3 W K⁻¹ for 4, 12, and 80 K stages, respectively. These values are consistent with a empirical calculation within 10% errors. This link is also effective to reduce mechanical vibration to be 6 μm (peak-to-peak) in the horizontal direction of the cartridge. This link is easily fabricated and is useful to various detectors which require to be cooled down.     

Characterization and developmental regulation of proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta isoforms

Protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta) is a receptor-like protein tyrosine phosphatase specifically expressed in the brain. Alternative splicing produces three isoforms of this molecule: PTPzeta-A, the full-length form of PTPzeta; PTPzeta-B, the short form of PTPzeta; and PTPzeta-S, an extracellular variant. Here, we identified all these isoforms, including PTPzeta-B, as chondroitin sulfate proteoglycans, and characterized their carbohydrate modification and expression profiles in the rat brain. The level of PTPzeta-A expression was maintained during the prenatal period and decreased rapidly after birth. PTPzeta-S was expressed in a similar manner, although the postnatal decrease was gradual. In contrast, relatively constant amounts of PTPzeta-B were observed from embryonic day 13 (E13) through adulthood. PTPzeta-A and -S were constantly expressed only as proteoglycans during development, but a substantial amount of PTPzeta-B was detected in a non-proteoglycan form at E13-15. Moreover, PTPzeta-B did not contain LeX, HNK-1 carbohydrate, or keratan sulfate, although PTPzeta-A and -S were generally modified with these carbohydrates. L cells transfected with PTPzeta-A and -B cDNAs expressed these proteins as enzymatically active chondroitin sulfate proteoglycans. The PTPzeta-A and -B in L cells showed essentially similar localizations in cell cortical structures on immunofluorescence microscopy, although immature or processed forms of PTPzeta-A were accumulated additively in intracellular patchy structures. These results show that the three isoforms of PTPzeta are differentially regulated during development, and that the extracellular deleted region in PTPzeta-B is important for determination of carbohydrate modification.     

Loss of biological activity due to Glu-->Arg mutation at residue 11 of the B subunit of cholera toxin

PURPOSE: To determine the maximum tolerated dose, toxicities, and potential antitumor activity of edatrexate (E), an antifolate agent with enhanced in vitro antitumor activity as compared with methotrexate (M), when given in combination with vinblastine, doxorubicin, cisplatin, and filgrastim (G-CSF) to patients with advanced malignancies. PATIENTS AND METHODS: Thirty-seven patients with advanced malignancies were treated with escalating doses of edatrexate in combination with vinblastine (V), doxorubicin (A), cisplatin (C), and filgrastim (EVAC/G-CSF) following three different subsequently developed schedules. Schedule 1 was patterned after the MVAC regimen, a combination chemotherapy program with activity against different epithelial malignancies, and consisted of E, 40 mg/m2/day, days 1/15/22; V, 3 mg/m2/day, days 2/15/22; A, 30 mg/m2/ day, day 2; C, 70 mg/m2/day, day 2; repeated every 28 days. Schedules 2 and 3 were designed to avoid observed dose-limiting toxicity on schedule 1 consisting of transient elevation of serum creatinine levels and delayed myelosuppression. Schedule 2 consisted of E, 40 or 60 mg/ m2/day, days 1 and 15; V, 3 mg/m2/day, days 2 and 15; A, 30 mg/m2/day, day 2; C, 30 mg/m2/day, days 1 and 2; cycled every 28 days. Schedule 3 consisted of E, 60 to 120 mg/m2/day, day 1; V, 3 mg/m2/day, day 2; A, 30 mg/m2/day, day 2; C, 30 mg/m2/day, days 1 and 2; cycled every 21 days. Filgrastim 5 micrograms/kg/day was given to all patients subcutaneously until the absolute neutrophil count was greater than 10,000/microL postnadir. Three patients were treated on schedule 1, 10 on schedule 2 (four at an E dose of 40 mg/m2/day and six at an E dose of 60 mg/m2/day), and 24 on schedule 3 (six at each of the following E dosages: 60, 80, 100, and 120 mg/m2/day). RESULTS: Dose-limiting toxicities of grade 3 to 4 leukopenia and transient elevation of serum creatinine values were observed in two of three patients treated on schedule 1. A dose-limiting toxicity of grade 3 to 4 leukopenia was noted in two of six patients treated on schedule 2 at an edatrexate dose of 60 mg/m2/day. Two of six patients treated on schedule 3 at an edatrexate dose of 120 mg/m2/day had a dose-limiting toxicity of grade 3 stomatitis (one patient) and grade 3 cytopenia (one patient). Nineteen of 37 patients with evaluable or measurable disease had a response to treatment (response rate 51%, 95% confidence intervals = 35%-67%). Nine of 15 patients with metastatic non-small cell lung cancer responded, including one complete remission (response rate 60%, confidence intervals = 35%-85%). A median survival of 517 days (confidence interval = 163-808 days) and a 1-year survival rate of 60% (confidence interval = 35%-85%) was seen in patients with advanced non-small cell lung cancer. CONCLUSIONS: The maximum tolerated dose and the recommended phase II dose of edatrexate is 100 mg/m2/day when administered as part of the EVAC/G-CSF program following schedule 3. Promising antineoplastic activity against non-small cell lung carcinomas was observed, and a phase II study is planned.     

Big insulin-like growth factor II-producing hepatocellular carcinoma associated with hypoglycemia

A 76-year-old female with a hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) was hospitalized because of fasting hypoglycemia. Her sera contained a low concentration of immunoreactive insulin and insulin-like growth factor (IGF)-I, while the IGF-II level was normal. However, most of the IGF-II consisted of the high molecular weight form (big IGF-II). The tumor tissue contained fetal type of IGF-II mRNA (6.0 kb). Furthermore, we found that one of the four patients examined with HCV-related HCC had big IGF-II in serum. This indicates that non-islet cell tumor hypoglycemia (NICTH) in HCV-related HCC might be accompanied by production of big IGF-II by the tumor.     

Studies on bacillary dysentery cases of overseas travellers--during 1979 to 1995

A total of 36,780,440 overseas travellers during 1979-1995 (17 years) were quarantined at Osaka and Kansai Airport Quarantine Station, 84,777 travellers reported themselves suffer from diarrhoea. Stools from 29,587 persons were bacteriologically examined. Various enteropathogenic bacteria were isolated from 9,766 (33.0%) patients of the stools examined. Isolated species were as follows: Plesiomonas shigelloides (3,234 cases); Salmonella spp. (2,236 cases); enterotoxgenic Escherichia coli (1,621 cases); Vibrio parahaemolyticus (1,959 cases); and Shigella spp. (1,242 cases). 1,278 different Shigella strains were isolated from 1,242 cases who were thus diagnosed as bacillary dysentery patients. The suspected regions or countries for infection of these cases were analysed. The serovars and antibiotic-sensitivities of the isolated strains were examined. Colicine typing of S. sonnei strains were also done. The results can be summarized as follows. 1) The most cases (53.4%) were infected in India. 2) The percentage distribution of sub-species of the strains was as follows; S. sonnei (57.8%), S flexneri (29.8%), S. boydii (8.4%), and S. dysenteriae (4.0%), respectively. 3) The major colicine type of S. sonnei strains were type 6 and 0. 4) The percentage of Antibiotic-resistant strains of each sub-species was S. dysenteriae (92.2%), S. sonnei (89.4%), S. flexneri (87.1%), and S. boydii (84.9%), respectively. The percentage of Antibiotic-resistant strains of S. flexneri were increased annually.