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We developed a method for classifying hydrometeor particle types, including cloud and precipitation phase and ice crystal habit, by a synergistic use of CloudSat/Cloud Profiling Radar (CPR) and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO)/Cloud-Aerosol LIdar with Orthogonal Polarization (CALIOP). We investigated how the cloud phase and ice crystal habit characterized by CALIOP globally relate with radar reflectivity and temperature. The global relationship thus identified was employed to develop an algorithm for hydrometeor type classification with CPR alone. The CPR-based type classification was then combined with CALIPSO-based type characterization to give CPR-CALIOP synergy classification. A unique aspect of this algorithm is to exploit and combine the lidar's sensitivity to thin ice clouds and the radar's ability to penetrate light precipitation to offer more complete picture of vertically resolved hydrometeor type classification than has been provided by previous studies. Given the complementary nature of radar and lidar detections of hydrometeors, our algorithm delivers thirteen hydrometeor types: warm water, supercooled water, randomly-oriented ice crystal (3D-ice), horizontally-oriented plate (2D-plate), 3D-ice+2D-plate, liquid drizzle, mixed-phase drizzle, rain, snow, mixed-phase cloud, water+liquid drizzle, water+rain and unknown. The global statistics of three-dimensional occurrence frequency of each hydrometeor type revealed that 3D-ice contributes the most to the total cloud occurrence frequency (53.8%), followed by supercooled water (14.3%), 2D-plate (9.2%), rain (5.9%), warm water (5.7%), snow (4.8%), mixed-phase drizzle (2.3%), and the remaining types (4.0%). This hydrometeor type classification provides useful observation-based information for climate model diagnostics in representation of cloud phase and their microphysical characteristics.

We have developed a circuit for determining an optimal supply voltage, VOPT, for which energy consumption will be minimized in devices suffering from high-leakage. This VOPT is determined on the basis of a trade-off between power consumption and operation time. Experimental results with a 90-nm CMOS device indicate that the proposed circuit successfully determines VOPT with high accuracy. VOPT operations with power gating at 40 MHz, and where VDD = 0.67 V, results in an energy reduction of 52.8% over that achieved with DVFS alone at 5 MHz (1/20 of maximum operational frequency). Further, we propose a scheme for suppressing determination error, one that results in voltage error of less than 50 mV.

We report measurements of the cross section and a complete set of polarization observables for the Si 28 ( p → , n → ) P 28 ( 6 − ) reaction at a bombarding energy of 198 MeV. The data are compared with distorted wave impulse approximation calculations employing response functions normalized to inelastic electron scattering. The spin-longitudinal polarized cross section I D q is slightly over-predicted by the calculations, while the normal spin-transverse polarized cross section I D n is significantly under-predicted. The calculated in-plane spin-transverse I D p and spin-scalar I D 0 polarized cross sections agree well with the experimental data. These results are consistent with those for Si 28 ( p → , p → ′ ) Si 28 ( 6 − , T = 1 ) scattering at the same energy, and thus it is concluded that isospin-mixing effects are not responsible for the discrepancy between theory and experiment in the ( p → , p → ′ ) case. Energy half-off-shell effects as medium effects on the effective nucleon–nucleon interaction are also investigated and found to be too small to be responsible for the discrepancy.

This paper describes newly developed delay and power monitoring schemes for minimizing power consumption by means of the dynamic control of supply voltage V/sub DD/ and threshold voltage V/sub TH/ in active and standby modes. In the active mode, on the basis of delay monitoring results, either VDD control or VTH control is selected to avoid any oscillation problem between them. In V/sub DD/ control, on the basis of delay monitoring results, VDD is adjusted so as to be maintained at the minimum value at which the chip is able to operate for a given clock frequency. In V/sub TH/ control, on the basis of power monitoring results, VTH is adjusted so as to maintain a certain switching current I/sub SW//leakage current I/sub LEAK/ ratio known to indicate minimum power consumption. In the standby mode, the precision of power monitoring (which detects optimum body bias by comparing subthreshold current I/sub SUBTH/ to substrate current I/sub SUB/) is improved by taking into consideration both the effects of lowering V/sub DD/ and the effects of the presence of gate-oxide leakage current. Experimental results with a 90-nm CMOS device indicate that use of the proposed power monitoring results in the successful minimizing of power consumption. It does so by making it possible to: 1) maintain the I/sub SW//ILEAK ratio in the active mode and 2) detect optimum body bias conditions (I/sub SUBTH/=ISUB) within an error of less than 20% with respect to actual minimum leakage current values in the standby mode.

We have developed a domino logic synthesis system with a new technology mapping algorithm based on a bin packing algorithm that reduces the levels of the circuits and considers the complexity of domino primitive cells. Domino logic circuits have 20–50% performance advantage over static circuits. By using this system, designing domino logic circuits becomes much easier than manual design. The primary reason is that logic design is completely automated by the system. The second reason is that domino primitive cell layout is simplified by our new technology mapping algorithms that considers the complexity of domino primitive cells.

To help overcome limits to the speed of conventional SRAMs, we have developed a read-static-noise-margin-free SRAM cell. It consists of seven transistors, several of which are low-Vth nMOS transistors used to achieve both low-VDD and high-speed operations. For the same speed, the area of our proposed SRAM is 23% smaller than that of a conventional SRAM. Further, we have fabricated a 64-kb SRAM macro using 90-nm CMOS technology and have obtained with it a minimum VDD of 440 mV and a 20-ns access time with a 0.5-V supply.

We report our experimental studies on (p, 2p) reactions from two kinds of view points, namely to investigate single particle properties of nuclei and to observe possible modification of NN interactions in nuclear field. Comparison of the cross section data with theoretical predictions and data of (e, e'p) reaction suggests that the reaction mechanizsm at incident energies of around 400 MeV is simple enough to extract spectroscopic information through the (p, 2p) reactions. In addition, some analyzing power data show anomaly which is not seen in cross section data and, therefore, which suggest importance of polarization studies. On the examination of the NN interaction, systematic study on analyzing powers for 1s1/2-proton knockout has been continued. A new systematics, a Q-value dependence the analyzing power was newly observed.

This paper describes floating-point (FP) datapaths developed for graphics and simulation applications. The datapaths are fabricated using 0.35 /spl mu/m CMOS technology and embedded in a 125 MHz, 291 MFLOPS vector pipelined processor for use in supercomputers. A new online test technique has been developed for the purpose of improving reliability under actual operating conditions. The technique makes it easy to detect not only static faults but also delay faults, which has traditionally been difficult.

The cross sections and analyzing powers for the $^{40}\mathrm{Ca}$($\mathrm{pP\vec},2p$) reaction were measured. The strength distributions for the deep-hole states were obtained by a multipole decomposition analysis. The centroid energies and widths of the hole-state strengths of the $1p$ and $1{s}_{1/2}$ orbitals in $^{40}\mathrm{Ca}$ were determined. The spectroscopic factors for the deeply bound $1p$ and $1{s}_{1/2}$ orbitals were extracted as $49\ifmmode\pm\else\textpm\fi{}10%$ and $78\ifmmode\pm\else\textpm\fi{}14%$ of the sum-rule limits of the independent-particle shell model, respectively. A strong influence of the nucleon-nucleon correlations on the spectroscopic factors is suggested.

Gamow-Teller (GT) unit cross sections, ${\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{\ensuremath{\sigma}}}_{\mathrm{GT}}$, are obtained at 198 and 297 MeV by measuring the double differential cross sections at ${0}^{\ifmmode^\circ\else\textdegree\fi{}}$ for the $(p,n)$ reaction on $^{58}\mathrm{Ni}$, $^{70}\mathrm{Zn}$, $^{114}\mathrm{Cd}$, $^{118}\mathrm{Sn}$, and $^{120}\mathrm{Sn}$. The mass dependence of ${\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{\ensuremath{\sigma}}}_{\mathrm{GT}}$ and the ratio of ${\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{\ensuremath{\sigma}}}_{\mathrm{GT}}$ to the Fermi unit cross section, ${\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{\ensuremath{\sigma}}}_{\mathrm{F}}$, $({R}^{2})$ are also derived in the mass region of $58\ensuremath{\leqslant}A\ensuremath{\leqslant}120$. The ${\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{\ensuremath{\sigma}}}_{\mathrm{GT}}$ value for $^{90}\mathrm{Zr}$ at 297 MeV interpolated using the $A$-dependence obtained herein agrees with that used in a previous analysis where the GT transition strength over a wide energy region up to the continuum was discussed. However, the deduced $^{64}\mathrm{Ni}$${\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{\ensuremath{\sigma}}}_{\mathrm{GT}}$ value at 198 MeV is 20% smaller than that obtained from the analysis of a previous $(n,p)$ measurement. The present ${R}^{2}$ values in the mass region heavier than $^{42}\mathrm{Ca}$ are larger than those in the region up to $^{42}\mathrm{Ca}$ and increase as a function of $A$.

The first single-chip 64-b vector-pipelined processor (VPP) ULSI is described. It executes vector operations indispensable to high-speed scientific computation. The VPP ULSI attains a 200-MFLOPS peak performance at a 100-MHz clock frequency. This extremely high performance is made possible by the integration on the VPP of a 64-b five-stage pipelined adder/shifter, a 64-b five-stage pipelined multiplier/divider/logic operation unit, and a 40-kb register file. Various new high-speed circuit techniques have been also developed for 100-MHz operations. The chip, which was fabricated with a 0.8- mu m BiCMOS and triple-layer metallization process technology, has a 17.2-mm*17.3-mm area and contains about 693 K transistors. It consumes 13.2 W at a 100-MHz clock frequency with a single 5-V power supply. >

The authors proposed a novel method of phase measurement of terahertz intermode beat in optical frequency comb, to enhance the dynamic-range of distance meter. Utilizing nonlinear optical process, distance measurement with 130 GHz equivalent frequency was realized.

The benefits of water quality improvement in municipal water use are measured empirically both from the supply side and from the demand side. On the supply side the benefits of water quality improvement are measured by means of a so-called cost-saving approach. On the demand side the costs of the averting behavior of consumers are considered to be one indicator of the benefits of water quality improvement. Whereas from the results of empirical application water quality improvement in Lake Biwa will bring cost saving of 40.8 billion yen year−1, the benefits on the demand side are estimated to be at least 200 billion yen year−1.

This paper describes an electrostatic micro valve which controls fuel in a portable direct methanol fuel cell (DMFC) system under development. A novel pressure balance mechanism is adopted to achieve both normally-closed operation against pressurized fuel and low voltage operation. The fabricated micro valve was tested using air as a working fluid in terms of leak pressure and driving voltage. The micro valve kept close state at input pressure from 0 kPa to 20 kPa. The driving voltage to fully open the micro valve was from 30 V to 60 V. These results well agree with the theoretical estimation.

We redefine write margin in order to be able to quantify the effect of both PVT variation and write-margin improvement. A write-margin monitoring circuit based on this definition is implemented in a 90nm CMOS process. This circuit can be applied to an SRAM power supply circuit to improve the write margin

Analyzing power data are reported for exclusive proton-induced proton knockout from the $1{s}_{1/2}$ states of 10 target nuclei ranging from $^{2}\mathrm{H}$ to $^{19}\mathrm{F}$ for an incident energy of 392 MeV. Compared to free proton-proton scattering, the data are significantly suppressed, the amount of suppression increasing monotonically as a function of increasing separation energies for the knocked-out protons. It is also possible to consider that this suppression increases monotonically as a function of the increasing effective mean density for most of the target nuclei, but data for $^{3}\mathrm{He}$ and $^{4}\mathrm{He}$ targets clearly deviate from such systematic change. The data are compared to model predictions based on the nonrelativistic and relativistic distorted-wave impulse approximation. Both relativistic plane wave model and a nonrelativistic distorted-wave model incorporating a relativistic correction associated with an effective nucleon mass predict a significant suppression of the analyzing power, but the magnitude of the suppression is not sufficient to explain the experimental data. However, a relativistic distorted wave model predicts values that are closer to the data, but the result is inconclusive in this work since recoil corrections are neglected.

We describe the neutron polarimeter NPOL3 for the measurement of polarization transfer observables $D_{ij}$ with a typical high resolution of $\sim$300 keV at $T_n$ $\simeq$ 200 MeV. The NPOL3 system consists of three planes of neutron detectors. The first two planes for neutron polarization analysis are made of 20 sets of one-dimensional position-sensitive plastic scintillation counters with a size of 100 cm $\times$ 10 cm $\times$ 5 cm, and they cover the area of 100 $\times$ 100 $\mathrm{cm}^2$. The last plane for detecting doubly scattered neutrons or recoiled protons is made of the two-dimensional position-sensitive liquid scintillation counter with a size of 100 cm $\times$ 100 cm $\times$ 10 cm. The effective analyzing powers $A_{y;\mathrm{eff}}$ and double scattering efficiencies $\epsilon_{\mathrm{D.S.}}$ were measured by using the three kinds of polarized neutrons from the ${}^{2}{\rm H}(\vec{p},\vec{n})pp$, ${}^{6}{\rm Li}(\vec{p},\vec{n}){}^{6}{\rm Be}(\mathrm{g.s.})$, and ${}^{12}{\rm C}(\vec{p},\vec{n}){}^{12}{\rm N}(\mathrm{g.s.})$ reactions at $T_p$ = 198 MeV. The performance of NPOL3 defined as $\epsilon_{\mathrm{D.S.}}(A_{y;\mathrm{eff}})^2$ are similar to that of the Indiana Neutron POLarimeter (INPOL) by taking into account for the counter configuration difference between these two neutron polarimeters., Comment: 28 pages, 18 figures, submitted to Nucl. Instrum. Methods Phys. Res. A

During the perioperative period for off-pump coronary artery bypass surgery (OPCAB) and on-pump coronary artery bypass surgery (on-pump CABG), the volume of extra cellular fluid (ECF) was measured. The subjects were elective adult coronary artery bypass surgery cases, consisting of 13 OPCAB cases and 7 on-pump CABG cases. The ECF volume was measured the day before surgery, immediately after surgery, and 2, 4, 6, 8, 12, 24 and 48 hours after surgery, with a bioimpedance analyzer (XITRON 4000 C). ECF volume variation was defined as the difference from the preoperative value divided by body weight, and was expressed in %BW. At the same time, respiratory-index and leukocyte count were measured. The maximum postoperative ECF volume was 3.13 +/- 2.6 %BW in the OPCAB group and 5.36 +/- 2.0 %BW in the on-pump CABG group, that is, significantly higher in the on-pump CABG group. The ECF volume started to increase in the on-pump CABG group immediately after surgery (4.38 +/- 1.8 %BW in the on-pump CABG group and 2.07 +/- 2.4 %BW in the OPCAB group), reaching its peak 6 hours after surgery in the on-pump CABG group and 4 hours after surgery in the OPCAB group. Thereafter, the volume gradually decreased, and 48 hours after surgery the volume decreased in the OPCAB group to 0.064 +/- 1.5 %BW, or to about the same value as the preoperative value, whereas in the on-pump CABG group the volume remained high: 1.9 +/- 2.9 % BW. There was no significant difference between the 2 groups in the change in respiratory-index. The leukocyte count remained significantly higher in the on-pump CABG group. The ECF volume was measured by the bioimpedance measuring method. This is a useful method of measuring the volume non-invasively and continuously. In the OPCAB group, the increase in postoperative ECF volume was less, and recovery to the preoperative level was faster than in the on-pump CABG group.

This paper describes a newly developed automatic direction-control-scheme for bi-directional bus repeaters with dynamic-collaborative-driving. Repeater directions are rapidly determined by detecting the direction of enable signal propagation through an additional enable signal line, which is driven by dynamic collaborative-drivers. Application to an on-chip peripheral bus reduced control circuits to half and a dynamically reconfigurable processor (DRP, a kind of innovative reconfigurable logic LSI) application could reduce configuration context data and transistor count to 25%. Experimental results from a 0.18-/spl mu/m CMOS implementation indicate that the proposed scheme improves signal propagation time four times faster than a conventional 3-state bus driver scheme.

A sensing circuit is developed in order to produce a 1 GHz SRAM macro to be used in sub-100 nm CMOS technology nodes. It employs a sense amplifier for each bit-line pair in high-speed operations. The amplifier's optimized composition consists of just ten transistors and helps to minimize area overhead.

High performance floating-point (FP) dividers are essential arithmetic units for graphics applications and simulations, and various algorithms and implementation techniques have been proposed. Using a 0.25 /spl mu/m CMOS technology, we have developed an FP divider, which supports IEEE-754 single-precision and double-precision formats. By using conventional static CMOS logic and (a) a radix-4 SRT algorithm (from the initials of Sweeny, Robertson and Tocher, who developed this algorithm at the same time) with a maximally redundant digit set, (b) a partially nonredundant remainder scheme and (c) a simple operand pre-scaling; the divider can calculate 4 quotient digits/cycle at over 250 MHz with a 2.5 V power supply.

The authors describe design for testability (DFT) techniques implemented in a 200 MFLOPS 64-bit floating point vector-pipelined processor (VPP) ULSI. Scan tests were implemented into the central control unit (CCU), as well as into the input/output buffers, which are served by a boundary scan (BS) chain. Newly developed random pattern built-in self tests (BISTs) were implemented into the register file (RF), as well as into two arithmetic units (ADD/SFT and MPY/DIV/LU). Fault coverage for the RF (2-port SRAMs) was 100%. Average fault coverage for pipelined arithmetic units, achieved by a BIST with approximately 1,000,000(2/sup 20/) random patterns, was 98%. Combination of scan test and BIST-internal partial scan-achieves a partial-scan test of the arithmetic units and 99.6% fault coverage for the MPY/DIV/LU. >

This paper describes floating point (FP) datapaths developed for graphics and simulation applications. The datapaths are fabricated using 0.35 /spl mu/m CMOS technology and embedded in a 125 MHz, 290 MFLOPS vector pipelined processor for use in supercomputers. A new on-line test technique has been developed for the purpose of improving reliability under actual operating conditions. The technique makes it easy to detect not only static faults but also delay faults, which have traditionally been difficult to detect.

A 0.25 /spl mu/m CMOS 2.7 ns latency multiplier capable of supporting a 400 MHz double-stage pipelined FPU consists of Booth recoders, partial product generators, a 4-to-2 compressor tree, and a 108 b final adder. The 4-to-2 compressor combines dual-rail domino and pass-transistor logic gates. The compressor consists of two carry-save adders (CSAs = full adders), and each of the CSAs includes two domino gates for generating carries and a pass-transistor logic gate for generating sums. The critical path in a 4-to-2 compressor tree has conventionally been its carry path. By designing the carry path, however, with domino gates, it has improved the critical delay time so that a 5-input XOR sum path becomes the critical path. Dual-rail pass-transistor logic is used to improve XOR speed, enabling a simple selector to be an XOR gate. The resulting speed is greater than that of a single-rail XOR gate.

The Gamow–Teller (GT) unit cross section, GT, is an essential quantity to deduce the GT transition strength, B(GT), from the (p, n) 0° cross section. (p, n) measurements at 200 and 300 MeV were performed using the Neutron Time-of-Flight (NTOF) facility at the Research Center for Nuclear Physics (RCNP). The GT values were determined, for the first time, for several nuclei in the region of A > 50 at Ep = 200 and 300 MeV. A significant difference between the B(GT) values obtained by (p, n) and (3He, t) measurements was found.

Background Efficacy and toxicity of methotrexate (MTX) differs among individual patients, suggesting the influence of genetic variations in enzymes associated with MTX metabolism and folate metabolic pathway. Recent advances in pharmacogenetics (PGx) may permit the prediction of an individual patient’s response to MTX. Objectives In order to create a prediction model for adverse events of MTX, we investigated the polymorphisms relevant to the hepatotoxicity using the DMET microarray and direct-sequencing (DS) method for detection of 1,971 variants in enzymes concerned in drug-metabolism. Methods: Study subjects A total of 200 RA patients treated with MTX were retrospectively recruited from the Center for Rheumatic Diseases, Shinko Hospital, and 33 patients with hepatotoxicity (AST or ALT > 40 IU/L with MTX ≤ 8mg/week) were sorted. Roughly age- and sex-matched 38 patients without hepatotoxicity (AST and ALT ≤ 40 IU/L with MTX ≥ 8mg/week) were also selected. Genotyping DNA samples were extracted from whole blood samples. We used DMET Plus array (Affymetrix, Inc.) for genotyping 1,934 variants in 231 genes related to pharmacokinetics. Additionally, the other 37 variants in 17 genes, formerly reported to be associated with MTX efficacy or toxicity, were genotyped by DS method 1, 2) . Statistical analysis We firstly compared frequencies of genotypes in the two groups by Fisher’s exact test, and the variants with p Results Among 37 variants in 17 genes reported formerly to be associated with MTX efficacy/toxicity, only 2 SNPs in 2 enzymes (MTRR and ADORA2A) were shown to be significantly associated with hepatotoxicity (p Next, frequency of genotypes in 1,971 variants of 246 genes for patients with and without hepatotoxicity was compared by Fisher’s exact test. 49 SNPs were extracted from a total of 1,971 variants with a significance level of p Finally, multiple logistic regression analysis was used to construct the prediction model for hepatotoxicity. By stepwise selection procedure, we obtained a prediction model in whicha combination of 12 SNPs could discriminate patients between with and without hepatotoxicity. The ROC analysis showed an AUC of 0.9857 with 97.0% sensitivity and 89.5% specificity. Conclusions We found a combination of 12 SNPs in genes related to drug metabolism/transport that could predict hepatotoxicity of MTX with high sensitivity and specificity. After validation in other cohort, this model may lead to appropriate usage of MTX with PGx. References Ranganathan P, McLeod HL: Methotrexate Pharmacogenetics. The Fist Step toward Individualized Therapy in Rheumatoid Arthritis. Arthritis Rheum. 54:1366-1377, 2006. Wessels JAM, et al: A Clinical Pharmacogenetic Model to Predict the Efficacy of Methotrexate Monotherapy in Recent-Onset Rheumatoid Arthritis. Arthritis Rheum. 56:1765-1775, 2007. Acknowledgements We are grateful to Ms. K. Otsuji and Ms. M. Yasuda for their excellent technical assistance. Disclosure of Interest S. Kumagai Grant/research support from: Sysmex Co. (Donation Lab.), G. Tsuji: None Declared, S. Sendo: None Declared, Y. Ichise: None Declared, R. Umeda: None Declared, Y. Hagihara: None Declared, H. Uga: None Declared, H. Kurata: None Declared

beta 2-Glycoprotein I (beta 2-GPI) is a cofactor in the recognition of the phospholipid antigen cardiolipin by anti-cardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examined the interactions of various forms of bovine beta 2-GPI, such as its intact form, desialylated form (Asialo-beta 2-GPI), N-terminal domain (Domain I), and modified forms of beta 2-GPI and Asialo-beta 2-GPI with nicks in their C-terminal domains, with phospholipid liposomes under different conditions of pH and ionic strength. We found that at neutral pH and low ionic strength, beta 2-GPI became bound to liposome membranes containing cardiolipin, phosphatidylglycerol, phosphatidylserine, phosphatidylserine, phosphatidic acid, or phosphatidylinositol, but not phosphatidylcholine alone. The number of phospholipids involved in the binding seemed to depend on the head group structure of the negatively charged phospholipids, but the dissociation constant did not, being about 10(-8) M, except that for the interaction with phosphatidylinositol, which was one order of magnitude lower. We also found that Domain I and Asialo-beta 2-GPI bound to liposome membranes containing negatively charged phospholipids, and that in the interaction with cardiolipin, their dissociation constants were about 10(-6) and 10(-8) M, respectively. At neutral pH and both low and high ionic strengths, the affinities of the nicked forms of beta 2-GPI and Asialo-beta 2-GPI for cardiolipin were both lower than those of their intact forms but similar to that of Domain I.(ABSTRACT TRUNCATED AT 250 WORDS)

The molten globule state has been assumed to be a major intermediate of protein folding. We compared the stability of the native and acidic molten globule states of horse ferricytochrome c against heat, urea and guanidine hydrochloride (Gdn-HCl) using the intact species and species modified by various degrees of acetylation of the lysyl epsilon-amino groups. After acetylation, the amino groups cannot protonate at acidic pH. Thermal and urea-induced unfolding transitions measured by far-UV circular dichroism and differential scanning calorimetry showed that, whereas acetylation stabilizes the molten globule state at pH 2, it destabilizes the native state at pH 7, suggesting a difference in their mechanisms of conformational stability. On the other hand, the effects of Gdn-Hcl were remarkable. Contrary to what was expected from the thermal and urea-induced unfolding transitions, the Gdn-HCl-induced unfolding transition of the native state at pH 7 was insensitive to the extent of acetylation. At pH 2, Gdn-HCl at low concentrations stabilized the molten globule state and, at high concentrations, destabilized it. Consideration of the difference in the effects of Gdn-HCl from those of urea or heat indicated that, whereas the net positive charge repulsion destabilizes the molten globule state at pH 2, the local negative charge repulsion produced by acetylation of amino groups, and not the net charge, critically destabilizes the native state at pH 7. These results predict that, because of its ionic nature, Gdn-HCl will produce substantially different effects on the conformational states of some proteins compared with those of urea.

Whereas the salt-dependent conformational transition of acid-denatured horse ferricytochrome c at pH 2 is approximated by a two-state mechanism from the acid-unfolded state to the molten globule state [Kataoka, M., Hagihara, Y., Mihara, K.,Goto, Y. (1993) J. Mol. Biol. 229, 591-596], the corresponding transition in D2O has been proposed to involve a noncompact, alpha-helical intermediate state (the pre-molten globule state) [Jeng, M.-F.,Englander, S. W. (1991) J. Mol. Biol. 221, 1045-1061]. To examine the proposed difference in the conformational transitions, we carried out the HCl and DCl titrations of cytochrome c in H2O and D2O, respectively, measured by far-UV circular dichroism, tryptophan fluorescence, and Soret absorption. In both D2O and H2O, unfolding from the native state to the acid-unfolded state and subsequent refolding to the molten globule state were observed. In either solvent, the conformational transitions were well approximated by a minimal three-state mechanism consisting of the native, molten globule, and acid-unfolded states. Thus, our results did not substantiate the presence of a pre-molten globule state in D2O. Acetylation of amino groups of cytochrome c is known to stabilize the molten globule state at pH 2. On the basis of the three-state mechanism, we constructed a conformational phase diagram for the effect of pH and the degree of acetylation. This phase diagram was similar to that of the pH- and salt-dependent conformational transition of cytochrome c, suggesting that the effects of acetylation on the conformational states are similar to those of salt.

Between November 1981 and December 1991, 755 patients underwent isolated coronary artery bypass grafting. We compared postoperative events, graft patency and survival rates of the patients who received at least one internal thoracic artery graft (n = 517) with those of the patients who had only saphenous vein bypass grafts (n = 238). No significant difference was found between the 2 groups in patient's age at the operation, female ratio and the incidence of emergency operation. The operative mortality was not significantly different in either group. Graft patency was better for internal thoracic artery grafts than for SVG (ITA grafts 97.1%, SVG 85.6% p less than 0.0001). Graft-LAD patency rate was also better for ITA grafts than for SVG (ITA grafts 97.7%, SVG 86.8%, p less than 0.0001). The incidence of late cardiac events (late cardiac death, reoperation, myocardial infarction) is lower in patients with ITA. Furthermore, patients who received ITA grafts had a better survival rate at 8 years (91.1% versus 85.3%, p = 0.048) than those who had vein bypass grafts alone. We conclude that the use of ITA grafts enhances the long-term benefits including long-term survival rate. This is the first observation in Japanese population.

In order to provide a macromolecular prodrug of 5-fluorouracil (5FU) with reduced side-effects and exhibiting strong antitumor activity, 5FU was covalently linked to poly(ethylene glycol) (PEG) via a urethane or urea bond. For the purpose of evaluating the release behavior of 5FU, the hydrolysis of the urethane or urea bond in the obtained conjugate of PEG-end capped with 5FU was investigated in vitro at 37 degrees C in aqueous solution media. The survival effect for the conjugate was assessed in vivo against p388 lymphocytic leukemia in female CDF1 mice by intraperitoneal (i.p.) transplantation/i.p. injection. The effects of a hydrophobic hexamethylene spacer group, the end group and the number n of ethylene oxide (EO) units in PEG on the release behavior of 5FU and the survival effect were investigated. The release rate of 5FU from the 5FU-terminated PEG conjugates via urethane or urea bond was very fast. However, it became slow with increasing n of EO units in PEG and was depressed by the introduction of hydrophobic spacer group. The 5FU-terminated PEG conjugates obtained exhibited significant survival effects against p388 leukemia mice i.p./i.p. Especially, the methoxy PEG (n = 113)/urethane/hexamethylene/urea/5FU conjugate showed the strongest survival effect among the synthesized 5FU-capped PEG conjugates via urethane or urea bond compared to free 5FU against p388 leukemia mice. These conjugates obtained did not display an acute toxicity even in high dose ranges.

The relationship between changes in cyclic AMP content and germ tube formation in exponential phase Candida albicans was investigated using two simple media containing glucose plus ammonium chloride, or N-acetyl-D-glucosamine (GlcNAc). The glucose medium did not promote germ tube formation unless the cells were starved before inoculation, whereas the GlcNAc medium promoted germ tube formation in both non-starved and starved cells. The cyclic AMP content of exponential phase cells, non-starved cells and starved cells was 0.21, 0.34 and 0.64 pmol mg-1 dry wt, respectively. In glucose medium, cyclic AMP content in both non-starved cells and starved cells increased for a period of 60 min after inoculation, but then decreased for a further 120 min. The cyclic AMP content of non-starved cells and starved cells was 0.16 and 0.29 pmol mg-1 dry wt, respectively, after 180 min. The maximum percentage of non-starved cells with germ tubes was around 20%. Starved cells with germ tubes were observed after 40 min and reached a maximum (around 90%) after 140 min. The number of germ tubes remained constant for the next 40 min. In GlcNAc medium, the cyclic AMP content of both non-starved cells and starved cells showed a tendency to increase for 180 min. The content of non-starved cells and starved cells was 2.02 and 1.75 pmol mg-1 dry wt, respectively, after 180 min. Germ tube formation in non-starved cells started after 70 min, reached around 80% after 150 min, and remained stable for the next 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

An attempt is made in this study to integrate considerations regarding the quality of the environment and the optimal use of resources. Particular attention is paid to water resources and it is considered how a water environment may be realized where clean water flows abundantly through a public water basin. Several water environmental systems are constructed with characteristics pertaining both to the quantity of water resources and to water quality. Water pricing relevant to these water environmental systems is examined. An area model is first constructed. Instead of an effluent fee (or charge), consumers of water resources should pay a consumption tax which reflects the shadow prices of both the quantity and the quality of water resources. The model is extended to the regional model which can be applied to a region including several cities located along a river. Since there are interarea spillovers, the price of water reflects the shadow prices both of water resources and of the spillovers.

This paper gives a modelling process of dynamic water resources allocation problem in the multi-objective aspect as optimal control process. The method of Maximum Principle including iterative goal programming is proposed as solution algorithm. The system equations presented in this paper is inherently general for water environmental system analysis, so they are available not only for water resources allocation, but, for example, for sewerage planning and so on. The trade-offs between regional developments and environmental impacts can partly be transformed into a decision-making problem of people in the basin, i.e., decision on satisfied and permitted level of objectives. Case study of Yamato-River Basin in Nara and Osaka prefectures of Japan clears that coverage ratio of sewerage system takes a main role of solving such a trade-off problem. And it implies that the balance between the goal of high urban activities and that of conserving water quality in river can be made through water resources allocation.