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For small thermodynamic systems in contact with a heat bath, we determine the free energy by imposing the following two conditions. First, the quasi-static work in any configuration change is equal to the free energy difference. Second, the temperature dependence of the free energy satisfies the Gibbs-Helmholtz relation. We find that these prerequisites uniquely lead to the free energy of a classical system consisting of $N$-interacting identical particles, up to an additive constant proportional to $N$. The free energy thus determined contains the Gibbs factorial $N!$ in addition to the phase space integration of the Gibbs-Boltzmann factor. The key step in the derivation is to construct a quasi-static decomposition of small thermodynamic systems., 11 pages, 2 figures

The maximum entropy principle determines the values of thermodynamic variables in thermally isolated equilibrium systems. This paper extends the principle to a variational principle that applies to liquid-gas coexistence in heat conduction. We show the uniqueness of the extension under the assumption that the variational principle and the fundamental thermodynamic relation are simultaneously extended in the linear response regime with the total energy fixed. Using the extended variational principle, we calculate the thermodynamic quantities in this steady state and find that the temperature of the liquid-gas interface deviates from the equilibrium transition temperature, which should be verified in experiments.

We propose a stochastic order parameter equation for describing phase coexistence in steady heat conduction near equilibrium. By analyzing the stochastic dynamics with a non-equilibrium adiabatic boundary condition, where total energy is conserved over time, we derive a variational principle that determines thermodynamic properties in non-equilibrium steady states. The resulting variational principle indicates that the temperature of the interface between the ordered region and the disordered region becomes greater (less) than the equilibrium transition temperature in the linear response regime when the thermal conductivity in the ordered region is less (greater) than that in the disordered region. This means that a super-heated ordered (super-cooled disordered) state appears near the interface, which was predicted by an extended framework of thermodynamics proposed in [N. Nakagawa and S.-i. Sasa, Liquid-gas transitions in steady heat conduction, Phys. Rev. Lett. {\bf 119}, 260602, (2017).], Comment: 30 pages, 13 figures; In ver.2, the presentation has been substantially revised. 31 pages, 14 figures

Most patients with homozygous or compound heterozygous pathogenic ACO2 variants present with muscular hypotonia features, namely, infantile cerebellar-retinal degeneration. Recently, two studies reported rare familial cases of ACO2 variants presenting as complex hereditary spastic paraplegia (HSP) with broad clinical spectra. Here, we report the case of a 20-year-old Japanese woman with complex HSP caused by compound heterozygous ACO2 variants, revealing a new phenotype of episodic visual loss during febrile illness.

We study fluctuating dynamics of a freely movable piston that separates an infinite cylinder into two regions filled with ideal gas particles at the same pressure but different temperatures. To investigate statistical properties of the time-averaged velocity of the piston in the long-time limit, we perturbatively calculate the large deviation function of the time-averaged velocity. Then, we derive an infinite number of effective Langevin equations yielding the same large deviation function as in the original model. Finally, we provide two possibilities for uniquely determining the form of the effective model., Comment: 9 pages

We statistically examine long time sequences of Brownian motion for a nonequilibrium version of the Rayleigh piston model and confirm that the third cumulant of a long-time displacement for the nonequilibrium Brownian motion linearly increases with the observation time interval. We identify a multiplicative Langevin equation that can reproduce the cumulants of the long-time displacement up to at least the third order, as well as its mean, variance and skewness. The identified Langevin equation involves a velocity-dependent friction coefficient that breaks the time-reversibility and may act as a generator of the directionality. Our method to find the Langevin equation is not specific to the Rayleigh piston model but may be applied to a general time sequence in various fields., Comment: 14 pages, 4 figures

We propose the concept of global temperature for spatially non-uniform heat conduction systems. With this novel quantity, we present an extended framework of thermodynamics for the whole system such that the fundamental relation of thermodynamics holds, which we call "global thermodynamics" for heat conduction systems. Associated with this global thermodynamics, we formulate a variational principle for determining thermodynamic properties of the liquid-gas phase coexistence in heat conduction, which corresponds to the natural extension of the Maxwell construction for equilibrium systems. We quantitatively predict that the temperature of the liquid-gas interface deviates from the equilibrium transition temperature. This result indicates that a super-cooled gas stably appears near the interface., Comment: 59 pages, 20 figures

We revisit and analyze the thermodynamic efficiency of the Feynman-Smoluchowski (FS) ratchet, a classical thought experiment describing an autonomous heat-work converter. Starting from the full kinetics of the FS ratchet and deriving the exact forms of the hidden dissipations resulting from coarse-graining, we restate the historical controversy over its thermodynamic efficiency. The existence of hidden entropy productions implies that the standard framework of stochastic thermodynamics applied to the coarse-grained descriptions fails in capturing the dissipative feature of the system. In response to this problem, we explore an extended framework of stochastic thermodynamics to reconstruct the hidden entropy production from the coarse-grained dynamics. The approach serves as a key example of how we can systematically address the problem of thermodynamic efficiency in a multi-variable fluctuating non-equilibrium system., 20 pages, 7 figures

Groundwater has been the primary source of daily water supplies for people living in the Red River Delta, the second largest delta in Vietnam. For this reason, identification of hydrogeochemical properties of the groundwater is indispensable for sustainable utilization of groundwater sources. In this study, the spatio-seasonal hydrogeochemical characteristics of groundwater in the unconfined aquifer of the Red River Delta have been investigated by systematically applying self-organizing maps (SOM) and Gibbs diagrams. The groundwater chemistry dataset used in the analysis is composed of eight major dissolved ions (i.e., Ca2+, Mg2+, Na+, K+, HCO 3 − , Cl−, SO 4 2 − , and CO 3 2 − ) and total dissolved solids that are collected from 47 groundwater monitoring wells within the study area during the dry and rainy seasons. The SOM application classified the hydrogeochemical data into five clusters, which revealed three basic representative water types: high salinity (one cluster), low salinity (two clusters), and freshwater (two clusters). The spatial distribution of clusters and water types were identified. In particular, the low-salinity type was found not only in the downstream area but also in the northeastern parts of the upstream and middle-stream areas, where the groundwater was mainly classified into one specific cluster, in which agricultural activities were considered to influence groundwater chemistry. Cluster changes from the dry to rainy seasons were detected in approximately one-fifth of the observations wells. Dilution by surface water may significantly affect the chemical characteristics of the unconfined aquifer during the rainy season. Based on Gibbs diagrams, rock weathering was found to be the main process in the evolution of chemical composition of freshwater type, whereas the chemical structure of the low- and high-salinity types was primarily controlled by saltwater intrusion or anthropogenic activities.

We study thermodynamic operations which bring a nonequilibrium steady state (NESS) to another NESS in physical systems under nonequilibrium conditions. We model the system by a suitable Markov jump process, and treat thermodynamic operations as protocols according to which the external agent varies parameters of the Markov process. Then we prove, among other relations, a NESS version of the Jarzynski equality and the extended Clausius relation. The latter can be a starting point of thermodynamics for NESS. We also find that the corresponding nonequilibrium entropy has a microscopic representation in terms of symmetrized Shannon entropy in systems where the microscopic description of states involves "momenta". All the results in the present paper are mathematically rigorous., 58 pages, 8 figures; many small improvements have been made in version 2

Summary The Red River Delta (RRD) is the second largest delta in Vietnam, and its local communities depend on groundwater sources for water supply. A clear understanding of the groundwater hydrogeochemical properties, particularly their changes from the dry to rainy seasons and spatial characteristics, is invaluable and indispensable for the management and protection of this important water resource. In this study, self-organizing maps was systematically applied for the first time to investigate the seasonal and spatial hydrogeochemical characteristics of groundwater in the Pleistocene confined aquifer of the RRD. The hydrogeochemical characteristics clustered by SOM were further examined using the Gibbs Diagrams. The groundwater chemistry dataset used in the analysis comprised eight major dissolved ions (i.e., Ca 2+ , Mg 2+ , Na + , K + , HCO 3 − , Cl − , SO 4 2− , and CO 3 2− ) and total dissolved solids that were collected from 52 groundwater monitoring wells within the study area during the dry and rainy seasons. Based on the results, the hydrogeochemical groundwater data of the confined aquifer monitoring wells for the delta were classified into 8 clusters, which revealed three basic representative water types: high salinity (2 clusters), low salinity (3 clusters), and freshwater (3 clusters). The high-salinity types were located in the middle-stream and coastal areas of the RRD, while the low-salinity types were observed near the western and northeastern boundaries of the delta. Cluster changes from the dry to rainy seasons were detected in approximately one-third of the observation wells. The increase in groundwater recharge during the rainy season is the main reason for these changes. Based on Gibbs diagrams, the source of soluble ions in the groundwater of the freshwater types was found to be the weathering of rock-forming minerals, while evaporation and marine activities (leaching from salty paleowater and salt water intrusion) were found to be the main factors affecting the chemistry of the groundwater characterized by the low- and high- salinity types, respectively.

We study liquid-gas transitions of heat conduction systems in contact with two heat baths under constant pressure in the linear response regime. On the basis of local equilibrium thermodynamics, we propose an equality with a global temperature, which determines the volume near the equilibrium liquid-gas transition. We find that the formation of the liquid-gas interface is accompanied by a discontinuous change in the volume when increasing the mean temperature of the baths. A super-cooled gas near the interface is observed as a stable steady state., 6 pages, 4 figures and 9 pages, 1 figure for supplemental material

In the Red River Delta, situated in the northern part of Vietnam, nearly its entire population depends solely on groundwater for daily water consumptions. For this reason, groundwater quality assessments must be carefully carried out using hydrogeochemical properties, to ensure effective groundwater resource planning for the Delta’s present and future groundwater use. In this study, the spatial and seasonal changes in the hydrogeochemical characteristics of groundwater in the two main aquifers of the RRD were investigated by analyzing the physicochemical data obtained in 2011 from 31 conjunctive wells in the Delta’s Holocene unconfined aquifer (HUA) and Pleistocene confined aquifer (PCA) using the Piper diagram and the Gibbs diagram. Results of the data analysis show that the groundwater in both aquifers in the upstream area of the delta is dominated by the [Ca 2+ –HCO 3 − ] water-type, while the [Na + –Cl − ] dominates along the middle-stream and downstream areas. Seasonal changes in the hydrogeochemical facies in both aquifers, comparing the results for the dry and the rainy seasons, were detected in about one third of the sampling wells, which were mainly located at the upstream portion of the Delta. The hydrogeochemical facies of HUA were different from that of PCA by about 45% of the sampling wells in both the dry and the rainy seasons, which were found mostly in the upstream and middle-stream areas.

Groundwater from the Holocene unconfined aquifer (HUA) and Pleistocene confined aquifer (PCA) is the major source of drinking and domestic water in Hanoi, Vietnam. A clear understanding of the groundwater hydrogeochemical properties, particularly their changes during the dry and rainy seasons, is invaluable for the management and protection of this important water resource. In this study, the changes in the hydrogeochemical properties of groundwater during the dry and rainy seasons were investigated by analyzing the major ions (Ca2+, Mg2+, Na+, K+, HCO3 −, SO4 2−, Cl−) that were recently obtained in 2011 from 13 conjunctive sampling wells for HUA and PCA in Hanoi. The hydrogeochemical assessment was carried out using the Piper and Gibbs diagrams. Based on the results, at least 30 % of the sampling wells in both aquifers exhibited changes in the hydrogeochemical facies during the dry and rainy seasons. Most of the changes occurred for the cation-type facies, while the anion type remained unchanged. Moreover, the hydrogeochemical facies of HUA was found to be different from that of PCA by approximately 50 % of the sampling wells for both the dry and rainy seasons. In addition, the Gibbs diagram showed apparent differences in the weight ratios Cl/(Cl + HCO3) between PCA and HUA. The results revealed that rock weathering is the main process involved in the evolution of chemical composition of groundwater, but agricultural activities and salty paleowater are the other important factors that affect the groundwater chemistry in some parts of the study area.

Acidic treatment of a mixture of caprazamycins (CPZs) A-G isolated from a screen of novel antimycobacterial agents gave caprazene, a core structure of CPZs, in high yield. Chemical modification of the resulting caprazene was performed to give its various derivatives. The structure-activity relationships of the caprazene derivatives against several mycobacterial species and pathogenic Gram-positive and Gram-negative bacteria were studied. Although caprazene showed no antibacterial activity, the antibacterial activity was restored for its 1'''-alkylamide, 1'''-anilide and 1'''-ester derivatives. Compounds 4b (CPZEN-45), 4d (CPZEN-48), 4f and 4g (CPZEN-51) exhibited more potent activities against Mycobacterium tuberculosis and M. avium complex strains than CPZ-B. These results suggest that caprazene would be a good precursor from which novel semisynthetic antibacterial antibiotics can be designed for the treatment of mycobacterial diseases such as tuberculosis and M. avium complex infection.

We numerically determine the global entropy for heat-conducting states, which is connected to the so-called excess heat considered as a basic quantity for steady-state thermodynamics in nonequilibrium. We adopt an efficient method to estimate the global entropy from the bare heat current and find that the obtained entropy agrees with the familiar local equilibrium hypothesis well. Our method possesses a wider applicability than local equilibrium and opens a possibility to compare thermodynamic properties of complex systems in nonequilibrium with those in the local equilibrium. We further investigate the global entropy for heat-conducting states and find that it exhibits both extensive and additive properties; however, the two properties do not degenerate each other differently from those at equilibrium. The separation of the extensivity and additivity makes it difficult to apply powerful thermodynamic methods to the nonequilibrium steady states.

Genetic diagnoses provide beneficial information to patients and families. However, traditional genetic diagnoses are often difficult even for experienced clinicians and require recognition of characteristic patterns of signs or symptoms to guide targeted genetic testing for the confirmation of diagnoses. Next-generation sequencing (NGS) is a powerful genetic diagnostic tool. However, whole-genome and whole-exome sequencing (WES) are expensive, and the interpretation of results is difficult. Hence, target gene capture sequencing of gene panels has recently been applied to genetic diagnoses. Herein, we demonstrate that targeted sequencing approaches using gene panel testing are highly efficient for the diagnosis of Mendelian disorders.NGS using TruSight one gene panel was performed in 17 families and 20 patients, and we developed a bioinformatic pipeline at our institution for detecting mutations.We detected causative mutations in 6 of 17 (35%) families. In particular, 11 (65%) families had syndromic diagnosis and 6 (35%) had no syndromic diagnosis before NGS testing. The number of positive diagnoses was 5 of 11 (45%) in the syndromic group and were 1 of 6 (17%) among patients of the no syndromic diagnosis group.Diagnostic yields in the present study were higher than in previous reports of genetic and chromosomal tests and WES. The present comprehensive gene-targeted panel test is a powerful diagnostic tool for Mendelian disorders.

A groundwater-monitoring network has been in operation in the Red River Delta, Vietnam, since 1995. Trends in groundwater level (1995–2009) in 57 wells in the Holocene unconfined aquifer and 63 wells in the Pleistocene confined aquifer were determined by applying the non-parametric Mann-Kendall trend test and Sen’s slope estimator. At each well, 17 time series (e.g. annual, seasonal, monthly), computed from the original data, were analyzed. Analysis of the annual groundwater-level means revealed that 35 % of the wells in the unconfined aquifer showed downward trends, while about 21 % showed upward trends. On the other hand, confined-aquifer groundwater levels experienced downward trends in almost all locations. Spatial distributions of trends indicated that the strongly declining trends (>0.3 m/year) were mainly found in urban areas around Hanoi where there is intensive abstraction of groundwater. Although the trend results for most of the 17 time series at a given well were quite similar, different trend patterns were detected in several. The findings reflect unsustainable groundwater development and the importance of maintaining groundwater monitoring and a database in the Delta, particularly in urban areas.

The Red River Delta is one of two biggest deltas in Vietnam. People living in the delta depend entirely on groundwater for their domestic water. However, the aquifer system in the whole Red River Delta remains poorly understood due to the lack of available data. Recently, we were nominated to construct a hydrogeological database. Using these valuable data contained in this database, this paper comprehensively analyzed the best number of 778 boreholes including well logs and their hydrogeological parameters obtained from pumping tests for the first time in order to identify the entire aquifer system and characterize hydrogeological conditions in the whole delta for potential groundwater resources. Great efforts have been made to establish and analyze hydrogeological maps, cross sections, and contour maps of main aquifers’ thickness and transmissivity. As for the results, we found that groundwater mainly exists in Quaternary unconsolidated sediments as porous water forming the topmost Holocene unconfined aquifer (HUA) and the shallow Pleistocene confined aquifer (PCA) sandwiching the Holocene-Pleistocene aquitard (HPA), while cleft and karst water exist in consolidated Neogene formations and Mesozoic rocks constituting the Neogene water bearing layer (NWL) and Mesozoic fractured zones (MFZ), respectively. PCA is almost entirely distributed over the delta. It serves as the highest groundwater potential and the most important aquifer for water supply. HUA is also widely distributed about 88% over the delta and has a high groundwater potential. NWL and MFZ, placed below PCA but exposed on the surface outside the delta, are minor sources for local domestic water supply only. These findings are indispensable for further groundwater analyses needed to ensure the sustainable groundwater development for the high-security water requirements in the delta, but have never been completed sufficiently before due to the unavailability of large-scale basic data sets.

Background: Immunochromatography (IC) tests are often used for the rapid diagnosis of influenza. Once influenza is diagnosed, an anti-influenza drug can be administered. Physicians claim, however, that they are not sufficiently sensitive, especially in the early phase of the disease. The aim of the present study was therefore to analyze the sensitivity of the IC test from the standpoint of virology. Methods: To evaluate the sensitivity of the IC test statistically, 736 nasopharyngeal specimens were subjected to the IC test and virus isolation (VI). The IC test (+) specimens were compared with VI (+) specimens in the early phase after fever onset. Amounts of the virus in IC(–)VI(+) specimens were compared with those in IC(+)VI(+) specimens on real-time reverse transcriptase–polymerase chain reaction. The isolated viruses from these specimens were subjected to the IC test at the same dose. The nucleotide sequences of NP genes were compared. Results: The IC test was less sensitive for diagnosis in the early phase of the disease. Amounts of virus were significantly lower in IC(–)VI(+) specimens than in IC(+)VI(+) specimens. No variations were observed in the isolated viruses. Conclusions: The IC test is not sufficiently sensitive owing to the low amount of virus in the nasopharyngeal tract in the early phase of the disease. Influenza should be diagnosed on the basis of clinical symptoms within 1 day after the fever onset.

In the 2004-2005 season, there was a large epidemic of the influenza B virus Yamagata group in Kobe, Japan. In hemagglutination inhibition tests, most of the clinical isolates from Kobe showed antigenicities similar to those of previous isolates (the vaccine-type virus). Only a few antigenic variants were isolated around the peak of the epidemic; however, Kobe residents developed antibodies against the variants during the season. The antigenic variants showed a one-point mutation of a nucleotide in the HA1 gene (C440A or G421A), which resulted in the substitution of one amino acid in the 150 loop of the HA molecule (T147N or G141R). The 150 loop is one of four epitopes of the hemagglutinin molecule of the influenza B virus. We established a system to detect one-point differences in the nucleotides of the 150 loop by means of high-resolution melting curve analysis with LCGreen. With this system, the isolates were determined to be the vaccine-type virus, antigenic variants, or a mixture of both. Some isolates were shown to be mixtures although they had been recognized as the vaccine-type virus with the hemagglutination inhibition tests. Thus, the antigenic variants appeared in the early period of the epidemic and were cocirculating with the vaccine-type virus during the epidemic.

In this study, the amount of domestic water use was quantified by estimating the usage rates of various water-related appliances. Tokyo Metropolis was selected as a case study because it was relatively easy to obtain detailed data from Tokyo Waterworks Bureau. In the analysis, the calculations for domestic water use reproduced actual usage figures from 1998 to 2006. From the maximum domestic water use per capita in 1997 the projected reduction was estimated to be 9% by 2025 and 10% by 2050. In addition, our results indicate that water use for both bath and toilet is expected to remain high in the future. We performed a simulation assuming that a 6 L-type toilet is installed by all consumers, with the results suggesting that domestic water use per capita per day could reduce to around 200 L. It was therefore concluded that the replacement of a conventional toilet with a water-saving-type toilet is one of the most effective solutions for reducing domestic water use.

Automated, high-throughput detection methods for single-nucleotide polymorphisms have been applied to the routine genotyping of genetic polymorphisms influencing drug metabolism. Melting curve analysis with LCGreen was introduced recently as one such technique which can be performed rapidly and easily. This technique was used to detect antigenic variants of the influenza B virus. The antigenic variants and vaccine-type strains of the influenza B virus are isolated from clinical specimens of one epidemic season, and they usually differ in one nucleotide in the HA1 gene, corresponding to one amino-acid substitution. By means of melting curve analysis with LCGreen, an antigenic variant clone and a vaccine-type clone were clearly distinguished. In addition, the proportions of the antigenic variants in the mixture-type isolates were estimated. The clinical isolates were detected as the vaccine-type strains, antigenic variants, or a mixture of both. It became clear that humans were infected with a mixture of the vaccine-type strains and the antigenic variants for a certain period after which the viral antigenicities vary. This technique will contribute to the analysis of antigenic shifts in influenza B virus.

Sustainable sanitation is an approach for more ecological and sustainable water resources management. In this paper, we proposed one of the new integrated waste treatment systems: an “sustainable sanitation system” that includes separation of the black water from water system by a non-flushing toilet (bio-toilet), and a gray water treatment based on a biological and ecological concept. Sustainable sanitation system also converts the domestic waste to soil conditioners and fertilizers, for farmland use. As one of the case studies, Environmentally Symbiotic Housing in which people actually live using the bio-toilet for the black water treatment and the household wastewater treatment facility for the gray water was introduced. The availability of this system was investigated by analyzing the sawdust used in the bio-toilet and the quality of the effluent in the household wastewater treatment facility. As the result, the water content of the sawdust did not exceed 60% in any of the sampling points and the BOD and COD of the effluent of the household wastewater treatment facility were below 10 and 20 mg/L respectively, due to the low loading. Compared to the pollution load on the water environment created by the conventional system, it was found that the effluent of the house has a lower load than the tertiary treatment and the volume of the water consumption is 75% of the conventional system.

Using the Gō model of a real protein, we explore the landscape of its metastable structures. First, we show how the inherent structure energy density can be obtained from the probability density determined by sampling molecular dynamics trajectories and quenching. The analysis of the inherent structure landscape can characterize the folding transition. Then we show how thermodynamics of the inherent states can be established to study the equilibrium properties of proteins. Our work brings some elements into the current discussion about the protein dynamical transition. The study uses a simplified model to illustrate the ideas, but, as the inherent structure landscape is much simpler than the free energy surface of the protein, it appears to be accessible for an all-atom model of a small protein, at the expense of much longer calculations.

The motion of a particle on a flexible one-dimensional base is investigated numerically. It is regarded as a barrier-overcoming process in a multi-dimensional phase space. Driving the system far from equilibrium, a directional flow of the particle is observed. In order to understand the appearance of the directionality, two kinds of transition states for the barrier-overcoming process are considered particularly: one of which is for the overcoming process from left to right and the other from right to left. System's conformations for these two transitions are found to be identical at equilibrium, but become different at non-equilibrium, which means that the transition states become direction dependent. The energy barrier heights defined for the two transition states are found to account for biased reaction rates for the directional flow. Thus, the barrier heights work as activation energy extended to far from equilibrium. From the viewpoint of phase space, the directional dependence of the transition states is understood as the symmetry violation of the reaction paths, the route of the reaction being selected depending on the overcoming direction. It should be noted that such a selection is brought about by autonomous dynamics of the system itself. These results suggest the possibility to define an effective potential for a class of dynamical systems in non-equilibrium situations.

The effectiveness of antibacterial agents against 70 strains of clinically isolated multiple-drug resistant Pseudomonas aeruginosa (MDRP) was measured by the micro dilution method. Fifty of all strains (71%) produced metallo-beta-lactamase and the IMP-1 gene was detected by polymerase chain reaction (PCR). The MIC90 (the minimum inhibitory concentration of an antibiotic necessary to inhibit the growth of 90% of bacterial strains) values of biapenem (BIPM), meropenem (MEPM), tazobactam/piperacillin (TAZ/PIPC), sulbactam/ cefoperazone (SBT/CPZ), cefepime (CFPM), ciprofloxacin (CPFX), pazufloxacin (PZFX), amikacin (AMK) and aztreonam (AZT) were found to be 265, 512, 256, 512, 512, 64, 128, 128 and 128 microg/mL, respectively. The in vitro combination effects of antibacterial agents were examined against 62 strains of MDRP and the synergy or additive effects were evaluated by fractional inhibitory concentration (FIC) index calculated by the checkerboard method. The combination of AMK and AZT showed synergy effects on 15/59 (25.4%) strains of MDRP. The synergy and additive effects on the MDRP strains were also found by the other antibacterial agents combination such as TAZ/PIPC and AMK, CFPM and AMK, and SBT/CPZ and AZT. These results suggested the necessity of further investigation of clinical usefulness.

Under a non-equilibrium steady state, an oriented motion of a particle on a one-dimensional flexible rail composed of a line with multiple binding sites of the particle is studied. The dynamical coupling among the particle and the sites allows the system's configuration to fluctuate rather flexibly. Our study focuses on the transition states for the change of the binding site. Due to the flexibility of the system, the transition states at non-equilibrium are found to deviate from those at equilibrium. The excess energy absorbed by the system from the heat baths to attain the transition states is also evaluated. These results consistently account the direction of the oriented motion.

水を使わずかつ資源回収が可能なコンポスト型トイレが現在の流域・都市の水循環が抱える問題を解決するものとして注目されている. しかし, コンポスト型トイレは水洗トイレとは異なり, 排泄物を生活環境内にとどめておくため病原微生物の二次感染について留意する必要があると考えられる. 本論文では, コンポスト型トイレの衛生学的安全性を調べることを目的とし, 従来の水系病原微生物リスク評価をコンポスト型トイレに適用して, 病原微生物の二次感染リスク評価を行い, コンポスト型トイレに要求される病原微生物除去率や必要処理時間について考察した. 結果としてウイルスの方がリスクが高く, それに応じてトイレ内での必要除去率も高くなることが示唆された. また, 井戸水を介した間接暴露においても, 直接暴露に匹敵するリスクが生じる可能性についても示唆された.

Inspired by recent experiments of molecular motors, a dynamical systems model for a flexible machine is proposed which converts injected energy to output directional motion. The output amount is distributed broadly, and thus the coupling between input energy and output motion is loose, as in the experiments. This energy conversion is shown to be robust against the change of surrounding environment. Stability analysis on the fixed point solutions of the model is presented, which suggests that transient chaotic motion, induced by temporal three-body motion, is relevant to the energy conversion.

We develop a unified treatment of pumping and nonequilibrium thermodynamics. We show that the pumping current generated through an adiabatic mechanical operation in equilibrium can be expressed in terms of the stationary distribution of the corresponding driven nonequilibrium system. We also show that the total transfer in pumping can be evaluated from the work imported to the driven counterpart. These findings lead us to a unified viewpoint for pumping and nonequilibrium thermodynamics., Comment: 9 pages, 7 figures

To study the neutralizing epitopes of influenza B virus Victoria group strains, two monoclonal antibodies (MAbs) were used to select antigenic variants of the virus. MAbs 10B8 and 8E6 were found to react with B/Victoria group strains in three tests, peroxidase–antiperoxidase staining, haemagglutination inhibition and neutralization tests; no reactivity with B/Yamagata group strains was observed. Analysis of the deduced amino acid sequences of 10B8-induced variants identified a single amino acid deletion at residue 165 or 170, as well as a single amino acid substitution at residues 164 (Asp→Tyr), 165 (Asn→Ser or Thr) or 203 (Lys→Thr or Asn). A single amino acid substitution at residue 241 (Pro→Ser) was observed in 8E6-induced variants. Three-dimensional analysis showed that the epitopes for both MAbs were situated in close proximity to each other. Since B/Yamagata group strains are characterized by amino acid deletions at residues 164–166, the epitope for MAb 10B8 is strictly specific for B/Victoria group strains.

中川尚子［サイエンスライター］

During the 1998-1999 influenza season, two distinct influenza B virus Yamagata group strains were isolated from the patients of a private clinic. Each responded differently to monoclonal antibodies (Mabs) 5H4 and 8B3 on staining, and hemagglutination inhibition and neutralizing tests. When the analysis of nucleotide sequences was undertaken, the identity of deduced amino acid sequences of the HA1 region was 94%, which suggested that they derived from different strains. They were termed 5H4-responding strains and 5H4-nonresponding strains, respectively. The analysis of laboratory-induced antigenic variants suggested that the amino acid at position 149 is important to the reactivity to 5H4. This residue was "Arg" in 5H4-responding strains and "Lys" in nonresponding strains. During the 1998-1999 season, a total of 100 influenza B virus strains were isolated and 5H4-responding strains were the major type (94 strains). In the 1999-2000 influenza season, only two influenza B virus strains were isolated. Neither responded to 5H4. However, analysis of the deduced amino acid sequences of the HA1 region suggested that one of the two strains was derived from the 5H4-responding strains of the previous season. The amino acid residue at position 149 was "Lys" in place of "Arg." These observations suggested that 5H4-nonresponding strains will increase in coming seasons.

We have attempted to reactivate human herpesvirus 6 (HHV-6) by infection with HHV-7 using childhood exanthem subitum patients in vitro. Peripheral blood mononuclear cells (PBMCs) were collected from children who had a history of exanthem subitum(ES) by HHV-6 and were infected by human herpesvirus 7 (HHV-7) in vitro. The antigen positive rate to HHV-6 started to increase 7 days after the infection and reached a maximum by Day 15 using an immunofluorescence antibody test. The copy number of HHV-6 DNA also increased in the samples in 10 days after infection in vitro. No antigen or increase in DNA was detected in PBMCs, that were mock-infected or infected with supernatant of stock virus after ultracentrifugation, suggesting that an infection by HHV-7 is necessary to reactivate HHV-6. In the paired sera samples during the acute and the convalescent phases of ES, seven to ten bands, that were specific for HHV-6, were recognized in samples from the acute phase, and at least 5 dominant polypeptides were found more intensively after HHV-7 infection.

Monoclonal antibodies (Mabs) against influenza B virus were obtained by immunizing mice with B/Nagasaki/1/87, one of the strains of the B/Victoria group. Immunoprecipitation analysis revealed that individual Mabs precipitated the nucleoprotein (NP), the matrix protein (M) or the hemagglutinin protein (HA). By using these Mabs by the peroxidase–antiperoxidase (PAP) staining method, a rapid detection and identification method for influenza B virus was established. Monolayers of Madin-Darby canine kidney cells in microplates were infected with each strain and incubated for about 24 h, and then were subjected to the PAP staining method using the Mabs as the first antibody. Influenza B virus strains are classified into two major phylogenetic trees, the B/Victoria group and the B/Yamagata group. When anti-NP and anti-M antibodies were used in the PAP staining method, all 13 influenza B virus strains isolated from clinical specimens between 1940 and 1994 were detected regardless of the antigenic drift of the influenza virus. On the other hand, several anti-HA Mabs which reacted specifically with the strains of the B/Victoria group, did not react with any strain of the B/Yamagata group. In the 1996/97 influenza season in Osaka Prefecture in Japan, two antigenically distinct groups of influenza B virus strains were isolated. They belonged to different phylogenetic trees and were clearly distinguishable by the PAP staining method with anti-HA Mabs.

Using polyclonal and monoclonal (MAbs) antibodies to human herpesvirus 7 (HHV-7), we have studied HHV-7-specific polypeptides. Human sera were obtained during the convalescent phase from patients with exanthem subitum due to HHV-7, and at least 16 HHV-7-specific polypeptides with apparent molecular masses of 26-210 kDa were immuno-precipitated. Sera prepared in mice also precipitated at least 17 HHV-7-specific polypeptides with molecular masses of 26-210 kDa. Among them, the most commonly observed antigenic protein had an apparent molecular mass of 52 kDa. Forty-two clones secreting MAbs against HHV-7-specific proteins, as determined by immunofluorescence assays, were established from BALB/c mice immunized with HHV-7-infected cell extracts. Seven MAbs which immunoprecipitated HHV-7-specific polypeptides were further characterized. Two of these, MAbs 5E12 and 5F12, reacted predominantly with glyco-proteins of 78 kDa and 85 kDa, respectively, and possessed neutralizing activity. This suggests that there are at least two neutralization-inducing proteins in HHV-7. MAb 16B4 reacted with the major immunogenic protein of 52 kDa. Five of the 42 MAbs also reacted in immunofluorescence assays with HHV-6 antigens to the same degree as to HHV-7. Two other MAbs, 7C10 and 10F1, recognized an HHV-7 protein of 40 kDa, and only 7C10 cross-reacted with an HHV-6 protein of 45 kDa.

For almost 20 years, the neutralizing-epitope site specific for influenza B virus Victoria group isolates was conserved at the “tip” of the hemagglutinin molecule; however, it was not detected in half of the isolates from the 2002-2003 epidemic in Japan. Amino acid substitutions (D164E or N165K) were observed at the “tip,” and the epitope was altered. The viral antigenicities were affected, and human antibodies did not substantially inhibit the hemagglutination in the hemagglutination inhibition tests. It is suspected that such variants will be important in future epidemics.

In recent years, the practice of environmental impact assessment (EIA) has created significant awareness on the role of environmentally sound projects in sustainable development. In view of the recent studies on the effects of climate change, the Philippine government has given high priority to the construction of flood control structures to alleviate the destructive effects of unmitigated floods, especially in highly urbanized areas like Metro Manila. EIA thus, should be carefully and effectively carried out to maximize or optimize the potential benefits that can be derived from structural flood mitigation measures (SFMMs). A utility-based environmental assessment approach may significantly aid flood managers and decision-makers in planning for effective and environmentally sound SFMM projects. This study proposes a utility-based assessment approach using the rapid impact assessment matrix (RIAM) technique, coupled with the evidential reasoning approach, to rationally and systematically evaluate the ecological and socio-economic impacts of 4 planned SFMM projects (i.e. 2 river channel improvements and 2 new open channels) in Metro Manila. Results show that the overall environmental effects of each of the planned SFMM projects are positive, which indicate that the utility of the positive impacts would generally outweigh the negative impacts. The results also imply that the planned river channel improvements will yield higher environmental benefits over the planned open channels. This study was able to present a clear and rational approach in the examination of overall environmental effects of SFMMs, which provides valuable insights that can be used by decision-makers and policy makers to improve the EIA practice and evaluation of projects in the Philippines.

For time-dependent states generated by an external operation, a generalized free energy may be introduced by the relative entropy with respect to an equilibrium state realized after sufficient relaxation from the time-dependent states. Recently, by studying over-damped systems, Sivak and Crooks presented a formula that relates the generalized free energy with measurable thermodynamic works. We re-derive this relation with emphasizing a connection to an extended Clausius relation proposed in the framework of steady state thermodynamics. As a natural consequence, we generalize this relation to be valid for systems with momentum degrees of freedom, where the Shannon entropy in the generalized free energy is replaced by a symmetric one., 5 pages, 2 figures

Abstract: The effect of S-(1,2-dicarboxyethyl)glutathione (DCE-GS) on glutathione (GSH) synthesis, especially γ -glutamylcysteine synthetase (γ-GCS), was studied in rat liver homogenate . It was found that the feedback inhibition of the γ-GCS by GSH was released by the addition of DCE-GS in the dose dependent manner. Namely, the activity of y-GCS decreased to 17% of the normal level when GSH at the concentration of 10 mM was added to the reaction mixture. However, the addition of DCE-GS offset the inhibition at 20 –μM and increased the γ -GCS activity to 1.7 and 3 times from the normal level at 50 and 100 -μM, respectively .These results suggest that DCE-GS plays a role in stimulating the GSH synthesis. Abstract: The effect of S-(1,2-dicarboxyethyl)glutathione(DCE-GS) on glutathione (GSH) synthesis, especially γ-glutamylcysteine synthetase (γ-GCS), was studied in rat liver homogenate . It was found that the feedback inhibition of the γ-GCS by GSH was released by the addition of DCE-GS in the dose dependent manner. Namely, the activity of γ-GCS decreased to 17% of the normal level when GSH at the concentration of 10 mM was added to the reaction mixture. However, the addition of DCE-GS offset the inhibition at 20 μM and increased the γ-GCS activity to 1.7 and 3 times from the normal level at 50 and 100 μM, respectively .These results suggest that DCE-GS plays a role in stimulating the GSH synthesis.