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This study investigates the decomposition of bath correlation functions (BCFs) in terms of complex exponential functions, with an eye on the realistic modeling of open quantum systems based on the hierarchical equations of motion. We introduce the theoretical background of various decomposition schemes in both time and frequency domains and assess their efficiency and accuracy by demonstrating the decomposition of various BCFs. We further develop a new procedure for the decomposition of BCFs originating from highly structured spectral densities with a high accuracy and compare it with existing fitting techniques. Advantages and disadvantages of each methodology are discussed in detail with special attention to their application to the corresponding quantum dynamical problem. This work provides fundamental tools for choosing and using a variety of decomposition techniques of BCFs for the study of open quantum systems in structured environments. [ABSTRACT FROM AUTHOR]

The dynamics of the sub-Ohmic spin-boson model under polarized initial conditions at finite temperatures is investigated by employing both analytical tools and the numerically accurate hierarchical equations of motion-tensor train method. By analyzing the features of nonequilibrium dynamics, we discovered a bifurcation phenomenon, which separates two regimes of the dynamics. It is found that before the bifurcation time, increasing temperature slows down the population dynamics, while the opposite effect occurs after the bifurcation time. The dynamics is highly sensitive to both initial preparation of the bath and thermal effects. [ABSTRACT FROM AUTHOR]

In a recent study, we developed a kinetic-energy density functional that can be utilized in orbital-free quantum mechanical/molecular mechanical (OF-QM/MM) simulations. The functional includes the nonlocal term constructed from the response function of the reference system of the QM solute. The present work provides a method to combine the OF-QM/MM with a theory of solutions based on the energy representation to compute the solvation free energy of the QM solute in solution. The method is applied to the calculation of the solvation free energy Δμ of a QM water solute in an MM water solvent. It is demonstrated that Δμ is computed as −7.7 kcal/mol, in good agreement with an experimental value of −6.3 kcal/mol. We also develop a theory to map the free energy δμ due to electron density polarization onto the coordinate space of electrons. The free energy density obtained by the free-energy mapping for the QM water clarifies that each hydrogen atom makes a positive contribution (+34.7 kcal/mol) to δμ, and the oxygen atom gives the negative free energy (−71.7 kcal/mol). It is shown that the small polarization free energy −2.4 kcal/mol is generated as a result of the cancellation of these counteracting energies. These analyses are made possible by the OF-QM/MM approach combined with a statistical theory of solutions. [ABSTRACT FROM AUTHOR]

A model of a bulk water system describing the vibrational motion of intramolecular and intermolecular modes is constructed, enabling analysis of its linear and nonlinear vibrational spectra as well as the energy transfer processes between the vibrational modes. The model is described as a system of four interacting anharmonic oscillators nonlinearly coupled to their respective heat baths. To perform a rigorous numerical investigation of the non-Markovian and nonperturbative quantum dissipative dynamics of the model, we derive discretized hierarchical equations of motion in mixed Liouville–Wigner space, with Lagrange–Hermite mesh discretization being employed in the Liouville space of the intramolecular modes and Lagrange–Hermite mesh discretization and Hermite discretization in the Wigner space of the intermolecular modes. One-dimensional infrared and Raman spectra and two-dimensional terahertz–infrared–visible and infrared–infrared–Raman spectra are computed as demonstrations of the quantum dissipative description provided by our model. [ABSTRACT FROM AUTHOR]

Development of the electronic kinetic-energy density functional is a subject of major interest in theoretical physics and chemistry. In this work, the nonlocal kinetic-energy functional is developed in terms of the response function for the molecular system to realize the orbital free density-functional theory (OF-DFT) to be utilized in the hybrid QM/MM (quantum mechanical/molecular mechanical) method. The present approach shows a clear contrast to the previous functionals where the homogeneous electron gas serves as a reference to build the response function. As a benchmark test, we apply the method to a QM water molecule in a dimer system and that embedded in a condensed environment to make comparisons with the results given by the QM/MM calculations employing the Kohn–Sham DFT. It was found that the energetics and the polarization density of the QM solute under the influence of the MM environment can be adequately reproduced with our approach. This work suggests the potential ability of the kinetic-energy functional based on the response functions for the molecular reference systems. [ABSTRACT FROM AUTHOR]

Background: Salivary duct carcinoma (SDC) is a high‐grade adenocarcinoma with a 5‐year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. Methods: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC‐graded prognostic assessment (GPA) score for disease prognostication. Results: Sixty‐five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2‐negative status, and locoregional uncontrolled disease were associated with poor OS. SDC‐GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001). Conclusion: The SDC‐GPA score emerged as a useful prognostication tool for patients with BM. [ABSTRACT FROM AUTHOR]

Background: Our previous research showed that a high rate of secondary carcinogenesis is observed during follow-up after transoral surgery in patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal cancers. We speculate that the contributing factors are alcohol drinking, smoking, and aging; however, we could not provide clear evidence. In this study, we aimed to identify the risk factors for secondary carcinogenesis in patients with these cancers, particularly factors associated with drinking and/or smoking. Methods: The medical records of all-stage laryngeal, oropharyngeal, and hypopharyngeal cancer patients who had undergone definitive treatment were retrospectively analyzed. Assessments included visual and endoscopic observations of the primary site, enhanced cervical CT or US of the primary site and regional lymph nodes, PET-CT, and enhanced whole-body CT. Clinical characteristics were compared in patients with and without secondary carcinogenesis and in patients with hypopharyngeal cancer and patients with other cancers. Results: Hypopharyngeal cancer was an independent risk factor for secondary cancer. The 5-year incidence rate of secondary cancer was 25.5%, 28.6%, and 41.2% in laryngeal, oropharyngeal, and hypopharyngeal cancers, respectively. Radiotherapy was defined as an independent risk factor in hypopharyngeal cancer patients with secondary cancers. No direct correlation was found between secondary carcinogenesis and alcohol consumption, smoking, or aging. Conclusions: Patients with hypopharyngeal cancer require close follow-up as they are at high risk of developing secondary cancer, possibly because out-of-field radiation exposure may induce systemic secondary carcinogenesis in hypopharyngeal cancer patients with genetic abnormality induced by alcohol consumption. [ABSTRACT FROM AUTHOR]

Background: It has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of combined intake of a short fructan (1-kestose [Kes]) and a long fructan (inulin ([Inu]) in an ovalbumin (OVA)-induced food allergy mouse model. Results: Oral administration of fructans lowered the allergenic symptom score and alleviated the decreases in rectal temperature and total IgA levels and increases in OVA-specific IgE and IgA levels induced by high-dose OVA challenge, and in particular, combined intake of Kes and Inu significantly suppressed the changes in all these parameters. The expression of the pro-inflammatory cytokine IL-4, which was increased in the allergy model group, was significantly suppressed by fructan administration, and the expression of the anti-inflammatory cytokine IL-10 was significantly increased upon Kes administration. 16 S rRNA amplicon sequencing of the gut microbiota and beta diversity analysis revealed that fructan administration may induce gut microbiota resistance to food allergy sensitization, rather than returning the gut microbiota to a non-sensitized state. The relative abundances of the genera Parabacteroides B 862,066 and Alloprevotella, which were significantly reduced by food allergy sensitization, were restored by fructan administration. In Parabacteroides, the relative abundances of Parabacteroides distasonis, Parabacteroides goldsteinii, and their fructan-degrading glycoside hydrolase family 32 gene copy numbers were increased upon Kes or Inu administration. The concentrations of short-chain fatty acids (acetate and propionate) and lactate were increased by fructan administration, especially significantly in the Kes + Inu, Kes, and Inu-fed (Inu, Kes + Inu) groups. Conclusion: Combined intake of Kes and Inu suppressed allergy scores more effectively than single intake, suggesting that Kes and Inu have different allergy-preventive mechanisms. This indicates that the combined intake of these short and long fructans may have an allergy-preventive benefit. [ABSTRACT FROM AUTHOR]

In an extended QM/MM (quantum mechanical/molecular mechanical) description of a solution, the solvent molecules surrounding the solute are incorporated into the QM region besides the solute. In a recent development, we introduced a simple and efficient method, referred to as boundary constraint with correction (BCC), to prevent the diffusion of the QM solvent into the bulk. The major purpose of the present work is to develop a method to compute the solvation free energy of a QM solute in an extended QM/MM simulation by means of the BCC method. The strategy of our development is to utilize the QM/MM-ER method which combines the QM/MM simulation and the theory of solutions termed energy representation (ER) to expedite the free energy calculation. A theory is, then, formulated to couple QM/MM-ER and the BCC method on the basis of the statistical mechanics. A notable feature of our method is that the effect of the constraint potentials on the free energy completely vanishes when the force field of the QM solvent coincides with that of the MM solvent. The method is applied to the calculations of the solvation free energies of a water molecule and a hydronium ion in water solutions. It turns out that the present method can offer a significant improvement in describing the free energy Δν of the hydronium ion, in particular, as compared with the conventional QM/MM approach. Explicitly, Δν is obtained as −98.0 kcal/mol showing a good agreement with an experimental value of −103.5 kcal/mol, while −86.1 kcal/mol by the conventional method. [ABSTRACT FROM AUTHOR]

Objectives: To identify patients suitable for endoscopic injection sclerotherapy (EIS) by evaluating their portal hemodynamics and liver function.Methods: We selected 58 patients with esophagogastric varices (EGV) and liver cirrhosis (LC) related to either hepatitis C virus (C) (n = 19), hepatitis B virus (n = 2), alcohol (AL) (n = 20), C + AL (n = 6), non-alcoholic steatohepatitis (n = 6), others (n = 3), or non-LC (n = 2). All patients underwent EIS. We measured their portal venous tissue blood flow (PVTBF) and hepatic arterial tissue blood flow (HATBF) using xenon computed tomography before and after EIS. We classified them into increased group and decreased group according to the PVTBF to identify the predictors that contribute to PVTBF increase post-EIS.Results: Low value of indocyanine green retention at 15 min (ICG-R15), the absence of paraesophageal veins, and low baseline PVTBF/HATBF (P/A) ratio predicted increased PVTBF in the multivariate logistic analysis (odds ratio (OR) 10.46, p = 0.0391; OR 12.45, p = 0.0088; OR 13.57, p = 0.0073). The protein synthetic ability improved 1 year post-EIS in increased group. Cox proportional hazards regression identified alcohol drinking (hazard ratio; 3.67, p = 0.0261) as an independent predictor of EGV recurrence.Conclusions: Patients with low ICG-R15, low P/A ratio, and the absence of paraesophageal veins were probable predictors of PVTBF improvement post-EIS. In addition, the improvement of hepatic hemodynamics likely enhanced liver function following EIS. [ABSTRACT FROM AUTHOR]

Background: UGT1A1 *28 and *6 polymorphism is associated with reduced enzyme activity and severe toxicities of irinotecan, especially in patients with homozygous or heterozygous for UGT1A1*28 or *6 polymorphism for both UGT1A1*28 and *6 (double-variant-type of UGT1A1 polymorphism, UGT1A1-DV). FOLFIRINOX is one of the standard treatments for metastatic pancreatic cancer (PC). The optimal dose of irinotecan as a component of the FOLFIRINOX has not been established yet for patients with UGT1A1-DV.Patients and Methods: Advanced PC patients with UGT1A1-DV who had received at least one cycle of FOLFIRINOX from December 2013 to March 2016 were collected retrospectively conducted at multicenter in Japan. We evaluated the patient characteristics, efficacy and safety of FOLFIRINOX and investigate the optimal initial dose of irinotecan in Japanese advanced PC patients with UGT1A1-DV.Results: A total of 31 patients were enrolled. Grade 4 neutropenia was seen more frequently (67%; 4/6) in patients who had received irinotecan at an initial dose of  ≥ 150 mg/m2 than in those who had received the drug at an initial dose of  ≤ 120 mg/m2 (20%; 5/24). The response rate (RR) and progression-free survival (PFS) in patients given irinotecan of  ≤ 120 mg/m2 were 21.4% and 8.1 months, respectively, which were consistent with previous report for patients without UGT1A1-DV.Conclusion: Based on our findings, we recommend that in Japanese advanced PC patients with UGT1A1- DV treated with FOLFIRINOX, irinotecan be administered at an initial dose of  ≤ 120 mg/m2. [ABSTRACT FROM AUTHOR]

Introduction: Although the seasonality of infectious diseases has been widely reported, the seasonality of peripheral venous catheter-related bloodstream infection (PV-CRBSI) has not been investigated. This study investigated the seasonality of PV-CRBSI and its relationship with meteorological conditions. Methods: A retrospective cohort study of PV-CRBSI at Tokyo Medical University Hospital (Tokyo, Japan), from 2009 to 2019, provided the data for descriptive and time series analyses used to evaluate the number of PV-CRBSI cases per 1000 admissions that occurred each month for each causative organism. By performing univariate and multivariate analyses, the researchers investigated the seasonality of cases and the relationships between meteorological conditions, other external factors, and PV-CRBSIs. Results: This study included a total of 184 PV-CRBSI cases. The mean numbers of PV-CRBSI cases per 1000 admissions caused by all organisms, Bacillus cereus, Gram-positive cocci, and Gram-negative rods were 0.67, 0.15, 0.37, and 0.16 per month, respectively, during the study period. The time series analysis showed that the incidences of PV-CRBSI cases associated with B. cereus and Gram-negative rods were significantly different in the winter/spring from those in the summer/autumn (P < 0.05). The incidence of PV-CRBSI cases caused by B. cereus peaked during summer. The incidence of PV-CRBSI cases caused by B. cereus was significantly positively associated with average monthly temperature, whereas the incidence of PV-CRBSIs caused by Gram-negative rods was significantly negatively associated with average daylight hours. Conclusion: The incidence of PV-CRBSIs caused by B. cereus showed seasonality, peaking during the summer, and a significant correlation was found between PV-CRBSIs caused by B. cereus and average monthly temperature. [ABSTRACT FROM AUTHOR]

A static correlation error (SCE) inevitably emerges when the dissociation of a covalent bond is described with a conventional density-functional theory (DFT) for electrons. The SCE gives rise to a serious overshoot in the potential energy (PE) at the dissociation limit even in the simplest molecules. The error is attributed to the basic framework of the approximate functional for the exchange correlation energy Exc which refers only to local properties at coordinate r , namely, the electron density n(r) and its derivatives. To solve the problem we developed a functional that uses the energy electron distribution ne(ϵ) as a fundamental variable in DFT. ne(ϵ) is obtained by projecting the density n(r) onto an energy coordinate ϵ defined by the external potential of interest. The functional was applied to the dissociations of single, double, and triple bonds in small molecules, showing reasonable agreement with the results given by a high-level molecular orbitals theory. We also applied the functional to the computation of the energy change associated with spin depolarization and symmetrization in a carbon atom, which made an improvement over the conventional functional. This work opens the way to develop a tougher functional that necessitates nonlocal properties of electrons, such as a kinetic energy functional. [ABSTRACT FROM AUTHOR]

We have developed a method of molecular simulations utilizing a polarizable force field in combination with the theory of energy representation (ER) for the purpose of establishing an efficient and accurate methodology to compute solvation free energies. The standard version of the ER method is, however, based on the assumption that the solute-solvent interaction is pairwise additive for its construction. A crucial step in the present method is to introduce an intermediate state in the solvation process to treat separately the many-body interaction associated with the polarizable model. The intermediate state is chosen so that the solute-solvent interaction can be formally written in the pairwise form, though the solvent molecules are interacting with each other with polarizable charges dependent on the solvent configuration. It is, then, possible to extract the free energy contribution δμ due to the many-body interaction between solute and solvent from the total solvation free energy Δμ. It is shown that the free energy δμ can be computed by an extension of the recent development implemented in quantum mechanical/molecular mechanical simulations. To assess the numerical robustness of the approach, we computed the solvation free energies of a water and a methanol molecule in water solvent, where two paths for the solvation processes were examined by introducing different intermediate states. The solvation free energies of a water molecule associated with the two paths were obtained as -5.3 and -5.8 kcal/mol. Those of a methanol molecule were determined as -3.5 and -3.7 kcal/mol. These results of the ER simulations were also compared with those computed by a numerically exact approach. It was demonstrated that the present approach produces the solvation free energies in comparable accuracies to simulations of thermodynamic integration (TI) method within a tenth of computational time used for the TI simulations. [ABSTRACT FROM AUTHOR]

Fertigation is characterized by greater efficiency in the use of inputs such as water and fertilizers, in addition to the ease of programming the application of nutrients according to crop requirements. The objective of this study was to evaluate two different forms of fertigation management using leachates resulting from the application of synthetic inputs in tomato cultivation (Lycopersicon esculentum Mill.). Management was based on the electrical conductivity (EC) and individual ion concentration (CI) in the leachate, with two initial base levels of nutrients (1.6 and 3.2 dS / m). Leachates were collected every week to analyse EC and IC of N, P, K, Ca, Mg and S, and based on this, manage nutrients in solution. When the EC value was less than or greater than 20% of the established value, the nutrient solution was diluted or concentrated in an equal percentage, adding water or a main solution (20 dS / m), respectively. Results showed that applications of N, P and K were higher in IC management, but not so for Ca and Mg, which affects the nutritional status of the plant. Phytotechnical parameters of tomato fruits presented better characteristics when CE is used as a criterion for fertigation management, while the increase in the initial level of nutrients was reflected in a higher production. [ABSTRACT FROM AUTHOR]

We present a simple and exact numerical approach to compute the free energy contribution δμ in solvation due to the electron density polarization and fluctuation of a quantum-mechanical solute in the quantum-mechanical/molecular-mechanical (QM/MM) simulation combined with the theory of the energy representation (QM/MM-ER). Since the electron density fluctuation is responsible for the many-body QM-MM interactions, the standard version of the energy representation method cannot be applied directly. Instead of decomposing the QM-MM polarization energy into the pairwise additive and non-additive contributions, we take sum of the polarization energies in the QM-MM interaction and adopt it as a new energy coordinate for the method of energy representation. Then, it is demonstrated that the free energy δμ can be exactly formulated in terms of the energy distribution functions for the solution and reference systems with respect to this energy coordinate. The benchmark tests were performed to examine the numerical efficiency of the method with respect to the changes in the individual properties of the solvent and the solute. Explicitly, we computed the solvation free energy of a QM water molecule in ambient and supercritical water, and also the free-energy change associated with the isomerization reaction of glycine from neutral to zwitterionic structure in aqueous solution. In all the systems examined, it was demonstrated that the computed free energy δμ agrees with the experimental value, irrespective of the choice of the reference electron density of the QM solute. The present method was also applied to a prototype reaction of adenosine 5′-triphosphate hydrolysis where the effect of the electron density fluctuation is substantial due to the excess charge. It was demonstrated that the experimental free energy of the reaction has been accurately reproduced with the present approach. [ABSTRACT FROM AUTHOR]

The relationship is investigated for QM/MM (quantum-mechanical/molecular-mechanical) systems between the fluctuations of the electronic state of the QM subsystem and of the solvation effect due to the QM-MM interaction. The free-energy change due to the electron-density fluctuation around its average is highlighted, and is evaluated through an approximate functional formulated in terms of distribution functions of the many-body coupling (pairwise non-additive) part of the QM-MM interaction energy. A set of QM/MM simulations are conducted in MM water solvent for QM water solute in ambient and supercritical conditions and for QM glycine solute in the neutral and zwitterionic forms. The variation of the electronic distortion energy of the QM solute in the course of QM/MM simulation is then shown to be compensated by the corresponding variation of the free energy of solvation. The solvation free energy conditioned by the electronic distortion energy is further analyzed with its components. It is found that the many-body contribution is essentially equal between the free energy and the average sum of solute-solvent interaction energy. [ABSTRACT FROM AUTHOR]

The isoalloxazine ring (flavin ring) is a part of the coenzyme flavin adenine dinucleotide and acts as an active site in the oxidation of a substrate. We have computed the free energy change Δμred associated with one-electron reduction of the flavin ring immersed in water by utilizing the quantum mechanical/molecular mechanical method combined with the theory of energy representation (QM/MM-ER method) recently developed. As a novel treatment in implementing the QM/MM-ER method, we have identified the excess charge to be attached on the flavin ring as a solute while the remaining molecules, i.e., flavin ring and surrounding water molecules, are treated as solvent species. Then, the reduction free energy can be decomposed into the contribution Δμred(QM) due to the oxidant described quantum chemically and the free energy Δμred(MM) due to the water molecules represented by a classical model. By the sum of these contributions, the total reduction free energy Δμred has been given as -80.1 kcal/mol. To examine the accuracy and efficiency of this approach, we have also conducted the Δμred calculation using the conventional scheme that Δμred is constructed from the solvation free energies of the flavin rings at the oxidized and reduced states. The conventional scheme has been implemented with the QM/MM-ER method and the calculated Δμred has been estimated as -81.0 kcal/mol, showing excellent agreement with the value given by the new approach. The present approach is efficient, in particular, to compute free energy change for the reaction occurring in a protein since it enables ones to circumvent the numerical problem brought about by subtracting the huge solvation free energies of the proteins in two states before and after the reduction. [ABSTRACT FROM AUTHOR]

In the present work, we have performed quantum chemical calculations to determine preferable species among the ionic complexes that are present in ambient water due to the autodissociation of water molecule. First, we have formulated the relative population of the hydrated complexes with respect to the bare ion (H3O+ or OH-) in terms of the solvation free energies of the relevant molecules. The solvation free energies for various ionic species (H3O+, H5O2+, H7O3+, H9O4+ or OH-, H3O2-, H5O3-, H7O4-, H9O5-), categorized as proton or hydroxide ion in solution, have been computed by employing the QM/MM-ER method recently developed by combining the quantum mechanical/molecular mechanical (QM/MM) approach with the theory of energy representation (ER). Then, the computed solvation free energies have been used to evaluate the ratio of the populations of the ionic complexes to that of the bare ion (H3O+ or OH-). Our results suggest that the Zundel form, i.e., H5O2+, is the most preferable in the solution among the cationic species listed above though the Eigen form (H9O4+) is very close to the Zundel complex in the free energy, while the anionic fragment from water molecules mostly takes the form of OH-. It has also been found that the loss of the translational entropy of water molecules associated with the formation of the complex plays a role in determining the preferable size of the cluster. [ABSTRACT FROM AUTHOR]

The Beckmann rearrangement of acetone oxime promoted by proton transfers in the supercritical water has been investigated by means of the hybrid quantum mechanical/molecular mechanical approach combined with the theory of energy representation (QM/MM-ER) recently developed. The transition state (TS) structures have been explored by ab initio calculations for the reaction of hydrated acetone oxime on the assumption that the reaction is catalyzed by proton transfers along the hydrogen bonds connecting the solute and the solvent water molecules. Up to two water molecules have been considered as reactants that take part in the proton transfers. As a result of the density functional theory calculations with B3LYP functional and aug-cc-pVDZ basis set, it has been found that participation of two water molecules in the reaction reduces the activation free energy by -12.3 kcal/mol. Furthermore, the QM/MM-ER simulations have revealed that the TS is more stabilized than the reactant state in the supercritical water by 2.7 kcal/mol when two water molecules are involved in the reaction. Solvation free energies of the reactant and the TS have been decomposed into terms due to the electronic polarization of the solute, electron density fluctuation, and others to elucidate the origin of the stabilization of the TS as compared with the reactant. It has been revealed that the promotion of the chemical reaction due to the hydration mainly originates from the interaction between the nonpolarized solute and the solvent water molecules at the supercritical state. [ABSTRACT FROM AUTHOR]

The free energy change associated with the isomerization reaction of glycine in water solution has been studied by a hybrid quantum mechanical/molecular mechanical (QM/MM) approach combined with the theory of energy representation (QM/MM-ER) recently developed. The solvation free energies for both neutral and zwitterionic form of glycine have been determined by means of the QM/MM-ER simulation. The contributions of the electronic polarization and the fluctuation of the QM solute to the solvation free energy have been investigated. It has been found that the contribution of the density fluctuation of the zwitterionic solute is estimated as -4.2 kcal/mol in the total solvation free energy of -46.1 kcal/mol, while that of the neutral form is computed as -3.0 kcal/mol in the solvation free energy of -15.6 kcal/mol. The resultant free energy change associated with the isomerization of glycine in water has been obtained as -7.8 kcal/mol, in excellent agreement with the experimental data of -7.3 or -7.7 kcal/mol, implying the accuracy of the QM/MM-ER approach. The results have also been compared with those computed by other methodologies such as the polarizable continuum model and the classical molecular simulation. The efficiency and advantage of the QM/MM-ER method has been discussed. [ABSTRACT FROM AUTHOR]

A novel quantum chemical approach recently developed has been applied to an ionic dissociation of a water molecule (2H2O→H3O++OH-) in ambient and supercritcal water. The method is based on the quantum mechanical/molecular mechanical (QM/MM) simulations combined with the theory of energy representation (QM/MM-ER), where the energy distribution function of MM solvent molecules around a QM solute serves as a fundamental variable to determine the hydration free energy of the solute according to the rigorous framework of the theory of energy representation. The density dependence of the dissociation free energy in the supercritical water has been investigated for the density range from 0.1 to 0.6 g/cm3 with the temperature fixed at a constant. It has been found that the product ionic species significantly stabilizes in the high density region as compared with the low density. Consequently, the dissociation free energy decreases monotonically as the density increases. The decomposition of the hydration free energy has revealed that the entropic term (-TΔS) strongly depends on the density of the solution and dominates the behavior of the dissociation free energy with respect to the variation of the density. The increase in the entropic term in the low density region can be attributed to the decrease in the translational degrees of freedom brought about by the aggregation of solvent water molecules around the ionic solute. © 2005 American Institute of Physics. [ABSTRACT FROM AUTHOR]

A methodology has been proposed to compute the solvation free energy of a molecule described quantum chemically by means of quantum mechanical/molecular mechanical method combined with the theory of energy representation (QM/MM-ER). The present approximate approach is quite simple to implement and requires much less computational cost as compared with the free energy perturbation or thermodynamic integration. Furthermore, the electron distribution can be treated faithfully as a quantum chemical object, and it is no longer needed to employ the artificial interaction site model, a reduced form of the realistic electron distribution, which is commonly used in the conventional solution theory. The point of the present approach is to employ the QM solute with electron density fixed at its average distribution in order to make the solute-solvent interaction pairwise. Then, the solvation free energy can be computed within the standard framework of the energy representation. The remaining minor contribution originating from the many-body effect inherent in the quantum mechanical description can be evaluated separately within a similar framework if necessary. As a test calculation, the method has been applied to a QM water solute solvated by MM water solvent in ambient and supercritical states. The results of the QM/MM-ER simulations have been in excellent agreement with the experimental values. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Purpose: Transforming growth factor-beta inhibitors may enhance the antitumor activity of gemcitabine with acceptable safety and tolerability. This open-label, multicenter, non-randomized phase 1b study assessed the safety/tolerability, pharmacokinetics, and tumor response of galunisertib plus gemcitabine in Japanese patients with advanced or metastatic pancreatic cancer.Methods: During each 28-day cycle, galunisertib 150 mg was administered orally twice daily (300 mg/day) for 14 days, followed by 14 days of rest. Gemcitabine 1000 mg/m2 was intravenously given on Days 8, 15, and 22. Safety was assessed by the incidence of dose-limiting toxicities (DLTs) in the first cycle and treatment-emergent adverse events (TEAEs). Efficacy was assessed by antitumor activity and changes in carbohydrate antigen 19-9 (CA19-9).Results: No DLTs were reported. All 7 enrolled patients had ≥1 TEAE, of which the most common included anorexia, decreased neutrophil count, and decreased white blood cell count. Grade ≥3 TEAEs were observed in 6 patients; 4 patients had Grade ≥3 TEAEs (decreased neutrophil, white blood cell, and lymphocyte count; hypophosphatemia) considered possibly related to study drug(s). The pharmacokinetic profile of galunisertib in combination with gemcitabine was similar to that previously observed for galunisertib alone. The clinical response [complete response (CR), partial response (PR), or stable disease] rate was 42.9%, and the median progression-free survival was 64 days; no CR/PR were achieved.Conclusion: Galunisertib plus gemcitabine had an acceptable safety/tolerability profile with evidence of efficacy in Japanese patients with advanced or metastatic pancreatic cancer. [ABSTRACT FROM AUTHOR]

An old anti-inflammatory/analgesic drug called Toradol is a racemic form of Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2 (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form and of COX-2 by the S-form, eventually down-regulating the production of prostaglandins. However, due to its COOH moiety which is clearly repulsive to negatively-charged phospholipid-based plasma membrane, its cell-permeability is rather poor (the IC 50 against the growth of human cancer cells such as A549 is around 13 μM). In an attempt to boost its anti-cancer activity, hopefully by increasing its cell-permeability through abolishing the negative charge, yet keeping its water-solubility, here we synthesized a 1,2,3-triazolyl ester of Toradol through “Click Chemistry”. The resultant water-soluble “azo” derivative called “15K” was found to be over 500 times more potent than Toradol with the IC 50 around 24 nM against the PAK1-dependent growth of A549 cancer cells, inactivating PAK1 in cell culture with the apparent IC 50 around 65 nM, and inhibiting COX-2 in vitro with the IC 50 around 6 nM. Furthermore, the Click Chemistry boosts the anti-cancer activity of Ketorolac by 5000 times against the PAK1-independent growth of B16F10 melanoma cells. Using a multi-drug-resistant (MDR) cancer cell line (EMT6), we found that the esterization of Ketorolac boosts its cell-permeability by at least 10 folds. Thus, the Click Chemistry dramatically boosts the anti-cancer activity of Ketorolac, at least in three ways: increasing its cell-permeability, the anti-PAK1 activity of R-form and anti-COX-2 activity of S-form. The resultant “15K” is so far among the most potent PAK1-blockers, and therefore would be potentially useful for the therapy of many different PAK1-dependent diseases/disorders such as cancers. [ABSTRACT FROM AUTHOR]

To provide the necessary oxygen for plant growth, the effectiveness of different generating methods of microbubbles (MB), a gas-water circulation type or a pressurization type (pressurization treatment), was investigated by comparing the growth characteristics and morphological observation ofBrassica campestrisL. var. Komatsuna Matsum. The plant growth in the pressurization treatment were significantly less than those in the circulation treatment at 3 weeks after planting. In plants grown in the pressurization treatment, epidermal cell abrasion and plasmolysis, indicators of cell death, were observed in root tip cells at 3 weeks after planting. The growth inhibition of plant in the pressurization treatment is suggested to be related to the oxidization of Fe in the nutrient solution under super-saturated dissolved oxygen conditions, the generation of hydroxyl radicals from MB, the oxidization of the root tip cell membrane, and osmotic stress to the roots. [ABSTRACT FROM PUBLISHER]

A 38-year-old woman had developed an abdominal distention, lower extremity edema, and dyspnea. Imaging examination revealed a large mass in the right atrium which was connected to lesions within the inferior vena cava. Although complete resection of the mass was not possible, partial surgical tumor resection was performed to avoid pulmonary embolization and circulatory collapse. Leiomyosarcoma was diagnosed histologically, and chemotherapy (doxorubicin) followed by radiotherapy was started. By reviewing papers published in the past 10 years that included 322 patients, we also discuss the clinical presentations and prognosis of leiomyosarcoma in the inferior vena cava. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new indole alkaloid was isolated from an Okinawan marine sponge Hyrtios sp. • The alkaloid is the third alkaloid with the canthin-6-one skeleton from sponges. • The alkaloid might be generated from l -arginine, l -histidine, and l -tryptophan. • The alkaloid exhibited moderate cytotoxicity against L1210 murine leukemia cells. Abstract A new indole alkaloid with the canthin-6-one skeleton, ishigadine A, has been isolated from an Okinawan marine sponge Hyrtios sp. The structure of ishigadine A was elucidated on the basis of spectroscopic analyses. Ishigadine A is a new canthin-6-one alkaloid possessing a hydroxy group, a 1,3-dimethyl-4-methylthioimidazolium, and a 1-propylguanidine. Ishigadine A is the third canthin-6-one alkaloid from sponges. Ishigadine A might be generated from l -arginine, l -histidine, and l -tryptophan. Ishigadine A exhibited moderate cytotoxicity against L1210 murine leukemia cells. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this multicenter cooperative study was to elucidate the clinical features of hepatitis B virus (HBV) reactivation by chemotherapeutic agents and the patient outcomes after HBV reactivation by a retrospective review of accumulated patients' medical records. Methods: Records of a total of 27 patients (hematological malignancy, 14 patients; solid tumor, 13 patients) from 11 institutions who were diagnosed between June 2005 and October 2010 as having HBV reactivation following chemotherapy were reviewed. Results: Of the 27 patients with reactivation, 16 patients were hepatitis B surface antigen (HBsAg) positive and 11 were HBsAg negative prior to the commencement of chemotherapy. Of the 11 patients who were HBsAg negative prior to the chemotherapy, 10 had hematological malignancies and one had a solid tumor. Of the 14 patients with hematological malignancies with HBV reactivation enrolled in the study, the reactivation occurred more than 12months after the completion of chemotherapy in five patients (36%); on the other hand, none of the patients (0%) with solid tumors developed HBV reactivation more than 12months after the completion of chemotherapy. Of the 24 patients who had acute liver dysfunction at the diagnosis of HBV reactivation, nine (38%) had severe hepatitis and seven (29%) died of liver failure. Conclusion: Most of the patients with HBV reactivation who were HBsAg negative prior to the chemotherapy had underlying hematological malignancies. Furthermore, patients with hematological malignancies often developed late-onset HBV reactivation. The prognosis of patients who develop acute liver dysfunction as a complication of HBV reactivation is extremely dismal. [ABSTRACT FROM AUTHOR]

It is a promising extension of the quantum mechanical/molecular mechanical (QM/MM) approach to incorporate the solvent molecules surrounding the QM solute into the QM region to ensure the adequate description of the electronic polarization of the solute. However, the solvent molecules in the QM region inevitably diffuse into the MM bulk during the QM/MM simulation. In this article, we developed a simple and efficient method, referred to as the “boundary constraint with correction (BCC),” to prevent the diffusion of the solvent water molecules by means of a constraint potential. The point of the BCC method is to compensate the error in a statistical property due to the bias potential by adding a correction term obtained through a set of QM/MM simulations. The BCC method is designed so that the effect of the bias potential completely vanishes when the QM solvent is identical with the MM solvent. Furthermore, the desirable conditions, that is, the continuities of energy and force and the conservations of energy and momentum, are fulfilled in principle. We applied the QM/MM-BCC method to a hydronium ion( H 3 O + ) in aqueous solution to construct the radial distribution function (RDF) of the solvent around the solute. It was demonstrated that the correction term fairly compensated the error and led the RDF in good agreement with the result given by an ab initio molecular dynamics simulation. [ABSTRACT FROM AUTHOR]

Background: Xenon computed tomography (Xe-CT) provides quantitative information on tissue blood flow (TBF). In the present study, Xe-CT was performed in patients with esophagogastric varices (EGV) before and after endoscopic injection sclerotherapy (EIS) to evaluate hepatic blood flow (HBF), hepatic arterial TBF (HATBF) and portal venous TBF (PVTBF). Methods: Subjects comprised of 88 patients with EGV (49 men, 39 women, average age 65.8 ± 11.5 years, median age 68 years, 30-86 years) and liver cirrhosis related to either hepatitis C virus (C) ( n = 33), hepatitis B virus (B) ( n = 3), alcohol (AL) ( n = 22), AL + C ( n = 7), AL + B ( n = 1), B + C + AL ( n = 1), nonalcoholic steatohepatitis (NASH) ( n = 4), autoimmune hepatitis (AIH) ( n = 5), primary biliary cirrhosis (PBC) ( n = 2), or cryptogenic ( n = 10) were enrolled. All patients, who were enrolled in this study, were performed EIS for prophylaxis. Xe-CT and measurement of the retention rate of indocyanine green 15 min after administration (ICG R15) were performed before and after EIS. Total hepatic TBF (THTBF) and PVTBF/HATBF ratio (P/A) were also calculated. Results: PVTBF, HATBF, THTBF, P/A and ICG R15 before EIS were 28.3 ± 8.91, 22.5 ± 14.4 and 50.8 ± 17.6 ml/100 ml/min, 1.62 ± 0.71 and 28.8 ± 12.7 %, respectively and those after EIS were 31.9 ± 10.0, 19.3 ± 11.6, and 51.2 ± 17.0 ml/100 ml/min, 1.92 ± 0.84 and 23.6 ± 11.3 %, respectively. PVTBF and P/A after EIS were significantly higher than those before EIS ( p = 0.00444, p = 0.0179, respectively), and HATBF and ICG R15 after EIS were significantly lower than those before EIS ( p = 0.00129, p < 0.001, respectively). Conclusions: Xenon computed tomography showed that PVTBF increased after EIS for EGV and HATBF decreased in response to an increase in PVTBF. [ABSTRACT FROM AUTHOR]

Highlights: [•] Inner pressure at small cavity is rigorously defined and calculated by molecular dynamics. [•] Validity of Young–Laplace equation and possible maximum pressure in the cavity are clarified. [•] Liquid argon and water show analogous behavior of the inner pressure. [Copyright &y& Elsevier]

Physalis peruviana L. well known in Colombia and originate in the South American Andes, has attracted some producers in Brazil for producing a fruit with high market value. Since this is a culture adapted to some Brazilian regions, the supply of nutrients is an important aspect that needs to be developed to increase productivity. The study aimed to establish the optimal ranges of concentration of nutrients, using the electrical conductivity of nutrient solution for Physalis. Looking for alternatives to successive cultivations in soil, which cause phytosanitary, environmental and nutritional problems, the experiment was conducted in a greenhouse of the Universidade Estadual de Londrina, Londrina, Paraná State in pots containing coarse sand, trickle fertigated. Were analyzed fresh fruit weight, dry weight of leaves, stems and fruit, productivity, soluble solids and total levels of nutrients in the vegetative organs of Physalis. Four treatments were constituted by the electrical conductivity of nutrient solution of 0.5, 1.0, 2.0 and 3. OdS m-1 with five replicates. Significant increases were observed in fruit production and the total contents of N.P.K in some of the evaluated organs (leaves, fruits and stems) when using the higher concentration of nutrients (electrical conductivity) in the nutrient solution. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this work was to develop a method of calculating blood flow and xenon solubility coefficient (λ) in the hepatic tissue by xenon-enhanced computed tomography (Xe-CT) and to demonstrate λ can be used as a measure of fat content in the human liver. Methods: A new blood supply model is introduced which incorporates both arterial blood and portal venous blood which join and together flow into hepatic tissue. We applied Fick's law to the model. It was theoretically derived that the time course of xenon concentration in the inflow blood (the mixture of the arterial blood and the portal venous blood) can be approximated by a monoexponential function. This approximation made it possible to obtain the time-course change rate (KI) of xenon concentration in the inflow blood using the time course of xenon concentration in the hepatic tissue by applying the algorithm we had reported previously. KI was used to calculate blood flow and λ for each pixel in the CT image of the liver. Twenty-six patients (49.2 ± 18.3 years) with nonalcoholic steatohepatitis underwent Xe-CT abdominal studies and liver biopsies. Steatosis of the liver was evaluated using the biopsy specimen and its severity was divided into ten grades according to the fat deposition percentage [(severity 1) <= 10%, 10 % <(severity 2) <= 20%, ..., 90% < (severity 10) <= 100%]. For each patient, blood flow and λ maps of the liver were created, and the average λ value ([formula]) was compared with steatosis severity and with the CT value ratio of the liver to the spleen (liver/spleen ratio). Results: There were good correlations between [formula] and steatosis severity (r = 0.914, P < 0.0001), and between [formula] and liver/spleen ratio (r = -0.881, P < 0.0001). Ostwald solubility for xenon in the hepatic tissue (tissue Xe solubility), which is calculated using [formula] and the hematocrit value of the patient, also showed a good correlation with steatosis severity (r = 0.910, P < 0.0001). [formula] ranged from 0.86 to 7.81, and tissue Xe solubility ranged from 0.12 to 1.16. This range of solubility is reasonable considering the reported Ostwald solubility coefficients for xenon in the normal liver and in the fat tissue are 0.10 and 1.3, respectively, at 37 °C. The average blood flow value ranged from 15.3 to 53.5 ml/100 ml tissue/min. Conclusions: A method of calculating blood flow and λ in the hepatic tissue was developed by means of Xe-CT. This method would be valid even if portosystemic shunts exist; it is shown that λ maps can be used to deduce fat content in the liver. As a noninvasive modality, Xe-CT would be applicable to the quantitative study of fatty change in the human liver. [ABSTRACT FROM AUTHOR]

Introduction: Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS. Materials and methods: We used Fick's principle and the Kety-Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt's classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups. Results: LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups. Conclusions: In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means. [ABSTRACT FROM AUTHOR]

It is well known that corrosion protection of pure Al is enormously improved by the formation of porous anodic oxide films and by pore sealing treatment. However, the effects of anodizing and pore sealing on corrosion protection for Al alloys are unclear, because the alloying elements included in Al alloys affect the structure of anodic oxide films. In the present study, porous anodic oxide films are formed on pure Al, 1050-, 3003- and 5052-Al alloys, and pore sealing was carried out in boiling water. Changes in the structure and corrosion protection ability of porous anodic oxide films on pure Al and the Al alloys by pore sealing, were examined by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). SEM observation showed that anodic oxide films formed on pure Al have a smooth surface after pore sealing, and that cracks are formed in anodic oxide films on 1050-, 3003- and 5052-aluminum alloys, after pore sealing. Corrosion protection after pore sealing increased with anodizing time on pure Al, but only slightly increased with anodizing time on the Al alloys. [ABSTRACT FROM AUTHOR]

Vibrational spectroscopic features of a strong hydrogen (H) bonding network at the vapor/water interface are elucidated by using molecular dynamics (MD) simulation combined with quantum chemical calculations. The strong H-bonding coupling is properly described with quantum electronic effects, including charge transfer. By incoϕorating these effects in quantum mechanics/molecular mechanics calculations of water surface, we proved that the long-standing controversy on the low-frequency feature in the sum-frequency spectrum is naturally resolved. This feature originates from the significant anisotropic response of O-H vibrations in the H-bonding network at the surface. The anisotropy of the H-bonding network is also revealed in the MD result that the tangential Η bonds are stronger than the normal ones at the interface, which is the origin of the high surface tension of water. [ABSTRACT FROM AUTHOR]

Abstract: Lettuce is one of the most widely consumed leaf vegetables. In hydroponic the growth depends upon the composition of nutrient solution. Due to its nutrient absorption, the conductivity and pH suffer continuous variations. This paper describes the development of a system completely managed by a lab-made software. It monitors the conductivity and pH throughout 24h during the whole cycle of production. Also, allows adjust automatically any variation, through solenoid valves which dispense solutions of acid/base or nutrient. The efficiency of the proposed instrumentation was evaluated by simultaneously cultivation of same kind of lettuce (Vanda) in two different ways, hydroponics in greenhouse controlled with the developed devices, and grown conventionally in soil, adopted as referential. Agronomic and chemical parameters of commercial interest were analyzed for both crop, attesting the precocity in harvest (64 against 71days) with reduced labor, better control and higher productivity, especially in fresh and dry matter of aerial parts, presenting 267.56 and 13.33g plant−1 respectively, using the developed system. The data sequence regarding the concentration of nutrients for the automated hydroponic system was similar to those obtained by the mentioned researchers, as follows: K>N>Ca>P>Mg>S>Fe>Zn>Mn>Cu. This similarity highlights the efficiency of controlling the parameters of conductivity and pH in the instrumental system applied to hydroponics, offering the producer an effective and viable alternative in the production of lettuce. [Copyright &y& Elsevier]

The anionic derivative of the pharmaceutical compound 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) is known to deactivate the free radicals in biological systems by donating its excess electron. For the purpose to investigate the mechanism that the MCI-186 anion exhibits the antioxidative activity in aqueous solutions, we have performed a series of quantum mechanical/molecular mechanical (QM/MM) simulations based on the density functional theory in combination with the theory of energy representation (QM/MM-ER). For the computational convenience, MCI-186 has been modeled by 1,3-dimethyl-2-pyrazolin-5-one (DMP) by substituting the phenyl group in MCI-186 by a methyl one. We have applied the QM/MM-ER approach to compute free energy change δ G associated with the electron detachment from DMP anion in water. To make comparisons, we have also performed the simulations for a natural radical scavenger, ascorbic acid modeled by 3,4-dihydroxy-furan-2-one (DHF). In the QM/MM-ER approach, the distribution functions of the solute-solvent interaction energy, which serve as fundamental variables to describe the free energy, are to be constructed with the QM/MM force field. The free energy changes δ G were computed as 99.1, 108.3 kcal/mol for DMP and DHF anions, respectively, whereas that for hydroxyl anion OH taken as a reference system was evaluated as 138.9 kcal/mol. Thus, it was revealed that the free energies δ G for DMP and DHF anions are much smaller than that for hydroxyl anion, which directly indicates the high activities of the molecules as electron donors. We found that the small δ G values can be mainly attributed to the small values in the absolutes of the solvation free energies. The fractional charge analyses provided the evidence that the delocalization of the excess charge on the solute gives rise to the destabilization of these radical scavengers in the solute-solvent interaction. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [ABSTRACT FROM AUTHOR]

Crystal structures and dynamic rearrangements of one-dimensional coordination polymers with 4,4'-dipyridylsulfide (dps) have been studied. Reaction of Ni(NO3)2·6H2O with dps in EtOH yielded [Ni(dps)2(NO3)2]·EtOH (1), which had channels filled with guest EtOH molecules among the four Ni(dps)2 chains. This coordination polymer reversibly transformed the channel structure responding to temperature variations. Immersion of 1 in m-xylene released guest EtOH molecules to yield a guest-free coordination polymer [Ni(dps)2(NO3)2] (2a), which was also obtained by treatment of Ni(NO3)2·6H2O with dps in MeOH. On the other hand, removal of the guest molecules from 1 upon heating at 130 °C under reduced pressure produced a guest-free coordination polymer [Ni(dps)2(NO3)2] (2b). Although the 2a and 2b guest-free coordination polymers have the same formula, they showed differences in the assembled structures of the one-dimensional chains. Exposure of 2b to EtOH vapor reproduced 1, while 2a did not convert to 1 in a similar reaction. Reaction of Ni(NO3)2·6H2O with dps in acetone provided [Ni(dps)(NO3)2(H2O)]·Me2CO (4) with no channel structure. When MeOH or acetone was used as a reaction solvent, the [Ni(dps)2(NO3)2]·(guest molecule) type coordination polymer ,which was observed in 1, was not formed. Nevertheless, the reaction of Ni(NO3)2·6H2O with dps in MeOH/acetone mixed solution produced [Ni(dps)2(NO3)2]·0.5(MeOH·acetone) (5), which has an isostructural Ni-dps framework to 1. [ABSTRACT FROM AUTHOR]

Background/Aims: Xenon computed tomography (Xe-CT) is a noninvasive method of quantifying and visualizing tissue blood flow (TBF). For the liver, Xe-CT allows separate measurement of hepatic arterial and portal venous TBF. The present study evaluated the usefulness of Xe-CT as a noninvasive diagnostic procedure for measuring hepatic TBF in alcoholic liver cirrhosis (AL-LC), compared with liver cirrhosis related to nonalcoholic steatohepatitis (NASH), (NASH-LC), and hepatitis C virus (HCV), (C-LC). Methods: Xe-CT was performed on 22 patients with AL-LC, 7 patients with NASH-LC, and 24 patients with C-LC. Severity of LC was classified according to Child-Pugh classification. Correlations between hepatic TBF, Child-Pugh classification, and indocyanin green retention (ICG) rate after 15 minutes (ICG15R) were examined. Correlations of hepatic TBF in Child-Pugh class A to AL-LC, NASH-LC, and C-LC were also examined. Results: Portal venous TBF (PVTBF) displayed a significant negative correlation with Child-Pugh score and ICG15R ( r = −0.432, p < 0.01, r = −0.442, p < 0.01, respectively). Moreover, ICG15R displayed a significant positive correlation with Child-Pugh score ( r = 0.661, p < 0.001). Meanwhile, mean PVTBF and total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC ( p < 0.05). Mean PVTBF was significantly lower in Child-Pugh class A to AL-LC and NASH-LC than in that to C-LC ( p < 0.05). Similarly, mean THTBF was significantly lower in Child-Pugh class A to NASH-LC than in that to C-LC ( p < 0.05). Conclusions: Measurement of hepatic TBF using Xe-CT is useful as a noninvasive, objective method of assessing the state of the liver in chronic liver disease. [ABSTRACT FROM AUTHOR]

The reaction mechanism for the dehydration of 1,4-butanediol in hot water has been investigated by means of the hybrid quantum mechanical/molecular mechanical approach combined with the theory of energy representation (QM/MM-ER). We have assumed that the proton transfers along the hydrogen bonds of the water molecules catalyze the reaction, where the transition state (TS) forms a singlet biradical electronic structure. It has been revealed by the simulation that the biradical electronic state at the TS changes to zwitterionic structure in solution due to the hydration of the polar solvent. Such the electronic structure change gives rise to the substantial stabilization of the TS in hot water. As a result, the water-catalytic path becomes more favorable in aqueous solution than another possible path that proceeds without proton transfers as opposed to the reaction mechanism in the gas phase. Furthermore, the activation free energy computed by the present method is in excellent agreement with the experimental result. [ABSTRACT FROM AUTHOR]

Abstract: We investigate a singlet diradical molecule (2-borapropane-1,3-diyl) involving a B atom in an electron donor solvent, i.e., water, from the viewpoint of controlling the (hyper)polarizability through tuning the diradical character. The quantum chemical calculations for a model system reveal that a donation from the O lone pair electrons of a water molecule to the vacant p orbital of the B atom increases the diradical character, leading to a large variation in the (hyper)polarizability of the B-containing compound. The effect of the bulk solvent determined within the PCM scheme is also shown to increase the degree of enhancement of the second hyperpolarizability in the intermediate diradical regime of the B-containing compound. [Copyright &y& Elsevier]

Dietary potassium (K) deficiency is accompanied by phosphaturia and decreased renal brush border membrane (BBM) vesicle sodium (Na)-dependent phosphate (Pi) transport activity. Our laboratory previously showed that K deficiency in rats leads to increased abundance in the proximal tubule BBM of the apical Na-Pi cotransporter NaPi-Ila, but that the activity, diffusion, and clustering of NaPi-Ila could be modulated by the altered lipid composition of the K-deficient BBM (Zajicek HK, Wang H, Puttaparthi K, Halaihel N, Markovich D, Shayman J, Beliveau R, Wilson P, Rogers T, Levi M. Kidney mt 60: 694-704, 2001; Inoue M, Digman MA, Cheng M, Breusegem SY, Halaihel N, Sorribas V. Mantulin WW, Gratton E, Barry NP, Levi M. J Biol Chem 279: 49160-49171, 2004). Here we investigated the role of the renal Na-P cotransporters NaPi-lIc and PiT-2 in K deficiency. Using Western blotting, immunofluorescence, and quantitative real-time PCR, we found that, in rats and in mice, K deficiency is associated with a dramatic decrease in the NaPi-lIc protein abundance in proximal tubular BBM and in NaPi-lIc mRNA. In addition, we documented the presence of a third Na-coupled P, transporter in the renal BBM, PiT-2, whose abundance is also decreased by dietary K deficiency in rats and in mice. Finally, electron microscopy showed subcellular redistribution of NaPi-lIc in K deficiency: in control rats, NaPi-lIc immunolabel was primarily in BBM microvilli, whereas, in K-deficient rats, NaPiTIc BBM label was reduced, and immunolabel was prevalent in cytoplasmic vesicles. In summary, our results demonstrate that decreases in BBM abundance of the phosphate transporter NaPi-lIc and also PiT-2 might contribute to the phosphaturia of dietary K deficiency, and that the three renal BBM phosphate transporters characterized so far can be differentially regulated by dietary perturbations. [ABSTRACT FROM AUTHOR]

Recently, we reported a method for discriminating a Japanese brand of chicken, the Hinai-jidori. As an application of this method for discriminating Hinai-jidori eggs, we here report an efficient method for extracting maternal DNA from eggshells. Eggshell powder was completely decalcified with EDTA solution, and then DNA was isolated by conventional phenol-chloroform extraction and ethanol precipitation. The efficiency of DNA recovery from eggshells was 50-fold higher than that of a previously reported method. The recovered DNA could be used for PCR, and 10 markers for identifying the Hinai-jidori chicken were detected. The genotypes of the Hinai-jidori exactly matched those of the Hinai-dori breed. Using this method, Hinai-jidori and Hinai-dori eggs could be distinguished from the eggs of Rhode Island Reds. This is the first report of a technique that can be used to discriminate the eggs of Hinai-jidori from those of other chickens, and it can also be utilized to validate the labeling of Hinai-jidori eggs in the market. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cerebellar metastases are considered a negative prognostic factor in patients with systemic cancers. We retrospectively reviewed the treatment and outcome of 109 patients with cerebellar metastases. Methods: A total of 1240 patients with metastatic brain tumors were identified and treated between January 1990 and December 2005. Results: Cerebellar metastases occurred in 109 (8.7%) of these patients. The primary site of carcinoma was lung in 43 patients, breast in 24 patients, and gastrointestinal in 19 patients. Seventy-three (67.0%) patients underwent surgical resection; and of those patients, 27 (24.8%) also received WBRT. In 68 patients with high performance status (KPS >70), the median survival time (MST) after the diagnosis of brain metastasis was 22.1 months compared to 13.4 months in 41 patients with pretreatment KPS of <70. The MST for 38 patients who had surgical resection alone was 20.5 months compared to 35.5 months for those (n = 27) who had surgical resection followed by radiotherapy. Conclusions: Aggressive treatment including surgical resection and radiotherapy for patients and high performance status (KPS of at least 70) are associated with longer survival for selected patients with cerebellar metastases. [Copyright &y& Elsevier]