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Heterogeneous noble metal catalysts exhibit various functions. Although their redox functions have been extensively studied, we focused on their soft Lewis acid functions. Supported Au, Pt, and Pd catalysts electrophilically attack the π-electrons of soft bases such as alkynes, alkenes, and aromatic compounds to perform addition and substitution reactions. Hydroamination, intramolecular cyclization of alkynyl carboxylic acids, isomerization of allylic esters, vinyl exchange reactions, Wacker oxidation, and oxidative homocoupling of aromatics are introduced based on a discussion of the active species and reaction mechanisms. Furthermore, the adsorption of sulfur compounds, which are soft bases, onto the supported AuNPs is discussed. The adsorption and removal of 1,3-dimethyltrisulfane (DMTS), which is the compound responsible for the stale odor of "hine-ka" in alcoholic beverages, particularly Japanese sake, is described., (© 2023 The Chemical Society of Japan & Wiley-VCH GmbH.)

Fragment molecular orbital (FMO) method is a powerful computational tool for structure-based drug design, in which protein-ligand interactions can be described by the inter-fragment interaction energy (IFIE) and its pair interaction energy decomposition analysis (PIEDA). Here, we introduced a dynamically averaged (DA) FMO-based approach in which molecular dynamics simulations were used to generate multiple protein-ligand complex structures for FMO calculations. To assess this approach, we examined the correlation between the experimental binding free energies and DA-IFIEs of six CDK2 inhibitors whose net charges are zero. The correlation between the experimental binding free energies and snapshot IFIEs for X-ray crystal structures was R 2  = 0.75. Using the DA-IFIEs, the correlation significantly improved to 0.99. When an additional CDK2 inhibitor with net charge of -1 was added, the DA FMO-based scheme with the dispersion energies still achieved R 2  = 0.99, whereas R 2 decreased to 0.32 employing all the energy terms of PIEDA., (© 2022 Wiley Periodicals LLC.)

We propose a novel force-field-parametrization procedure that fits the parameters of potential functions in a manner that the pair distribution function (DF) of molecules derived from candidate parameters can reproduce the given target DF. Conventionally, approaches to minimize the difference between the candidate and target DFs employ radial DFs (RDF). RDF itself has been reported to be insufficient for uniquely identifying the parameters of a molecule. To overcome the weakness, we introduce energy DF (EDF) as a target DF, which describes the distribution of the pairwise energy of molecules. We found that the EDF responds more sensitively to a small perturbation in the pairwise potential parameters and provides better fitting accuracy compared to that of RDF. These findings provide valuable insights into a wide range of coarse graining methods, which determine parameters using information obtained from a higher-level calculation than that of the developed force field. © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc., (© 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.)

Simultaneous suppression of rice ( L.) uptake of As and Cd is challenging because these toxic elements are immobilized under contrasting redox conditions. Given the notion that oxygen diffusion governs redox conditions in temporarily drained paddy soil, we assume that the key to simultaneous suppression of dissolved As and Cd concentrations is air-filled porosity (AFP) of soil. The objectives of this study were to reveal relationships between AFP and dissolved As and Cd concentrations in paddy soils and to identify the optimum water management, in terms of AFP, for simultaneous reduction of As and Cd. Dissolved As and Cd concentrations were determined in soil cores collected at different depths and times during rice growing seasons. Dissolved As concentrations were appreciable (>3 µg L) only when AFP was below a threshold value of 0.04 to 0.10 m m, suggesting that dissolved As was rapidly immobilized once AFP exceeded the threshold value on drainage. Dissolved Cd concentrations were roughly proportional to AFP, with higher concentrations associated with lower soil pH. Although dissolved As concentrations tended to be low in soil samples with high dissolved Cd concentrations and vice versa, both concentrations were low when AFP was slightly above the threshold value for As immobilization. The results suggest that dissolved As and Cd can be simultaneously kept at low levels by appropriate water management practices that produce AFP slightly above the threshold value for As immobilization., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

Aims: Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear., Methods and Results: We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06-1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05-2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level., Conclusion: A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: The effectiveness of additional chemotherapy in preventing intrahepatic distant tumor recurrence of hepatocellular carcinoma (HCC) has not been fully established. The authors compared the efficacy of 2 platinum-based chemotherapeutic agents in combination with radical local treatment for preventing intrahepatic distant recurrence (IDR)., Methods: Seventy-eight patients with stage I/II HCC aged 45 to 85 years underwent transcatheter arterial chemoembolization and/or radiofrequency ablation after they received hepatic arterial infusion (HAI) of platinum compounds. The HAI consisted of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) in 25 patients and cis-diamminedichloroplatinum (II) (cisplatin) in 53 patients. Multivariate analysis was used to identify independent factors that were associated with IDR., Results: Cumulative IDR rates at 1 year, 2 years, and 3 years were 21.7%, 52.2% and 75.7%, respectively, in the carboplatin group and 8.1%, 22.7%, and 36.9%, respectively, in the cisplatin group. The cisplatin group had a significantly lower IDR rate compared with the carboplatin group. The selection of a platinum agent was 1 of the independent factors for IDR in a multivariate Cox proportional hazards model., Conclusions: HAI chemotherapy with cisplatin before radical local treatment was effective in patients with HCC. The authors concluded that radical local treatment with concurrent HAI using cisplatin may contribute to a longer progression-free period, which could be predicted with intrahepatic imaging in patients with stage I/II HCC., (Cancer 2011 © 2011 American Cancer Society.)

Background and Purpose: Dot-like low-intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted (-w) brain magnetic resonance imaging (MRIs) are frequently associated with cerebral small vessel disease (SVD), including deep intracerebral hemorrhages and lacunar infarctions. This study investigated how numbers of newly appeared dotHSs contribute to recurrent SVD., Methods: We prospectively analyzed numbers of newly appeared dotHSs in 12 patients with prior SVD (8 males, 4 females; mean 67.6 +/- 10.7 years old) readmitted with recurring SVD between October 2001 and March 2003. Numbers of appeared dotHSs per year were counted on T2*-w MRI scans after SVD recurrence and compared to previous MRIs. Seventy-one outpatients (35 males, 36 females; mean 64.3 +/- 9.6 years old) with histories of intracerebral hemorrhages (ICH) that came to the hospital during the study period served as controls. The hazard ratio (HR) for recurrence was estimated from a multivariate logistic regression model, using the number of appeared dotHSs (per year) and other risk factors., Results: Multivariate analyses revealed that an elevated rate of recurrence was found in patients with substantial numbers of appeared dotHSs (>or=5/year) (HR, 7.34; P= 0.0008). We also analyzed factors associated with the numbers of appeared dotHSs. A number of appeared dotHSs (>or=5/year) was significantly and independently associated with the initial number of dotHSs (>or=10) on T2*-w MRIs following the first SVD (HR, 18.6; P= 0.0001)., Conclusions: Though a small sample size limited the power of our analyses, our findings suggest that a number of newly appeared dotHSs may be associated with SVD recurrence.

Background and Purpose: Dot-like low intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted MRI have been histologically diagnosed to represent old cerebral microbleeds associated with microangiopathies. They have also been correlated to the fragility of small vessels and the tendency to bleed. Therefore, a substantial number of dotHSs might be associated with a large-sized, deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old microbleeds that did not enlarge to symptomatic size., Methods: To investigate how dotHSs are related to the size (maximal diameter) of primary deep ICH, we analyzed the diameter and the number of dotHSs in 151 patients with deep ICH not associated with subarachnoid hemorrhage or intraventricular hemorrhage (75 males and 76 females, age ranged from 37 to 90 [65.7 +/- 11.3 years old] who were consecutively admitted to Hakodate Municipal Hospital. The hazard ratio (HR) for a maximal diameter of deep ICH < or =2 cm was estimated, using the number of dotHSs and risk factors for stroke., Results: The number of dotHSs associated with the diameter < or =2 cm was 9.2 +/- 11.5, significantly larger than that with the diameter > or =2 cm (4.7 +/- 7.0, P= .012). Multivariate analysis revealed that a maximal diameter of deep ICH of < or =2 cm was found in patients with dotHS (HR, 3.7; 95% confidence interval [CI], 1.4-10.1; P= .009)., Conclusion: Though small sample size limited the power of our analyses, these findings suggest that the number of dotHSs may be associated with a small diameter of deep ICH.

Background and Purpose: Dotlike hemosiderin spots ongradient-echo T2(*)-weighted magnetic resonance imaging of the brain have been histologically diagnosed as old microbleeds associated with small vessel disease (SVD). The authors hypothesize that the presence of many dotHSs may be correlated with the fragility of small vessels and the recurrence of SVD, including lacunar infarction and deep intracerebral hemorrhage (ICH)., Methods: To investigate how dotHSs are related to past history of SVD, the number of subcortical or deep dotHSs was investigated in 146 patients with lacunar infarctions (95 men, 51 women, age 38 to 90 [66.6+/-9.4] years). They were divided into 2 subgroups according to history of deep ICHs or lacunar infarctions. The odds ratio (OR) for past history was estimated from logistic regression analyses with the number of subcortical or deep dotHSs as well as other factors., Results: Of 146 patients with lacunar infarctions, 11 had past symptomatic ICHs and 19 had past symptomatic lacunar infarctions. An elevated rate of history of ICH was found for lacunar infarction patients with many deep dotHSs (>or=3; OR, 9.1; 95% confidence interval, 1.6-51, P=.015). However, history of lacunar infarction was not significantly associated with the number of subcortical or deep dotHSs., Conclusions: Our findings suggest that many deep dotHSs on T2(*)-weighted magnetic resonance imaging may be correlated with deep ICH-lacunar infarction type of SVD recurrence but not lacunar infarction-lacunar infarction type.

Background and Purpose: Lipohyalinosis is considered an important cause of cerebral small vessel disease (SVD), including hypertensive intracerebral hematoma (ICH) and lacunar infarction. Dot-like low-intensity spots (dot-like hemosiderin spots [dotHSs]) on gradient-echo T2*-weighted (T2*-w) magnetic resonance imaging (MRI) have been histologically diagnosed as old microbleeds associated with microangiopathies (lipohyalinosis, amyloid angiopathy) and located in territories of perforating arteries (deep dotHSs) and subcortical regions (subcortical dotHSs). If dotHSs indicate the severity of lipohyalinosis, larger numbers of deep dotHSs may be associated with past history of SVD., Methods: The number of dotHSs was investigated in 213 patients with deep ICH (106 men, 107 women, 37 to 94 years old, mean age = 65.8 +/- 11.2 years). Patients were divided into 2 subgroups according to past history of SVD. Odds ratio (OR) for the history was estimated from logistic regression analyses of the number of deep or subcortical dotHSs, as well as other factors., Results: Of 213 patients, 36 had a past history of SVD (symptomatic deep ICH in 18, symptomatic lacunar infarction in 17, and both in 1). An increased rate of history of SVD was found for patients with subcortical dotHSs. The OR per 1 subcortical dotHS was 1.09 (95% confidence internal (CI), 1.03-1.17; P =.005), and per deep dotHS, the OR was 1.07 (95% CI, 1.00-1.13; P =.039)., Conclusions: The findings suggest that deep and subcortical dotHSs on T2*-w MRI may indicate the severity of microangiopathy and may predict recurrence of SVD in patients with deep ICH.

De novo design programs such as LEGEND, LUDI, and LeapFrog can identify novel structures that are predicted to fit the active site of a target protein. However, in the conventional de novo design strategy, the output structures obtained from the programs can be problematic with regard to synthetic accessibility and binding affinity prediction. Thus it has been practically difficult to obtain novel lead compounds that are appropriate for medicinal chemists through the de novo design strategy. Since the late 1990s, several new strategies for lead identification have been reported and the successful examples have been disclosed. One of the strategies is validation of small fragments, which can be substructures of de novo ligands, by using NMR, X-ray, or MS spectra. Another method is prioritization of output structures obtained from de novo design programs by chemical accessibility. This review describes these new strategies with practical applications and future perspectives of de novo design., (Copyright 2003 Wiley Periodicals, Inc.)

The authors observed dotlike, low-intensity spots in T2*-weighted magnetic resonance imaging (MRI), subsequently diagnosed histologically as previous microbleeds associated with lipofibrohyalinosis, amyloid angiopathy, and small vessel disease. The nature of dotlike hemosiderin spots (dotHSs), however, is still unknown. This case report seeks to demonstrate the dynamics of dotHSs associated with an intracerebral hematoma (ICH). T2*-weighted MRI of a 72-year-old man with a history of hypertension demonstrated 4 dotHSs 24 months after a left putaminal hemorrhage. Follow-up T2*-weighted MRI 40 months after the acute event demonstrated the asymptomatic formation of 3 more dotHSs, even with good control of blood pressure. Fifty months after the stroke, T2*-weighted MRI showed that 2 of the new dotHSs had become fainter, whereas the hemosiderin associated with the ICH scar remained detectable. To the authors' knowledge, this is the first description of dotHS dynamics associated with ICH.

Solid-state CD spectroscopy can provide valuable information on conformation, intermolecular interactions, including chirality induction, and enantioselective reactions which occur specifically in the solid state. The technique can, however, suffer from serious artifacts. Some examples of solid-state CD are given and potential artifacts are discussed. Copyright 2000 Wiley-Liss, Inc.

The efficacy and safety of intrapleural LC9018 (Yakult Co. Ltd., Tokyo, Japan) with or without doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) were evaluated in a randomized, controlled trial performed in 95 patients with malignant pleural effusions secondary to lung cancer. Seventy-six patients were eligible for the assessment of efficacy. The response rate for treatment with intrapleural doxorubicin plus LC9018 (38 patients) was 73.7%, which was significantly higher than the response rate of 39.5% for the control group treated with doxorubicin alone (38 patients) (P less than 0.01). The LC9018 group also showed a significantly greater improvement in performance status (PS) and symptoms (chest pain, chest discomfort, and anorexia) than the control group (P less than 0.05). A significant prolongation of survival was noticed in the LC9018 group (P less than 0.05). The main side effects of LC9018 were fever and transient hepatic dysfunction, but there were no serious adverse reactions. These results suggest that the intrapleural instillation of LC9018 can be recommended for the treatment of malignant pleural effusions.