An accurate density functional theory based estimation of pK(a) values of polar residues combined with experimental data: from amino acids to minimal proteins

We report a scheme for estimating the acid dissociation constant (pK(a)) based on quantum-chemical calculations combined with a polarizable continuum model, where a parameter is determined for small reference molecules. We calculated the pK(a) values of variously sized molecules ranging from an amino acid to a protein consisting of 300 atoms. This scheme enabled us to derive a semiquantitative pK(a) value of specific chemical groups and discuss the influence of the surroundings on the pK(a) values. As applications, we have derived the pK(a) value of the side chain of an amino acid and almost reproduced the experimental value. By using our computing schemes, we showed the influence of hydrogen bonds on the pK(a) values in the case of tripeptides, which decreases the pK(a) value by 3.0 units for serine in comparison with those of the corresponding monopeptides. Finally, with some assumptions, we derived the pK(a) values of tyrosines and serines in chignolin and a tryptophan cage. We obtained quite different pK(a) values of adjacent serines in the tryptophan cage; the pK(a) value of the OH group of Ser13 exposed to bulk water is 14.69, whereas that of Ser14 not exposed to bulk water is 20.80 because of the internal hydrogen bonds.     

Redox-responsive conformational alteration of aromatic amides bearing N-quinonyl system

Redox-induced conformational alteration of N-aryl-N-phenylamides, in which the N-aryl group consists of a hydroquinone–p-quinone system, was examined. The reduced form bearing a dihydroxyphenyl or dimethoxyphenyl group exists mainly in the E-form, whereas the oxidized form bearing a N-benzoquinone moiety takes the Z-form both in the crystal and in solution. This redox-induced conformational alteration is associated with a marked change in optical properties. This system appears to have suitable properties for use in external redox stimulus-responsive functional switching.     

Andirolides H–P from the flower of andiroba (Carapa guianensis,Meliaceae)

Three new gedunins, an andirobin, three mexicanolides, and two phragmalin-type limonoids named andirolides H (1), I (2), J (3), K (4), L (5), M (6), N (7), O (8), and P (9) were isolated from an oil of the flower of Carapa guianensis Aublet (Meliaceae). Their structures including the absolute configurations were determined by means of the NMR and CD spectra as well as FABMS. Andirolide H (1) showed antimalarial activity against Plasmodium falciparum in vitro.     

Rupestines F-M, new guaipyridine sesquiterpene alkaloids from Artemisia rupestris

Eight new guaipyridine sesquiterpene alkaloids, rupestines F-M (1-8) were isolated from the leaves of Artemisia rupestris and their structures were elucidated on the basis of 2D-NMR data. The absolute configurations of 1-8 have been assigned by comparison of their experimental and calculated circular dichroism (CD) spectra.     

Diffusional kurtosis imaging of cingulate fibers in Parkinson disease: Comparison with conventional diffusion tensor imaging

Objective

The pathological changes in Parkinson disease begin in the brainstem; reach the limbic system and ultimately spread to the cerebral cortex. In Parkinson disease (PD) patients, we evaluated the alteration of cingulate fibers, which comprise part of the limbic system, by using diffusional kurtosis imaging (DKI).

Methods

Seventeen patients with PD and 15 age-matched healthy controls underwent DKI with a 3-T MR imager. Diffusion tensor tractography images of the anterior and posterior cingulum were generated. The mean kurtosis (MK) and conventional diffusion tensor parameters measured along the images in the anterior and posterior cingulum were compared between the groups. Receiver operating characteristic (ROC) analysis was also performed to compare the diagnostic abilities of the MK and conventional diffusion tensor parameters.

Results

The MK and fractional anisotropy (FA) in the anterior cingulum were significantly lower in PD patients than in healthy controls. The area under the ROC curve was 0.912 for MK and 0.747 for FA in the anterior cingulum. MK in the anterior cingulum had the best diagnostic performance (mean cutoff, 0.967; sensitivity, 0.87; specificity, 0.94).

Conclusions

DKI can detect alterations of the anterior cingulum in PD patients more sensitively than can conventional diffusion tensor imaging. Use of DKI can be expected to improve the ability to diagnose PD.     

Functional Changes in the Care-needing Elderly after Surface Electrical Stimulation to the Abdomen

Background: Strength of the trunk muscles is a key component of motor control, but it declines easily with the process of aging and/or disuse. Objectives: To investigate the effects of surface electrical stimulation (ES) to the abdominal muscles and the motor performance for care-needing elderly. Design: Controlled trial. Participants: Twenty-one elderly people (60–90 years) with care-needing, who were admitted to a nursing home or hospital for daily care and their score of Barthel Index had been stable from 55.3 ± 19.4 to 55.3 ± 19.8 during 3 months before intervention. Intervention: Common physical/occupational therapy was performed for all of the subjects during the study period. ES was applied to the abdomen of 15 subjects (ES group) twice a day for 8 weeks. Measurements: Functional measurements were performed before and after beginning of the study with some parameters as follows: grip strength; movement time for sitting up (MSU); maximum walking speed (WS). Results: No significant differences between two groups were noted for characteristics at baseline. In the ES group, MSU (from 21.1 ± 21.4 to 10.4 ± 8.3 sec) significantly improved (p < 0.05) after 8weeks. WS (from 17.7 ± 12.1 to 24.3 ± 15.3 m/min) were also improved (p < 0.05) after 8 weeks. Limitations: A limitation of this study was the small sample size. Conclusions: ES to the abdominal area has the potential to improve motor function in the care-needing elderly through reinforcement of the abdominal muscles.     

Moment maps associated with holomorphic isometric actions on K?hler manifolds

We give a new formula which writes down the moment map for holomorphic isometric action on a K?hler manifold using the motion of a charged particle when the action of is Hamiltonian.     

Molecularly imprinted solid-phase extraction for the selective determination of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs in human whole blood by gas chromatography-mass spectrometry

A novel method is described for the extraction of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxy-methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine, and 3,4-(methylenedioxyphenyl)-2-butanamine, from human whole blood using molecularly imprinted solid-phase extraction as highly selective sample clean-up technique. Whole blood samples were diluted with 10 mmol/L ammonium acetate (pH 8.6) and applied to a SupelMIP-Amphetamine molecularly imprinted solid-phase extraction cartridge. The cartridge was then washed to eliminate interferences, and the amphetamines of interest were eluted with formic acid/methanol (1:100, v/v). After derivatization with trifluoroacetic anhydride, the analytes were quantified using gas chromatography-mass spectrometry. Recoveries of the seven amphetamines spiked into whole blood were 89.1-102%. The limits of quantification for each compound in 200 μL of whole blood were between 0.25 and 1.0 ng. The maximum intra- and inter-day coefficients of variation were 9.96 and 13.8%, respectively. The results show that methamphetamine, amphetamine, and methylenedioxyphenylalkyl-amine designer drugs can be efficiently extracted from crude biological samples such as whole blood by molecularly imprinted solid-phase extraction with good reproducibility. This extraction method will be useful for the pretreatment of human samples before gas chromatography-mass spectrometry.     

Enhanced memory window of Au/BaTiO3/SrTiO3/Si(001) MFIS structure with high c-axis orientation for non-volatile memory applications

Metal?Cferroelectric?Cinsulator?Csemiconductor (MFIS) structures with BaTiO₃ (BTO) as a ferroelectric film and SrTiO₃ (STO) as an insulating buffer layer were fabricated on p-type Si(001) substrates using an ion beam sputter deposition technique. The effect of out-of-plane orientation on the electrical properties of the MFIS structures, including leakage current density and memory window behavior, were studied using the growth of the BTO ferroelectric film on Si substrate buffered by highly c-axis-oriented and random-oriented STO buffer layers. The experimental results show that the out-of-plane orientations of the BTO films were almost identical to those of the STO buffer layers. The MFIS structure with a high c-axis orientation exhibited a maximum clockwise capacitance-voltage memory window of 1.17?V with a low leakage current of 1.05×10^?7?A/cm² at an applied voltage of 4?V, which is a significant improvement compared to the MFIS structure with a random orientation. The difference in the electrical properties of the MFIS structures with both types of orientation is discussed in detail. The results obtained from this study indicate that the Au/BTO/STO/p-Si MFIS structure with high c-axis orientation has good potential for use in non-volatile memory applications.     

Coupling plasmons and dyakonons

We study the coupling of plasmons and Dyakonov surface waves propagating at the interfaces between isotropic-birefringent-metal layered structures. Efficient coupling is shown to occur with a proper choice of the crystal birefringence, the refractive index of the isotropic medium, and the light propagation direction relative to the crystal optical axis. In the case of low-loss metals, coupling efficiencies as high as 90% are predicted to be possible.