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Background: We investigated the efficacy and safety of twice‐daily bilayer sustained‐release tramadol hydrochloride tablets (35% immediate‐release; 65% sustained‐release) in patients with postherpetic neuralgia. Methods: This was a Phase III treatment‐withdrawal study with 1–4‐week dose‐escalation, 1‐week fixed‐dose, and 4‐week randomized, double‐blind, placebo‐controlled withdrawal periods performed at 43 medical institutions in Japan. Patients aged ≥20 years, ≥3 months after the onset of herpes zoster with localized, persistent pain despite fixed‐dose analgesics for ≥2 weeks before enrollment were eligible. Patients started tramadol at 100 mg/day and its dose escalated to a maximum of 400 mg/day to achieve a reduction in their Numeric Rating Scale (NRS) for pain of ≥2 points. Eligible patients were randomized to continue tramadol or switched to placebo for 4 weeks (double‐blind period). Patients were withdrawn due to inadequate analgesia (NRS deteriorated on ≥2 consecutive days) or their request. Results: Overall, 252 patients started tramadol and 173 were randomized (tramadol: 85; placebo: 88). Tramadol was superior to placebo for the primary endpoint (time from randomization to an inadequate analgesic effect) with log‐rank test p = 0.0005. The hazard ratio was 0.353 (95% confidence interval 0.190–0.657) in favor of tramadol and fewer patients in the tramadol group experienced inadequate analgesic effects (16.9% vs. 39.8%). Adverse events in ≥10% of patients in the open‐label period were constipation (43.8%), nausea (34.9%), somnolence (18.5%), and dizziness (11.6%). The frequencies of adverse events in the double‐blind period were similar in both groups. Conclusion: Sustained‐release tramadol tablets with an immediate‐release component are effective and well tolerated for managing postherpetic neuralgia. [ABSTRACT FROM AUTHOR]

The homopolymerization of ethene (ET), propene (PP), 1-butene (BT), 1-hexene (HX), and styrene (ST) by the rac-[Zr{1-Me2Si(3-Pr-(η5-C9H5))(3-H-(η5-C9H5))Cl2}] ansa-zirconocene catalyst was investigated using Density Functional Theory (DFT) calculations. This study unveiled the following: (i) ansa-zirconocene is a regio- and stereoselective catalyst for PP, BT, HX, ST polymerization; (ii) the regio- and stereoselectivities depend on the orientation of the growing chain and the incoming olefin monomers; (iii) primary (1,2)-insertion is preferred over secondary (2,1)-insertion for linear olefins (PP, BT, and HX) while it is the opposite for ST; (iv) the activity of olefin polymerization by ansa-zirconocene is controlled by the thermodynamics of π-complex formation and the kinetics of insertion. Our results revealed that the regio- and stereoselectivity of the catalyst can be described by the steric interaction between the incoming monomer and the isobutyl group of the growing chain. For ET polymerization, the effect of the catalyst structure on the productivity of the process was examined and QSPR models were constructed based on experimental activities and theoretical calculations. The model suggests that potent ansa-zirconocene catalysts should have a lower dipole moment and a more positive charge on the Zr metal atom. This information will provide clues for the design of more potent ansa-zirconocene catalysts for ethylene polymerization. [ABSTRACT FROM AUTHOR]

To investigate the transport mechanism of MeV protons in tapered glass capillaries, spatially resolved energy spectra were measured for proton microbeams focused by 20-μm-outlet capillaries having various taper angles. Three-dimensional Monte Carlo (MC) simulations were also performed to support the experiments and trace each particle in the capillary in more detail. The dependence of the proton energy distribution on the outgoing angle proved that the capillary-focused proton beam consists of two different components, protons traveling straight through the capillary without colliding with the capillary wall and protons scattered by the capillary inner wall. Moreover, the focusing effect of the tapered glass capillary was found to be mainly due to the scattered beam component. The MC simulations well reproduced the experimental results and showed that beam focusing ratios of 1.6-2.4 are possible with capillaries having a convex inner wall. The flight distance of the scattered proton in the capillary glass body was found to play an important role in determining transport efficiency of the protons through the capillary. [ABSTRACT FROM AUTHOR]

The SAC(symmetry adapted cluster)/SAC-CI method is applied to the calculations of the ground, excited, and ionized states of the free base porphin. The electronic spectrum of porphin is well reproduced and new assignments for the B (Soret), N, L, and M bands are proposed. The present result shows that the four-orbital model is strongly perturbed for the B and N bands by the excitations from the lower 4b1u MO and that the σ electron correlations are important for the description of the excited states. The absorption peaks in the ionization spectrum are assigned and the reorganization effect is found to be large especially for the n and σ electron ionizations. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Highly active bifunctional metalloporphyrin catalysts were developed for the coupling reaction of epoxides with CO2 to produce cyclic carbonates. The bifunctional catalysts have both quaternary ammonium halide groups and a metal center. To elucidate the roles of these catalytic groups, DFT calculations were performed. Control reactions using tetrabutylammonium halide as a catalyst were also investigated for comparison. In the present article, the results of our computational studies are overviewed. The computational results are consistent with the experimental data and are useful for elucidating the structure-activity relationship. The key features responsible for the high catalytic activity of the bifunctional catalysts are as follows: 1) the cooperative action of the halide anion (nucleophile) and the metal center (Lewis acid); 2) the near-attack conformation, leading to the efficient opening of the epoxide ring in the rate-determining step; and 3) the conformational change of the quaternary ammonium cation to stabilize various anionic species generated during catalysis, in addition to the robustness (thermostability) of the catalysts. [ABSTRACT FROM AUTHOR]

A platinum-catalyzed amide reduction through hydrosilylation with 1,2-bis(dimethylsilyl)benzene (BDSB) was investigated on a theoretical basis. While the platinum-catalyzed hydrosilylation of alkenes is well known, that of carbonyl groups rarely occurs. The only exception involves the use of bifunctional hydrosilanes having dual, closely located Si–H groups, which accelerate the hydrosilylation of carbonyl groups, leading to successful reduction of amides to amines under mild conditions. In the present study, we determined through density functional theory calculations that the platinum-catalyzed hydrosilylation of the C=O bond proceeds via a Pt(iv)-disilyl-dihydride intermediate with an associated activation energy of 29.6 kcal mol−1. Although it was believed that the hydrosilylation of carbonyl groups does not occur via the classical Chalk–Harrod cycle, the computational results support a mechanism involving the insertion of the amide C=O bond into a Pt–H bond. This insertion readily occurs because a Pt–H bond in the Pt(iv)-disilyl-dihydride intermediate is highly activated due to the strong σ-donating interaction of the silyl groups. The modified Chalk–Harrod mechanism that occurs preferentially in rhodium-catalyzed hydrosilylation as well as the ionic outer sphere mechanism associated with iridium-catalyzed amide reduction were both safely ruled out as mechanisms for this platinum-catalyzed amide reduction, because of the unexpectedly large activation barrier (＞40 kcal mol−1) for the Si–O bond formation. [ABSTRACT FROM AUTHOR]

On March 11, 2011, Japan’s northeast Pacific coast was hit by a gigantic earthquake and subsequent tsunami. Soma City in Fukushima Prefecture is situated approximately 44 km north of Fukushima Daiichi Nuclear Power Plant. Soma General Hospital is the only hospital in Soma City that provides full-time otolaryngological medical care. We investigated the changes in new patients from one year before to three years after the disaster. We investigated 18,167 new patients treated at our department during the four years from April 1, 2010 to March 31, 2014. Of the new patients, we categorized the diagnoses into Meniere’s disease, acute low-tone sensorineural hearing loss, vertigo, sudden deafness, tinnitus, and facial palsy as neuro-otologic symptoms. We also investigated the changes in the numbers of patients whom we examined at that time concerning other otolaryngological disorders, including epistaxis, infectious diseases of the laryngopharynx, and allergic rhinitis. The total number of new patients did not change remarkably on a year-to-year basis. Conversely, cases of vertigo, Meniere’s disease, and acute low-tone sensorineural hearing loss increased in number immediately after the disaster, reaching a plateau in the second year and slightly decreasing in the third year. Specifically, 4.8% of patients suffering from these neuro-otologic diseases had complications from depression and other mental diseases. With regard to new patients in our department, there was no apparent increase in the number of patients suffering from diseases other than neuro-otologic diseases, including epistaxis, and allergic rhinitis. Patients suffering from vertigo and/or dizziness increased during the first few years after the disaster. These results are attributed to the continuing stress and tension of the inhabitants. This investigation of those living in the disaster area highlights the need for long-term support. [ABSTRACT FROM AUTHOR]

In this work, we tested a setup of X-ray fluorescence (XRF) excited by proton-induced quasi-monochromatic X-rays (proton-induced XRF (PIXRF)) as a low-radiation dose analytical technique for precious cultural heritage samples. The low-dose performance of the PIXRF is experimentally assessed in comparison with the performance of a conventional XRF. For this assessment, we prepared test samples, which simulated original Japanese paintings with copper-bearing pigments. By introducing a figure-of-merit, the PIXRF is found to potentially give a better performance in terms of the radiation dose to the sample and the limit of detection, albeit the degraded multi-elemental analytical capability. PIXRF can be a cost-effective method to perform low dose measurements of precious samples, if introduced in an existing PIXE facility. [ABSTRACT FROM AUTHOR]

Aim To clarify the association between nutritional status and the prevalence of geriatric conditions in dependent older adults. Methods A cross-sectional observational study of dependent older adults aged 65years or older who were living either in the community ( n = 511, mean age 81.2years) or in nursing homes ( n = 587, mean age 85.2years) was carried out. Data included the participants' demographic characteristics, basic activities of daily living, Charlson Comorbidity Index and the prevalence of eight geriatric conditions (visual impairment, hearing impairment, falls, bladder control problems, cognitive impairment, impaired mobility, swallowing disturbance and loss of appetite). Nutritional status was assessed by the Mini Nutritional Assessment short form ( MNA-SF). Results Of 1098 participants, 21.4% ( n = 235) were categorized as 'malnourished', according to the MNA-SF classification. Participants in the 'malnourished' group had a greater number of geriatric conditions than those in the other two groups. A higher prevalence of all the geriatric conditions except for falls was detected in the group with poorer nutritional status. Multivariate logistic regression analysis showed that malnutrition was associated with the number of geriatric conditions, but not with that of comorbidities, even after controlling for confounders. Conclusions Malnutrition was confirmed to have significant associations with geriatric conditions in dependent older adults. Geriatr Gerontol Int 2014; 14: 198-205. [ABSTRACT FROM AUTHOR]

Abstract: Beam focusing properties of cone optics were systematically investigated by Monte Carlo simulations under various combinations of beam and cone parameters. To optimize the cone optic design for accelerator-driven WDM experiments, the beam intensity gains after cone focusing were evaluated from the simulation results as functions of cone wall material and shape parameters such as taper angle and wall curvature. The uniformity of the cone-focused beam was also examined by considering not only various cone parameters but also the cases involving the misalignment of the cone optic. From the results, a parabolic gold cone was found to be the best choice at least for relatively light ions such as lithium having MeV energies. It is also found that although smaller taper angle improves the total beam transport efficiency in the optic, it brings more difficulties in the alignment of the optic because the alignment accuracy should be less than a half of the taper angle to obtain acceptable uniformity in the beam energy deposition on the target. [Copyright &y& Elsevier]

We establish a new generating theorem of even triangulations of the projective plane using an operation called a Q 4 -reduction. That is, every even triangulation of the projective plane can be obtained from one of the Q 4 -irreducible even triangulations, which contains a special subgraph named a projective-triangular cupola (or simply PTC) as its subembedding, by a sequence of Q 4 -expansions. By the result, we show that the set of (P 4 , Q 4) -irreducible even triangulations coincides with that of (P , Q) -irreducible ones on the projective plane as well as the spherical case. However, we show that the property does not hold in general for the other closed surfaces. [ABSTRACT FROM AUTHOR]

Abstract: Solvatochromic effect in proteins and solutions was described by a configuration interaction singles (CIS) wave function with fragment-localized molecular orbitals. Coarse-grained analysis indicated that the CI wave function can be described by local excitations and charge-transfer (CT) excitations between the chromophore and the environment. We developed an atomic-orbital direct runcated CIS code and applied the excited states of retinal chromophore in bacteriorhodopsin and MeOH environments, and those of s-trans-acrolein in water. Number of excitation operators was significantly reduced by eliminating the CT excitations between the environmental fragments. The truncated CIS wave functions reproduced the original excitation energies very well. [Copyright &y& Elsevier]

Purpose: To develop a general strategy for optimizing monoclonal antibody (MAb) formulations. Methods: Colloidal stabilities of four representative MAbs solutions were assessed based on the second virial coefficient ( B) at 20°C and 40°C, and net charges at different NaCl concentrations, and/or in the presence of sugars. Conformational stabilities were evaluated from the unfolding temperatures. The aggregation propensities were determined at 40°C and after freeze-thawing. The electrostatic potential of antibody surfaces was simulated for the development of rational formulations. Results: Similar B values were obtained at 20°C and 40°C, implying little dependence on temperature. B correlated quantitatively with aggregation propensities at 40°C. The net charge partly correlated with colloidal stability. Salts stabilized or destabilized MAbs, depending on repulsive or attractive interactions. Sugars improved the aggregation propensity under freeze-thaw stress through improved conformational stability. Uneven and even distributions of potential surfaces were attributed to attractive and strong repulsive electrostatic interactions. Conclusions: Assessment of colloidal stability at the lowest ionic strength is particularly effective for the development of formulations. If necessary, salts are added to enhance the colloidal stability. Sugars further improved aggregation propensities by enhancing conformational stability. These behaviors are rationally predictable according to the surface potentials of MAbs. [ABSTRACT FROM AUTHOR]

The excitation energy transfer (EET) between a fluorescent resonance energy transfer (FRET) pair, cyan fluorescent protein chromophore (CFPc)/ green fluorescent protein chromophore (GFPc), is used for measuring molecular proximity in experimental studies. In this article, the role of the bridging protein media has been investigated using the quantum chemical calculations for the EET electronic coupling. We adopted a model peptide connecting GFPc and CFPc, a GFPc-X-CFPc model, and examined the X (amino acids) dependence. The major part of the EET coupling element arises from the direct interaction between GFPc and CFPc via the Förster mechanism. The magnitude of the through-X interactions vary for the type of residues. The contribution of the X was, however, at most 10% of the total value. Together with the contributions from through-peptide and charge-transfer types, X gives minor modifications to the total coupling via the super-exchange mechanism. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: The nature of π-conjugated wire is characterized by the decay constant β of electron tunneling. To evaluate the decay constant, intramolecular magnetic exchange interaction was calculated by density functional theory for organic biradicals: nitronyl nitroxide and verdazyl were chosen for the radical substituent and oligophenylene and oligo(phenylene ethynylene) were chosen for the wire. For phenylene and phenylene ethynylene units, β was calculated to be 0.42Å−1 and 0.24Å−1, respectively, and the β value was independent of radical species. The obtained β values are in good agreement with the experimental value of the molecular tunneling conductance. [Copyright &y& Elsevier]

The aim of this report is to describe the long-term hearing prognosis of the transmastoid trans-superior semicircular canal approach. Three patients with small petrous bone cholesteatoma of the supralabyrinthine type removed by partial removal of the superior semicircular canal (SSCC) were followed up for 13, 9, and 10 years, respectively. All patients showed good bone conduction hearing during the follow-up period without postoperative complications, including longstanding disequilibrium causing a reduction in the quality of life. As an approach to petrous bone cholesteatoma of supralabyrinthine type that occupies a small area medial to the SSCC, the transmastoid trans-superior semicircular canal approach is less invasive and is considered to be a recommended approach. [ABSTRACT FROM AUTHOR]

Abstract: Three patients with a middle ear malformation characterized by the absence of the oval window and complicated by facial nerve anomalies were treated by surgery. Hearing ability of all the patients was improved. A variety of facial nerve anomalies were observed. Fenestration of the vestibule above the facial nerve was performed in the case of 2 of the 3 patients. In the other patient, fenestration of the scala vestibuli below the facial nerve was performed. In the case of all the 3 patients, hearing ability improved after the surgery and remained stable for a long time. Surgery for this disease has been considered difficult because of a high risk of complications. Because all the 3 patients showed excellent long-term surgical results, we suggest that fenestration of the inner ear should be considered one of the main options for the management and treatment of an absent oval window associated with facial nerve anomalies. [Copyright &y& Elsevier]

The kinetics of carbamate formation from the reaction of carbon dioxide with α-amino acids in D2O was first investigated by means of nuclear magnetic resonance spectroscopy. Potassium carbonate was used as the CO2 source. For each amino acid, the maximum carbamate yield, the apparent rate constant for the carbamate formation kapp, and the rate constants for the formation k1 and the breakdown k−1 of the carbamate were estimated. Plots of log k1 or log k−1 versus p Ka of amino acids indicated that the formation rate k1 increased with the basicity (p Ka) of amino acid, while the decomposition rate k−1 decreased. A Brϕnsted β value of 0.39 was obtained from the former plot, being in good agreement with the previously reported ones (0.26-0.43). The observed negative p Ka dependence of log k−1 (Brϕnsted α = 0.34) is reasonable, because the carbamate decomposition is acid-catalyzed and the steady-state concentration of H+ should be higher for weaker basic amines. The charge (σ) and the lone-pair energy ( EN) at the nitrogen atom of the amino group were calculated. Although log k1 correlated with σ and EN, log k−1 was unrelated with both of these parameters. Considering that the carbamate formation ( k1) is not only base-catalyzed but should also be promoted by the nucleophilicity of the amino nitrogen, its correlation with σ and EN in addition to p Ka is rational. The irrelevance of log k−1 to σ and EN is not surprising, because σ and EN are not a direct measure of [H+] of the solution. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In visual information processing, feedforward projection from primary to secondary visual cortex (V1-to-V2) is essential for integrating combinations of oriented bars in order to extract angular information embedded within contours that represent the shape of objects. For feedback (V2-to-V1) projection, two distinct types of pathways have been observed: clustered projection and diffused projection. The former innervates V1 domains with a preferred orientation similar to that of V2 cells of origin. In contrast, the latter innervates without such orientation specificity. V2 cells send their axons to V1 domains with both similar and dissimilar orientation preferences. It is speculated that the clustered feedback projection has a role in contour integration. The role of the diffused feedback projection, however, remains to be seen. We simulated a minimal, functional V1-V2 neural network model. The diffused feedback projection contributed to achieving ongoing-spontaneous subthreshold membrane oscillations in V1 cells, thereby reducing the reaction time of V1 cells to a pair of bars that represents specific angular information. Interestingly, the feedback influence took place even before V2 responses, which might stem largely from ongoing-spontaneous signaling from V2. We suggest that the diffusive feedback influence from V2 could act early in V1 responses and accelerate their reaction speed to sensory stimulation in order to rapidly extract angular information. [ABSTRACT FROM AUTHOR]

Purpose: To investigate relationship between second virial coefficient B and viscosity and aggregation propensity of highly concentrated monoclonal antibody (MAbs) solutions. Methods: Intermolecular interactions of 3 MAbs solutions with varying pH were characterized according to B estimated by analytical ultracentrifugation sedimentation equilibrium with initial loading concentrations <10 mg/mL. Viscosity measurements and stability assessments of MAb solutions at concentrations higher than 100 mg/mL were conducted. Results: B of all MAb solutions depended on solution pH and have qualitative correlation with viscosity and aggregation propensity. The more negative the B values, the more viscous the solution, acquiring increased propensity to aggregate. Solutions with B values of ~2 × 10 mL·mol/g acquire similar viscosity and aggregation propensity regardless of amino acid sequences; for solutions with negative B values, viscosity and aggregation propensity differed depending on sequences. Results suggest attractive intermolecular interactions represented by negative B values are influenced by surface properties of individual MAbs. Conclusions: B can be used, within certain limitations, as an effective indicator of viscosity and aggregation propensity of highly concentrated MAb solutions. [ABSTRACT FROM AUTHOR]

Abstract: The performance of a compact micro-PIXE system using a tapered glass capillary for beam focusing was examined with the help of Monte-Carlo simulations. The effective beam spot size was evaluated by an edge-scanning method and a two-dimensional element mapping was successfully demonstrated by using a copper fine-mesh target. The spatially resolved energy-spectrum measurement revealed that even protons scattered at the inner wall of the capillary have kinetic energies enough to induce the X-ray emission in the target. Monte-Carlo simulations showed that the beam-focusing factors of the capillaries used in this study are about 1.7. The uniformity of the beam does not depend so much on the distance from the capillary outlet, but the beam radius was found to be twice larger than its original size even at 1mm from the capillary outlet, which was consistent with the effective beam spot size measurement. [Copyright &y& Elsevier]

Quantum chemical calculations were performed to analyze the excited states and the redox potentials of a recently synthesised fluorine-containing porphycene, 2,7,12,17-tetraethyl-3,6,13,16-tetrakis(trifluoromethyl) porphycene. The reduction and oxidation potentials of the porphycenes measured by cyclic voltammetry were semiquantitatively reproduced using density-functional theory (DFT) and polarizable continuum model calculations, in which solvent effect and basis-sets extension effect were indispensable. Symmetry-adapted cluster configuration interaction and time-dependent (TD) DFT calculations were performed to analyze the visible region of the absorption spectra, and the results were in good agreement with the experimental data. The results of the calculations showed that both structural distortion and electronic effects cause specifically large stabilization of the LUMO level and become the origin of the particularly large positive-side shift of the reduction potential and the red-shift in the Q band absorption. [ABSTRACT FROM AUTHOR]

Abstract: A molecular-orbital (MO) localization scheme for peptide molecules has been proposed. Combining the minimum orbital deformation (MOD) and population localization methods, the present scheme produces MOs localized within predefined fragment regions. Because the transformed MOs become similar to externally-introduced reference MOs, we can introduce MO representations commonly used in chemistry. Calculated Löwdin populations and overlap integrals showed that the extent of localization was satisfactory. The transformed MOs were applied to the configuration interaction singles (CIS) calculations. The results clearly showed that the chemically-intuitive MO localization simplified not only one-electron orbitals, but also the structure of the excited-state wave functions. [Copyright &y& Elsevier]

Therapeutic antibodies often suffer from degradation due to various modifications during storage. We detected a degradation of immunoglobulin gamma 1 (IgG1) stored for 6 month at 40 °C, and identified the modification as the racemization of Cys220 in the hinge sequence S219CDKTHT225 of the heavy chain by tryptic peptide mapping and tandem mass spectrometry. The rate of racemization at Cys220 was enhanced deliberately by incubating the protein at 50 °C and pH 9.0, while all the other cysteine residues were not affected. The racemization of Cys220 was confirmed by mass spectrometry in conjunction with extracted ion chromatography of the tryptic digest of IgG1 forced to degrade in D2O and a series of synthetic hinge fragments containing d-amino acid, as well as the detection of d-cysteine in the acid hydrolysate. To rationalize the possible relationship between the racemization of Cys220 and isopeptide formation at the neighboring residue of Asp221, we suggest a new reaction mechanism that assumes a base catalyst to initiate these reactions by activating the amide nitrogen of Lys222. Due to the highly flexible nature of the hinge region, Lys222 can participate in either the formation of a cyclic imidazoline intermediate involving the α-carbonyl carbon of Cys220 to facilitate the racemization of Cys220 or that of a succinimide structure leading to the isomerization of Asp221. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the study was to examine the effect of informal care levels on overall discontinuation of living at home, all-cause death, hospital admission, and long-term care placement for community-dwelling older people using various community-based services during a 3-year period. Prospective cohort study of 1582 community-dwelling disabled elderly and paired informal caregivers was conducted. Baseline data included the recipients and caregivers’ demographic characteristics, comorbidities, informal care levels (sufficient, moderate, and insufficient care), which were evaluated by trained visiting nurses, and the level of formal community-based service use. Among 1582 participants, 97 died at home, 692 were admitted to hospitals, 318 died during their hospital stay, and 117 were institutionalized in long-term care facilities during 3 years of follow-up. A multivariate Cox hazard model demonstrated that when compared with a sufficient informal care level, an insufficient informal care level was associated with overall discontinuation of living at home, all-cause mortality, hospitalization, and institutionalization during 3 years of follow-up (hazard ratio: 1.65, 95% confidence interval: 1.15–2.36; 1.98, 1.17–3.34; 1.56, 1.04–2.35; 2.93, 1.25–6.86, respectively). The results suggested that informal caregiving is an important factor in the prevention of overall discontinuation of living at home in a population of disabled older people. [Copyright &y& Elsevier]

Abstract: Objectives: To clarify the clinical risk factors that aggravate deep neck infection. Patients and methods: Sixty-five patients with deep neck infection (abscess or cellulitis), 42 males and 23 females, who were treated at the ear, nose, and throat department in Iwaki Kyoritsu General Hospital in the past 10 years, were retrospectively reviewed. Cases of inflammation of the upper airway including the oral cavity, laryngopharynx, palate tonsil and salivary gland, and cases of lymphadenitis were investigated. These patients were divided into five localized types and one wide range type according to the abscess locations as follows: oral cavity floor type, upper deep cervical type, submandibular type, submental type, retropharyngeal type, and wide range type. Results: Seventeen of the 65 patients had diabetes, and significantly more diabetics had the wide range type than the localized type (P <0.05, Fisher''s test). Diabetes complication was more often seen in the upper deep cervical type among patients aged 61 years or older, and in the wide range type among males aged 41 years or older and elderly women aged 61 years or older. No patients with odontogenic infection or sialolithiasis had associated diabetes mellitus. Two cases developed mediastinitis, and one was caused by retrotonsillar abscess and needed thoracic drainage. More than half of the wide range type cases and more than a quarter of each of the localized type cases except the upper deep cervical type also had laryngeal edema, and eight of them needed emergency tracheotomy. Thirteen of the 40 cases had bacteria belonging to the Streptococcus milleri group (SMG), and all were detected in patients who underwent surgical drainage. Four of the 13 cases where SMG was detected showed drug resistance to some sorts of antibiotics. Conclusion: Oral disorders can develop deep neck infection independently of the presence of diabetes mellitus, compared with other causes. The presence of diabetes mellitus is associated with deep neck infection, aggravating parotitis and wide spread of inflammation. Retrotonsillar abscess often spreads to the retropharyngeal and parapharyngeal spaces, causing mediastinitis, so caution is necessary. Infection due to SMG tends to form abscess independently of diabetes mellitus. Since more than half of the wide range type and more than a quarter of each of the localized types except the upper deep cervical type were associated with laryngeal edema, airway management should be considered. [Copyright &y& Elsevier]

Abstract: We present a procedure to overcome the quasi-degeneracy problem in the CCSD and SACSD methods. A multi-configuration bra state in the SACSD equations (MRbra-SACSD equation) together with a second-order perturbation correction gives quantitatively correct potential curves for bond dissociations. The benchmark results for HF, F2, and H2O show that the perturbative triple correction reduces the deviations from Full-CI energies to within 3mHartree (1.9kcal/mol). Within the benchmark calculations, the results of the present method are comparable with the recent post-CCSD corrections, the CR-CCSD(T) and CCSD(2) T methods, and are slightly less accurate than the CR-CC(2,3) method. [Copyright &y& Elsevier]

Abstract: Numerous risk factors of falls, including urinary incontinence and behavioral symptoms have been identified among elderly people in long-term care settings. However, it remains uncertain whether incontinence or behavioral symptoms are associated with recurrent falls and injurious falls. The purpose of this research was to examine the association between various types of falls and urinary incontinence or behavioral symptoms among the residents of long-term care facilities using the Cox proportional hazards models. The participants were 1082 older people (327 men and 755 women) who were admitted to facilities between 1 April 2003 and 31 March 2004. Fall experience, urinary incontinence, and behavioral symptoms were followed for up to 6 months or until death or discharge. The functional status, comorbidity, and prescribed medications were determined at the baseline. Multivariate analysis revealed that urinary incontinence and behavioral symptoms were independent risk factors of falls during the follow-up period. However, urinary incontinence was a risk factor for recurrent falls but not for injurious falls. In contrast, behavioral symptoms were an independent risk factor for injurious but not for recurrent falls. The results suggested that treatment or management of urinary incontinence and behavioral symptoms should be considered to prevent falls in long-term care settings. [Copyright &y& Elsevier]

In this article, we present the multicore (mc) QM/MM method, a QM/MM method that can optimize the structure of chromophore aggregate in protein. A QM region is composed of the sum of the QM subregions that are small enough to apply practical electronic structure calculations. QM/MM energy gradient calculations are performed for each QM subregion. Several benchmark examinations were carried out to figure out availabilities and limitations. In the interregion distances of more than 3.5–4.0 Å, the mcQM/MM energy gradient is very close to that obtained by the ordinary QM/MM method in which all the QM subregions were treated together as a single QM region. In van der Waals complex, the error exponentially drops with the distance, while the error decreases slowly in a hydrogen bonding complex. On the other hand, the optimized structures were reproduced with reasonable accuracy in both cases. The computational efficiency is the best advantage in the mcQM/MM approach, especially when the QM region is significantly large and the QM method used is computationally demanding. With this approach, we could optimize the structures of a bacterial photosynthetic reaction center protein in the ground and excited states, which consists of more than 14,000 atoms. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009 [ABSTRACT FROM AUTHOR]

Abstract: Electrostatic interactions between firefly oxyluciferin and the surrounding proteins were analyzed, and the amino acids important for controlling emission energy were identified. We propose Arg223Ala, Glu344Ala, and Asp422Ala mutations in firefly oxyluciferase of Photinus pyralis, which artificially change the luminescence color by tuning the electrostatic effect from the luciferase proteins. In the theoretical mutation simulation, the emission energy of the triple mutant was estimated to be 2.05eV (602nm, reddish-orange), which is 0.18eV lower than that of the wild type (2.23eV, 557nm, yellow–green). For calculating the emission energies, we used the symmetry-adapted cluster-configuration interaction (SAC-CI) method. [Copyright &y& Elsevier]

Abstract: The chemical denaturation of Pseudomonas aeruginosa cytochrome c 551 variants was examined at pH 5.0 and 3.6. All variants were stabilized at both pHs compared with the wild-type. Remarkably, the variants carrying the F34Y and/or E43Y mutations were more stabilized than those having the F7A/V13M or V78I ones at pH 5.0 compared with at pH 3.6 by ~3.0–4.6 kJ/mol. Structural analyses predicted that the side chains of introduced Tyr-34 and Tyr-43 become hydrogen donors for the hydrogen bond formation with heme 17-propionate at pH 5.0, but less efficiently at pH 3.6, because the propionate is deprotonated at the higher pH. Our results provide an insight into a stabilization strategy for heme proteins involving variation of the heme electronic state and introduction of appropriate mutations. [Copyright &y& Elsevier]

Abstract: A compact micro-beam system, containing a tapered glass capillary tube with a tip diameter on the order of 10μm, was constructed to examine the applicability of capillary-generated micro-beams to high-contrast radiography based on proton-induced quasi-monochromatic X-rays. The transport efficiency of swift protons (2–3MeV) through the capillary was examined as a function of the capillary tilt angle and the capillary tip diameter. We obtained transport efficiencies of approximately three times larger than would be expected from the geometrical shape of the capillary. This enhancement indicates that a focusing effect occurred in the capillary. A metallic thin foil was irradiated with the micro-beam and quasi-monochromatic X-rays were produced. By calculating the X-ray yields induced by proton bombardment in the foil and comparing them with the X-ray counts observed at the detector, the throughput efficiency of the X-ray imaging system was evaluated. We demonstrated magnification radiography of a small object to show that a spatial resolution on the order of 10μm was achievable in our system. [Copyright &y& Elsevier]

Excited states of fluorescent proteins were studied using symmetry-adapted cluster-configuration interaction (SAC-CI) method. Protein-environmental effect on the excitation and fluorescence energies was investigated. In green fluorescent protein (GFP), the overall protein-environmental effect on the first excitation energy is not significant. However, glutamine (Glu) 94 and arginine (Arg96) have the red-shift contribution as reported in a previous study (Laino et al., Chem Phys 2004, 298, 17). The excited states of GFP active site (GFP-W22-Ser205-Glu222-Ser65) were also calculated. Such large-scale SAC-CI calculations were performed with an improved code containing a new algorithm for the perturbation selection. The SAC-CI results indicate that a charge-transfer state locates at 4.19 eV, which could be related to the channel of the photochemistry as indicated in a previous experimental study. We also studied the excitation and fluorescence energies of blue fluorescent protein, cyan fluorescent protein, and Y66F. The SAC-CI results are very close to the experimental ones. The protonation state of blue fluorescent protein was determined. Conformation of cyan fluorescent protein indicated by the present calculation agrees to the experimentally observed structure. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [ABSTRACT FROM AUTHOR]

The present research was intended to determine the suitability of the CALUX assay as a screening method for dioxins in fish oil used as a feed ingredient in Japan. Alteration of TEQ in fish oil according to newly proposed toxic equivalency factors (TEF) is also discussed. In the analysis, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in 41 fish oil samples were determined by using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) and CALUX bioassay. The mean TEQ values derived from 1998 WHO-TEF of PCDD/Fs and DL-PCBs were 2.6 and 9.9pgg−1 (ww), respectively. The levels of TEQ derived from the recently re-evaluated 2005 WHO-TEF were slightly lower than those of the former in both groups. Notably, the contribution of mono-ortho DL-PCBs to total 2005 WHO-TEQ was considerably decreased compared to the case of 1998 WHO-TEQ, resulting from the reduction in its TEF values, while the non-ortho DL-PCBs contribution was increased. The mean TEQ determined by CALUX assay for PCDD/Fs was approximately three times higher, whereas DL-PCBs was approximately two times lower than WHO-TEQ determined by HRGC/HRMS; the sum of PCDD/Fs and DL-PCBs was very similar by both methods. The correlation coefficients of TEQ between the CALUX assay and HRGC/HRMS analysis were 0.84, 0.89, and 0.90 for PCDD/Fs, DL-PCBs, and the sum, respectively. These results suggest that the CALUX assay is a very useful method for the screening of dioxin-related compounds in fish oils. [Copyright &y& Elsevier]

The yellow-green luminescence from firefly luciferase has long been understood to be the emission from enol-oxyluciferin. However, a recent experiment showed that an oxyluciferin constrained to the keto form produced a yellow-green emission in luciferase (Branchini, B. R.; Murtiashaw, M. H.; Magyar, R. A.; Portier, N. C.; Ruggiero, M. C.; Stroh, J. G. J. Am. Chem. Soc. 2002, 124,2112-2113). The present quantum mechanical/molecular mechanical and symmetry-adapted cluster-configuration interaction (SAC-Cl) theoretical study supports the keto-form to be the yellow-green bioluminescence state in luciferase. We give the theoretically optimized structure of the excited state of oxyluciferin within luciferase, which gives luminescence calculated by the SAC-Cl method that is close to the experimental value. Coulombic interactions with neighboring residues, in particular Arg218 and the phosphate group of AMP, play important roles in the color-tuning mechanism. Transformation to the enol form is energetically unfavorable in the luciferase environment. The twisted intramolecular charge-transfer (TICT) state is meta stable and would be easily relaxed to the co-planer structure. Further analyses were performed to verify the spectral-tuning mechanism based on the protonation state and the resonance structure of oxyluciferin. [ABSTRACT FROM AUTHOR]

Abstract: We developed a thin-foil-discharge (TFD) plasma target for beam–plasma interaction experiments. A discharge current of several tens of kilo-amperes rapidly heated and ionized a thin aluminum foil of sub- to several micrometers thick. The target areal density seen by projectiles was expected to be almost constant during several hundred nanoseconds from the ignition of the discharge because the size of the thin foil was chosen to be much larger than the cross-section of the incident beam. The optical observation of the plasma using a fast framing camera showed that the TFD plasma expanded one-dimensionally in the early stage of the discharge. We determined the plasma density and temperature from the observed plasma thickness and the deposited electrical power with equation-of-state data. A one-dimensional plasma expansion model was developed and used to examine the expected plasma parameters under various initial conditions. We also performed beam–plasma interaction experiments with fully stripped ions of . The energy loss of silicon ions was measured as a function of time by the TOF method. [Copyright &y& Elsevier]

Abstract: The excited states of a flavin-related compound, lumiflavin, were studied by the symmetry-adapted cluster (SAC)-configuration interaction (CI) method. The absorption peaks observed in the experimental spectrum were theoretically assigned. Transition energy of some low-lying n–π* states were obtained. The energy minimum structures of the first singlet and triplet excited states were calculated by the SAC-CI method. The structural changes upon excitation were at most 0.05Å. The solvation effect on the absorption energy in aqueous solution was investigated using polarizable continuum model (PCM) and by including water molecules into the computational model. The solvatochromic shift of the second peak (31A′ state) originates from both microscopic (hydrogen bonding) and macroscopic (electronic polarization of solvent) solvation effects. [Copyright &y& Elsevier]

Abstract: The MEG (multi-exponentially generated)/EX (excited)-MEG method, which is a multi-reference version of the SAC (symmetry-adapted cluster)/SAC-CI (configuration interaction) method, has been applied to the valence excited and ionized states of ozone that has a quasi-degenerate bi-radical nature in its ground state. The MEG/EX-MEG result shows a remarkable improvement over the single-reference SAC/SAC-CI general-R one in both the correlation energy and the ionization potential. The present results were compared with the previous theoretical and experimental data. The theoretical ionization spectrum reproduced the experimental spectrum observed from outer- to inner-valence regions (∼28eV). This is the first report that gives a theoretical interpretation up to a high-energy region. [Copyright &y& Elsevier]

Abstract: Color-tuning mechanism of Human-Blue pigment, visual color-receptor in the cone cells of the eye, has been investigated. Based on a previous Homology-modeling structure and experimental evidences, a working model was constructed, and the structure has been optimized by QM(B3LYP)/MM(AMBER) method. SAC-CI calculation was performed to obtain photo-absorption energy. The calculated absorption energy reasonably agrees with the experiment. A decomposition analysis was performed and compared with the case of Bovine rhodopsin. The electrostatic effect from the opsin is primarily important for the color-tuning. The electronic interaction (quantum effect) of the counter-residue is indispensable for quantitative calculation of the absorption energy. [Copyright &y& Elsevier]

Based on our previous study for the O2 binding of the Fe–Por complex, this study investigates the O2 binding mechanism in the Fe–porphyrin isomers, Fe–porphycene (FePc), and Fe–corrphycene (FeCor) complexes. By calculating the potential energy surface of the O2 binding, the present study explains the reason for the dramatic increase of O2 affinities observed in the FePc complex. In the case of FeCor–O2, the O2 binding process includes the intersystem crossing from a triplet to singlet state, as in the FePor–O2 complex. However, FePc–O2 uses only a singlet surface. This is because the ground state of the FePc complex in the deoxy state is a triplet state, while those of FePor and FeCor are a quintet state. Such difference originates from character of the SOMO. We estimated an equilibrium constant for the O2 binding that reasonably reproduced the trend observed in the experiments. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1363–1372, 2006 [ABSTRACT FROM AUTHOR]

Abstract: Symmetry-adapted cluster–configuration interaction (SAC–CI) method was applied to calculate electronic CD spectrum of a nucleoside, uridine. Based on the theoretical CD and absorption spectra, the observed peaks in the experimental spectra were assigned. The excited states of uracil, the base part of uridine, were also calculated for comparison. The origin of CD rotational strength for the low-lying π–π∗ and n–π∗ excited states was analyzed. Rotational strength of the π–π∗ transition depends on the magnitude of the electric and magnetic transition dipole moments, while that of the n–π∗ originates from the angle between the two transition moments. [Copyright &y& Elsevier]

Conclusions. Quality of hearing is one of the key conditions promoting habitual sniffing associated with closing failure of the Eustachian tube and sniffing may stop with deterioration of hearing due to progression of the disease. Objective: To examine habitual sniffing associated with closing failure of the Eustachian tube and hearing level in patients with cholesteatoma. Patients and methods. A total of 171 patients with middle ear cholesteatoma treated in Tohoku University Hospital (106 sides in 101 patients, 63 males and 38 females, mean age 43.3 years), and Sendai Ear Surgi Center (70 sides in 70 patients, 37 males and 33 females, mean age 42.7 years) were included. The patients were divided into two groups based on the presence or absence of habitual sniffing, and pre- and postoperative hearing was compared between the two groups. Results. Habitual sniffing was not found in patients with air conduction hearing level worse than 60 dB or air–bone gap larger than 40 dB. Habitual sniffing disappeared in all patients with expanded air–bone gaps in lower frequency regions after surgery. [ABSTRACT FROM AUTHOR]

Summary: Reliable synaptic transmission depends not only on the release machinery and the postsynaptic response mechanism but also on removal or degradation of transmitter from the synaptic cleft. Accumulating evidence indicates that postsynaptic and glial excitatory amino acid transporters (EAATs) contribute to glutamate removal. However, the role of presynaptic EAATs is unclear. Here, we show in the mouse retina that glutamate is removed from the synaptic cleft at the rod to rod bipolar cell (RBC) synapse by presynaptic EAATs rather than by postsynaptic or glial EAATs. The RBC currents evoked by electrical stimulation of rods decayed slowly after pharmacological blockade of EAATs. Recordings of the evoked RBC currents from EAAT subtype-deficient mice and the EAAT-coupled anion current reveal that functional EAATs are localized to rod terminals. Model simulations suggest that rod EAATs are densely packed near the release site and that rods are equipped with an almost self-sufficient glutamate recollecting system. [Copyright &y& Elsevier]

Electronic mechanism of the reversible O2 binding by heme was studied by using Density Functional Theory calculations. The ground state of oxyheme was calculated to be open singlet state [Fe(S =1/2) + O2(S = 1/2)]. The potential energy surface for singlet state is associative, while that for triplet state is dissociative. Because the ground state of the O2+ deoxyheme system is triplet in the dissociation limit [Fe(S = 2) + O2(S = 1)], the O2 binding process requires relativistic spin-orbit interaction to accomplish the intersystem crossing from triplet to singlet states. Owing to the singlet-triplet crossing, the activation energies for both O2 binding and dissociation become moderate, and hence reversible. We also found that the deviation of the Fe atom from the porphyrin plane is also important reaction coordinate for O2 binding. The potential surface is associative/dissociative when the Fe atom locates in-plane/out-of-plane. © 2006 Wiley Periodicals, Inc. J Comput Chem 4: 426–433, 2006 [ABSTRACT FROM AUTHOR]

Abstract: p-Octyloxyphenylmethanethiol and p-dodecylbenzenethiol were prepared as new odorless organosulfur reagents. Thiosugars and thioglycosides were synthesized using these reagents without encountering any malodorous procedures. [Copyright &y& Elsevier]

Abstract: The SAC-CI and QM/MM methods were applied to calculations of the absorption peaks of the five retinal proteins, bovine rhodopsin (Rh), bacteriorhodopsin (bR) in BR, K, and KL states, and sensory rhodopsin II (sRII). The results nicely agree with the experimental excitation energies and provided an insight into the mechanism of the large blue shifts in Rh and sRII from BR: geometric distortion in Rh and protein electrostatic effect in sRII. These results indicate that the present approach is useful for studying the excitation spectra and the mechanism of the color tuning in the retinal proteins. [Copyright &y& Elsevier]

This paper discusses evaluation of the concentration of stomach wall fold patterns by using abdominal X-ray CT images. It has been noted that most stomach cancers are accompanied by concentration of folds at the pathological site. Consequently, if the extent of concentration can be represented quantitatively on the basis of an image, it will help with quantitative diagnosis of stomach cancer and make it possible to reduce the labor of image reading. Evaluation of the concentration of stomach wall folds reduces to the problem of evaluating the concentration in a line figure on a curved surface. The paper proposes, as the first step, a new method of calculation of the concentration by combining the local projection of the curved surface figure and the conventional two-dimensional concentration index calculation. Then, using this method, a procedure for stomach cancer site detection from abdominal CT images is developed. The method is applied to two real cases of cancer accompanied by fold concentration, and it is verified that a high concentration index is obtained at the cancer site. The result is significant because it demonstrates for the first time the possibility of quantitative diagnosis of stomach cancer from three-dimensional CT images. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 88(9): 48–57, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20207 [ABSTRACT FROM AUTHOR]

Abstract: Phytochrome, an important photoreceptor in green plants, contains a cofactor, phytochromobilin, which shows photo-isomerization to respond as a sensor of light. The SAC-CI method was applied to the absorption spectra of several structural isomers of phytochromobilin and successfully identified the structure of the key isomers, Pr and Pfr forms which have long been discussed. The Pr and Pfr forms of the phytochromobilin are identified to be ZZZasa and ZZEass isomers, respectively, in their protonated forms. The results also indicated that the structures of the lumi-R and meta-Ra forms, the intermediates during the photochemical cycle, would be ZZEasa isomers. [Copyright &y& Elsevier]

This paper presents a method for extracting stomach wall fold regions from abdominal X-ray CT images using three-dimensional morphology operations. The phenomenon of stomach wall folds concentrating in the direction of lesions is observed in over 60% of stomach cancer patients. Thus, the running pattern of stomach wall folds is an important clue in diagnosing stomach cancer. The method proposed in this paper is composed of three steps of preliminary processing, fold enhancement, and fold extraction and uses three-dimensional top-hat transformation which is a kind of light-dense morphology operations in the enhancement step. Better results than those obtained in the past have been obtained by applying the proposed procedure to nine cases of actual CT images. In addition, effects of differences in imaging environments on the extraction results have been studied in samples in which the body positions during imaging and the amounts of the foaming medium administered orally had been varied. The results obtained provide important findings on the possibility of diagnosing stomach cancer using three-dimensional CT images. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 87(2): 37–46, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10214 [ABSTRACT FROM AUTHOR]