Prediction of low-frequency structure-borne sound in concrete structures using the finite-difference time-domain method.

Due to limitations of computers, prediction of structure-borne sound remains difficult for large-scale problems. Herein a prediction method for low-frequency structure-borne sound transmissions on concrete structures using the finite-difference time-domain scheme is proposed. The target structure is modeled as a composition of multiple plate elements to reduce the dimensions of the simulated vibration field from three-dimensional discretization by solid elements to two-dimensional discretization. This scheme reduces both the calculation time and the amount of required memory. To validate the proposed method, the vibration characteristics using the numerical results of the proposed scheme are compared to those measured for a two-level concrete structure. Comparison of the measured and simulated results suggests that the proposed method can be used to simulate real-scale structures.

Effects of microphone mounting location and gender on accuracy in speech recognition using a throat microphone.

Speech recognition using air-conduction microphones is less accurate under high noise conditions and when the volume of the speaker's voice is relatively low. In this study, the effect of mounting location of throat microphones (which are less susceptible to ambient noise) on recognition accuracy was experimentally investigated. The results confirmed that mounting position and speaker gender affected recognition accuracy, regardless of any other factor or speech recognition system. In addition, relatively lower recognition accuracy was observed in the upper part of the neck near the mandibular angle for both males and females.

Evaluation of eustachian tube function using a portable device.

The present paper investigates a portable eustachian-tube-function testing device by sonotubometry based on pure-tone sound transmission via the eustachian tube (ET). The measured results obtained by the proposed method were validated through comparison with the existing testing technique based on broadband sound inspection. The measurement results for the ET opening time (Topen) and the sound pressure difference in the ear canal between open and closed ETs (ΔL) obtained using pure-tone sounds with tonal frequency components of 7.0 and 9.5 kHz generally agreed with the results obtained by the existing technique with broadband testing sound.

Desickling of sickled erythrocytes by pulsed radio-frequency field.

Electric fields were found to deform sickled erythrocytes. When the intensity of applied fields exceeded a threshold value, sickled erythrocytes transformed into a spherical shape. Prolonged application of the field usually caused hemolysis of erythrocytes. Deformation of red blood cells could be partly reversed if the field was turned off at an early stage. The cause of desickling may be the interaction of the field with the erythrocyte membrane and also with gelled intracellular hemoglobin S molecules.

Human sickle hemoglobin in transgenic mice.

DNA molecules that contain the human alpha- and beta s-globin genes inserted downstream of erythroid-specific, deoxyribonuclease I super-hypersensitive sites were coinjected into fertilized mouse eggs and a transgenic mouse line was established that synthesizes human sickle hemoglobin (Hb S). These animals were bred to beta-thalassemic mice to reduce endogenous mouse globin levels. When erythrocytes from these mice were deoxygenated, greater than 90 percent of the cells displayed the same characteristic sickled shapes as erythrocytes from humans with sickle cell disease. Compared to controls the mice have decreased hematocrits, elevated reticulocyte counts, lower hemoglobin concentrations, and splenomegaly, which are all indications of the anemia associated with human sickle cell disease.

Synthesis of functional human hemoglobin in transgenic mice.

Human alpha- and beta-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human beta-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human alpha- and beta-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease.

First report of hepatobiliary Mycobacterium avium infection developing obstructive jaundice in a patient with neutralizing anti-interferon-gamma autoantibodies.

This study describes a patient who experienced hepatobiliary Mycobacterium avium infection associated with neutralizing anti-interferon gamma (IFN-γ) autoantibodies during treatment for disseminated M. avium disease. Hepatobiliary M. avium infection should be considered in jaundiced patients with neutralizing anti-IFN-γ autoantibodies, including those receiving antimycobacterial therapy for disseminated M. avium disease.

Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process.

Syntaxin-1 is a component of the synaptic vesicle docking and/or membrane fusion soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex (7S and 20S complexes) in nerve terminals. Syntaxin-1 also forms a heterodimer with Munc18/n-Sec1/rbSec1 in a complex that is distinct from the 7S and 20S complexes. In this report, we identify a novel syntaxin-1-binding protein, tomosyn, that is capable of dissociating Munc18 from syntaxin-1 and forming a novel 10S complex with syntaxin-1, soluble N-etyhlmaleimide-sensitive factor attachment (SNAP) 25, and synaptotagmin. The 130 kDa isoform of tomosyn is specifically expressed in brain, where its distribution partly overlaps with that of syntaxin-1 in nerve terminals. High level expression of either syntaxin-1 or tomosyn results in a specific reduction in Ca2+-dependent exocytosis from PC12 cells. These results suggest that tomosyn is an important component in the neurotransmitter release process where it may stimulate SNARE complex formation.

Insulin delivery with FlexPen: dose accuracy, patient preference and adherence.

The introduction of insulin pens has helped improve adherence in Type 1 or 2 diabetes, and reduce inaccurate dosing, fear of injection, and social embarrassment associated with vial and syringe. This report presents the published evidence base for the accuracy, patient preference and economic evaluation of one prefilled pen, FlexPen (Novo Nordisk A/S, Bagsvaerd, Denmark) and discusses recent changes to the design of this pen. Primary research publications that included the study of FlexPen were identified from various sources. Several studies have shown that FlexPen delivers high, medium and low doses of insulin significantly more accurately than vial and syringe, SoloStar (sanofi-aventis, Paris, France) or OptiClik (sanofi-aventis, Paris, France). Patients have also found FlexPen easier to use than vial and syringe. A Next Generation FlexPen has been developed, which maintains the demonstrated accuracy of FlexPen and is accompanied by a reduced injection force for simpler and more comfortable use, and clear colour scheme for insulin type to avoid medication errors.

Modification of the hepatic mitochondrial proteome in response to ischemic preconditioning following ischemia-reperfusion injury of the rat liver.

BACKGROUND/AIM: Ischemic preconditioning (IPC) may reduce hepatic ischemia-reperfusion (IR) injury, but efficacy of IPC on mitochondrial proteome is not demonstrated. We investigated how IPC modifies the mitochondrial proteome after IR injury. METHODS: Rats were subjected to 25 min of portal triad crossclamping (IR group, n = 8). In the IPC group (n = 8), 10 min of temporal portal triad clamping was performed before 25 min of portal clamping. Samples were obtained after 24 h. The mitochondrial inner-membrane potential was measured by the uptake of a lipophilic cationic carbocyanine probe and mitochondrial proteome was also investigated using 2-dimensional differential in-gel electrophoresis and liquid chromatography-tandem mass spectrometry. RESULTS: Mitochondrial inner-membrane potential and glutathione were lower and serum transaminase was higher in the IPC group than in the IR group. The mitochondrial precursor of aldehyde dehydrogenase 2 and alpha-methylacyl-CoA-racemase were upregulated in the IPC group in comparison to the IR group. In contrast, protein disulfide-isomerase A3 precursor, 60S acid ribosomal protein P0, carbonic anhydrase 3 and superoxide dismutase were significantly more downregulated in the IPC group than in the IR group. CONCLUSIONS: A hepatoprotective effect by IPC was not shown; however, IPC caused significant up- or downregulation of several mitochondrial proteins.

Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital.

BACKGROUND: Little is known about the clinical characteristics and health-related quality of life (HQOL) of elderly patients with pulmonary Mycobacterium avium complex (pMAC) disease. OBJECTIVES: To evaluate HQOL using the 36-Item Short-Form Health Survey and St George's Respiratory Questionnaire (SGRQ) and to investigate the predictors of HQOL changes among elderly patients with pMAC disease. METHODS: This prospective cohort registry was conducted at Keio University Hospital, Tokyo, Japan, between May 2012 and July 2015 and included 84 patients with pMAC disease aged 75 years who had completed the HQOL questionnaire and 48 patients with pMAC disease who had been followed up and completed the HQOL questionnaire in cross-sectional and longitudinal analyses, respectively. RESULTS: In cross-sectional analyses, elderly patients with pMAC disease had significantly lower role-physical, general health, vitality, social functioning, role-emotional and role/social component scores than the general Japanese elderly population. Analysis of covariance revealed that patients with cavitary lesions had significantly worse physical functioning and SGRQ scores (P < 0.05). Longitudinal analysis showed that under-treatment, short duration of disease and positive sputum smear at baseline were predictors of worse HQOL at 12 months. CONCLUSIONS: Elderly patients with pMAC disease have reduced HQOL. Further large studies on HQOL are required to refine the use of this parameter in the treatment of these patients.

Effect of cetiedil on cation and water movements in erythrocytes.

Cetiedil is a potential antisickling agent whose major effect appears to be at the erythrocyte membrane. To test the hypothesis that cetiedil alters cation transport, we studied the effect of the drug in promoting changes in cell water (Wc), cell sodium (Nac), and cell potassium (Kc). Results are quite different depending on the presence or near absence of intracellular ATP. With fresh cells, 100 microM cetiedil causes little in the net cation or water movements compared with control cells incubated for 2 h. At cetiedil concentrations greater than 100 microM, however, net movements of sodium and potassium increase considerably, and cell swelling results from a net Nac gain that exceeds a net Kc loss. All water movements can be accounted for by cetiedil-induced net cation movements. When 100 microM ouabain is added along with cetiedil, net Nac gain, net Kc loss, and net Wc gain are all increased compared with results obtained with cetiedil alone. External calcium inhibits cetiedil-induced changes in cation transport. With cells depleted of their ATP, cetiedil inhibits the typical potassium loss that occurs in the presence of external calcium; net sodium uptake changes little under these conditions, regardless of the presence or absence of external calcium. Our findings indicate a complex mode of action for cetiedil on the erythrocyte membrane, and support the hypothesis that the erythrocyte membrane, and support the hypothesis that the antisickling effect of the drug observed in vitro results from dilution of intracellular hemoglobin secondary to net salt and water gain.

Denatured hemoglobin in sickle erythrocytes.

To study the nature of numerous inclusion bodies seen in red cells from patients with sickle cell disease (Hb SS), we have prepared red cell ghosts free of oxyhemoglobin and analyzed them by spectrophotometric and heme extraction methods. The absorption spectrum in the visible region of the ghost suspensions was typical of hemichromes. The spectrum was similar to that of denatured hemoglobin repared by treatment of oxyhemoglobin S with mechanical shaking or heat. Similar treatment of cells containing only normal hemoglobin (Hb AA) showed a very small amount of denatured hemoglobin, approximately one-fifth of the amount in Hb SS cells. The amount of denatured hemoglobin determined after solution of membrane with 2.5% sodium dodecyl sulfate was 0.158+/-0.070% (1 SD) of the total cellular heme in Hb SS patients. In controls, the amount was 0.030+/-0.016%. Persons with Hb AA and reticulocytosis did not have an elevated amount of membrane-associated heme. In patients with hereditary spherocytosis and autoimmune hemolytic anemia, denatured stromal hemoglobin was normal or slightly elevated before and after splenectomy. The increased amount of denatured hemoglobin in Hb SS red cells may be related to the instability of sickle oxyhemoglobin.

Measurement of radical-scavenging ability in small bowel ischemia/reperfusion injury in rats using an in vivo and ex vivo electron paramagnetic resonance technique.

Reperfusion of ischemic tissues results in the formation of toxic reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals, hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, fully capable of damaging cellular membranes by lipid peroxidation. In this study, we applied for the first time the in vivo electron paramagnetic resonance (EPR)/spin probe and ex vivo EPR technique to provide direct evidence of ROS following experimentally induced small bowel ischemia/reperfusion (I/R) injury. The decay rate (spin clearance rate) was determined over the first 3 minutes at 6 hours after reperfusion. Decay rates in rats subjected to I/R injury were lower than those in the sham group. Superoxide scavenging activity (SSA) in rats subjected to I/R injury was significantly lower than that in the sham group. In conclusion, this study demonstrated that it is possible to detect the accumulation of ROS following experimentally induced small intestine I/R injury using an in vivo and an ex vivo EPR technique with a spin probe.

Protective effects of MnM2Py4P and Mn-salen against small bowel ischemia/reperfusion injury in rats using an in vivo and an ex vivo electron paramagnetic resonance technique with a spin probe.

BACKGROUND: Reperfusion of ischemic tissues results in the formation of toxic reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals, hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, capable of damaging cellular membranes by lipid peroxidation. In the present study, we applied an in vivo electron paramagnetic resonance (EPR)/spin probe and an ex vivo EPR technique to provide direct evidence of ROS following experimentally induced small bowel ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: We used a rat model of small bowel I/R injury to explore the possibility that MnM2Py4P or Mn-salen can prevent the accumulation of ROS species following experimentally induced I/R injury. We examined the ability of MnM2Py4P and Mn-salen to scavenge radicals in living Sprague-Dawley (SD) rats using an in vivo and an ex vivo EPR technique with a spin probe. RESULTS: The CP decay rates in the MnM2Py4P- and Mn-salen-treated rats were significantly higher than those in the untreated rats and almost equal to those in sham group rats. There were no significant differences between the MnM2Py4P-treated group and the Mn-salen-treated group. Superoxide scavenging activities (SSA) in the MnM2Py4P- and EUK-8-treated group were higher than those in the untreated group and almost equal to the sham group. CONCLUSION: The present study suggested that the protective effects of MnM2Py4P and Mn-salen against small bowel IR injury were mediated by the inhibition of O2, H2O2, and NO production.

Isolation and characterization of a novel actin filament-binding protein from Saccharomyces cerevisiae.

We purified a novel actin filament (F-actin)-binding protein from the soluble fraction of Saccharomyces cerevisiae by successive column chromatographies by use of the 125I-labeled F-actin blot overlay method. The purified protein showed a minimum Mr of about 140 kDa on SDS-polyacrylamide gel electrophoresis and we named it ABP140. A search with the partial amino acid sequences of ABP140 against the Saccharomyces Genome Database revealed that the open reading frame of the ABP140 gene (ABP140) corresponded to YOR239W fused with YOR240W by the +1 translational frame shift. The encoded protein consisted of 628 amino acids with a calculated Mr of 71,484. The recombinant protein interacted with F-actin and showed the activity to crosslink F-actin into a bundle. Indirect immunofluorescence study demonstrated that ABP140 was colocalized with both cortical actin patches and cytoplasmic actin cables in intact cells. However, elimination of ABP140 by gene disruption did not show a deleterious effect on cell growth or affect the organization of F-actin. These results indicate that ABP140 is not required for cell growth but may be involved in the reorganization of F-actin in the budding yeast.

Interaction of serum albumin with normal and sickle hemoglobins.

The stability of oxyhemoglobin S during mechanical shaking was enhanced by the addition of human serum albumin. The stabilizing effect was maximum when the concentration of serum albumin approached that of oxyhemoglobin, suggesting a molecular level interaction between them. The effects of serum albumin on oxyhemoglobin A were essentially similar to those on oxyhemoglobin S. Deoxy- and methemoglobins were also stabilized by serum albumin. The addition of human serum albumin to a solution containing sickle cell oxyhemoglobin slowly formed a compound which had an absorbance peak at 620 nm. After purification by Sephadex G-200 column chromatography, this compound was identified as methemalbumin. Comparison of the rates of formation of methemalbumin from hemoglobin with various ligand states and human serum albumin showed that the rate of formation from hemichrome was much faster than from met-, oxy- and deoxyhemoglobin. About 60% of the heme was transferred from hemichrome to albumin when the mixture was kept standing at room temperature for 5 min, in contrast to only 5% from methemoglobin. This result suggests that hemichrome, rather than methemoglobin, is the intermediate in the formation of methemalbumin from oxyhemoglobin and human serum albumin. This hypothesis is supported by the finding that the rate of formation of methemalbumin was faster at alkaline pH values than at acid pH values. Serum albumin from various animal sources showed different stabilizing effects. The formation of methemalbumin from these animal albumins was far less than that from human albumin.

Denaturation of oxyhemoglobulin S by mechanical shaking.

The oxy form of sickle hemoglobin precipitates rapidly during mechanical shaking. The rate of precipitation depends on shaking conditions such as stroke amplitude, frequency, angle between the vial axis and the shaking motion, volume and viscosity of hemoglobin solution and temperature. The rate increases linearly with either stroke (S) or frequency (n) above a certain value (S = 5 mm or n = 10Hz). The rate constant was maximum when the angle 0 between the vial axis and the shaking direction was 30 degrees. The rate of precipitation of sickle oxyhemoglobin was faster at high temperatures and always about 10 times greater than that of normal hemoglobin. The activation energies of precipitation of hemoglobin S and A are 20.3 and 21.3 kcal/mol, respectively. The thermogram of hemoglobin was measured by a differential scanning calorimeter. The denaturation temperatures determined from the peak of denaturation curves were 83.5 degrees C for oxyhemoglobin S and 85 degrees C for oxyhemoglobin A. The precipitated hemoglobin after mechanical shaking did not show any denaturation peak indicating that the protein molecules are irreversibly denatured by shaking.

Efflux of gamma-aminobutyric acid from and appearance of free arachidonic acid inside synaptosomes.

When synaptosomes were depolarized in the presence of Ca2+, or when Ca2+ was added to synaptosomes pretreated with Ca2+ ionophore (A23187), free arachidonic acid was clearly increased within synaptosomes, and at the same time an efflux of gamma-aminobutyric acid from synaptosomes was observed. Moreover, when synaptosomes labelled with [14C]arachidonic acid were depolarized in the presence of Ca2+, there was a significant decrease in the radioactivity of the fatty acid of phosphatidylinositol and phosphatidylcholine. Exogenously added arachidonic acid, but not other fatty acids, stimulated the efflux of gamma-aminobutyric acid in the absence of Ca2+. These observations suggest that the release of arachidonic acid from phospholipids is an intrinsic part of the biochemical mechanism that modulates the gamma-aminobutyric acid efflux.

Aggregation of hemoglobin S modified by bifunctional imidoesters.

Sickle hemoglobin (Hb S) was cross-linked by two types of bifunctional imidoesters, dimethyladipimidate (DMA) and dimethyl-3,3'-dithiobispropionimidate (DTBP). These modified hemoglobins were separated into monomer, dimer and polymer fractions by gel filtration. All of these modified hemoglobins showed extremely left-shifted oxygen equilibrium curves with no cooperativity. The stabilities of these hemoglobins were also decreased. The solubilities of these modified hemoglobins in high-phosphate buffers were lower than those of native Hb S. Studies on the kinetics of the aggregation of these modified hemoglobins showed that intracross-linked Hb S with DMA and DTBP (DMA- and DTBP-modified monomeric Hb S) still retained the capability of aggregation with a delay time, while intercross-linked Hb S with DMA and DTBP (DMA- and DTBP-modified oligomeric Hb S) aggregated without a delay time. When the kinetics of aggregation was measured for mixtures of modified and native deoxy-Hb S, DMA-modified monomeric deoxy-Hb S shortened the delay time prior to aggregation of native deoxy-Hb S. The other modified deoxy-Hb S did not affect the delay time, suggesting that these modified oligomeric hemoglobins neither participate in the formation of nuclei nor copolymerize with native deoxy-Hb S.