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A semilinear wave equation possesses propagation with a finite speed, while a parabolic equation has propagation with infinite speed. This paper proposes a reaction-diffusion system whose solutions approximate those of a semilinear wave equation under some assumptions of a reaction term. The proof is based on the energy method. [ABSTRACT FROM AUTHOR]

Aim: Previous studies have reported that patients with rheumatoid arthritis (RA) have a higher risk of developing cardiovascular disease (CVD) than the general population. A major cause of CVD is atherosclerosis, which can be evaluated with carotid ultrasonography (US). As far as we know, there have been no large‐scale carotid artery US studies in Japanese patients with RA. The aim of this study was to identify the risk factors for atherosclerosis in Japanese patients with RA. Methods: The study subjects underwent physical examinations, laboratory tests and US examination, and answered a questionnaire about their lifestyle. Carotid US was performed to measure the maximum carotid intima media thickness (max cIMT) and to detect plaques. Results: Atherosclerosis was detected in 238 patients (52%). Age, hypertension, and total/high‐density lipoprotein cholesterol ratio were positively related to max cIMT. Presence of plaques was related to age, Disease Activity Score of 28 joints—erythrocyte sedimentation rate (DAS28‐ESR), smoking, and any biological treatment. DAS28‐ESR correlated positively not with cIMT but with the development of plaques in our patients with low disease activity (average DAS28‐ESR of 2.7). Conclusion: Disease Activity Score of 28 joints—erythrocyte sedimentation rate was related to the size and number of plaques, whereas only traditional risk factors were related to max cIMT. This indicated that the inflammatory conditions of RA could affect the formation of atherosclerotic plaques. For the management of CVD in patients with RA, it may be important to control not only traditional risk factors, but also RA disease activity. [ABSTRACT FROM AUTHOR]

Abstract The crystal structure of the orthorhombic polyoxymethylene (POM) has been refined by analyzing the synchrotron X-ray diffraction data measured for a micrometer-size single crystal of moth-type morphology. The 3-dimensional elastic and compliance constants tensors were calculated for both the trigonal and orthorhombic phases on the basis of the thus-obtained accurate structure information. The crystal structure information allowed us also to discuss the solid-state phase transition behavior from the orthorhombic to the trigonal phase occurring at around 78 °C. For this purpose, we have performed the temperature-dependent synchrotron X-ray scattering measurement for a tiny moth-type single crystal and revealed the geometrical relation between these two crystals. The free energy was calculated as a function of temperature for these two accurately-analyzed crystal forms using a density functional theory (DFT). The result showed that the orthorhombic phase is thermodynamically more stable than the trigonal phase in a low temperature region, and the stability was reversed at about 225 K. This temperature corresponds to the phase transition point from the orthorhombic to trigonal phase, which is however considerably lower compared with the actually-observed transition point. The large discrepancy might be ascribed to the additional contribution of the entropy term due to the structural disorder and/or the thermal motion of chains with a large amplitude, which was not taken into account in the DFT calculation. Graphical abstract Image 1 Highlights • Single crystal structure of orthorhombic polyoxymethylene was refined with synchrotron X-ray diffraction data. • Ultimate mechanical properties of orthorhombic and trigonal polyoxymethylene were calculated. • Phase transition from orthorhombic to trigonal form of polyoxymethylene was clarified experimentally and theoretically. [ABSTRACT FROM AUTHOR]

In recent years, spatial long range interactions during developmental processes have been introduced as a result of the integration of microscopic information, such as molecular events and signaling networks. They are often called nonlocal interactions. If the profile of a nonlocal interaction is determined by experiments, we can easily investigate how patterns generate by numerical simulations without detailed microscopic events. Thus, nonlocal interactions are useful tools to understand complex biosystems. However, nonlocal interactions are often inconvenient for observing specific mechanisms because of the integration of information. Accordingly, we proposed a new method that could convert nonlocal interactions into a reaction-diffusion system with auxiliary unknown variables. In this review, by introducing biological and mathematical studies related to nonlocal interactions, we will present the heuristic understanding of nonlocal interactions using a reaction-diffusion system. [ABSTRACT FROM AUTHOR]

The crystal structure and phase transition behavior of poly(nonamethylene terephthalamide) (PA9T, -[CO-C 6 H 4 -CONH-(CH 2 ) 9 -NH] n -) and its related model compounds (AT m ,C 6 H 5 -CONH-(CH 2 ) m -NHCO-C 6 H 5 ( m = 7–12)) have been investigated by carrying out the temperature dependent measurements of wide-angle X-ray diffraction (WAXD), small-angle X-ray scattering (SAXS) and infrared spectra along with the DSC measurement. The crystal structure of PA9T at room temperature was determined by analyzing the X-ray diffraction diagram measured for the uniaxially-oriented sample. The nonamethylene segmental part takes the zigzag conformation, which was supported by the quantitative analysis of the methylene progression bands observed in the infrared spectra. The temperature dependence of WAXD, SAXS and infrared spectra of PA9T revealed the existence of the 2-staged order-to-disorder phase transitions: at room temperature this polymer exists as phase I, the crystal structure of which was analyzed as mentioned above. In the relatively low and wide temperature region (190–270 °C for the unoriented sample), phase I transforms to phase II, in which the methylene conformation is disordered, the aromatic amide part is slightly rotated and the intermolecular hydrogen bonds become weaker but the hydrogen bonds are still kept alive. In the temperature region immediately below the melting point (270–310 °C for the unoriented sample), the phase II is melted once and recrystallizes into phase III, where the intermolecular hydrogen bonds are mostly broken in addition to the further disordering of the methylene segments and aromatic amide groups. The thus-occurring violent thermal motions cause a remarkable increase of the long period in this transition region. The molecular chains are still highly oriented and so the phase III may be assumed to be in a kind of liquid crystalline state. The crystal structural changes detected in these phase transitions of PA9T were confirmed by the analysis of the X-ray diffraction and IR spectral data collected for the low molecular-weight model compounds. [ABSTRACT FROM AUTHOR]

Detailedcrystal structure analysis has been carried out for fourcrystalline forms (I, I′, II, and high-temperature phase, HT)of uniaxially oriented specimens from a novel polyethylene-like polymer,−[(CH2)20–CHBr]n– on the basis of the 2-dimensional X-ray diffractionpatterns and polarized FTIR spectral data. This polymer has Br atomsplaced regularly on each and every 21st backbone carbon. The preciseBr placement along the polyethylene backbone allows drastically differentchain conformation and chain packing modes between the group of formsI and I′ and the group of form II and HT phase. In forms Iand I′, the molecule is fully extended adopting a planar all-transzigzag conformation with layers of Br atoms normalto the chain axis. Conformational disorder and mismatch in relativeheight of Br atom between the neighboring chains distinguish formI from form I′. In forms II and HT phase, the molecular chainsbend at the Br substitutional point and take a large zigzag form consistingof long methylene segmental arms. The molecular bends are caused bythe generation of nonplanar gaucheconformers atthe C–C bonds adjacent to the CHBr groups, while the CH2segments maintain the all-transconformation.The major difference between form II and HT is conformational disorderwithin the methylene runs. Heating at T< 65 °Cunder unrestrained condition causes an irreversible transition fromform I′ to form I, and form I transforms irreversibly to formII in a narrow temperature range of 65–66 °C. The highertemperature heating induces the reversible and apparently continuoustransition of form II to the HT phase. On the other hand, the tensilestretching at room temperature causes the irreversible transitionof forms I and II to the form I′. [ABSTRACT FROM AUTHOR]

Abstract: Relationship between the chain conformation in the crystal lattice and the ultimate Young's modulus has been discussed on the basis of the crystal structural information revealed by the X-ray diffraction analysis for a series of arylate polyesters with long methylene segments (–[–COC6H4CO–O(CH2) m O–] n –). The X-ray structural analysis revealed that the molecular chains take the all-trans-zigzag conformations for all of the even-numbered polyesters and their model compounds as well as the odd-numbered polyesters with the methylene segmental length longer than (CH2)14. These chain conformations have been correlated well to the ultimate Young's modulus along the chain axis or the crystallite modulus E c , which has been estimated experimentally by the X-ray diffraction method under a constant stress and also predicted theoretically using the X-ray-analyzed crystal structures on the basis of the molecular mechanics method. The E c was found to show the minimum at around m = 4–6 and increased gradually with an increment of m and approached the crystallite modulus of polyethylene, 235 GPa (X-ray value) ∼ 316 GPa (calculate) at an infinite m value. This behavior of E c as a function of the number of methylene segmental units m was reasonably interpreted by developing the theoretical equation of E c for a simplified zigzag chain model composed of a repetition of two linear rods representing the benzene–ester and methylene segmental parts respectively. These findings may promise that the mechanical property of arylate polyester can be controlled by adjusting the methylene segmental length m. [Copyright &y& Elsevier]

The simultaneous measurement of Fouriertransform infrared (FTIR)transmission spectra and 2-dimensional wide-angle X-ray diffraction(WAXD) and small-angle X-ray scattering (SAXS) patterns has been performedsuccessfully to investigate the hierarchical structure changes occurringin the stress-induced phase transition phenomenon of uniaxially orientedpoly(tetramethylene terephthalate) film. The molar fraction of theβ-crystal form, evaluated from the IR and WAXD data analyses,increased steeply in the plateru region of the stress–straincurve as already known well. The 2D SAXS data have revealed the remarkableand reversible change in the stacked lamellar structure just afterthe α-to-β phase transition was completed, where the tiltingangle of the stacked lamellae measured from the draw axis of the orientedsample became zero, and the lamellar thickness increased due to theinclusion of amorphous region located in the boundary part of thecrystalline lamellae. In parallel, the X-ray reflection spots in awider diffraction angle region became diffuse in the observed WAXDpattern of the β form, indicating the packing disorder of themechanically stressed chains. In this way, the simultaneous combinationof the 3 different types of equipments has allowed us to deduce thedetailed structural change from the various levels: the stress-inducedα–β transition was found to occur not only withthe remarkable changes in the molecular chain conformation and chainpacking mode in the crystal lattice, but also with the large and reversiblechange in the lamellar stacking structure. The stress-induced changesin lamellar thickness and long period were simulated using a mechanicalmodel with these hierarchical structure changes taken into account,giving relatively good reproduction of the observed data. [ABSTRACT FROM AUTHOR]

Crystal structures have been determined by the X-ray diffraction analyses for a series of aromatic polyesters –[–O(CH2) m O–COC6H4CO–] n – (mGT) with the long methylene sequence (m = 9–20) and their model compounds. The X-ray diffraction spots of these polyesters were observed more or less to shift upward and downward slightly from the averaged horizontal layer lines, indicating the tilting phenomenon of the molecular chains from the draw direction, the analysis of which was helpful for the definite determination of the unit cell parameters. For example, the c axis of 10 GT was found to be tilted by about 1° from the drawn axis in the 10 tilt plane. The unit cell parameters obtained by the quantitative analysis of the tilting phenomenon were a = 4.77 ± 0.01 Å, b = 5.66 ± 0.01 Å, c (f.a.) = 20.7 ± 0.1 Å, α = 108.2 ± 0.1°, β = 122.7 ± 0.2°, and γ = 97.1 ± 0.1°. In the case of 20 GT, the tilting phenomenon was not observed in the X-ray fiber diagram. The triclinic unit cell parameters were determined for 20 GT: a = 4.59 ± 0.02 Å, b = 5.75 ± 0.02 Å, c (f.a.) = 33.3 ± 0.1 Å, α = 113.2 ± 0.2°, β = 116.6 ± 0.2°, and γ = 98.1 ± 0.2°. The space group was P for both of 10 GT and 20 GT. One chain is included in the unit cell. The chain conformation is of the all-trans-zigzag type. The reliability factor or the measure of the agreement between the observed and calculated X-ray diffraction intensity was 18.8% for 10 GT (90 reflections in total) and 18.5% for 20 GT (67 reflections). The crystal structures of 12 GT and 16 GT were found to be essentially the same as those of 10 GT and 20 GT. As for the odd-numbered mGT or 9 GT, 11 GT and 15 GT, the most plausible structure models were built up, which gave the good correspondence to the observed diffraction patterns semi-quantitatively. As the total number of methylene monomeric units was increased, the chain conformation was found to change from the trans-gauche combined form (3 GT and 5 GT) to the all-trans form (15 GT). The single crystal structure analysis of the low-molecular-weight model compounds confirmed the reasonableness of the crystal structures of the corresponding polymers. [ABSTRACT FROM AUTHOR]

The development in the crystal structure analysis of synthetic polymers using the hybridized combination of wide-angle X-ray and neutron diffraction (WAXD and WAND, respectively) techniques has been reviewed with many case studies performed by the authors. At first, the technical development was reviewed, in which the usage of high-energy synchrotron X-ray source was emphasized for increasing the total number of the observable diffraction peaks, and several examples were introduced. Secondly, the usage of the WAND method was introduced, in which the successful extraction of hydrogen atomic positions was described. The third example is to show the importance for the hybrid combination of these two diffraction methods. The quantitative WAXD data analysis gave the crystal structures of at-poly(vinyl alcohol) (at-PVA) and at-PVA-iodine complex. However, the thus-proposed structure models were found not to reproduce the observed WAND data very much. The reason came from the remarkable difference in the atomic scattering powers of the constituting atomic species between WAXD and WAND phenomena. The introduction of statistical disorder solved this serious problem, which reproduced both of the observed WAXD and WAND data consistently. The more systematic combination of WAXD and WAND methods, or the so-called X-N method, was applied also to the quantitative evaluation of the bonded electron density distribution along the skeletal chains, where the results about polydiacetylene single crystals were presented as the first successful study. Finally, the application of WAND technique in the trace of structural changes induced under the application of external stress or temperature was described. The future perspective is described for the development of structural science of synthetic polymers on the basis of the combined WAXD/WAND techniques. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between caries assessment using a laser fluorescence device (DIAGNOdent), and bacterial invasion in arrested carious dentin detected by polymerase chain reaction (PCR). The ten extracted human molars used in this study had black or dark brown, hard occlusal carious lesions, and were found to be only weakly stained or unstained with a caries detector dye of 1% acid red in propylene glycol. In those extracted human molars, dentin was removed in the direction of the pulp chamber at 150-μm intervals. During each removal (104 sections in total), the dentin surface was assessed with DIAGNOdent, and a dentinal tissue sample was taken with a round bur. Bacterial DNA of each tissue sample was examined using PCR and primers based on the nucleotide sequence of a conserved region of bacterial 16S rDNA. Rates of bacterial detection increased as the DIAGNOdent values increased. When the DIAGNOdent values were <10, the rate of bacterial detection was 0%. The area under the receiver operating characteristic curve of the DIAGNOdent values was 0.87. These results indicate that the DIAGNOdent values of arrested dentinal carious lesion were closely related to the rates of bacterial detection. [ABSTRACT FROM AUTHOR]

Fluoride (F) distribution in human teeth was measured using an in-air micro-PIGE and micro-PIXE system. Class V cavities in the extracted teeth were prepared with Fluoro-Bond Shake One to provide a thin layer of an F-releasing material (FRM). The cavities were then filled with Beautifil Flow F10 (FRM, Group I) or LITE FIL IIP (non-FRM, Group II). Following a four-year period, specimens were cut longitudinally perpendicular to the cavity floor. The F distribution was measured at the floor of the cut surface. The position including 90% of the intact Ca level was defined as the wall surface. Based on this demarcation, indices of F distribution (surface F concentration and F penetration depth) were determined. Thickness of FRM thin layers varied (≈339 μm) and did not affect F distribution. Both values of F distribution indices in Group I [821-8763 (mean 3797) ppm, 34-668 (mean 241) μm] were significantly larger than those in Group II [0-7064 (mean 1865) ppm, 0-143 (mean 21) μm]. The F distribution in Group I was affected more by the filling material than by the FRM thin layer during the four-year exposure. Methodologies using this system may give insightful information for the development of new dental materials. [ABSTRACT FROM AUTHOR]

Abstract: The present study was designed to investigate the anti-allodynic effects of current analgesic agents, such as pregabalin, amitriptyline, mexiletine, morphine, and diclofenac, in a rat model of streptozotocin (STZ)-induced diabetic neuropathy. Diabetic rats developed a sustained decrease in withdrawal threshold response to the von Frey test within 8 weeks after a single injection of STZ (45 mg/kg, i.v.). The anti-allodynic effects of analgesic agents were examined after a single oral or subcutaneous administration at 3 and 7 weeks after beginning of STZ-treatment. Pregabalin (3–30 mg/kg, p.o.), an antiepileptic agent, dose-dependently blocked the mechanical allodynia in rats treated both at 3 and 7 weeks. Mexiletine (10–100 mg/kg, p.o.), a sodium channel blocker, dose-dependently ameliorated mechanical allodynia in rats treated at 3 weeks; however, the efficacy was diminished at 7 weeks. Morphine (1–10 mg/kg, s.c.) was effective in rats treated at 3 weeks; however, it was ineffective at 7 weeks. Conversely, an antidepressant amitriptyline (0.3–3 mg/kg, p.o.) improved mechanical allodynia in rats treated at 7 weeks, whereas it was ineffective at 3 weeks. Diclofenac, a non-steroidal anti-inflammatory drug, was ineffective at both time points. These results demonstrate that, except for diclofenac, the standard analgesic agents tested can effectively alleviate the mechanical allodynia seen in STZ-induced diabetic neuropathy. Their efficacies varied depending on the duration of the diabetic condition, suggesting that temporal changes in pharmacodynamic factors could affect the responsiveness of this model to analgesic agents. [Copyright &y& Elsevier]

Embryonic stem (ES) cells can grow rapidly and permanently while maintaining their differentiation capacity. To gain insight into how the cell cycle progression of undifferentiated murine ES cells is regulated, we have examined the expression patterns of various replication and cell cycle regulators. Most factors including cyclins, Cdc6, and geminin are rather constitutively expressed during the cell cycle of ES cells. Furthermore, the transcript levels of almost all the cell cycle regulators we investigated except for p21 and p27 are higher in undifferentiated ES cells than in murine embryonic fibroblasts (MEFs), and the increased stability of mRNA in ES cells may be partially responsible for this at least with some of the factors. More strikingly, the transcriptional levels of these factors are strongly correlated with the acetylated state of histone H3 at their promoter regions. However, the methylation state of histone or CpG methylation of the promoter region is not generally correlated significantly with the expression pattern of these factors in both cell types. On the protein level, Cdc6, ASK, cyclin A2, and cyclin B1 are extremely abundant in ES cells compared with MEFs. Furthermore, they are rapidly down-regulated upon induction of differentiation of ES cells. The significance of these findings is discussed in relation to the unusual proliferative properties of ES cells in an undifferentiated state. [ABSTRACT FROM AUTHOR]

We have proposed the multirate discrete Fourier transform (MR-DFT) as one of the DFT algorithms. The feature of the MR-DFT is that only one multiplication is used for each Fourier coefficient. Therefore, the number of multiplications can be decreased compared with the conventional DFT. In this paper, for applications of the MR-DFT, we consider how the noise affects the estimation performance of the MR-DFT. Then we propose two improved algorithms of the estimation performance, that is, a shifted multirate discrete Fourier transform (SMR-DFT) and a parallel shifted multirate discrete Fourier transform (PSMR-DFT). The SMR-DFT prevents an aliasing of the additive noise by a frequency modulation. The PSMR-DFT performs the parallel processing of the SMR-DFT with different sample points using the periodicity of an input signal. The estimation performances of the proposed algorithms are compared with MR-DFT by computer simulations. The SMR-DFT could prevent the degradation of the estimation performance of the MR-DFT in the lower components caused by the wide bandwidth noise. Hence its estimation variance could become 0.61 times that of the MR-DFT. Furthermore, the PSMR-DFT could improve the estimation variance of the SMR-DFT to 0.46 times. Comparing the number of operations of the proposed algorithms with the MR-DFT, the number of additions has increased, however, the number of multiplications has the same complexity. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 150(2): 20–27, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20044 [ABSTRACT FROM AUTHOR]

Investigates the thermostabilization process of ovalbumin with different loop structures, in order to address the loop-insertion problem for S-ovalbumin production. Thermostabilization of recombinant ovalbumin by an alkaline treatment; Limited proteolysis of ovalbumin and S-ovalbumin with serine proteases.

Very-long-chain acyl-coenzyme A dehydrogenase deficiency ( VLCADD) is a rare and life-threatening disease characterized by an enzymatic defect in the fatty acid β-oxidation pathway. A nulliparous woman with VLCADD showed improvements in serum levels of the long-chain acylcarnitine moiety ( C14:1) during pregnancy and successfully delivered a healthy infant vaginally. Pregnancy and vaginal delivery can be successfully completed in patients with VLCADD with careful management. [ABSTRACT FROM AUTHOR]

We have demonstrated the first surfactant-free synthesis of fluorescent Pt nanoclusters in N,N-dimethylformamide (DMF) solution. The Pt nanoclusters consist of 4 to 6 Pt atoms. They form highly stable dispersions in water, under both acidic (pH 2) and basic conditions (pH 12), and at ionic strengths of 1 M NaCl. [ABSTRACT FROM AUTHOR]

The Jeans instability is a key concept that facilitates our understanding of galaxy and star formation in astrophysics. To understand this dynamics, we consider the dynamics of the three-dimensional compressible Navier–Stokes–Poisson system. We extract the reduction equations using the center manifold theory and analyze its bifurcation structure. Consequently, we obtain solutions corresponding to the growth mode, a symmetric pattern, and a layer pattern on the center manifold of class C 2. These solutions are selected according to the thermal state of the gas. • The Jeans instability for compressible viscous gases is controlled by the Mach number. • The dynamics of the Jeans instability depends on thermodynamic state. • The viscosity of gases does not affect the local dynamics of instability essentially. • Exponential growth, symmetric pattern and layer pattern appear. [ABSTRACT FROM AUTHOR]

Time-resolved simultaneous measurements of wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) (and FTIR spectra) were performed for various kinds of crystalline polymers in isothermal melt-crystallization processes, from which the common features of the structural evolution process as well as the different behaviors intrinsic to the individual polymer species were extracted. The polymers targeted here were polyethylene, isotactic polypropylene, polyoxymethylene, aliphatic nylon, vinylidene fluoride copolymer, trans-polyisoprene, and poly(alkylene terephthalate). A universal concept of the microscopically viewed structural evolution process in isothermal crystallization may be described as follows: (i) the small domains composed of locally regular but more or less disordered helical chain segments are created in the melt (this important information was obtained by the IR spectral data analysis); (ii) these domains grow larger as the length and number of more regular helical segments increase with time; (iii) the correlation among the domains becomes stronger and they approach each other; and (iv) they merge into the stacked lamellar structure consisting of the regularly arranged crystalline lattices. The inner structure of the domains is different depending on the polymer species, as known from the IR spectral data. [ABSTRACT FROM AUTHOR]

Cardiotocography records fetal heart rates and their temporal relationship to uterine contractions. To identify high risk fetuses, obstetricians inspect cardiotocograms (CTGs) by eye. Therefore, CTG traces are often interpreted differently among obstetricians, resulting in inappropriate interventions. However, few studies have focused on quantitative and nonbiased algorithms for CTG evaluation. In this study, we propose a newly constructed deep neural network model (CTG-net) to detect compromised fetal status. CTG-net consists of three convolutional layers that extract temporal patterns and interrelationships between fetal heart rate and uterine contraction signals. We aimed to classify the abnormal group (umbilical artery pH < 7.20 or Apgar score at 1 min < 7) and the normal group from CTG data. We evaluated the performance of the CTG-net with the F1 score and compared it with conventional algorithms, namely, support vector machine and k-means clustering, and another deep neural network model, long short-term memory. CTG-net showed the area under the receiver operating characteristic curve of 0.73 ± 0.04, which was significantly higher than that of long short-term memory. CTG-net, a quantitative and automated diagnostic aid system, enables early intervention for putatively abnormal fetuses, resulting in a reduction in the number of cases of hypoxic injury. [ABSTRACT FROM AUTHOR]

Dental materials that are antimicrobial and acid-resistant can inhibit bacterial colonization and demineralization, thereby preventing caries. Zinc and copper are well-known for their antibacterial effect, as is nanostructured ZnO–CuO composite. Minerals such as fluorine and calcium, can remineralize and demineralize teeth. Therefore, we developed novel fluoride-containing ZnO–CuO (ZCF) nanocomposites; to the best of our knowledge, these are the first nanocomposites of this kind. The fluoride concentrations and antibacterial effects of the ZCF nanocomposites were evaluated. Nanocomposites comprising zinc and copper (ZC), and zinc, copper, and fluorine (ZCF), were prepared by a simple one-step homogeneous coprecipitation method at a low temperature (80 °C), without the use of organic solvent or surfactant. The structure and composition of the ZC and ZCF nanocomposites were examined by scanning electron microscopy–energy-dispersive spectroscopy (SEM-EDS). Quantitative analysis of the mass concentration was performed by using ZAF correction methods. The fluorine content in nanocomposites was evaluated by using proton-induced gamma emission (PIGE) at the Takasaki Advanced Radiation Research Institute in Japan. By using 96-well microtiter plates, we analyzed the antibiotic susceptibility of ZC, ZCF, and the control buffer (phosphate-buffered saline) with Streptococcus mutans (ATCC 25175). The SEM images showed that ZC and ZCF nanocomposites were composed of 3D flower-like microstructures with diameters of approximately 1 μm. Environmental SEM-EDS analysis revealed that ZC contained 43.2% Cu, 55.1% Zn, 2.2% F, and 0.1% Cl, whereas ZCF contained 47.5% Cu, 40.5% Zn, 6.7% F, and 5.9% Cl. Analysis by PIGE showed that ZCF nanocomposite contained 2553.6 ± 199.2 ppm fluorine, whereas no fluoride was detected in ZC. The control buffer enabled bacterial growth to 4 × 107 ± 9 × 106 CFU/mL, whereas ZC allowed growth of 12 ± 8 CFU/mL, and ZCF showed no bacterial growth. Thus, we developed novel fluoride-containing ZnO–CuO nanocomposites, which exhibited antibacterial effects and have the potential for remineralization, thereby demonstrating their potential as multifunctional dental materials. [ABSTRACT FROM AUTHOR]

There are many kinds of dental luting materials (cements) in the market. Some luting materials are fluoride-releasing to prevent secondary caries. The purpose of this study was to evaluate the release of fluorine from fluoride-containing luting materials to adjacent dentin by in-air micro PIXE/PIGE (µPIXE/PIGE) system at Takasaki Advanced Radiation Research Institute. Each extracted human tooth crown was cut to expose a flat dentin surface. A 2-mm thick acrylic resin plate was cemented to each tooth using one of four fluoride-containing luting materials on the dentin surface: Fuji Luting EX (FL); Fuji I (FO); SA Luting plus (SA); and BeautiCem SA (BC). The specimens were sectioned and exposed to automated pH cycling (pH 4.5 and 7.0; simulate oral condition) for 4 or 8 weeks. After pH cycling, calcium and fluorine distributions were analyzed by the µPIXE/PIGE system with a 1.7-MeV 1H+ microbeam. The cumulative fluorine concentration (fluorine uptake) and calcium concentration in each specimen was calculated at a distance of 100 µm from the outermost surface. The results of our study indicated that FL had the highest concentration of fluorine uptake among all test materials in the 8-week group. The other three materials did not differ significantly from each other in terms of fluorine uptake. FL showed higher calcium content than SA in the 8-week group. Findings from this study suggest that the amount of fluorine penetration into dentin is likely to be dependent on the amount of fluoride released from each material, and also related to the amount of calcium present. [ABSTRACT FROM AUTHOR]

Recent years have seen the introduction of non-local interactions in various fields. A typical example of a non-local interaction is where the convolution kernel incorporates short-range activation and long-range inhibition. This paper presents the relationship between non-local interactions and reaction-diffusion systems in the following sense: (a) the relationship between the instability induced by non-local interaction and diffusion-driven instability; (b) the realization of non-local interactions by reaction-diffusion systems. More precisely, it is shown that the non-local interaction of a Mexican-hat kernel destabilizes the stable homogeneous state and that this instability is related to diffusion-driven instability. Furthermore, a reaction-diffusion system that approximates the non-local interaction system with any even convolution kernel is shown to exist. [ABSTRACT FROM AUTHOR]

[Display omitted] • Zinc, released from bioactive materials, was incorporated into dentin with in approximately 50 µm. • Zinc-doped dentin demonstrated 30% less acid solubility, helping to improve its anti-carcinogenicity. • Zinc was incorporated into dentin in a four-fold coordination , indicating a newly generated covalent bond. • Quantum beam and synchrotron radiation technologies help in analyzing the bonding states of dentinal elements. Dental caries, the world's most prevalent infectious disease, is caused by the diffusion of hydroxyl ions into tooth structures. To prevent dental caries, the application of fluoride (F) and zinc (Zn) ions to teeth surfaces are potential effective measures. In this study, The ionic influence, especially the chemical bond of F and Zn, on the acid resistance of dentin were investigated by particle induced X-ray / gamma-ray emission, X-ray diffraction, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy. The results showed Zn was distributed in the limited surface layer of dentin without altering its crystal structure. From the Zn K edge extended X-ray absorption fine structure, Zn incorporated into dentin was surrounded by oxygen and demonstrated four-fold coordination. The bond length and chemical state of Zn–O in Zn doped dentin suggested newly generated Zn–O covalent bond, which may improve acid resistance of dentin. This study showed that the atomic and molecular structures, such as the molecular distances and chemical state, influenced acid resistance of teeth, emphasizing the validity of chemical state analysis for understanding properties in biomaterials. [ABSTRACT FROM AUTHOR]

Despite recent advances in bonding restorations, which are the basis of restorative dentistry, secondary caries are still able to form. Previously, a novel fluoride-containing zinc and copper (ZCF) nanocomposite was introduced to prevent the formation of caries due to its antibacterial activity. In this study, we studied the impact of ZCF nanoparticles on the adhesive strength of bonding restorations through micro-tensile bond strength (µTBS) testing. The impact of antibacterial and matrix metalloproteinase (MMP) inhibitors on the nanoparticles was also examined. The nanocomposites were prepared using a simple one-step homogeneous co-precipitation method at a low temperature. A self-etch adhesive was applied to 10 extracted caries-free human molars with (test group) and without (control group) the ZCF nanoparticles. This was followed by composite resin build-up and µTBS testing, MMP activity assays, and evaluation of the antibacterial effects. The results showed no significant differences in the µTBS between the ZCF and the control groups. However, the ZCF exhibited a significant inhibitory effect against MMP-2, MMP-8, and MMP-9, in addition to an antibacterial effect on Streptococcus mutans. Therefore, the present study demonstrated that the addition of ZCF nanoparticles to adhesive systems can result in MMP inhibition and antibacterial action while maintaining the mechanical properties of the bonding restorations. [ABSTRACT FROM AUTHOR]

Whether fluorine penetrated from material completely incorporates into tooth mineral is a matter of debate, although it is well known that the fluoride from material penetrates directly into tooth structures. The purpose of this study is to determine tooth-bound fluoride uptake from fluoride-containing materials using PIGE/PIXE system at the Wakasa Wan Energy Research Center. Class V cavities in buccal surfaces of eighteen extracted human teeth were drilled and filled with six fluoride-containing materials. After being stored in distilled water for one year, a longitudinal section including materials was obtained from each tooth. Fluorine and calcium distribution of specimens were evaluated using PIGE/PIXE system. After evaluation, the specimens were immersed in 10 mL of 1M KOH solution and were agitated at room temperature for 24 h to remove a KOH soluble fluoride. The specimens were washed with 200 mL distilled water and left to dry. Again, to estimate tooth-bound fluorine (KOH-insoluble fluoride) uptake, the same portion of the specimens after KOH treatment were evaluated using PIGE/PIXE system. It was confirmed that fluorine penetrated from material partly incorporated into tooth mineral. This tooth-bound fluoride have the potential to prevent dental caries after loss of the bond between the filling material and tooth structure. [ABSTRACT FROM AUTHOR]

Abstract: The use of fluoride for the prevention of caries is based on the transformation of hydroxylapatite to fluoroapatite in the presence of fluoride ions, thereby strengthening tooth structure. Adhesion of dentin and resin composite (tooth-colored restoration material) requires a dentin bonding system, since resin composite is not able to adhere to dentin directly. Demineralization of dentin by acid etching is an important step in the dentin bonding system, however, demineralization also introduces weaknesses in tooth structure. If the demineralized dentin could be strengthened by the application of fluoride, then the dentin–resin composite bond strength might also improve. To test this hypothesis, the present study evaluated the influence of fluoride applications on the strength of the dentin–resin composite bond by (1) tensile strength testing analyses, (2) SEM analyses of tooth structure, and (3) detection of calcium (Ca) and fluorine (F) distribution patterns by micro proton-induced X-ray emission (μ-PIXE) and micro proton-induced gamma-ray emission (μ-PIGE) analyses conducted at the Takasaki Ion Accelerators for Advanced Radiation Application (TIARA) at the Takasaki Advanced Radiation Research Institute (TARRI). In this study, the dentin in extracted human molars was exposed by grinding and the dentin was etched with 35% phosphoric acid. Fluoride was applied at two concentrations, 0.022% (100ppm F) and 2.21% (10,000ppm F) NaF solution, for two time periods, 30 and 60s, prior to bonding the resin composite with the treated dentin. Controls were prepared in the same manner, but without the fluoride application. Bond strength was measured with a micro-tensile testing unit, and the fluorine and calcium distributions at the interface between dentin and resin composite were detected by μ-PIGE and μ-PIXE analysis, respectively. Results indicate that the 10,000ppm F applications resulted in higher bond strengths than observed in either the 100ppm F applications or the control group. In addition, PIGE analyses showed high concentrations of fluorine in the hybrid bonding layer of the 10,000ppm F samples, suggesting that the fluorine contributes to the strength of the dentin–resin composite bond. Detection of fluoroapatite within the hybrid bonding layer suggests that bond strength involves remineralization processes. [Copyright &y& Elsevier]

Although amphotericin B (AmB) is thought to exert its antifungal activity by forming transmembrane ion-permeable self-assemblies together with ergosterol, no previous study has directly proven AmB-ergosterol interaction. To establish the interaction, we measured 2H NMR using deuterium-labeled sterols and AmB. The 2H NMR spectra of deuterated ergosterol in palmitoyloleoylphosphatidylcholine (POPC) bilayers showed that fast axial diffusion of erogosterol was almost completely inhibited by the coexistence of AmB. Conversely, cholesterol mobility in POPC membrane was essentially unchanged with or without AmB. These results unequivocally demonstrate that ergosterol has significant interaction with AmB in POPC bilayers. In addition, we examined the mobility of AmB using deuterium-labeled AmB, and found that, although AmB is almost immobilized in sterol-free and cholesterol-containing POPC membranes, a certain ratio of AmB molecules acquires mobility in the presence of ergosterol. The similar mobility of AmB and ergosterol in POPC bilayers confirmed the idea of the direct intermolecular interaction between ergosterol and AmB. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This laboratory study evaluated the objectivity of caries removal with a caries detector dye by color and bacterial evaluations. Methods: In 41 cases of dentin caries (32 extracted human molars), carious tissues were removed using a caries detector dye. Images of dentin surfaces with color-matching stickers were acquired using a CCD camera, and dentinal tissue samples were collected with new round burs. Corrected L*, a* and b* values (CIE 1976 L*a*b* color system) of dentin surfaces were calculated from the sticker color changes. In addition, bacterial DNA in dentinal tissues was detected by the polymerase chain reaction. Results: The intra-class correlation coefficient of the corrected L*, a* and b* values was 0.34, 0.30 and 0.49, respectively. There were significant inter-operator differences (P <0.05). Seventeen of 41 specimens contained bacterial DNA after caries removal. Conclusions: Results showed that objectivity of caries removal using the caries detector dye with visual inspection was low. [Copyright &y& Elsevier]

Abstract: Immunophilin ligands are neuroregenerative agents, characterized by binding to FK506 binding proteins (FKBPs), which stimulate recovery of neurons in a variety of injury paradigms. Here we report the discovery of a novel, non-immunosuppressive immunophilin ligand, FK1706. FK1706, a derivative of FK506, showed similarly high affinity for two FKBP subtypes, FKBP-12 and FKBP-52, but inhibited T-cell proliferation and interleukin-2 cytokine production with much lower potency and efficacy than FK506. FK1706 (0.1 to 10 nM) significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in SH-SY5Y cells, as did FK506. This neurite potentiation could be blocked by an anti-FKBP-52 antibody, as well as by specific pharmacological inhibitors of phospholipase C (PLC), phosphatidylinositol 3-kinase (PI3K), and the Ras/Raf/Mitogen-Activated Protein Kinase (MAPK) signaling pathway. FK1706 also potentiated NGF-induced MAPK activation, with a similar dose-dependency to that necessary for potentiating neurite outgrowth. Taken together, these data suggest that FK1706 is a non-immunosuppressive immunophilin ligand with significant neurotrophic effects, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway, and therefore that FK1706 may have therapeutic potential in a variety of neurological disorders. [Copyright &y& Elsevier]

A 56-year-old man receiving treatment for hypertension experienced sudden-onset dizziness and was admitted to our hospital. Computed tomography of the brain revealed a small high-density lesion in the right rostral midbrain. Subsequent magnetic resonance imaging revealed a small hemorrhagic lesion in the same position. The patient complained of double vision affecting the right side when viewing a horizontal linear target. Vergence was intact, but vertical gaze was severely restricted downward and moderately restricted upward. Vestibulo-ocular reflex maneuvers did not alleviate the patient's vertical gaze palsy. By 40 days after the incident, his motility had recovered and he could begin to tilt his head to the left. Consecutive Hess tests demonstrated a skew deviation of right hypertropia, which continued for over two years. Funduscopic examination revealed left extorsion but no right intorsion. A diagnosis of posterior canal-type ocular tilt reaction (OTR) was made from these signs. The patient's course indicated that periaqueductal syndrome dominated in the acute stage whilst unilateral symptoms became more apparent in the chronic stage. The rostral interstitial nucleus of the medial longitudinal fasciculus and the posterior commissure were estimated to contain the main causative lesion for the acute symptoms, whereas the interstitial nucleus of Cajal (INC) was implicated in the chronic stage. Posterior canal-type OTR caused by unilateral INC lesion has been reported only rarely. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the feasibility of proximal surface caries detection using a laser fluorescence device. DIAGNOdent, through the sound dentin surrounding the cavity wall after removal of occlusal caries. Extracted sound human molars were ground to prepare horizontal and vertical dentin plates 1.4 mm thick. Extracted carious human molars were reduced in thickness horizontally from the occlusal surfaces until exposure of the dentin caries. The dentin plate was placed on the carious tooth. Before and after gradual thinning of the dentin plate from approximately 1.4 mm to 0.2 mm thick, the dentin caries was measured 10 times through the plate by the laser fluorescence device with a cone-shaped tip or a broad tip. When the dentin plate was reduced to less than 0.3 mm thick (using a combination of a horizontal plate and cone-shaped tip) or 0.2 mm thick (using the other combinations), the values measured with the laser fluorescence device were significantly larger than the values before reducing the thickness of the dentin. Based on these results, the device offers potential use as one of the screening tests for proximal surface caries detection through sound dentin when the sound dentin between tip and caries is thin. [ABSTRACT FROM AUTHOR]

The receptor for advanced glycation end-products (RAGE) and the G protein-coupled angiotensin II (AngII) type I receptor (AT1) play a central role in cardiovascular diseases. It was recently reported that RAGE modifies AngII-mediated AT1 activation via the membrane oligomeric complex of the two receptors. In this study, we investigated the presence of the different directional crosstalk in this phenomenon, that is, the RAGE/AT1 complex plays a role in the signal transduction pathway of RAGE ligands. We generated Chinese hamster ovary (CHO) cells stably expressing RAGE and AT1, mutated AT1, or AT2 receptor. The activation of two types of G protein α-subunit, Gq and Gi, was estimated through the accumulation of inositol monophosphate and the inhibition of forskolin-induced cAMP production, respectively. Rat kidney epithelial cells were used to assess RAGE ligand-induced cellular responses. We determined that RAGE ligands activated Gi, but not Gq, only in cells expressing RAGE and wildtype AT1. The activation was inhibited by an AT1 blocker (ARB) as well as a RAGE inhibitor. ARBs inhibited RAGE ligand-induced ERK phosphorylation, NF-κB activation, and epithelial–mesenchymal transition of rat renal epithelial cells. Our findings suggest that the activation of AT1 plays a central role in RAGE-mediated cellular responses and elucidate the role of a novel molecular mechanism in the development of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background. Kawasaki disease (KD) is typically characterized by fever, oral cavity erythematous changes, bilateral bulbar conjunctival injection, skin rash, erythema and edema of the hands and feet, and cervical lymphadenopathy. Some atypical patients with KD initially develop cervical and pharyngeal cellulitis; however, an initial presentation with inguinal cellulitis is extremely rare. In addition, to our knowledge, no report has documented the cytokine profile in a KD patient with cellulitis. Case presentation. A previously healthy 8-year-old Japanese girl was hospitalized following a 2-day history of fever and a 5-day history of pain and erythema in the left inguinal region. She was diagnosed with bacterial inguinal cellulitis and was administered antibiotics. The next day, a polymorphous rash emerged on her trunk. After 3 days of antibiotics, however, her fever continued and the cellulitis had spread over the entire lower abdomen. Simultaneously, the bilateral bulbar conjunctival injection without exudate became more prominent and her lips became erythematous. In addition, erythematous changes on her palms appeared a few hours later, which led to the diagnosis of KD. Since she had a high risk score that predicted no response to initial intravenous immunoglobulin (IVIG) at the initiation of treatment, she was treated with IVIG, intravenous prednisolone (PSL), and oral aspirin. The KD symptoms improved the next day, but the cellulitis did not completely resolve until 2 months after discharge. The patient's serum cytokine profile at admission had an IL-6 dominant pattern which was consistent with that of patients with KD despite her initial lack of KD symptoms, and the pattern observed at admission was sustained until IVIG and PSL administration. Conclusion. KD should be included in the differential diagnosis for patients presenting with inguinal cellulitis who are unresponsive to initial empiric antibiotics. [ABSTRACT FROM AUTHOR]

Postpartum hemorrhage (PPH) remains a leading cause of maternal death worldwide, and it is important to understand the relative contributions of different risk factors. We assessed the incidence of these among cases of transvaginal delivery. Between June 2013 and July 2016, a prospective cohort study was conducted at a tertiary perinatal medical facility in Japan. Women were administered a questionnaire to ascertain risk factors for PPH, defined as a blood loss of 1,000 ml or more assessed using a calibrated under-buttocks drape and collection vessel at childbirth. We analyzed 1,068 transvaginal deliveries of singleton pregnancies. The incidence of PPH was 8.7%, and of severe PPH (1,500 ml blood loss or more) was 2.1%. Risk factors for postpartum hemorrhage among the deliveries were: fetal macrosomia (over 4000 g); pregnancy-induced hypertension; pregnancy generated by assisted reproductive technology; severe vaginal or perineal lacerations; and weight gain over 15 kg during pregnancy. Such high weight gain significantly increased the incidence of PPH compared with women showing less than 10 kg weight gain during pregnancy. Monitoring these identified risk factors could enable extra vigilance during labor, and preparedness for managing PPH in all women giving birth. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) patients often have altered body composition including reduced muscle mass and increased fat mass. Some RA patients are likely to increase visceral fat without obesity [Body Mass Index (BMI) ≥ 25]. The objective of the study was to determine the association between obesity and/or visceral adiposity and the risk for atherosclerosis in Japanese RA patients. Obesity was evaluated using the BMI, with visceral adiposity evaluated using the visceral fat area (VFA) and the visceral/subcutaneous fat ratio (V/S ratio), quantified using the dual bioelectrical impedance method. Atherosclerosis was evaluated based on the intima-media thickness (IMT) and Plaque score (PS) of the carotid artery, measured using ultrasonography. Multivariate analysis was performed to determine the factors associated with IMT and PS. IMT and PS were compared among groups of patients sub-classified according to BMI and VFA levels. The V/S ratio was higher in RA patients than healthy controls, after adjustment for age, BMI, and waist circumference. On multivariate analysis, the V/S ratio, but not the BMI, was independently associated with the IMT and PS. Among the sub-classifications for BMI and VFA, non-obese patients with a high visceral adiposity (18.5 ≤ BMI < 25 kg/m2 and VFA ≥ 100 cm2) had the highest IMT (mean IMT, 0.93 ± 0.29 mm; maximum IMT, 1.44 ± 0.71 mm) and PS (1.43 ± 0.61), compared to all other BMI and VFA subgroups. RA patients have increased visceral adiposity, which is associated with a high prevalence of atherosclerotic of plaques. Non-obese RA patients who have visceral adiposity have a specifically higher risk for atherosclerosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message Our patient was diagnosed as having discordant twin growth with Ebstein's anomaly in the larger fetus. Cardiac function was deteriorated in accordance with progression of gestational age. Our observation indicated cardiac failure of the larger fetus. The most important issue in this situation is management of the timing of delivery. [ABSTRACT FROM AUTHOR]

Chorioamnionitis is usually caused by migration of cervicovaginal flora through the cervical canal in women with ruptured membranes. Common causative pathogens are genital mycoplasmas, anaerobes, enteric gram-negative bacilli, and group B streptococcus. There have been only seven previous reports of chorioamnionitis due to Staphylococcus aureus and their clinical courses are characterized by rapid disease progression and poor prognosis. This case report describes a case of acute chorioamnionitis due to S. aureus , which was successfully managed with immediate cesarean section and postoperative intensive care. A 22-year-old woman presented at 39 weeks' gestation with a fever and acute lower abdominal pain. Fetal heart monitoring showed fetal distress. Immediate cesarean delivery was performed under general anesthesia. A male infant weighing 2450 g was born. He had Apgar scores of 3 and 7 at 1 and 5 min, respectively. He was immediately intubated and admitted to the neonatal intensive care unit. Maternal blood culture, vaginal culture, neonatal nares, and blood and gastric fluid culture all showed methicillin-sensitive S. aureus . Histopathology of the placenta demonstrated focal acute funisitis and acute chorioamnionitis. Interestingly, most of the patients in the previous reports developed chorioamnionitis due to S. aureus despite the presence of intact membranes, as in our case. Bacterial spread in the absence of membrane rupture and the presence of bacteremia suggests hematogenous, rather than ascending, etiology of S. aureus chorioamnionitis. [ABSTRACT FROM AUTHOR]

Malignant lymphoma of the uterine cervix is exceedingly rare and is difficult to diagnose by cervical cytology. The current study presents a case of malignant lymphoma of the uterine cervix that was presumptively diagnosed by cervical cancer screening in which the patient had no clinical symptoms. The anterior lip of the uterine cervix was occupied by a macroscopic hemorrhagic tumor. The obtained tumor cells exhibited typical cytological features of malignant lymphoma and were positive for CD20. The final diagnosis was diffuse large B cell lymphoma of the uterine cervix, stage IIEA (Ann Arbor classification). The patient received 6 courses of R-CHOP chemotherapy and achieved complete remission. Despite its rarity, the possibility of malignant lymphoma should be considered while screening for cervical cancers using Pap smears. The Pap test screening may be useful for the early diagnosis of malignant lymphoma of the uterine cervix in certain cases. By reaching a rapid and accurate diagnosis, immediate treatment may be initiated and surgery may be avoided. [ABSTRACT FROM AUTHOR]

At present, polylactide (PLA) film with high toughness is on expectation, but in general, it is brittle with 45 MPa tensile strength and only 3% elongation at break. The present work clarifies that isotropically small crystalline lamellae is the key microstructure to obtain super-tough PLA (180 MPa tensile strength and 80% elongation at break). The systematic study on two parameters of biaxial-stretching technique, i.e. , stretching rate and draw ratio, allows us understanding the development of microstructure, especially the crystalline phase, the regular chain packing in the crystal lattice, and the evolution of the higher-order structure. The integrated structural analyses based on Fourier transform infrared spectroscopy (FTIR), 2D-wide angle X-ray diffraction (2D-WAXD) and 2D-small angle X-ray scattering (2D-SAXS) declare that the structurally-irregular amorphous PLA starts to develop the mesophase and δ -crystal (including α -crystal) with the crystallite size of several tens of nanometers by slow biaxial-stretching (3 mm/s). At this stage, the biaxially oriented PLA (BOPLA) still shows relatively poor mechanical properties. When the stretching rate and the draw ratio increased above a certain level, i.e. , 75 mm/s and 5 × 5, respectively, the small δ -crystallites of about 10 nm size with isotropic orientation are mainly formed. This structural evolution has been found to result in the drastic increase of the toughness of BOPLA film, which is about 4 times higher than the PLA film produced by conventional stretching. In this way, the present work shows for the first time that the simple way to toughen the PLA film is to induce a well-dispersed higher-order structure consisting of many but small δ -crystallites as seen in the model case of BOPLA. [ABSTRACT FROM AUTHOR]

Aim The 9p21 region has been pointed out by the genome-wide association studies as a hot spot for disease-associated variants. Most of the diseases linked with the locus are aging-related conditions, such us cardiovascular disease, diabetes and cancer. Centenarians are known to present a reduced risk and delayed onset for these conditions. Here, we aimed to assess if the 9p21 variants contribute to this protection by possibly altering basic aging mechanisms. Methods We genotyped 15 tag single-nucleotide polymorphisms ( SNP) along the CDKN2 A/ B/ ANRIL locus in 1505 individuals. The participants were divided in three groups: centenarians, septuagenarians and young controls. Centenarians were 593 participants (age range 100-116 years, mean 105.9 years), septuagenarians were 434 volunteers aged between 69 and 71 years (mean 70.1 ± 0.9 years) and the 478 young controls were under the age of 50 years (range 14-50 years, mean 41.8 years). We genotyped the SNP rs1333049 in an additional sample of 231 coronary artery disease patients to confirm the 9p21 association. Results The leading coronary artery disease-associated SNP rs1333049 was associated with coronary artery disease; however, none of the 9p21 SNP evaluated in the present study were associated with extreme longevity. Conclusions Our findings suggest that the 9p21 disease-associated polymorphisms do not contribute to the life-long protection from cardiovascular and other age-related diseases observed in centenarians. It is likely that this protection is mediated by mechanisms different from the ones underlying the 9p21 association. Geriatr Gerontol Int 2015; 15: 797-803. [ABSTRACT FROM AUTHOR]

Arabidopsis ubiquitin ligases ATL31 and homologue ATL6 control the carbon/nitrogen nutrient and pathogen responses. A mutant with the loss-of-function of both atl31 and atl6 developed light intensity-dependent pale-green true leaves, whereas the single knockout mutants did not. Plastid ultrastructure and Blue Native-PAGE analyses revealed that pale-green leaves contain abnormal plastid structure with highly reduced levels of thylakoid proteins. In contrast, the pale-green leaves of the atl31/atl6 mutant showed normal Fv/Fm. In the pale-green leaves of the atl31/atl6, the expression of HEMA1, which encodes the key enzyme for 5-aminolevulinic acid synthesis, the rate-limiting step in chlorophyll biosynthesis, was markedly down-regulated. The expression of key transcription factor GLK1, which directly promotes HEMA1 transcription, was also significantly decreased in atl31/atl6 mutant. Finally, application of 5-aminolevulinic acid to the atl31/atl6 mutants resulted in recovery to a green phenotype. Taken together, these findings indicate that the 5-aminolevulinic acid biosynthesis step was inhibited through the down-regulation of chlorophyll biosynthesis-related genes in the pale-green leaves of atl31/atl6 mutant. [ABSTRACT FROM AUTHOR]

Background: The Cilostazol Stroke Prevention Study 2 (CSPS 2) showed that cilostazol significantly reduced the risk of stroke by 25.7% relative to aspirin, with significantly fewer hemorrhagic events, in patients with prior ischemic stroke, excluding cardioembolic stroke. However, whether the benefit of cilostazol is sustained in patients with a high risk of bleeding has not been examined. Methods: We conducted a subanalysis of CSPS 2 to examine whether known risk factors for hemorrhagic stroke, such as stroke subtype and systolic blood pressure (SBP), influence the efficacy of the study drugs on hemorrhagic stroke. The relative risk reduction of hemorrhagic stroke was determined from the incidences calculated by the person-year method. The cumulative incidence rates of ischemic stroke and hemorrhagic stroke were estimated and plotted using the Kaplan-Meier method. Incidences of serious hemorrhage and hemorrhage requiring hospital admission were also evaluated in the two treatment groups. Hazard ratios (HR) and 95% confidence intervals (95% CI) calculated by the Cox proportion hazard model for cilostazol versus aspirin were assessed, and a log-rank test was used for the comparison between treatments. Results: The incidence of hemorrhagic stroke was significantly lower in the cilostazol group than in the aspirin group among patients with prior lacunar stroke (0.36 vs. 1.20% in person-year, HR 0.35, 95% CI 0.18-0.70, p < 0.01), but not among those with prior atherothrombotic stroke (0.31 vs. 0.59% in person-year, HR 0.53, 95% CI 0.14-2.0, p = 0.34). The incidence of hemorrhagic stroke was significantly lower in the cilostazol group than in the aspirin group throughout all SBP categories (Poisson regression model including time-dependent covariates, p < 0.01) including SBP above 140 mm Hg (cilostazol 0.45% vs. aspirin 1.44% in person-year; Poisson regression model including time-dependent covariates, p = 0.02). Cilostazol, compared with aspirin, significantly reduced the incidence of cerebral hemorrhage (HR 0.36, 95% CI 0.19-0.70, p < 0.01), overall hemorrhage requiring hospital admission (HR 0.53, 95% CI 0.29-0.97, p = 0.04), and gastrointestinal (GI) bleeding requiring hospital admission (HR 0.44, 95% CI 0.21-0.90, p = 0.03). Conclusions: Hemorrhagic stroke was less frequent in the cilostazol group than in the aspirin group among patients with lacunar stroke as well as those with increased blood pressure levels. As for extracranial hemorrhage requiring hospitalization, GI bleeding was also less frequent in the cilostazol than in the aspirin group. Cilostazol is supposed to be a therapeutic option to replace aspirin for secondary stroke prevention, especially in these subgroups with high risks for hemorrhagic events. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: AS1069562 is the (+)-isomer of indeloxazine, which had been clinically used as a cerebral activator for the treatment of cerebrovascular diseases with serotonin and norepinephrine reuptake inhibition (SNRI) and neuroprotection. Here, we compared the analgesic effects of repeated treatment with AS1069562 and duloxetine, a selective SNRI, on pain-related behavior in a rat model of streptozotocin (STZ)-induced diabetic neuropathy. Further, we also evaluated the effects on the expression of neurotrophic factors and nerve conduction velocity. AS1069562 and duloxetine by single daily administration for 4 weeks significantly improved mechanical allodynia in STZ-induced diabetic rats and did not affect plasma glucose level or body weight. Interestingly, the analgesic effect of AS1069562 continued after a consecutive 1-week treatment discontinuation, although the plasma concentration of AS1069562 was reduced to undetectable levels. In contrast, the efficacy of duloxetine disappeared after treatment discontinuation. Expression analysis demonstrated that AS1069562 significantly restored decreased insulin-like growth factor 1 and fibroblast growth factor 2 mRNA levels in dorsal root ganglion and spinal cord, respectively, whereas duloxetine did not affect the expression levels of neurotrophic factors. In addition, AS1069562 reversed the slowing of nerve conduction velocity. The results of this study indicate that the analgesic effect of repeated dosing of AS1069562 but not duloxetine is persistent even after a 1-week drug discontinuation in STZ-induced diabetic rats. Restoration of neurotrophic factors may be involved in the curative-like pharmacological effect of this agent. Thus, AS1069562 may potentially offer a better treatment option for patients with painful diabetic neuropathy than duloxetine via different mechanisms. [Copyright &y& Elsevier]

ACE type 2 (ACE2) functions as a negative regulator of the reninangiotensin system by cleaving angiotensin II (AII) into angiotensin 1-7 (A1-7). This study assessed the role of endogenous ACE2 in maintaining insulin sensitivity. Twelve-week-old male ACE2 knockout (ACE2KO) mice had normal insulin sensitivities when fed a standard diet. AII infusion or a high-fat, high-sucrose (HFHS) diet impaired glucose tolerance and insulin sensitivity more severely in ACE2KO mice than in their wild-type (WT) littermates. The strain difference in glucose tolerance was not eliminated by an AII receptor type 1 (AT1) blocker but was eradicated by A1-7 or an AT1 blocker combined with the A1-7 inhibitor (A779). The expression of GLUT4 and a transcriptional factor, myocyte enhancer factor (MEF) 2A, was dramatically reduced in the skeletal muscles of the standard diet-fed ACE2KO mice. The expression of GLUT4 and MEF2A was increased by A1-7 in ACE2KO mice and decreased by A779 in WT mice. A1-7 enhanced upregulation of MEF2A and GLUT4 during differentiation of myoblast cells. In conclusion, ACE2 protects against high- calorie diet-induced insulin resistance in mice. This mechanism may involve the transcriptional regulation of GLUT4 via an A1-7-dependent pathway. [ABSTRACT FROM AUTHOR]

Abstract: Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis. Objective: We assessed the hypothesis that 9p21 locus polymorphisms influence the expression of the transcripts in the region (ANRIL, CDKN2A/B) and that these transcripts contribute to atherogenesis through the modulation of proliferation in VSMC. Methods: We genotyped 18 SNPs (r 2 <0.8 and MAF>0.05) across the region of interest: CDKN2A/B and ANRIL, encompassing the CVD-associated region. RNA and DNA were extracted from the blood of 57 volunteers (69–72years old). Carotid ultrasound was performed in 56 subjects. CDKN2A/B and ANRIL (exons 1–2 and 17–18) expression was measured employing RT-PCR. Gene expression and cell growth were evaluated in cultured VSMC after the siRNA-mediated knock-down of ANRIL. Results: The risk alleles for atherosclerosis-related phenotypes were consistently associated with a lower expression of ANRIL when evaluating exons 1–2. Common carotid artery stenosis was associated with a significantly lower (P <0.01) expression of ANRIL (exons 1–2). ANRIL knock-down in VSMC caused significant variation in expression of CDKN2A/B (P <0.05) and reduction of cell growth (P <0.05) in vitro. Conclusion: Disease-associated SNPs at the 9p21 locus predominantly affect the expression of ANRIL. Overall, our results suggest that several CVD-associated SNPs in the 9p21 locus affect the expression of ANRIL, which, in turn modulate cell growth, possibly via CDKN2A/B regulation. [Copyright &y& Elsevier]

To disclose the neuropathological progression course of Machado-Joseph disease (MJD), magnetic resonance imaging (MRI) findings of six genetically confirmed MJD cases (four males and two females, including an autopsied female, all unrelated to one another) were further investigated on neurodegeneration. Brain MRI studies were repeated in all cases at different stages of the disease. Ages at the first MRI study ranged from 47 to 65 years (55.2 ± 7.1), with observation periods from 4.5 to 10.6 years (6.95 ± 2.48). We paid particular attention to two types of previously reported MRI findings detectable using T2-weighted images. One is located just outside the internal capsules, and another in the pons. A linear high-intensity change along the internal capsules was detected in all cases, and showed progression during the observation period. A comparison between MRI and autopsy findings suggested that the lesion might reflect degeneration with neuronal loss, astrocytosis, and gliosis in the internal segment of the globus pallidus. A cross-shaped high-intensity change in the pons was well advanced but still incomplete in all cases. In this region, pontine transverse fibers were atrophic, while longitudinal fibers remained intact. Pontine nuclei showed apparent nerve cell loss, and the remaining cells had many 1C2-positive intranuclear inclusions. Since these findings were detected both by lifetime images and by postmortem examination, MRI intensity changes could track the progression of neurodegeneration. Based on a comparison between MRI findings and neuropathology, the degeneration of an internal segment of the globus pallidus (one of the pathological features of MJD) had progressed following the initial symptoms. [ABSTRACT FROM AUTHOR]

Summary: Background: The antiplatelet drug cilostazol is efficacious for prevention of stroke recurrence compared with placebo. We designed the second Cilostazol Stroke Prevention Study (CSPS 2) to establish non-inferiority of cilostazol versus aspirin for prevention of stroke, and to compare the efficacy and safety of cilostazol and aspirin in patients with non-cardioembolic ischaemic stroke. Methods: Patients aged 20–79 years who had had a cerebral infarction within the previous 26 weeks were enrolled at 278 sites in Japan and allocated to receive 100 mg cilostazol twice daily or 81 mg aspirin once daily for 1–5 years. Patients were allocated according to a computer-generated randomisation sequence by means of a dynamic balancing method using patient information obtained at registration. All patients, study personnel, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was the first occurrence of stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage). The predefined margin of non-inferiority was an upper 95% CI limit for the hazard ratio of 1·33. Analyses were by full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT00234065. Findings: Between December, 2003, and October, 2006, 2757 patients were enrolled and randomly allocated to receive cilostazol (n=1379) or aspirin (n=1378), of whom 1337 on cilostazol and 1335 on aspirin were included in analyses; mean follow-up was 29 months (SD 16). The primary endpoint occurred at yearly rates of 2·76% (n=82) in the cilostazol group and 3·71% (n=119) in the aspirin group (hazard ratio 0·743, 95% CI 0·564–0·981; p=0·0357). Haemorrhagic events (cerebral haemorrhage, subarachnoid haemorrhage, or haemorrhage requiring hospital admission) occurred in fewer patients on cilostazol (0·77%, n=23) than on aspirin (1·78%, n=57; 0·458, 0·296–0·711; p=0·0004), but headache, diarrhoea, palpitation, dizziness, and tachycardia were more frequent in the cilostazol group than in the aspirin group. Interpretation: Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol could be used for prevention of stroke in patients with non-cardioembolic stroke. Funding: Otsuka Pharmaceutical. [Copyright &y& Elsevier]

Growth-blocking peptide (GBP) is a hormone-like peptide that suppresses the growth of the host armyworm. Although the 23-amino acid GBP (1-23 GBP) is expressed in nonparasitized armyworm plasma, the parasitization by wasp produces the 28-amino acid GBP (1-28 GBP) through an elongation of the C-terminal amino acid sequence. In this study, we characterized the GBP variants, which consist of various lengths of the C-terminal region, by comparing their biological activities and threedimensional structures. The results of an injection study indicate that 1-28 GBP most strongly suppresses larval growth. NMR analysis shows that these peptides have basically the same tertiary structures and that the extension of the C-terminal region is disordered. However, the C-terminal region of 1-28 GBP undergoes a conformational transition from a random coiled state to an a-helical state in the presence of dodecylphosphocholine micelles. This suggests that binding of the C-terminal region would affect larval growth activity. [ABSTRACT FROM AUTHOR]