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In principle, reconstruction in macrostomia requires symmetry and accurate positioning of the newly reconstructed commissure. The proper position of the new commissure can be determined by several methods. In the determination of the new commissure of bilateral cases, generally the average length of the lips or the distance from anatomical landmarks other than the lips, such as the pupils or tragi, has been used. A new approach was reported by Tse et al in 2018: the anatomic approximation approach. Macrostomia repair refers to anatomical landmarks in the lips to determine the new commissure. The authors performed surgery using this anatomic approximation approach for bilateral macrostomia and achieved the good results.

In this study, we found that nuclear receptors FXR and LXR (originally characterized as regulatory factors involved in cholesterol/bile acid homeostasis) regulate the expression of Oct3/4, a marker for cell differentiation, in both normal renal-derived cell line HK-2 and renal adenocarcinoma cell line ACHN. Down-regulation of Oct3/4 expression by activating FXR and LXR occurs only in normal renal cell-derived HK-2 cells. We also found that the RNA-binding protein, ELAVL2, oppositely regulates Oct3/4 expressions in HK-2 and ACHN cells. Moreover, we revealed that LXR-alpha and LXR-beta regulate each other's expression. Although an LXR-beta-specific agonist is assumed to be the basis for an anti-arteriosclerotic drug that only stimulates reverse cholesterol transport, our findings show that the development of such an anti-arteriosclerotic drug would require further elucidation of the complex mechanism of LXR-alpha and LXR-beta regulation.

SIRT1, an NAD+-dependent deacetylase, causes deacetylation and down-regulation of its target p53. Given that p53 is an upstream regulator of the transcription of the cyclin-dependent kinase inhibitor p21/Cip1, SIRT1 is hypothesized to play a stimulatory role in carcinoma cell proliferation. We previously reported that down-regulation of SIRT1 caused the increase in p21/Cip1 in a post-transcriptional manner, suggesting that p53 is not involved in the p21/Cip1 increase and raising the question whether SIRT1 exhibits the activity other than deacetylase. In the present study, we examined whether SIRT1 down-regulation and the inhibitor for SIRT1 deacetylase activity affects p21/Cip1 and p53 expression in renal adenocarcinoma cells and normal renal cells. SIRT1 knockdown caused an increase in p53 and p21/Cip1 protein levels in renal adenocarcinoma ACHN cells but not normal renal-derived HK-2 cells. The increase in p53 in ACHN cells is unlikely to contribute to the upregulation of p21/Cip1 expression, given that SIRT1 knockdown did not increase p21/Cip1 mRNA levels in these cells. In contrast to the SIRT1-knock down assay, SIRT1 deacetylase inhibitor did not affect p53 or p21/Cip1 protein levels in ACHN cells. Therefore, SIRT1-knockdown likely stimulates p53 and p21/Cip1 protein expression in a deacetylase-independent manner.

The spirostanol saponin AU-1 from Agavaceae plants stimulates the expression of the glycolytic enzyme phosphoglycerate mutase (PGAM) in ACHN cells. We hypothesized that this may arise from the downregulation of the NAD+-dependent deacetylase SIRT1. In this article, we showed that, unlike in renal adenocarcinoma cells, AU-1 does not affect the expression of SIRT1 in the normal renal cell-derived cell line HK-2. Consistent with the lack of a downregulation of SIRT1, AU-1 did not upregulate, but rather decreased PGAM expression. Moreover, AU-1 inhibited the increase in PGAM levels that results from the knock-down of SIRT1. Our results suggest that AU-1 may prevent carcinogenesis caused by increased cellular PGAM.

The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor which is abundant in the liver, intestine, and kidney. FXR is a pivotal factor in cholesterol/bile acid homeostasis but is involved in the growth of hepatocellular carcinoma cells. In the present study, we investigated whether FXR is also involved in the growth of renal adenocarcinoma cells. The cell growth of renal adenocarcinoma cell line ACHN was inhibited by FXR knockdown and stimulated by FXR ligand, while that of a normal renal cell-derived cell line, HK-2, was not affected. The carcinoma-specific stimulation of cell growth by FXR was found to arise from down-regulation of p53 and p21/Cip1 mRNA expression. Our study showed that FXR stimulates proliferation of renal adenocarcinoma cells and that FXR knockdown is useful for growth suppression of renal adenocarcinoma without cytotoxicity to normal renal cells.

Development of type 2 diabetes mellitus and insulin resistance is associated with a quality of dietary fatty acids such as saturated and unsaturated fatty acids. Dietary fatty acids also include transform of unsaturated fatty acids and intake of transform of oleate (elaidate) is associated with cardiovascular disease. However, little is known about the roles of elaidate in insulin responsiveness. We show here that elaidate impairs insulin-dependent glucose uptake in adipocytes. Differentiation with 10 μM elaidate, which is close to physiological plasma concentration, reduces insulin-dependent glucose uptake. Furthermore, insulin-dependent GLUT4 translocation is disturbed in adipocytes differentiated with elaidate. In addition, analysis of lipolysis and gene expression shows that deteriorative effects of elaidate on insulin responsiveness are limited but not general. Thus, our findings reveal that differentiation with elaidate tends to affect insulin-dependent glucose uptake through alternation of GLUT4 translocation from cytosol to the plasma membrane.

In this study, we established a new method to analyze the characteristic flavor of beer: selectable one-dimensional or two-dimensional GC-olfactometry/MS (1D- or 2DGC-O/MS). We attempted to identif...

By using a piezoelectric actuator, a real steel bridge can be accelerated locally to detect the effect of small damage like fatigue crack and connection damage as a response to change of vibration. Power spectrum density (PSD) function of the response can give us the indication of the extent of damage before and after the damage. Detailed analysis of PSD before and after damage can give us the location and size (area) of damage. This paper shows the experimental result of damage detection by using local excitation method on a real bridge.

The Bridge Engineering Laboratory in Kitami Institute of Technology, Japan has introduced a number of different damage identification techniques to detect structural damage and identify its location utilizing piezoelectric actuators as a localized excitation source. Several spectral functions, such as cross spectral density, power spectral density, phase angle and transfer function estimate, were used to estimate the dynamic response of the structure. Each function’s magnitude, measured in a specified frequency range, is used in the damage identification methods. The change of the spectral function magnitude between the baseline state and the current state is then used to identify the location of possible damage in the structure. It is then necessary to determine which spectral function is best able to estimate the dynamic response and which algorithm is best able to identify the damage. The first part of this paper compares the performance of different spectral functions when their magnitude is used in one damage identification algorithm using experimental data from a railway steel bridge. The second part of this paper compares the performance of different damage identification algorithms using the same data.

Purpose Following initial positive reports of the use of bone marrow aspirate concentrate (BMAC) in combination with bovine bone mineral (BBM) in augmentation procedures, the technique was evaluated in patients with mandibular deficiency. Materials and methods Two adult patients required surgical correction of a deficient alveolar ridge (one patient showed horizontal deficiency only, and the other patient presented with horizontal and vertical deficiency) prior to dental implant placement. In both patients, the reconstruction was performed with BBM in combination with mononuclear cells concentrated by the BMAC method using different techniques. Results The patients recovered well from all surgical procedures. Histologically, there was uniform bone formation, which allowed placement of dental implants. Conclusion The results suggest that the use of BMAC in combination with BBM, without autogenous bone, has the potential to restore horizontal and vertical mandibular alveolar defects, providing a functional bone structure and allowing dental implant placement for subsequent prosthetic rehabilitation.

This paper deals with the detection of damage in a lightly reinforced concrete beam using dynamic measurements. An algorithm based on changes in the power spectral density (PSD) is presented. The algorithm is used to detect damage, predict the location and assess the extent of damage in the reinforced concrete beam. The method is based on the measured data on the beam after introducing some damage at salient locations. A tuneable piezoelectric actuator was used to produce additional peaks in the dynamic response of the system in the frequency domain. These additional peaks were adjusted over the frequency band by tuning the actuator. It was noticed from the results, that the PSD method detected the damage, determine the location and could monitor the increase in damage in the beam

Purpose: The purpose of this work was to evaluate the potential of substituting autogenous bone (AB) by bone marrow aspirate concentrate (BMAC). Both AB and BMAC were tested in combination with a bovine bone mineral (BBM) for their ability of new bone formation (NBF) in a multicentric, randomized, controlled, clinical and histological noninferiority trial.Materials and Methods: Forty-five severely atrophied maxillary sinus from 26 patients were evaluated in a partial cross-over design. As test arm, 34 sinus of 25 patients were augmented with BBM and BMAC containing mesenchymal stem cells. Eleven control sinus from 11 patients were augmented with a mixture of 70% BBM and 30% AB. Biopsies were obtained after a 3-4-month healing period at time of implant placement and histomorphometrically analyzed for NBF.Results: NBF was 14.3%+/- 1.8% for the control and nonsignificantly lower (12.6%+/- 1.7%) for the test (90% confidence interval: -4.6 to 1.2). Values for BBM (31.3%+/- 2.7%) were significantly higher for the test compared with control (19.3%+/- 2.5%) (p Conclusions: NBF after 3-4 months is equivalent in sinus, augmented with BMAC and BBM or a mixture of AB and BBM. This technique could be an alternative for using autografts to stimulate bone formation.

In this paper, a new approach for damage detection in beam-like structures is presented. The method can be used without the need for baseline modal parameters of the undamaged structure. Another advantage of the proposed method is that it can be implemented using a small number of sensors. In the proposed technique, the measured dynamic signals are decomposed into the wavelet packet decomposition (WPD) components, the power spectrum density (PSD) of each component is estimated and then a damage localisation indicator is computed to indicate the structural damage. The proposed method is firstly illustrated with a simulated beam and the identified damage is satisfactory with assumed damage. Then, the method is applied to a steel beam. The effect of damage location and the effects of wavelet type and the decomposition level are examined. The results show that the proposed method has great potential in crack detection of beam-like structures.

Several studies have reported certain bone morphogenic proteins (BMPs) to have positive effects on bone generation. Although some investigators have studied the effects of human recombinant BMP (rhBMP-2) in sinus augmentation in sheep, none of these studies looked at the placement of implants at the time of sinus augmentation. Furthermore, no literature could be found to report on the impact that different implant systems, as well as the positioning of the implants had on bone formation if rhBMP-2 was utilized in sinus-lift procedures.The aim of this study was to compare sinus augmentation with rhBMP-2 on a poly-d, l-lactic-co-glycolic acid gelatine (PLPG) sponge with sinus augmentation with autologous pelvic cancellous bone in the maxillary sinus during the placement of different dental implants.Nine adult female sheep were submitted to bilateral sinus-floor elevation. In one side (test group) the sinus lift was performed with rhBMP-2 on a PLPG-sponge, while the contralateral side served as the control by using cancellous bone from the iliac crest. Three different implants (Bränemark(®), 3i(®) and Straumann(®)) were inserted either simultaneously with the sinus augmentation or as a two staged procedure 6 weeks later. The animals were sacrificed at 6 and 12 weeks for histological and histomorphometrical evaluations during which bone-to-implant contact (BIC) and bone density (BD) were evaluated.BD and BIC were significantly higher at 12 weeks in the test group if the implants were placed at the time of the sinus lift (p0.05). No difference was observed between the different implant systems or positions.The use of rhBMP-2 with PLPG-sponge increased BIC as well as BD in the augmented sinuses if compared to autologous bone. Different implant systems and positions of the implants had no effect on BIC or BD.

Our aim was to compare the osteogenic potential of mononuclear cells harvested from the iliac crest combined with bovine bone mineral (BBM) (experimental group) with that of autogenous cancellous bone alone (control group). We studied bilateral augmentations of the sinus floor in 6 adult sheep. BBM and mononuclear cells (MNC) were mixed and placed into one side and autogenous bone in the other side. Animals were killed after 8 and 16 weeks. Sites of augmentation were analysed radiographically and histologically. The mean (SD) augmentation volume was 3.0 (1.0) cm 3 and 2.7 (0.3) cm 3 after 8 and 16 weeks in the test group, and 2.8 (0.3) cm 3 (8 weeks) and 2.8 (1.2) cm 3 (16 weeks) in the control group, respectively. After 8 weeks, histomorphometric analysis showed 24 (3)% BBM, and 19 (11)% of newly formed bone in the test group. The control group had 20 (13%) of newly formed bone. Specimens after 16 weeks showed 29 (12%) of newly formed bone and 19 (3%) BBM in the test group. The amount of newly formed bone in the control group was 16 (6%). The results show that mononuclear cells, including mesenchymal stem cells, in combination with BBM as the biomaterial, have the potential to form bone.

We previously demonstrated that FGD1, the Cdc42 guanine nucleotide exchange factor (GEF) responsible for faciogenital dysplasia, and its homologue FGD3 are targeted by the ubiquitin ligase SCF(FWD1) upon phosphorylation of two serine residues in their DSGIDS motif and subsequently degraded by the proteasome. FGD1 and FGD3 share highly homologous Dbl homology (DH) and adjacent pleckstrin homology (PH) domains, both of which are responsible for GEF activity. However, their function and regulation are remarkably different. Here we demonstrate extracellular signal-responsive translocation of FGD1, but not FGD3. During the wound-healing process, translocation of FGD1 to the leading edge membrane occurs in cells facing to the wound. Furthermore, epidermal growth factor (EGF) stimulates the membrane translocation of FGD1, but not FGD3. As the most striking difference, FGD3 lacks the N-terminal proline-rich domain that is conserved in FGD1, indicating that proline-rich domain may play a crucial role in signal-responsive translocation of FGD1. Indeed, there is a faciogenital dysplasia patient who has a missense mutation in proline-rich domain of FGD1, by which the serine residue at position 205 is substituted with isoleucine. When expressed in cells, the mutant FGD1 with S(205)/I substitution fails to translocate to the membrane in response to the mitogenic stimuli. Thus we present a novel mechanism by which the activity of FGD1, a GEF for Cdc42, is temporally and spatially regulated in cells.

We previously demonstrated that FGD1, the Cdc42 guanine nucleotide exchange factor (GEF) responsible for faciogenital dysplasia, is targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. Here we show that FGD3, which was identified as a homologue of FGD1 but has been poorly characterized, has conserved the same motif and is down-regulated similarly by SCF(FWD1/beta-TrCP). Although FGD3 and FGD1 share strikingly similar Dbl homology (DH) domains and adjacent pleckstrin homology (PH) domains, both of which are responsible for guanine nucleotide exchange, there also exist remarkable differences in their structures. Indeed, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells: whereas FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. Furthermore, FGD1 and FGD3 reciprocally regulated cell motility: when inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration whereas FGD3 inhibited it. Thus we demonstrate that the highly homologous GEFs, FGD1 and FGD3 play different roles to regulate cellular functions but that their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP).

Introduction The aim of this work was to analyse the suitability of mesenchymal stem cell isolation by FICOLL density centrifugation and the closed bone marrow aspirate concentrate (BMAC) system for sinus augmentation with bovine bone mineral (BBM) in the sheep model. Methods 16 sheep underwent sinus augmentation with BBM and MSCs; they were divided between two groups with survival points of 8 and 16 weeks. For the FICOLL control arm three, and for the BMAC test arm, five augmentations were performed for each time point. The derived cell numbers were counted; a colony forming unit (CFU) assay was performed; the pluripotency of the MSCs was proved; histological and histomorphometrical analysis were performed. Results The approach of using BBM and MSCs in combination with fibrin adhesive was sufficient for new bone formation as the FICOLL experiment indicated. However, due to significantly lower cell numbers isolated using the BMAC in sheep, less new bone was formed in the test arm. Conclusions The BMAC system is well suited for human MSC isolation but it needs to be optimized to fit sheep cell characteristics if it is to be used in this animal model.

This paper presents structural damage detection method based on changes in Transfer Function Estimate (TFE) for detecting damage, predicting its location and monitoring the growth in damage. This method assumes that the displacement or the acceleration response time histories at various locations along the structure both before and after damage are available for damage assessment These responses are used to estimate TFE. The change of TFE between the baseline state and the current state is then used to identify the location of possible damage in the structure. TI1e method is applied to the experimental and numerical data obtained from a railway steel bridge that is no longer in service. Several damage scenarios were introduced to the main girder of the test structure. Results show the method can be used to detect the damage, determine the exact location and measure the growth in damage with very good accuracy. The use of piezoelectric actuators as a local excitation source for large structures such as steel bridges is also presented. Experimental and numerical results show that the proposed approach may be successfully implemented on-line to detect the damage and to locate regions where damage occurred., application/pdf

An experimental investigation was conducted to strengthen shear deficient reinforced concrete columns using ferrocement jacketing. Three scale model specimens, identical to the actual bridge piers, were tested. One of the piers was tested under as-built condition while the other two were strengthened with layers of wire mesh before being tested. All the specimens were subjected to a simulated seismic loading and constant axial load. It was observed from the experimental results that the ferrocement-jacketed specimens exhibited enhanced stiffness, strength, energy dissipation and ductility and the mode of failure changed from brittle shear failure to a ductile flexural failure. The control specimens failed by shear at a relatively low lateral displacement. A finite element model was developed and the results obtained from the numerical analysis compared well with the experimental results. A design methodology for strengthening piers with square/rectangular columns with inadequate shear strength using ferro...

Fatty acid hydroperoxide lyase (HPL), a member of cytochrome P450 (CYP74), produces aldehydes and oxo-acids involved in plant defensive reactions. In monocots, HPL that cleaves 13-hydroperoxides of fatty acids has been reported, but HPL that cleaves 9-hydroperoxides is still unknown. To find this type of HPL, in silico screening of candidate cDNA clones and subsequent functional analyses of recombinant proteins were performed. We found that AK105964 and AK107161 (Genbank accession numbers), cDNAs previously annotated as allene oxide synthase (AOS) in rice, are distinctively grouped from AOS and 13-HPL. Recombinant proteins of these cDNAs produced in Escherichia. coli cleaved both 9- and 13-hydroperoxide of linoleic and linolenic into aldehydes, while having only a trace level of AOS activity and no divinyl ether synthase activity. Hence we designated AK105964 and AK107161 OsHPL1 and OsHPL2 respectively. They are the first CYP74C family cDNAs to be found in monocots.

The sophisticated arrangement of confinement in columns using closely spaced stirrups not only interrupts the continuity and creates a plane of weakness between core and concrete cover, but also adds to the problem of congestion. This is the reason why most of the time it may not be possible to confine the structure sufficiently by providing laterals alone, and supplementary confinement such as ferrocement composites may be necessary. The success of the ferrocement technology is attributed to the ready availability of its component materials, low level of technology needed for construction and low cost. In the past decades, ferrocement has emerged as a very good rehabilitating/restrengthening material because of its superior mechanical properties, high in-plane strength and mouldability. In the present paper a review of the research on ferrocement confinement of plain and reinforced concrete with applications to column retrofitting is presented.

本論文は橋梁全体の資産価値を評価するため, まず橋梁各部材の資産的評価を計算する手法を検討した. これまでの多くの橋梁の施工実績経費から橋梁各部材の単価的な建設必要経費を算出するとともに, 橋梁全体の初期建設費としての資産価値を評価できる手法を検討した. また橋梁点検要領による点検結果のランクを損傷係数として用いて現存する橋梁の現在の残存資産価値を算出した. これらの残存資産価値と初期建設費との比を橋梁健全度指数 (BHI) と呼び, 現存する橋梁の劣化を考慮した健全度をあらわす指標とした. またこれらの健全度指数についての解析結果を著者らが前論文において解析した橋梁総合健全度に関する解析結果と比較検討して, 橋梁健全度指数 (BHI) の有効性について検討した.