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In the field of materials science and engineering, statistical analysis and machine learning techniques have recently been used to predict multiple material properties from an experimental design. These material properties correspond to response variables in the multivariate regression model. This study conducts a penalized maximum likelihood procedure to estimate model parameters, including the regression coefficients and covariance matrix of response variables. In particular, we employ $l_1$-regularization to achieve a sparse estimation of regression coefficients and the inverse covariance matrix of response variables. In some cases, there may be a relatively large number of missing values in response variables, owing to the difficulty in collecting data on material properties. A method to improve prediction accuracy under the situation with missing values incorporates a correlation structure among the response variables into the statistical model. The expectation and maximization algorithm is constructed, which enables application to a data set with missing values in the responses. We apply our proposed procedure to real data consisting of 22 material properties., 18 pages

We show relation between sign of Gaussian curvature of cuspidal edge and geometric invariants through types of singularities of Gauss map. Moreover, we define and characterize positivity/negativity of cusps of Gauss maps by geometric invariants of cuspidal edges, and show relation between sign of cusps and of the Gaussian curvature., Comment: 12 pages, 14 figures

Metformin is widely used for the treatment of type 2 diabetes, and increasing numbers of studies have shown that metformin also ameliorates tumor progression, inflammatory disease, and fibrosis. However, the ability of metformin to improve non-diabetic glomerular disease and chronic kidney disease (CKD) has not been explored. To investigate the effect of metformin on non-diabetic glomerular disease, we used a mouse model of Alport syndrome (Col4a5 G5X) which were treated with metformin or losartan, used as a control treatment. We also investigated the effect of metformin on adriamycin-induced glomerulosclerosis model. Pathological and biochemical analysis showed that metformin or losartan suppressed proteinuria, renal inflammation, fibrosis, and glomerular injury and extended the lifespan in Alport syndrome mice. Transcriptome analysis showed that metformin and losartan influenced molecular pathways-related to metabolism and inflammation. Metformin altered multiple genes including metabolic genes not affected by losartan. Metformin also suppressed proteinuria and glomerular injury in the adriamycin-induced glomerulosclerosis mouse model. Our results showed that metformin ameliorates the glomerular sclerosis and CKD phenotype in non-diabetic chronic glomerular diseases. Metformin may have therapeutic potential for not only diabetic nephropathy but also non-diabetic glomerular disease including Alport syndrome.

We study singularities of Gauss maps of fronts and give characterizations of types of singularities of Gauss maps by geometric properties of fronts which are related to behavior of bounded principal curvatures. Moreover, we investigate relation between a kind of boundedness of Gaussian curvatures near cuspidal edges and types of singularities of Gauss maps of cuspidal edges. Further, we consider extended height functions on fronts with non-degenerate singular points., Comment: 19 pages, 12 figures

We investigate behavior of principal curvatures and principal vectors near a non-degenerate singular point of the first kind of frontals. As an application, we extend the notion of Ribaucour transformations to frontals with singular points.

Nephrotic syndrome (NS) is a renal disorder that is characterized by massive proteinuria, hypoalbuminemia and edema. One of the main causes of NS is focal segmental glomerulosclerosis (FSGS), which has extremely poor prognosis. Although steroids and immunosuppressants are the first line of treatment, some FSGS cases are refractory, prompting the need to find new therapeutic strategies. We have previously demonstrated that an optimized combination treatment of mild electrical stimulation (MES) and heat shock (HS) has several biological benefits including the amelioration of the pathologies of the genetic renal disorder Alport syndrome. Here, we investigated the effect of MES + HS on adriamycin (ADR)-induced NS mouse model. MES + HS suppressed proteinuria and glomerulosclerosis induced by ADR. The expressions of pro-inflammatory cytokines and pro-fibrotic genes were also significantly downregulated by MES + HS. MES + HS decreased the expression level of cleaved caspase-3 and the number of TUNEL-positive cells, indicating that MES + HS exerted anti-apoptotic effect. Moreover, MES + HS activated the Akt signaling and induced the phosphorylation and inhibition of the apoptotic molecule BAD. In in vitro experiment, the Akt inhibitor abolished the MES + HS-induced Akt-BAD signaling and anti-apoptotic effect in ADR-treated cells. Collectively, our study suggested that MES + HS modulates ADR-induced pathologies and has renoprotective effect against ADR-induced NS via regulation of Akt-BAD axis.

A surface in the Lorentz-Minkowski $3$-space is generally a mixed type surface, namely, it has the lightlike locus. We study local differential geometric properties of such a locus on a mixed type surface. We define a frame field along a lightlike locus, and using it, we define two lightlike ruled surfaces along a lightlike locus which can be regarded as lightlike approximations of the surface along the lightlike locus. We study a relationship of singularities of these lightlike surfaces and differential geometric properties of the lightlike locus. We also consider the intersection curve of two lightlike approximations, which gives a model curve of the lightlike locus., 16 pages, 3 figures

We investigate geometric properties of surfaces given by certain formulae. In particular, we calculate the singular curvature and the limiting normal curvature of such surfaces along the set of singular points consisting of singular points of the first kind. Moreover, we study fold singular points of smooth maps., 18 pages, 3 figures

We characterize singularities of focal surfaces of wave fronts in terms of differential geometric properties of the initial wave fronts. Moreover, we study relationships between geometric properties of focal surfaces and geometric invariants of the initial wave fronts., Comment: 12 pages, 2 figures

Background Alport syndrome (AS) is a hereditary, progressive nephritis caused by mutation of type IV collagen. Previous studies have shown that activation of signal transducer and activator of transcription 3 (STAT3) exacerbates other renal diseases, but whether STAT3 activation exacerbates AS pathology is still unknown. Here we aim to investigate the involvement of STAT3 in the progression of AS. Method Phosphorylated STAT3 expression was assessed by immunoblotting analysis of kidneys and glomeruli of an AS mouse model (Col4a5 G5X mutant). To determine the effect of blocking STAT3 signaling, we treated AS mice with the STAT3 inhibitor stattic (10 mg/kg i.p., three times per week for 10 weeks; n = 10). We assessed the renal function [proteinuria, blood urea nitrogen (BUN), serum creatinine] and analyzed the glomerular injury score, fibrosis and inflammatory cell invasion by histological staining. Moreover, we analyzed the gene expression of nephritis-associated molecules. Results Phosphorylated STAT3 was upregulated in AS kidneys and glomeruli. Treatment with stattic ameliorated the progressive renal dysfunction, such as increased levels of proteinuria, BUN and serum creatinine. Stattic also significantly suppressed the gene expression levels of renal injury markers (Lcn2, Kim-1), pro-inflammatory cytokines (Il-6, KC), pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) and Mmp9. Stattic treatment decreased the renal fibrosis congruently with the decrease of transforming growth factor beta (TGF-β) protein and increase of antifibrosis-associated markers p-Smad1, 5 and 8, which are negative regulators of TGF-β signaling. Conclusion STAT3 inhibition significantly ameliorated the renal dysfunction in AS mice. Our finding identifies STAT3 as an important regulator in AS progression and provides a promising therapeutic target for AS.

The conditions for a cuspidal edge, swallowtail and other fundamental singularities are given in the context of Lie sphere geometry. We then use these conditions to study the Lie sphere transformations of a surface., Comment: 18 pages, 3 figures

We study parallel surfaces and dual surfaces of cuspidal edges. We give concrete forms of principal curvature and principal direction for cuspidal edges. Moreover, we define ridge points for cuspidal edges by using those. We clarify relations between singularities of parallel and dual surfaces and differential geometric properties of initial cuspidal edges., Comment: 9 pages, 2 figures

A mixed type surface is a connected regular surface in a Lorentzian 3-manifold with non-empty spacelike and timelike point sets. The induced metric of a mixed type surface is a signature-changing metric, and their lightlike points may be regarded as singular points of such metrics. In this paper, we investigate the behavior of Gaussian curvature at a non-degenerate lightlike point of a mixed type surface. To characterize the boundedness of Gaussian curvature at a non-degenerate lightlike points, we introduce several fundamental invariants along non-degenerate lightlike points, such as the lightlike singular curvature and the lightlike normal curvature. Moreover, using the results by Pelletier and Steller, we obtain the Gauss-Bonnet type formula for mixed type surfaces with bounded Gaussian curvature., 34 pages, 3 figures

We study singularities of surfaces which are given by Kenmotsu-type formula with prescribed unbounded mean curvature., Comment: 17 pages, 2 figures

We compute the differential geometric invariants of cuspidal edges on flat surfaces in hyperbolic $3$-space and in de Sitter space. Several dualities of invariants are pointed out., Comment: 16 pages

For Legendre curves, we consider surfaces of revolution of frontals. The surface of revolution of a frontal can be considered as a framed base surface. We give the curvatures and basic invariants for surfaces of revolution by using the curvatures of Legendre curves. Moreover, we give properties of surfaces of revolution with singularities and cones., Comment: 24 pages, 9 figures

We give an explicit formula for singular surfaces of revolution with prescribed unbounded mean curvature. Using it, we give conditions for singularities of that surfaces. Periodicity of that surface is also discussed., 9 pages 11 figures

Summary Alport syndrome is a hereditary glomerular disease caused by mutation in type IV collagen α3–α5 chains (α3–α5(IV)), which disrupts trimerization, leading to glomerular basement membrane degeneration. Correcting the trimerization of α3/α4/α5 chain is a feasible therapeutic approach, but is hindered by lack of information on the regulation of intracellular α(IV) chain and the absence of high-throughput screening (HTS) platforms to assess α345(IV) trimer formation. Here, we developed sets of split NanoLuc-fusion α345(IV) proteins to monitor α345(IV) trimerization of wild-type and clinically associated mutant α5(IV). The α345(IV) trimer assay, which satisfied the acceptance criteria for HTS, enabled the characterization of intracellular- and secretion-dependent defects of mutant α5(IV). Small interfering RNA-based and chemical screening targeting the ER identified several chemical chaperones that have potential to promote α345(IV) trimer formation. This split luciferase-based trimer formation assay is a functional HTS platform that realizes the feasibility of targeting α345(IV) trimers to treat Alport syndrome.

A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.

We give criteria for which a principal curvature becomes a bounded $C^\infty$-function at non-degenerate singular points of wave fronts by using geometric invariants. As applications, we study singularities of parallel surfaces and extended distance squared functions of wave fronts. Moreover, we relate these singularities to some geometric invariants of fronts., 13 pages, 3 figures

Seasonal changes in leaf photosynthetic rate and partitioning of 13C taken up by leaves were compared in relation to the development of early watercore using susceptible ‘Orin’ and resistant ‘Fuji’ apples (Malus domestica Borkh.). There was no difference between the cultivars in leaf photosynthetic rate from mid-July to mid-October. The extent of watercore in ‘Orin’ increased from mid-July and peaked in late-August, followed by a decrease through mid-October, while no watercore was detected during the experimental period in ‘Fuji’. Fruit fresh weight and soluble solids content (SSC) were higher in ‘Orin’ than ‘Fuji’ during the earlier stages. Leaf dry weight of ‘Orin’ was higher than that of ‘Fuji’ throughout the experimental period. Accumulation of dry matter in the fruit increased in both cultivars and ‘Orin’ kept significantly higher level than ‘Fuji’ from mid-July to mid-October. The amount of 13C distributed to ‘Orin’ fruit at 5 days after labeling was significantly higher than ‘Fuji’ in mid-July just before watercore started to occur. 13C taken up by ‘Orin’ fruit with prevalent watercore was also higher than ‘Fuji’ in late-August but the difference was not significant. In mid-October when early watercore was gradually reducing, 13C recovered by ‘Orin’ fruit decreased and was significantly lower than ‘Fuji’. The difference of partitioning pattern of 13C between the cultivars was associated with the susceptibility to early watercore as well as the changes in fruit growth and SSC. The seasonal changes in the amount of 13C distributed to ‘Orin’ fruit were also related to the fluctuations in watercore severity. The results suggest that active phloem transport might be the cause of early watercore in our previous work, which might be induced by the increased partitioning of assimilates to the fruit during summer in susceptible ‘Orin’ compared to resistant ‘Fuji’ and not by the higher potential of leaf photosynthesis.

Energy recycling of recycled plastic-resin is focused in this investigation. Polyethylene terephthalate resin powder is employed as an auxiliary fuel, whereas high temperature oxidizing atmosphere is generated downstream of the annular burner. Temperature and O2 concentration fields downstream of the annular burner without PET-powder supply are first examined by varying the slit-jet and nozzle-jet velocities with both equivalence ratios kept constant at 1.0. PET-powder is then introduced into the high temperature oxidizing region by varying the slit-jet velocity, the nozzle-jet velocity and the median diameter of PET-powder. Variations of temperature and O2 concentration fields with PET-powder combustion are discussed qualitatively. According to the results, the dependency of the PET-powder unburnt rate on the properties of high temperature oxidizing atmosphere is examined.

This study was conducted to assess whether respiratory frequency can be used as a valid parameter for estimating ventilatory threshold and for examining differences in exercise modes such as a cycle ergometer and a treadmill. 24 men and 12 women performed an incremental exercise test to exhaustion on a cycle ergometer and on a treadmill. Oxygen uptake, carbon dioxide output, pulmonary ventilation, ventilatory frequency, and heart rate were measured continuously every 30 sec. during the test. Three different and independent reviewers detected the ventilatory threshold point and break point of respiratory rate, which were then compared. Analysis indicated that (1) ventilatory threshold was well correlated with break point of respiratory rate for both cycle ( r = .88, p

This study was undertaken to establish an approach for the investigation of age-related changes in indices of body composition during childhood in Japan. It provides current reference values for total body fat mass (TBFM) and lean body mass (LBM) as indices of body composition in an urban population of 3- to 6-year-old Japanese children. Moreover, we assessed the age-specific patterns of body fat distribution [subcutaneous fat mass (SFM) and internal fat mass (IFM)] during childhood. Measurements of body composition by bioelectrical impedance were made in 141 boys and 139 girls, all apparently healthy, aged 3-6 years. Determinations of impedance were made using a four-terminal impedance analyzer (TP-95K; Toyo Physical, Inc., Fukuoka, Japan). LBM was calculated using the equation of Kushner et al. (1992) and Goran et al. (1993). SFM was calculated using a modification of the equation derived by Skerjl et al. (1953). IFM was calculated as the difference between TBFM and SFM. From ages 3 through 6 years, the mean LBM increased with age in boys and girls, and showed significant age differences. Between the ages of 3 and 6, the average increment in LBM was 5.1 kg in boys and 4.4 kg in girls. On average, boys gained 0.5 kg of TBFM each year, whereas girls gained 0.4 kg of TBFM each year. Furthermore, both groups gained 0.3 kg of SFM each year. Percentage body fat decreased in both genders until approximately the age of 5, and increased again slightly at the age of 6. The age-specific pattern of fat accumulation during childhood was characterized by an almost linear increase in SFM in girls, but a transient decrease in IFM in boys. We conclude that further research is required, including longitudinal assessment of body composition variables, in order to unravel the dynamics of body composition change in Japanese children.