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One of the most common causes of discontinued peritoneal dialysis is impaired peritoneal function. However, its molecular mechanisms remain unclear. Previously, by microarray analysis of mouse peritoneum, we showed that MMP (matrix metalloproteinase)-10 expression is significantly increased in mice with peritoneal fibrosis, but its function remains unknown. Chlorhexidine gluconate (CG) was intraperitoneally injected to wild-type and MMP-10 knockout mice to induce fibrosis to elucidate the role of MMP-10 on peritoneal injury. We also examined function of peritoneal macrophages and mesothelial cells obtained from wild-type and MMP-10 knockout mice, MMP-10-overexpressing macrophage-like RAW 264.7 cells and MeT-5A mesothelial cells, investigated MMP-10 expression on peritoneal biopsy specimens, and the association between serum proMMP-10 and peritoneal solute transfer rates determined by peritoneal equilibration test on patients. MMP-10 was expressed in cells positive for WT1, a mesothelial marker, and for MAC-2, a macrophage marker, in the thickened peritoneum of both mice and patients. Serum proMMP-10 levels were well correlated with peritoneal solute transfer rates. Peritoneal fibrosis, inflammation, and high peritoneal solute transfer rates induced by CG were all ameliorated by MMP-10 deletion, with reduction of CD31-positive vessels and VEGF-A-positive cells. Expression of inflammatory mediators and phosphorylation of NFκΒ subunit p65 at S536 were suppressed in both MMP-10 knockout macrophages and mesothelial cells in response to lipopolysaccharide stimulation. Overexpression of MMP-10 in RAW 264.7 and MeT-5A cells upregulated pro-inflammatory cytokines with phosphorylation of NFκΒ subunit p65. Thus, our results suggest that inflammatory responses induced by MMP-10 are mediated through the NFκΒ pathway, and that systemic deletion of MMP-10 ameliorates peritoneal inflammation and fibrosis caused by NFκΒ activation of peritoneal macrophages and mesothelial cells.

Chronic kidney disease (CKD) is a syndrome characterized by a gradual loss of kidney function with decreased estimated glomerular filtration rate (eGFR), which may be accompanied by an increase in the urine albumin-to-creatinine ratio (UACR). Although trans-ethnic genome-wide association studies (GWASs) have been conducted for kidney-related traits, there have been few analyses in the Japanese population, especially for the UACR trait. In this study, we conducted a GWAS to identify loci related to multiple kidney-related traits in Japanese individuals. First, to detect loci associated with CKD, eGFR, and UACR, we performed separate GWASs with the following two datasets: 475 cases of CKD diagnosed at seven university hospitals and 3471 healthy subjects (dataset 1) and 3664 cases of CKD-suspected individuals with eGFR <60 ml/min/1.73 m2or urinary protein ≥ 1+ and 5952 healthy subjects (dataset 2). Second, we performed a meta-analysis between these two datasets and detected the following associated loci: 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among the loci detected, 22 have never been reported previously. Half of the significant loci for CKD were shared with those for eGFR, whereas most of the loci associated with UACR were different from those associated with CKD or eGFR. The GWAS of the Japanese population identified novel genetic components that were not previously detected. The results also suggest that the group primarily characterized by increased UACR possessed genetically different features from the group characterized by decreased eGFR.

Podocytes are highly specialized cells within the glomerulus that are essential for ultrafiltration. The slit diaphragm between the foot processes of podocytes functions as a final filtration barrier to prevent serum protein leakage into urine. The slit-diaphragm consists mainly of Nephrin and Neph1, and localization of these backbone proteins is essential to maintaining the integrity of the glomerular filtration barrier. However, the mechanisms that regulate the localization of these backbone proteins have remained elusive. Here, we focused on the role of membrane-associated guanylate kinase inverted 2 (MAGI-2) in order to investigate mechanisms that orchestrate localization of slit-diaphragm backbone proteins. MAGI-2 downregulation coincided with a reduced expression of slit-diaphragm backbone proteins in human kidneys glomerular disease such as focal segmental glomerulosclerosis or IgA nephropathy. Podocyte-specific deficiency of MAGI-2 in mice abrogated localization of Nephrin and Neph1 independently of other scaffold proteins. Although a deficiency of zonula occuldens-1 downregulated the endogenous Neph1 expression, MAGI-2 recovered Neph1 expression at the cellular edge in cultured podocytes. Additionally, overexpression of MAGI-2 preserved Nephrin localization to intercellular junctions. Co-immunoprecipitation and pull-down assays also revealed the importance of the PDZ domains of MAGI-2 for the interaction between MAGI-2 and slit diaphragm backbone proteins in podocytes. Thus, localization and stabilization of Nephrin and Neph1 in intercellular junctions is regulated mainly via the PDZ domains of MAGI-2 together with other slit-diaphragm scaffold proteins. Hence, these findings may elucidate a mechanism by which the backbone proteins are maintained.

The rectangular-structured resin with one of its triangular long-period fiber grating surface is designed and printed out by using a high resolution 3D printer, so called long-period fiber grating (LPFG) resin. This LPFG resin is directly pressed on the bare single-mode fiber by a digital force meter to filter out partial band of light inside the fiber. The grating period is expanded by tilting the resin from the initial fiber axis. The optical filter is observed as resonant wavelengths from the broadband wavelength. The results show that the resonant wavelength shift is a linear function of the grating period with the coefficient of determination over 0.99. The proposed scheme has a great potential to be employed as a sensor such as a selective optical filter and a buried intrusion sensor.

Focal segmental glomerulosclerosis (FSGS) is a common cause of steroid-resistant nephrotic syndrome. Spontaneous remission of FSGS is rare and steroid-resistant FSGS frequently progresses to renal failure. Many inheritable forms of FSGS have been described, caused by mutations in proteins that are important for podocyte function. Here, we show that a basic leucine zipper transcription factor, MafB, protects against FSGS. MAFB expression was found to be decreased in the podocytes of patients with FSGS. Moreover, conditional podocyte-specific MafB-knockout mice developed FSGS with massive proteinuria accompanied by depletion of the slit diaphragm-related proteins (Nphs1 and Magi2), and the podocyte-specific transcription factor Tcf21. These findings indicate that MafB plays a crucial role in the pathogenesis of FSGS. Consistent with this, adriamycin-induced FSGS and attendant proteinuria were ameliorated by MafB overexpression in the podocytes of MafB podocyte-specific transgenic mice. Thus, MafB could be a new therapeutic target for FSGS.

Fabrication processes of a magneto-optic waveguide with a Si guiding layer for an optical isolator employing a nonreciprocal guided-radiation mode conversion are investigated. The optical isolator is constructed on a silicon-on-insulator (SOI) structure. The magneto-optic waveguide is fabricated by bonding the Si guiding layer with a cerium-substituted yttrium iron garnet (Ce:YIG). The relationship of waveguide geometric parameters is determined at a wavelength of 1550 nm. The results show that larger tolerance for isolator operation can be obtained at smaller gaps between Si and Ce:YIG. Bonding processes including photosensitive adhesive bonding and surface activated bonding are then compared. It is found that the surface activated bonding process is easier to control and more promising than the photosensitive adhesive bonding.

Natriuretic peptides exert not only blood-lowering but also kidney-protective effects through guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. Signaling through GC-A has been shown to protect podocytes from aldosterone-induced glomerular injury, and a p38 mitogen-activated protein kinase (MAPK) inhibitor reduced glomerular injury in aldosterone-infused podocyte-specific GC-A knockout mice. To explore the role of p38 MAPK in podocytes, we constructed podocyte-specific p38 MAPK and GC-A double knockout mice (pod-double knockout mice). Unexpectedly, aldosterone-infused and high salt-fed (B-ALDO)-treated pod-double knockout mice resulted in elevated serum creatinine, massive albuminuria, macrophage infiltration, foot process effacement, nephrin and podocin reduction, and additionally, intra-capillary fibrin thrombi,indicating endothelial injury. Microarray analysis showed increased plasminogen activator inhibitor-1 (PAI-1) in glomeruli of B-ALDO-treated pod-double knockout mice. In B-ALDO-treated pod-double knockout mice, PAI-1 increased in podocytes, and treatment with PAI-1 neutralizing antibody ameliorated intra-capillary thrombus formation. In vitro, deletion of p38 MAPK by the CRISPR/Cas9 system and knockdown of GC-A in human cultured podocytes upregulated PAI-1 and transforming growth factor- β1 (TGF-β1). When p38 MAPK knockout podocytes, transfected with a small interfering RNA to suppress GC-A, were co-cultured with glomerular endothelial cells in a transwell system, the expression of TGF-β1 was increased in glomerular endothelial cells. PAI-1 inhibition ameliorated both podocyte and endothelial injury in the transwell system signifying elevated PAI-1 in podocytes is a factor disrupting normal podocyte-endothelial crosstalk. Thus, our results indicate that genetic dual deletion of p38 MAPK and GC-A in podocytes accelerates both podocyte and endothelial injuries, suggesting these two molecules play indispensable roles in podocyte function.

An optical isolator employing a nonreciprocal guided-radiation mode conversion is described. The optical isolator composes of a magneto-optic waveguide with a Si guiding layer, which can be realized by photosensitive adhesive bonding. The optical isolator was designed at a wavelength of 1.55 um. Relationship of waveguide parameters was clarified for isolator operation. Dependence of the thickness of an adhesive layer was investigated for the design of the optical isolator.

An optical isolator employing a nonreciprocal guided-radiation mode conversion has been investigated. The optical isolator is comprised of a strip-loaded magneto-optic waveguide. Only backward-traveling TM modes can couple to TE radiation modes so that the device acts as a TM-mode optical isolator. Fabrication tolerance of waveguide parameters are discussed for a strip-loaded magneto-optic waveguide optical isolator and a rib waveguide optical isolator.

An integrating technique between a laser diode and an optical isolator is proposed. The optical isolator has a magneto-optic waveguide with a Si guiding layer. The laser diode is integrated with the optical isolator by use of photosensitive adhesive bonding. A coupling efficiency between an active layer of the laser diode and a passive waveguide is discussed. Photosensitive adhesive bonding between a garnet crystal and a SiO2 substrate is demonstrated.

Peritoneal dialysis (PD) solution contains high concentrations of glucose and glucose degradation products (GDPs). One of several GDPs—3,4-dideoxyglucosone-3-ene (3,4-DGE)—was recently identified as the most reactive and toxic GDP in PD fluids. In vitro, 3,4-DGE has been shown to induce mesothelial cell damage; however, its role in peritoneal fibrosis in vivoremains unclear. In the present study, we intraperitoneally administered chlorhexidine gluconate (CG) for mild peritoneal injury, and we then injected 3,4-DGE [38μmol/L (low concentration) or 145μmol/L (high concentration)] 5 times weekly for 4 weeks. Significant thickening of the parietal peritoneal membrane was observed only when treatment with low or high concentrations of 3,4-DGE occurred after CG administration, but not when either CG or 3,4-DGE alone was given. The combination of CG and 3,4-DGE also caused upregulation of messenger RNA expression of transforming growth factor β1, connective tissue growth factor, fibronectin, collagen type 1 α1 chain, alpha smooth muscle actin (α–SMA), vascular endothelial growth factor 164, NADPH oxidase 1 and 4, p22phox, p47phox, and gp91phox in peritoneal tissue. Treatment with CG alone was sufficient to cause significant F4/80-positive macrophage infiltration, appearance of α–SMA-positive cells, and vessel formation in the submesothelial layer. Addition of 3,4-DGE markedly enhanced those changes and induced apoptosis, mainly in leukocytes. The concentration of 3,4-DGE in the abdominal cavity declined more rapidly in CG-treated mice than in PBS-treated mice. Peritoneal membrane permeability determined by peritoneal equilibration test showed high transport conditions in peritoneum treated with both CG and 3,4-DGE. These results indicate that, when mild peritoneal damage is already present, 3,4-DGE causes peritoneal thickening and fibrosis, resulting in deterioration of peritoneal membrane function.

Although subcortical vascular dementia, the major subtype of vascular dementia, is caused by a disruption in white matter integrity after cerebrovascular insufficiency, no therapy has been discovered that will restore cerebral perfusion or functional cerebral vessels. Because adrenomedullin (AM) has been shown to be angiogenic and vasoprotective, the purpose of the study was to investigate whether AM may be used as a putative treatment for subcortical vascular dementia.

Augmentation of the CD36 pathway, which involves the uptake of several endogenous ligands including free fatty acids and oxidized low-density lipoprotein, contributes to the damage of proximal tubules and podocytes, whereas ablation of CD36 attenuates renal injury. Souza et al.demonstrate that 5A peptide can inhibit CD36 signaling, attenuate chronic kidney disease progression, and ameliorate inflammation and tubulointerstitial fibrosis by reducing the expression of inflammatory cytokines and chemokines, suggesting the therapeutic potential of 5A peptide against CD36-mediated renal injury.

An interferometric optical isolator, with a Si guiding layer, employing a nonreciprocal phase shift has been studied. The optical isolator is comprised of a magneto-optic waveguide with a magnetic garnet / Si / SiO2 structure, which is fabricated by wafer bonding technique. The nonreciprocal phase shift was calculated for magneto-optic waveguides with various layer structures. Wafer bonding between a garnet crystal and Si was also investigated.

CCN1 (cysteine-rich protein 61; Cyr61) is an extracellular matrix-associated signaling molecule that functions in cell migration, adhesion, and differentiation. We previously reported that CCN1 is induced at podocytes in rat anti-Thy-1 glomerulonephritis, a well-known model of reversible glomerular injury, but its expression and significance in the human kidney remain totally unknown (Sawai K, Mori K, Mukoyama M, Sugawara A, Suganami T, Koshikawa M, Yahata K, Makino H, Nagae T, Fujinaga Y, Yokoi H, Yoshioka T, Yoshimoto A, Tanaka I, Nakao K. J Am Soc Nephrol14: 1154–1163, 2003). Here we report that, in the human kidney, CCN1 expression was confined to podocytes in normal adult and embryonic glomeruli from the capillary loop stage. Podocyte CCN1 expression was decreased in IgA nephropathy, diabetic nephropathy, and membranous nephropathy, whereas it remained unchanged in minimal change disease and focal segmental glomerulosclerosis. Downregulation of CCN1 was significantly greater in diseased kidneys with severe mesangial expansion. CCN1 protein was also localized in the thick ascending limb of Henle's loop, distal and proximal tubules, and collecting ducts, which was not altered in diseased kidneys. In vitro, recombinant CCN1 protein enhanced endothelial cell adhesion, whereas it prominently inhibited mesangial cell adhesion. CCN1 also completely suppressed mesangial cell migration, suggesting its role as a mesangial-repellent factor. In cultured podocytes, CCN1 markedly induced the expression of cyclin-dependent kinase inhibitor p27Kip1as well as synaptopodin in a dose-dependent manner and suppressed podocyte migration. These data indicate that CCN1 is expressed in podocytes, can act on glomerular cells to modulate glomerular remodeling, and is downregulated in diseased kidneys, suggesting that impairment of CCN1 expression in podocytes may contribute to the progression of glomerular disease with mesangial expansion.

Background. Significance of podocyte injury in the progression of diabetic nephropathy is not well-understood. In this study, we examined whether alteration of gap junction protein connexin43 (Cx43) expression in podocytes is associated with the progression of overt diabetic nephropathy.Methods. We recruited 29 type 2 diabetic patients with overt nephropathy who underwent renal biopsy. Nephrectomized kidney samples obtained from seven subjects with localized neoplasm and biopsy specimens from five patients diagnosed as minor glomerular abnormalities were used as controls. Cx43 staining on paraffin-embedded kidney sections were studied by immunohistochemistry.Results. In controls, Cx43 was expressed at podocytes in a linear pattern along the glomerular basement membrane. In contrast, downregulation and loss of uniformly linear staining of Cx43 (Cx43 heterogeneity) in podocytes were observed in diabetic nephropathy. Cx43 intensity correlated with current renal function (R = 0.647, P < 0.005), whereas the magnitude of Cx43 heterogeneity correlated well with the degree of future decline in renal function (R = −0.705, P < 0.001).Conclusions. Alteration of Cx43 expression in podocytes was closely associated with the progression of overt diabetic nephropathy. These results indicate that change in Cx43 expression at podocytes represents a progressive stage in overt diabetic nephropathy and that it may be a convenient way to predict future decline in renal function.

An interferometric optical isolator that employs a nonreciprocal phase shift was studied. The optical isolator consisted of an interferometer with distinct layer structures. A traveling light wave underwent distinct nonreciprocal phase shifts such that the optical isolator could be operated in a unidirectional magnetic field. The optical isolator, in which the waveguide had a HfO_2 cladding layer in one of the arms, was designed at a wavelength of 1.55 μm. The propagation distance of the nonreciprocal phase shifter required for the isolator’s operation was less than 1.5 mm. The device’s total length was less than 2 mm. An optical isolator with distinct layer structures was fabricated and evaluated. An isolation ratio of approximately 9.9 dB was obtained in the unidirectional magnetic field.

Optical nonreciprocal devices with a silicon guiding layer fabricated by wafer bonding are proposed. The optical nonreciprocal devices are composed of a magneto-optic waveguide with a magnetic garnet/Si/SiO_2 structure. Nonreciprocal characteristics are obtained by an evanescent field penetrating into the upper magnetic garnet cladding layer. Several kinds of the optical nonreciprocal device are investigated with the magneto-optic waveguide and designed at a wavelength of 1.55 μm. As a preliminary experiment, wafer bonding between Gd_3Ga_5O_12 and Si was studied. Wafer bonding was successfully achieved with heat treatment at 220 °C in H_2 ambient.

Elimination of a back-reflected TE mode traveling in a TM-mode optical isolator was investigated. The optical isolator had a Mach-Zehnder interferometer that included a polarization-dependent reciprocal phase shifter in one of the arms. The reciprocal phase shift was achieved by an optical path difference between the two arms. By adjustment of the length of the reciprocal phase shifter, the interferometer prevented the back-reflected TE mode from coupling into an input port of the isolator. An extinction ratio of more than 18 dB was obtained against the back-reflected TE mode at a wavelength of 1.55 µm.

Connective tissue growth factor (CTGF) is one of the candidate factors mediating downstream events of transforming growth factor-β (TGF-β), but its role in fibrogenic properties of TGF-β and in tubulointerstitial fibrosis has not yet been clarified. Using unilateral ureteral obstruction (UUO) in rats, we analyzed gene expression of TGF-β1, CTGF, and fibronectin. We further investigated the effect of blockade of endogenous CTGF on TGF-β-induced fibronectin expression in cultured rat renal fibroblasts by antisense oligodeoxynucleotide (ODN) treatment. After UUO, CTGF mRNA expression in the obstructed kidney was significantly upregulated subsequent to TGF-β1, followed by marked induction of fibronectin mRNA. By in situ hybridization, CTGF mRNA was detected mainly in the interstitial fibrotic areas and tubular epithelial cells as well as in parietal glomerular epithelial cells in the obstructed kidney. The interstitial cells expressing CTGF mRNA were also positive for α-smooth muscle actin. CTGF antisense ODN transfected into cultured renal fibroblasts significantly attenuated TGF-β-stimulated upregulation of fibronectin mRNA and protein compared with control ODN transfection, together with inhibited synthesis of type I collagen. With the use of a reporter assay, rat fibronectin promoter activity was increased by 2.5-fold with stimulation by TGF-β1, and this increase was abolished with antisense CTGF treatment. Thus CTGF plays a crucial role in fibronectin synthesis induced by TGF-β, suggesting that CTGF blockade could be a possible therapeutic target against tubulointerstitial fibrosis.

Few case reports have shown the presence of metastatic tumor cells in renal glomeruli. We report one case with intraglomerular metastasis proved at renal biopsy. A 60-year-old man suffered from weight loss and fever of unknown origin. Urinalysis revealed proteinuria with cellular and granular casts. Because vasculitis was suspected, renal biopsy was performed. Presence of tumor cells occupying the glomerular capillary lumina was shown by means of light microscopy and electron microscopy. Laboratory findings revealed elevated leukocyte count (28.9 [times ] 103[sol ]mm3), serum granulocyte colony-stimulating factor (G-CSF) (77 pg[sol ]mL), and serum CA 19-9 (21,885 U[sol ]mL). The patient soon developed disseminated intravascular coagulation and died. Autopsy findings revealed pancreatic cancer showing positive staining for G-CSF and CA 19-9. Tumor cells in the glomerular capillary lumina showed positive staining for CA 19-9 and proliferating cell nuclear antigen (PCNA). These results suggest that the pancreatic tumor cells producing G-CSF were entrapped in the glomerular capillary lumina where they proliferated. This may have been the first step in renal metastasis.

We present the experimental study of an optical isolator with a semiconductor guiding layer that was obtained by use of a nonreciprocal phase shift. The isolator is equipped with an optical interferometer composed of tapered couplers, nonreciprocal phase shifters, and a reciprocal phase shifter. The nonreciprocal phase shifter was constructed by wafer direct bonding between the semiconductor guiding layer and the magneto-optic cladding layer. The isolator, designed for the 1.55-µm wavelength, was fabricated to investigate the characteristics of each component. By applying an external magnetic field to the nonreciprocal phase shifter, we achieved an isolation ratio of approximately 4.9 dB in the interferometric isolator.

The experimental study of an optical isolator by use of a nonreciprocal phase shift is demonstrated. The isolator has an optical interferometer composed of tapered couplers, nonreciprocal phase shifters, and a reciprocal phase shifter. The isolator, designed for a 1.55-µm wavelength, was fabricated to investigate the characteristics of each component. The branching and coupling characteristics of the tapered coupler were measured. The nonreciprocal and reciprocal phase shifts were also evaluated. By applying an external magnetic field to the interferometer, we confirmed the nonreciprocal phase shift in the interferometric isolator.

An interferometric optical isolator with a Si guiding layer employing a nonreciprocal phase shift was proposed. The optical isolator can be operated in a unidirectional external magnetic field owing to the optical interferometer with distinct layer structures. A nonreciprocal phase shifter and a multimode interference coupler were designed at a wavelength of 1.55 μm. Branching characteristics of the multimode interference coupler were measured.

The pulse timing of a mode-locked Er-doped fiber laser was stabilized to a reference pulse train from a Cr:forsterite mode-locked laser by all-optical passive synchronization scheme. The reference pulses were injected into a ring cavity of the fiber laser by using a 1.3-1.5 μm wavelength-division multiplexer. The spectral shift induced by cross-phase modulation between copropagating two-color pulses realizes self-synchronization due to intracavity group-delay dispersion. The rms integration of timing jitter between the fiber laser pulse and the reference pulse was 3.7 fs in a Fourier frequency range from 1 Hz to 100 kHz.

Altered DNA methylation plays an important role in the onset and progression of kidney disease. However, little is known about how the changes arise in disease states. Here, we report that KAT5-mediated DNA damage repair is essential for the maintenance of kidney podocytes and is associated with DNA methylation status. Podocyte-specific KAT5-knockout mice develop severe albuminuria with increased DNA double-strand breaks (DSBs), increased DNA methylation of the nephrin promoter region, and decreased nephrin expression. Podocyte KAT5 expression is decreased, whereas DNA DSBs and DNA methylation are increased in diabetic nephropathy; moreover, KAT5 restoration by gene transfer attenuates albuminuria. Furthermore, KAT5 decreases DNA DSBs and DNA methylation at the same nephrin promoter region, which indicates that KAT5-mediated DNA repair may be related to DNA methylation status. These results suggest a concept in which an environment of DNA damage repair, which occurs with decreased KAT5, may affect DNA methylation status.

The temperature dependence of the optical isolator employing a nonreciprocal guided-radiation mode conversion is investigated. The optical isolator consists of a rib-type magnetooptic waveguide with an amorphous Si (a-Si:H) guiding layer. The nonreciprocal phase shift in the optical isolator is calculated at a wavelength of 1.55 um. The relationship of rib height and rib width for the isolator operation is clarified for various operating temperatures. Refractive indices of layers in the magnetooptic waveguide are considered since proper refractive indices can circumvent waveguide parameter deviation due to the temperature shift. The results show that athermal operation can be achieved by the negative temperature dependence of the refractive index of the upper cladding layer, and the relationship of waveguide parameters varies only slightly with the selected upper cladding layer.

A photosensitive adhesive bonding process for a magnetooptic waveguide for an optical isolator employing a nonreciprocal guided-radiation mode conversion is investigated at 1.55 um. The magnetooptic waveguide is a straight rib type, and it is fabricated by bonding the Si guiding layer to a magnetic garnet. In the fabrication process, an adhesive material is diluted to obtain a certain thickness before depositing on a silicon-on-insulator (SOI) substrate. The relationship between the percent dilution ratio and the thickness of the adhesive layer is considered. The smallest gap thickness is found to be 0.66 um at a dilution ratio of 2%.

An optical isolator with a Si guiding layer that employs a nonreciprocal guided-radiation mode conversion is discussed. The Si guiding layer was sputter-deposited on a magnetic-garnet cladding layer. A magnetooptic waveguide in the optical isolator had an air/Si/magnetic-garnet structure. A nonreciprocal phase shift in the magnetooptic waveguide was calculated at a wavelength of 1.55 μm. The optical isolator employing the nonreciprocal guided-radiation mode conversion was designed for 1.55 μm.

An optical isolator employing a nonreciprocal guided-radiation mode conversion is described. The optical isolator composes of a magneto-optic waveguide with a Si guiding layer, which can be realized by photosensitive adhesive bonding. The optical isolator was designed at a wavelength of 1.55 μm. Relationship of waveguide parameters was clarified for isolator operation. Dependence of the thickness of an adhesive layer was investigated for the design of the optical isolator.

An optical isolator employing a nonreciprocal guided-radiation mode conversion has been investigated. The optical isolator is comprised of a strip-loaded magneto-optic waveguide. Only backward-traveling TM modes can couple to TE radiation modes so that the device acts as a TM-mode optical isolator. Fabrication tolerance of waveguide parameters are discussed for a strip-loaded magneto-optic waveguide optical isolator and a rib waveguide optical isolator.

An integrating technique between a laser diode and an optical isolator is proposed. The optical isolator has a magneto-optic waveguide with a Si guiding layer. The laser diode is integrated with the optical isolator by use of photosensitive adhesive bonding. A coupling efficiency between an active layer of the laser diode and a passive waveguide is discussed. Photosensitive adhesive bonding between a garnet crystal and a SiO2 substrate is demonstrated.

Aldosterone plays an important role in pathophysiology of renal injury. We already reported that natriuretic peptide receptor guanylyl cyclase-A (GC-A) signaling, with potential anti-aldosterone actions, exerts renoprotective effects in various mouse nephropathies including subtotal nephrectomy, immune-mediated renal injury and diabetic nephropathy. Furthermore, we demonstrated that GC-A knockout (KO) mice with aldosterone and sodium overload exhibited accelerated hypertension with massive proteinuria (∼300-fold urinary albumin excretion from baseline). Aldosterone infusion also increased phosphorylation of ERK and p38 MAP kinase (MAPK) mainly in podocytes of GC-A KO mice, but their role remains elusive.

An optical isolator with a Si guiding layer that makes use of a nonreciprocal phase shift is discussed. The Si guiding layer is sputter-deposited on a garnet substrate. The magnetooptic waveguide in the optical isolator has an air/Si/magnetic-garnet structure. The optical isolator can be operated in a unidirectional magnetic field owing to an interferometer with distinct layer structures. Various layer structures will be proposed for unidirectional magnetic field operation.

An interferometric optical isolator, with a Si guiding layer, employing a nonreciprocal phase shift has been studied. The optical isolator is comprised of a magneto-optic waveguide with a magnetic garnet / Si / SiO2 structure, which is fabricated by wafer bonding technique. The nonreciprocal phase shift was calculated for magneto-optic waveguides with various layer structures. Wafer bonding between a garnet crystal and Si was also investigated.

GaInAsP surfaces with various treatments were analyzed by contact-angle measurement for wafer direct bonding between GaInAsP and garnet crystals. The contact angle of a water droplet was measured to estimate the hydrophilicity of the wafer surfaces. The most hydrophilic surface was obtained after an O2plasma activation process. Direct bonding was successfully achieved between GaInAsP activated by O2plasma and garnet crystals.

Magnetic garnet layers with the composition of (LuNdBi)3(FeAl)5O12have been grown on (111)-oriented Gd3Ga5O12(GGG) substrates, which are patterned with stripes of different widths using a Ti mask, by liquid-phase epitaxy to fabricate one-step grown magnetic garnet waveguides. The garnet layers were investigated by scanning electron microscopy, X-ray diffraction measurements, energy-dispersive X-ray analysis and reflection high-energy electron diffraction. The layers grown on Ti-masked regions had a coarse and uneven surface, which is attributed to the damage in the surface of GGG substrates during the growth. The waveguiding experiment indicated that the light waves could be guided within the waveguide with a propagation loss of approximately 0.7 dB/mm.