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Deposition of black carbon (BC) aerosol in the Arctic lowers snow albedo, thus contributing to warming in the region. However, the processes and impacts associated with BC deposition are poorly understood because of the scarcity and uncertainties of measurements of BC in snow with adequate spatiotemporal resolution. We sampled snowpack at two sites (11 m and 300 m above sea level) at Ny‐Ålesund, Spitsbergen, in April 2013. We also collected falling snow near the surface with a windsock from September 2012 to April 2013. The size distribution of BC in snowpack and falling snow was measured using a single‐particle soot photometer combined with a characterized nebulizer. The BC size distributions did not show significant variations with depth in the snowpack, suggesting stable size distributions in falling snow. The BC number and mass concentrations (CNBCand CMBC) at the two sites agreed to within 19% and 10%, respectively, despite the sites' different snow water equivalent (SWE) loadings. This indicates the small influence of the amount of SWE (or precipitation) on these quantities. Average CNBCand CMBCin snowpack and falling snow at nearly the same locations agreed to within 5% and 16%, after small corrections for artifacts associated with the sampling of the falling snow. This comparison shows that the dry deposition was a small contributor to the total BC deposition. CMBCwere highest (2.4 ± 3.0 μg L−1) in December–February and lowest (1.2 ± 1.2 μg L−1) in September–November. The concentrations of black carbon measured in snowpack in Spitsbergen were somewhat insensitive to the snow water equivalentConcentrations of black carbon in falling snow and ambient air in midwinter were higher than those in fall on averageThe BC concentrations in snowpack measured by this study were lower than those previously reported by factors of 2–6

Residual stress distribution in a carbon steel component with collar manufactured by partial diameter-enlarging (PDE) process was evaluated using the angular dispersion and time-of-flight neutron diffraction methods in the interior and X-ray diffraction method at the surface of the collar. The residual stresses in the PDE specimen were smaller compared with those of a specimen with the similar shape and dimension made by a simple compression (SC) process. The hoop residual stress varied from −98 to 2 MPa around the circumference at the surface of the collar in the PDE specimen, whereas it was nearly constant in the SC one. The residual stresses in the central region of the both specimens were nearly in a hydrostatic compressive stress condition.

Residual stress distribution in a carbon steel component with collar manufactured by partial diameter-enlarging (PDE) process was evaluated using the angular dispersion and time-of-flight neutron diffraction methods in the interior and X-ray diffraction method at the surface of the collar. The residual stresses in the PDE specimen were smaller compared with those of a specimen with the similar shape and dimension made by a simple compression (SC) process. The hoop residual stress varied from -98 to 2 MPa around the circumference at the surface of the collar in the PDE specimen, whereas it was nearly constant in the SC one. The residual stresses in the central region of the both specimens were nearly in a hydrostatic compressive stress condition.

We have investigated crystal structures of martensite and intermediate phases in stoichiometric Ni2MnGa. The neutron diffraction profile of the martensite phase measured at T = 4.2 K exhibits four satellites between [2 0 0]P*and [0 2 0]P*reflections (P stands for the parent phase) at incommensurate positions of [h 2-h 0]P*with h = 0.428, 0.863, 1.136 and 1.572. The profile of the intermediate phase measured at T = 210K exhibits two satellites between [2 0 0]P*and [0 2 0]P*reflections at incommensurate positions of [h 2-h 0]P*with h = 0.343 and 1.657. Although each satellite of the martensite phase moves toward its nearest fundamental reflection as temperature increases, that of the intermediate phase does not move significantly. On the contrary, the intensity of each satellite decreases significantly in the intermediate phase as temperature increases while not in the martensite phase. A synchrotron X-ray diffraction and a Rietveld analysis of the result reveal that, for both the phases, the displacement of atoms from the parent phase are represented by a sine wave whose propagation vector is parallel to [1 1 0]P.

Ultrahigh-voltage SiC flip-type n-channel implantation and epitaxial (IE)-IGBTs were developed, and the static and dynamic performance was investigated. A large device (8 mm × 8mm) with a blocking voltage greater than 16 kV was achieved, and an on-state current of 20 A was obtained at the low on-state voltage (Von) of 4.8 V. RonAdiff was 23 mΩ·cm2 at Von = 4.8 V. In order to evaluate the switching characteristics of the IE-IGBT, ultrahigh-voltage power modules were assembled. A chopper circuit configuration was used to evaluate the switching characteristics of the IE-IGBT. Smooth turn-off waveforms were successfully obtained at VCE = 6.5 kV and ICE = 60 A in the temperature range from room temperature to 250°C.

Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5- HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.

Mice with severe combined immunodeficiency (SCID), lacking functional T and B lymphocytes, were each infected with 40 Echinostoma trivolvismetacercarial cysts on day 0. The mice of the test group were given intramuscular injections of dexamethasone (DEX) daily for 2 weeks and necropsied on days 5, 8, 12, 15, 20 and 30 post-infection (p. i.). The control mice, not treated with DEX, were each infected with 40 echinostome cysts on day 0 and necropsied on the same days as the DEX-treated mice. In the control mice, worm rejection began about day 8 p. i. and the worms were completely rejected by day 15 p. i., corresponding to the peak in goblet cell hyperplasia, about day 12 p. i. In the DEX-treated mice, goblet cell hyperplasia was significantly suppressed and the worms were retained until day 15 p. i., and then rejected after the last treatment with DEX. The number of mucosal mast cells, that increased with worm infection and peaked about day 15 p. i., was apparently suppressed by treatment with DEX. The eosinophi number in the controls increased on day 15 p. i. approximately and then decreased. The eosinophil number in the DEX-treated mice increased as in the controls, but was significantly suppressed compared to that of the controls during the period of the experiment. Enzyme-linked immunosorbent assay (ELISA) showed no marked rise in titres of the sera IgM, IgA and IgG throughout the experiment in both groups. These results indicate that DEX-treatment delayed the rejection of E. trivolvisfrom the small intestine of SCID mice in association with the suppression of goblet cell hyperplasia. It is concluded that the host immune system is not involved in the rejection of E. trivolvisand the effector cells for worm rejection are goblet cells that markedly increase in numbers by infection with E. trivolvis.

Single Crystals of Eu-Doped Calcium Orthoborate Have Been Grown by Micro-Pulling (μ-PD) Technique with Radio Frequency Heating System, and its Transmittance, Photoluminescence and Radiation Responses Were Investigated. In Transmittance Spectra, Eu-Doped Crystal Showed Broad Absorption Band around 200-450 nm, which Is due to the Complex of Charge Transfer (CT) Transition and 4f-4f Transition of Eu3+. Intense Eu2+ 5f-4f and Eu3+ 4f-4f Emission Peaks Were Observed when Excited to 265 nm and 385 nm, and the Calculated Decay Times Were 230 ns and 1.5 ms, Respectively. 241Am 5.5 Mev α-Ray Excited Radioluminescence Spectra Indicated both Eu2+ 5f-4f and EuSuperscript text3+ 4f-4f Emission Peaks.

Two topics were focused. The first one was about the gamma-ray scintillator, Pr3+:Lu3Al5O12(LuAG). The second one was about neutron scintillator, Ce3+:6LiCaAlF6and Eu2+:6LiCaAlF6(6LiCAF). Those scintillators have been developed very recently for modern imaging applications in the medical and homeland security fields. In both cases, the rare earth ions are playing the crucial role as emission centers. Pr3+in LuAG provided fast 5d→4f transition providing noticeably shorter decay time than that of Ce3+. Among several candidate hosts, LuAG showed the best performance. Bulk crystal growth, basic scintillation properties, two-dimensional gamma-ray imaging and positron emission mammography (PEM) application were demonstrated. Due to the international situation, the homeland security was compromized by illicit traffic of explosives, drugs, nuclear materials, etc. and the ways to its improvement became an important R&D topic. For this purpose the Ce and Eu doped LiCAF appeared competitive candidates. Especially, when substitution of 3He neutron detectors was considered, the discrimination ability of gamma-ray from alpha-ray was important. Bulk crystal growth, basic scintillation properties and two-dimensional neutron imaging were demonstrated.

We have investigated crystal structures of martensite and intermediate phases in stoichiometric Ni2MnGa. The neutron diffraction profile of the martensite phase measured at T = 4.2?K exhibits four satellites between [2 0 0]P*and [0 2 0]P*reflections (P stands for the parent phase) at incommensurate positions of [h 2-h 0]P*with h = 0.428, 0.863, 1.136 and 1.572. The profile of the intermediate phase measured at T = 210K exhibits two satellites between [2 0 0]P*and [0 2 0]P*reflections at incommensurate positions of [h 2-h 0]P*with h = 0.343 and 1.657. Although each satellite of the martensite phase moves toward its nearest fundamental reflection as temperature increases, that of the intermediate phase does not move significantly. On the contrary, the intensity of each satellite decreases significantly in the intermediate phase as temperature increases while not in the martensite phase. A synchrotron X-ray diffraction and a Rietveld analysis of the result reveal that, for both the phases, the displacement of atoms from the parent phase are represented by a sine wave whose propagation vector is parallel to [1 1 0]P.

Abstract.: We have investigated crystal structures of martensite and intermediate phases in stoichiometric Ni2MnGa. The neutron diffraction profile of the martensite phase measured at T = 4.2 K exhibits four satellites between [2 0 0]P* and [0 2 0]P* reflections (P stands for the parent phase) at incommensurate positions of [h 2-h 0]P* with h = 0.428, 0.863, 1.136 and 1.572. The profile of the intermediate phase measured at T = 210K exhibits two satellites between [2 0 0]P* and [0 2 0]P* reflections at incommensurate positions of [h 2-h 0]P* with h = 0.343 and 1.657. Although each satellite of the martensite phase moves toward its nearest fundamental reflection as temperature increases, that of the intermediate phase does not move significantly. On the contrary, the intensity of each satellite decreases significantly in the intermediate phase as temperature increases while not in the martensite phase. A synchrotron X-ray diffraction and a Rietveld analysis of the result reveal that, for both the phases, the displacement of atoms from the parent phase are represented by a sine wave whose propagation vector is parallel to [1 1 0]P.

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 μg/body). Dietary supplementation with 1.0% CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules.

This paper describes section topography using an X-ray microbeam and a novel slit having a V-shaped crevice (V-slit). The V-slit is characterized by a sharp-pointed exponential transmission curve, which enables depth-resolved imaging with high spatial resolution. An iterative deconvolution for image restoration is effectively executable, providing submicron resolution in cross-sectional diffraction imaging. The new method is applied to the analysis of screw dislocation in a SiC diode. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We describe highly reliable operation of a novel planar inner stripe blue-violet laser diode (BV-LD). A planar regrowth technique makes it possible to simultaneously fabricate a low-resistive superlattice (SL) structure both on the current-injecting narrow stripe area and on the AlN current-blocking layer. This allows for low operating voltage and over 1000 h stable operation at a single-mode output power of 200 mW at 80 °C. The results obtained here clearly indicate that this inner stripe laser structure is a desirable candidate for a reliable high-power light source for the next generation of optical disc systems. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We report the 1000 mW single mode operation of a planar blue-violet laser diode with inner stripe waveguide. Kink-free output surpassed 400 mW (CW) and 600 mW (50 ns pulsed, duty 50%) at temperatures up to 90 °C. Precise optical field design for narrow stripe waveguide as well as damage-free stripe formation was a key to achieving watt class output. By utilizing buried AlN as optical and current confinement layers, a damage-free inner stripe as narrow as 1.0 μm wide was successfully fabricated. Planar inner stripe structure also has the advantage of a small increase in the electrical resistance for such a narrow stripe, which is favorable for high power operations. The results here indicate the potential of this planar blue-violet laser diode for high power applications as the next generation of optical disc systems. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Objective:Articular cartilage is an avascular tissue in which chondrocytes are exposed to hypoxic conditions. We previously demonstrated that reactive oxygen species (ROS) induced apoptosis of chondrocytes. We also demonstrated that nitric oxide (NO) was induced when chondrocytes were exposed to hypoxia and that NO inhibited the ROS-induced apoptosis. Hyaluronan (HA) is a high molecular weight glycosaminoglycan whose antioxidative effects have been reported. The purpose of the present study was to determine whether HA synthesis was induced in chondrocytes exposed to hypoxia, and, if so, whether the hypoxia-induced HA synthesis is regulated by NO.

Accurate identification of aspermic Fasciola forms in Japan remains difficult because of their morphological variations. In order to characterize the forms genetically, nucleotide sequences of ribosomal internal transcribed spacer (ITS1 and ITS2) and mitochondrial cytochrome c oxidase I (COI) and NADH dehydrogenase I (NDI) genes in 34 liver flukes from 16 prefectures in Japan were analysed. Two major forms represented by Fsp 1 and Fsp 2 had sequences identical to or closely resembling those of F. hepatica and F. gigantica, respectively, in all the 4 DNA markers and were mainly distributed in northern and eastern-western parts of Japan, respectively. Fsp 1 and Fsp 2 would have been introduced into Japan with infected cattle of 2 distinct lineages via the Korean Peninsula and spread through limited parts of Japan (northern and eastern-western parts) together with the movement of each cattle lineage. The Japanese form (Fsp 1/2), which showed heterozygosity in ribosomal DNA and Fsp 2 haplotype in mitochondrial DNA, may have originated in interspecific cross hybridization between paternal F. hepatica and maternal F. gigantica.

An optical beam scanning array (OBSA) integrating two mirror arrays and a collimator-lens array was fabricated. The passive self-alignment inserting a pin into a through-hole was carried out for integration of the mirror arrays and the collimator-lens array. The mirror arrays consist of a mirror substrate with 35 single-axis-rotational mirrors and an electrode substrate for actuating the corresponding mirror by electrostatic force. Each substrate includes two kinds of through-holes: one for passing a collimated-optical beam through, the other for inserting a pin. The conditions for deep-reactive-ion etching (DRIE) of silicon were optimized to form through-holes suitable for passive self-alignment. DRIE from both surfaces of a silicon wafer under the optimized DRIE conditions-a C4F8/SF6gas-flow ratio of 90% and a bias power in SF6gas of 110 W-formed precision through-holes with an average undercut of 3.4 µm and an average sidewall angle of 89.9°. The passive self-alignment then yielded an assembly deviation of less than 17.5 µm, which meets the specification of less than 50 µm. This means that passive self-alignment using a through-hole formed under the optimized DRIE conditions can be exploited to make OBSAs without requiring optical alignment of mirrors and lenses.

To realize safer and effective drug administration, novel well-defined and biocompatible amphiphilic block copolymers containing phospholipid polymer sequences were synthesized. At first, the homopolymer of 2-methacryloyloxyethylphosphorylcholine (MPC) was synthesized in water by reversible addition−fragmentation chain transfer (RAFT) controlled radical polymerization. The “living” polymerization was confirmed by the fact that the number-average molecular weight increased linearly with monomer conversion while the molecular weight distribution remained narrow independent of the conversion. The poly(MPC) thus prepared is end-capped with a dithioester moiety. Using the dithioester-capped poly(MPC) as a macro chain transfer agent, AB diblock copolymers of MPC and n-butyl methacrylate (BMA) were synthesized. Associative properties of the amphiphilic block copolymer (pMPCm-BMAn) with varying poly(BMA) block lengths were investigated using NMR, fluorescence probe, static light scattering (SLS), and quasi-elastic light scattering (QELS) techniques. Proton NMR data in D2O indicated highly restricted motions of the n-butyl moieties, arising from hydrophobic associations of poly(BMA) blocks. Fluorescence spectra of N-phenyl-1-naphthylamine indicated that the probes were solubilized in the polymer micelles in water. The formation of polymer micelles comprising a core with poly(BMA) blocks and shell with hydrophilic poly(MPC) blocks was suggested by SLS and QELS data. The size and mass of the micelle increased with increasing poly(BMA) block length. With an expectation of a pharmaceutical application of pMPCm-BMAn, solubilization of a poorly water-soluble anticancer agent, paclitaxel (PTX), was investigated. PTX dissolved well in aqueous solutions of pMPCm-BMAn as compared with pure water, implying that PTX is incorporated into the hydrophobic core of the polymer micelle. Since excellent biocompatible poly(MPC) sequences form an outer shell of the micelle, pMPCm-BMAn may find application as a promising reagent to make a good formulation with a hydrophobic drug.

Objective:Because articular cartilage has no vascular supply, chondrocytes are hypoxic under normal physiological conditions. Nitric oxide (NO) plays an important role in chondrocyte damage, such as apoptosis. Although oxygen stress with hydrogen peroxide was found to cause chondrocyte damage, these data were obtained under normoxic (21% O 2) conditions. We investigated the effects of hypoxia on hydrogen peroxide-induced chondrocyte damage Methods:Bovine articular chondrocytes were used in this study. Proteoglycan (PG) synthesis and the induction of apoptosis were analyzed with [ 35S]-sulfate incorporation and annexin V staining, respectively. The induction of NO was examined using a fluorescent probe and RT-PCR. Results:Cells maintained at 5% O 2 had the maximum PG synthesis. Under normoxic conditions, hydrogen peroxide inhibited PG synthesis and induced annexin V positive cells in a dose-dependent fashion. However, in those cells cultured under hypoxic (5%) conditions, the hydrogen peroxide-induced annexin V expression was attenuated. Chondrocytes exposed to hypoxia showed induction of NO. When the hypoxia-induced NO was inhibited, the hypoxia-enhanced PG synthesis was abolished and hydrogen peroxide clearly induced cell damage. Conclusions:Endogenous NO induced by hypoxia protects chondrocytes from apoptosis induced by an oxidative stress.

Synchrotron X-ray topographs were taken for bonded silicon-on-insulator wafers. Under the grazing incident condition, the topographs of the top Si layer and the substrate are similar, which represent the variation in incident angle due to surface undulation. Furthermore, a circular concentric pattern was observed in the topographs of the top Si layer both at the grazing and higher incident angles. This shows that the concentric pattern is not due to surface undulation, but due to lattice distortion.

Objective:Mechanical stress is an essential factor in the pathogenesis of osteoarthrosis. We sought to determine whether the strain-mediated alteration in proteoglycan (PG) synthesis was modulated by nitric oxide (NO) synthesis. Methods:Cyclic tensile strain was applied to bovine articular chondrocytes. PG and NO synthesis were determined by [ 35S] sulfate incorporation and chemiluminescence analysis, respectively. To determine the expression of inducible NO synthase (iNOS), quantitative RT-PCR was used. Results:Enhanced PG and NO synthesis were evident when cyclic tensile strain was applied to chondrocytes seeded on fibronectin-coated plates. When NO production was inhibited, PG synthesis was further enhanced. Conclusions:Cyclic tensile strain loaded on the chondrocytes enhanced NO synthesis and this enhanced NO inhibited PG synthesis. Abbreviations:Inducible NO synthase (iNOS), proteoglycan (PG), L-N-monomethylarginine (L-NMA), nitric oxide (NO)

Synchrotron X-ray topographs were taken for bonded silicon-on-insulator wafers. Under the grazing incident condition, the topographs of the top Si layer and the substrate are similar, which represent the variation in incident angle due to surface undulation. Furthermore, a circular concentric pattern was observed in the topographs of the top Si layer both at the grazing and higher incident angles. This shows that the concentric pattern is not due to surface undulation, but due to lattice distortion.

A ternary system consisting of a surface-active organic-crystalline powder (fluorinated calcium N-lauroyl taurate powder), fluorinated oil (perfluoropolymethylisopropyl ether, PFPE), and silicone oil (dimethylpolysiloxane, DMS) has been studied to examine the self-assembling behavior of the powder. Mixed states of the ternary system were classified into eight regions:  (i) network-structured state, (ii) O/F emulsion state (O/F emulsion means DMS-in-PFPE type emulsion), (iii) O/F emulsion state with excess PFPE and DMS phases, (iv) separated state, (v) powdery state, (vi) granular state, (vii) powder dispersion state with excess PFPE and DMS phases, and (viii) dispersion state of powder and PFPE. The separated state, in which a transparent DMS phase was separated from a milky white phase containing the powder and PFPE, was observed first in this system. The O/F emulsion was able to contain a larger amount of DMS oil than the ternary system having a spherical surface-active resin powder reported in our previous paper [Langmuir 2002, 18, 10163]. Shear-stress curve and contact angle measurements as well as theoretical analysis indicated that these interesting observations originated from the plate-type shape of the organic-crystalline powder and its characteristic network in the fluorinated oil.

Multilayer ultrathin films composed of exfoliated nanosheets of manganese oxide and poly(diallyldimethylammonium) (PDDA) ions have been fabricated onto various substrates via electrostatic self-assembly technique. Dense monolayer coverage of the substrate surface by the nanosheets was confirmed by atomic force microscopy. UV−vis absorption spectroscopy provided evidence for subsequent growth of multilayer film, exhibiting progressive enhancement of optical absorption due to manganese oxide nanosheets. Evolution of a Bragg peak in the layer-by-layer deposition process also supported the growth of a nanostructured film of PDDA/MnO2 nanosheets with a repeating periodicity of ca. 0.9 nm. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy revealed the inorganic−organic hybrid nature of the obtained multilayer assemblies. Calcination of the films at temperatures above 500 °C removed the polycations, yielding an ultrathin film of manganese oxide Mn2O3. Cyclic voltammogram measurements revealed one reduction peak and two oxidation peaks for a monolayer film, which are attributable to the electrochemical conversion between Mn^III and Mn^IV in manganese oxide nanosheets.

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Uraemic patients with advanced secondary hyperparathyroidism (2HPT) have nodular hyperplastic glands with a decreased vitamin D receptor (VDR) density. Previous studies have shown that nodular hyperplasia expressed a significantly lower VDR density as compared with diffuse hyperplasia, and the VDR density negatively correlated with both the glandular weight and the marker of cell proliferation. However, the mechanism by which the decreased VDR density leads to parathyroid cell proliferation remains unclear. In the myelomonocytic cell line, active vitamin D₃ is known to activate the transcription of both p21 and p27, cyclin-dependent kinase inhibitors (CDKIs), regulating the transition from the G₁ to the S phase of the cell cycle, in a VDR-dependent manner. Moreover, the overexpression of p21 and p27 inhibits cell proliferation. In order to elucidate the mechanism of parathyroid cell proliferation, the expression of CDKIs, p21 and p27, and the VDR was analysed immunohistochemically, and compared among nodular and diffuse hyperplastic parathyroid glands, and histologically normal parathyroid glands. The VDR expression in nodular hyperplasias was significantly decreased compared with either diffuse hyperplasias or normal parathyroid glands. The expression of both p21 and p27 was also significantly lower in nodular hyperplasias than in diffuse hyperplasias or normal parathyroid glands. Sections of parathyroid glands with a high expression of nuclear VDR highly expressed both p21 and p27. In nodular hyperplasias, the expression of both p21 and p27 correlated either positively with the nuclear VDR expression or inversely with the glandular weight. Therefore, the reduced expression of p21 and p27, being VDR dependent, is a major pathogenic factor for nodular parathyroid gland growth in advanced 2HPT.