Controlling 229Th isomeric state population in a VUV transparent crystal.

The radioisotope thorium-229 (229Th) is renowned for its extraordinarily low-energy, long-lived nuclear first-excited state. This isomeric state can be excited by vacuum ultraviolet (VUV) lasers and 229Th has been proposed as a reference transition for ultra-precise nuclear clocks. To assess the feasibility and performance of the nuclear clock concept, time-controlled excitation and depopulation of the 229Th isomer are imperative. Here we report the population of the 229Th isomeric state through resonant X-ray pumping and detection of the radiative decay in a VUV transparent 229Th-doped CaF2 crystal. The decay half-life is measured to 447(25) s, with a transition wavelength of 148.18(42) nm and a radiative decay fraction consistent with unity. Furthermore, we report a new "X-ray quenching" effect which allows to de-populate the isomer on demand and effectively reduce the half-life. Such controlled quenching can be used to significantly speed up the interrogation cycle in future nuclear clock schemes.

Importance of Awareness and Careful Follow-Up of Suspected IgG4-Related Periaortitis.

IgG4-related disease may cause large vessel vasculitis, which often affects males in their 60s. Here, we report a case of suspected IgG4-related periaortitis in a 76-year-old man with lower left-side chest pain and hypertension based on computed tomography findings of thickened lesions surrounding the abdominal aorta and mesenteric arteries after ruling out acute cardiovascular diseases. His serum IgG4 levels were high, but the C-reactive protein and D-dimer levels were within normal limits. Because IgG4-related periaortitis was suspected, the patient was carefully monitored for blood pressure control, inflammatory markers, and renal function. Steroid therapy was not initiated, however, due to the difficulties performing a biopsy targeting periaortitis to obtain a definitive diagnosis and possible severe complications. During follow-up observation, IgG4-related kidney disease was suspected based on a slight increase in the serum creatinine levels and a renal biopsy was considered. Just before performing the renal biopsy, we observed left renal hydronephrosis caused by spreading retroperitoneal fibrosis. Immediate ureteral stent implantation and initiation of steroid therapy successfully improved the renal function and decreased the serum IgG4 level, respectively. Although relatively rare, IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis should be considered in the differential diagnosis of aortic diseases, even after ruling out serious major acute cardiovascular diseases. Cardiologists should also be aware of the possible progression and systemic spread of this disease.

On-machine self-calibration of rotary encoders in the normal vector tracing method.

We developed a nano-profiler to determine the shape from slope distribution data for highly accurate free-form surface shape measurement; for example, high-precision optical systems are required in the x-ray and semiconductor fields. An accuracy of ±0.2 µrad is required to achieve a shape measurement accuracy of 30 nm. The angle of the rotary stage is controlled by the rotary encoder, and the calibration curve of the rotary encoder is guaranteed by the national standard machine. However, the error associated with assembling the rotary encoder to the device is not included in the national standard machine's calibration data. Therefore, we propose a method that combines self-calibration with six encoder heads and calibration with a national standard machine. Using this method reduces the extent of calibration by the national standard machine and minimizes the influence of the assembly error. Furthermore, to verify whether the calibration in the proposed method is appropriate, a new encoder for evaluation was installed and evaluated. The results revealed that the influence of the assembly error was reduced to the minimum, and the difference in the calibration between the encoder for evaluation and the national standard machine was 0.027 µrad.

A Ser252Trp substitution in mouse FGFR2 results in hyperplasia of embryonic salivary gland parenchyma.

OBJECTIVES: Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene are responsible for several severe forms of craniosynostotic disorders, such as Apert and Crouzon syndromes. Patients with craniosynostotic disorders caused by a mutation in Fgfr2 present with several clinical symptoms, including hypersalivation. Here we used a transgenic mouse model of Apert syndrome (Fgfr2+/S252W mice) to evaluate the morphology of the submandibular glands at embryonic day 15.5 (E15.5), the time point reported to mark the start of lumen formation. METHODS: Fgfr2+/S252W mice were generated by crossing ACTB-Cre+/+ and Fgfr2+/Neo-S252W mice. After measuring body weight, the submandibular glands were collected at E15.5. H&E staining, immunostaining, and RT-qPCR were performed to investigate the development of the submandibular gland. RESULTS: The number of ducts and acini in Fgfr2+/S252W mice was significantly higher than in control littermates; however, lumen formation was not affected. The mRNA expression of Fgf1, Fgfr1, Mmp2, Bmp4, Bmp7, Dusp6, and Etv5 in Fgfr2+/S252W mice was significantly higher compared to control littermates. Immunoreactivity for FGF3, FGF1, BMP4, and F4/80 was detected in the parenchyma of Fgfr2+/S252W mice. The area of apoptotic cells stained with TUNEL in Fgfr2+/S252W mice was significantly larger than that of the control littermates. CONCLUSIONS: These results suggested that increased FGFR1 signaling and apoptosis in the submandibular glands of Fgfr2+/S252W mice occurred at E15.5, leading to parenchymal hyperplasia. This study demonstrated that a Ser252Trp substitution in mouse FGFR2 resulted in hyperplasia of the submandibular gland parenchyma during development.

Absolute X-ray energy measurement using a high-accuracy angle encoder.

This paper presents an absolute X-ray photon energy measurement method that uses a Bond diffractometer. The proposed system enables the prompt and rapid in situ measurement of photon energies over a wide energy range. The diffractometer uses a reference silicon single-crystal plate and a highly accurate angle encoder called SelfA. The performance of the system is evaluated by repeatedly measuring the energy of the first excited state of the potassium-40 nuclide. The excitation energy is determined as 29829.39 (6) eV, and this is one order of magnitude more accurate than the previous measurement. The estimated uncertainty of the photon energy measurement was 0.7 p.p.m. as a standard deviation and the maximum observed deviation was 2 p.p.m.

X-ray pumping of the 229Th nuclear clock isomer.

The metastable first excited state of thorium-229, 229mTh, is just a few electronvolts above the nuclear ground state1-4 and is accessible by vacuum ultraviolet lasers. The ability to manipulate the 229Th nuclear states with the precision of atomic laser spectroscopy5 opens up several prospects6, from studies of fundamental interactions in physics7,8 to applications such as a compact and robust nuclear clock5,9,10. However, direct optical excitation of the isomer and its radiative decay to the ground state have not yet been observed, and several key nuclear structure parameters-such as the exact energies and half-lives of the low-lying nuclear levels of 229Th-remain unknown11. Here we present active optical pumping into 229mTh, achieved using narrow-band 29-kiloelectronvolt synchrotron radiation to resonantly excite the second excited state of 229Th, which then decays predominantly into the isomer. We determine the resonance energy with an accuracy of 0.07 electronvolts, measure a half-life of 82.2 picoseconds and an excitation linewidth of 1.70 nanoelectronvolts, and extract the branching ratio of the second excited state into the ground and isomeric state. These measurements allow us to constrain the 229mTh isomer energy by combining them with γ-spectroscopy data collected over the past 40 years.

Maldevelopment of the submandibular gland in a mouse model of apert syndrome.

BACKGROUND: Apert syndrome is characterized by craniosynostosis and bony syndactyly of the hands and feet. The cause of Apert syndrome is a single nucleotide substitution mutation (S252W or P253R) in fibroblast growth factor receptor 2 (FGFR2). Clinical experience suggests increased production of saliva by Apert syndrome patients, but this has not been formally investigated. FGFR2 signaling is known to regulate branching morphogenesis of the submandibular glands (SMGs). With the Apert syndrome mouse model (Ap mouse), we investigated the role of FGFR2 in SMGs and analyzed the SMG pathology of Apert syndrome. RESULTS: Ap mice demonstrated significantly greater SMG and sublingual gland (SMG/SLG complex) mass/body weight and percentage of parenchyma per unit area of the SMG compared with control mice. Furthermore, gene expression of Fgf1, Fgf2, Fgf3, Pdgfra, Pdgfrb, Mmp2, Bmp4, Lama5, Etv5, and Dusp6 was significantly higher in the SMG/SLG complex of Ap mice. FGF3 and BMP4 exhibited altered detection patterns. The numbers of macrophages were significantly greater in SMGs of Ap mice than in controls. Regarding functional evaluations of the salivary glands, no significant differences were observed. CONCLUSIONS: These results suggest that the gain-of-function mutation in FGFR2 in the SMGs of Ap mice enhances branching morphogenesis. Developmental Dynamics 247:1175-1185, 2018. © 2018 Wiley Periodicals, Inc.

16 kDa vasoinhibin binds to integrin alpha5 beta1 on endothelial cells to induce apoptosis.

Many functions of vasoinhibins have been reported, but its receptor has not been clarified yet. Vasoinhibins, 11-18 kDa N-terminal fragments of prolactin, have anti-angiogenic activity and act on endothelial cells to induce apoptosis and to inhibit migration and proliferation, which are opposite to the effects of prolactin. Although vasoinhibins bind to the prolactin receptor, its binding activity is very weak compared to prolactin. Therefore, in this study, we evaluated the binding activity between 16 kDa vasoinhibin and integrin beta1, alpha5 beta1, alpha1 beta1 and alphaV beta3 to identify a specific receptor for vasoinhibins. Moreover, we examined whether 16 kDa vasoinhibin induced apoptosis through integrin beta1 and alpha5 beta1 in endothelial cells. In this study, binding assays and co-immunoprecipitation experiments demonstrated that 16 kDa vasoinhibin could bind strongly to integrin beta1 and alpha5 beta1. Moreover, neutralizing with integrin beta1 and alpha5 beta1 antibody could inhibit 16 kDa vasoinhibin-induced apoptosis in endothelial cells. These findings suggest that vasoinhibins can act on endothelial cells through integrin alpha5 beta1 to induce apoptosis.

Reduced Lateral Confinement and Its Effect on Stability in Patterned Strong Polyelectrolyte Brushes.

The stability of strong polyelectrolyte brushes (PEBs) was studied in bulk and in patterned structures. Thick PEBs of poly([(2-methacryloyloxy)ethyl]trimethylammonium chloride) with thicknesses >100 nm were synthesized using single electron transfer living radical polymerization. Brush patterning was identified using deep-ultraviolet photolithography by means of either a top-down (TD) or bottom-up (BU) method, with features as small as 200 nm. The brushes were soaked in water under a range of pH or temperature conditions, and the hydrolysis was monitored through dry-state ellipsometry and atomic force microscopy measurements. BU patterns showed reduced degrafting for smaller patterns, which was attributed to increased stress relaxation at such dimensions. In contrast to the already relaxed BU-patterned brush, a TD-patterned brush possesses perpendicular structures that result from the use of orthogonal lithography. It was found that the TD process induces cross-linking on the sidewall, which subsequently fortifies the sidewall materials. This modification of the polymer brushes hindered the stress relaxation of the patterns, and the degrafting trends became irrelevant to the pattern sizes. With proper tuning, the cross-linking on the sidewall was minimized and the degrafting trends were again relaxation-dependent.

Fabrication and electrolyte characterization of uniaxially-aligned anion conductive polymer nanofibers.

We report the anion transport properties of anion conductive polymer nanofibers fabricated using an electrospinning method. The aligned nanofibers were prepared to evaluate the anion conductivity of the nanofibers. The aligned nanofibers had 10-15 times higher conductivity (up to 160 mS cm-1 at 90 °C and 95%RH) and lower activation energy (23-25 kJ mol-1) than the corresponding membranes, even though the nanofibers showed lower water uptake than the corresponding membranes. The anion conductivity measurement of nanofibers with different IEC values and anion species revealed that the dependency of anion conductivity on these factors was smaller in the nanofibers than in the corresponding membranes. These results indicate that effective ion transport pathways were formed in the nanofibers due to the phase separation and the polymer chain orientation along the nanofiber axis. These nanofibers are expected to be useful for future applications in alkaline fuel cells, air batteries, and other energy- and environment-related devices regardless of the ion species.

Vasoinhibins, N-terminal mouse prolactin fragments, participate in mammary gland involution.

Vasoinhibins are a family of peptides that act on endothelial cells to suppress angiogenesis and promote apoptosis-mediated vascular regression. Vasoinhibins include the N-terminal fragments from prolactin (PRL), GH, and placental lactogen. One of the vasoinhibins, the N-terminal PRL fragment of 16 kDa, is generated by the lysosomal representative protease cathepsin D (Cath D). Because the normal growth and involution of the mammary gland (MG) are profoundly affected by the expansion and regression of blood vessels and also because PRL stimulates the growth and differentiation of MG, we proposed that intact PRL produced during lactation contributes to MG angiogenesis and increased blood flow, whereas during involution, the N-terminal PRL fragment would have proapoptotic effects on mammary epithelial cells (MECs). Therefore, we investigated the production of the N-terminal PRL fragment and its direct effect on the MG. Mouse PRL (mPRL) was proteolytically cleaved by Cath D between amino acids 148 and 149. N-terminal PRL fragment and Cath D expression increased during MG involution. Furthermore, incubation of MG fragments and MCF7 with recombinant 16 kDa mPRL revealed a proapoptotic effect in MECs. Ectopic mPRL in MECs was cleaved to 16 kDa PRL by Cath D in the MG lysosomal fraction. The majority of PRL derived from pituitary gland was cleaved to 16 kDa PRL in culture medium. Therefore, N-terminal PRL fragment increases during the involution period, has a proapoptotic effect on MECs, and is mainly generated by secreted Cath D in the extracellular space of MG.

Effects from applying adhesive agents onto silanated porcelain surface on the resin bond durability.

This study examined the effects on the bond durability of resins arising from the application of adhesive agent on porcelain surface, silanated by a ceramic primer consisting of gamma-methacryloxypropyltrimethoxysilane (gamma-MPTS), by comparing shear bond strengths before and after thermocycling. When an adhesive agent was applied to a porcelain surface which had been silanated by a ceramic primer for 10 seconds, a significant reduction in resin bonding durability was observed. Extending the silanating period of the ceramic primer to 60 minutes resulted in an increase in resin bonding durability to the porcelain surface. However, the effect on resin bonding durability resulting from the application of adhesive agent was nearly the same as that without adhesive agent application, even though the porcelain surface was silanated for 60 minutes. In other words, positive effects arising from adhesive agent application on resin bonding durability were not observed.

[Bonding of resin cement to bleached dental enamel].

PURPOSE: The effects of bleaching times, types of etching agent and storage period of bleached bovine tooth on the shear bond strength of resin cement to the enamel were examined. MATERIALS AND METHODS: Bovine teeth were repeatedly bleached 0, 1, 3, and 5 times then stored in 37 degrees C water for 1 week. The effect of bleaching number of the bovine tooth on the bond strength of resin cement to the enamel was investigated using 40% phosphoric acid (EG) etching technique. Next, the effects of types of etching agent and of storage period of bleached bovine tooth with three times in 37 degrees C water on the bond strength were studied using 10% citric acid-3% ferric chloride (10-3) or 10% citric acid (10-0) solution. RESULTS: The bleaching of bovine tooth allowed for a dramatic decrease in the bond strength from 18.3 MPa to 9.8 MPa (1 time), and 3.9 MPa (3 times), even though the bovine enamel was etched by EG. However, when 10-3 or 10-0 solution was applied to the three times bleached enamel, bond strengths were 13.9 and 10.0 MPa, respectively. Furthermore, prolonging of the storage period of the three times bleached bovine tooth in water to 2 months resulted in a increase in the bond strength from 3.9 to 10.1 MPa, even if bovine enamel was etched by EG, and close to that obtained from the 10-3 etching. CONCLUSION: To obtain the expected bond strength to bleached enamel, it is better to wait for 2 months for a restoration and use the 10-3 etching.

[Studies evaluating measurement accuracy of CMS-JAW, a jaw motion tracking device with six degrees of freedom using an ultrasonic recording system].

PURPOSE: For diagnoses of temporomandibular dysfunction, reports indicate the importance of analyzing jaw movements using a jaw motion tracking device with six degrees of freedom. However, such devices are not widely applied in clinical practice, due to difficulty of use. To determine whether CMS-JAW (a newly developed six degrees of freedom jaw motion tracking device that features easy analysis of jaw movements) offers the measurement accuracy required for clinical use, we evaluated the device by measuring condyle translation and rotation during jaw movement. METHODS: In this study, we evaluated measurement accuracy by comparing measurements of condyle movements obtained from the Win Jaw System, a comparable jaw motion tracking device with six degrees of freedom based on an ultrasonic recording system; the Gnathohexagraph II, a device based on a different measurement principle; and the CMS-JAW. In the experiment, we confirmed the condyle translations and rotations obtained by each device by measuring distances and angles, respectively, with a micro slider for three-dimensional measurements (to an accuracy of 0.01 mm and 0.02 mm) and a digital protractor (to an accuracy of 0.1 degrees). RESULTS: No significant distortions were observed in the space replicated based on the range of condyle translations obtained with CMS-JAW. Deviations from theoretical values were greatest along the z-axis, with a maximum error of 0.20 mm and root mean square (RMS) error of 0.10 mm. The maximum error for angles of condyle rotation was 0.50 degrees; RMS errors ranged from 0.05 to 0.30 degrees. CONCLUSION: Our analysis of condyle movement demonstrates that the CMS-JAW provides acceptable measurement accuracy for clinical applications.