Proof-of-Principle Experiment for Testing Strong-Field Quantum Electrodynamics with Exotic Atoms: High Precision X-Ray Spectroscopy of Muonic Neon.

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

Development of a targeted gene panel for the diagnosis of Gorlin syndrome.

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the PTCH1, PTCH2, and SUFU genes. Each symptom of the disease has a different time point of onset, which makes early diagnosis based solely on symptoms challenging. In this study, a gene panel was developed to overcome the challenges in the diagnosis of Gorlin syndrome and allow diagnosis using a single test. A custom panel was generated for four genes associated with Gorlin syndrome: PTCH1, PTCH2, SMO, and SUFU. Twenty-seven samples from 12 patients with Gorlin syndrome and three asymptomatic blood relatives of the patients were examined. This panel was highly reliable with a high Q30 quality score, on-target ratio, and coverage. The panel was time- and cost-efficient and enabled the detection of more mutations than whole-exome sequencing for the same patient. Pathogenic mutations in both PTCH1 and PTCH2 were detected in five of the 12 patients with Gorlin syndrome who were diagnosed based on clinical symptoms. Using this panel, the same mutation was identified in the patients and their blood relatives. In summary, this panel facilitated the highly reliable genetic diagnosis of Gorlin syndrome at a low cost, using only blood samples.

Deexcitation Dynamics of Muonic Atoms Revealed by High-Precision Spectroscopy of Electronic K X Rays.

We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the asymmetric broad profile of the electronic characteristic Kα and Kß x rays together with the hypersatellite K^{h}α x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K- and L-shell hole production and their temporal evolution on the 10-20 fs scale during the muon cascade process.

Photodissociation spectroscopy of N2O+ in the ion storage ring RICE.

The A2Σ+-X2Π electronic transition of the nitrous oxide cation, N2O+, was measured via photodissociation spectroscopy in a cryogenic electrostatic ion storage ring. Rotationally resolved spectra of the N-O stretching vibrational sequence were obtained by detecting neutral N fragments produced via N2O+ → NO+ + N predissociation channels. A new set of molecular constants was determined for the high-lying vibrational levels of the A2Σ+ state.

Radiative cooling of cationic carbon clusters, CN+, N = 8, 10, 13-16.

The radiative cooling of highly excited carbon cluster cations of sizes N = 8, 10, 13-16 has been studied in an electrostatic storage ring. The cooling rate constants vary with cluster size from a maximum at N = 8 of 2.6 × 104 s-1 and a minimum at N = 13 of 4.4 × 103 s-1. The high rates indicate that photon emission takes place from electronically excited ions, providing a strong stabilizing cooling of the molecules.

A cryogenic linear ion trap beamline for providing keV ion bunches.

A new cryogenic linear ion trap beamline has been constructed and commissioned, which serves to inject cold molecular and cluster ions into the RIKEN cryogenic electrostatic ring (RICE). Ions are created with an electrospray ion source, and a quadrupole mass filter is used for mass-selection prior to trap injection. The radio frequency octupole ion trap can be continuously loaded with ions and features a fast ion extraction mode to create short ion bunches with tens of µs duration. We report here on the simulations and development of the ion trap beamline and validate performance with the moderately heavy molecular cation methylene blue. Characterization of the novel trap design with additional wedge-shaped electrodes was carried out, which includes the determination of the temporal and spatial shape of the ion bunch and the total number of ions after extraction. Finally, these ion bunches are synchronized with the switching of a pulsed high-voltage acceleration device downstream of the trap, where the ions obtain a kinetic energy of up to 20 keV. The preparation and control of the keV ion beam are demonstrated for the ion injection into RICE.

Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro.

BACKGROUND AND OBJECTIVE: Induced pluripotent stem cells (iPSCs) are a candidate cell source in periodontal regenerative therapy. Enamel matrix derivative (EMD) has been shown to regenerate periodontal tissues, and atelocollagen sponge (ACS) is considered a suitable scaffold or carrier for growth factors. This study aimed to investigate the effect of combined use of EMD and an ACS scaffold on cell behaviors and differentiation of mouse iPSCs (miPSCs) in vitro. MATERIAL AND METHODS: Following embryonic body formation from miPSCs, dissociated cells (miPS-EB-derived cells) were seeded onto ACS with or without EMD, and cultured in osteoblast differentiation medium. Scanning electron microscopy and histological analyses were used to assess cell morphology and infiltration within the ACS. Cell viability (metabolism) was determined using an MTS assay, and expression of mRNA of osteoblastic differentiation markers was assessed by quantitative RT -PCR. Alkaline phosphatase (ALP) staining intensity and activity were evaluated. Mineralization was assessed by von Kossa staining, and calcium content was quantitated using the methylxylenol blue method. RESULTS: By 24 hours after seeding, miPS-EB-derived cells in both the EMD and control groups had attached to and infiltrated the ACS scaffold. Scanning electron microscopy images revealed that by day 14, many cytoplasmic protrusions and extracellular deposits, suggestive of calcified matrix, were present in the EMD group. There was a time-dependent increase in cell viability up to day 3, but no difference between groups was observed at any time point. The levels expressed of ALP and osterix genes were significantly higher in the EMD group than in the control group. Expression of runt-related transcription factor 2 was increased in the EMD group compared with the control group on day 7. EMD upregulated the expression of bone sialoprotein and osteopontin on day 14, whereas expression of osteocalcin was lower at all time points. The staining intensity and activity of ALP were higher in the EMD group than in the control group. Mineralization levels and calcium contents were significantly higher in the EMD group throughout the observation period. CONCLUSION: These data suggest that combining ACS with EMD increases levels of osteoblastic differentiation and mineralization in miPS-EB-derived cells, compared with ACS used alone.

Design and commissioning of the RIKEN cryogenic electrostatic ring (RICE).

A new electrostatic ion storage ring, the RIKEN cryogenic electrostatic ring, has been commissioned with a 15-keV ion beam under cryogenic conditions. The ring was designed with a closed ion beam orbit of about 2.9 m, where the ion beam is guided entirely by electrostatic components. The vacuum chamber of the ring is cooled using a liquid-He-free cooling system to 4.2 K with a temperature difference of 0.4 K at most within all the positions measured by calibrated silicon diode sensors. The first cryogenic operation with a 15-keV Ne+ beam was successfully performed in August 2014. During the measurement, the Ne+ beam was stored under a ring temperature of 4.2 K with a residual-gas lifetime of more than 10 min. This permits an estimation of the residual gas density at a few 104 cm-3, which corresponds to a room-temperature-equivalent pressure of around 1×10-10 Pa. An effect of longitudinal pulse compression at the bunching cavity in the ring was clearly identified by monitoring the pick-up beam detector. The detailed design and mechanical structure of the storage ring, as well as the results from the commissioning run, are reported.

Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro.

While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid-gas phase that is transformable upon exposure to ultrasound. 9E5 is a monoclonal antibody targeting epiregulin (EREG). We found that 9E5-conjugated PCNDs are selectively internalised into targeted cancer cells and kill the cells dynamically by ultrasound-induced intracellular vaporisation. In vitro experiments show that 9E5-conjugated PCND targets 97.8% of high-EREG-expressing cancer cells and kills 57% of those targeted upon exposure to ultrasound. Furthermore, direct observation of the intracellular vaporisation process revealed the significant morphological alterations of cells and the release of intracellular contents.

The effects of administration of the Lactobacillus gasseri strain CP2305 on quality of life, clinical symptoms and changes in gene expression in patients with irritable bowel syndrome.

AIMS: To clarify the effects of Lactobacillus gasseri CP2305 (CP2305) on quality of life and clinical symptoms and its functional mechanisms in patients with irritable bowel syndrome (IBS). METHODS AND RESULTS: After the patients were administered CP2305 daily for 4 weeks, the IBS-severity index score was significantly improved compared with that of the placebo group, and this improvement was accompanied by a reduction in health-related worry and changes in intestinal microbiota. The gene expression profiling of the peripheral blood leucocytes showed that CP2305 treatment significantly up-regulated genes related to eukaryotic initiation factor 2 (EIF2) signalling. Eighty-two genes were down-regulated in IBS patients compared with healthy controls. The expression of 23 of these genes exhibited a CP2305-dependent increase associated with an improvement in IBS severity. The majority of the restored genes were related to EIF2 signalling. CONCLUSIONS: CP2305 administration is a potential candidate therapeutic option for patients with IBS. SIGNIFICANCE AND IMPACT OF THE STUDY: Although probiotics have been proposed to benefit IBS patients, objective clinical evidence and elucidation of the functional mechanism remain insufficient. Our study demonstrated that CP2305 administration beneficially influences IBS patients in both subjective and objective evaluations, and gene expression profiling provided insights into the functional mechanism.

Gingival condition and tooth-brushing behavior after alcohol consumption.

BACKGROUND AND OBJECTIVE: Various studies have reported the relationship between alcohol consumption and gingival condition. However, they focus on the direct effects of alcohol consumption or alcohol sensitivity on gingival condition, and it is unclear how oral health behaviors relate these relationships. The aims of this study were to assess the inter-relationships between gingival condition, tooth-brushing behavior after drinking alcohol and alcohol sensitivity in university students who drink more than once per week on average. MATERIAL AND METHODS: A total of 808 students (541 males, 267 females) that habitually consume alcohol were analyzed. The disease activity of gingival condition was assessed as the percentage of bleeding on probing (%BOP). Additional information regarding alcohol sensitivity and oral health behaviors, including tooth-brushing behavior after drinking, were also collected. RESULTS: Thirteen percent of the current participants reported neglecting tooth-brushing after drinking, and their alcohol consumption was higher than those who did not neglect tooth-brushing. Logistic regression analysis showed that high %BOP (%BOP ≥ 20) was associated with male (OR = 1.53; 95% CI, 1.01-2.33), neglect of tooth-brushing after drinking (OR = 2.60; 95% CI, 1.20-5.61) and debris index (OR = 8.38; 95% CI, 4.24-16.60) in participants with low alcohol sensitivity. In participants with high alcohol sensitivity, high %BOP was associated with debris index (OR = 7.60; 95% CI, 3.12-18.51), but not with any oral health behaviors. CONCLUSIONS: The study revealed that alcohol consumption was indirectly related to gingival disease activity through the neglect of tooth-brushing after drinking alcohol in university students with low alcohol sensitivity.

Relationship between xerostomia and gingival condition in young adults.

BACKGROUND AND OBJECTIVE: Xerostomia is a subjective symptom of dryness in the mouth. Although a correlation between xerostomia and oral conditions in the elderly has been reported, there are few such studies in the young adults. The aim of this study was to examine the relationship of xerostomia with the gingival condition in university students. MATERIAL AND METHODS: A total of 2077 students (1202 male subjects and 875 female subjects), 18-24 years of age, were examined. The disease activity and severity of the gingival condition were assessed as the percentage of teeth with bleeding on probing (%BOP) and the presence of teeth with probing pocket depth of ≥ 4 mm, respectively. Additional information on xerostomia, oral health behaviors, coffee/tea intake and nasal congestion was collected via a questionnaire. Path analysis was used to test pathways from xerostomia to the gingival condition. RESULTS: One-hundred and eighty-three (8.8%) students responded that their mouths frequently or always felt dry. Xerostomia was related to %BOP and dental plaque formation, but was not related to the presence of probing pocket depth ≥ 4 mm. In the structural model, xerostomia was related to dental plaque formation (p < 0.01), and a lower level of dental plaque formation was associated with a lower %BOP. Xerostomia was associated with coffee/tea intake (p < 0.01) and nasal congestion (p < 0.001). CONCLUSION: Xerostomia was indirectly related to gingival disease activity through the accumulation of dental plaque. Nasal congestion and coffee/tea intake also affected xerostomia. These findings suggest that xerostomia should be considered in screening for gingivitis risk in young adults.

Interferon-γ-producing B cells induce the formation of gastric lymphoid follicles after Helicobacter suis infection.

Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-γ (IFN-γ) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-γ expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-γ produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-γ-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection.

Cooling dynamics of photoexcited C6(-) and C6H(-).

We report conclusive evidence of an efficient cooling mechanism via the electronic radiative transitions of hot small molecular anions isolated in vacuum. We stored C6(-) and C6H(-) in an ion storage ring and observed laser-induced electron detachment with delays up to several milliseconds. The terminal hydrogen atom caused a drastic change in the decay profiles. The decay of photoexcited C6H(-) is slow and nonexponential, which can be explained by depletion cooling, whereas that for C6(-) occurs extremely fast, on a time scale below 0.1 ms and can only be explained by electronic radiative cooling via low-lying electronic excited states.

Radiative cooling of C7⁻.

The spontaneous and photo-induced neutralization of C7⁻ produced in a laser ablation source was measured in an electrostatic storage ring. The measurements provide three independent determinations of the radiative cooling of the ions, based on the short time spontaneous decay and on the integrated amplitude and the shape of the photo-induced neutralization signal. The amplitude of the photo-induced signal was measured between 0.5 ms and 35 ms and found to depend on photon wavelength and ion storage time. All three signals can be reproduced with identical thermal IR radiative cooling rates with oscillator strengths equal to theoretical predictions. In addition, the measurements provide the excitation energy distribution.

Anti-CXCL13 antibody can inhibit the formation of gastric lymphoid follicles induced by Helicobacter infection.

Helicobacter suis infects the stomachs of both animals and humans, and can induce gastric mucosa-associated lymphoid tissue (MALT) lymphomas. It is known that CXC chemokine ligand 13 (CXCL13) is highly expressed in the Helicobacter-infected mice and gastric MALT lymphoma patients, but the pathway that links the activation of CXCL13 and the formation of gastric MALT lymphomas remains unclear. In this study, we examined whether CXCL13 neutralization would interfere with the formation of gastric lymphoid follicles including B cells, CD4+T cells, dendritic cells (DCs), and follicular DCs (FDCs) in germinal centers to determine the role of CXCL13 in the formation of B-cell aggregates after H. suis infection. Moreover, the expression of genes associated with the lymphoid follicle formation was also effectively suppressed by anti-CXCL13 antibody treatment. These results suggest that the upregulation of CXCL13 has an important role in the development of gastric MALT lymphomas and highlight the potential of anti-CXCL13 antibody for protection against Helicobacter-induced gastric diseases.

Direct observation of internal energy distributions of C5(-).

Photon induced decay of C5(-) has been measured in an electrostatic storage ring. The time dependence of the photo-enhanced decay is close to a 1∕t decay which indicates a thermal process. The deviation from the expected power of -1 is quantitatively explained by the small heat capacity of the anion. Measurements of the photo-enhanced decay at different storage times and photon energies allow a determination of the radiative cooling rate and the energy distribution of the ions. The average energy content between 15 and 70 ms is found to vary as time to the power -0.72, and at 50 ms the ions contain an average excitation energy of 0.5 eV. The time dependent energy distribution is consistent with cooling by infrared photon emission if published oscillator strengths are reduced by a factor 2.5, in contrast to cooling of larger molecular carbon-based ions where electronic transitions cause a much stronger cooling.

Anti-aging effects of co-enzyme Q10 on periodontal tissues.

Oxidative stress is associated with age-related reactions. The anti-oxidative effects of a reduced form of co-enzyme Q10 (rCoQ10) suppress oxidative stress, which may contribute to the prevention of age-related inflammatory reactions. We examined the effects of topically applied rCoQ10 on periodontal inflammatory reactions in a rat aging model. Male Fischer 344 rats, 2 (n = 6) and 4 mos (n = 18) of age, were used. All of the two-month-old rats and 6 of the four-month-old rats were sacrificed and 12 remaining four-month-old rats received topically applied ointment with or without 1% rCoQ10 on the gingival surface until they reached 6 mos of age. The rats showed an age-dependent increase in circulating oxidative stress. RCoQ10 decreased oxidative DNA damage and tartrate-resistant acid-phosphatase-positive osteoclasts in the periodontal tissue at 6 mos of age as compared with the control. The same conditions lowered gene expression of caspase-1 and interleukin-1ß in the periodontal tissue. Furthermore, Nod-like receptor protein 3 inflammasomes were less activated in periodontal tissues from rCoQ10-treated rats as compared with the control rats. Our results suggest that rCoQ10 suppresses age-related inflammatory reactions and osteoclast differentiation by inhibiting oxidative stress.

Effects of electrical stimulation on periodontal tissue remodeling in rats.

BACKGROUND AND OBJECTIVE: Electric current is used to promote wound healing. However, it is unclear whether electrical stimulation contributes to gingival tissue remodeling. This study examined the effects of electrical stimulation on gingival tissue remodeling in a rat periodontitis model. MATERIAL AND METHODS: Male Wistar rats (n = 28, 8 wks of age) were divided into four groups of seven rats each. The control group did not receive any treatment for 6 wks. In the other groups, periodontitis was ligature-induced for 4 wks. After 4 wks, the rats with periodontitis were given daily electrical stimulation of 0, 50 or 100 µA for 2 wks. RESULTS: The periodontitis group stimulated with 0 µA showed a higher density of polymorphonuclear leukocytes and a lower density of collagen in gingival tissue compared with the control group (p < 0.05). The two remaining groups treated with 50 or 100 µA of electrical stimulation exhibited a lower density of polymorphonuclear leukocytes (p < 0.05) and a higher density of collagen than the group stimulated with 0 µA (p < 0.05). They also showed higher expression of fibroblast growth factor-2 than the group treated with 0 µA of electrical stimulation (p < 0.05). CONCLUSION: Electric stimulation may offer a novel approach to promote gingival tissue remodeling in periodontal lesions.