Local thickness and composition measurements from scanning convergent-beam electron diffraction of a binary non-crystalline material obtained by a pixelated detector.

The nanometer-scale spatial distributions of local thickness or composition of noncrystalline materials are generally measured by spectroscopy with scanning transmission electron microscopy (STEM). Since spectroscopy requires a high electron dose and causes irradiation damage, alternative non-spectroscopic methods are required to measure the local thickness or composition of electron-sensitive noncrystalline materials. Here, we focus on the radial distribution function (RDF) of the electron diffraction of non-crystalline materials. We confirm that the RDF of the electron diffraction obtained by simulation contains information on the thickness and composition. Next, we demonstrate the determination of both thickness and composition from experimentally obtained RDFs. Although some constraints are required, we determine the local thickness and composition of a BaO-SiO2 glass sample by comparing the RDFs of diffraction measured by a high-speed pixelated detector with those of the simulated diffractions. Collaterally, this determination method can improve the quality of STEM images.

Downward Terrestrial Gamma-Ray Flash Observed in a Winter Thunderstorm.

During a winter thunderstorm on 24 November 2017, a strong burst of gamma rays with energies up to ∼10 MeV was detected coincident with a lightning discharge, by scintillation detectors installed at the Kashiwazaki-Kariwa Nuclear Power Station at sea level in Japan. The burst had a subsecond duration, which is suggestive of photoneutron production. The leading part of the burst was resolved into four intense gamma-ray bunches, each coincident with a low-frequency radio pulse. These bunches were separated by 0.7-1.5 ms, with a duration of ≪1 ms each. Thus, the present burst may be considered as a "downward" terrestrial gamma-ray flash (TGF), which is analogous to upgoing TGFs observed from space. Although the scintillation detectors were heavily saturated by these bunches, the total dose associated with them was successfully measured by ionization chambers, employed by nine monitoring posts surrounding the power plant. From this information and Monte Carlo simulations, the present downward TGF is suggested to have taken place at an altitude of 2500±500 m, involving 8_{-4}^{+8}×10^{18} avalanche electrons with energies above 1 MeV. This number is comparable to those in upgoing TGFs.

Spheroid culture enhances osteogenic potential of periodontal ligament mesenchymal stem cells.

OBJECTIVE AND BACKGROUND: Human periodontal ligament mesenchymal stem cells (hPDLMSCs) are reported to be responsible for homeostasis and regeneration of periodontal tissue. Although hPDLMSCs are commonly cultured in monolayers, monolayer cultures have been reported as inferior to 3-dimensional cultures such as spheroids, which are spherical clusters of cells formed by self-assembly. The aim of this study was to examine the osteogenic phenotype of spheroids of hPDLMSCs, compared with monolayer cultures of hPDLMSC, in vitro and in vivo. MATERIAL AND METHODS: Spheroids were formed using microwell chips that were tagged with polyethylene glycol. Mesenchymal stem cell (MSC) markers in hPDLMSC spheroids were examined by flow cytometer. Real-time polymerase chain reaction analysis was examined to measure the expressions of stemness markers and osteogenesis-related genes in monolayer and spheroid-cultured hPDLMSCs. Immunofluorescence analysis was performed to confirm protein expressions of stemness markers in PDLMSC spheroids. Nodule formation assay, alkaline phosphatase (ALP) activity assay and transplantation assay in a mouse calvarial defect model were performed to confirm the osteogenic potential of hPDLMSC spheroids. To elucidate the mechanism of spheroid culture enhanced osteogenesis in hPDLMSCs with osteoinductive medium (OIM), a small interfering RNA (siRNA) assay targeted with secreted frizzled-related protein 3 (SFRP3) was examined. The levels of SFRP3 expression in monolayer and spheroid-cultured hPDLMSCs with OIM were measured by real-time polymerase chain reaction and western blotting analysis. ALP gene expression and ALP activity were examined in SFRP3-deficient hPDLMSC spheroids. RESULTS: The hPDLMSC spheroids expressed MSC markers, which were similar to hPDLMSCs grown in monolayer cultures. Intriguingly, the protein and mRNA expressions of transcription factors that regulate "stemness" were significantly increased in hPDLMSC spheroids, compared with hPDLMSCs in monolayer cultures. Nodule formation by hPDLMSCs was significantly increased in spheroid cultures grown with OIM, compared with monolayer-cultured hPDLMSCs. ALP activity and expression of osteogenesis-related genes were also significantly enhanced in hPDLMSC spheroids, compared with monolayer cultures. Treatment with hPDLMSC spheroids significantly enhanced new bone formation in a murine calvarial defect model, compared with hPDLMSCs in monolayer culture. Finally, to elucidate mechanisms by which spheroid culture enhances ALP activation in hPDLMSCs grown with OIM, an siRNA assay was used to manipulate expression of SFRP3, a Wnt signaling antagonist. Knockdown of SFRP3 suppressed ALP gene expression in hPDLMSCs grown in OIM; further, it suppressed ALP activity in spheroid culture. These data suggest that the enhancement of osteogenic potential in hPDLMSC spheroids is regulated through SFRP3-mediated ALP activation. CONCLUSION: Spheroid cultures of hPDLMSCs may be a novel and useful tool in regenerative medicine.

On-ground detection of an electron-positron annihilation line from thunderclouds.

Thunderclouds can produce bremsstrahlung gamma-ray emission, and sometimes even positrons. At 00:27:00 (UT) on 13 January 2012, an intense burst of gamma rays from a thundercloud was detected by the GROWTH experiment, located in Japan, facing the Sea of Japan. The event started with a sharp gamma-ray flash with a duration of <300 ms coincident with an intracloud discharge, followed by a decaying longer gamma-ray emission lasting for ∼60 s. The spectrum of this prolonged emission reached ∼10 MeV, and contained a distinct line emission at 508±3(stat.)±5(sys.) keV, to be identified with an electron-positron annihilation line. The line was narrow within the instrumental energy resolution (∼80keV), and contained 520±50 photons which amounted to ∼10% of the total signal photons of 5340±190 detected over 0.1-10 MeV. As a result, the line equivalent width reached 280±40 keV, which implies a nontrivial result. The result suggests that a downward positron beam produced both the continuum and the line photons.

Mechanical and neural changes in plantar-flexor muscles after spinal cord injury in humans.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To determine the effect of injury duration on plantar-flexor elastic properties in individuals with chronic spinal cord injury (SCI) and spasticity. SETTING: National Rehabilitation Center for Persons with Disabilities, Japan. METHODS: A total of 16 chronic SCI patients (age, 33±9.3 years; injury localization, C6-T12; injury duration, 11-371 months) participated. Spasticity of the ankle plantar-flexors was assessed using the Modified Ashworth Scale (MAS). The calf circumference and muscle thickness of the medial gastrocnemius (MG), lateral gastrocnemius and soleus were assessed using tape measure and ultrasonography. In addition, the ankle was rotated from 10° plantar-flexion to 20° dorsiflexion at 5 deg s(-1) with a dynamometer, and the ankle angle and torque were recorded. After normalizing the data (the initial points of angle and torque were set to zero), we calculated the peak torque and energy. Furthermore, angle-torque data (before and after normalization) were fitted with a second- and fourth-order polynomial, and exponential (Sten-Knudsen) models, and stiffness indices (SISOP, SIFOP, SISK) and AngleSLACK (the angle at which plantar-flexor passive torque equals zero) were calculated. The stretch reflex gain and offset were determined from 0-10° dorsiflexion at 50, 90, 120 and 150 deg s(-1). After logarithmic transformation, Pearson's correlation coefficients were calculated. RESULTS: MAS, calf circumference, MG thickness, peak torque and SIFOP significantly decreased with injury duration (r log-log=-0.63, -0.69, -0.63, -0.53 and -0.55, respectively, P<0.05). The peak torque and SIFOP maintained significant relationships even after excluding impacts from muscle morphology. CONCLUSION: Plantar-flexor elasticity in chronic SCI patients decreased with increased injury duration.

Soft x-ray intensity profile measurements of electron cyclotron heated plasmas using semiconductor detector arrays in GAMMA 10 tandem mirror.

Temporally and spatially resolved soft x-ray analyses of electron cyclotron heated plasmas are carried out by using semiconductor detector arrays in the GAMMA 10 tandem mirror. The detector array has 16-channel for the measurements of plasma x-ray profiles so as to make x-ray tomographic reconstructions. The characteristics of the detector array make it possible to obtain spatially resolved plasma electron temperatures down to a few tens eV and investigate various magnetohydrodynamic activities. High power electron cyclotron heating experiment for the central-cell region in GAMMA 10 has been started in order to reduce the electron drag by increasing the electron temperature.

Risk factors for early hemorrhagic complications after endovascular coiling of ruptured intracranial aneurysms.

BACKGROUND AND PURPOSE: The risk factors of early hemorrhagic complications after endovascular coiling are not well-known. We identified the factors affecting early hemorrhagic complications, defined as any expansion or appearance of hemorrhage shown by head CT in the initial 48 hours after coiling. MATERIALS AND METHODS: We retrospectively reviewed a series of 93 patients who underwent coiling for a ruptured saccular aneurysm between 2006 and 2012 at our hospital. RESULTS: Five patients showed early hemorrhagic complications, and all involved an expansion of the existing intracerebral hematoma immediately after coiling. The associated risk factors were accompanying intracerebral hemorrhage at onset (P < .001), postoperative antiplatelet therapy (P < .001), and thromboembolic complications (P = .044). In the accompanying intracerebral hemorrhage group, the associated risk factors were postoperative antiplatelet therapy (P = .044) and earlier initiation of coiling (9.8 ± 6.5 versus 28.1 ± 24.0 hours, P = .023). Early hemorrhagic complications were significant risk factors for worse clinical outcome (modified Rankin Scale, 2.02 ± 2.21 versus 4.4 ± 2.30, P = .022). None of the 93 patients showed further hemorrhage after the initial 48 hours after coiling. CONCLUSIONS: The accompanying intracerebral hemorrhage at onset, thromboembolic complications, postoperative antiplatelet therapy, and earlier initiation of coiling were the risk factors for early hemorrhagic complications.

Prognostic significance of CD44 variant 2 upregulation in colorectal cancer.

BACKGROUND: CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis. METHODS: CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples. RESULTS: CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2(low) group (n=83, 5-OS: 0.88). CONCLUSIONS: CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants.

Possible evidence for free precession of a strongly magnetized neutron star in the magnetar 4U 0142+61.

Magnetars are a special type of neutron stars, considered to have extreme dipole magnetic fields reaching ∼ 10(11) T. The magnetar 4 U 0142+61, one of the prototypes of this class, was studied in broadband x rays (0.5-70 keV) with the Suzaku observatory. In hard x rays (15-40 keV), its 8.69 sec pulsations suffered slow phase modulations by ± 0.7 sec, with a period of ∼ 15 h. When this effect is interpreted as free precession of the neutron star, the object is inferred to deviate from spherical symmetry by ∼ 1.6 × 10(-4) in its moments of inertia. This deformation, when ascribed to magnetic pressure, suggests a strong toroidal magnetic field, ∼ 10(12) T, residing inside the object. This provides one of the first observational approaches towards toroidal magnetic fields of magnetars.

Hardening and termination of long-duration γ rays detected prior to lightning.

We report the first observation of 3-30 MeV prolonged gamma-ray emission that was abruptly terminated by lightning. The gamma-ray detection was made during winter thunderstorms on December 30, 2010, by the Gamma-Ray Observation of Winter Thunderclouds experiment carried out in a coastal area along the Sea of Japan. The gamma-ray flux lasted for less than 3 min, continuously hardening closer to the lightning occurrence. The hardening at energies of 3-10 MeV energies was most prominent. The gamma-ray flux abruptly ceased less than 800 ms before the lightning flash that occurred over 5 km away from the experimental site. In addition, we observed a clear difference in the duration of the 3-10 MeV gamma rays and those >10 MeV, suggesting that the area of >10 MeV gamma-ray emission is considerably smaller than that of the lower-energy gamma rays. This work may give a manifestation that a local region emitting prolonged gamma rays connects with a distant region to initiate lightning.

Glue embolization for gastroduodenal ulcer bleeding: contribution to hemodynamics and healing process.

BACKGROUND: Although the morbidity of bowel ischemic events after glue embolization has been suggested, a causal relationship between glue and ischemia has not been clearly established. PURPOSE: To evaluate the efficiency and safety of transcatheter arterial embolization with n-butyl cyanoacrylate (NBCA-TAE) for upper gastrointestinal hemorrhage (GIH). MATERIAL AND METHODS: Between October 2006 and October 2012, 21 patients with upper GIH underwent NBCA-TAE, and endoscopic data were obtained within 30 days of follow-up. Shock index prior to and immediately after NBCA-TAE were compared to determine changes in hemodynamics. Days to Forrest type III, as assessed by follow-up endoscopy, was used as an indicator of the healing process. Other clinical outcomes included days for starting ingestion and for hospital discharge. RESULTS: Sixteen gastric and five duodenal ulcers, classified into Forrest type I, were treated. Immediate hemostasis was achieved in all the patients, and no re-bleeding occurred within the follow-up period. Shock index significantly (P < 0.001) improved from before (0.99 ± 0.076) to immediately after NBCA-TAE (0.67 ± 0.038). Sequential mucosal healing processes were observed in all the patients, and the number of days to Forrest type III was 9.6 ± 7.1. The number of days for starting ingestion and hospital discharge was 9.0 ± 4.5 and 15 ± 7.7 days, respectively. CONCLUSION: NBCA-TAE is an effective and safe method for the control of nonvariceal upper GIH, in terms of contribution to hemodynamics and healing process of the gastroduodenal mucosa.

Step frequency and lower extremity loading during running.

The purpose of the present study was to ascertain whether increase in step frequency at a given velocity during running reduces the lower extremity loading variables, which is associated with tibial stress fracture in runner. We hypothesized that the lower extremity loading variables at a given speed would be minimized at around +15% f step. 10 male subjects were asked to run at 2.5 m/s on a treadmill-mounted force platform. 5 step frequencies were controlled using a metronome: the preferred, below preferred (-15 and -30%) and above preferred (+15 and +30%). From the vertical ground reaction force, we measured following lower extremity loading variables; vertical impact peak (VIP), vertical instantaneous loading rate (VILR) and vertical average loading rate (VALR). We found that there were significant differences in lower extremity loading variables among 5 step frequency conditions. Furthermore, quadratic regression analyses revealed that the minimum loading variable frequencies were 17.25, 17.55, and 18.07% of preferred step frequency for VIP, VILR and VIAR, respectively. Thus, adopting a step frequency greater than one's preferred may be practical in reducing the risk of developing a tibial stress fracture by decreasing lower extremity loading variables.

Characterization of human-type monoclonal antibodies against reduced form of hemin binding protein 35 from Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: The gram-negative anaerobe Porphyromonas gingivalis has been implicated as an important pathogen in the development of adult periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. We previously identified a 35 kDa surface protein (hemin binding protein 35; HBP35) from P. gingivalis that exhibited coaggregation activity, while additional analysis suggested that this protein possessed an ability to bind heme molecules. For development of passive immunotherapy for periodontal diseases, human-type monoclonal antibodies have been prepared using HBP35 as an antigen in TransChromo mice. In the present study, we focused on a single antibody, TCmAb-h13, which is known to inhibit heme binding to recombinant HBP35. The aim of our investigation was to clarify the redox-related function of HBP35 and consider the benefits of human-type monoclonal antibodies. MATERIAL AND METHODS: To examine the antigen recognition capability of TCmAbs with immunoblotting and Biacore techniques, we used the native form as well as several Cys-to-Ser variants of recombinant HBP35. RESULTS: We found that the redox state of recombinant HBP35 was dependent on two Cys residues, (48) C and (51) C, in the thioredoxin active center (WCGxCx). Furthermore, TCmAb-h13 recognized the reduced forms of recombinant HBP35, indicating its inhibitory effect on P. gingivalis growth. CONCLUSION: Hemin binding protein 35 appears to be an important molecule involved in recognition of the redox state of environmental conditions. In addition, TCmAb-h13 had an inhibitory effect on heme binding to recombinant HBP35, thereby interfering with P. gingivalis growth.

Acute effects of exercise on posture in arthritic patients.

In this study, we aimed to investigate the acute effects of exercise on postural measures in arthritic patients. We obtained posturographic measurements of 8 women with lower extremity arthritis for 30 s before and after a 60-min aquatic exercise. The center of pressure (COP) was recorded while the volunteers were in an upright position with their eyes open. The time domain measures and the frequency domain measures of the COP time series in the anterior-posterior (AP) and medial-lateral (ML) directions were calculated. In addition, the frequency domain measures were calculated for the COP velocity time series. A paired T-test revealed no significant differences in any time domain measures between pre- and post-exercise; however, there were significant decreases in the 95% power frequency of the COP in the AP direction (0.834 ± 0.296 to 0.627 ± 0.230 Hz, p=0.027) for the frequency domain measures. For the velocity time series, the mean power frequency in both the AP (1.47 ± 0.528 to 1.22 ± 0.360 Hz, p=0.047) and ML (1.28 ± 0.245 to 1.13 ± 0.151 Hz, p=0.022) directions, and the 95% power frequency in the ML direction (3.41 ± 0.653 to 2.96 ± 0.468 Hz, p=0.038) decreased significantly in the post-exercise condition. This study reports that a single session of exercise has a subtle but detectable acute effect on postural balance in arthritic patients.

Revascularization by percutaneous transluminal angioplasty improved abruptly deteriorated ischaemic symptoms in cutaneous polyarteritis nodosa.

We report a patient with cutaneous polyarteritis nodosa, who had a 3-year history of recurrent leg and foot ulcers. Symptoms of ischaemia in the left foot, including severe pain, coldness, paraesthesia and violaceous discoloration, deteriorated abruptly, because of complete occlusion of the left anterior tibial artery. The occluded segment was revascularized by percutaneous transluminal angioplasty, resulting in a dramatic improvement in the ischaemic symptoms.

Chronic stress-induced hippocampal dendritic retraction requires CA3 NMDA receptors.

Chronic stress induces dendritic retraction in the hippocampal CA3 subregion, but the mechanisms responsible for this retraction and its impact on neural circuitry are not well understood. To determine the role of NMDA (N-methyl-d-aspartic acid) receptor (NMDAR)-mediated signaling in this process, we compared the effects of chronic immobilization stress (CIS) on hippocampal dendritic morphology, hypothalamic-pituitary-adrenal (HPA) axis activation, and anxiety-related and hippocampus-dependent behaviors, in transgenic male mice in which the NMDAR had been selectively deleted in CA3 pyramidal cells and in non-mutant littermates. We found that CIS exposure for 10 consecutive days in non-mutant mice effectively induces HPA axis activation and dendritic retraction of CA3 short-shaft pyramidal neurons, but not CA3 long-shaft pyramidal neurons, suggesting a differential cellular stress response in this region. Dendritic reorganization of short-shaft neurons occurred throughout the longitudinal axis of the hippocampus and, in particular, in the ventral pole of this structure. We also observed a robust retraction of dendrites in dorsal CA1 pyramidal neurons in the non-mutant C57BL/6 mouse strain. Strikingly, chronic stress-induced dendritic retraction was not evident in any of the neurons in either CA3 or CA1 in the mutant mice that had a functional lack of NMDARs restricted to CA3 pyramidal neurons. Interestingly, the prevention of dendritic retraction in the mutant mice had a minimal effect on HPA axis activation and behavioral alterations that were induced by chronic stress. These data support a role for NMDAR-dependent glutamatergic signaling in CA3 in the cell-type specific induction of dendritic retraction in two hippocampal subregions following chronic stress.

Effect of spinal cord injury and its lesion level on stretch reflex modulation by cold stimulation in humans.

OBJECTIVE: To determine how short-latency stretch reflex amplitude in the soleus muscle is modulated by cold stimulation in able-bodied individuals and individuals with complete spinal cord injury. METHODS: An initial 100-s baseline period was followed by 50-s cold stimulation periods. Stretch reflex of the right soleus muscle was elicited for 10-s intervals, while cold stimulation was applied to the left thigh. RESULTS: Peak-to-peak amplitude of the stretch reflex increased significantly during cold stimulation up to 127 ± 21% of the baseline in the able-bodied group (n=9, P<0.01). Similarly, stretch reflex increased up to 125 ± 11% in a group with injury level at or below thoracic 10 (n=4), although this increase was not significant. On the other hand, stretch reflex decreased significantly down to 78 ± 20% in a group with injury level at or above thoracic 6 (n=8, P<0.05). CONCLUSIONS: Effect of afferent inputs induced by cold stimulation on stretch reflex modulation is different depending on the extent of central nervous systems participating in the modulation. SIGNIFICANCE: Our findings provide a better understanding of some basic changes in afferent-efferent spinal reflex pathways which are probably not monosynaptic in nature.

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis.

OBJECTIVES: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). METHODS: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. RESULTS: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. CONCLUSIONS: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.