Precise Spectroscopy of the 3n and 3p Systems via the

To search for low-energy resonant structures in isospin T=3/2 three-body systems, we have performed the experiments ^{3}H(t,^{3}He)3n and ^{3}He(^{3}He,t)3p at intermediate energies. For the 3n experiment, we have newly developed a thick Ti-^{3}H target that has the largest tritium thickness among targets of this type ever made. The 3n experiment for the first time covered the momentum-transfer region as low as 15 MeV/c, which provides ideal conditions for producing fragile systems. However, in the excitation-energy spectra we obtained, we did not observe any distinct peak structures. This is in sharp contrast to tetraneutron spectra. The distributions of the 3n and 3p spectra are found to be similar, except for the displacement in energy due to Coulomb repulsion. Comparisons with theoretical calculations suggest that three-body correlations exist in the 3n and 3p systems, although not enough to produce a resonant peak.

Tracing Photoinduced Hydrogen Migration in Alcohol Dications from Time-Resolved Molecular-Frame Photoelectron Angular Distributions.

The recent implementation of attosecond and few-femtosecond X-ray pump/X-ray probe schemes in large-scale free-electron laser facilities has opened the way to visualize fast nuclear dynamics in molecules with unprecedented temporal and spatial resolution. Here, we present the results of theoretical calculations showing how polarization-averaged molecular-frame photoelectron angular distributions (PA-MFPADs) can be used to visualize the dynamics of hydrogen migration in methanol, ethanol, propanol, and isopropyl alcohol dications generated by X-ray irradiation of the corresponding neutral species. We show that changes in the PA-MFPADs with the pump-probe delay as a result of intramolecular photoelectron diffraction carry information on the dynamics of hydrogen migration in real space. Although visualization of this dynamics is more straightforward in the smaller systems, methanol and ethanol, one can still recognize the signature of that motion in propanol and isopropyl alcohol and assign a tentative path to it. A possible pathway for a corresponding experiment requires an angularly resolved detection of photoelectrons in coincidence with molecular fragment ions used to define a molecular frame of reference. Such studies have become, in principle, possible since the first XFELs with sufficiently high repetition rates have emerged. To further support our findings, we provide experimental evidence of H migration in ethanol-OD from ion-ion coincidence measurements performed with synchrotron radiation.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

Three-dimensional conformal radiation therapy for canine aortic body tumour: 6 cases (2014-2019).

OBJECTIVE: To determine the feasibility of three-dimensional conformal radiation therapy for canine aortic body tumours. MATERIALS AND METHODS: Medical records of dogs that had undergone three-dimensional conformal radiation therapy with presumptive diagnosis of aortic body tumour were reviewed for clinical characteristics, treatment modality and outcomes. RESULTS: Eight dogs were diagnosed with aortic body tumour and were treated with three-dimensional conformal radiation therapy. One dog had proliferation of a mass in the right atrium during treatment and died of respiratory distress. Another dog did not undergo follow-up CT to evaluate the treatment response due to the increased blood urea nitrogen values. The remaining 6 dogs were included in the case series. Radiotherapy was performed using a median dose per fraction of 7 Gy (3.3-7.14 Gy), a median of seven divided doses (7-15) and a total median dose of 49 Gy (45-50 Gy). The median number of CT scans during the follow-up period was 5 (range: 3-8 times). CT revealed acute side effects in four dogs-grade 1 effects related to the lung (n = 4) and skin (n = 2). Self-limiting or asymptomatic late side effects (grade 1 lung-related effect) were observed in three dogs. After therapy, one dog demonstrated a complete response, another demonstrated a partial response and the disease remained stable in four animals. The median follow-up period was 514.5 (235-1219) days. After three-dimensional conformal radiation therapy, the aortic body tumour reduced gradually over time without regrowth in all these 6 dogs. CLINICAL SIGNIFICANCE: In this small case series, aortic body tumours responded to three-dimensional conformal radiation therapy. Transient and self-limiting side effects of the treatments were common. Further controlled studies are required to prove the effectiveness and the safety of this intervention.

Influence of loading rate and limb position on patellar tendon mechanical properties in vivo.

BACKGROUND: The aims of this study were to clarify the changes of patellar tendon length during isometric knee joint extension and the double leg squat position using ultrasonography. METHODS: The left legs of 17 healthy adults were investigated. Isometric knee extension motion was performed at three positions of knee flexion 30° (knee 30°), knee flexion 60° (knee 60°), knee flexion 90° (knee 90°), and at each limb position, 0% (0% peak torque (PT)), 40% (40% PT), 50% (50% PT), and 60% (60% PT) of the maximum knee joint extension torque were executed at random. Both double leg squat motions were randomly performed in three positions: hip flexion 30°, knee flexion 30°, ankle dorsiflexion 10° (squat 30°); hip joint flexion 60°, knee joint flexion 60°, ankle dorsiflexion 20° (squat 60°); and hip joint flexion 90°, knee joint flexion 90°, ankle dorsiflexion 30° (squat 90°). Ultrasonography was used to measure patellar tendon length. FINDINGS: There were no significant changes in patellar tendon length and strain between knee flexion angles of 30°, 60°, and 90° in isometric knee joint extension and the double leg squat limb position. INTERPRETATION: The loading rate and limb position do not appear to affect the length and strain of the patellar tendon.

Cold acclimation increases cold tolerance independently of diapause programing in the bean bug, Riptortus pedestris.

The bean bug (Riptortus pedestris) is a pest of soybeans and other legumes in Japan and other Asian countries. It enters a facultative adult diapause on exposure to short days. While photoperiodism and diapause are well understood in R. pedestris, knowledge of cold tolerance is very limited, as is information on the effect of diapause on cold tolerance. We examined the effect of photoperiod, cold acclimation, and feeding status on cold tolerance in R. pedestris. We found that cold acclimation significantly increased survival at -10°C in both long- and short-day adult R. pedestris. Since the difference in cold survival between long- and short-day cold-acclimated groups was only marginal, we conclude that entering diapause is not crucial for R. pedestris to successfully pass through cold acclimation and become cold tolerant. We observed similar effects in 5th instar nymphs, with both long- and short-day cold-acclimated groups surviving longer cold exposures compared with non-acclimated groups. Starvation, which was tested only in adult bugs, had only a negligible and negative impact on cold survival. Although cold tolerance significantly increased with cold acclimation in adult bugs, supercooling capacity unexpectedly decreased. Our results suggest that changes in supercooling capacity as well as in water content are unrelated to cold tolerance in R. pedestris. An analysis of metabolites revealed differences between the treatments, and while several metabolites markedly increased with cold acclimation, their concentrations were too low to have a significant effect on cold tolerance.

Role of Multichance Fission in the Description of Fission-Fragment Mass Distributions at High Energies.

Fission-fragment mass distributions were measured for ^{237-240}U, ^{239-242}Np, and ^{241-244}Pu populated in the excitation-energy range from 10 to 60 MeV by multinucleon transfer channels in the reaction ^{18}O+^{238}U at the Japan Atomic Energy Agency tandem facility. Among them, the data for ^{240}U and ^{240,241,242}Np were observed for the first time. It was found that the mass distributions for all the studied nuclides maintain a double-humped shape up to the highest measured energy in contrast to expectations of predominantly symmetric fission due to the washing out of nuclear shell effects. From a comparison with the dynamical calculation based on the fluctuation-dissipation model, this behavior of the mass distributions was unambiguously attributed to the effect of multichance fission.

Microvascular proliferation of brain metastases mimics glioblastomas in squash cytology.

OBJECTIVE: Although microvascular proliferation is a key feature in the diagnosis of high-grade glioma, the characteristics of metastatic tumour vessels in smear preparations have not been documented. In this study, the vascular changes in metastatic brain tumours, using squash cytology to examine the vascular patterns in brain metastases, were reviewed. METHODS: One hundred and forty-three squash smears of brain tissue, including 25 normal or reactive tissue, 23 malignant lymphomas, 8 grade I glioma (pilocytic astrocytoma), 23 grade II glioma (diffuse astrocytoma and oligodendroglioma), 42 grade IV glioma (glioblastoma), and 22 metastasis, were assessed. Two vascular patterns were assessed: thick and branching, and glomeruloid. The vessel density, nuclear layer and the number of vessel branches were compared. Furthermore, tumour vessels of brain metastases were analysed by histology and for immunohistochemical expression of CD34, α-smooth muscle actin (SMA) and high-molecular-weight caldesmon (h-CD). RESULTS: Among 22 metastatic tumours, thick and branching vessels were found in 17 (77%) and glomeruloid vessels in 13 (59%). These incidences of microvascular proliferation patterns were similar to those of glioblastomas or pilocytic astrocytomas. Vessel density, nuclear layer and vessel wall branches were significantly higher in metastatic tumours than malignant lymphomas, grade II gliomas or normal brain tissues. Glomeruloid vessels consisted of CD34-positive cells and α-SMA-positive cells, and α-SMA-positive cells had a low h-CD expression. These immunohistochemical patterns were similar to those of high-grade gliomas. CONCLUSIONS: The vascular features of metastatic brain tumours are similar to those of glioblastomas, suggesting that these microvascular proliferations contribute to the progression of metastatic tumours.

Immunocytochemistry for Claudin-18 and Maspin in biliary brushing cytology increases the accuracy of diagnosing pancreatobiliary malignancies.

OBJECTIVE: Biliary brush cytology is an important diagnostic tool in the evaluation of pancreatobiliary malignancies. However, it is difficult to distinguish between malignant and benign cells. The present study evaluated the utility of immunocytochemical expression of Claudin-18 and Maspin in brushing cytology specimens of pancreatobiliary lesions in the diagnosis of pancreatobiliary malignancies. METHODS: The study retrospectively assessed biliary and pancreatic duct brushing cytology specimens of 43 patients whose pancreatobiliary lesions were histologically diagnosed at the University of Miyazaki Hospital. Scanty cellularity slides and cases with no histological confirmation were excluded. Alcohol-fixed and Papanicolaou-stained slides were immunostained with monoclonal antibodies to Claudin-18 and Maspin. RESULTS: Of the 43 patients, 35 (81.4%) were finally histologically diagnosed with invasive adenocarcinomas. The sensitivity of routine cytology for the detection of malignancy was 63%, and the specificity was 100%. The sensitivity of cytology in combination with immunocytochemical expression of Claudin-18 (89%) or Claudin-18 and/or Maspin (97%) was significantly higher than that of cytology alone (P < 0.01). CONCLUSION: Immunocytochemical staining for Claudin-18 and Maspin improved the diagnostic sensitivity for pancreatobiliary adenocarcinomas.

Ultra-strong and damage tolerant metallic bulk materials: A lesson from nanostructured pearlitic steel wires.

Structural materials used for safety critical applications require high strength and simultaneously high resistance against crack growth, referred to as damage tolerance. However, the two properties typically exclude each other and research efforts towards ever stronger materials are hampered by drastic loss of fracture resistance. Therefore, future development of novel ultra-strong bulk materials requires a fundamental understanding of the toughness determining mechanisms. As model material we use today's strongest metallic bulk material, namely, a nanostructured pearlitic steel wire, and measured the fracture toughness on micron-sized specimens in different crack growth directions and found an unexpected strong anisotropy in the fracture resistance. Along the wire axis the material reveals ultra-high strength combined with so far unprecedented damage tolerance. We attribute this excellent property combination to the anisotropy in the fracture toughness inducing a high propensity for micro-crack formation parallel to the wire axis. This effect causes a local crack tip stress relaxation and enables the high fracture toughness without being detrimental to the material's strength.

Therapeutic potential of zoledronate-activated autologous Gamma-DeltaT cells in atopic dermatitis

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Factor VII promotes hepatocellular carcinoma progression through ERK-TSC signaling.

We previously demonstrated PAR2 starts upstreamed with tissue factor (TF) and factor VII (FVII), inhibited autophagy via mTOR signaling in HCC. However, the mechanism underlying for merging functions of PAR2 with the coagulation system in HCC progression remained unclear. The present study aimed to investigate the role of TF, FVII and PAR2 in tumor progression of HCC. The expressions of TF, FVII and PAR2 from HCC specimens were evaluated by immunohistochemical stains and western blotting. We found that the expression of FVII, but not TF and PAR2, directly related to the vascular invasion and the clinical staging. Importantly, a lower level of FVII expression was significantly associated with the longer disease-free survival. The addition of FVII but not TF induced the expression of PAR2 and phosphorylation of ERK1/2, whereas knockdown of FVII decreased PAR2 expression and ERK1/2 phosphorylation in HCC cell lines. Furthermore, levels of phosphor-TSC2 (Ser664) were increased after treatment with FVII and PAR2 agonist whereas these were significantly abolished in the presence of a potent and specific MEK/ERK inhibitor U0126. Moreover, mTOR knockdown highly reduced Hep3B migration, which could be reverted by FVII but not TF and PAR2. These results indicated that FVII/PAR2 signaling through MEK/ERK and TSC2 axis for mTOR activation has potent effects on the migration of HCC cells. In addition, FVII/PAR2 signaling elicits an mTOR-independent signaling, which promotes hepatoma cell migration in consistent with the clinical observations. Our study indicates that levels of FVII, but not TF, are associated with tumor migration and invasiveness in HCC, and provides clues that evaluation of FVII expression in HCC may be useful as a prognostic indicator in patients with HCC and may form an alternative target for further therapy.

Usefulness of mandibular third molar coronectomy assessed through clinical evaluation over three years of follow-up.

The aim of this study was to investigate the 3-year morbidity of coronectomy of the lower third molar and to monitor the behaviour and migration pattern of the retained roots postoperatively. A total of 92 patients (111 teeth) who had undergone a coronectomy between October 2005 and July 2009 were investigated. Patients were followed up at 3 months and 1, 2, and 3 years for clinical evaluation and dental computed tomography imaging of the coronectomy sites. In total, 10 cases (9%) required tooth root extraction within the 3 years after coronectomy. In seven of them, the distal pocket of the lower second molars remained connected to the roots within the first year. Of the cases in whom a pocket did not remain at an early stage, none showed peri-apical lesions on transmission images of the retained roots in the apical area, which usually result from necrosis of the pulp. Root migration increased in the first 2 years after coronectomy but stabilized between the second and third years. In addition, a significant difference was noted in root migration between patients of different ages and sex. Retained roots after coronectomy in the lower third molars led to no complications in terms of infection or the development of pathologies within the first 3 years postoperatively.

Preoperative ultrasonographic evaluation of the contralateral patent processus vaginalis at the level of the internal inguinal ring is useful for predicting contralateral inguinal hernias in children: a prospective analysis.

PURPOSE: The current study aimed to verify the usefulness of preoperative ultrasonographic evaluation of contralateral patent processus vaginalis (PPV) at the level of the internal inguinal ring. METHODS: This was a prospective study of patients undergoing unilateral inguinal hernia repair at two institutions during 2010-2011. The sex, age at initial operation, birth weight, initial operation side, and the preoperative diameter of the contralateral PPV as determined using ultrasonography (US) were recorded. We analyzed the incidence of contralateral inguinal hernia, risk factors, and the usefulness of the preoperative major diameter of the contralateral PPV. The follow-up period was 36 months. RESULTS: All 105 patients who underwent unilateral hernia repair completed 36 months of follow-up, during which 11 patients (10.5 %) developed a contralateral hernia. The following covariates were not associated with contralateral hernia development: sex (p = 0.350), age (p = 0.185), birth weight (p = 0.939), and initial operation side (p = 0.350). The preoperative major diameter of the contralateral PPV determined using US was significantly wider among patients with a contralateral hernia than those without a contralateral hernia (p = 0.001). When the 105 patients were divided into two groups according to cut-off values of the preoperative major diameter of the contralateral PPV (wide group, >2.0 mm; narrow group, ≤2.0 mm), a significant association was observed between the preoperative major diameter of the contralateral PPV and patient outcomes (p = 0.001). CONCLUSIONS: We used US and confirmed the usefulness of a preoperative evaluation of the major diameter of the contralateral PPV at the level of the internal inguinal ring in pediatric patients with unilateral inguinal hernias.

Use of intraspecific variation in thermal responses for estimating an elevational cline in the timing of cold hardening in a sub-boreal conifer.

To avoid winter frost damage, evergreen coniferous species develop cold hardiness with suitable phenology for the local climate regime. Along the elevational gradient, a genetic cline in autumn phenology is often recognised among coniferous populations, but further quantification of evolutionary adaptation related to the local environment and its responsible signals generating the phenological variation are poorly understood. We evaluated the timing of cold hardening among populations of Abies sachalinensis, based on time series freezing tests using trees derived from four seed source populations × three planting sites. Furthermore, we constructed a model to estimate the development of hardening from field temperatures and the intraspecific variations occurring during this process. An elevational cline was detected such that high-elevation populations developed cold hardiness earlier than low-elevation populations, representing significant genetic control. Because development occurred earlier at high-elevation planting sites, the genetic trend across elevation overlapped with the environmental trend. Based on the trade-off between later hardening to lengthen the active growth period and earlier hardening to avoid frost damage, this genetic cline would be adaptive to the local climate. Our modelling approach estimated intraspecific variation in two model components: the threshold temperature, which was the criterion for determining whether the trees accumulated the thermal value, and the chilling requirement for trees to achieve adequate cold hardiness. A higher threshold temperature and a lower chilling requirement could be responsible for the earlier phenology of the high-elevation population. These thermal responses may be one of the important factors driving the elevation-dependent adaptation of A. sachalinensis.

Selective ß2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement.

Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. ß2-Adrenergic receptor (ß2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that ß-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via ß2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific ß2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via ß2-AR blocking.

Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma.

Autophagy has an important role in tumor biology of hepatocellular carcinoma (HCC). Recent studies demonstrated that tissue factor (TF) combined with coagulation factor VII (FVII) has a pathological role by activating a G-protein-coupled receptor called protease-activated receptor 2 (PAR2) for tumor growth. The present study aimed to investigate the interactions of autophagy and the coagulation cascade in HCC. Seventy HCC patients who underwent curative liver resection were recruited. Immunohistochemical staining and western blotting were performed to determine TF, FVII, PAR2 and light chain 3 (LC3A/B) expressions in tumors and their contiguous normal regions. We found that the levels of autophagic marker LC3A/B-II and coagulation proteins (TF, FVII and PAR2) were inversely correlated in human HCC tissues. Treatments with TF, FVII or PAR2 agonist downregulated LC3A/B-II with an increased level of mTOR in Hep3B cells; in contrast, knockdown of TF, FVII or PAR2 increased LC3A/B. Furthermore, mTOR silencing restored the impaired expression of LC3A/B-II in TF-, FVII- or PAR2-treated Hep3B cells and activated autophagy. Last, as an in vivo correlate, we administered TF, FVII or PAR2 agonist in a NOD/severe combined immunodeficiency xenograft model and showed decreased LC3A/B protein levels in HepG2 tumors with treatments. Overall, our present study demonstrated that TF, FVII and PAR2 regulated autophagy mainly via mTOR signaling. The interaction of coagulation and autophagic pathways may provide potential targets for further therapeutic application in HCC.

Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats.

Adipose-derived mesenchymal stem cells (ASCs) have been considered to be attractive and readily available adult mesenchymal stem cells (MSCs) and are becoming increasingly popular for use in regenerating cell therapy. However, recent evidence attributed a fibrotic potential to MSCs which differentiated into myofibroblasts with highly increased α-smooth muscle actin (α-SMA) expression while transplanted into an injured/regenerating liver in mice. In this study, we studied the role of miR-27b in ASCs and their regenerative potential after partial liver resection in rats. ASCs transfected with control siRNA or miR-27b were intravenously injected into autologous rats undergoing 70% partial hepatectomy (PH). Our data showed that the regenerative capacities of ASCs with overexpressed miR-27b were significantly higher compared with control ASCs. However, the enhanced regeneration, hepatic differentiation, and suppressed liver inflammation, as well as fibrotic activity, were significantly reverted by ZnPP coadministration (heme oxygenase-1 [HO-1] inhibitor) indicating an important role of HO-1 in the regenerating and cytoprotective activities of miR-27b-transfected ASCs. We demonstrated that administration of autologous ASCs overexpressed with miR-27b enhances rapid and early liver regeneration and, importantly, preserves function after PH. The ASCs with miR-27b overexpression might offer a viable therapeutic option to facilitate rapid recovery after liver resection.

Novel multipole Wien filter as three-dimensional spin manipulator.

Spin polarized electron beam is often used in material characterizations which relates to magnetism as well as in the high energy particle physics. The manipulation of the spin polarization toward the arbitrary direction is indispensable in such studies. In the present work, a novel multipole Wien filter is proposed as the three-dimensional spin manipulator, and a prototype 8-pole Wien filter is developed. It is applied to spin polarized low energy electron microscopy, and the variation of the magnetic contrast with managing the spin polarization is evaluated. It is confirmed that the novel multipole Wien filter can manipulate the spin polarization three-dimensionally.