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.

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.

Prediction of hemorrhagic transformation after acute thrombolysis following major artery occlusion using relative ADC ratio: A retrospective study.

BACKGROUND: The relative apparent diffusion coefficient (ADC) ratio can be used to evaluate the extent of ischemia. We investigated the risk factors for, and correlation between, relative ADC ratio and hemorrhagic transformation (HT) after thrombolysis. METHODS: This single-center, retrospective study involved 105 patients with acute occlusion of the anterior circulation. Relative ADC ratio was calculated as the ratio of ADC pixel values, within the affected territory to ADC pixel values in the contralateral normal region. HT was determined by computed tomography and T2* weighted magnetic resonance imaging after endovascular revascularization. RESULTS: Data for 80 of the 105 patients were analyzed. Comparing the number of patients between the HT group (n=25) and the non-HT group (n=55), a significant difference was noted in tissue plasminogen activator (tPA) use (P=0.028), time from onset to reperfusion ≥380min (P<0.001), fluid-attenuated inversion recovery (FLAIR) hyperintensity (P=0.009), and relative ADC ratio<0.650 (P<0.001). Multivariable logistic regression analysis identified relative ADC ratio<0.650 as the only independent predictor of HT (odds ratio 7.79; 95% confidence interval 2.22-27.3; P=0.001). Twenty-nine patients (including 20 in the HT group) had a relative ADC ratio<0.650. Multivariable logistic regression analysis identified use of tPA as the only independent predictor of HT (odds ratio 13.8; 95% confidence interval 1.35-125.5; P=0.010). CONCLUSIONS: Relative ADC ratio<0.650 with use of tPA may be important for predicting HT.

A hollow-fibre column system to effectively prepare washed platelets.

BACKGROUND AND OBJECTIVES: We developed a hollow-fibre column system specifically adapted to prepare washed platelet concentrates (WPCs). This study was performed to evaluate the efficacy of the hollow-fibre column system for preparing WPCs. MATERIALS AND METHODS: First, the percentages of platelet (PLT) recovery and remaining plasma proteins were calculated by determining the PLT count, volume and plasma protein levels in both the prewash and postwash. Secondly, washed PLTs and unwashed control PLTs were stored for 5 days, and the changes during this 5-day storage of in vitro PLT characteristics were determined. RESULTS: The hollow-fibre column system effectively removed >98% of plasma in platelet concentrates (PCs), and the PLT recovery was 97% on an average. The CD62P-expression level on washed PLTs immediately after washing was approximately twofold higher than that on prewashed PLTs as well as on PLTs washed via manual methods or cell washing devices. Until day 5 during storage, PLT aggregability, hypotonic shock response and swirling scores of washed PLTs were not significantly different from those of the control PCs. CONCLUSION: Our novel hollow-fibre column system proved valuable in preparing washed PLTs with <2% of residual plasma proteins and high recovery of PLTs.

REPEATED INTRANODAL LYMPHANGIOGRAPHY FOR THE TREATMENT OF LYMPHATIC LEAKAGE.

Treatment of patients with chylous or non-chylous lymphatic leakage can be difficult. An approach using therapeutic lymphangiography can reduce the lymphatic leakage, but it seldom stops the leakage immediately and subsequent conservative treatment is necessary. We report three cases in which intranodal lymphangiography was performed multiple times to inhibit lymphatic leakage. In each case, the lymph node was punctured under ultrasound guidance using a 23-gauge needle and lipiodol was injected manually at a rate of 1 ml/3 min. The procedure was repeated twice in two cases of gastrointestinal carcinoma and four times in one case of lymphoma. In all three cases, the postoperative lymphatic leakage stopped after the repeated intranodal lymphangiography.

Visceral fat accumulation is associated with cerebral small vessel disease.

BACKGROUND AND PURPOSE: Obesity is associated with the risk of coronary artery disease and stroke. Visceral fat plays a significant role in the atherogenic effects of obesity. Whether visceral fat accumulation, as measured by computed tomography (CT), is an independent risk factor for the presence of cerebral small vessel disease (SVD) was investigated. METHODS: This study comprised 506 Japanese subjects 35-74 years of age (mean 55.3 years) without a history of symptomatic cerebrovascular disease who underwent health screening tests, including brain magnetic resonance imaging, carotid echography and measurements of the visceral fat area (VFA) and subcutaneous fat area (SFA) on abdominal CT. Visceral fat accumulation was defined as VFA ≥ 100 cm(2) . Logistic regression analysis was performed to examine the associations between visceral fat accumulation and cerebral SVD such as white matter lesions (WMLs) and silent lacunar infarction (SLI). RESULTS: The prevalence of WMLs and SLI but not carotid plaque were significantly higher in subjects with VFA ≥ 100 cm(2) than those with VFA < 100 cm(2) . A VFA ≥ 100 cm(2) was associated with WMLs and SLI independent of age, cardiovascular risk factors and other measurements of obesity, such as waist circumference and body mass index. A large waist circumference was independently associated with SLI. SFA, the combination of VFA and SFA, and body mass index were not associated with WMLs or SLI. CONCLUSIONS: Visceral fat accumulation was independently associated with the presence of cerebral SVD in subjects without a history of symptomatic cerebrovascular disease.

Evaluation of genetic introgression from domesticated pigs into the Ryukyu wild boar population on Iriomote Island in Japan.

We evaluated genetic introgression from domesticated pigs into the Ryukyu wild boar (RWB) population on Iriomote Island based on their genetic structure and diversity. We used a combination of mitochondrial DNA D-loop region (596 bp) polymorphisms and 23 microsatellite markers. RWBs (n = 130) were collected from 18 locations on Iriomote Island and compared with 66 reference samples of European and Asian domestic pigs. We identified six distinct haplotypes, involving 22 single nucleotide polymorphisms (including one insertion) in the RWB population. The phylogenetic tree had two branches: the RWB group and domestic lineage. Fourteen of 130 RWBs (10.8%) belonged to the European domestic lineage, including 11 RWBs from the Panari Islands, northwest of Iriomote Main Island (IMI). The heterozygosity values, total number of alleles, number of effective alleles and polymorphism information content of the RWB groups were lower than those of the European domestic groups. The RWB population on IMI had a lower heterozygous deficiency index (FIS = 0.059) than did the other populations, which indicates that this population was more inbred. There was a large genetic distance (FST = 0.560) between RWBs on IMI and the Meishan populations. Structure analysis using the 23 microsatellite markers revealed that 16 RWBs had an admixture pattern between RWB and domesticated pig breeds. These results suggest that gene flow may have occurred from domestic pigs to RWBs and demonstrate that there was low genetic variation in the IMI population.

Design of soft x-ray varied-line-spacing (VLS) high-dispersion laminar-type grating coated with super-mirror-type (SMT) multilayer for flat-field spectrograph in a region of 2-4 keV.

A soft x-ray varied-line-spacing (VLS) laminar-type spherical grating with a super-mirror-type (SMT) multilayer was designed for a soft x-ray high resolution flat-field spectrograph in a region of 2-4 keV. The effective groove density of the designed VLS grating is 3200 lines/mm, and the local groove density varies from 2700 to 3866 lines/mm. The geometrical imaging property was evaluated by numerical calculations. The resolving power estimated by means of ray tracing was up to ∼103. For the evaluation of diffraction efficiency, the SMT multilayer structure designed for 3200 lines/mm in our previous work, Koike et al., Rev. Sci. Instrum. 94, 045109 (2023), was employed, and the numerical calculation was performed considering the local groove density of VLS grooves and the local incidence angle being affected by the curvature of the spherical surface and the geometrical relation between the source and incidence point on the grating. The results showed that the SMT multilayer-coated grating exhibited about an order of magnitude higher diffraction efficiency compared with an Au-coated grating.

Design of soft x-ray laminar-type gratings coated with supermirror-type multilayer to enhance diffraction efficiency in a region of 2-4 keV.

Soft x-ray diffraction gratings coated with a supermirror-type multilayer were designed to enhance diffraction efficiency in the energy range of 2-4 keV by means of numerical calculations. The optimized groove depth and incidence angle are 2.05 nm and 88.65°, respectively, for the grating having a groove density of 3200 grooves/mm. Regarding the multilayer structure, the optimum number of B4C/W layers pair was 11 and the thickness of B4C was increased from bottom to top, while that of W was kept constant. The replacement of the top layer of W by either Co, Cr, or Ni was an effective means of obtaining uniform diffraction efficiency. In the region of 2-4 keV, the calculated diffraction efficiency of the designed gratings was up to ∼5.3%, on average, and almost eight times larger than that of ∼0.7% of an Au coated grating.

Role of natural killer T cells in the mouse colitis-associated colon cancer model.

Invariant natural killer T (iNKT) cells are considered innate-like lymphocytes, and regulate the immunity against inflammation and tumorigenesis. However, the impact of iNKT cells in inflammation-associated tumorigenesis remains unclear. In this study, we examined the physiological role of iNKT cells in a mouse colitis-associated colorectal cancer model. C57BL/6 (B6) and Jα18 NKT cell-deficient KO (KO) mice were used. Colitis-associated colorectal cancer was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The resulting inflammation and tumours were examined. The surface markers of mononuclear cells from the liver and the colon were assessed by FACS. The levels of IL-13 from the colon were measured by ELISA. α-galactosylceramide (GC), or its close analog OCH, was administered intraperitoneally on the first day of each cycle of DSS-administration. In the AOM/DSS model, hepatic iNKT cells were significantly decreased. In KO mice there were significantly greater numbers of colon tumours and more severe inflammation than in B6 mice. FACS analysis revealed that the population of NK1.1 (+) T cells (non-invariant NKT cells) in the colon was increased when compared to B6 mice. The secretion of IL-13 was increased in the colon of KO mice after AOM/DSS. The number of colon tumours was significantly decreased in the GC-treated group compared to the control group. GC-treatment significantly inhibited IL-13 secretion from the colonic mononuclear cells and the number of colonic NK1.1 (+) T cells was significantly decreased. These results suggest that iNKT cells may play a critical role in the prevention of tumour progression and inflammation in the AOM/DSS model.

Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern.

To investigate the efficacy of long-term lamivudine (3TC) and adefovir dipivoxil (ADV) combination therapy in 3TC-resistant chronic hepatitis B virus (HBV) infected patients, we analysed 28 3TC-resistant patients treated with the combination therapy during 47 months (range, 9-75). At 12, 24, 36, and 48 months, the rates of virological response with undetectable HBV DNA (≤ 2.6 log copies/mL) were 56, 80, 86, and 92%, respectively. Among 17 hepatitis B e antigen (HBeAg)-positive patients, HBeAg disappeared in 24% at 12 months, 25% at 24 months, 62% at 36 months, and 88% at 48 months. When HBV genotypes were compared, patients with genotype B achieved virological response significantly more rapidly than those with genotype C (P=0.0496). One patient developed virological breakthrough after 54 months, and sequence analysis of HBV obtained from the patient was performed. An rtA200V mutation was present in the majority of HBV clones, in addition to the 3TC-resistant mutations of rtL180M+M204V. The rtN236T ADV-resistant mutation was observed in only 25% clones. In vitro analysis showed that the rtA200V mutation recovered the impaired replication capacity of the clone with the rtL180M+M204V mutations and induced resistance to ADV. Moreover, rtT184S and rtS202C, which are known entecavir-resistant mutations, emerged in some rtL180M+M204V clones without rtA200V or rtN236T. In conclusion, 3TC+ADV combination therapy was effective for most 3TC-resistant patients, especially with genotype B HBV, but the risk of emergence of multiple drug-resistant strains with long-term therapy should be considered. The mutation rtA200V with rtL180M+M204V may be sufficient for failure of 3TC+ADV therapy.

The water-soluble extract from cultured medium of Ganoderma lucidum (Reishi) mycelia (Designated as MAK) ameliorates murine colitis induced by trinitrobenzene sulphonic acid.

Ganoderma lucidum Karst is well known as 'Reishi', a traditional food in China and Japan. It contains a polysaccharide component known to induce granulocyte macrophage colony-stimulating factor (GM-CSF) production from murine splenocytes. Moreover, GM-CSF may be a therapeutic agent for Crohn's disease. In this study, we investigated the water-soluble, polysaccharide components of Reishi (designated as MAK) in murine colitis induced by trinitrobenzene sulphonic acid (TNBS). We examined the concentration of GM-CSF in peritoneal macrophage cells (PMs) of C57BL/6 mice during in vitro and in vivo stimulation with MAK. After feeding with chow or MAK for 2 weeks, 2 mg of TNBS/50% ethanol was administered to each mouse. After 3 days of TNBS treatment, intestinal inflammation was evaluated, and mononuclear cells of the mesenteric lymph nodes (MLNs) and colon were cultured for ELISA. To determine the preventive role of GM-CSF, the mice were pre-treated with or without anti-GM-CSF antibody before TNBS administration. In vitro and in vivo MAK-stimulated PMs produced GM-CSF in a dose-dependent manner. Intestinal inflammation by TNBS was improved by feeding with MAK. MLNs of mice treated with TNBS produced IFN-γ, which was inhibited by feeding with MAK. In contrast, MLNs of mice treated with TNBS inhibited GM-CSF production, which was induced by feeding with MAK. The colon organ culture assay also revealed that IFN-γ was decreased and GM-CSF was increased by MAK. The preventive effect was blocked by the neutralization of GM-CSF. We concluded that the induction of GM-CSF by MAK may provide the anti-inflammatory effect.

A norovirus outbreak associated with environmental contamination at a hotel.

SUMMARYIn December 2006, an outbreak of gastroenteritis occurred involving 372 guests and 72 employees at a hotel after a guest vomited in corridors on the third (F3) and 25th (F25) floors. Norovirus with identical genotype was confirmed by real-time reverse transcription-polymerase chain reaction in faecal samples from guest cases and employees. Spread of the outbreak on F25 was compared with that on F3. The attack rate in the guests who visited F25 alone (15·0%, 106/708 guests) was significantly higher than in those who visited F3 alone (3·5%, 163/4710 guests) (relative risk 4·3, 95% confidence interval 3·4-5·5, P < 0·001). The outbreak on F3 ended within 2 days, while that on F25 extended over 7 days. The environmental ratios of F3 to F25 were 7·4 for volume, 6·9 for floor area and 7·6 for ventilation rate. This outbreak suggests that environmental differences can affect the propagation and persistence of a norovirus outbreak following environmental contamination.

A fatal case of severe methemoglobinemia presumably due to chlorate ingestion.

A fatal case due to severe methemoglobinemia is presented. A male in his forties was found unconscious in his house and, despite intensive care, death was confirmed approximately 11 hours later. Toxicological analysis using ion chromatography revealed the presence of chlorate in the stomach contents. However, chlorate was not detected in the blood, and no other drugs or ethanol were detected in the blood either. We concluded that the cause of death was presumably due to chlorate poisoning, based on the results of the autopsy and the toxicological examination.

Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa.

We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SRalpha promoter developed chronic colitis in concert with the expression of SRalpha/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4-12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell-depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell type 1 CD4+ T cells. Flow cytometric analysis demonstrated that CD4+ intraepithelial T cells were increased, but T cell receptor gamma/delta T cells and CD8alpha/alpha cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell-derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.

Differential transcriptional characteristics of small and large biliary epithelial cells derived from small and large bile ducts.

Biliary epithelial cells (BEC) are morphologically and functionally heterogeneous. To investigate the molecular mechanism for their diversities, we test the hypothesis that large and small BEC have disparity in their target gene response to their transcriptional regulator, the biliary cell-enriched hepatocyte nuclear factor HNF6. The expression of the major HNF (HNF6, OC2, HNF1b, HNF1a, HNF4a, C/EBPb, and Foxa2) and representative biliary transport target genes that are HNF dependent were compared between SV40-transformed BEC derived from large (SV40LG) and small (SV40SM) ducts, before and after treatment with recombinant adenoviral vectors expressing HNF6 (AdHNF6) or control LacZ cDNA (AdLacZ). Large and small BEC were isolated from mouse liver treated with growth hormone, a known transcriptional activator of HNF6, and the effects on selected target genes were examined. Constitutive Foxa2, HNF1a, and HNF4a gene expression were 2.3-, 12.4-, and 2.6-fold, respectively, higher in SV40SM cells. This was associated with 2.7- and 4-fold higher baseline expression of HNF1a- and HNF4a-regulated ntcp and oatp1 genes, respectively. Following AdHNF6 infection, HNF6 gene expression was 1.4-fold higher (P = 0.02) in AdHNF6 SV40SM relative to AdHNF6 SV40LG cells, with a corresponding higher Foxa2 (4-fold), HNF1a (15-fold), and HNF4a (6-fold) gene expression in AdHNF6-SV40SM over AdHNF6-SV40LG. The net effects were upregulation of HNF6 target gene glucokinase and of Foxa2, HNF1a, and HNF4a target genes oatp1, ntcp, and mrp2 over AdLacZ control in both cells, but with higher levels in AdH6-SV40SM over AdH6-SV40LG of glucokinase, oatp1, ntcp, and mrp2 (by 1.8-, 3.4-, 2.4-, and 2.5-fold, respectively). In vivo, growth hormone-mediated increase in HNF6 expression was associated with similar higher upregulation of glucokinase and mrp2 in cholangiocytes from small vs. large BEC. Small and large BEC have a distinct profile of hepatocyte transcription factor and cognate target gene expression, as well as differential strength of response to transcriptional regulation, thus providing a potential molecular basis for their divergent function.

Scoring System to Predict pt2 in Gallbladder Cancer Based on Carcinoembryonic Antigen and Tumor Diameter.

BACKGROUND AND AIMS: T2 gallbladder cancer requires lymph node dissection for curative resection, whereas simple cholecystectomy is adequate to treat T1 gallbladder cancer. Hence, this study aimed to develop an accurate scoring system to preoperatively predict pT2 in gallbladder cancer. MATERIAL AND METHODS: We retrospectively assessed data from 57 patients with suspected gallbladder cancer who underwent curative resection between September 2003 and May 2017. Six with apparent invasion of adjacent organs on preoperative images were excluded. We evaluated preoperative computed tomography, magnetic resonance and endoscopic ultrasonographic images, blood biochemistry, and the maximum standard uptake value in fluorodeoxyglucose-positron emission tomography images. We analyzed whether correlations between preoperative findings and the depth of tumor invasion could predict pT2. RESULTS: The pathological diagnosis was gallbladder cancer in 30 (58.8%) patients, of whom 21 (69.9%) had pT2 or worse. Multivariate analyses selected carcinoembryonic antigen and tumor diameter as independent predictors of pT2 or worse (odds ratios = 1.741 and 1.098, respectively; 95% confidence intervals = 1.004-3.020 and 1.008-1.197, respectively). A regression formula was created using carcinoembryonic antigen and tumor diameter to calculate pT2 predictive scores. The area under the receiver operating characteristics curve of the pT2 predictive score was 0.873. CONCLUSION: We created a scoring system to predict pT2 in gallbladder cancer using carcinoembryonic antigen and tumor diameter. The present findings suggested that carcinoembryonic antigen is important for the preoperative evaluation of gallbladder cancer.

Coherent transfer of orbital angular momentum to excitons by optical four-wave mixing.

We demonstrate the coherent transfer of optical orbital angular momentum (OAM) to the center of mass momentum of excitons in semiconductor GaN using a four-wave mixing (FWM) process. When we apply the optical vortex (OV) as an excitation pulse, the diffracted FWM signal exhibits phase singularities that satisfy the OAM conservation law, which remain clear within the exciton dephasing time (approximately 1ps). We also demonstrate the arbitrary control of the topological charge in the output signal by changing the OAM of the input pulse. The results provide a way of controlling the optical OAM through carriers in solids. Moreover, the time evolution of the FWM with OAM leads to the study of the closed-loop carrier coherence in materials.

Laser-stimulated luminescence used to measure x-ray diffraction of a contracting striated muscle.

An integrating x-ray area detector that operates on the basis of laser-stimulated luminescence was used in a diffraction study of muscle contraction. The area detector has a dynamic range of 1 to 10(5), a sensitivity about 60 times greater with approximately 1/300 as much fog background as x-ray film. It is erasable and reusable but, like film, can integrate at a practically unlimited counting rate. The high sensitivity and wide dynamic range of the detector resulted in a sufficient reduction in the exposure time to make possible the recording of a clear x-ray diffraction pattern, with up to 2.0-nanometer axial spacing, from a contracting frog skeletal muscle in as little as 10 seconds with synchrotron radiation. During the isometric contraction of the muscle, most of the actin diffraction lines increased in intensity without noticeable changes in their peak positions. Changes also occurred in diffraction intensities from the myosin heads. The results indicate that during contraction the structure of the actin filaments differs from that in the rigor state, suggesting a possible structural change in the actin subunits themselves; the myosin heads during contraction retain the axial periodicity of the myosin filament and become aligned in a more perpendicular manner to the actin filaments.