SPring-8 BL36XU: Catalytic Reaction Dynamics for Fuel Cells

A tapered undulator beamline BL36XU was constructed at SPring-8 to conduct structural and electronic analysis of dynamic events on polymer electrolyte fuel cell (PEFC) cathode catalysts for the development of next-generation PEFCs. BL36XU provides various time and spatially resolved XAFS techniques in an energy range from 4.5 to 35 keV for investigating PEFCs under the operating conditions. In addition, we developed in-situ complementary measurement systems, such as in-situ time-resolved XAFS/XRD and ambient pressure HAXPES systems. This report describes the performance and present status of the BL36XU

Early Intervention with Mepolizumab, Corticosteroids, and Intravenous Immunoglobulin for Dupilumab-Triggered Eosinophilic Granulomatosis with Polyangiitis: A Case Report

Shota Kaburaki, Toru Tanaka, Koichiro Kamio, Yosuke Tanaka, Kazuo Kasahara, Masahiro Seike Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, JapanCorrespondence: Shota Kaburaki, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan, Email [email protected]: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare complication during dupilumab therapy. However, the optimal treatment strategy for dupilumab-triggered EGPA remains unclear, particularly the timing and role of anti-interleukin-5 therapy.Case Study: A 48-year-old female with severe eosinophilic rhinosinusitis and asthma, increased blood eosinophils (2098/μL) and myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) (46.1 U/mL) without vasculitic symptoms, developed systemic symptoms, including fever, arthralgia, and peripheral neuropathy immediately after dupilumab administration.Results: Physical assessment revealed bilateral expiratory wheezes and laboratory tests revealed marked elevations in blood eosinophil (11,889/μL) and MPO-ANCA levels (125.0 U/mL). Other conditions, including parasitic infections, allergic bronchopulmonary aspergillosis, and FIP1L1-PDGFRA-positive disease, were excluded. Early intervention with mepolizumab (300 mg), methylprednisolone pulse therapy, and intravenous immunoglobulin (IVIG) was initiated after discontinuing dupilumab, resulting in rapid normalization of blood eosinophil counts and clinical improvement. Residual neuropathy was successfully treated with intravenous immunoglobulin (IVIg). Prednisolone was reduced to 15 mg daily with negative MPO-ANCA one month after treatment initiation.Conclusion: This case emphasizes the importance of monitoring preexisting MPO-ANCA and blood eosinophils before and during dupilumab therapy. Early intervention with mepolizumab combined with conventional therapy is considered an optimal treatment strategy for dupilumab-triggered EGPA.Keywords: antibodies, antineutrophil, cytoplasmic, mepolizumab, eosinophils, Churg-Strauss syndrome, dupiluma

AMPLITUDE DEPENDENT BETATRON OSCILLATION CENTER SHIFT BY NON-LINEARITY AND BEAM INSTABILITY INTERLOCK

Abstract As a result of the even symmetry of the Sextupole field, it creates the horizontal shift of the averaged position of horizontal and vertical betatron oscillation and the amount of the shift depends on its oscillation amplitude. This shift can be observed with usual slow orbit beam position monitor. At the SPring-8 storage ring, this shift is used to detect the excitation of the betatron oscillation for the interlock system for the protection of the vacuum components from strong radiation of insertion devices. AMPLITUDE DEPENDENT BETATRON OSCILLATION CENTER SHIFT The transverse beam instability drives a horizontal or vertical betatron oscillation, and if this occurs in light sources, the strong synchrotron radiation from insertion devices also oscillates as the beam and cause heat damages on beam pipe components if the radiation continuously hit them. The even symmetry of the sextupole field produces the horizontal shift of the time averaged horizontal position if the horizontal and vertical betatron oscillation exists. Here we call it an amplitude dependent betatron oscillation center shift (ADCS). The ADCS on the sextupole strength can be derived by a canonical perturbation theory as the first order effect by sextupole field [1] as where the symbols with overline are the time averaged values, J z and φ z ( z = x, y ) are the action and the phase, respectively, and related to the position and beta function β z s The sextupole strength is expressed as for the magnetic field

Ambient Oxygen Levels Regulate Intestinal Dysbiosis and GVHD Severity After Allogeneic Stem Cell Transplantation

The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases

Level of arterial ligation in total mesorectal excision (TME): an anatomical study

Introduction: High-tie ligation is a common practice in rectal cancer surgery. However, it compromises perfusion of the proximal limb of the anastomosis. This anatomical study was designed to assess the value of low-tie ligation in order to obtain a tension-free anastomosis. Materials and methods: Consecutive high- and low-tie resections were performed on 15 formalin-fixed specimens, with or without splenic flexure mobilization. If the proximal colon limb could reach the superior aspect of the symphysis pubis with more than 3 cm, the limb would be long enough for a tension-free colorectal anastomosis. Results: In 80% of cases, it was not necessary to perform high-tie ligation as sufficient length was gained with low-tie ligation. The descending branch of the left colic artery was the limiting factor in the other 20% of cases. Resecting half the sigmoid resulted in four times as many tension-free anastomoses after low-tie resection. Conclusion: In the majority of cases, it was not necessary to perform high-tie ligation in order to create a tension-free anastomosis. Low-tie ligation was applicable in 80% of cases and might prevent anastomotic leakage due to insufficient blood supply of the proximal colon limb

Challenge and promise: the role of miRNA for pathogenesis and progression of malignant melanoma

microRNAs are endogenous noncoding RNAs that are implicated in gene regulation. More recently, miRNAs have been shown to play a pivotal role in multiple cellular processes that interfere with tumorigenesis. Here we summarize the essential role of microRNAs for human cancer with special focus on malignant melanoma and the promising perspectives for cancer therapies

Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients

Slug, a member of the Snail family of transcription factors, plays a crucial role in the regulation of epithelial-mesenchymal transition (EMT) by suppressing several epithelial markers and adhesion molecules including E-cadherin. Recently, several studies have reported Slug to be expressed in breast carcinoma, oesophageal carcinoma accompanied with shorter survival. In this study, we first investigated expression of Slug mRNA in five colorectal carcinoma cell lines by reverse transcription–polymerase chain reaction. Furthermore, we investigated Slug and E-cadherin expression by immunohistochemistry in 138 patients with colorectal carcinoma. Slug mRNA was clearly expressed in four out of five colorectal carcinoma cell lines. Positive expression of Slug and E-cadherin was observed in 37 and 58% of cases, respectively. The positive expression of Slug was significantly associated with Dukes stage and distant metastasis (P=0.0027 and 0.0007), and the positive expression of Slug had a significant impact on patient overall survival (P<0.0001, log-rank test). Moreover, patients with positive expression of Slug and reduced expression of E-cadherin showed the worst prognosis (P<0.0001, log-rank test). Multivariate analysis indicated that Slug expression was an independent prognostic factor. These results suggest that positive Slug expression in colorectal carcinoma patients may become a significant parameter of poor prognosis

Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis

The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain