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The ASACUSA collaboration at the Antiproton Decelerator of CERN aims at a precise measurement of the antihydrogen ground-state hyperfine structure as a test of the fundamental CPT symmetry. A beam of antihydrogen atoms is formed in a CUSP trap, undergoes Rabi-type spectroscopy and is detected downstream in a dedicated antihydrogen detector. In parallel measurements using a polarized hydrogen beam are being performed to commission the spectroscopy apparatus and to perform measurements of parameters of the Standard Model Extension (SME). The current status of antihydrogen spectroscopy is reviewed and progress of ASACUSA is presented. [ABSTRACT FROM AUTHOR]

The aim of the ASACUSA-CUSP experiment at CERN is to produce a cold, polarised antihydrogen beam and perform a high precision measurement of the ground-state hyperfine transition frequency of the antihydrogen atom and compare it with that of the hydrogen atom using the same spectroscopic beam line. Towards this goal a significant step was successfully accomplished: synthesised antihydrogen atoms have been produced in a CUSP magnetic configuration and detected at the end of our spectrometer beam line in 2012 [1]. During a long shut down at CERN the ASACUSA-CUSP experiment had been renewed by introducing a new double-CUSP magnetic configuration and a new semi-cylindrical tracking detector (AMT) [2], and by improving the transport feature of low energy antiproton beams. The new tracking detector monitors the antihydrogen synthesis during the mixing cycle of antiprotons and positrons. In this work the latest results and improvements of the antihydrogen synthesis will be presented including highlights from the last beam time. [ABSTRACT FROM AUTHOR]

Background:Host immunity has critical roles in tumour surveillance. Tertiary lymphoid organs (TLOs) are induced in various inflamed tissues. The aim of this study was to investigate the clinicopathological and pathobiological characteristics of tumour microenvironment in pancreatic ductal carcinoma (PDC) with TLOs.Methods:We examined 534 PDCs to investigate the clinicopathological impact of TLOs and their association with tumour-infiltrating immune cells, the cytokine milieu, and tissue characteristics.Results:There were two different localisations of PDC-associated TLOs, intratumoral and peritumoral. A better outcome was observed in patients with intratumoral TLOs, and this was independent of other survival factors. The PDC tissues with intratumoral TLOs showed significantly higher infiltration of T and B cells and lower infiltration of immunosuppressive cells, as well as significantly higher expression of Th1- and Th17-related genes. Tertiary lymphoid organs developed with an association with arterioles, venules, and nerves. These structures were reduced in an association with cancer invasion in PDC tissues, except for those with intratumoral TLOs. The PDC tissues with intratumoral TLOs had capillaries consisting of mature endothelial cells covered by pericytes.Conclusions:Our results suggest that the presence of intratumoral TLOs represents a microenvironment that has an active immune reaction, and shows a relatively intact vascular network retained. [ABSTRACT FROM AUTHOR]

Background:Phyllodes tumours are rare fibroepithelial tumours of the breast, that include benign, borderline, and malignant lesions. Although the molecular basis of phyllodes tumours largely remains unknown, a recent exome study identified MED12 mutations as a sole recurrent genetic alteration in fibroadenoma, a common benign fibroepithelial tumour that shares some histological features with the phyllodes tumour.Methods:Forty-six phyllodes tumours and 58 fibroadenomas of the breast were analysed for MED12 mutations by using Sanger sequencing.Results:MED12 mutations were identified in 37 out of the 46 phyllodes tumours (80%). The prevalence of MED12 mutations was similar among benign (15/18, 83%), borderline (12/15, 80%), and malignant tumours (10/13, 77%). MED12 mutations were also identified in 36 of the 58 fibroadenomas (62%). The mutations were frequent among intracanalicular-type (24/32, 75%) and complex-type lesions (4/6, 67%), but were significantly less common among the pericanalicular-type lesions (8/20, 40%). A microdissection-based analysis showed that MED12 mutations were confined to the stromal components in both phyllodes tumours and fibroadenomas.Conclusions:MED12 mutations were frequent among the phyllodes tumours of the breast, regardless of the tumour grade. Phyllodes tumours and fibroadenomas share, at least in part, a common genetic background. [ABSTRACT FROM AUTHOR]

Background:Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds.Methods:We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS, KRAS, and BRAF mutations.Results:Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS-mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation.Conclusions:A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours. [ABSTRACT FROM AUTHOR]

Aerosols from the Fukushima Dai-ichi Nuclear Power Plant accident were collected at the Geological Survey of Japan. The temporal patterns of the Cs/Cs, Cs/Cs, and Te/Cs activity ratios were consistent with expectations based on their half-lives. Those for I and Te decreased with some fluctuations. Ag/Cs declined more rapidly than expected and Nb/Cs increased with time. The results suggest that the temporal patterns depended not only on their half-lives but also on many factors such as chemical speciation, the diversity of sources, changes in the temperature and discharge rate from the reactors, and the processes of transport. [ABSTRACT FROM AUTHOR]

Background:Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer.Methods:Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53.Results:L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis.Conclusions:L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer. [ABSTRACT FROM AUTHOR]

Purpose: (18)F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. (18)F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of (18)F-FAMT uptake in patients with oesophageal cancer.Methods: From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both (18)F-FAMT PET/CT and (18)F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of (18)F-FAMT uptake.Results: High uptake of (18)F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that (18)F-FAMT was specifically transported by LAT1.Conclusions: The uptake of (18)F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of (18)F-FAMT accumulation. [ABSTRACT FROM AUTHOR]

Background:ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear.Methods:One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort.Results:ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients.Conclusions:ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery. [ABSTRACT FROM AUTHOR]

Background:The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact.Methods:Using immunohistochemistry, we examined tumour-infiltrating CD68+ pan-macrophages, HLA-DR+CD68+ M1 macrophages (M1), CD163+ or CD204+ M2 macrophages (M2), CD66b+ neutrophils (Neu), CD4+ T cells (CD4+T), CD8+ T cells (CD8+T), and FOXP3+CD4+ regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model.Results:Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4+T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4+T, CD8+T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4+Thigh/CD8+Thigh/%Treglow and tumour-infiltrating %M1high/M2low. Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.Conclusion:Tumour-infiltrating CD4+Thigh/CD8+Thigh/%Treglow and %M1high/M2low are independent prognosticators useful for evaluating the immune microenvironment of PDC. [ABSTRACT FROM AUTHOR]

Background:The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown.Methods:Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line.Results:A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (0-9%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo.Conclusion:Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN. [ABSTRACT FROM AUTHOR]

The ASACUSA collaboration has been making a path to realize high precision microwave spectroscopy of ground-state hyperfine transitions of antihydrogen atom in flight for stringent test of the CPT symmetry. For this purpose, an efficient extraction of a spin polarized antihydrogen beam is essential. In 2010, we have succeeded in synthesizing our first cold antihydrogen atoms employing a CUSP trap. The CUSP trap confines antiprotons and positrons simultaneously with its axially symmetric magnetic field to form antihydrogen atoms. It is expected that antihydrogen atoms in the low-field-seeking states are preferentially focused along the cusp magnetic field axis whereas those in the high-field-seeking states are defocused, resulting in the formation of a spin-polarized antihydrogen beam. [ABSTRACT FROM AUTHOR]

Background:The expression of L-type amino-acid transporter 1 (LAT1) is tumour-specific and has been shown to have essential roles in cell growth and survival. However, little is known regarding the clinical significance of LAT1 expression in pancreatic cancer. This study was conducted to determine the prognostic significance of LAT1 expression.Methods:A total of 97 consecutive patients with surgically resected pathological stage I-IV pancreatic ductal adenocarcinoma were retrospectively reviewed. Tumour sections were stained by immunohistochemistry for LAT1, CD98, Ki-67 and vascular endothelial growth factor (VEGF), and microvessel density was determined by CD34 and p53.Results:L-type amino-acid transporter 1 and CD98 were highly expressed in 52.6% (51/97) and 56.7% (55/97) of cases, respectively (P=0.568). The expression of LAT1 within pancreatic cancer cells was significantly associated with disease stage, tumour size, Ki-67, VEGF, CD34, p53 and CD98. L-type amino-acid transporter 1 expression was confirmed to be a significant prognostic factor for predicting poor outcome by multivariate analysis.Conclusion:L-type amino-acid transporter 1 expression is a promising pathological marker for the prediction of outcome in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Electrical control over electron spin is a prerequisite for spintronics spin-based quantum information processing. In particular, control over the interaction between the orbital motion and the spin state of electrons would be valuable, because this interaction influences spin relaxation and dephasing. Electric fields have been used to tune the strength of the spin-orbit interaction in two-dimensional electron gases, but not, so far, in quantum dots. Here, we demonstrate that electrical gating can be used to vary the energy of the spin-orbit interaction in the range 50-150 µeV while maintaining the electron occupation of a single self-assembled InAs quantum dot. We determine the spin-orbit interaction energy by observing the splitting of Kondo effect features at high magnetic fields. [ABSTRACT FROM AUTHOR]

During the analysis of phosphotyrosine-containing proteins in scirrhous gastric carcinoma cell lines, we observed an unusual expression of Arf-GAP with Rho-GAP domain, ankyrin repeat and PH domain 3 (ARAP3), a multimodular signaling protein that is a substrate of Src family kinases. Unlike other phosphotyrosine proteins, such as CUB domain-containing protein 1 (CDCP1) and Homo sapiens chromosome 9 open reading frame 10/oxidative stress-associated Src activator (C9orf10/Ossa), which are overexpressed and hyperphosphorylated in scirrhous gastric carcinoma cell lines, ARAP3 was underexpressed in cancerous human gastric tissues. In this study, we found that overexpression of ARAP3 in the scirrhous gastric carcinoma cell lines significantly reduced peritoneal dissemination. In vitro studies also showed that ARAP3 regulated cell attachment to the extracellular matrix, as well as invasive activities. These effects were suppressed by mutations in the Rho-GTPase-activating protein (GAP) domain or in the C-terminal two tyrosine residues that are phosphorylated by Src. Thus, the expression and phosphorylation state of ARAP3 may affect the invasiveness of cancer by modulating cell adhesion and motility. Our results suggest that ARAP3 is a unique Src substrate that suppresses peritoneal dissemination of scirrhous gastric carcinoma cells. [ABSTRACT FROM AUTHOR]

Background: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC).Methods: We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC.Results: Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was 'almost perfect' (κ-value of 0.87).Conclusion: Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients. [ABSTRACT FROM AUTHOR]

We have performed precision atomic spectroscopy of trapped radioactive Be isotopes aiming at studies of the charge and magnetization radii of these nuclei especially for a single-neutron halo nucleus 11Be . Some experimental results and the status of the analysis are discussed. [ABSTRACT FROM AUTHOR]

Our group “ASACUSA MUSASHI” has established an efficient way for accumulating antiprotons and extracting them as intense ultra-slow mono-energetic beams at the CERN-AD facility. This novel beam opens new frontiers for investigating a variety of physics. For realizing H̄ spectroscopy and the test for charge-parity-time symmetry, we have also developed the cusp trap, a combination of an anti-Helmholz superconducting coil and a multi-ring electrode trap, for trapping both antiprotons and positrons and then synthesizing antihydrogens. Recently, the cusp trap was practically used to accumulate antiprotons. The last piece for synthesizing antihydrogens in the cusp trap is the positron accumulator. We have developed a compact system to effectively accumulate positrons based on N2 gas-buffer scheme with a specially designed high precision cylindrical multi-ring electrode trap. The recent progress of the developing work is an important milestone for upcoming antihydrogen science of ASACUSA MUSASHI. [ABSTRACT FROM AUTHOR]

Epigenetic therapy using DNA methylation inhibitors and histone deacetylase (HDAC) inhibitors has clinical promise for the treatment of human malignancies. To investigate roles of microRNAs (miRNAs) on epigenetic therapy of gastric cancer, the miRNA expression profile was analysed in human gastric cancer cells treated with 5-aza-2′-deoxycytidine (5-Aza-CdR) and 4-phenylbutyric acid (PBA). miRNA microarray analysis shows that most of miRNAs activated by 5-Aza-CdR and PBA in gastric cancer cells are located at Alu repeats on chromosome 19. Analyses of chromatin modification show that DNA demethylation and HDAC inhibition at Alu repeats activates silenced miR-512-5p by RNA polymerase II. In addition, activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells. These results suggest that chromatin remodeling at Alu repeats plays critical roles in the regulation of miRNA expression and that epigenetic activation of silenced Alu-associated miRNAs could be a novel therapeutic approach for gastric cancer.Oncogene (2009) 28, 2738–2744; doi:10.1038/onc.2009.140; published online 8 June 2009 [ABSTRACT FROM AUTHOR]

Purpose: We developed a new type of scintillation detector ring for positron emission tomography (PET). In this device the scintillation detectors were connected with 2.6 m length optic fibers to transport scintillation light to a photomultiplier (PMT) located apart from the detector rings. The present study aimed to test the possibility of simultaneous imaging with PET and magnetic resonance imaging (MRI) by means of the present PET device in ex vivo rat brain.Materials and Methods: The scintillation detector ring of 4 cm diameter was located in a magnetic field of 0.15 T open MRI. Simultaneous measurements of PET and MRI were performed in ex vivo rat brain after injection of (18)F-fluorodeoxyglucose ((18)F-FDG) 37 MBq and (18)F-NaF 37 MBq. Simultaneous data acquisition was performed for 10 min for PET and 5 min for T1-weighted MRI.Results: Simultaneous imaging of PET and MRI was possible without noticeable image distortion in the PET and MRI scans. In the fusion images, high uptake of (18)F-FDG was identified in the Harderian glands and striatum. High uptake of (18)F-NaF was found in the skull base and vault.Conclusions: The present study indicated the possibility of simultaneous imaging of PET and MRI by means of optic fiber-based scintillation detectors. [ABSTRACT FROM AUTHOR]

Guiding of beams through flat insulating capillaries has been investigated. A flat capillary guides a beam at inclination of the capillary plane with respect to the beam direction. It is found that a beam can be guided by rotation of a flat capillary around the axis oriented perpendicularly to its plane, i.e., without changing the plane orientation. This effect has been referred to as double guiding. Theoretical models are proposed to explain guiding and double guiding of an ion beam through a flat capillary. [ABSTRACT FROM AUTHOR]

Objective: A planar positron imaging system (PPIS) enables whole-body dynamic imaging of radiopharmaceuticals labeled with positron-emitting nuclides. We evaluated the difference in the brain and whole-body pharmacokinetics of (11)C-diphenylhydantoin ((11)C-DPH) between intravenous and duodenal administration in rats. Methods: Male Wistar rats (8 weeks old, mean body weight 250 g) were examined under anesthesia. A tracer amount of (11)C-DPH (2 microg or less; about 5 MBq) was injected into the tail vein (n = 3) or duodenum (n = 3). Immediately following the administration, PPIS scans were obtained for 20 min. Regions of interest (ROIs) were set on the brain, heart, liver, intestinal field, and urinary bladder, identified on the integrated images. The relative uptake value (RUV, %) was calculated as the regional count divided by the whole-body count multiplied by 100. Sequential changes in the RUV for each ROI were analyzed for the brain and other organs. Results: Following intravenous injection of (11)C-DPH, the RUV in the brain was 1.59 +/- 0.07%, 1.53 +/- 0.09%, 1.40 +/- 0.09%, and 1.38 +/- 0.08% at 5 min, 10 min, 15 min, and 20 min after the injection, respectively. After duodenal administration, the corresponding values were 0.54 +/- 0.16%, 1.01 +/- 0.12%, 1.43 +/- 0.24%, and 1.52 +/- 0.06%, respectively. The (11)C-DPH distribution was significantly lower at 5 min and 10 min following duodenal administration than after intravenous injection (P < 0.01). Radioactivity in the urinary bladder was identified by 20 min after both intravenous injection and duodenal administration. Conclusions: The present study demonstrated a difference in the brain distribution of (11)C-DPH between intravenous and duodenal administration in rats. Use of the PPIS is feasible for the evaluation of the pharmacokinetics in both the target organ and the whole body in small animals. [ABSTRACT FROM AUTHOR]

The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I-III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; P<0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I-III NSCLC. [ABSTRACT FROM AUTHOR]

A next-generation slow radioactive nuclear ion beam facility (SLOWRI) which provides slow, high-purity and small emittance ion beams of all elements is being build as one of the principal facilities at the RIKEN RI-beam factory (RIBF). High energy radioactive ion beams from the projectile fragment separator BigRIPS are thermalized in a large gas catcher cell. The thermalized ions in the gas cell are guided and extracted to a vacuum environment by a combination of dc electric fields and inhomogeneous rf fields (rf carpet ion guide). From there the slow ion beam is delivered via a mass separator and a switchyard to various devices: such as an ion trap, a collinear fast beam apparatus, and a multi-reflection time of flight mass spectrometer. In the R&D works at the present RIKEN facility, an overall efficiency of 5% for a 100 A MeV 8Li ion beam from the present projectile fragment separator RIPS was achieved and the dependence of the efficiency on the ion beam intensity was investigated. Recently our first spectroscopy experiment at the prototype SLOWI was performed on Be isotopes. Energetic ions of 10Be and 7Be from the RIPS were trapped and laser cooled in a linear rf trap and the specific mass shifts of these isotopes were measured for the first time. [ABSTRACT FROM AUTHOR]

The WT1 gene is overexpressed in human primary leukemia and a wide variety of solid cancers. The WT1 gene is alternatively spliced at two sites, yielding four isoforms: 17AA(+)KTS(+), 17AA(+)KTS(−), 17AA(−)KTS(+), and 17AA(−)KTS(−). Here, we showed that 17AA(+)WT1-specific siRNA induced apoptosis in three WT1-expressing leukemia cell lines (K562, HL-60, and Kasumi-1), but not in WT1-non-expressing lymphoma cell line (Daudi). 17AA(+)WT1-specific siRNA activated caspase-3 and -9 in the intrinsic apoptosis pathway but not caspase-8 in the extrinsic one. On the other hand, 17AA(−)WT1-specific siRNA did not induce apoptosis in the three WT1-expressing cell lines. The apoptosis was associated with activation of proapoptotic Bax, which was activated upstream of the mitochondria. Constitutive expression of 17AA(+)WT1 isoforms inhibited apoptosis of K562 leukemia cells induced by apoptosis-inducing agents, etoposide and doxorubicin, through the protection of mitochondrial membrane damages, and DNA-binding zinc-finger region of 17AA(+)WT1 isoform was essential for the antiapoptotic functions. We further studied the gene(s) whose expression was altered by the expression of 17AA(+)WT1 isoforms and showed that the expression of proapoptotic Bak was decreased by the expression of 17AA(+)KTS(−)WT1 isoform. Taken together, these results indicated that 17AA(+)WT1 isoforms played antiapoptotic roles at some points upstream of the mitochondria in the intrinsic apoptosis pathway.Oncogene (2006) 25, 4217–4229. doi:10.1038/sj.onc.1209455; published online 6 March 2006 [ABSTRACT FROM AUTHOR]

Geological and geochemical events were elucidated in by using U series nuclides in combination with chemical leaching technique. Two examples were examined: (1) in the apatite-bearing sediment column samples U(VI) is moving, while U(IV) in the samples is almost retained, and (2) the redistribution of U occurred along the column under the monsoon climate. On the other hand, U in the conglomerate sample is divided into 5 categories by the leaching technique, which are related with exchangeable, carbonate, iron oxide, organic/sulfide and silicate components, respectively. Uranium is shown to be abundant in the carbonate and iron rich fractions of conglomerate sediment. Appropriate models are proposed in each case study. [ABSTRACT FROM AUTHOR]

E-cadherin, the major intercellular adhesion molecule of epithelial cells, is important in determining the architecture of sarcomas, especially those showing epithelioid features. In addition to its role in cell adhesion, beta-catenin, a cadherin undercoat protein, has been shown to function as a downstream transcriptional activator of the Wnt/Wingless signaling pathway. In order to evaluate the significance of the cadherin cell adhesion system and the Wnt/Wingless signaling pathway in the morphogenesis and/or tumorigenesis of synovial sarcoma (a major type of sarcoma with epithelioid features), immunoreactivity for pan-cadherin, E-cadherin, and their undercoat proteins (alpha-, beta-,and gamma-catenins and p120) was evaluated in 15 synovial sarcomas. Immunoreactivity for pan-cadherin, E-cadherin, alpha-catenin, beta-catenin, and p120 was observed in all 15 specimens. Immunoreactivity for pan-cadherin was stronger than that for E-cadherin. Expression of gamma-catenin was detected in ten specimens. Although beta-catenin was observed only at the cell-cell boundaries in four specimens, it was present in the nucleus and cytoplasm and at the cell-cell boundaries in the other 11, suggesting constitutional activation of the Wnt/Wingless signaling pathway in synovial sarcoma. Direct sequencing for exon 3 of the beta-catenin gene, however, revealed no mutations in any of the 15 specimens. In conclusion, other types of cadherin besides E-cadherin, together with cadherin undercoat proteins, may play a role in cell adhesion in synovial sarcoma. Furthermore, mechanisms other than mutation of exon 3 of the beta-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor. [ABSTRACT FROM AUTHOR]

Age-related alterations in binding sites of major second messengers and a selective adenosine 3′,5′-cyclic monophosphate (cyclic-AMP) phospho-diesterase (PDE) in the gerbil brain were analysed by receptor autoradiography. [H]Phorbol 12,13-dibutyrate (PDBu), [H]inositol 1,4,5-trisphosphate (IP), [H]forskolin, [H]cyclic-AMP, and [H]rolipram were used to label protein kinase C (PKC), IP receptor, adenylate cyclase, cyclic-AMP dependent protein kinase (PKA), and Ca/calmodulin-mdependent cyclic-AMP PDE, respectively. In middle-aged gerbils (16 months old), [H]PDBu binding was significantly reduced in the hippocampal CA 1 sector, thalamus, substantia nigra, and cerebellum, compared with young animals (1 month old). [H]IP binding revealed significant elevations in the nucleus accumbens, hippocampal CA 1 sector, dentate gyrus, and a significant reduction in cerebellum of middle-aged gerbils. [H]Forskolin binding in middle-aged animals was significantly increased in the nucleus accumbens and hilus of dentate gyrus, but was diminished in the substantia nigra and cerebellum. On the other hand, in middle-aged animals, [H]cyclic-AMP binding revealed a significant elevation only in the hippocampal CA3 sector, whereas [H] rolipram binding showed a significant reduction in the thalamus and cerebellum. Thus, the age-related alteration in these binding sites showed different patterns among various brain regions in middle-aged gerbils indicating that the binding sites of PKC, IP, and adenylate cyclase are more markedly affected by aging than those of PKA and cyclicAMP PDE and that the hippocampus and cerebellum are more susceptible to these aging processes than other brain regions. The findings suggest that in-tracellular signal transduction is affected at an early stage of senescence and this may lead to neurological deficits. [ABSTRACT FROM AUTHOR]

We have measured the target thickness dependence of K-vacancy production probabilities and total cross sections for 40.6 MeV Ar ions hitting Ca and Cu targets. The probabilities were measured as a function of the scattering angle between 0.13° and 1.4° by means of a K x-ray-particle coincidence. By integrating the measured probabilities over the impact parameter a significantly lower total cross section was obtained than the directly measured value. The maximum seen in the impact parameter dependent probability varies with decreasing target thickness towards the results obtained with molecular and atomic gas targets. From these observations a multiple collision L-vacancy process prior to 2 pπ-2 pσ rational coupling is concluded. [ABSTRACT FROM AUTHOR]

We have measured the impact parameter dependent K-shell ionization probabilities P ( b) of Ca, Cr and Cu from collisions with 4.04 MeV He ions by particle- K X ray coincidences. A dependence on the target thickness was investigated to study a possible influence of multiple collisions on P( b). We measured the total cross section σ for K vacancy production simultaneously with P( b) and σ agrees within 30% with the integrated P( b). A comparison of the P( b) and σ with SCA calculations of Trautmann et al. using RHFS wavefunctions for united atom and separated atom states is discussed. [ABSTRACT FROM AUTHOR]

Rabbits infected with the L strain of rinderpest virus (RV) produced high titres of antinuclear antibodies (ANA) which reached a maximum two weeks after inoculation but rapidly disappeared by 6-8 weeks. These ANAs reacted with HeLa cells by indirect immunofluorescence test resulting in a homogeneous nuclear fluorescence. In order to investigate the target antigens of ANAs, the effects on the nuclear fluorescence pattern of pretreating HeLa cells were examined: DNase 1 treatment resulted in a decrease in the fluorescence whereas no changes were evident after RNase A treatment. Some group of sera showed decreased fluorescence in the cells from which histones were acid extracted, but other groups did not change in fluorescence. Sera which had failed to react with acid extracted cells gave positive fluorescence following histone reconstitution. The results indicate that DNA and nucleohistone are the major target antigens for ANAs. In addition, antibodies against nucleoli and extractable nuclear antigens were induced in some rabbits. [ABSTRACT FROM AUTHOR]

Changes in lectin bindings of mouse trophoblastic giant cells (TGCs) were examined by light and electron microscopy. Neither Griffonia simplicifolia agglutinin (GS)-II nor succinyl-wheat germ agglutinin (s-WGA) bound to the 1st and 2nd TGCs on day 6.5 post coitum (p.c.), but did so from days 8.5 to 12.5 p.c. Positive reactions with s-WGA were localized in the perinuclear region and cell surface of both 1st and 2nd TGCs; while GS-II bound only to the perinuclear region, where it appeared as network-like deposits. This region was identified as well-developed Golgi lamellae by electron microscopy. Moreover, SDS-PAGE and lectin-blot analysis of the 1st TGCs indicated that the intensity of s-WGA and GS-II bindings increased in the glycoproteins of approximately 43, 40, 37, and 26 kDa and in those of 43 and 38 kDa, respectively, during the 8.5th to 10.5th day p.c. The reaction with GS-I was detected on cell surface of both the 1st and 2nd TGCs on day 6.5 p.c. The reaction in the 1st TGCs was intensely positive throughout their development, whereas the reactivity decreased in the 2nd TGCs on day 10.5 p.c. and completely disappeared on day 12.5 p.c. The GS-I reaction in TGCs was more intense at the maternal side than at the embryonic side. These results suggest that certain Gal and/or GlcNAc glycoproteins on the cell surface and in Golgi lamellae of TGCs dynamically change from the 8.5th to 10.5th day p.c. in association with mouse placentation. [ABSTRACT FROM AUTHOR]

Changes in the expression pattern and intracellular localization of Forssman glycolipid (FA) and GM1 ganglioside (GM1) in fetal mouse gonads were examined during germ cell differentiation by immunofluorescence microscopy and immunoelectron microscopy. In male germ cells from the 12th to 14th day p.c., anti-FA binding was localized in granular structures aggregated on one side of the cytoplasm and/or in the plasma membrane. On day 16 p.c., some germ cells still showed patch-like positive reactions in the plasma membrane, but by day 18 p.c., positive reactions for FA had completely disappeared. The female germ cells showed granular bindings of anti-FA scattered throughout their cytoplasm during the 13th to 16th day p.c., although the positive reactions in female germ cells on day 12 p.c. tended to be found in one side of cytoplasm and/or plasma membrane similar to those in male germ cells from 12th to 14th day p.c. On day 18 p.c., positive reactions remained in the plasma membrane of some germ cells, but these positive reactions disappeared before birth. Immunoelectron microscopic observation showed that the sites of anti-FA bindings were equivalent to the 'small dense bodies' (SDB) and the Golgi lamellae both in male and female germ cells. On the other hand, GM1 was not detected in male germ cells at any time during fetal testicular development, whereas an anti-GM1 reaction was detected in the plasma membrane of female germ cells from the 16th to 18th day p.c. (oocytes in the first meiotic prophase). Therefore, these results indicate that kinetic translocation of FA between the plasma membrane and the SDB and Golgi lamellae takes place during germ cell differentiation in fetal gonads. Moreover, the ganglioside composition containing GM1 seems to change in association with the first meiotic prophase. [ABSTRACT FROM AUTHOR]

Changes in lectin binding of developing fetal mouse testes and ovaries were examined by light and electron microscopy, with much attention paid particularly to those in carbohydrates of germ cells. Characteristic binding patterns were observed with three lectins (BPA, GS-I, and GS-II) in the germ cells and the somatic cells during the process of testicular and ovarian development. GS-I and BPA, which showed similar binding patterns, preferentially bound to the plasma membrane and small dense bodies (SDB) of germ cells in both testes and ovaries during the 12th to 14th day post coitum (p.c.). In the fetal testes on day 16 p.c., the reaction with both GS-I and BPA completely disappeared. While, in the ovaries, a weak reaction with these lectins was retained as it was in germ cells until the 16th day p.c. The reaction with GS-II was restricted to Sertoli cells in the fetal testes during the 12th to 14th day p.c., and thereafter disappeared on day 16 p.c. The distribution of GS-II binding sites was in agreement with that of the glycogen granules. No positive staining with GS-II was seen in the ovaries throughout their development. These results indicate that certain glycoconjugates containing d-galactose and N-acetyl- d-galactosamine residues are expressed on the cell surface and in the SDB of germ cells during the period of the 12th to 14th day p.c., and that striking changes in function as well as in structure may take place in both germ cells and somatic cells during the 14th to 16th day p.c. in association with testicular and ovarjan development. [ABSTRACT FROM AUTHOR]

We investigated the long-term changes that occur in the gerbil brain following transient cerebral ischemia using histology and receptor autoradiography. Transient ischemia was induced for 3 and 10 min, and animals were allowed to survive for 8 months. A histological study showed that 3-min ischemia caused neuronal damage and mild atrophy only in the hippocampal CA1 sector, and that 10-min ischemia produced severe neuronal damage and marked shrinkage in the hippocampal CA1 and CA3 sectors. Furthermore, severe neuronal damage was seen in the striatum after 10-min ischemia. Autoradiography study revealed that 3-min ischemia caused a significant reduction in [H] naloxone binding in the frontal cortex, striatum, dentate gyrus, and thalamus, whereas [H]SCH 23390 and [H] forskolin binding was not significantly altered in all regions, In contrast, 10-min ischemia produced marked alteration in these binding sites in the striatum, hippocampus, thalamus, and substantia nigra. The alteration was especially notable in the hippocampal region and substantia nigra. These results indicate that hippocampal damage after transient ischemia, compared with that in other regions, is not static, but particularly progressive. Furthermore, they demonstrate a reduction in adenylate cyclase system in the striatum and substantia nigra after transient ischemia. Moreover, our results suggest that long-term survival after ischemia may induce synaptic modification of neurotransmitter and adenylate cyclase system in the hippocampus. [ABSTRACT FROM AUTHOR]

The inhibitory action of Purkinje cells on vestibulospinal tract (VST) cells was examined in rats deprived of climbing fibers with 3-acetylpyridine (3-AP) intoxication. In order to resolve discrepancies raised in previous studies with various means, special efforts were devoted to directly estimate Purkinje cell inhibition at synaptic levels by using intracellular recording, to avoid sampling bias by using a systematic survey of VST cells in each rat, and to evaluate the time-dependence of the effects of climbing fiber deafferentation by regular testing at 10 day intervals until 160 days after 3-AP intoxication. As compared with 661 VST cells impaled in 15 control rats, 1771 VST neurons impaled in 29 3-AP-treated rats revealed four basic changes in the monosynaptic inhibitory postsynaptic potentials (IPSPs) induced by stimulation of Purkinje cell axons in the white matter of the cerebellar anterior lobe. First, the rate of IPSP occurrence among VST cells was 0.64 in control rats; at more than 10 days after 3-AP intoxication it decreased gradually, down to 0.37-0.38 at the 70th-81st days, and thereafter increased up to 0.53 by the 160th day. The rate of IPSP occurrence varied considerably between the rostral and caudal regions, and also between the dorsal and ventral divisions of the VST cell population, but its reduction after 3-AP intoxication occurred approximately in parallel in all divisions. Second, IPSPs evoked with standard 500 μA pulse stimuli were smaller in size on and after day 10. The reduction of IPSP size was by as much as 53% of control values at the 70th-101st days in the dorsal division, but no significant change occurred in the ventral division of the VST cell population. Third, the latency of the IPSPs was prolonged by about 0.25 ms on and after day 10. Analysis of the relationship between the IPSP latency and the dorsoventral location of VST cells in the medulla suggests that the major cause for the prolongation of IPSP latency is an increased synaptic delay at Purkinje cell axon terminals. Fourth, the cerebellar stimulation threshold for evoking IPSPs was almost always below 100 μA in control rats, but values of 100-250 μA were common after the 40th day. Thus, climbing fiber deafferentation exerts long-term influences on excitability of Purkinje cell axons, and on the connectivity and synaptic transmission from Purkinje cell axons to VST cells. [ABSTRACT FROM AUTHOR]

The ASACUSA (Atomic Spectroscopy And Collisions Using Slow Antiprotons) collaboration plans to measure the ground-state hyperfine splitting of antihydrogen in a beam at the CERN Antiproton Decelerator with initial relative precision of 10 - 6 or better, to test the fundamental CPT (combination of charge conjugation, parity transformation and time reversal) symmetry between matter and antimatter. This challenging goal requires a polarised antihydrogen beam with a sufficient number of antihydrogen atoms in the ground state. The first measurement of the quantum state distribution of antihydrogen atoms in a low magnetic field environment of a few mT is described. Furthermore, the data-driven machine learning analysis to identify antihydrogen events is discussed. [ABSTRACT FROM AUTHOR]

The ASACUSA collaboration at the Antiproton Decelerator of CERN aims at a precise measurement of the antihydrogen ground-state hyperfine structure as a test of the fundamental CPT symmetry. A beam of antihydrogen atoms is formed in a CUSP trap, undergoes Rabi-type spectroscopy and is detected downstream in a dedicated antihydrogen detector. In parallel measurements using a polarized hydrogen beam are being performed to commission the spectroscopy apparatus and to perform measurements of parameters of the Standard Model Extension (SME). The current status of antihydrogen spectroscopy is reviewed and progress of ASACUSA is presented. [ABSTRACT FROM AUTHOR]

Ejected electrons from helium-like doubly-excited carbon and boron ions, produced by C and B with He collisions, were measured by the zero-degree electron spectroscopy technique. Electrons from configurations 21nl were observed in a wide energy range. [ABSTRACT FROM AUTHOR]

A correction to the article "Electrically Tuned Spin-Orbit Interaction in an InAs Self-Assembled Quantum Dot," by Y. Kanai and colleagues that was published online on July 24, 2011.

We have performed precision atomic spectroscopy of trapped radioactive Be isotopes aiming at studies of the charge and magnetization radii of these nuclei especially for a single-neutron halo nucleus 11Be . Some experimental results and the status of the analysis are discussed. [ABSTRACT FROM AUTHOR]