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.
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.
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.
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.
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.
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.
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(+)T(high)/CD8(+)T(high)/%Treg(low) and tumour-infiltrating %M1(high)/M2(low). Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.
Tumour-infiltrating CD4(+)T(high)/CD8(+)T(high)/%Treg(low) and %M1(high)/M2(low) are independent prognosticators useful for evaluating the immune microenvironment of PDC.
The second survey of the molecular clouds in the Large Magellanic Cloud in super(12)CO was carried out by NANTEN. The sensitivity of this survey is twice as high as that of the previous NANTEN ...survey, leading to a detection of molecular clouds with image M sub(image). We identified 272 molecular clouds, 230 of which are detected at three or more observed positions. We derived the physical properties, such as size, line width, and virial mass, of the 164 GMCs that have an extent more than the beam size of NANTEN in both the major and minor axes. The CO luminosity and virial mass of the clouds show a good correlation of image, with a Spearman rank correlation of 0.8, suggesting that the clouds are in nearly virial equilibrium. Assuming the clouds are in virial equilibrium, we derived an X sub(CO)-factor of image cm super(-2) (K km s super(-1)) super(-1). The mass spectrum of the clouds is fitted well by a power law of image above the completeness limit of image M sub(image). The slope of the mass spectrum becomes steeper if we fit only the massive clouds, e.g., image for image M sub(image).
Devices to generate on-demand non-local spin entangled electron pairs have potential application as solid-state analogues of the entangled photon sources used in quantum optics. Recently, Andreev ...entanglers that use two quantum dots as filters to adiabatically split and separate the quasi-particles of Cooper pairs have shown efficient splitting through measurements of the transport charge but the spin entanglement has not been directly confirmed. Here we report measurements on parallel quantum dot Josephson junction devices allowing a Josephson current to flow due to the adiabatic splitting and recombination of the Cooper pair between the dots. The evidence for this non-local transport is confirmed through study of the non-dissipative supercurrent while tuning independently the dots with local electrical gates. As the Josephson current arises only from processes that maintain the coherence, we can confirm that a current flows from the spatially separated entangled pair.
The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown.
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.
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.
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.
Aerosols from the Fukushima Dai-ichi Nuclear Power Plant accident were collected at the Geological Survey of Japan. The temporal patterns of the
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Cs/
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Cs,
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Cs/
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Cs, and
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Te/
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Cs ...activity ratios were consistent with expectations based on their half-lives. Those for
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I and
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Te decreased with some fluctuations.
110m
Ag/
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Cs declined more rapidly than expected and
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Nb/
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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.
We previously applied a neural network detector (NND) to the low-density parity-check (LDPC) coding and iterative decoding system in a shingled magnetic recording (SMR) system. In this study, we ...evaluate the performance of iterative decoding using a new NND by computer simulation. The conventional NND gets the log-likelihood ratio (LLR) as the reliability of the sequence recorded from the two-dimensional finite impulse response (TD-FIR) filter output and the sum-product (SP) decoder output, but the new NND finds the LLR by adding the SP decoder input in order to consider the difference between the SP decoder input and the decoding result. Furthermore, we clarify that the new NND brings the almost same effect as the a posteriori probability (APP) decoder in the iterative decoding system.
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.
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.
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.
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.
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