4,864 research outputs found
Reconstructing the Star Formation History of the Galaxy
The evolution of the star formation rate in the Galaxy is one of the key
ingredients quantifying the formation and determining the chemical and
luminosity evolution of galaxies. Many complementary methods exist to infer the
star formation history of the components of the Galaxy, from indirect methods
for analysis of low-precision data, to new exact analytic methods for analysis
of sufficiently high quality data. We summarise available general constraints
on star formation histories, showing that derived star formation rates are in
general comparable to those seen today. We then show how colour-magnitude
diagrams of volume- and absolute magnitude-limited samples of the solar
neighbourhood observed by Hipparcos may be analysed, using variational calculus
techniques, to reconstruct the local star formation history. The remarkable
accuracy of the data coupled to our maximum-likelihood variational method
allows objective quantification of the local star formation history with a time
resolution of ~ 50 Myr. Over the past 3Gyr, the solar neighbourhood star
formation rate has varied by a factor of ~ 4, with characteristic timescale
about 0.5Gyr, possibly triggered by interactions with spiral arms.Comment: 12 pages, Proc. of the Sept. 20-24, 1999 Vulcano Workshop ``The
chemical evolution of the Milky Way: stars vs. clusters'', eds. F. Matteucci
& F. Giovanell
Tumor deposits in colorectal cancer: improving the value of modern staging - a systematic review and meta-analysis
PURPOSE: Colorectal cancer (CRC) treatment is largely determined by tumor stage. Despite improvements made in the treatment of various types of metastatic disease, staging has not been refined. The role of tumor deposits (TD) in staging remains under debate. We have assessed the relation of TD with metastatic pattern, to evaluate whether TD might add significant new information to staging. METHODS: We performed a systematic literature search focused on the role of TD in CRC. Studies with neoadjuvant treated patients were excluded. Data on stage, histological factors and outcome were extracted. Data from four large cohorts were analyzed for the relevance of the presence of TD, lymph node metastases (LNM) and extramural vascular invasion (EMVI) on the pattern of metastases and outcomes. RESULTS: Of the 10,106 included CRC patients 22% presented with TD. TD are invariably associated with poor outcome. The presence of TD was associated with the presence of LNM and EMVI. In a pair wise comparison, the effects of TD were stronger than both LNM and EMVI. In the logistic regression model, TD in combination with LNM is the strongest predictor for liver (odds ratio (OR) 5.5), lung (OR 4.3) and peritoneal metastases (OR 7.0). The presence of EMVI adds information for liver and lung metastases, but not for peritoneal metastases. CONCLUSION: We have shown that TD are not equal to LNM or EMVI, with respect to biology and outcome. We lose valuable prognostic information by allocating TD into nodal category N1c and only considering TD in the absence of LNM. Therefore, we propose that the number of TD should be added to the number of LNM to derive a final N stage
Prioritized Sweeping Neural DynaQ with Multiple Predecessors, and Hippocampal Replays
During sleep and awake rest, the hippocampus replays sequences of place cells
that have been activated during prior experiences. These have been interpreted
as a memory consolidation process, but recent results suggest a possible
interpretation in terms of reinforcement learning. The Dyna reinforcement
learning algorithms use off-line replays to improve learning. Under limited
replay budget, a prioritized sweeping approach, which requires a model of the
transitions to the predecessors, can be used to improve performance. We
investigate whether such algorithms can explain the experimentally observed
replays. We propose a neural network version of prioritized sweeping
Q-learning, for which we developed a growing multiple expert algorithm, able to
cope with multiple predecessors. The resulting architecture is able to improve
the learning of simulated agents confronted to a navigation task. We predict
that, in animals, learning the world model should occur during rest periods,
and that the corresponding replays should be shuffled.Comment: Living Machines 2018 (Paris, France
Heterogenous expression of beta-catenin, p16, e-cadherin, and c-myc in multi-stage colorectal carcinogenesis detected by tissue microarray
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Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression
Aim: To investigate the expression pattern of clusterin in colorectal adenoma-carcinoma-metastasis series, and to explore the potential role of clustelin in multistage colorectal tumorigenesis and progression. Methods: A colorectal carcinoma (CRC)-tissue microarray (TMA), which contained 85 advanced CRCs including 43 cases of Dukes B, 21 of Dukes C and 21 of Dukes D tumors, were used for assessing the expression of clusterin (clone 41D) and tumor cell apoptotic index (AI) by immunohistochemistry and TUNEL assay, respectively. Moreover the potential correlation of clusterin expression with the patient's clinical-pathological features were also examined. Results: The positive staining of clusterin in different colorectal tissues was primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal colorectal mucosa, 17% of the adenomas, 46% of the primary CRCs, and 57% of the CRC metastatic lesions. In addition, a significant positive correlation between overexpression of clusterin and advanced clinical (Dukes) stage was observed (P<0.01). Overexpression of cytoplasmic clusterin in CRCs was inversely correlated with tumor apoptotic index (P<0.01), indicating the anti-apoptotic function of cytoplasmic clusterin in CRCs. Conclusion: These data suggests that overexpression of cytoplasmic clusterin might be involved in the tumorigenesis and/or progression of CRCs. The anti-apoptotic function of cytoplasmic clusterin may be responsible, at least in part, for the development and biologically aggressive behavior of CRC. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio
Heparin-Binding Protein Promotes Acute Lung Injury in Sepsis Mice by Blocking the Aryl Hydrocarbon Receptor Signaling Pathway
Kun Ye,1 Xiang Lin,2 Tai-Zhi Chen,2 Long-Hui Wang,2 Sheng-Xing Liu2 1Department of Orthopaedics, Qiantang Campus of Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, 310018, People’s Republic of China; 2Department of Orthopaedics, The Second Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of ChinaCorrespondence: Sheng-Xing Liu, Email [email protected]: This study aimed to explore the therapeutic effect and potential mechanism of heparin-binding protein (HBP) reduction on sepsis-related acute lung injury.Methods: We utilized a murine model of sepsis-induced by intraperitoneal injection of lipopolysaccharides (LPS) in C57BL/6J mice divided into four groups: Control, LPS, Anti-HBP, and ceftriaxone (CEF). Following sepsis induction, Anti-HBP or CEF treatments were administered, and survival rates were monitored for 48 h. We then used reverse-transcription quantitative PCR to analyze the expression levels of HBP in lung tissues, immunohistochemistry for protein localization, and Western blotting for protein quantification. Pulmonary inflammation was assessed using enzyme-linked immunosorbent assays of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and interferon-γ). The activation state of the aryl hydrocarbon receptor (AhR) signaling pathway was determined via Western blotting, evaluating both cytoplasmic and nuclear localization of AhR and the expression of cytochrome P450 1A1 protein by its target gene.Results: Anti-HBP specifically reduced HBP levels. The survival rate of mice in the Anti-HBP and CEF groups was much higher than that in the LPS group. The severity of lung injury and pulmonary inflammatory response in the Anti-HBP and CEF groups was significantly lower than that in the LPS group. AhR signaling pathway activation was observed in the Anti-HBP and CEF groups. Additionally, there was no significant difference in the above indices between the Anti-HBP and CEF groups.Conclusion: HBP downregulation in lung tissues significantly improved LPS-induced lung injury and the pulmonary inflammatory response, thereby prolonging the survival of sepsis mice, suggesting activation of the AhR signaling pathway. Moreover, the effect of lowering the HBP level was equivalent to that of the classical antibiotic CEF.Trial Registration: Not applicable.Keywords: sepsis, acute lung injury, heparin-binding protein, aryl hydrocarbon receptor signaling pathwa
Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure
Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality
Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab
We evaluated neoadjuvant ipilimumab in patients with surgically operable regionally advanced melanoma in order to define markers of activity in the blood and tumor as assessed at baseline (before ipilimumab) and early on-treatment. Patients were treated with ipilimumab (10 mg/kg intravenously every 3 weeks x2 doses) bracketing surgery. Tumor and blood biospecimens were obtained at baseline and at surgery. Flow cytometry and immunohistochemistry for select biomarkers were performed. Thirty five patients were enrolled; IIIB (3; N2b), IIIC (32; N2c, N3), IV (2). Worst toxicities included Grade 3 diarrhea/colitis (5; 14%), hepatitis (2; 6%), rash (1; 3%), elevated lipase (3; 9%). Median follow up was 18 months: among 33 evaluable patients, median progression free survival (PFS) was 11 months, 95% CI (6.2-19.2). There was a significant decrease in circulating myeloid derived suppressor cells (MDSC). Greater decrease in circulating monocyte gate MDSC Lin1-/HLA-DR-/CD33+/CD11b+ was associated with improved PFS (p = 0.03). There was a significant increase in circulating regulatory T cells (Treg; CD4+CD25hi+Foxp3+) that, unexpectedly, was associated with improved PFS (HR = 0.57; p = 0.034). Baseline evidence of fully activated type I CD4+ and CD8+ antigen-specific T cell immunity against cancer-testis (NY-ESO-1) and melanocytic lineage (MART-1, gp100) antigens was detected and was significantly potentiated after ipilimumab. In tumor, there was a significant increase in CD8+ T cells after ipilimumab (p = 0.02). Ipilimumab induced increased tumor infiltration by fully activated (CD69+) CD3+/CD4+ and CD3 +/CD8+ T cells with evidence of induction/potentiation of memory T cells (CD45RO+). The change in Treg observed within the tumor showed an inverse relationship with clinical benefit and greater decrease in tumor MDSC subset Lin1-/HLA-DR-/CD33+/CD11b+ was associated with improved PFS at one year. Neoadjuvant evaluation revealed a significant immunomodulating role for ipilimumab on Treg, MDSC and effector T cells in the circulation and tumor microenvironment that warrants further pursuit in the quest for optimizing melanoma immunotherapy. © 2014 Tarhini et al
An invisibility cloak using silver nanowires
In this paper, we use the parameter retrieval method together with an
analytical effective medium approach to design a well-performed invisible
cloak, which is based on an empirical revised version of the reduced cloak. The
designed cloak can be implemented by silver nanowires with elliptical
cross-sections embedded in a polymethyl methacrylate host. This cloak is
numerically proved to be robust for both the inner hidden object as well as
incoming detecting waves, and is much simpler thus easier to manufacture when
compared with the earlier proposed one [Nat. Photon. 1, 224 (2007)].Comment: 7 pages, 4 figures, 2 table
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