1,413 research outputs found

    Automated Theorem Prover Axiom Management

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    Automated Theorem Provers (ATPs), are computer programs that use collections of axioms,which are logical statements assumed to be true, in order to prove conjectures. NASA uses these programs to verify safety and functional requirements in domains like Guidance, Navigation, and Control. There are about 30 axioms on each major topic including the theory of coordinate systems, elementary arithmetic and linear algebra. These axioms have been created over the duration of many projects and combined into a single file. One task is to manage the axioms by arranging them into logical sections, deleting unnecessary ones and rewriting some into a more general case. This will help reduce the time required to run the provers, resulting in a more efficient program. When testing a conjecture, verification conditions (VCs) are generated to prove a safety requirement. The VCs then produce dynamic axioms which are sent to the provers along with the original VCs and the static axioms. They are then run through the prover, producing a pass or fail for the conjecture. Each change done to the axiom file must be checked in order to verify that the conjectures are still proven true

    Multidecadal Signal of Solar Variability in the Upper Troposphere During the 20th Century

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    Studies based on data from the past 25-45 years show that irradiance changes related to the 11-yr solar cycle affect the circulation of the upper troposphere in the subtropics and midlatitudes. The signal has been interpreted as a northward displacement of the subtropical jet and the Ferrel cell with increasing solar irradiance. In model studies on the 11-yr solar signal this could be related to a weakening and at the same time broadening of the Hadley circulation initiated by stratospheric ozone anomalies. Other studies, focusing on the direct thermal effect at the Earth's surface on multidecadal scales, suggest a strengthening of the Hadley circulation induced by an increased equator-to-pole temperature gradient. In this paper we analyse the solar signal in the upper troposphere since 1922, using statistical reconstructions based on historical upper-air data. This allows us to address the multidecadal variability of solar irradiance, which was supposedly large in the first part of the 20th century. Using a simple regression model we find a consistent signal on the 11-yr time scale which fits well with studies based on later data. We also find a significant multidecadal signal that is similar to the 11-yr signal, but somewhat stronger. We interpret this signal as a poleward shift of the subtropical jet and the Ferrel cell. Comparing the magnitude of the two signals could provide important information on the feedback mechanisms involved in the solar climate relationship with respect to the Hadley and Ferrel circulations. However, in view of the uncertainty in the solar irradiance reconstructions, such interpretations are not currently possibl

    The combined immunohistochemical expression of AMBRA1 and SQSTM1 identifies patients with poorly differentiated cutaneous squamous cell carcinoma at risk of metastasis: A proof of concept study

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    \ua9 2024 AMLo Biosciences Ltd. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to increase globally with, as of yet, an unmet need for reliable prognostic biomarkers to identify patients at increased risk of metastasis. The aim of the present study was to test the prognostic potential of the combined immunohistochemical expression of the autophagy regulatory biomarkers, AMBRA1 and SQSTM1, to identify high-risk patient subsets. Methods: A retrospective cohort of 68 formalin-fixed paraffin-embedded primary cSCCs with known 5-year metastatic outcomes were subjected to automated immunohistochemical staining for AMBRA1 and SQSTM1. Digital images of stained slides were annotated to define four regions of interest: the normal and peritumoral epidermis, the tumor mass, and the tumor growth front. H-score analysis was used to semi-quantify AMBRA1 or SQSTM1 expression in each region of interest using Aperio ImageScope software, with receiver operator characteristics and Kaplan–Meier analysis used to assess prognostic potential. Results: The combined loss of expression of AMBRA1 in the tumor growth front and SQSTM1 in the peritumoral epidermis identified patients with poorly differentiated cSCCs at risk of metastasis (*p < 0.05). Conclusions: Collectively, these proof of concept data suggest loss of the combined expression of AMBRA1 in the cSCC growth front and SQSTM1 in the peritumoral epidermis as a putative prognostic biomarker for poorly differentiated cSCC

    The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

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    Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x
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