Condition monitoring indicators for pitting detection in planetary gear units

In industrial field, there is an increasing demand for monitoring systems enabling predictive maintenance programs. In this context, the present work concerns the monitoring of distributed wear (pitting) in planetary gearboxes. For this purpose, some metrics of the synchronous average of the vibration signal, based on the statistical moment of the fourth order, are present in literature; in this paper, a new indicator is proposed, namely NA4mod. The effectiveness of this metric in identifying the early stage of pitting has been evaluated by conducting an accelerated life test of about 700 hours on a test bench using a back-to-back configuration. The paper introduces the proposed metric, describes the test, presents and dis-cusses the results. Metric NA4mod exhibits satisfactory capability to detect pitting with better reliability than other metrics in literature. In addition, the metric is shown to be sensitive to both early stage damage and pitting severity in the final stage. Results are verified by means of wavelet-transform analysis

Immune Mechanisms of Resistance to Cediranib in Ovarian Cancer

This paper investigates mechanisms of resistance to the VEGF receptor inhibitor cediranib in high-grade serous ovarian cancer, HGSOC, and defines rational combination therapies. We used three different syngeneic orthotopic mouse HGSOC models that replicated the human tumor microenvironment, TME. After 4-5 weeks treatment of established tumors, cediranib had anti-tumor activity with increased tumor T cell infiltrates and alterations in myeloid cells. However, continued cediranib treatment did not change overall survival or the immune microenvironment in two of the three models. Moreover, treated mice developed additional peritoneal metastases not seen in controls. Cediranib-resistant tumors had intrinsically high levels of IL-6 and JAK/STAT signaling and treatment increased endothelial STAT3 activation. Combination of cediranib with a murine anti-IL-6 antibody was superior to monotherapy, increasing mouse survival, reducing blood vessel density and pSTAT3, with increased T cell infiltrates in both models. In a third HGSOC model, that had lower inherent IL-6 JAK/STAT3 signaling in the TME but high PD1 signaling, long-term cediranib treatment significantly increased overall survival. When the mice eventually relapsed, pSTAT3 was still reduced in the tumors but there were high levels of immune cell PD1 and PDL1. Combining cediranib with an anti-PD1 antibody was superior to monotherapy in this model, increasing T cells and decreasing blood vessel densities. Bioinformatics analysis of two human HGSOC transcriptional datasets revealed distinct clusters of tumors with IL-6 and PD-1 pathway expression patterns that replicated the mouse tumors. Combination of anti-IL-6 or anti-PD1 in these patients may increase activity of VEGFR inhibitors and prolong disease-free survival

The POLAR gamma-ray burst polarization catalog

Context. Despite over 50 years of research, many open questions remain about the origin and nature of gamma-ray bursts (GRBs). Linear polarization measurements of the prompt emission of these extreme phenomena have long been thought to be key to answering a range of these questions. The POLAR detector was designed to produce the first set of detailed and reliable linear polarization measurements in the 50 − 500 keV energy range. During late 2016 and early 2017, POLAR detected a total of 55 GRBs. The analysis results of 5 of these GRBs have been reported, and were found to be consistent with a low or unpolarized flux. However, previous reports by other collaborations found high levels of linear polarization, including some as high as 90%. Aims. We study the linear polarization for the 14 GRBs observed by POLAR for which statistically robust inferences are possible. Additionally, time-resolved polarization studies are performed on GRBs with sufficient apparent flux. Methods. A publicly available polarization analysis tool, developed within the Multi-Mission Maximum Likelihood framework (3M

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

BACKGROUND: Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-α production by monocytes. METHODOLOGY/PRINCIPAL FINDINGS: Pediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n = 38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes obtained pre-operatively for ex vivo LPS stimulations and TNF-α and IL-6 production was measured by flow cytometry. LPS-induced p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation by patient plasma was assessed by Western blotting. A cell-permeable peptide inhibitor was used to block STAT3 signaling. We found that plasma samples obtained 4 h after surgery, regardless of pre-operative dexamethasone treatment, potently inhibited LPS-induced TNF-α but not IL-6 synthesis by monocytes. This was not associated with attenuation of p38 MAPK activation or IκB-α degradation. However, abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-α production in the presence of suppressive patient plasma. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that STAT3 signaling plays a crucial role in the downregulation of TNF-α synthesis by human monocytes in the course of systemic inflammation in vivo. Thus, STAT3 might be a potential molecular target for pharmacological intervention in clinical syndromes characterized by systemic inflammation