Development of a monoclonal antibody to ITPRIPL1 for immunohistochemical diagnosis of non-small cell lung cancers: accuracy and correlation with CD8+ T cell infiltration

Introduction: Cancer biomarkers are substances or processes highly associated with the presence and progression of cancer, which are applicable for cancer screening, progression surveillance, and prognosis prediction in clinical practice. In our previous studies, we discovered that cancer cells upregulate inositol 1,4,5-triphosphate receptor-interacting protein-like 1 (ITPRIPL1), a natural CD3 ligand, to evade immune surveillance and promote tumor growth. We also developed a monoclonal ITPRIPL1 antibody with high sensitivity and specificity. Here, we explored the application of anti-ITPRIPL1 antibody for auxiliary diagnosis of non-small cell lung cancer (NSCLC).Methods: NSCLC patient tissue samples (n = 75) were collected and stained by anti-ITPRIPL1 or anti-CD8 antibodies. After excluding the flaked samples (n = 15), we evaluated the expression by intensity (0-3) and extent (0-100%) of staining to generate an h-score for each sample. The expression status was classified into negative (h-score < 20), low-positive (20-99), and high-positive (≥ 100). We compared the h-scores between the solid cancer tissue and stroma and analyzed the correlation between the h-scores of the ITPRIPL1 and CD8 expression in situ in adjacent tissue slices.Results: The data suggested ITPRIPL1 is widely overexpressed in NSCLC and positively correlates with tumor stages. We also found that ITPRIPL1 expression is negatively correlated with CD8 staining, which demonstrates that ITPRIPL1 overexpression is indicative of poorer immune infiltration and clinical prognosis. Therefore, we set 50 as the cutoff point of ITPRIPL1 expression H scores to differentiate normal and lung cancer tissues, which is of an excellent sensitivity and specificity score (100% within our sample collection).Discussion: These results highlight the potential of ITPRIPL1 as a proteomic immunohistochemical NSCLC biomarker with possible advantages over the existing NSCLC biomarkers, and the ITPRIPL1 antibody can be applied for accurate diagnosis and prognosis prediction

Experimental and Numerical Model Investigations of the Underwater Towing of a Subsea Module

In underwater towing operations, the drag force and vertical offset angle of towropes are important considerations when choosing and setting up towing equipment. The aim of this paper is to study the variation in drag force, vertical offset angle, resistance, and attitude for towing operations with a view to optimizing these operations. An underwater experiment was conducted using a 1:8 scale physical model of a subsea module. A comprehensive series of viscous Computational Fluid Dynamics (CFD) simulations were carried out based on Reynolds-averaged Navier–Stokes equations for uniform velocity towing. The results of the simulation were compared with experimental data and showed good agreement. Numerical results of the vorticity field and streamlines at the towing speeds were presented to analyze the distribution of vortexes and flow patterns. The resistance components were analyzed based on the numerical result. It was found that the lateral direction was a better direction for towing operations because of the smaller drag force, resistance, and offset angle. Similar patterns and locations of streamlines and vortexes were present in both the longitudinal and lateral directions, the total resistance coefficient decreases at a Reynolds number greater than that of a cylinder

Numerical Simulations of Dynamic Pipeline-Vessel Response on a Deepwater S-Laying Vessel

The dynamic action induced on offshore pipelines by deepwater S-laying is significant, and directly determines how the pipeline structures are designed and installed. Existing research has not fully investigated the benefits of coupling models of pipeline and pipelaying vessel motions. Therefore, this paper presents a coupled time-domain numerical model for examining the effect of coupled dynamic reactions. The coupled model takes into account the motion of the pipelaying vessel, surface waves, ocean currents, wind forces, pipeline dynamics, and contact between the rollers and the pipeline. A proportional, integral, derivative (PID) controller was used for simulating the control of the pipelaying vessel. The hydrodynamic forces that the pipeline experiences were modeled using the Morison equation. The model was solved using Newmark’s method and verified using OrcaFlex software. The model was then used to analyze practical operations: the laying of a 22″ gas export pipeline on the seabed by the pipelaying vessel HYSY201 in the Pingbei-Huangyan gas fields in the East China Sea. The effects of coupled factors on pipelaying vessel motions and pipeline dynamics were approximated. These effects included configurations, axial tensions, and bending moments. The results show a significant connection between the dynamic responses of the pipelines and pipelaying vessel motions