Expression of RCAS1 Correlates with Urothelial Bladder Cancer Malignancy

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.     

Relationship Between the Thermodynamic Parameters,Structure, and Anticorrosion Properties of Al-Zr-Ni-Fe-Y Alloys

Metallurgical and Materials Transactions A - The influence of the chemical composition on the crystallization process, amorphous phase formation, and the anticorrosion properties of Al-Zr-Ni-Fe-Y...     

Magnetic Resonance Signal Amplification by Reversible Exchange of Selective PyFALGEA Oligopeptide Ligands Towards Epidermal Growth Factor Receptors

The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H₂ results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the ¹H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan ¹H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide.     

A practical assessment of risk-averse approaches in production lot-sizing problems

ABSTRACT

This paper presents an empirical assessment of four state-of-the-art risk-averse approaches to deal with the capacitated lot-sizing problem under stochastic demand. We analyse two mean-risk models based on the semideviation and on the conditional value-at-risk risk measures, and alternate first and second-order stochastic dominance approaches. The extensive computational experiments based on different instances characteristics and on a case-study suggest that CVaR exhibits a good trade-off between risk and performance, followed by the semideviation and first-order stochastic dominance approach. For all approaches, enforcing risk-aversion helps to reduce the cost-standard deviation substantially, which is usually accomplished via increasing production rates. Overall, we can say that very risk-averse decision-makers would be willing to pay an increased price to have a much less risky solution given by CVaR. In less risk-averse settings, though, semideviation and first-order stochastic dominance can be appealing alternatives to provide significantly more stable production planning costs with a marginal increase of the expected costs.