Value creation by Indian companies: A comparative study over two time periods

Abstract. The objective of this paper is to derive economic profit generated by Indian companies over two time periods and see whether there has been any fundamental change in the performance of companies and the sectors within which they belong. We focus on non-finance companies. The purpose is two-fold. First, to get an idea about how Indian companies have fared over the two time periods and whether there has been any structural change. Second, to help companies decide on their next strategic move and allocate funds for the purpose. The study also focusses on the relationship between size and economic profit, where invested capital and market capitalization represents size. The methodology presented in the paper enables us to understand the performance of Indian companies and also the sectors within which they belong.Keywords. Economic profit, Invested capital, Quintile distribution, Market capitalization, Sector.JEL. G11, G14, G32, L25, E22

Basal ganglia contributions during the learning of a visuomotor rotation: Effect of dopamine, deep brain stimulation and reinforcement

It is commonly thought that visuomotor adaptation is mediated by the cerebellum while reinforcement learning is mediated by the basal ganglia. In contrast to this strict dichotomy, we demonstrate a role for the basal ganglia in visuomotor adaptation (error-based motor learning) in patients with Parkinson's disease (PD) by comparing the degree of motor learning in the presence and absence of dopamine medication. We further show similar modulation of learning rates in the presence and absence of subthalamic deep brain stimulation. We also report that reinforcement is an essential component of visuomotor adaptation by demonstrating the lack of motor learning in patients with PD during the ON-dopamine state relative to the OFF-dopamine state in the absence of a reinforcement signal. Taken together, these results raise the possibility that the basal ganglia modulate the gain of visuomotor adaptation based on the reinforcement received at the end of the trial

Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer

Abstract Microsatellite-stable colorectal cancer (MSS-CRC) is highly refractory to immunotherapy. Understanding tumor-intrinsic determinants of immunotherapy resistance is critical to improve MSS-CRC patient outcomes. Here, we demonstrate that high tumor expression of the core autophagy gene ATG16L1 is associated with poor clinical response to anti-PD-L1 therapy in KRAS-mutant tumors from IMblaze370 (NCT02788279), a large phase III clinical trial of atezolizumab (anti-PD-L1) in advanced metastatic MSS-CRC. Deletion of Atg16l1 in engineered murine colon cancer organoids inhibits tumor growth in primary (colon) and metastatic (liver and lung) niches in syngeneic female hosts, primarily due to increased sensitivity to IFN-γ-mediated immune pressure. ATG16L1 deficiency enhances programmed cell death of colon cancer organoids induced by IFN-γ and TNF, thus increasing their sensitivity to host immunity. In parallel, ATG16L1 deficiency reduces tumor stem-like populations in vivo independently of adaptive immune pressure. This work reveals autophagy as a clinically relevant mechanism of immune evasion and tumor fitness in MSS-CRC and provides a rationale for autophagy inhibition to boost immunotherapy responses in the clinic