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Nakahashi, A.

Publications and source records attributed to Nakahashi, A..

2 recordsLinked to original sources

Preference shifts during multi-attribute decision-making

When choosing between options with multiple attributes, do we decide by integrating all of the attributes into a unified measure for comparison, or does the comparison occur at the level of each attribute, involving independent competitive processes that can dynamically influence each other? What happens when independent sensory features all carry information about the same decision factor, such as reward value? To investigate these questions, we asked human participants to perform a two-alternative forced choice task in which the reward value of a target was indicated by two independent visual attributes - its brightness ("bottom-up" feature) and its orientation ("top-down" feature). If decisions always occur after integration of both features, there should be no difference in the reaction time (RT) distribution regardless of the attribute combinations that drove the choice. Counter to that prediction, almost two-thirds of the participants exhibited RT differences that depended on the attribute combinations of given targets. The RT was shortest when both attributes were congruent or when the choice was based on the bottom-up feature, and longer when the attributes were in conflict (favoring opposite options), especially when choosing the option favored by the top-down feature. We also observed mid-reach changes-of-mind in a subset of conflict trials, mostly changing from the bottom-up to the top-down-favored target. These data suggest that multi-attribute value-based decisions are better explained by a distributed competition among different features than by a competition based on a single, integrated estimate of choice value. New & NoteworthyThis study showed that during value-based decisions, humans do not always take all information about reward value into account to make their choice, but instead can "jump the gun" using partial information. In particular, when different sources of information were in conflict, early decisions were mostly based on fast bottom-up information, and sometimes followed by corrective changes-of-mind based on slower top-down information. Our results suggest that parallel decision processes occur among different information sources, as opposed to between a single integrated "common currency".

neuroscience↗

Discovery of S-217622, a Non-Covalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Despite the rapid global spread of COVID-19 vaccines, effective oral antiviral drugs are urgently needed. Here, we describe the discovery of S-217622, the first oral non-covalent, non-peptidic SARS-CoV-2 3CL protease inhibitor clinical candidate. S-217622 was discovered via virtual screening followed by biological screening of an in-house compound library, and optimization of the hit compound using a structure-based drug-design strategy. S-217622 exhibited antiviral activity in vitro against current outbreaking SARS-CoV-2 variants and showed favorable pharmacokinetic profiles in vivo for once-daily oral dosing. Furthermore, S-217622 dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice, indicating that this novel non-covalent inhibitor could be a potential oral agent for treating COVID-19.

biochemistry↗