Copper-Catalyzed Oxidative Acetalization of Boronic Esters: An Umpolung Strategy for Cyclic Acetal Synthesis.

A protocol for the acetalization of boronic esters is described. The reaction is catalyzed by copper, and the conditions proved to be mild and were amenable to a variety of functional groups. We expanded the Chan-Lam coupling to include C(sp3) nucleophiles and converted them into corresponding acetals. This method allows for the orthogonal acetalization of substrates with reactive, acid-sensitive functional groups.

Beyond Reward Prediction Errors: Human Striatum Updates Rule Values During Learning.

Humans naturally group the world into coherent categories defined by membership rules. Rules can be learned implicitly by building stimulus-response associations using reinforcement learning or by using explicit reasoning. We tested if the striatum, in which activation reliably scales with reward prediction error, would track prediction errors in a task that required explicit rule generation. Using functional magnetic resonance imaging during a categorization task, we show that striatal responses to feedback scale with a "surprise" signal derived from a Bayesian rule-learning model and are inconsistent with RL prediction error. We also find that striatum and caudal inferior frontal sulcus (cIFS) are involved in updating the likelihood of discriminative rules. We conclude that the striatum, in cooperation with the cIFS, is involved in updating the values assigned to categorization rules when people learn using explicit reasoning.

Voltammetric Study of Some 3-Aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide Derivatives with Anti-Tumor Activities.

The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible or quasireversible and is attributed to reduction of the N-oxide moiety to form a radical anion. The second reduction of the diazine ring was found to be irreversible. Compounds containing a nitro group on the 3-phenyl ring also exhibited a reduction process that may be attributed to that group. There was good correlation between molecular structure and reduction potential, with reduction being facilitated by an enhanced net positive charge at the electroactive site created by electron withdrawing substituents. Additionally, the reduction potential was calculated using two common basis sets, 6-31g and lanl2dz, for five of the test molecules. There was a strong correlation between the computational data and the experimental data, with the exception of the derivative containing the nitro functionality. No relationship between the experimentally measured reduction potentials and reported cytotoxic activities was evident upon comparison of the data.

Dissociating motivation from reward in human striatal activity.

Neural activity in the striatum has consistently been shown to scale with the value of anticipated rewards. As a result, it is common across a number of neuroscientific subdiscliplines to associate activation in the striatum with anticipation of a rewarding outcome or a positive emotional state. However, most studies have failed to dissociate expected value from the motivation associated with seeking a reward. Although motivation generally scales positively with increases in potential reward, there are circumstances in which this linkage does not apply. The current study dissociates value-related activation from that induced by motivation alone by employing a task in which motivation increased as anticipated reward decreased. This design reverses the typical relationship between motivation and reward, allowing us to differentially investigate fMRI BOLD responses that scale with each. We report that activity scaled differently with value and motivation across the striatum. Specifically, responses in the caudate and putamen increased with motivation, whereas nucleus accumbens activity increased with expected reward. Consistent with this, self-report ratings indicated a positive association between caudate and putamen activity and arousal, whereas activity in the nucleus accumbens was more associated with liking. We conclude that there exist regional limits on inferring reward expectation from striatal activation.

Light-Mediated Cross-Coupling of Anomeric Trifluoroborates.

Stereoselective reactions at the anomeric carbon constitute the cornerstone of preparative carbohydrate chemistry. Here, we report stereoselective C-arylation and etherification reactions of anomeric trifluoroborates derived from BMIDA esters. These reactions are characterized by high anomeric selectivities for 2-deoxysugars and broad substrate scope (24 examples), including disaccharides and trifluoroborates with free hydroxyl groups. Taken together, this new class of carbohydrate reagents adds the palette of anomeric nucleophile reagents suitable for efficient installation of C-C bonds.

Limited TCR repertoire and ENTPD1 dysregulation mark late-stage COVID-19.

T cell exhaustion and dysfunction are hallmarks of severe COVID-19. To gain insights into the pathways underlying these alterations, we performed a comprehensive transcriptome analysis of peripheral-blood-mononuclear-cells (PBMCs), spleen, lung, kidney, liver, and heart obtained at autopsy from COVID-19 patients and matched controls, using the nCounter CAR-T-Characterization panel. We found substantial gene alterations in COVID-19-impacted organs, especially the lung where altered TCR repertoires are noted. Reduced TCR repertoires are also observed in PBMCs of severe COVID-19 patients. ENTPD1/CD39, an ectoenzyme defining exhausted T-cells, is upregulated in the lung, liver, spleen, and PBMCs of severe COVID-19 patients where expression positively correlates with markers of vasculopathy. Heightened ENTPD1/CD39 is paralleled by elevations in STAT-3 and HIF-1α transcription factors; and by markedly reduced CD39-antisense-RNA, a long-noncoding-RNA negatively regulating ENTPD1/CD39 at the post-transcriptional level. Limited TCR repertoire and aberrant regulation of ENTPD1/CD39 could have permissive roles in COVID-19 progression and indicate potential therapeutic targets to reverse disease.

A conjugate Lewis base-Brønsted acid catalyst for the sulfenylation of nitrogen containing heterocycles under mild conditions.

Catalysts that contain a thiourea tethered to a carboxylic acid were found to affect the sulfenylation of indoles and other N-heterocycles on the hour time scale at room temperature. The mild nature of these conditions allowed for the incorporation of diverse functionalities into more complex heterocycles.

Theories of willpower affect sustained learning.

Building cognitive abilities often requires sustained engagement with effortful tasks. We demonstrate that beliefs about willpower-whether willpower is viewed as a limited or non-limited resource-impact sustained learning on a strenuous mental task. As predicted, beliefs about willpower did not affect accuracy or improvement during the initial phases of learning; however, participants who were led to view willpower as non-limited showed greater sustained learning over the full duration of the task. These findings highlight the interactive nature of motivational and cognitive processes: motivational factors can substantially affect people's ability to recruit their cognitive resources to sustain learning over time.