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Photoredox catalysis is a powerful means to generate odd-electron species under mild reaction conditions from a wide array of radical precursors. Herein, we present the application of this powerful catalytic manifold to address the hydroalkylation and hydroaminoalkylation of electronically diverse vinylarenes. This reaction allows for generalized alkene hydroalkylation leveraging common alkyl radical precursors, such as organotrifluoroborate salts and carboxylic acids. Furthermore, utilizing easily accessible α-silyl amine reagents or tertiary amines directly, secondary and tertiary amine moieties can be installed onto monoaryl and diaryl alkenes to access valuable products, including γ,γ-diarylamines pharmacophores. Thus, under a unified system, both hydroalkylation and hydroaminoalkylation of alkenes are achieved. The substrate scope is evaluated through 57 examples, the synthetic utility of the method is demonstrated, and preliminary mechanistic insights are presented.

 

In mammals, the circadian clock coordinates cell physiological processes including inflammation. Recent studies suggested a crosstalk between these two pathways. However, the mechanism of how inflammation affects the clock is not well understood. Here, we investigated the role of the proinflammatory transcription factor NF-κB in regulating clock function. Using a combination of genetic and pharmacological approaches, we show that perturbation of the canonical NF-κB subunit RELA in the human U2OS cellular model altered core clock gene expression. While RELA activation shortened period length and dampened amplitude, its inhibition lengthened period length and caused amplitude phenotypes. NF-κB perturbation also altered circadian rhythms in the master suprachiasmatic nucleus (SCN) clock and locomotor activity behavior under different light/dark conditions. We show that RELA, like the clock repressor CRY1, repressed the transcriptional activity of BMAL1/CLOCK at the circadian E-box cis-element. Biochemical and biophysical analysis showed that RELA binds to the transactivation domain of BMAL1. These data support a model in which NF-kB competes with CRY1 and coactivator CBP/p300 for BMAL1 binding to affect circadian transcription. This is further supported by chromatin immunoprecipitation analysis showing that binding of RELA, BMAL1 and CLOCK converges on the E-boxes of clock genes. Taken together, these data support a significant role for NF-κB in directly regulating the circadian clock and highlight mutual regulation between the circadian and inflammatory pathways. 

Transition from laminar to turbulent flow occurring over a smooth surface is a particularly important route to chaos in fluid dynamics. It often occurs via sporadic inception of spatially localized patches (spots) of turbulence that grow and merge downstream to become the fully turbulent boundary layer. A long-standing question has been whether these incipient spots already contain properties of high-Reynolds-number, developed turbulence. In this study, the question is posed for geometric scaling properties of the interface separating turbulence within the spots from the outer flow. For high-Reynolds-number turbulence, such interfaces are known to display fractal scaling laws with a dimension$D\approx 7/3$, where the 1/3 excess exponent above 2 (smooth surfaces) follows from Kolmogorov scaling of velocity fluctuations. The data used in this study are from a direct numerical simulation, and the spot boundaries (interfaces) are determined by using an unsupervised machine-learning method that can identify such interfaces without setting arbitrary thresholds. Wide separation between small and large scales during transition is provided by the large range of spot volumes, enabling accurate measurements of the volume–area fractal scaling exponent. Measurements show a dimension of$D=2.36\pm 0.03$over almost 5 decades of spot volume, i.e., trends fully consistent with high-Reynolds-number turbulence. Additional observations pertaining to the dependence on height above the surface are also presented. Results provide evidence that turbulent spots exhibit high-Reynolds-number fractal-scaling properties already during early transitional and nonisotropic stages of the flow evolution.