This paper analyzes the effect of anthem protests on viewership for National Football League (NFL) games controlling for measures of NFL market-specific political beliefs and other demand ...determinants. To capture the effect of the protests on viewership, we create two classes of protests (unambiguous and ambiguous protests) and support the classification based on the meaning of the protest, actions by NFL owners, and statements by Donald Trump. Using data from all early and late-afternoon Sunday games from the 2014 through 2017 regular NFL seasons, we show that: (1) unambiguous protests reduce viewership in the week following the protests by about 15% while ambiguous protests do not generally produce statistically significant reductions in viewership; (2) the negative effect of unambiguous protests on viewership is particularly strong in metro locations that voted more heavily for Donald Trump in 2016; and (3) following Donald Trump's statements in week 3 of the 2017 season, both ambiguous and unambiguous protests increased and the increase in ambiguous protests was particularly large.
The second pulse of the Late Ordovician mass extinction occurred around the Hirnantian-Rhuddanian boundary (~444 Ma) and has been correlated with expanded marine anoxia lasting into the earliest ...Silurian. Characterization of the Hirnantian ocean anoxic event has focused on the onset of anoxia, with global reconstructions based on carbonate δ
U modeling. However, there have been limited attempts to quantify uncertainty in metal isotope mass balance approaches. Here, we probabilistically evaluate coupled metal isotopes and sedimentary archives to increase constraint. We present iron speciation, metal concentration, δ
Mo and δ
U measurements of Rhuddanian black shales from the Murzuq Basin, Libya. We evaluate these data (and published carbonate δ
U data) with a coupled stochastic mass balance model. Combined statistical analysis of metal isotopes and sedimentary sinks provides uncertainty-bounded constraints on the intensity of Hirnantian-Rhuddanian euxinia. This work extends the duration of anoxia to >3 Myrs - notably longer than well-studied Mesozoic ocean anoxic events.
Few topics in geobiology have been as extensively debated as the role of Earth's oxygenation in controlling when and why animals emerged and diversified. All currently described animals require ...oxygen for at least a portion of their life cycle. Therefore, the transition to an oxygenated planet was a prerequisite for the emergence of animals. Yet, our understanding of Earth's oxygenation and the environmental requirements of animal habitability and ecological success is currently limited; estimates for the timing of the appearance of environments sufficiently oxygenated to support ecologically stable populations of animals span a wide range, from billions of years to only a few million years before animals appear in the fossil record. In this light, the extent to which oxygen played an important role in controlling when animals appeared remains a topic of debate. When animals originated and when they diversified are separate questions, meaning either one or both of these phenomena could have been decoupled from oxygenation. Here, we present views from across this interpretive spectrum—in a point–counterpoint format—regarding crucial aspects of the potential links between animals and surface oxygen levels. We highlight areas where the standard discourse on this topic requires a change of course and note that several traditional arguments in this “life versus environment” debate are poorly founded. We also identify a clear need for basic research across a range of fields to disentangle the relationships between oxygen availability and emergence and diversification of animal life.
Uranium isotopes (238U/235U) have been used widely over the last decade as a global proxy for marine redox conditions. The largest isotopic fractionations in the system occur during U reduction, ...removal, and burial. Applying this basic framework, global U isotope mass balance models have been used to predict the extent of ocean floor anoxia during key intervals throughout Earth's history. However, there are currently minimal constraints on the isotopic fractionation that occurs during reduction and burial in anoxic and iron‐rich (ferruginous) aquatic systems, despite the consensus that ferruginous conditions are thought to have been widespread through the majority of our planet's history. Here we provide the first exploration of δ238U values in natural ferruginous settings. We measured δ238U in sediments from two modern ferruginous lakes (Brownie Lake and Lake Pavin), the water column of Brownie Lake, and sedimentary rocks from the Silurian‐Devonian boundary that were deposited under ferruginous conditions. Additionally, we provide new δ238U data from core top sediments from anoxic but nonsulfidic settings in the Peru Margin oxygen minimum zone. We find that δ238U values from sediments deposited in all of these localities are highly variable but on average are indistinguishable from adjacent oxic sediments. This forces a reevaluation of the global U isotope mass balance and how U isotope values are used to reconstruct the evolution of the marine redox landscape.
Key Points
δ238U values were measured in iron‐rich, anoxic (ferruginous) modern natural environments, and Paleozoic shales deposited under ferruginous conditions
δ238U fractionations in these environments are highly variable and generally indistinguishable from isotopic fractionations associated with oxic settings
δ238U fractionations in these environments are highly variable and generally indistinguishable from isotopic fractionations associated with oxic settings
Immunomodulatory drugs are a class of drugs approved for the treatment of multiple myeloma. These compounds exert their clinical effects by inducing interactions between the CRL4CRBN E3 ubiquitin ...ligase and a C2H2 zinc finger degron motif, resulting in degradation of degron-containing targets. However, although many cellular proteins feature the degron motif, only a subset of those are degradable via this strategy. Here, we demonstrated that FPFT-2216, a previously reported “molecular glue” compound, degrades PDE6D, in addition to IKZF1, IKZF3, and CK1α. We used FPFT-2216 as a starting point for a focused medicinal chemistry campaign and developed TMX-4100 and TMX-4116, which exhibit greater selectivity for degrading PDE6D and CK1α, respectively. We also showed that the region in PDE6D that interacts with the FPFT-2216 derivatives is not the previously pursued prenyl-binding pocket. Moreover, we found that PDE6D depletion by FPFT-2216 does not impede the growth of KRASG12C-dependent MIA PaCa-2 cells, highlighting the challenges of drugging PDE6D-KRAS. Taken together, the approach we described here represents a general scheme to rapidly develop selective degraders by reprogramming E3 ubiquitin ligase substrate specificity.
The synthesis, characterization, and theoretical analysis of meridional americium tribromide tris(tricyclohexylphosphine oxide),
mer
-AmBr
3
(OPcy
3
)
3
, has been achieved and is compared with its ...early lanthanide (La to Nd) analogs. The data show that homo
trans
ligands display significantly shorter bonds than the
cis
or hetero
trans
ligands. This is particularly pronounced in the americium compound. DFT along with multiconfigurational CASSCF calculations show that the contraction of the bonds relates qualitatively with overall covalency,
i.e.
americium shows the most covalent interactions compared to lanthanides. However, the involvement of the 5p and 6p shells in bonding follows a different order, namely cerium > neodymium ∼ americium. This study provides further insight into the mechanisms by which ITI operates in low-valent f-block complexes.
Structural, spectroscopic and theoretical analyses of
mer
-MBr
3
(OPcy
3
)
3
(M = Am, Nd, Pr, Ce, La) reveal significant amounts of metal based p-orbital contribution.
Introduction
Unsupervised digital cognitive testing is an appealing means to capture subtle cognitive decline in preclinical Alzheimer's disease (AD). Here, we describe development, feasibility, and ...validity of the Boston Remote Assessment for Neurocognitive Health (BRANCH) against in‐person cognitive testing and amyloid/tau burden.
Methods
BRANCH is web‐based, self‐guided, and assesses memory processes vulnerable in AD. Clinically normal participants (n = 234; aged 50–89) completed BRANCH; a subset underwent in‐person cognitive testing and positron emission tomography imaging. Mean accuracy across BRANCH tests (Categories, Face‐Name‐Occupation, Groceries, Signs) was calculated.
Results
BRANCH was feasible to complete on participants’ own devices (primarily smartphones). Technical difficulties and invalid/unusable data were infrequent. BRANCH psychometric properties were sound, including good retest reliability. BRANCH was correlated with in‐person cognitive testing (r = 0.617, P < .001). Lower BRANCH score was associated with greater amyloid (r = –0.205, P = .007) and entorhinal tau (r = –0.178, P = .026).
Discussion
BRANCH reliably captures meaningful cognitive information remotely, suggesting promise as a digital cognitive marker sensitive early in the AD trajectory.
Early Paleozoic bottom waters were mainly ferruginous, like the Neoproterozoic, with a shift to increased euxinia in the Devonian.
The extent to which Paleozoic oceans differed from Neoproterozoic ...oceans and the causal relationship between biological evolution and changing environmental conditions are heavily debated. Here, we report a nearly continuous record of seafloor redox change from the deep-water upper Cambrian to Middle Devonian Road River Group of Yukon, Canada. Bottom waters were largely anoxic in the Richardson trough during the entirety of Road River Group deposition, while independent evidence from iron speciation and Mo/U ratios show that the biogeochemical nature of anoxia changed through time. Both in Yukon and globally, Ordovician through Early Devonian anoxic waters were broadly ferruginous (nonsulfidic), with a transition toward more euxinic (sulfidic) conditions in the mid–Early Devonian (Pragian), coincident with the early diversification of vascular plants and disappearance of graptolites. This ~80-million-year interval of the Paleozoic characterized by widespread ferruginous bottom waters represents a persistence of Neoproterozoic-like marine redox conditions well into the Phanerozoic.
•High-gamma memory activity in IEEG corresponds to specific BOLD changes in resting-state data.•HGA-memory regions had lower hubness relative to control brain nodes in both epilepsy patients and ...healthy controls.•HGA-memory network displayed hubness and participation (interaction) values distinct from other cognitive networks.•HGA-memory network shared regional membership and interacted with other cognitive networks for successful memory encoding.•HGA-memory network hubness predicted both concurrent task (phasic) and baseline (tonic) verbal-memory encoding success.
High gamma activity (HGA) of verbal-memory encoding using invasive-electroencephalogram has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these memory linkages remains uncertain. By integrating this electrophysiological biomarker of memory encoding from IEEG with resting-state BOLD fluctuations, we estimated the segregation and hubness of HGA-memory regions in drug-resistant epilepsy patients and matched healthy controls. HGA-memory regions express distinctly different hubness compared to neighboring regions in health and in epilepsy, and this hubness was more relevant than segregation in predicting verbal memory encoding. The HGA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires integrating brain functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.
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