A
bstract
The Rényi entropies and entanglement entropy of 1+1 CFTs with gravity duals can be computed by explicit construction of the bulk spacetimes dual to branched covers of the boundary geometry. ...At the classical level in the bulk this has recently been shown to reproduce the conjectured Ryu-Takayanagi formula for the holographic entanglement entropy. We study the one-loop bulk corrections to this formula. The functional determinants in the bulk geometries are given by a sum over certain words of generators of the Schottky group of the branched cover. For the case of two disjoint intervals on a line we obtain analytic answers for the one-loop entanglement entropy in an expansion in small cross-ratio. These reproduce and go beyond anticipated universal terms that are not visible classically in the bulk. We also consider the case of a single interval on a circle at finite temperature. At high temperatures we show that the one-loop contributions introduce expected finite size corrections to the entanglement entropy that are not present classically. At low temperatures, the one-loop corrections capture the mixed nature of the density matrix, also not visible classically below the Hawking-Page temperature.
An important function of sleep is the consolidation of memories, and features of sleep, such as rapid eye movement (REM) or sleep spindles, have been shown to correlate with improvements in discrete ...memory domains. Because of the methodological difficulties in modulating sleep, however, a causal link between specific sleep features and human memory consolidation is lacking. Here, we experimentally manipulated specific sleep features during a daytime nap via direct pharmacological intervention. Using zolpidem (Ambien), a short-acting GABAA agonist hypnotic, we show increased sleep spindle density and decreased REM sleep compared with placebo and sodium oxybate (Xyrem). Naps with increased spindles produced significantly better verbal memory and significantly worse perceptual learning but did not affect motor learning. The experimental spindles were similar to control spindles in amplitude and frequency, suggesting that the experimental intervention enhanced normal sleep processes. Furthermore, using statistical methods, we demonstrate for the first time a critical role of spindles in human hippocampal memory performance. The gains in memory consolidation exceed sleep-alone or control conditions and demonstrate the potential for targeted, exceptional memory enhancement in healthy adults with pharmacologically modified sleep.
Directed evolution relies on iterative cycles of randomization and selection. The outcome of an artificial evolution experiment is crucially dependent on (i) the numbers of variants that can be ...screened and (ii) the quality of the assessment of each clone that forms the basis for selection. Compartmentalization of screening assays in water-in-oil emulsion droplets provides an opportunity to screen vast numbers of individual assays with good signal quality. Microfluidic systems have been developed to make and sort droplets, but the operator skill required precludes their ready implementation in nonspecialist settings. We now establish a protocol for the creation of monodisperse double-emulsion droplets in two steps in microfluidic devices with different surface characteristics (first hydrophobic, then hydrophilic). The resulting double-emulsion droplets are suitable for quantitative analysis and sorting in a commercial flow cytometer. The power of this approach is demonstrated in a series of enrichment experiments, culminating in the successful recovery of catalytically active clones from a sea of 1 000 000-fold as many low-activity variants. The modular workflow allows integration of additional steps: the encapsulated lysate assay reactions can be stopped by heat inactivation (enabling ready control of selection stringency), the droplet size can be contracted (to concentrate its contents), and storage (at −80 °C) is possible for discontinuous workflows. The control that can be thus exerted on screening conditions will facilitate exploitation of the potential of protein libraries compartmentalized in droplets in a straightforward protocol that can be readily implemented and used by protein engineers.
Ideally, the charge carrier lifetime in a solar cell is limited by the radiative free carrier recombination in the absorber which is a second‐order process. Yet, real‐life cells suffer from severe ...nonradiative recombination in the bulk of the absorber, at interfaces, or within other functional layers. Here, the dynamics of photogenerated charge carriers are probed directly in pin‐type mixed halide perovskite solar cells with an efficiency >20%, using time‐resolved optical absorption spectroscopy and optoelectronic techniques. The charge carrier dynamics in complete devices is fully consistent with a superposition of first‐, second‐, and third‐order recombination processes, with no admixture of recombination pathways with non‐integer order. Under solar illumination, recombination in the studied solar cells proceeds predominantly through nonradiative first‐order recombination with a lifetime of 250 ns, which competes with second‐order free charge recombination which is mostly if not entirely radiative. Results from the transient experiments are further employed to successfully explain the steady‐state solar cell properties over a wide range of illumination intensities. It is concluded that improving carrier lifetimes to >3 µs will take perovskite devices into the radiative regime, where their performance will benefit from photon‐recycling.
To enhance the photovoltaic performances of perovskite solar cells, an in‐depth understanding of recombination processes in full devices is necessary. To gain this insight, transient opto‐electronic measurements are applied, revealing that in full devices a superposition of first‐, second‐, and third‐order recombination fully describes the recombination adequately, nonradiative first‐order recombination dominating under solar illumination conditions.
The amyloid cascade hypothesis, according to which the self-assembly of amyloid-β peptide (Aβ) is a causative process in Alzheimer's disease, has driven many therapeutic efforts for the past 20 ...years. Failures of clinical trials investigating Aβ-targeted therapies have been interpreted as evidence against this hypothesis, irrespective of the characteristics and mechanisms of action of the therapeutic agents, which are highly challenging to assess. Here, we combine kinetic analyses with quantitative binding measurements to address the mechanism of action of four clinical stage anti-Aβ antibodies, aducanumab, gantenerumab, bapineuzumab and solanezumab. We quantify the influence of these antibodies on the aggregation kinetics and on the production of oligomeric aggregates and link these effects to the affinity and stoichiometry of each antibody for monomeric and fibrillar forms of Aβ. Our results reveal that, uniquely among these four antibodies, aducanumab dramatically reduces the flux of Aβ oligomers.
BACKGROUNDValvular heart disease is an important contributor to cardiovascular morbidity and mortality and remains underdiagnosed. Deep learning analysis of electrocardiography (ECG) may be useful in ...detecting aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR). OBJECTIVESThis study aimed to develop ECG deep learning algorithms to identify moderate or severe AS, AR, and MR alone and in combination. METHODSA total of 77,163 patients undergoing ECG within 1 year before echocardiography from 2005-2021 were identified and split into train (n = 43,165), validation (n = 12,950), and test sets (n = 21,048; 7.8% with any of AS, AR, or MR). Model performance was assessed using area under the receiver-operating characteristic (AU-ROC) and precision-recall curves. Outside validation was conducted on an independent data set. Test accuracy was modeled using different disease prevalence levels to simulate screening efficacy using the deep learning model. RESULTSThe deep learning algorithm model accuracy was as follows: AS (AU-ROC: 0.88), AR (AU-ROC: 0.77), MR (AU-ROC: 0.83), and any of AS, AR, or MR (AU-ROC: 0.84; sensitivity 78%, specificity 73%) with similar accuracy in external validation. In screening program modeling, test characteristics were dependent on underlying prevalence and selected sensitivity levels. At a prevalence of 7.8%, the positive and negative predictive values were 20% and 97.6%, respectively. CONCLUSIONSDeep learning analysis of the ECG can accurately detect AS, AR, and MR in this multicenter cohort and may serve as the basis for the development of a valvular heart disease screening program.
Background Evidence linking OSA with hypertension in population studies is conflicting. We examined longitudinal and cross-sectional associations of previously unrecognized OSA, including OSA ...occurring in rapid eye movement (REM) sleep, with hypertension. Methods The Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study is a longitudinal study of community-dwelling men in Adelaide, South Australia. Biomedical assessments at baseline (2002-2006) and follow-up (2007-2010) identified hypertension (systolic ≥ 140 mm Hg and/or diastolic ≥ 90 mm Hg, or medication) and risk factors. In 2010 to 2011, 837 men without a prior diagnosis of OSA underwent full in-home unattended polysomnography of whom 739 recorded ≥ 30 min of REM sleep. Hypertension at follow-up (concomitant with OSA status) was defined as prevalent hypertension. Recent-onset hypertension was defined as hypertension at biomedical follow-up (56 months mean follow-up range, 48-74) in men free of hypertension at baseline. Results Severe REM OSA (apnea hypopnea index ≥30/h) showed independent adjusted associations with prevalent (OR, 2.40, 95% CI, 1.42-4.06), and recent-onset hypertension (2.24 1.04-4.81). Significant associations with non-REM AHI were not seen. In men with AHI < 10, REM OSA (apnea hypopnea index) ≥ 20/h was significantly associated with prevalent hypertension (2.67 1.33-5.38) and the relationship with recent-onset hypertension was positive but not statistically significant (2.32 0.79-6.84). Similar results were seen when analyses were confined to men with non-REM AHI < 10. Conclusions In men not considered to have OSA (AHI < 10), hypertension was associated with OSA during REM sleep. REM OSA may need consideration as an important clinical entity requiring treatment but further systematic assessment and evidence is needed.
Marijuana intoxication appears to impair response inhibition, but it is unclear if impaired inhibition and associated brain abnormalities persist after prolonged abstinence among adolescent users. We ...hypothesized that brain activation during a go/no-go task would show persistent abnormalities in adolescent marijuana users after 28 days of abstinence.
Adolescents with (n = 16) and without (n = 17) histories of marijuana use were compared on blood oxygen level dependent (BOLD) response to a go/no-go task during functional magnetic resonance imaging (fMRI) after 28 days of monitored abstinence. Participants had no neurological problems or Axis I diagnoses other than cannabis abuse/dependence.
Marijuana users did not differ from non-users on task performance but showed more BOLD response than non-users during inhibition trials in right dorsolateral prefrontal, bilateral medial frontal, bilateral inferior and superior parietal lobules, and right occipital gyri, as well as during "go" trials in right prefrontal, insular, and parietal cortices (p < 0.05, clusters > 943 microl). Differences remained significant even after controlling for lifetime and recent alcohol use.
Adolescent marijuana users relative to non-users showed increased brain processing effort during an inhibition task in the presence of similar task performance, even after 28 days of abstinence. Thus, increased brain processing effort to achieve inhibition may predate the onset of regular use or result from it. Future investigations will need to determine whether increased brain processing effort is associated with risk to use.
PDF
