Real-time finite-temperature correlators from AdS/CFT

In this paper we use AdS/CFT ideas in conjunction with insights from finite temperature real-time field theory formalism to compute 3-point correlators of ${\cal N}{=}4$ super Yang-Mills operators, in real time and at finite temperature. To this end, we propose that the gravity field action is integrated only over the right and left quadrants of the Penrose diagram of the Anti de Sitter-Schwarzschild background, with a relative sign between the two terms. For concreteness we consider the case of a scalar field in the black hole background. Using the scalar field Schwinger-Keldysh bulk-to-boundary propagators, we give the general expression of a 3-point real-time Green's correlator. We then note that this particular prescription amounts to adapting the finite-temperature analog of Veltman's circling rules to tree-level Witten diagrams, and comment on the retarded and Feynman scalar bulk-to-boundary propagators. We subject our prescription to several checks: KMS identities, the largest time equation and the zero-temperature limit. When specializing to a particular retarded (causal) 3-point function, we find a very simple answer: the momentum-space correlator is given by three causal (two retarded and one advanced) bulk-to-boundary propagators, meeting at a vertex point which is integrated from spatial infinity to the horizon only. This result is expected based on analyticity, since the retarded n-point functions are obtained by analytic continuation from the imaginary time Green's function, and based on causality considerations.Comment: 43 pages, 6 figures Typos fixed, reference added, one set of plots update

Determinants of TRPV4 Activity following Selective Activation by Small Molecule Agonist GSK1016790A

TRPV4 (Transient Receptor Potential Vanilloid 4) channels are activated by a wide range of stimuli, including hypotonic stress, non-noxious heat and mechanical stress and some small molecule agonists (e.g. phorbol ester 4α-PDD). GSK1016790A (GSK101) is a recently discovered specific small molecule agonist of TRPV4. Its effects on physical determinants of TRPV4 activity were evaluated in HeLa cells transiently transfected with TRPV4 (HeLa-TRPV4). GSK101 (10 nM) causes a TRPV4 specific Ca2+ influx in HeLa-TRPV4 cells, but not in control transfected cells, which can be inhibited by ruthenium red and Ca2+-free medium more significantly at the early stage of the activation rather than the late stage, reflecting apparent partial desensitization. Western blot analysis showed that GSK101 activation did not induce an increase in TRPV4 expression at the plasma membrane, but caused an immediate and sustained downregulation of TRPV4 on the plasma membrane in HeLa-TRPV4 cells. Patch clamp analysis also revealed an early partial desensitization of the channel which was Ca2+-independent. FRET analysis of TRPV4 subunit assembly demonstrated that the GSK101-induced TRPV4 channel activation/desensitization was not due to alterations in homotetrameric channel formation on the plasma membrane. It is concluded that GSK101 specifically activates TRPV4 channels, leading to a rapid partial desensitization and downregulation of the channel expression on the plasma membrane. TRPV4 subunit assembly appears to occur during trafficking from the ER/Golgi to the plasma membrane and is not altered by agonist stimulation

SQUARE: Strategic Quantum Ancilla Reuse for Modular Quantum Programs via Cost-Effective Uncomputation

Compiling high-level quantum programs to machines that are size constrained (i.e. limited number of quantum bits) and time constrained (i.e. limited number of quantum operations) is challenging. In this paper, we present SQUARE (Strategic QUantum Ancilla REuse), a compilation infrastructure that tackles allocation and reclamation of scratch qubits (called ancilla) in modular quantum programs. At its core, SQUARE strategically performs uncomputation to create opportunities for qubit reuse. Current Noisy Intermediate-Scale Quantum (NISQ) computers and forward-looking Fault-Tolerant (FT) quantum computers have fundamentally different constraints such as data locality, instruction parallelism, and communication overhead. Our heuristic-based ancilla-reuse algorithm balances these considerations and fits computations into resource-constrained NISQ or FT quantum machines, throttling parallelism when necessary. To precisely capture the workload of a program, we propose an improved metric, the "active quantum volume," and use this metric to evaluate the effectiveness of our algorithm. Our results show that SQUARE improves the average success rate of NISQ applications by 1.47X. Surprisingly, the additional gates for uncomputation create ancilla with better locality, and result in substantially fewer swap gates and less gate noise overall. SQUARE also achieves an average reduction of 1.5X (and up to 9.6X) in active quantum volume for FT machines.Comment: 14 pages, 10 figure

Life Course Socioeconomic Position: associations with cardiac structure and function at age 60-64 years in the 1946 British Birth Cohort

Although it is recognized that risks of cardiovascular diseases associated with heart failure develop over the life course, no studies have reported whether life course socioeconomic inequalities exist for heart failure risk. The Medical Research Council’s National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and measures of cardiac structure [left ventricular (LV) mass index and relative wall thickness (RWT)] and function [systolic: ejection fraction (EF) and midwall fractional shortening (mFS); diastolic: left atrial (LA) volume, E/A ratio and E/e’ ratio)]. Different life course models were compared with a saturated model to ascertain the nature of the relationship between socioeconomic position across the life course and each cardiac marker. Findings showed that models where socioeconomic position accumulated over multiple time points in life provided the best fit for 3 of the 7 cardiac markers: childhood and early adulthood periods for the E/A ratio and E/e’ ratio, and all three life periods for LV mass index. These associations were attenuated by adjustment for adiposity, but were little affected by adjustment for other established or novel cardio-metabolic risk factors. There was no evidence of a relationship between socioeconomic position at any time point and RWT, EF, mFS or LA volume index. In conclusion, socioeconomic position across multiple points of the lifecourse, particularly earlier in life, is an important determinant of some measures of LV structure and function. BMI may be an important mediator of these associations

Diesel exhaust particles distort lung epithelial progenitors and their fibroblast niche

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by inflammation and impaired tissue regeneration, and is reported as the fourth leading cause of death worldwide by the Centers for Disease Control and Prevention (CDC). Environmental pollution and specifically motor vehicle emissions are known to play a role in the pathogenesis of COPD, but little is still known about the molecular mechanisms that are altered following diesel exhaust particles (DEP) exposure. Here we used lung organoids derived from co-culture of alveolar epithelial progenitors and fibroblasts to investigate the effect of DEP on the epithelial-mesenchymal signaling niche in the distal lung, which is essential for tissue repair. We found that DEP treatment impaired the number as well as the average diameter of both airway and alveolar type of lung organoids. Bulk RNA-sequencing of re-sorted epithelial cells and fibroblasts following organoid co-culture shows that the Nrf2 pathway, which regulates antioxidants' activity, was upregulated in both cell populations in response to DEP; and WNT/β-catenin signaling, which is essential to promote epithelial repair, was downregulated in DEP-exposed epithelial cells. We show that pharmacological treatment with anti-oxidant agents such as N-acetyl cysteine (NAC) or Mitoquinone mesylate (MitoQ) reversed the effect of DEP on organoids growth. Additionally, a WNT/β-catenin activator (CHIR99021) successfully restored WNT signaling and promoted organoid growth upon DEP exposure. We propose that targeting oxidative stress and specific signaling pathways affected by DEP in the distal lung may represent a strategy to restore tissue repair in COPD

College Students as Facilitators in Reducing Adolescent Obesity Disparity in Southern Appalachia: Team up for Healthy Living

The proportion of obese adolescents in Southern Appalachia is among the highest in the nation. Through funding from the National Institute on Minority Health and Health Disparities — National Institutes of Health, the Team Up for Healthy Living project was a cluster-randomized trial targeting obesity prevention in adolescents through a cross-peer intervention. The specific aims of the project were to: 1) develop a peer-based health education program focusing on establishing positive peer norms towards healthy eating and physical activity (PA) among high school students, 2) test program efficacy, and 3) explore mechanisms underlying the program. The study was guided by the Theory of Planned Behavior, which presupposes that human behavior is primarily driven by attitude, subjective norms, perceived behavioral control, and social support. To deliver the intervention, undergraduate students from the disciplines of public health, nutrition, and kinesiology were hired as peer facilitators. Ten area high schools were invited to participate, were matched on demographics and then randomized to intervention or control. The primary outcomes of the study included body mass status, dietary behaviors, PA, and sedentary behaviors which were assessed at baseline and at three and twelve months post baseline. Intervention schools received Team Up for Healthy Living curriculum, which consists of eight 40-minute sessions. The curriculum focused on improving nutrition awareness, PA, leadership and communication. Control schools received their regularly scheduled Lifetime Wellness curriculum. The long-term goal of the study was to establish an effective academia–community partnership program to address adolescent obesity disparity in Southern Appalachia

Congenital anomalies in low- and middle-income countries: the unborn child of global surgery.

Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Longitudinal variability of time-location/activity patterns of population at different ages: a longitudinal study in California

<p>Abstract</p> <p>Background</p> <p>Longitudinal time-activity data are important for exposure modeling, since the extent to which short-term time-activity data represent long-term activity patterns is not well understood. This study was designed to evaluate longitudinal variations in human time-activity patterns.</p> <p>Method</p> <p>We report on 24-hour recall diaries and questionnaires collected via the internet from 151 parents of young children (mostly under age 55), and from 55 older adults of ages 55 and older, for both a weekday and a weekend day every three months over an 18-month period. Parents also provided data for their children. The self-administrated diary and questionnaire distinguished ~30 frequently visited microenvironments and ~20 activities which we selected to represent opportunities for exposure to toxic environmental compounds. Due to the non-normal distribution of time-location/activity data, we employed generalized linear mixed-distribution mixed-effect models to examine intra- and inter-individual variations. Here we describe variation in the likelihood of and time spent engaging in an activity or being in a microenvironment by age group, day-type (weekday/weekend), season (warm/cool), sex, employment status, and over the follow-up period.</p> <p>Results</p> <p>As expected, day-type and season influence time spent in many location and activity categories. Longitudinal changes were also observed, e.g., young children slept less with increasing follow-up, transit time increased, and time spent on working and shopping decreased during the study, possibly related to human physiological changes with age and changes in macro-economic factors such as gas prices and the economic recession.</p> <p>Conclusions</p> <p>This study provides valuable new information about time-activity assessed longitudinally in three major age groups and greatly expands our knowledge about intra- and inter-individual variations in time-location/activity patterns. Longitudinal variations beyond weekly and seasonal patterns should be taken into account in simulating long-term time-activity patterns in exposure modeling.</p