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One possible formation mechanism for Hot Jupiters is that high-eccentricity gas giants experience tidal interactions with their host star that cause them to lose orbital energy and migrate inwards. We study these types of tidal interactions in an eccentric Hot Jupiter called HAT-P-2 b, which is a system where a long-period companion has been suggested and hints of orbital evolution were detected. Using 5 additional years of radial velocity (RV) measurements, we further investigate these phenomena. We investigated the long-period companion by jointly fitting RVs and Hipparcos-Gaia astrometry and confirmed this long-period companion, significantly narrowed down the range of possible periods ( P2=8500−1500+2600 days), and determined that it must be a substellar object ( 10.7−2.2+5.2 M j). We also developed a modular pipeline to simultaneously model rapid orbital evolution and the long-period companion. We find that the rate and significance of evolution are highly dependent on the long-period companion modeling choices. In some cases the orbital rates of change reached de/dt=3.28−1.72+1.75×10−3 yr−1, d ω/dt = 1.12° ± 0.22° yr−1, which corresponds to a ∼321 yr apsidal precession period. In other cases, the data is consistent with de/dt = 7.67 ± 18.6 × 10−4 yr−1, d ω/dt = 0.76° ± 0.24° yr−1. The most rapid changes found are significantly larger than the expected relativistic precession rate and could be caused by transient tidal planet–star interactions. To definitively determine the magnitude and significance of potential orbital evolution in HAT-P-2 b, we recommend further monitoring with RVs and precise transit and eclipse timings.

Hot Jupiters are expected to form far from their host star and move to a close-in, circular orbit through a smooth, monotonic decay due to mild and constant tidal dissipation. Yet, systems exhibiting planet-induced stellar pulsations have recently been found, suggesting unexpectedly strong tidal interactions. Here we combine stellar evolution and tide models to show that dynamical tides raised by eccentric gas giants can excite chains of resonance locks with several modes, which enriches the dynamics seen in single-mode resonance locking of circularized systems. These series of resonance locks yield orders of magnitude larger changes in eccentricity and harmonic pulsations relative to those expected from a single episode of resonance locking or non-resonant tidal interactions. Resonances become more frequent as a star evolves off the main sequence, which provides an alternative explanation for the origin of some stellar pulsators and leads to the concept of ‘dormant migrating giants’. Evolution trajectories are characterized by competing episodes of inward and outward migration and the spin-up or spin-down of the star, which are sensitive to the system parameters. This is a new challenge in modelling migration paths and in contextualizing the observed populations of giant exoplanets and stellar binaries. This sensitivity, however, offers a new window for constraining the stellar properties of planetary hosts through tidal asteroseismology. A state-of-the-art model for planet–star interactions shows that migrating planets may coevolve with their pulsating stars through episodic resonances that drive substantial orbital migration and produce detectable tidal oscillations.

Hot Jupiters are expected to form far from their host star and move toward close-in, circular orbits via a smooth, monotonic decay due to mild and constant tidal dissipation. Yet, three systems have recently been found exhibiting planet-induced stellar pulsations suggesting unexpectedly strong tidal interactions. Here we combine stellar evolution and tide models to show that dynamical tides raised by eccentric gas giants can give rise to chains of resonance locks with multiple modes, enriching the dynamics seen in single-mode resonance locking of circularized systems. These series of resonance locks yield orders-of-magnitude larger changes in eccentricity and harmonic pulsations relative to those expected from a single episode of resonance locking or nonresonant tidal interactions. Resonances become more frequent as a star evolves off the main sequence providing an alternative explanation to the origin of some stellar pulsators and yielding the concept of \"dormant migrating giants\". Evolution trajectories are characterized by competing episodes of inward/outward migration and spin-up/-down of the star which are sensitive to the system parameters, revealing a new challenge in modeling migration paths and in contextualizing the observed populations of giant exoplanets and stellar binaries. This sensitivity however offers a new window to constrain the stellar properties of planetary hosts via tidal asteroseismology.

This dissertation presents an innovative approach to the study of residential burglary. A simulation model is built upon the integration of Cellular Automata (CA) and Multi-Agent Systems (MAS), which utilizes journey-to-crime (JTC), social disorganization (SD), and routine activity (RA) theories to predict locations of residential burglary targets. Offenders are implemented as MAS agents on top of CA automata of targets and places. Each offender has a certain motivation to commit a crime, determined by his/her age, race and gender background. Likewise, each possible location has a particular attractiveness to the offender, such as target desirability and place lack-of-guardianship, which are dependent on neighborhood characteristics, such as median income, race composition, commute time and length of tenure. This model employs two novel calibration methods to derive the simulation weight parameters: automatic Analytic Hierarchy Process (AHP) and hierarchical Genetic Algorithms (GA). Unlike traditional AHP where pairwise comparisons are conducted manually and subjectively, automatic AHP calibrates the pairwise comparison scoring to derive parameter weights for the model using a pseudo-binary search based on empirical data. The hierarchical GA calibration exploits the crime model's hierarchical structure to create a modified GA, which incorporates new composite crossover, composite mutation, and infeasibility repair techniques into the residential burglary weight parameter selection process. The hybrid CA/MAS residential burglary model results showed realistic predictions by the automatic AHP and hierarchical GA calibration methods in terms of RMSE and crime pattern analysis. Also, through the analysis of the calibrated weights, it was found that the JTC theory contributed the most toward producing realistic predictions, followed by RA, then SD. Future work on this project may include parallel processing, additional datasets, and new distance measures and neighborhood representations.

One possible formation mechanism for Hot Jupiters is that high-eccentricity gas giants experience tidal interactions with their host star that cause them to lose orbital energy and migrate inwards. We study these types of tidal interactions in an eccentric Hot Jupiter called HAT-P-2 b, which is a system where a long-period companion has been suggested, and hints of orbital evolution (de Wit et al. 2017) were detected. Using five additional years of radial velocity (RV) measurements, we further investigate these phenomena. We investigated the long-period companion by jointly fitting RVs and Hipparcos-Gaia astrometry and confirmed this long-period companion, significantly narrowed down the range of possible periods (\\(P_2 = 8500_-1500^+2600\\) days), and determined that it must be a substellar object (\\(10.7_-2.2^+5.2\\) \\(M_j\\)). We also developed a modular pipeline to simultaneously model rapid orbital evolution and the long-period companion. We find that the rate and significance of evolution are highly dependent on the long-period companion modeling choices. In some cases the orbital rates of change reached \\(de/dt = 3.28_-1.72^+1.75 10^-3\\)/year, \\(d/dt = 1.12 0.22 ^\\)/year which corresponds to a \\( 321\\) year apsidal precession period. In other cases, the data is consistent with \\(de/dt = 7.67 18.6 10^-4\\)/year, \\(d/dt = 0.76 0.24 ^\\)/year. The most rapid changes found are significantly larger than the expected relativistic precession rate and could be caused by transient tidal planet-star interactions. To definitively determine the magnitude and significance of potential orbital evolution in HAT-P-2 b, we recommend further monitoring with RVs and precise transit and eclipse timings.

Social-evaluative stressors—experiences in which people feel they could be judged negatively—pose a major threat to adolescent mental health 1 – 3 and can cause young people to disengage from stressful pursuits, resulting in missed opportunities to acquire valuable skills. Here we show that replicable benefits for the stress responses of adolescents can be achieved with a short (around 30-min), scalable 'synergistic mindsets' intervention. This intervention, which is a self-administered online training module, synergistically targets both growth mindsets 4 (the idea that intelligence can be developed) and stress-can-be-enhancing mindsets 5 (the idea that one’s physiological stress response can fuel optimal performance). In six double-blind, randomized, controlled experiments that were conducted with secondary and post-secondary students in the United States, the synergistic mindsets intervention improved stress-related cognitions (study 1, n  = 2,717; study 2, n  = 755), cardiovascular reactivity (study 3, n  = 160; study 4, n  = 200), daily cortisol levels (study 5, n  = 118 students, n  = 1,213 observations), psychological well-being (studies 4 and 5), academic success (study 5) and anxiety symptoms during the 2020 COVID-19 lockdowns (study 6, n  = 341). Heterogeneity analyses (studies 3, 5 and 6) and a four-cell experiment (study 4) showed that the benefits of the intervention depended on addressing both mindsets—growth and stress—synergistically. Confidence in these conclusions comes from a conservative, Bayesian machine-learning statistical method for detecting heterogeneous effects 6 . Thus, our research has identified a treatment for adolescent stress that could, in principle, be scaled nationally at low cost. An online training module that synergistically targets two different mindsets can reduce stress levels in adolescents in the context of social-evaluative stressors—stressful experiences in which individuals fear that others are judging them negatively.

A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104-106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to those occurring in transplant patients on immunosuppressive therapy and consistent with development of an immunosuppressive state. Whether reactivated latent viruses contribute to morbidity and mortality in sepsis remains unknown.

Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus–associated metastatic cervical cancer after tumor-infiltrating adoptive Tcell therapy. Remarkably, immunodominant Tcell reactivities were directed againstmutated neoantigens or a cancer germline antigen, rather than canonical viral antigens.Tcells targeting viral tumor antigens did not display preferential in vivo expansion. Both viral and nonviral tumor antigen–specific Tcells resided predominantly in the programmed cell death 1 (PD-1)–expressing Tcell compartment, which suggests that PD-1 blockade may unleash diverse antitumor Tcell reactivities. These findings suggest a new paradigm of targeting nonviral antigens in immunotherapy of virally associated cancers.

Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell function. Oct1(HI) cells in the colon and small intestine co-express known stem cell markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with the frequency of CD24(LO)CD44(HI) cancer-initiating cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI) and dye efflux(HI) cells, and increasing Oct1 increases the proportion of ALDH(HI) cells. Normal ALDH(HI) cells harbor elevated Oct1 protein but not mRNA levels. Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes hematopoietic stem cell engraftment potential in competitive and serial transplants. In addition to previously described Oct1 transcriptional targets, we identify four Oct1 targets associated with the stem cell phenotype. Cumulatively, the data indicate that Oct1 regulates normal and cancer stem cell function.

To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF). Cross-sectional brain Magnetic Resonance I (MRI) study. Community based cohort in three U.S. sites. A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study. 3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function. Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01). In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.