Neutron stars in Gauss-Bonnet gravity -- nonlinear scalarization and gravitational phase transitions

It was recently discovered that scalarized neutron stars in scalar-tensor theories can undergo a gravitational phase transition to a non-scalarized (GR) state. Surprisingly, even though the driving mechanism is totally different, the process resembles closely the first-order matter phase transition from confined nuclear matter to deconfined quark matter in neutron star cores. The studies until now were limited, though, to only one theory of gravity and a limited range of parameters. With the present paper, we aim at demonstrating that gravitational phase transitions are more common than expected. More specifically, we show that the phenomenon of nonlinear scalarization is present for neutron stars in Gauss-Bonnet gravity leading to the possibility of gravitational phase transition. Moreover, it can be observed for a wide range of parameters so no fine-tuning is needed. This solidifies the conjecture that gravitational phase transitions are an important phenomenon for compact objects and their astrophysical implications deserve an in-depth study.Comment: 16 pages, 5 figure

Assessment of water resources management strategy under different evolutionary optimization techniques

Competitive optimization techniques have been developed to address the complexity of integrated water resources management (IWRM) modelling; however, model adaptation due to changing environments is still a challenge. In this paper we employ multi-variable techniques to increase confidence in model-driven decision-making scenarios. Here, water reservoir management was assessed using two evolutionary algorithm (EA) techniques, the epsilon-dominance-driven self-adaptive evolutionary algorithm (∈-DSEA) and the Borg multi-objective evolutionary algorithm (MOEA). Many objective scenarios were evaluated to manage flood risk, hydropower generation, water supply, and release sequences over three decades. Computationally, the ∈-DSEA's results are generally reliable, robust, effective and efficient when compared directly with the Borg MOEA but both provide decision support model outputs of value

Trait-Like Brain Activity during Adolescence Predicts Anxious Temperament in Primates

Early theorists (Freud and Darwin) speculated that extremely shy children, or those with anxious temperament, were likely to have anxiety problems as adults. More recent studies demonstrate that these children have heightened responses to potentially threatening situations reacting with intense defensive responses that are characterized by behavioral inhibition (BI) (inhibited motor behavior and decreased vocalizations) and physiological arousal. Confirming the earlier impressions, data now demonstrate that children with this disposition are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension. To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG) high-resolution Positron Emission Tomography (PET) in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children. Imaging the same animal in stressful and secure contexts, we examined the relation between regional metabolic brain activity and a trait-like measure of anxious temperament that encompasses measures of BI and pituitary-adrenal reactivity. Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray) that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and depression. In addition, the findings provide an explanation for why individuals with anxious temperament have difficulty relaxing in environments that others perceive as non-stressful

Decision-making challenges of sustainable groundwater strategy under multi-event pressure in arid environments : the Diyala River Basin in Iraq

A robust decision-making tool is needed to meet sustainability challenges and to manage water resources that are under development pressure, water scarcity, and climate change impact. To tackle such challenges, optimization modelling can be employed to explore regional sustainable management scenarios of groundwater exploitation. Multi-objective management modelling of various alternatives was developed for the Diyala River Basin in Iraq using Borg multi-objectives evolutionary algorithm (MOEA) and "-DSEA algorithms. In almost all modelled cases, the upper aquifer storage is predicted to be depleted after 40 years due to large water demands and regional recharge scarcity. Hence, there is a need to develop a strategy to reduce water stresses by 45% to achieve sustainability within the next 25 years. Optimization modelling successfully generated future predictions that can be used by decision makers to manage the predicted groundwater shortages in the future

Women and Heart Disease: Neglected Directions for Future Research

Before age 65, women have less heart disease than men. For many years, estrogen was the most popular explanation for this female advantage, and observational studies through the 1980s showed a lower risk of heart attacks in postmenopausal women taking “replacement” estrogen. But the Women’s Health Initiative (WHI), the first placebo-controlled trials of hormone therapy with the size and statistical power necessary to study clinical cardiovascular outcomes, did not confirm the hormone-healthy heart hypothesis. Now, at least 5 years later, the most unexpected WHI result may be how resilient the estrogen hypothesis has been. Where, beyond estrogen therapy, should we go from here to explain the striking sex differences in heart disease rates? A broader spectrum of research about the female cardiovascular advantage and its translation is needed

Optimum socio-environmental flows approach for reservoir operation strategy using many-objectives evolutionary optimization algorithm

Water resource system complexity, high-dimension modelling difficulty and computational efficiency challenges often limit decision makers' strategies to combine environmental flow objectives (e.g. water quality, ecosystem) with social flow objectives (e.g. hydropower, water supply and agriculture). Hence, a novel Optimum Social-Environmental Flows (OSEF) with Auto-Adaptive Constraints (AAC) approach introduced as a river basin management decision support tool. The OSEF-AAC approach integrates Socio-Environmental (SE) objectives with convergence booster support to soften any computational challenges. Nine SE objectives and 396 decision variables modelled for Iraq's Diyala river basin. The approach's effectiveness evaluated using two non-environmental models and two inflows' scenarios. The advantage of OSEF-AAC approved, and other decision support alternatives highlighted that could enhance river basin SE sectors' revenues, as river basin economic benefits will improve as well. However, advanced land use and water exploitation policy would need adoption to secure the basin's SE sectors

Inhibiting the coregulator CoREST impairs Foxp3+ Treg function and promotes antitumor immunity

Foxp3+ Tregs are key to immune homeostasis, but the contributions of various large, multiprotein complexes that regulate gene expression remain unexplored. We analyzed the role in Tregs of the evolutionarily conserved CoREST complex, consisting of a scaffolding protein, Rcor1 or Rcor2, plus Hdac1 or Hdac2 and Lsd1 enzymes. Rcor1, Rcor2, and Lsd1 were physically associated with Foxp3, and mice with conditional deletion of Rcor1 in Foxp3+ Tregs had decreased proportions of Tregs in peripheral lymphoid tissues and increased Treg expression of IL-2 and IFN-\u3b3 compared with what was found in WT cells. Mice with conditional deletion of the gene encoding Rcor1 in their Tregs had reduced suppression of homeostatic proliferation, inability to maintain long-term allograft survival despite costimulation blockade, and enhanced antitumor immunity in syngeneic models. Comparable findings were seen in WT mice treated with CoREST complex bivalent inhibitors, which also altered the phenotype of human Tregs and impaired their suppressive function. Our data point to the potential for therapeutic modulation of Treg functions by pharmacologic targeting of enzymatic components of the CoREST complex and contribute to an understanding of the biochemical and molecular mechanisms by which Foxp3 represses large gene sets and maintains the unique properties of this key immune cell

Deletion of Forkhead Box M1 Transcription Factor from Respiratory Epithelial Cells Inhibits Pulmonary Tumorigenesis

The Forkhead Box m1 (Foxm1) protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1−/− mice) prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT). Decreased lung tumorigenesis in epFoxm1−/− mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2α (TOPO-2α), a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2α mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2α promoter region, indicating that TOPO-2α is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2α expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy

Prediction of a gene regulatory network linked to prostate cancer from gene expression, microRNA and clinical data

Motivation: Cancer is a complex disease, triggered by mutations in multiple genes and pathways. There is a growing interest in the application of systems biology approaches to analyze various types of cancer-related data to understand the overwhelming complexity of changes induced by the disease

Expression of Foxm1 Transcription Factor in Cardiomyocytes Is Required for Myocardial Development

Forkhead Box M1 (Foxm1) is a transcription factor essential for organ morphogenesis and development of various cancers. Although complete deletion of Foxm1 in Foxm1−/− mice caused embryonic lethality due to severe abnormalities in multiple organ systems, requirements for Foxm1 in cardiomyocytes remain to be determined. This study was designed to elucidate the cardiomyocyte-autonomous role of Foxm1 signaling in heart development. We generated a new mouse model in which Foxm1 was specifically deleted from cardiomyocytes (Nkx2.5-Cre/Foxm1fl/f mice). Deletion of Foxm1 from cardiomyocytes was sufficient to disrupt heart morphogenesis and induce embryonic lethality in late gestation. Nkx2.5-Cre/Foxm1fl/fl hearts were dilated with thinning of the ventricular walls and interventricular septum, as well as disorganization of the myocardium which culminated in cardiac fibrosis and decreased capillary density. Cardiomyocyte proliferation was diminished in Nkx2.5-Cre/Foxm1fl/fl hearts owing to altered expression of multiple cell cycle regulatory genes, such as Cdc25B, Cyclin B1, Plk-1, nMyc and p21cip1. In addition, Foxm1 deficient hearts displayed reduced expression of CaMKIIδ, Hey2 and myocardin, which are critical mediators of cardiac function and myocardial growth. Our results indicate that Foxm1 expression in cardiomyocytes is critical for proper heart development and required for cardiomyocyte proliferation and myocardial growth