A Statistical Approach Reveals Designs for the Most Robust Stochastic Gene Oscillators

The engineering of transcriptional networks presents many challenges due to the inherent uncertainty in the system structure, changing cellular context, and stochasticity in the governing dynamics. One approach to address these problems is to design and build systems that can function across a range of conditions; that is they are robust to uncertainty in their constituent components. Here we examine the parametric robustness landscape of transcriptional oscillators, which underlie many important processes such as circadian rhythms and the cell cycle, plus also serve as a model for the engineering of complex and emergent phenomena. The central questions that we address are: Can we build genetic oscillators that are more robust than those already constructed? Can we make genetic oscillators arbitrarily robust? These questions are technically challenging due to the large model and parameter spaces that must be efficiently explored. Here we use a measure of robustness that coincides with the Bayesian model evidence, combined with an efficient Monte Carlo method to traverse model space and concentrate on regions of high robustness, which enables the accurate evaluation of the relative robustness of gene network models governed by stochastic dynamics. We report the most robust two and three gene oscillator systems, plus examine how the number of interactions, the presence of autoregulation, and degradation of mRNA and protein affects the frequency, amplitude, and robustness of transcriptional oscillators. We also find that there is a limit to parametric robustness, beyond which there is nothing to be gained by adding additional feedback. Importantly, we provide predictions on new oscillator systems that can be constructed to verify the theory and advance design and modeling approaches to systems and synthetic biology

Hyperstars - Main Origin of Short Gamma Ray Bursts?

The first well-localized short-duration gamma ray bursts (GRBs), GRB 050509b, GRB 050709 and GRB 050724, could have been the narrowly beamed initial spike of a burst/hyper flare of soft gamma ray repeaters (SGRs) in host galaxies at cosmological distances. Such bursts are expected if SGRs are young hyperstars, i.e. neutron stars where a considerable fraction of their neutrons have converted to hyperons and/or strange quark matter.Comment: Invited talk to be published in the proceedings of the intl. Workshop `High Energy Cosmic Sources' May 23-28, 2005, Vulcano, Italy 200

Carbon Free Boston: Social equity report 2019

OVERVIEW: In January 2019, the Boston Green Ribbon Commission released its Carbon Free Boston: Summary Report, identifying potential options for the City of Boston to meet its goal of becoming carbon neutral by 2050. The report found that reaching carbon neutrality by 2050 requires three mutually-reinforcing strategies in key sectors: 1) deepen energy efficiency while reducing energy demand, 2) electrify activity to the fullest practical extent, and 3) use fuels and electricity that are 100 percent free of greenhouse gases (GHGs). The Summary Report detailed the ways in which these technical strategies will transform Boston’s physical infrastructure, including its buildings, energy supply, transportation, and waste management systems. The Summary Report also highlighted that it is how these strategies are designed and implemented that matter most in ensuring an effective and equitable transition to carbon neutrality. Equity concerns exist for every option the City has to reduce GHG emissions. The services provided by each sector are not experienced equally across Boston’s communities. Low-income families and families of color are more likely to live in residences that are in poor physical condition, leading to high utility bills, unsafe and unhealthy indoor environments, and high GHG emissions.1 Those same families face greater exposure to harmful outdoor air pollution compared to others. The access and reliability of public transportation is disproportionately worse in neighborhoods with large populations of people of color, and large swaths of vulnerable neighborhoods, from East Boston to Mattapan, do not have ready access to the city’s bike network. Income inequality is a growing national issue and is particularly acute in Boston, which consistently ranks among the highest US cities in regards to income disparities. With the release of Imagine Boston 2030, Mayor Walsh committed to make Boston more equitable, affordable, connected, and resilient. The Summary Report outlined the broad strokes of how action to reach carbon neutrality intersects with equity. A just transition to carbon neutrality improves environmental quality for all Bostonians, prioritizes socially vulnerable populations, seeks to redress current and past injustice, and creates economic and social opportunities for all. This Carbon Free Boston: Social Equity Report provides a deeper equity context for Carbon Free Boston as a whole, and for each strategy area, by demonstrating how inequitable and unjust the playing field is for socially vulnerable Bostonians and why equity must be integrated into policy design and implementation. This report summarizes the current landscape of climate action work for each strategy area and evaluates how it currently impacts inequity. Finally, this report provides guidance to the City and partners on how to do better; it lays out the attributes of an equitable approach to carbon neutrality, framed around three guiding principles: 1) plan carefully to avoid unintended consequences, 2) be intentional in design through a clear equity lens, and 3) practice inclusivity from start to finish

Regulation of Placental Development and Its Impact on Fetal Growth—New Insights From Mouse Models

The placenta is the chief regulator of nutrient supply to the growing embryo during gestation. As such, adequate placental function is instrumental for developmental progression throughout intrauterine development. One of the most common complications during pregnancy is insufficient growth of the fetus, a problem termed intrauterine growth restriction (IUGR) that is most frequently rooted in a malfunctional placenta. Together with conventional gene targeting approaches, recent advances in screening mouse mutants for placental defects, combined with the ability to rapidly induce mutations in vitro and in vivo by CRISPR-Cas9 technology, has provided new insights into the contribution of the genome to normal placental development. Most importantly, these data have demonstrated that far more genes are required for normal placentation than previously appreciated. Here, we provide a summary of common types of placental defects in established mouse mutants, which will help us gain a better understanding of the genes impacting on human placentation. Based on a recent mouse mutant screen, we then provide examples on how these data can be mined to identify novel molecular hubs that may be critical for placental development. Given the close association between placental defects and abnormal cardiovascular and brain development, these functional nodes may also shed light onto the etiology of birth defects that co-occur with placental malformations. Taken together, recent insights into the regulation of mouse placental development have opened up new avenues for research that will promote the study of human pregnancy conditions, notably those based on defects in placentation that underlie the most common pregnancy pathologies such as IUGR and pre-eclampsia

The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism

The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. Interestingly, exposure to lighting conditions that disrupt circadian rhythms improve their glucose tolerance. This improvement occurs through an increase in glucose clearance by skeletal muscle and is food intake and body weight independent. Restoring Mc4r expression to the paraventricular nucleus prevents the improvement in glucose tolerance, supporting a role for the paraventricular nucleus in the integration of circadian light cues and metabolism. Altogether these data suggest that Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system

Galaxy Pairs in the Sloan Digital Sky Survey - III: Evidence of Induced Star Formation from Optical Colours

We have assembled a large, high quality catalogue of galaxy colours from the Sloan Digital Sky Survey Data Release 7, and have identified 21,347 galaxies in pairs spanning a range of projected separations (r_p < 80 h_{70}^{-1} kpc), relative velocities (\Delta v < 10,000 km/s, which includes projected pairs that are essential for quality control), and stellar mass ratios (from 1:10 to 10:1). We find that the red fraction of galaxies in pairs is higher than that of a control sample matched in stellar mass and redshift, and demonstrate that this difference is likely due to the fact that galaxy pairs reside in higher density environments than non-paired galaxies. We detect clear signs of interaction-induced star formation within the blue galaxies in pairs, as evidenced by a higher fraction of extremely blue galaxies, along with blueward offsets between the colours of paired versus control galaxies. These signs are strongest in close pairs (r_p < 30 h_{70}^{-1} kpc and \Delta v < 200 km/s), diminish for more widely separated pairs (r_p > 60 h_{70}^{-1} kpc and \Delta v < 200 km/s) and disappear for close projected pairs (r_p < 30 h_{70}^{-1} kpc and \Delta v > 3000 km/s). These effects are also stronger in central (fibre) colours than in global colours, and are found primarily in low- to medium-density environments. Conversely, no such trends are seen in red galaxies, apart from a small reddening at small separations which may result from residual errors with photometry in crowded fields. When interpreted in conjunction with a simple model of induced starbursts, these results are consistent with a scenario in which close peri-centre passages trigger induced star formation in the centres of galaxies which are sufficiently gas rich, after which time the galaxies gradually redden as they separate and their starbursts age.Comment: 17 pages. Accepted for publication in MNRA

Galaxy Pairs in the Sloan Digital Sky Survey - II: The Effect of Environment on Interactions

We use a sample of close galaxy pairs selected from the Sloan Digital Sky Survey Data Release 4 (SDSS DR4) to investigate in what environments galaxy mergers occur and how the results of these mergers depend on differences in local galaxy density. The galaxies are quantified morphologically using two-dimensional bulge-plus-disk decompositions and compared to a control sample matched in stellar mass, redshift and local projected density. Lower density environments have fractionally more galaxy pairs with small projected separations (r_p) and relative velocities (Delta v), but even high density environments contain significant populations of pairs with parameters that should be conducive to interactions. Metrics of asymmetry and colour are used to identify merger activity and triggered star formation. The location of star formation is inferred by distinguishing bulge and disk colours and calculating bulge fractions from the SDSS images. Galaxies in the lowest density environments show the largest changes in star formation rate, asymmetry and bulge-total fractions at small separations, accompanied by bluer bulge colours. At the highest local densities, the only galaxy property to show an enhancement in the closest pairs is asymmetry. We interpret these results as evidence that whilst interactions (leading to tidal distortions) occur at all densities, triggered star formation is seen only in low-to-intermediate density environments. We suggest that this is likely due to the typically higher gas fractions of galaxies in low density environments. Finally, by cross-correlating our sample of galaxy pairs with a cluster catalogue, we investigate the dependence of interactions on clustercentric distance. It is found that for close pairs the fraction of asymmetric galaxies is highest in the cluster centres.Comment: Accepted by MNRAS, 15 page

Prospectus, January 24, 1990

https://spark.parkland.edu/prospectus_1990/1001/thumbnail.jp