Bioluminescence rhythms from cellular reporters have become the most common method used to quantify oscillations in circadian gene expression. These experimental systems can reveal phase and ...amplitude change resulting from circadian disturbances, and can be used in conjunction with mathematical models to lend further insight into the mechanistic basis of clock amplitude regulation. However, bioluminescence experiments track the mean output from thousands of noisy, uncoupled oscillators, obscuring the direct effect of a given stimulus on the genetic regulatory network. In many cases, it is unclear whether changes in amplitude are due to individual changes in gene expression level or to a change in coherence of the population. Although such systems can be modeled using explicit stochastic simulations, these models are computationally cumbersome and limit analytical insight into the mechanisms of amplitude change. We therefore develop theoretical and computational tools to approximate the mean expression level in large populations of noninteracting oscillators, and further define computationally efficient amplitude response calculations to describe phase-dependent amplitude change. At the single-cell level, a mechanistic nonlinear ordinary differential equation model is used to calculate the transient response of each cell to a perturbation, whereas population-level dynamics are captured by coupling this detailed model to a phase density function. Our analysis reveals that amplitude changes mediated at either the individual-cell or the population level can be distinguished in tissue-level bioluminescence data without the need for single-cell measurements. We demonstrate the effectiveness of the method by modeling experimental bioluminescence profiles of light-sensitive fibroblasts, reconciling the conclusions of two seemingly contradictory studies. This modeling framework allows a direct comparison between in vitro bioluminescence experiments and in silico ordinary differential equation models, and will lead to a better quantitative understanding of the factors that affect clock amplitude.
WANs are often over-provisioned to accommodate worst-case operating conditions, with many links typically running at only around 30% capacity. In this paper, we show that in-network congestion ...management can play an important role in increasing network utilization. To mitigate the effects of in-network congestion caused by rapid variations in traffic demand, we propose using high-frequency traffic control (HFTraC) algorithms that exchange real-time flow rate and buffer occupancy information between routers to dynamically coordinate their link-service rates. We show that the design of such dynamic link-service rate policies can be cast as a distributed optimal control problem that allows us to systematically explore an enlarged design space of in-network congestion management algorithms. This also provides a means of quantitatively comparing different controller architectures: we show, perhaps surprisingly, that centralized control is not always better. We implement and evaluate HFTraC in the face of rapidly varying UDP and TCP flows and in combination with AQM algorithms. Using a custom experimental testbed, a Mininet emulator, and a production WAN, we show that HFTraC leads to up to 66% decreases in packet loss rates at high link utilizations as compared to FIFO policies.
Kepler-16: A Transiting Circumbinary Planet Doyle, Laurance R.; Carter, Joshua A.; Fabrycky, Daniel C. ...
Science (American Association for the Advancement of Science),
09/2011, Letnik:
333, Številka:
6049
Journal Article
Recenzirano
Odprti dostop
We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses ...of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20 and 69% as massive as the Sun and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5° of a single plane, suggesting that the planet formed within a circumbinary disk.
System level synthesis Anderson, James; Doyle, John C.; Low, Steven H. ...
Annual reviews in control,
2019, 2019-00-00, Letnik:
47
Journal Article
Recenzirano
Odprti dostop
This article surveys the System Level Synthesis framework, which presents a novel perspective on constrained robust and optimal controller synthesis for linear systems. We show how SLS shifts the ...controller synthesis task from the design of a controller to the design of the entire closed loop system, and highlight the benefits of this approach in terms of scalability and transparency. We emphasize two particular applications of SLS, namely large-scale distributed optimal control and robust control. In the case of distributed control, we show how SLS allows for localized controllers to be computed, extending robust and optimal control methods to large-scale systems under practical and realistic assumptions. In the case of robust control, we show how SLS allows for novel design methodologies that, for the first time, quantify the degradation in performance of a robust controller due to model uncertainty – such transparency is key in allowing robust control methods to interact, in a principled way, with modern techniques from machine learning and statistical inference. Throughout, we emphasize practical and efficient computational solutions, and demonstrate our methods on easy to understand case studies.
In preterm infants, chronic lung disease (CLD) is associated with an increased risk for cerebral palsy (CP). However, systemic postnatal corticosteroid therapy to prevent or treat CLD, although ...effective in improving lung function, may cause CP. The objective of this study was to determine the effect of systemic postnatal corticosteroid treatment on death and CP and to assess any modification of effect arising from risk for CLD.
Randomized, controlled trials of postnatal corticosteroid therapy for prevention or treatment of CLD in preterm infants that reported rates of both mortality and CP were reviewed and their data were synthesized. Twenty studies with data on 1721 randomized infants met eligibility criteria. The relationship between the corticosteroid effect on the combined outcome, death or CP, and the risk for CLD in control groups was analyzed by weighted meta-regression.
Among all infants who were randomized, a significantly higher rate of CP after corticosteroid treatment (typical risk difference RD: 0.05; 95% confidence interval CI: 0.02, 0.08) was partly offset by a nonsignificant reduction in mortality (typical RD: -0.02; 95% CI: -0.06 to 0.02). Consequently, there was no significant effect of corticosteroid treatment on the combined rate of mortality or CP (typical RD: 0.03; 95% CI: -0.01 to 0.08). However, on meta-regression, there was a significant negative relationship between the treatment effect on death or CP and the risk for CLD in control groups. With risks for CLD below 35%, corticosteroid treatment significantly increased the chance of death or CP, whereas with risks for CLD exceeding 65%, it reduced this chance.
The effect of postnatal corticosteroids on the combined outcome of death or CP varies with the level of risk for CLD.
The correlation method from brain imaging has been used to estimate functional connectivity in the human brain. However, brain regions might show very high correlation even when the two regions are ...not directly connected due to the strong interaction of the two regions with common input from a third region. One previously proposed solution to this problem is to use a sparse regularized inverse covariance matrix or precision matrix (SRPM) assuming that the connectivity structure is sparse. This method yields partial correlations to measure strong direct interactions between pairs of regions while simultaneously removing the influence of the rest of the regions, thus identifying regions that are conditionally independent. To test our methods, we first demonstrated conditions under which the SRPM method could indeed find the true physical connection between a pair of nodes for a spring-mass example and an RC circuit example. The recovery of the connectivity structure using the SRPM method can be explained by energy models using the Boltzmann distribution. We then demonstrated the application of the SRPM method for estimating brain connectivity during stage 2 sleep spindles from human electrocorticography (ECoG) recordings using an
electrode array. The ECoG recordings that we analyzed were from a 32-year-old male patient with long-standing pharmaco-resistant left temporal lobe complex partial epilepsy. Sleep spindles were automatically detected using delay differential analysis and then analyzed with SRPM and the Louvain method for community detection. We found spatially localized brain networks within and between neighboring cortical areas during spindles, in contrast to the case when sleep spindles were not present.
Fixing the MRI R2‐iron calibration in liver Doyle, Eamon; Ghugre, Nilesh; Coates, Thomas D. ...
American journal of hematology,
20/May , Letnik:
95, Številka:
5
Journal Article
We present putative global minima for the micro-hydrated sulfite SO32−(H2O)N and chlorate ClO3−(H2O)N systems in the range 3≤N≤15 found using basin-hopping global structure optimization with an ...empirical potential. We present a structural analysis of the hydration of a large number of minimized structures for hydrated sulfite and chlorate clusters in the range 3≤N≤50. We show that sulfite is a significantly stronger net acceptor of hydrogen bonding within water clusters than chlorate, completely suppressing the appearance of hydroxyl groups pointing out from the cluster surface (dangling OH bonds), in low-energy clusters. We also present a qualitative analysis of a highly explored energy landscape in the region of the global minimum of the eight water hydrated sulfite and chlorate systems.
This article is part of the theme issue 'Modern theoretical chemistry'.
The correlation of healthy states with heart rate variability (HRV) using time series analyses is well documented. Whereas these studies note the accepted proximal role of autonomic nervous system ...balance in HRV patterns, the responsible deeper physiological, clinically relevant mechanisms have not been fully explained. Using mathematical tools from control theory, we combine mechanistic models of basic physiology with experimental exercise data from healthy human subjects to explain causal relationships among states of stress vs. health, HR control, and HRV, and more importantly, the physiologic requirements and constraints underlying these relationships. Nonlinear dynamics play an important explanatory role––most fundamentally in the actuator saturations arising from unavoidable tradeoffs in robust homeostasis and metabolic efficiency. These results are grounded in domain-specific mechanisms, tradeoffs, and constraints, but they also illustrate important, universal properties of complex systems. We show that the study of complex biological phenomena like HRV requires a framework which facilitates inclusion of diverse domain specifics (e.g., due to physiology, evolution, and measurement technology) in addition to general theories of efficiency, robustness, feedback, dynamics, and supporting mathematical tools.
This article examines the impact of early- and later-life circumstances on loneliness among people aged 65+ in Ireland.
Data are from the first wave of the Irish Longitudinal Study on Ageing, a ...nationally representative sample of community-dwelling adults aged 50+. The participants (N = 2,645) aged 65+ were included in the analysis. Because of the large number of never married persons in the older Irish population, we first used a multinomial logistic model to examine which childhood circumstances are associated with current marital status. We then estimated multiple regression models for loneliness, in stages conforming to the life course, to examine the extent to which early events are mediated by later events.
Poor childhood socioeconomic status (for men and women) and parental substance abuse (for men) have direct effects on loneliness at older ages.
The results indicate the significance of the childhood environment for understanding loneliness in later life. Future research should examine possible pathways not currently measured that may be responsible for the association of early environment and later-life loneliness and explore the links between childhood and other measures of well-being in old age. The relationship of childhood socioeconomic deprivation and parental substance abuse with adult well-being should be an important consideration in social policy planning.
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