Reverse Engineering of Biological Complexity Csete, Marie E.; Doyle, John C.
Science (American Association for the Advancement of Science),
03/2002, Letnik:
295, Številka:
5560
Journal Article
Recenzirano
Advanced technologies and biology have extremely different physical implementations, but they are far more alike in systems-level organization than is widely appreciated. Convergent evolution in both ...domains produces modular architectures that are composed of elaborate hierarchies of protocols and layers of feedback regulation, are driven by demand for robustness to uncertain environments, and use often imprecise components. This complexity may be largely hidden in idealized laboratory settings and in normal operation, becoming conspicuous only when contributing to rare cascading failures. These puzzling and paradoxical features are neither accidental nor artificial, but derive from a deep and necessary interplay between complexity and robustness, modularity, feedback, and fragility. This review describes insights from engineering theory and practice that can shed some light on biological complexity.
Fire in the Earth System Bowman, David M.J.S; Balch, Jennifer K; Artaxo, Paulo ...
Science (American Association for the Advancement of Science),
04/2009, Letnik:
324, Številka:
5926
Journal Article
Recenzirano
Fire is a worldwide phenomenon that appears in the geological record soon after the appearance of terrestrial plants. Fire influences global ecosystem patterns and processes, including vegetation ...distribution and structure, the carbon cycle, and climate. Although humans and fire have always coexisted, our capacity to manage fire remains imperfect and may become more difficult in the future as climate change alters fire regimes. This risk is difficult to assess, however, because fires are still poorly represented in global models. Here, we discuss some of the most important issues involved in developing a better understanding of the role of fire in the Earth system.
Network protocols in layered architectures have historically been obtained on an ad hoc basis, and many of the recent cross-layer designs are also conducted through piecemeal approaches. Network ...protocol stacks may instead be holistically analyzed and systematically designed as distributed solutions to some global optimization problems. This paper presents a survey of the recent efforts towards a systematic understanding of layering as optimization decomposition, where the overall communication network is modeled by a generalized network utility maximization problem, each layer corresponds to a decomposed subproblem, and the interfaces among layers are quantified as functions of the optimization variables coordinating the subproblems. There can be many alternative decompositions, leading to a choice of different layering architectures. This paper surveys the current status of horizontal decomposition into distributed computation, and vertical decomposition into functional modules such as congestion control, routing, scheduling, random access, power control, and channel coding. Key messages and methods arising from many recent works are summarized, and open issues discussed. Through case studies, it is illustrated how layering as Optimization Decomposition provides a common language to think about modularization in the face of complex, networked interactions, a unifying, top-down approach to design protocol stacks, and a mathematical theory of network architectures
There is a continuing rise in the occurrence of multidrug-resistant bacterial infections. Antibiotic resistance to currently available antibiotics has become a global health issue leading to an ...urgent need for alternative antibacterial strategies. There has been a renewed interest in the development of antibacterial agents from natural sources, and trans-cinnamaldehyde is an example of a naturally occurring compound that has received significant attention in recent years. Trans-Cinnamaldehyde has been shown to possess substantial antimicrobial activity, as well as an array of other medicinal properties, and represents an intriguing hit compound from which a number of derivatives have been developed. In some cases, these derivatives have been shown to possess improved activity, not only compared to trans-cinnamaldehyde but also to commonly used antibiotics. Therefore, understanding the antibacterial mechanisms of action that these compounds elicit is imperative in order to facilitate their development and the development of new antibacterial agents that could exploit similar mechanistic approaches. The purpose of this review is to provide an overview of current knowledge on the antibacterial activity and mechanisms of action of cinnamaldehyde and its derivatives, and to highlight significant contributions made in this research area. It is hoped that the findings presented in this work will aid the future development of new antibacterial agents.
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The "Robust Yet Fragile" Nature of the Internet Doyle, John C.; David L. Alderson; Lun Li ...
Proceedings of the National Academy of Sciences - PNAS,
10/2005, Letnik:
102, Številka:
41
Journal Article
Recenzirano
Odprti dostop
The search for unifying properties of complex networks is popular, challenging, and important. For modeling approaches that focus on robustness and fragility as unifying concepts, the Internet is an ...especially attractive case study, mainly because its applications are ubiquitous and pervasive, and widely available expositions exist at every level of detail. Nevertheless, alternative approaches to modeling the Internet often make extremely different assumptions and derive opposite conclusions about fundamental properties of one and the same system. Fortunately, a detailed understanding of Internet technology combined with a unique ability to measure the network means that these differences can be understood thoroughly and resolved unambiguously. This article aims to make recent results of this process accessible beyond Internet specialists to the broader scientific community and to clarify several sources of basic methodological differences that are relevant beyond either the Internet or the two specific approaches focused on here (i.e., scale-free networks and highly optimized tolerance networks).
Purpose
CPMG spin echo acquisitions are attractive for diagnosing and monitoring liver iron concentration in iron overload disorders due to their time efficiency and potential to reveal unique ...information about tissue iron distribution. Clinical adoption remains low due to the insensitivity of CPMG‐based R2 estimates to liver iron concentration (LIC) when common fitting techniques are applied. In this work, we demonstrate that the inclusion of a proton density estimator (PDE) derived from the CPMG acquisition increase the sensitivity of CPMG R2 estimates to LIC in both simulated and in‐vivo human data.
Theory and Methods
CPMG R2 acquisitions from 50 clinically indicated MRI studies in patients with iron overload were analyzed with and without PDE constraints. Liver regions of interest were fit to monoexpontial and nonexponential signal decay equations. LIC by R2∗ served as the reference standard. The observed calibration between CPMG R2 values and LIC were compared to results predicted from a previously validated Monte Carlo model.
Results
The sensitivity of CPMG‐derived R2 triples when a proton density constraint is applied. When compared with R2∗‐LIC estimates, both monoexponential and nonexponential models were unbiased but demonstrated broad 95% confidence intervals particularly for LIC values below 12 mg/g. Absolute error did not increase with LIC.
Conclusion
A proton density constraint can increase the sensitivity of CPMG‐based models to iron. CPMG acquisitions are time‐efficient and could potentially improve the dynamic range of single spin echo techniques as well as providing insight into tissue iron distribution.
Kepler-47: A Transiting Circumbinary Multiplanet System Orosz, Jerome A.; Welsh, William F.; Carter, Joshua A. ...
Science (American Association for the Advancement of Science),
09/2012, Letnik:
337, Številka:
6101
Journal Article
Recenzirano
Odprti dostop
We report the detection of Kepler-47, a system consisting of two planets orbiting around an eclipsing pair of stars. The inner and outer planets have radii 3.0 and 4.6 times that of Earth, ...respectively. The binary star consists of a Sun-like star and a companion roughly one-third its size, orbiting each other every 7.45 days. With an orbital period of 49.5 days, 18 transits of the inner planet have been observed, allowing a detailed characterization of its orbit and those of the stars. The outer planet's orbital period is 303.2 days, and although the planet is not Earth-like, it resides within the classical "habitable zone," where liquid water could exist on an Earth-like planet. With its two known planets, Kepler-47 establishes that close binary stars can host complete planetary systems.
Animals move smoothly and reliably in unpredictable environments. Models of sensorimotor control, drawing on control theory, have assumed that sensory information from the environment leads to ...actions, which then act back on the environment, creating a single, unidirectional perception-action loop. However, the sensorimotor loop contains internal delays in sensory and motor pathways, which can lead to unstable control. We show here that these delays can be compensated by internal feedback signals that flow backward, from motor toward sensory areas. This internal feedback is ubiquitous in neural sensorimotor systems, and we show how internal feedback compensates internal delays. This is accomplished by filtering out self-generated and other predictable changes so that unpredicted, actionable information can be rapidly transmitted toward action by the fastest components, effectively compressing the sensory input to more efficiently use feedforward pathways: Tracts of fast, giant neurons necessarily convey less accurate signals than tracts with many smaller neurons, but they are crucial for fast and accurate behavior. We use a mathematically tractable control model to show that internal feedback has an indispensable role in achieving state estimation, localization of function (how different parts of the cortex control different parts of the body), and attention, all of which are crucial for effective sensorimotor control. This control model can explain anatomical, physiological, and behavioral observations, including motor signals in the visual cortex, heterogeneous kinetics of sensory receptors, and the presence of giant cells in the cortex of humans as well as internal feedback patterns and unexplained heterogeneity in neural systems.
In this paper, we study fundamental limitations of disturbance attenuation of feedback systems, under the assumption that the controller has a finite horizon preview of the disturbance. In contrast ...with prior work, we extend Bode's integral equation for the case where the preview is made available to the controller via a general, finite capacity, communication system. Under asymptotic stationarity assumptions, our results show that the new fundamental limitation differs from Bode's only by a constant, which quantifies the information rate through the communication system. In the absence of asymptotic stationarity, we derive a universal lower bound which uses Shannon's entropy rate as a measure of performance. By means of a case-study, we show that our main bounds may be achieved
As we begin to design increasingly complex synthetic biomolecular systems, it is essential to develop rational design methodologies that yield predictable circuit performance. Here we apply ...mathematical tools from the theory of control and dynamical systems to yield practical insights into the architecture and function of a particular class of biological feedback circuit. Specifically, we show that it is possible to analytically characterize both the operating regime and performance tradeoffs of an antithetic integral feedback circuit architecture. Furthermore, we demonstrate how these principles can be applied to inform the design process of a particular synthetic feedback circuit.
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