A geometric and structural approach to the analysis and design of biological circuit dynamics: a theory tailored for synthetic biology

Much of the progress in developing our ability to successfully design genetic circuits with predictable dynamics has followed the strategy of molding biological systems to fit into conceptual frameworks used in other disciplines, most notably the engineering sciences. Because biological systems have fundamental differences from systems in these other disciplines, this approach is challenging and the insights obtained from such analyses are often not framed in a biologically-intuitive way. Here, we present a new theoretical framework for analyzing the dynamics of genetic circuits that is tailored towards the unique properties associated with biological systems and experiments. Our framework approximates a complex circuit as a set of simpler circuits, which the system can transition between by saturating its various internal components. These approximations are connected to the intrinsic structure of the system, so this representation allows the analysis of dynamics which emerge solely from the system's structure. Using our framework, we analyze the presence of structural bistability in a leaky autoactivation motif and the presence of structural oscillations in the Repressilator

NGC 1058: Gas motions in an extended, quiescent spiral disk

Researchers investigate in detail the motion of gas in the galaxy NGC 1058 using the very large array (VLA) to map the emission in the 21-cm line. This galaxy is so nearly face-on that the contribution to the line width due to the variation of the rotational velocity across the D-array beam is small compared with the random z-motion of the gas. Researchers confirm results of earlier studies (Lewis 1987, A. and A. Suppl., 63, 515; van der Kruit and Shostak 1984, A. and A., 134, 258) of the galaxy's total neutral hydrogen (HI) and kinematics, including the fact that the rotation curve drops faster than Keplerian at the outer edge of the disk, which is interpreted as a fortuitous twist of the plane of rotation in the outer disk. However, their very high velocity resolution (2.58 km s(exp -1) after Hanning smoothing) coupled with good spatial resolution, allows researchers to measure more accurately the line width, and even to some extent its shape, throughout the disk. One of the most interesting results of this study is the remarkable constancy of the line width in the outer disk. From radius 90 to 210 seconds the Gaussian velocity dispersion (sigma sub nu) of the 21-cm line has a mean value of 5.7 km s(exp -1) (after correcting for the spectral resolution) with a dispersion of less than 0.9 km s(exp -1) (after correcting for the spectral resolution) with a dispersion of less than 0.9 km s(exp -1). Translating this directly into a kinetic temperature (Doppler temperature): T sub Dopp equals 121K (sigma sub mu exp 2/(km s(exp -1) (exp 2) gives 4000 K, with a dispersion of less than 1500 K over the outer disk. This constancy is observed even when comparing the spiral arms versus inter-arm regions, which in the radius range from 100 to 150 seconds the surface density modulates (defined as the ratio N sub peak -N sub trough/N sub peak + N sub trough) from 0.5 to 0.25 in the range 150 to 200 seconds

Development of Charter School Teacher Development Inventory

The aim of the present study was to develop and examine the initial psychometrics of an instrument, the Charter School Teacher Development Inventory (CSTDI), designed to measure the professional learning opportunities available in U.S. charter schools. Items on the CSTDI were derived from a review of relevant literature and were intended to gather information on how frequently U.S. charter schools employ traditional professional development methods and the five areas of more effective professional development (content focus, active learning, collaboration, coherence, and duration). The final form of the CSTDI was sent electronically to 6322 charter school administrators and 2428 returned completed surveys. Exploratory factor analysis performed on a randomly assigned half of the sample (n =1214) suggested that the CSTDI was comprised of five factors: traditional, content, coherence, duration, and active learning/collaboration. Confirmatory factor analysis was performed on the second half of the sample and provided additional support for a five factor structure of the CSTDI. Reliability coefficients for each of the five factors were above .90. This study provides promising support for a five-factor instrument that assesses professional development practices in charter schools. While the CSTDI was developed for use with charter school administrators, further research is warranted to determine if it may be relevant for use with teachers and administrators in both traditional public schools and charter schools

Nonlinear controllers for non-integrable systems: the Acrobot example

Recent developments in the theory of geometric nonlinear control provide powerful methods for controller design for a large class of nonlinear systems. Many systems, however, do not satisfy the restrictive conditions necessary for either full state linearization [6, 5] or input-output linearization with internal stability [2]. In this paper, we present an approach to controller design based on finding a linearizable nonlinear system that well approximates the true system over a desirable region. We outline an engineering procedure for constructing the approximating nonlinear system given the true system. We demonstrate this approach by designing a nonlinear controller for a simple mechanical system patterned after a gymnast performing on a single parallel bar

Biophysical evidence for intrinsic disorder in the C-terminal tails of the epidermal growth factor receptor (EGFR) and HER3 receptor tyrosine kinases

The epidermal growth factor receptor (EGFR)/ErbB family of receptor tyrosine kinases includes oncogenes important in the progression of breast and other cancers, and they are targets for many drug development strategies. Each member of the ErbB family possesses a unique, structurally uncharacterized C-terminal tail that plays an important role in autophosphorylation and signal propagation. To determine whether these C-terminal tails are intrinsically disordered regions, we conducted a battery of biophysical experiments on the EGFR and HER3 tails. Using hydrogen/deuterium exchange mass spectrometry, we measured the conformational dynamics of intracellular half constructs and compared the tails with the ordered kinase domains. The C-terminal tails demonstrate more rapid deuterium exchange behavior when compared with the kinase domains. Next, we expressed and purified EGFR and HER3 tail-only constructs. Results from circular dichroism spectroscopy, size exclusion chromatography with multiangle light scattering, dynamic light scattering, analytical ultracentrifugation, and small angle X-ray scattering each provide evidence that the EGFR and HER3 C-terminal tails are intrinsically disordered with extended, non-globular structure in solution. The intrinsic disorder and extended conformation of these tails may be important for their function by increasing the capture radius and reducing the thermodynamic barriers for binding of downstream signaling proteins

Defining the Costs of an Outbreak of Karnal Bunt of Wheat

In determining the economic impact of a possible outbreak of the quarantinable wheat disease Karnal Bunt, an examination was made of the detailed components of the costs involved. The costs were classified as: (a) Direct costs (yield and quality losses); (b) Reaction costs (export bans, quality down-grading, seed industry costs); and (c) Control costs (quarantine zones, fungicides, spore destruction). The relative importance of each of these cost components is measured for a hypothetical outbreak of Karnal Bunt in the European Union, as a means of ensuring that the policy responses to such an outbreak are appropriate considering the costs involved.disease, quarantine, cost, wheat, Agricultural and Food Policy, Crop Production/Industries,

Productivity and Market Integration in American Communal Dairying, 1830-1875

In our late twentieth century experience, survival of an economy seems critically dependent on well established rights to private property and a return to labor that rewards greater effort. But that need not be so. History provides examples of micro-socialist economies that internally, at least, allow for little private property for participants and a constant return to labor that is independent of effort. Some such economies may even be termed \u27successful,\u27 if success is taken to mean survival over several generations. If these communities survived without conditions that are generally thought to be necessary for success, a question worth asking is how this occurred, for we can then shed some light on what really is necessary for economic survival. Addressing this issue emphasizes the critical role of time, for even if the microsocialist economies that we study here eventually became the merest shadow of their former selves, the fact that they did flourish for so long makes them a valuable counterexample, and hence, a phenomenon in need of explanation. We consider here the dairy industry of the Shakers, which was characterized by intensive efforts to increase productivity, in part through the use of market signals, but efforts that were also limited by the ideological goals of the community. The Shakers were (and are, but since it is the historical Shakers that concern this paper, the past tense will be used) a Christian communal group. Some of their distinctive beliefs included the existence of a male and female Godhead, from which followed sexual equality, and active communication between Believers (a Shaker term for members of the sect) and denizens of the spirit world. Practices of the Society (their official name is the United Society of Believers in Christ\u27s Second Appearing, the second appearing being in the body of their foundress, an illiterate Englishwoman named Ann Lee) included pacifism, celibacy, confession of sins to elders, and joint or communal ownership of the Society\u27s assets. Each Shaker received the same return for his or her labor: room, board, clothing, and the experience of divine proximity in a community of like minded Believers (Stein 1992)

An Innovative Cold-formed Floor System

Optimizing the use of building materials has always been one of the primary goals of engineers. It is a constant challenge to seek innovative methods to build lighter weight structures. Sometimes this is achieved through the development of new building materials, other times it can be accomplished by creating entirely new types of structural systems. Often lightweight structures can be more asthetically pleasing because of their stream-lined appearance. However, in general the motivating factor in building lightweight structures is to reduce the overall cost. One portion of a structure which offers tremendous potential for weight reduction is the floor system. The floor system is one of the heaviest components in typical steel framed buildings. A reduction in the dead load of this component will result in a subsequent reduction in the total weight of the building structural system