Model-guided design of ligand-regulated RNAi for programmable control of gene expression

Progress in constructing biological networks will rely on the development of more advanced components that can be predictably modified to yield optimal system performance. We have engineered an RNA-based platform, which we call an shRNA switch, that provides for integrated ligand control of RNA interference (RNAi) by modular coupling of an aptamer, competing strand, and small hairpin (sh) RNA stem into a single component that links ligand concentration and target gene expression levels. A combined experimental and mathematical modelling approach identified multiple tuning strategies and moves towards a predictable framework for the forward design of shRNA switches. The utility of our platform is highlighted by the demonstration of fine-tuning, multi-input control, and model-guided design of shRNA switches with an optimized dynamic range. Thus, shRNA switches can serve as an advanced component for the construction of complex biological systems and offer a controlled means of activating RNAi in disease therapeutics

Synthetic control of a fitness tradeoff in yeast nitrogen metabolism

Background: Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology. Results: Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae. We found that noise in the expression of a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth in low nitrogen environments and stress resistance in high ammonia environments. We implemented synthetic control of an endogenous Gdh1p regulatory network to construct an engineered strain in which the fitness of the population was tunable in response to an exogenously-added small molecule across a range of ammonia environments. Conclusion: The ability to tune fitness and biological tradeoffs will be important components of future efforts to engineer microbial communities

Analysis of SMA Hybrid Composite Structures in MSC.Nastran and ABAQUS

A thermoelastic constitutive model for shape memory alloy (SMA) actuators and SMA hybrid composite (SMAHC) structures was recently implemented in the commercial finite element codes MSC.Nastran and ABAQUS. The model may be easily implemented in any code that has the capability for analysis of laminated composite structures with temperature dependent material properties. The model is also relatively easy to use and requires input of only fundamental engineering properties. A brief description of the model is presented, followed by discussion of implementation and usage in the commercial codes. Results are presented from static and dynamic analysis of SMAHC beams of two types; a beam clamped at each end and a cantilever beam. Nonlinear static (post-buckling) and random response analyses are demonstrated for the first specimen. Static deflection (shape) control is demonstrated for the cantilever beam. Approaches for modeling SMAHC material systems with embedded SMA in ribbon and small round wire product forms are demonstrated and compared. The results from the commercial codes are compared to those from a research code as validation of the commercial implementations; excellent correlation is achieved in all cases

Pioneer Venus polarimetry and haze optical thickness

The Pioneer Venus mission provided us with high-resolution measurements at four wavelengths of the linear polarization of sunlight reflected by the Venus atmosphere. These measurements span the complete phase angle range and cover a period of more than a decade. A first analysis of these data by Kawabata et al. confirmed earlier suggestions of a haze layer above and partially mixed with the cloud layer. They found that the haze exhibits large spatial and temporal variations. The haze optical thickness at a wavelength of 365 nm was about 0.06 at low latitudes, but approximately 0.8 at latitudes from 55 deg poleward. Differences between morning and evening terminator have also been reported by the same authors. Using an existing cloud/haze model of Venus, we study the relationship between the haze optical thickness and the degree of linear polarization. Variations over the visible disk and phase angle dependence are investigated. For that purpose, exact multiple scattering computations are compared with Pioneer Venus measurements. To get an impression of the variations over the visible disk, we have first studied scans of the polarization parallel to the intensity equator. After investigating a small subset of the available data we have the following results. Adopting the haze particle characteristics given by Kawabata et al., we find a thickening of the haze at increasing latitudes. Further, we see a difference in haze optical thickness between the northern and southern hemispheres that is of the same order of magnitude as the longitudinal variation of haze thickness along a scan line. These effects are most pronounced at a wavelength of 935 nm. We must emphasize the tentative nature of the results, because there is still an enormous amount of data to be analyzed. We intend to combine further polarimetric research of Venus with constraints on the haze parameters imposed by physical and chemical processes in the atmosphere

Configurational temperature control for atomic and molecular systems

A new configurational temperature thermostat suitable for molecules with holonomic constraints is derived. This thermostat has a simple set of motion equations, can generate the canonical ensemble in both position and momentum space, acts homogeneously through the spatial coordinates, and does not intrinsically violate the constraints. Our new configurational thermostat is closely related to the kinetic temperature Nosé-Hoover thermostat with feedback coupled to the position variables via a term proportional to the net molecular force. We validate the thermostat by comparing equilibrium static and dynamic quantities for a fluid of n-decane molecules under configurational and kinetic temperature control. Practical aspects concerning the implementation of the new thermostat in a molecular dynamics code and the potential applications are discussed

Civil airports from a landscape perspective: A multi-scale approach with implications for reducing bird strikes

Collisions between birds and aircraft are a global problem that jeopardizes human safety and causes economic losses. Although landscape features have been suggested as one of a number of factors contributing to bird strikes, no evidence exists to support this suggestion. We investigated the effects of landscape structure on the adverse effect (AE) bird strike rate at 98 civil airports in the United States. The number of reported AE bird strikes was standardized by air carrier movements between 2009 and 2015. Land use structure and composition were quantified within 3, 8, and 13 km radii extents from airports. We predicted large amounts and close arrangements of aquatic habitat, open space, and high landscape diversity would positively influence the AE strike rate based on the habitat requirements of many species hazardous to aviation. The rate of AE bird strikes was positively influenced by large areas and close proximity of wetlands, water, and cultivated crops at the 8- and 13- km extents. Within 3 km of an airport, increasing landscape diversity and the amount of crop area increased the strike rate. We conclude that landscape structure and composition are predictors of the AE bird strike rate at multiple spatial scales. Our results can be used to promote collaborative management among wildlife professionals, airport planners, and landowners near airports to create an environment with a lower probability of an AE bird strike. Specific priorities are to minimize the area of crops, especially corn, and increase the distances between patches of open water

Mass production of volume phase holographic gratings for the VIRUS spectrograph array

The Visible Integral-field Replicable Unit Spectrograph (VIRUS) is a baseline array of 150 copies of a simple, fiber-fed integral field spectrograph that will be deployed on the Hobby-Eberly Telescope (HET). VIRUS is the first optical astronomical instrument to be replicated on an industrial scale, and represents a relatively inexpensive solution for carrying out large-area spectroscopic surveys, such as the HET Dark Energy Experiment (HETDEX). Each spectrograph contains a volume phase holographic (VPH) grating with a 138 mm diameter clear aperture as its dispersing element. The instrument utilizes the grating in first-order for 350-550 nm. Including witness samples, a suite of 170 VPH gratings has been mass produced for VIRUS. Here, we present the design of the VIRUS VPH gratings and a discussion of their mass production. We additionally present the design and functionality of a custom apparatus that has been used to rapidly test the first-order diffraction efficiency of the gratings for various discrete wavelengths within the VIRUS spectral range. This device has been used to perform both in-situ tests to monitor the effects of adjustments to the production prescription as well as to carry out the final acceptance tests of the gratings' diffraction efficiency. Finally, we present the as-built performance results for the entire suite of VPH gratings.Comment: 16 pages, 11 figures, 2 tables. To be published in Proc. SPIE, 2014, "Advances in Optical and Mechanical Technologies for Telescopes and Instrumentation", 9151-53. The work presented in this article follows from arXiv:1207:448