Top PDF Application, Computation, and Theory for Synthetic Gene Circuits

Application, Computation, and Theory for Synthetic Gene Circuits

Application, Computation, and Theory for Synthetic Gene Circuits

These methods are known to struggle in cases where the distributions are bimodal, but in some cases using a moment-based inference method can successfully predict an ob- served bimodal experimental data set [96]. In other cases, moment based methods can be used to characterize the causal relationships between different genes [51]. In [78], mo- ment based inference in conjunction with an optimal experiment design technique based on maximizing the expected Fisher information is used to characterize a light inducible synthetic gene circuit. The limitation of moment closure methods is that the equations for the N th order moments usually depend on higher order moments, and so to avoid having an infinite dimensional system of ODE’s, the higher order moments have to be assumed to have some known form. In some case, the higher order moments can be computed from the lower order moments if the distribution is of a known type such as a normal or log-normal distribution [82]. In other cases, the third order cumulants are assumed to be zero [96]. A data-based identification procedure based on moment closure has also been developed, in which the reaction rate parameters are identified from the mean mo- ment equations and the covariance values are plugged in from experimentally measured data [10]. In this way, no prior assumption on the distributions of the chemical species are required. Finally, semidefinite programming can be used to compute upper and lower bounds on the moments of a stochastic differential equation [47]. This approach is more computationally expensive than simple moment closure but provides a theoretical guar- antee that the moment of interest lies within a specific interval.
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Application of Group Theory for Computation Reduction in Microwave Imaging of Human Breast Model at 500 MHz

Application of Group Theory for Computation Reduction in Microwave Imaging of Human Breast Model at 500 MHz

form of all matrices. Computation time to solve Eqs. (22) and (23) is given in [1] for single iteration. In this paper, overall computation time to solve inverse scattering problem is calculated with and without group theory. In order to compute overall simulation time, Eqs. (22) and (23) are solved with the same initial guess about matrix R . Number of iterations is 200 for both. Value of λ is calculated using general concepts given in [20].

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High  Performance  Multi-Party  Computation  for  Binary  Circuits  Based  on  Oblivious  Transfer

High Performance Multi-Party Computation for Binary Circuits Based on Oblivious Transfer

key/MAC for each share value. In [DPSZ12], called the SPDZ protocol hereafter, the authors obtain a more efficient online protocol by replacing the MACs from [BDOZ11] with global MACs which authenticate the shared values a, as opposed to the shares themselves. The authentication is also done with respect to a fixed global MAC key (and not pairwise and data dependent). This method was improved in [DKL + 13], where it is shown how to verify these global MACs without revealing the secret global key. In [DZ13] the authors adapt the technique from [DPSZ12] for the case of small finite fields, in a way which allows one to authenticate multiple field elements at the same time, without requiring multiple MACs. This is performed using a novel application of ideas from coding theory, and results in a reduced overhead for the online phase.
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Modeling, Computation, and Characterization to Accelerate the Development of Synthetic Gene Circuits in Cell-Free Extracts

Modeling, Computation, and Characterization to Accelerate the Development of Synthetic Gene Circuits in Cell-Free Extracts

The small parameter ε in Equation (4.27) is used to capture the effects of large reaction rate constants in chemical kinetics, which lead to fast transient dynamics. These fast dynamics are modeled by the variable z , whose rate of change gets scaled by 1/ε , and hence becomes very large. Being able to apply tools from singular perturbation theory involves bringing the mass action dynamical equations into the above form as a necessary prerequisite. Singular perturbation theory also requires that there exists at least one asymptotically stable equilibrium (isolated from any others that might exist) to which the trajectories of the variable z , for each allowable x , converge. We defer a discussion of the properties of the equilibria for the moment, and focus on finding a set of state variables that allow us to bring the system into the standard form in the first place. To this end, we will discuss why species concentrations are not appropriate to use as a state variables for the purposes of bringing a system into the standard form, and elaborate on a variable transformation which provides a better system of coordinates.
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Engineering of Gene Circuits for Cellular Computation

Engineering of Gene Circuits for Cellular Computation

Information processing in living cells involves integrating multiple inputs, performing computations on these signals, storing information in memory and actuating outputs. These highly complex biological nanocomputers in living cells have the potential to dynamically interrogate and respond to the environment [1,2]. Synthetic biology involves the construction and manipulation of the biological systems from the molecules such as DNA and RNA to the functional cellular level [3,4]. The modeling component of synthetic biology allows the designing of biological circuits and the analysis of its expected behaviour. The experimental component merges models with real systems by providing quantitative data and sets of available biological units that can be used to construct circuits [5,6]. Sufficient progress has been made in the combined use of modeling and experimental methods, which reinforces the idea of using biological databases from different available genomes and engineered the microbes as a technological platform [7]. Integrated and extensible biological design cycles enable engineers/researchers to develop high-level conceptual designs, translate these designs into potential circuit implementations using libraries of well-characterized model/devices, construct the designs in an automated fashion and modulate the resulting constructs for proper operation [8].
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A frame-shifted gene, which rescued its function by non-natural start codons and its application in constructing synthetic gene circuits

A frame-shifted gene, which rescued its function by non-natural start codons and its application in constructing synthetic gene circuits

Results: Here we report that the function of gene circuits is rescued by a frame-shifted gene, which functions by translating from a non-natural start codon. We report a single nucleotide deletion mutation that developed in the λ -repressor cI within a synthetic genetic NOT gate in Escherichia coli during growth and through this mutation, a non-functional synthetic gene circuit became functional. This mutation resulted in a frame-shifted cI, which showed effective functionality among genetic NOT-gates in Escherichia coli with high regulatory ranges (> 300) and Hill coefficient (> 6.5). The cI worked over a large range of relative copy numbers between the frame-shifted gene and its target promoter. These properties make this frame-shifted gene an excellent candidate for building synthetic gene circuits. We hypothesized a new operating mechanism and showed evidence that frame-shifted cI was translated from non-natural start codon. We have engineered and tested a series of NOT gates made from a library of cI genes, each of which starts from a different codon within the first several amino acids of the frame-shifted cI. It is found that one form with start codon ACA, starting from the 3rd codon had similar repression behavior as the whole frame-shifted gene. We demonstrated synthetic genetic NAND and NOR logic-gates with frame-shifted cI. This is the first report of synthetic-gene-circuits made from a frame-shifted gene.
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Expanding the Toolkit for Synthetic Biology: Frameworks for Native like Non natural Gene Circuits

Expanding the Toolkit for Synthetic Biology: Frameworks for Native like Non natural Gene Circuits

Synthetic biology aims to take advantage of biological processes to engineer systems and devices with novel and useful functions. One promising application is the engineering of organisms to produce a wide range of products from fuels to cosmetics to pharmaceuticals. Perhaps the most successful example of the potential of synthetic biology is the story of artemisinin, a potent anti-malarial drug. Researchers engineered yeast to produce artemisinic acid, a precursor of artemisinin, in a practical and scalable way [1]. This method of producing artemisinic acid was used by Sanofi Aventis as part of a fully implemented industrial process to produce the drug semi-synthetically [2]. The process involves the fermentation of artemisinic acid by genetically modified yeast developed by Keasling and Amyris, followed by an efficient synthetic process to convert artemisinic acid to artemisinin. In 2014, sixty tons of artemisinin were produced in this way, supplementing the highly volatile supply which involves the drugs extraction from the leaves of Artemisia annua [2]. While highlighting the promise of synthetic biology as a transformative technology, the artemisinin story is also informative to the areas where research and development are needed in order for synthetic biology to realize its full potential.
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Synthetic Gene Circuits Enable Systems-Level Biosensor Trigger Discovery at the Host-Microbe Interface

Synthetic Gene Circuits Enable Systems-Level Biosensor Trigger Discovery at the Host-Microbe Interface

IMPORTANCE The gut is a largely obscure and inaccessible environment. The use of live, engineered probiotics to detect and respond to disease signals in vivo repre- sents a new frontier in the management of gut diseases. Engineered probiotics have also shown promise as a novel mechanism for drug delivery. However, the design and construction of effective strains that respond to the in vivo environment is hin- dered by our limited understanding of bacterial behavior in the gut. Our work ex- pands the pool of environmentally responsive synthetic circuits for the healthy and diseased gut, providing insight into host-microbe interactions and enabling future development of increasingly complex biosensors. This method also provides a framework for rapid prototyping of engineered systems and for application across bacterial strains and disease models, representing a practical step toward the con- struction of clinically useful synthetic tools.
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Circuits of Labour: A Labour Theory of the iPhone Era

Circuits of Labour: A Labour Theory of the iPhone Era

Abstract: This paper questions the binary of material and immaterial labour in the information era. Instead, we propose a “circuits of labour” model, a holistic framework that helps connect various con- cepts and traditions in the study of labour and ICT (information and communication technology). In- spired by du Gay et al’s “circuit of culture”, we argue conventional frameworks need to be synthesized and updated to reflect fundamental changes and persisting issues of labor in our contemporary era, of which the iPhone is emblematic. On the one hand, our model consists of formal circuits, in which hier- archical domination is imposed by capital over the body of labour. On the other hand, it consists of informal circuits where relationships are defined communally between embodied practices and social and communicative capital. The informal and formal circuits of labour are “short-circuited” by survival labour and ‘playbour’, meaning either circuit may absorb productive energy from the other. This article then uses the case of Foxconn, the world’s largest electronic manufacturer that also produces iPhones, to illustrate the usefulness of the “circuits of labour” model. We finally discuss the broader implications and questions for future research.
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Prototyping Diverse Synthetic Biological Circuits in a Cell Free Transcription Translation System

Prototyping Diverse Synthetic Biological Circuits in a Cell Free Transcription Translation System

Typical studies of membrane proteins rely on proteins produced from cells and solubilized cell membrane using detergents, liposomes, or other membrane-like materials. Although this approach may have advantages in terms of protein yield, it is not well-suited for high-throughput assays since for each construct transformation, cell growth, lysis, membrane solubilization, and purification are involved [75]. Furthermore, these techniques are not suitable for biocircuits prototyping either because the membrane proteins have to be in functional conformations right after expression for the circuits to work without further solubilization or purification processes. As a result, the best way to approach it would be to express membrane proteins in vitro in presence of a membrane-like material. There have been several studies on using detergents, liposomes, or nanodiscs to help solubilize and stabilize membrane proteins generated in cell free system [75-81], but there are limitations of these methods in translating results to circuit prototyping in TX-TL.
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Synthetic Biology: DNA Digital Storage, Computation and the Organic Computer

Synthetic Biology: DNA Digital Storage, Computation and the Organic Computer

BioBrick are the basic unit in the three levels of synthetic biology: parts, devices, and systems. BioBricks can be considered as active elements generating signals (proteins) when stimu[r]

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Abstraction/Representation Theory and the Natural Science of Computation

Abstraction/Representation Theory and the Natural Science of Computation

There is first an issue at the level of the theory: The minimization is approx- imate. Nakagaki et al. (2000) report results from 19 experiments. In two cases no path formed. In three cases the slime mold did not fully contract, occupying all branches. When it did contract to a single route, for the β routes differing by only 2 percent, it chose the shorter route five times and the longer route six times. When it contracted to a single α route, which differ by 20 percent, it always chose the shorter route. So the theory would be better stated that the slime mold contracts to approximately the shortest path, most of the time, for mazes of this size. Hence, to use this system as a computer, we have to be willing to accept a quite large ε, and run the computation several times. Addi- tionally, there is no evidence that the approach can be scaled to large mazes. It requires further scientific experiments to determine the domain of applicability and the degree of approximation. Note also the potentially considerable com- putation required in the form of image processing during the representation stage for detecting the position of the slime mold within the maze. Such addi- tional computation needs to be considered when calculating the computational power of a physical device.
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Transcriptional Regulation and Combinatorial Genetic Logic in Synthetic Bacterial Circuits

Transcriptional Regulation and Combinatorial Genetic Logic in Synthetic Bacterial Circuits

The luciferase operon is ideal for measuring fast responses and large dynamic ranges. No excitation needed for luminometry: the sensitivity is determined by the catalytic efficiency of luciferase, the efficiency (and “dark-current”) of the detection apparatus, and the measurement interval. The luciferase genes are remarkably non-toxic. Full induction of very strong promoters has little effect on the growth of E. coli. It is possible to measure gene expression over five orders of magnitude with this system (Bjarnason et al. 2003). Since the luciferase operon consists of five genes, it is possible for the rate-limiting step in light production to change at different expression levels, resulting in nonlinear response. For population-level measurements, luciferase expression can be detected at less than one enzyme per cell. As with LacZ, specific systems have been developed to maximize sensitivity for single-cell measurements of gene expression (Balaban et al. 2004). Luciferase is an unstable reporter, and highly dependent on growth conditions. It is therefore important to carefully design measurement assays to maximize repeatability. For example, in Chapter 2, growing cells at 25 ° C greatly decreased replicate variation when compared to similar measurements of cells growing at 37 ° C. With a well-designed assay, luciferase is an ideal reporter for measuring gene expression over extreme ranges of response.
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Innovative theory for the compliance computation in rotors

Innovative theory for the compliance computation in rotors

The proposed theory is veried in this section through four examples. The verication is done for both of the stress intensity factor and the compliance. In spite of the classical fracture mechanics in which the parameters are empirical, the proposed theory is exact. The proposed stress intensity factor is compared with the results in the literature in Examples 1 and 2. Example 1: The stress intensity factor is dened by the ASTM special committee E-399 for bend specimen, BSTP (see Figure 7) [31] as:

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Section 1 - Number Theory and Computation

Section 1 - Number Theory and Computation

When rounding off a number to the specified number of decimal places, we look at the digit value that follows, reading from left to right. If the digit value that follows is 5 or more[r]

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Constant-Overhead  Secure  Computation  of  Boolean  Circuits  using  Preprocessing

Constant-Overhead Secure Computation of Boolean Circuits using Preprocessing

Abstract. We present a protocol for securely computing a Boolean cir- cuit C in presence of a dishonest and malicious majority. The protocol is unconditionally secure, assuming a preprocessing functionality that is not given the inputs. For a large number of players the work for each player is the same as computing the circuit in the clear, up to a constant factor. Our protocol is the first to obtain these properties for Boolean circuits. On the technical side, we develop new homomorphic authenti- cation schemes based on asymptotically good codes with an additional multiplication property. We also show a new algorithm for verifying the product of Boolean matrices in quadratic time with exponentially small error probability, where previous methods only achieved constant error.
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An Introduction to the Theory of Computation   Eitan Gurari pdf

An Introduction to the Theory of Computation Eitan Gurari pdf

The pushdown transducer enters state q 0 whenever the portion of the input read so far contains the same number of a's and b's. The pushdown transducer enters state q a whenever the portion of the input read so far contains more a's than b's. Similarly, the pushdown transducer enters state q b whenever the portion of the input read so far contains more b's than a's. The pushdown store is used for recording the difference between the number of a's and the number of b's, at any given instant of a computation. On input aabbba the pushdown transducer M has only one computation. M starts the computation by moving from state q 0 to state q a , while reading a, writing c, and pushing a into the pushdown store. In the second move M reads a, writes c, pushes a into the pushdown store, and goes back to q a . In the third and fourth moves M reads b, pops a from the pushdown store, and goes back to state q a . In the fifth move M goes to state q 0 without reading, writing, or changing the content of the pushdown store. In the sixth move M reads b, pushes b into the pushdown store, and moves to state q b . In its seventh move M reads a, pops b from the pushdown store, writes c, and goes back to q b . The computation terminates in an accepting configuration by a move from state q b to state q 0 in which no input is read, no output is written, and no change is made in the content of the pushdown store.
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Essays on the Application and Computation of Real Options

Essays on the Application and Computation of Real Options

In certain cases however, it is natural to view the agent as having not only this type of discrete control, but also one or more continuous controls that may take on one of an infinite number of values. An excellent example of this class of hybrid control models is the application considered in the seminal paper of Brennan and Schwartz [1985]. They analyze the case of optimal resource extraction in the form of a firm operating a mine under an uncertain output price. The firm has a discrete control over the status of operations, whether the mine is open or closed, in addition to continuous control in the rate of extrac- tion. This type of combined optimal switching and stochastic control model for natural resource management was extended by Lumley and Zervos [2001]. Other uses for such hybrid controls include the behavior of firms in imperfect markets. Chapter 2 examines the case of investments in brownfield remediation and redevelopment projects. During the development phase the firm has the ability to adjust the sale price through a continuous stochastic control but also holds a discrete control representing the options to suspend or abandon the project.
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Gene detection with synthetic oligonucleotide sequences

Gene detection with synthetic oligonucleotide sequences

Several groups have developed alternative strategies for isolating mammalian genes from genomic DNA which involve using a retroviral construct to trap exons by RNA splicing (Reilly et al, 1990; Buckler et al, 1991; Auch and Reth, 1990; Duyk et al, 1990). The procedure involves the "shotgun" cloning of fragments of genomic DNA or cloned genomic DNA into a specially constructed retroviral vector. The cloning site is situated either between a viral donor and acceptor site from the HIV-1 tat gene (Buckler et al, 1991), or between a donor and acceptor site from the rat preproinsulin gene (Auch and Reth, 1990). Alternatively the clone is inserted downstream of a human beta globin donor site (Duyk et al, 1990). The cloned fragments are then transfected into COS cells where the retroviral DNA is transcribed. Recombinant molecules that contain a functional splice acceptor and donor site, cloned in the correct orientation, may undergo RNA splicing. RNA is then harvested from the cytoplasm and reverse transcribed into cDNA. Using PGR primers specific for the sequences flanking the retroviral donor and acceptor sites, the "trapped" exons are then amplified. The amplified "trapped" exons can then be detected on an agarose gel and be cloned into a sequencing vector (such as Bluescript) to create an "exon library". "Trapped" exons can then be sequenced.
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An advanced synthetic eddy method for the computation of aerofoil-turbulence interaction noise

An advanced synthetic eddy method for the computation of aerofoil-turbulence interaction noise

The generation of synthetic turbulent flows is currently one of the chal- lenging issues in computational aeroacoustics (CAA). It has a significant impact on the simulation of important engineering problems such as aerofoil- turbulence interaction noise that is related to turbofan engines, open rotors, wind turbines, helicopters, etc. There are a few crucial properties that a syn- thetic turbulence has to satisfy/offer in order to achieve a successful CAA simulation: 1) divergence-free condition, 2) synchronised convection with the mean flow, 3) statistical characteristics of realistic turbulence and 4) gen- uinely three-dimensional capabilities. Failure to meet all these criteria would result in either spurious noise that contaminates the far-field acoustic data or incorrect source mechanisms at the near field. In addition, the generation of synthetic turbulence should be numerically efficient not to overload the entire simulation.
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