A condition-specific codon optimization approach for improved heterologous gene expression in Saccharomyces cerevisiae

All authors are with the Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St. Stop C0400, Austin, TX 78712, USA -- Hal S. Alper is with the Institute for Cellular and Molecular Biology, The University of Texas at Austin, 2500 Speedway Avenue, Austin, TX 78712, USA -- Amanda M. Lanza Current Address: Bristol-Myers Squibb, Biologics Development, 35 South Street, Hopkinton, MA 01748, USABackground: Heterologous gene expression is an important tool for synthetic biology that enables metabolic engineering and the production of non-natural biologics in a variety of host organisms. The translational efficiency of heterologous genes can often be improved by optimizing synonymous codon usage to better match the host organism. However, traditional approaches for optimization neglect to take into account many factors known to influence synonymous codon distributions. Results: Here we define an alternative approach for codon optimization that utilizes systems level information and codon context for the condition under which heterologous genes are being expressed. Furthermore, we utilize a probabilistic algorithm to generate multiple variants of a given gene. We demonstrate improved translational efficiency using this condition-specific codon optimization approach with two heterologous genes, the fluorescent protein-encoding eGFP and the catechol 1,2-dioxygenase gene CatA, expressed in S. cerevisiae. For the latter case, optimization for stationary phase production resulted in nearly 2.9-fold improvements over commercial gene optimization algorithms. Conclusions: Codon optimization is now often a standard tool for protein expression, and while a variety of tools and approaches have been developed, they do not guarantee improved performance for all hosts of applications. Here, we suggest an alternative method for condition-specific codon optimization and demonstrate its utility in Saccharomyces cerevisiae as a proof of concept. However, this technique should be applicable to any organism for which gene expression data can be generated and is thus of potential interest for a variety of applications in metabolic and cellular engineering.Chemical EngineeringInstitute for Cellular and Molecular [email protected]

Underlap counterdoping as an efficient means to suppress lateral leakage in the electron\u2013hole bilayer tunnel FET

The electron\u2013hole bilayer tunnel (EHBTFET)\uf0a0has been proposed as a density of states (DOS) switch capable of achieving a subthreshold slope lower than 60mV/decade at room temperature; however, one of the main challenges is the control of the lateral band-to-band tunneling (BTBT) leakage in the OFF state. In this work, we show that by using oppositely doped underlap regions; the unwanted penetration of the wavefunction into the underlap region at low gate biases is prevented; thereby drastically reducing the lateral BTBT leakage without any penalty on the ON current. The method is verified using a full-quantum 2D Schr\uf6dinger\u2013Poisson solver under the effective mass approximation. For a channel thickness of 10 nm, an In0.53Ga0.47As EHBTFET with counterdoping can exhibit an ON-current up to 20 mA mm and an average subthreshold swing (SS) of about 30 mV/dec. Compared to previous lateral leakage suppression solutions, the proposed method can be fabricated using template-assisted selective epitaxy

A Semantic Grid Oriented to E-Tourism

With increasing complexity of tourism business models and tasks, there is a clear need of the next generation e-Tourism infrastructure to support flexible automation, integration, computation, storage, and collaboration. Currently several enabling technologies such as semantic Web, Web service, agent and grid computing have been applied in the different e-Tourism applications, however there is no a unified framework to be able to integrate all of them. So this paper presents a promising e-Tourism framework based on emerging semantic grid, in which a number of key design issues are discussed including architecture, ontologies structure, semantic reconciliation, service and resource discovery, role based authorization and intelligent agent. The paper finally provides the implementation of the framework.Comment: 12 PAGES, 7 Figure

The dependability of students\u27 ratings of preceptors

No abstract provided

Geometric invariant theory of syzygies, with applications to moduli spaces

We define syzygy points of projective schemes, and introduce a program of studying their GIT stability. Then we describe two cases where we have managed to make some progress in this program, that of polarized K3 surfaces of odd genus, and of genus six canonical curves. Applications of our results include effectivity statements for divisor classes on the moduli space of odd genus K3 surfaces, and a new construction in the Hassett-Keel program for the moduli space of genus six curves.Comment: v1: 23 pages, submitted to the Proceedings of the Abel Symposium 2017, v2: final version, corrects a sign error and resulting divisor class calculations on the moduli space of K3 surfaces in Section 5, other minor changes, In: Christophersen J., Ranestad K. (eds) Geometry of Moduli. Abelsymposium 2017. Abel Symposia, vol 14. Springer, Cha

Higher-Order QCD Corrections to Inclusive Particle Production in p anti-p Collisions

Inclusive single-particle production cross sections have been calculated including higher-order QCD corrections. Transverse-momentum and rapidity distributions are presented and the scale dependence is studied. The results are compared with experimental data from the CERN S(p anti-p)S Collider and the Fermilab Tevatron.Comment: 28 pages, [12 uuencoded PS figures, 3 available under request]. Preprint DESY 92-13