Rational Design and Optimization of Fed-Batch and Continuous Fermentations

2007 ◽  
pp. 43-64
Author(s):  
Wenhui Zhang ◽  
Mehmet Inan ◽  
Michael M. Meagher
2014 ◽  
Vol 1070-1072 ◽  
pp. 357-360
Author(s):  
Dao Xiang Shen ◽  
Yao Li Zhang ◽  
Qi Xun Guo

A travelling wave reactor (TWR) is an advanced nuclear reactor which is capable of running for decades given only depleted uranium fuel, it is considered one of the most promising solutions for nonproliferation. A preliminary core design was proposed in this paper. The calculation was performed by Monte Carlo method. The burning mechanism of the reactor core design was studied. Optimization on the ignition zone was performed to reduce the amount of enriched uranium initially deployed. The results showed that the preliminary core design was feasible. The optimization analysis showed that the amount of enriched uranium could be reduced under rational design.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Debadrita Paria ◽  
Chi Zhang ◽  
Ishan Barman

Abstract In biology, sensing is a major driver of discovery. A principal challenge is to create a palette of probes that offer near single-molecule sensitivity and simultaneously enable multiplexed sensing and imaging in the “tissue-transparent” near-infrared region. Surface-enhanced Raman scattering and metal-enhanced fluorescence have shown substantial promise in addressing this need. Here, we theorize a rational design and optimization strategy to generate nanostructured probes that combine distinct plasmonic materials sandwiching a dielectric layer in a multilayer core shell configuration. The lower energy resonance peak in this multi-resonant construct is found to be highly tunable from visible to the near-IR region. Such a configuration also allows substantially higher near-field enhancement, compared to a classical core-shell nanoparticle that possesses a single metallic shell, by exploiting the differential coupling between the two core-shell interfaces. Combining such structures in a dimer configuration, which remains largely unexplored at this time, offers significant opportunities not only for near-field enhancement but also for multiplexed sensing via the (otherwise unavailable) higher order resonance modes. Together, these theoretical calculations open the door for employing such hybrid multi-layered structures, which combine facile spectral tunability with ultrahigh sensitivity, for biomolecular sensing.


2011 ◽  
Vol 29 (6) ◽  
pp. 869-878 ◽  
Author(s):  
Tiago Vicente ◽  
José P.B. Mota ◽  
Cristina Peixoto ◽  
Paula M. Alves ◽  
Manuel J.T. Carrondo

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Li Chen ◽  
Wen-Tao Hou ◽  
Tao Fan ◽  
Banghui Liu ◽  
Ting Pan ◽  
...  

ABSTRACT The wall teichoic acid (WTA) is a major cell wall component of Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), a common cause of fatal clinical infections in humans. Thus, the indispensable ABC transporter TarGH, which flips WTA from cytoplasm to extracellular space, becomes a promising target of anti-MRSA drugs. Here, we report the 3.9-Å cryo-electron microscopy (cryo-EM) structure of a 50% sequence-identical homolog of TarGH from Alicyclobacillus herbarius at an ATP-free and inward-facing conformation. Structural analysis combined with activity assays enables us to clearly decode the binding site and inhibitory mechanism of the anti-MRSA inhibitor Targocil, which targets TarGH. Moreover, we propose a “crankshaft conrod” mechanism utilized by TarGH, which can be applied to similar ABC transporters that translocate a rather big substrate through relatively subtle conformational changes. These findings provide a structural basis for the rational design and optimization of antibiotics against MRSA. IMPORTANCE The wall teichoic acid (WTA) is a major component of cell wall and a pathogenic factor in methicillin-resistant Staphylococcus aureus (MRSA). The ABC transporter TarGH is indispensable for flipping WTA precursor from cytoplasm to the extracellular space, thus making it a promising drug target for anti-MRSA agents. The 3.9-Å cryo-EM structure of a TarGH homolog helps us to decode the binding site and inhibitory mechanism of a recently reported inhibitor, Targocil, and provides a structural platform for rational design and optimization of potential antibiotics. Moreover, we propose a “crankshaft conrod” mechanism to explain how a big substrate is translocated through subtle conformational changes of type II exporters. These findings advance our understanding of anti-MRSA drug design and ABC transporters.


1989 ◽  
Vol 172 ◽  
Author(s):  
Alan J. Hurd

Rational design and optimization for the next generation of fiber optics requires fundamental knowledge of the processes at each step of production [1], not the least of which is the formation and deposition of the glass precursor particles. Currently, gas-phase synthesis dominates the industry, owing, in part, to the high purity possible for gaseous reagents. However, the production engineer has relatively little control over the microstructure of the boule from which the fiber is drawn because many complex mechanisms take part in the growth and thermophoretic deposition of the precursors. Although it is desirable, for example, to obtain a porous boule in order to facilitate the removal of deleterious hydroxyls, connected porosity is by no means guaranteed. The successful attainment of high porosity depends on a number of variables such as the size distribution [2], internal structure, shape distribution, viscosity, and surface tension of the particles at the instant of deposition.


2019 ◽  
Author(s):  
Milenko Tokic ◽  
Ljubisa Miskovic ◽  
Vassily Hatzimanikatis

AbstractA high tolerance ofPseudomonas putidato toxic compounds and its ability to grow on a wide variety of substrates makes it a promising candidate for the industrial production of biofuels and biochemicals. Engineering this organism for improved performances and predicting metabolic responses upon genetic perturbations requires reliable descriptions of its metabolism in the form of stoichiometric and kinetic models. In this work, we developed large-scale kinetic models ofP. putidato predict the metabolic phenotypes and design metabolic engineering interventions for the production of biochemicals. The developed kinetic models contain 775 reactions and 245 metabolites. We started by a gap-filling and thermodynamic curation of iJN1411, the genome-scale model ofP. putidaKT2440. We then applied the redGEM and lumpGEM algorithms to reduce the curated iJN1411 model systematically, and we created three core stoichiometric models of different complexity that describe the central carbon metabolism ofP. putida. Using the medium complexity core model as a scaffold, we employed the ORACLE framework to generate populations of large-scale kinetic models for two studies. In the first study, the developed kinetic models successfully captured the experimentally observed metabolic responses to several single-gene knockouts of a wild-type strain ofP. putidaKT2440 growing on glucose. In the second study, we used the developed models to propose metabolic engineering interventions for improved robustness of this organism to the stress condition of increased ATP demand. Overall, we demonstrated the potential and predictive capabilities of developed kinetic models that allow for rational design and optimization of recombinantP. putidastrains for improved production of biofuels and biochemicals.


2020 ◽  
Author(s):  
Mickaël Mateos ◽  
Kenneth D. Harris ◽  
Benoit Limoges ◽  
Véronique Balland

On account of their low-cost, earth abundance, eco-sustainability, and high theoretical charge storage capacity, MnO<sub>2</sub> cathodes have attracted a renewed interest in the development of rechargeable aqueous batteries. However, they currently suffer from limited gravimetric capacities when operating under the preferred mild aqueous conditions, which leads to lower performance as compared to similar devices operating in strongly acidic or basic conditions. Here, we demonstrate how to overcome this limitation by combining a well-defined 3D nanostructured conductive electrode, which ensures an efficient reversible MnO<sub>2</sub>-to-Mn<sup>2+</sup> conversion reaction, with a mild acid buffered electrolyte (pH 5). A reversible gravimetric capacity of 560 mA·h·g<sup>-1</sup> (close to the maximal theoretical capacity of 574 mA·h·g<sup>-1</sup> estimated from the MnO<sub>2</sub> average oxidation state of 3.86) was obtained over rates ranging from 1 to 10 A·g<sup>-1</sup>. The rate capability was also remarkable, demonstrating a capacity retention of 435 mA·h·g<sup>-1</sup> at a rate of 110 A·g<sup>-1</sup>. These good performances have been attributed to optimal regulation of the mass transport and electronic transfer between the three process actors, <i>i.e.</i> the 3D conductive scaffold, the MnO<sub>2</sub> active material filling it, and the soluble species involved in the reversible conversion reaction. Additionally, the high reversibility and cycling stability of this conversion reaction is demonstrated over 900 cycles with a Coulombic efficiency > 99.4 % at a rate of 44 A·g<sup>-1</sup>. Besides these good performances, also demonstrated in a Zn/MnO<sub>2</sub> cell configuration, we discuss the key parameters governing the efficiency of the MnO<sub>2</sub>-to-Mn<sup>2+</sup> conversion. Overall, the present study provides a comprehensive framework for the rational design and optimization of MnO<sub>2</sub> cathodes involved in rechargeable mild aqueous batteries.


MedChemComm ◽  
2016 ◽  
Vol 7 (9) ◽  
pp. 1694-1715 ◽  
Author(s):  
Jesse A. Jones ◽  
Kristopher G. Virga ◽  
Giuseppe Gumina ◽  
Kirk E. Hevener

Long past the historical “golden era” of antibacterial drug discovery, the modern “resistance era” is being countered by new legislation and advances in the rational design of antibacterial agents.


2012 ◽  
Vol 20 (11) ◽  
pp. 11953 ◽  
Author(s):  
Vladimir Liberman ◽  
Ronen Adato ◽  
Thomas H. Jeys ◽  
Brian G. Saar ◽  
Shyamsunder Erramilli ◽  
...  

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