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We calculate the leading radiative corrections to the axial current in the chiral separation effect in dense QED in a magnetic field. Contrary to the conventional wisdom suggesting that the axial current should be exactly fixed by the chiral anomaly relation and is described by the topological contribution on the

We calculate the leading radiative corrections to the axial current in the chiral separation effect in dense QED in a magnetic field. Contrary to the conventional wisdom suggesting that the axial current should be exactly fixed by the chiral anomaly relation and is described by the topological contribution on the lowest Landau level in the free theory, we find in fact that the axial current receives nontrivial radiative corrections. The direct calculations performed to the linear order in the external magnetic field show that the nontrivial radiative corrections to the axial current are provided by the Fermi surface singularity in the fermion propagator at nonzero fermion density.

ContributorsShovkovy, Igor (Author) / Gorbar, E. V. (Author) / Miransky, V. A. (Author) / Wang, Xinyang (Author) / College of Integrative Sciences and Arts (Contributor)
Created2013
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Description

Significance: Modification of cysteine thiols dramatically affects protein function and stability. Hence, the abilities to quantify specific protein sulfhydryl groups within complex biological samples and map disulfide bond structures are crucial to gaining greater insights into how proteins operate in human health and disease. Recent Advances: Many different molecular probes

Significance: Modification of cysteine thiols dramatically affects protein function and stability. Hence, the abilities to quantify specific protein sulfhydryl groups within complex biological samples and map disulfide bond structures are crucial to gaining greater insights into how proteins operate in human health and disease. Recent Advances: Many different molecular probes are now commercially available to label and track cysteine residues at great sensitivity. Coupled with mass spectrometry, stable isotope-labeled sulfhydryl-specific reagents can provide previously unprecedented molecular insights into the dynamics of cysteine modification. Likewise, the combined application of modern mass spectrometers with improved sample preparation techniques and novel data mining algorithms is beginning to routinize the analysis of complex protein disulfide structures. Critical Issues: Proper application of these modern tools and techniques, however, still requires fundamental understanding of sulfhydryl chemistry as well as the assumptions that accompany sample preparation and underlie effective data interpretation. Future Directions: The continued development of tools, technical approaches, and corresponding data processing algorithms will, undoubtedly, facilitate site-specific protein sulfhydryl quantification and disulfide structure analysis from within complex biological mixtures with ever-improving accuracy and sensitivity. Fully routinizing disulfide structure analysis will require an equal but balanced focus on sample preparation and corresponding mass spectral dataset reproducibility.

ContributorsBorges, Chad (Author) / Sherma, Nisha (Author) / Biodesign Institute (Contributor)
Created2014-07-20
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Description

Recently fabricated two-dimensional phosphorene crystal structures have demonstrated great potential in applications of electronics. In this paper, strain effect on the electronic band structure of phosphorene was studied using first-principles methods including density functional theory (DFT) and hybrid functionals. It was found that phosphorene can withstand a tensile stress and

Recently fabricated two-dimensional phosphorene crystal structures have demonstrated great potential in applications of electronics. In this paper, strain effect on the electronic band structure of phosphorene was studied using first-principles methods including density functional theory (DFT) and hybrid functionals. It was found that phosphorene can withstand a tensile stress and strain up to 10 N/m and 30%, respectively. The band gap of phosphorene experiences a direct-indirect-direct transition when axial strain is applied. A moderate −2% compression in the zigzag direction can trigger this gap transition. With sufficient expansion (+11.3%) or compression (−10.2% strains), the gap can be tuned from indirect to direct again. Five strain zones with distinct electronic band structure were identified, and the critical strains for the zone boundaries were determined. Although the DFT method is known to underestimate band gap of semiconductors, it was proven to correctly predict the strain effect on the electronic properties with validation from a hybrid functional method in this work. The origin of the gap transition was revealed, and a general mechanism was developed to explain energy shifts with strain according to the bond nature of near-band-edge electronic orbitals. Effective masses of carriers in the armchair direction are an order of magnitude smaller than that of the zigzag axis, indicating that the armchair direction is favored for carrier transport. In addition, the effective masses can be dramatically tuned by strain, in which its sharp jump/drop occurs at the zone boundaries of the direct-indirect gap transition.

ContributorsPeng, Xihong (Author) / Wei, Qun (Author) / Copple, Andrew (Author) / College of Integrative Sciences and Arts (Contributor)
Created2014-08-04
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Description

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein–DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity.

ContributorsFu, Jinglin (Author) / Yang, Yuhe (Author) / Johnson-Buck, Alexander (Author) / Liu, Minghui (Author) / Liu, Yan (Author) / Walter, Nils G. (Author) / Woodbury, Neal (Author) / Yan, Hao (Author) / Biodesign Institute (Contributor)
Created2014-07-01
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Description

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.

Created2014-07-31
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Description

Background: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects,

Background: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects, the bacterial carrier invades and releases its cargo into host cells where the plasmid expresses viral RNAs and proteins for reconstitution of attenuated influenza virus. Here we aimed to construct a mouse Poll-driven plasmid for efficient production of influenza virus. Results: A plasmid was constructed to express all influenza viral RNAs and proteins. This all-in-one plasmid resulted in 10(5)-10(6) 50 % tissue culture infective dose (TCID50)/mL of influenza A virus in baby hamster kidney (BHK-21) cells on the third day post-transfection, and also reconstituted influenza virus in Madin-Darby canine kidney (MDCK) and Chinese hamster ovary (CHO) cells. A 6-unit plasmid was constructed by deleting the HA and NA cassettes from the all-in-one plasmid. Cotransfection of BHK-21 cells with the 6-unit plasmid and the two other plasmids encoding the HA or NA genes resulted in influenza virus titers similar to those produced by the 1-plasmid method. Conclusions: An all-in-one plasmid and a 3-plasmid murine Poll-driven reverse genetics systems were developed, and efficiently reconstituted influenza virus in BHK-21 cells. The all-in-one plasmid may serve as a tool to determine the factors inhibiting virus generation from a large size plasmid. In addition, we recommend a simple and robust "1 + 2" approach to generate influenza vaccine seed virus.

Created2015-06-22
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Description

The land, water, and energy requirements of hydroponics were compared to those of conventional agriculture by example of lettuce production in Yuma, Arizona, USA. Data were obtained from crop budgets and governmental agricultural statistics, and contrasted with theoretical data for hydroponic lettuce production derived by using engineering equations populated with

The land, water, and energy requirements of hydroponics were compared to those of conventional agriculture by example of lettuce production in Yuma, Arizona, USA. Data were obtained from crop budgets and governmental agricultural statistics, and contrasted with theoretical data for hydroponic lettuce production derived by using engineering equations populated with literature values. Yields of lettuce per greenhouse unit (815 m(2)) of 41 +/- 6.1 kg/m(2)/y had water and energy demands of 20 +/- 3.8 L/kg/y and 90,000 +/- 11,000 kJ/kg/y (+/- standard deviation), respectively. In comparison, conventional production yielded 3.9 +/- 0.21 kg/m(2)/y of produce, with water and energy demands of 250 +/- 25 L/kg/y and 1100 +/- 75 kJ/kg/y, respectively. Hydroponics offered 11 +/- 1.7 times higher yields but required 82 +/- 11 times more energy compared to conventionally produced lettuce. To the authors' knowledge, this is the first quantitative comparison of conventional and hydroponic produce production by example of lettuce grown in the southwestern United States. It identified energy availability as a major factor in assessing the sustainability of hydroponics, and it points to water-scarce settings offering an abundance of renewable energy (e.g., from solar, geothermal, or wind power) as particularly attractive regions for hydroponic agriculture.

ContributorsBarbosa, Guilherme Lages (Author) / Gadelha, Francisca Daiane Almeida (Author) / Kublik, Natalya (Author) / Proctor, Alan (Author) / Reichelm, Lucas (Author) / Weissinger, Emily (Author) / Wohlleb, Gregory (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2015-06-01
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Description

The impetus for discovery and evaluation of protein biomarkers has been accelerated by recent development of advanced technologies for rapid and broad proteome analyses. Mass spectrometry (MS)-based protein assays hold great potential for in vitro biomarker studies. Described here is the development of a multiplex mass spectrometric immunoassay (MSIA) for

The impetus for discovery and evaluation of protein biomarkers has been accelerated by recent development of advanced technologies for rapid and broad proteome analyses. Mass spectrometry (MS)-based protein assays hold great potential for in vitro biomarker studies. Described here is the development of a multiplex mass spectrometric immunoassay (MSIA) for quantification of apolipoprotein C-I (apoC-I), apolipoprotein C-II (apoC-II), apolipoprotein C-III (apoC-III) and their proteoforms. The multiplex MSIA assay was fast (∼40 min) and high-throughput (96 samples at a time). The assay was applied to a small cohort of human plasma samples, revealing the existence of multiple proteoforms for each apolipoprotein C. The quantitative aspect of the assay enabled determination of the concentration for each proteoform individually. Low-abundance proteoforms, such as fucosylated apoC-III, were detected in less than 20% of the samples. The distribution of apoC-III proteoforms varied among samples with similar total apoC-III concentrations. The multiplex analysis of the three apolipoproteins C and their proteoforms using quantitative MSIA represents a significant step forward toward better understanding of their physiological roles in health and disease.

ContributorsTrenchevska, Olgica (Author) / Schaab, Matthew (Author) / Nelson, Randall (Author) / Nedelkov, Dobrin (Author) / Biodesign Institute (Contributor)
Created2015-06-15
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Description

Traditionally, hazardous chemicals have been regulated in the U.S. on a one-by-one basis, an approach that is slow, expensive and can be inefficient, as illustrated by a decades-long succession of replacing one type of organohalogen flame retardants (OHFRs) with another one, without addressing the root cause of toxicity and associated

Traditionally, hazardous chemicals have been regulated in the U.S. on a one-by-one basis, an approach that is slow, expensive and can be inefficient, as illustrated by a decades-long succession of replacing one type of organohalogen flame retardants (OHFRs) with another one, without addressing the root cause of toxicity and associated public health threats posed. The present article expounds on the need for efficient monitoring strategies and pragmatic steps in reducing environmental pollution and adverse human health impacts. A promising approach is to combine specific bioassays with state-of-the-art chemical screening to identify chemicals and chemical mixtures sharing specific modes of action (MOAs) and pathways of toxicity (PoTs). This approach could be used to identify and regulate hazardous chemicals as classes or compound families, featuring similar biological end-points, such as endocrine disruption and mutagenicity. Opportunities and potential obstacles of implementing this approach are discussed.

ContributorsVenkatesan, Arjunkrishna (Author) / Halden, Rolf (Author) / Biodesign Institute (Contributor)
Created2015-08-28