Engineering antimicrobial supramolecular polymer assemblies

Antibacterial resistance against conventional antibiotics has emerged as a global health problem. To address this problem, antimicrobial peptides (AMPs) have been recognized as alternatives due to their fast-killing activity and less propensity to induce resistance. Here, the AMPs are engineered via a supramolecular fashion to control and increase their biological performance. The AMPs are modified with ureido-pyrimidinone (UPy) to obtain UPy-AMP monomers, followed by modular self-assembling to realize antibacterial UPy-AMP supramolecular polymers. These positively charged assemblies are illustrated as stable, short fibrous or rod-like UPy-AMP nanostructures with enhanced antibacterial activity and modulable cytotoxicity. Moreover, these antibacterial UPy-AMP assemblies can be internalized by both THP-1 derived macrophages and human kidney cells, which would be an effective potential therapy to deliver the AMPs into mammalian cells to address intracellular infections. Overall, the results present here demonstrate that supramolecular engineering of AMPs provides a powerful tool to enhance the antibacterial activity, modulate cytotoxicity and accelerate the clinical application of AMPs.</p

Engineering antimicrobial supramolecular polymer assemblies

Antibacterial resistance against conventional antibiotics has emerged as a global health problem. To address this problem, antimicrobial peptides (AMPs) have been recognized as alternatives due to their fast-killing activity and less propensity to induce resistance. Here, the AMPs are engineered via a supramolecular fashion to control and increase their biological performance. The AMPs are modified with ureido-pyrimidinone (UPy) to obtain UPy-AMP monomers, followed by modular self-assembling to realize antibacterial UPy-AMP supramolecular polymers. These positively charged assemblies are illustrated as stable, short fibrous or rod-like UPy-AMP nanostructures with enhanced antibacterial activity and modulable cytotoxicity. Moreover, these antibacterial UPy-AMP assemblies can be internalized by both THP-1 derived macrophages and human kidney cells, which would be an effective potential therapy to deliver the AMPs into mammalian cells to address intracellular infections. Overall, the results present here demonstrate that supramolecular engineering of AMPs provides a powerful tool to enhance the antibacterial activity, modulate cytotoxicity and accelerate the clinical application of AMPs.</p

Feasibility studies of a compact mm-wave linac FEL

Short wavelength FELs impose stringent requirements on the quality of the electron beams. The key factor in obtaining a single-pass UV or x-ray FEL is the generation of small emittance electron beams with ultra-high brightness. The pioneering work at Los Alamos National Laboratory in the last decade has resulted in a dramatic improvement in the production of high electron beam brightness and small beam emittance using rf photocathode gun. The lower bound on the emittance of a 1-nC bunch without any emittance compensation is on the order of 3 {pi} mm-mrad. This is well within the emittance requirement being considered here. Although the original R&D work at Argonne, in collaboration with the University of Illinois at Chicago and University of Wisconsin-Madison, has produced encouraging results in the area of rf structure design, x-ray mask fabrication, and LIGA processing (Lithography, Electroforming, and Molding), the goal to prove feasibility has not yet been achieved. In this paper, we will present feasibility studies for a compact single-pass mm-linac FEL based on LIGA technology. This system will consist of a photocathode rf gun operated at 30 GHz, a 50-MeV superconducting constant gradient structure operated at 60 GHz, and a microundulator with 1-mm period

An overview of the APS 352-MHz rf systems

The Advanced Photon Source (APS) is a 7-GeV full energy positron storage ring for generating synchrotron radiation with an injector. The booster synchrotron rf system consists o a single 1-MW klystron which drives four five-cell cavities at 352 MHz. The storage ring cavities consist of four groups of four single cells powered by two 1-MW klystrons for 100-mA operation. An overview of the operation of the APS 352-MHz rf systems is presented

Quantum Ferromagnetism and Phase Transitions in Double-Layer Quantum Hall Systems

Double layer quantum Hall systems have interesting properties associated with interlayer correlations. At $\nu =1/m$ where $m$ is an odd integer they exhibit spontaneous symmetry breaking equivalent to that of spin $1/2$ easy-plane ferromagnets, with the layer degree of freedom playing the role of spin. We explore the rich variety of quantum and finite temperature phase transitions in these systems. In particular, we show that a magnetic field oriented parallel to the layers induces a highly collective commensurate-incommensurate phase transition in the magnetic order.Comment: 4 pages, REVTEX 3.0, IUCM93-013, 1 FIGURE, hardcopy available from: [email protected]

Skyrmion Excitations in Quantum Hall Systems

Using finite size calculations on the surface of a sphere we study the topological (skyrmion) excitation in quantum Hall system with spin degree of freedom at filling factors around $\nu=1$. In the absence of Zeeman energy, we find, in systems with one quasi-particle or one quasi-hole, the lowest energy band consists of states with $L=S$, where $L$ and $S$ are the total orbital and spin angular momentum. These different spin states are almost degenerate in the thermodynamic limit and their symmetry-breaking ground state is the state with one skyrmion of infinite size. In the presence of Zeeman energy, the skyrmion size is determined by the interplay of the Zeeman energy and electron-electron interaction and the skyrmion shrinks to a spin texture of finite size. We have calculated the energy gap of the system at infinite wave vector limit as a function of the Zeeman energy and find there are kinks in the energy gap associated with the shrinking of the size of the skyrmion. breaking ground state is the state with one skyrmion of infinite size. In the presence of Zeeman energy, the skyrmion size is determined by the interplay of the Zeeman energy and electron-electronComment: 4 pages, 5 postscript figures available upon reques

Functional characterization of a melon alcohol acyl-transferase gene family involved in the biosynthesis of ester volatiles. Identification of the crucial role of a threonine residue for enzyme activity

Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT). We demonstrate here that, in Charentais melon (Cucumis melo var. cantalupensis), AAT are encoded by a gene family of at least four members with amino acid identity ranging from 84% (Cm-AAT1/Cm-AAT2) and 58% (Cm-AAT1/Cm-AAT3) to only 22% (Cm-AAT1/Cm-AAT4). All encoded proteins, except Cm-AAT2, were enzymatically active upon expression in yeast and show differential substrate preferences. Cm-AAT1 protein produces a wide range of short and long-chain acyl esters but has strong preference for the formation of E-2-hexenyl acetate and hexyl hexanoate. Cm-AAT3 also accepts a wide range of substrates but with very strong preference for producing benzyl acetate. Cm-AAT4 is almost exclusively devoted to the formation of acetates, with strong preference for cinnamoyl acetate. Site directed mutagenesis demonstrated that the failure of Cm-AAT2 to produce volatile esters is related to the presence of a 268-alanine residue instead of threonine as in all active AAT proteins. Mutating 268-A into 268-T of Cm-AAT2 restored enzyme activity, while mutating 268-T into 268-A abolished activity of Cm-AAT1. Activities of all three proteins measured with the prefered substrates sharply increase during fruit ripening. The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. The data presented in this work suggest that the multiplicity of AAT genes accounts for the great diversity of esters formed in melon

MM-wave cavity/klystron developments using deep x-ray lithography at the Advanced Photon Source.

Recent microfabrication technologies based on LIGA (German acronym for Li thographe, G alvanoformung, und A bformung) have been applied to build high-aspect-ratio, metallic or dielectric, planar structures suitable for high frequency rf cavity structures. The cavity structures would be used as parts of linear accelerators, microwave undulators, and mm-wave amplifiers. The microfabrication process includes manufacturing of precision x-ray masks, exposure of positive resist by x-rays through the mask, resist development, and electroforming of the final microstructure. Prototypes of a 32-cell, 108-GHz constant impedance cavity and a 66-cell, 94-GHz constant-gradient cavity were fabricated using the synchrotron radiation sources at APS. Preliminary design parameters for a 91- GHz modulator klystron along with an overview of the new technology are discussed

Tracking echovirus eleven outbreaks in Guangdong, China

In April 2019, a suspect cluster of enterovirus cases was reported in a neonatology department in Guangdong, China, resulting in five deaths. We aimed to investigate the pathogen profiles in fatal cases, the circulation and transmission pattern of the viruses by combining metatranscriptomic, phylogenetic, and epidemiological analyses. Metatranscriptomic sequencing was used to characterize the enteroviruses. Clinical and environmental surveillance in the local population was performed to understand the prevalence and genetic diversity of the viruses in the local population. The possible source(s), evolution, transmission, and recombination of the viruses were investigated by incorporating genomes from the current outbreak, from local retrospective surveillance, and from public databases. Metatranscriptomic analysis identified Echovirus 11 (E11) in three fatal cases. Seroprevalence of neutralization antibody to E11 was 35 to 44 per cent in 3–15 age groups of general population, and the viruses were associated with various clinical symptoms. From the viral phylogeny, nosocomial transmissions were identified and all E11 2019 outbreak strains were closely related with E11 strains circulating in local population 2017–19. Frequent recombination occurred among the 2019 Guangdong E11 outbreak strains and various genotypes in enterovirus B species. This study provides an example of combining advanced genetic technology and epidemiological surveillance in pathogen diagnosis, source(s), and transmission tracing during an infectious disease outbreak. The result highlights the hidden E11 circulation and the risk of viral transmission and infection in the young age population in China. Frequent recombination between Guangdong-like strains and other enterovirus genotypes also implies the prevalence of these emerging E11 strains