ANTIBIOTICS TARGETING TUBERCULOSIS: BIOSYNTHESIS OF A-102395 AND DISCOVERY OF NOVEL ACTINOMYCINS

The increase in antibiotic resistance of many bacterial strains including multidrug-resistant tuberculosis (MDR-TB) due to over- and misuse of antibiotics is a serious medical and economical problem. Therefore discovery and development of new antibiotics are urgently needed. Two projects were undertaken to address the need for new anti-tuberculosis antibiotics. 1. Discovery of new chemical entities. A-102395, a new nucleoside inhibitor of bacterial MraY (translocase I, EC 2.7.8.13) that is essential for bacterial survival, was isolated from the culture broth of Amycolatopsis sp. SANK 60206 in 2007. Although A-102395 is a potent inhibitor of translocase I with IC50 of 11 nM, it contradictingly does not have any antibiotic activity. A-102395 is a derivative of capuramycin with a unique aromatic side chain. A semisynthetic derivative of capuramycin is currently in clinical trials as an anti-tuberculosis antibiotic, suggesting potential for using A-102395 as a starting point for antibiotic discovery. The biosynthetic gene cluster of A-102395 was identified, including 35 putative open reading frames responsible for biosynthesis and resistance. A series of gene inactivation abolished the A-102395 production, indicating those genes within the cluster are essential for A-102395 biosynthesis. Functional characterization of Cpr17, which has sequence similarity to aminoglycoside phosphotransferases, revealed that it functions as a phosphotransferase conferring self-resistance by using GTP as phosphate donor. Furthermore the enzyme is characterized by low substrate specificity, as Cpr17 was capable of modifying a large series of natural or semi-synthesized analogues of capuramycins. A series of organism-specific high-throughput screening models for potential antibacterial agents targeting on bacterial cell wall synthesis have been established, including Escherichia coli and Mycobacterium tuberculosis. For this screen ten enzymes were successfully used to reconstitute cell wall biosynthesis in vitro. This screening is expected to allow us to identify the targets of novel antibiotics rapidly and in a cost-efficient manner. 2. Rediscovering old antibiotics. As part of our long term goal of discovering and developing novel anti-tuberculosis antibiotics, four novel actinomycins were isolated from the scale-up fermentation of Streptomyces sp. Gö-GS12, and their structures were characterized using mass spectrometry and 1D and 2D NMR. Their antibacterial activity against Gram-positive and Gram-negative strains were determined, as well as their cytotoxicity

High Performance Metasurface Antennas

Recently, metasurfaces (MSs) have received tremendous attention because their electromagnetic properties can be controlled at will. Generally, metasurface with hyperbolic phase distributions, namely, focusing metasurface, can be used to design high-gain antennas. Besides, metasurface has the ability of controlling the polarization state of electromagnetic wave. In this chapter, we first propose a new ultrathin broadband reflected MS and take it into application for high-gain planar antenna. Then, we propose multilayer multifunctional transmitted MSs to simultaneously enhance the gain and transform the linear polarization to circular polarization of the patch antenna. This kind of high-gain antenna eliminates the feed-block effect of the reflected ones

UAV-enabled optimal position selection for secure and precise wireless transmission

In this letter, two unmanned-aerial-vehicle (UAV) optimal position selection schemes are proposed. Based on the proposed schemes, the optimal UAV transmission positions for secure precise wireless transmission (SPWT) are given, where the maximum secrecy rate (SR) can be achieved without artificial noise (AN). In conventional SPWT schemes, the transmission location is not considered which impacts the SR a lot. The proposed schemes find the optimal transmission positions based on putting the eavesdropper at the null point. Thus, the received confidential message energy at the eavesdropper is zero, and the maximum SR achieves. Simulation results show that proposed schemes have improved the SR performance significantly

Superhydrophobicity of micro-structured surfaces on zirconia by nanosecond pulsed laser

This paper presents a systematic approach to improve the hydrophobicity of microstructured surfaces. It includes a contact angle prediction model for microstructures obtained by nanosecond pulsed laser. Combining with the theoretical constraints for stable Cassie-Baxter state this approach can be used to optimize microstructures dimensions for maximising surface hydrophobicity. Laser machining experiments were conducted to evaluate the prediction model. It shows that the proposed systematic approach can accurately predict the contact angle and obtain microstructures dimensions for maximising surface hydrophobicity. The results also indicate that the contact angle increases with the decrease of pitch of the microstructures. Superhydrophobicity with maximum contact angle of 155.7° is obtained, for the first time, on a micro structured surface (P030) of Zirconia with a pitch of 30 μm machined under a laser power at 8W

Editorial for the special issue on ultra precision technologies for micromachining, volume II

With the increasing demand for ultra-high-precision products and micro-products in fields such as aerospace, national defense, military, transportation, and people's livelihoods, it has become an important development trend in the field of machining to realize ultra-high-precision machining and miniaturization with a higher level and higher quality [...]

Acceleration feedback control for enhancing dynamic stiffness of fast tool servo system considering the sensor imperfections

Lorentz type fast tool servo devices have found wide applications in freeform machining but they face problems of insufficient stiffness with large depth of cut. Acceleration feedback control is an alternative way to enhance the dynamic stiffness without the need for a large inertia, which is strictly limited in fast tool servo devices. However, the current knowledge gap in the understanding of the influences of limited sensor bandwidth and sensor noises on positioning performance has impeded the application of acceleration feedback control approach in fast tool servo devices. This paper established an analytical model to reveal, for the first time, how much positioning errors are caused by the added sensor noises and how the acceleration feedback technique changes the closed loop stiffness. The measured positioning error spectrum agrees with the modelled one with different acceleration gains. The stiffness model is verified through frequency response tests. It is found that the dynamic stiffness is significantly improved by 5.6 folds within the acceleration sensor bandwidth, while the stiffness deteriorates at frequencies beyond the bandwidth due to the low-pass characteristics in the acceleration loop. The stiffness analysis results are further verified in the intermittent facing cut experiments. The measured surface form errors can be mapped to the low frequency and high frequency vibrations caused by the cutting forces. The analysis model provides a theoretical basis for adopting acceleration feedback technique, paving the way for its practical implementations in ultra-precision applications