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

Hydrophobicity of pyramid structures fabricated by micro milling

Surgical site infection is the most common infection, which occurs after surgery in the part of the body where the surgery took place. Hydrophobic structure is an effective method to improve the anti-infection ability of surgical tools. The hydrophobic surface prepared by the conventional chemical coating method has poor durability. In this study, the micro-milling method was used to process the microstructure efficiently. 6 different sizes of microstructure is designed and manufactured on 7C27Mo2 which is commonly used for surgical tools. The capability of applying micro-milling for these structures is assessed. The optimal microstructure size is obtained. The experimental results show that the smooth surface of 7C27Mo2 is hydrophilic with contact angle of 64.1°. However, after micro-cutting, the hydrophilic surface can be converted into the hydrophobic surface, the contact angle contact angle nearly doubled (from 64.1° to 127.3°). This study lays the foundation for the manufacture of surgical tools with hydrophobicity and antibacterial properties

Influential factors on water footprint: A focus on wheat production and consumption in virtual water import and export regions

Agriculture is a key sector and a major consumer of water resources; therefore, a clear understanding of the agricultural water demand for crop production and consumption is imperative for addressing water scarcity problems, particularly in water export regions. This study provides new insights into the influential factors driving the changes in the agricultural production water footprint (WFprod) and consumption water footprint (WFcon) in the net water import and net water export regions. The WFprod and WFcon of wheat are evaluated in Beijing city (the net water import region) and Heilongjiang province (the net water export region) over the period 1996–2015. The statistical significances of the influential factors, i.e., climate change, gross domestic product, population, dietary demand and technology update are determined using a multivariate linear regression model (LRM) and nonlinear regression model (NLRM). The results indicate that the gross domestic product and population were the dominant positive influential factors, whereas technology update and dietary demand were the dominant negative influential factors affecting the changes in the WFprod and WFcon in the net water import region. In the net water export region, technology update was the dominant negative influential factor affecting the changes in the WFprod and WFcon. Climate change did not contribute significantly to the changes in the WFprod and WFcon of wheat; however, it was an important factor (especially precipitation for the green WF with an average relative importance of more than 22% and the blue WF with an average relative importance of more than 15%) affecting the changes in the WFprod and WFcon of the crop. An in-depth analysis of the influential factors that contribute to the changes in the WFs is fundamentally important for decision-makers to develop countermeasures and strategic planning implementations to mitigate water resource pressure in China

A real-time interpolator for parametric curves

Driven by the ever increasing need for the high-speed high-accuracy machining of freeform surfaces, the interpolators for parametric curves become highly desirable, as they can eliminate the feedrate and acceleration fluctuation due to the discontinuity in the first derivatives along the linear tool path. The interpolation for parametric curves is essentially an optimization problem, and it is extremely difficult to get the time-optimal solution. This paper presents a novel real-time interpolator for parametric curves (RTIPC), which provides a near time-optimal solution. It limits the machine dynamics (axial velocities, axial accelerations and jerk) and contour error through feedrate lookahead and acceleration lookahead operations, meanwhile, the feedrate is maintained as high as possible with minimum fluctuation. The lookahead length is dynamically adjusted to minimize the computation load. And the numerical integration error is considered during the lookahead calculation. Two typical parametric curves are selected for both numerical simulation and experimental validation, a cubic phase plate freeform surface is also machined. The numerical simulation is performed using the software (open access information is in the Acknowledgment section) that implements the proposed RTIPC, the results demonstrate the effectiveness of the RTIPC. The real-time performance of the RTIPC is tested on the in-house developed controller, which shows satisfactory efficiency. Finally, machining trials are carried out in comparison with the industrial standard linear interpolator and the state-of-the-art Position-Velocity-Time (PVT) interpolator, the results show the significant advantages of the RTIPC in coding, productivity and motion smoothness

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

A new grinding force model for micro grinding RB-SiC ceramic with grinding wheel topography as an input

The ability to predict grinding force for hard and brittle materials is important to optimize and control the grinding process. However, it is a difficult task to establish a comprehensive grinding force model that takes into account of brittle fracture, grinding conditions and random distribution of grinding wheel topography. Therefore, this study developed a new grinding force model for micro-grinding of RB-SiC ceramics. First, the grinding force components and grinding trajectory were analyzed based on the critical depth of rubbing, ploughing and brittle fracture. Afterwards, the corresponding individual grain force were established and the total grinding force was derived through incorporating the single grain force with dynamic cutting grains. Finally, a series of calibration and validation experiments were conducted to obtain the empirical coefficient and verify the accuracy of the model. It was found that ploughing and fracture were the dominate removal modes, which illustrate the force components decomposed is correct. Furthermore, the values predicted according to proposed model are consistent with the experimental data, with the average deviation of 6.793% and 8.926% for the normal and tangential force, respectively. This suggests that the proposed model is acceptable and can be used to simulate the grinding force for RB-SiC ceramics in practical

Fabrication of hydrophobic structures by nanosecond pulse laser

In this paper, a feasibility study of manufacturing anti-bacteria surface on stainless steel 7C27Mo2 used for surgical tools by using nanosecond pulse laser is presented. The effect of laser power on the depth of groove was studied through laser cutting experiment. Micro-pillar arrays of different dimensions and spacing were generated by laser cutting. The wetting characteristics of micro-structured surfaces were assessed by using the static contact angle measurement approach. The measurement results show that the original hydrophilic stainless steel surface can be converted into a hydrophobic surface by using laser structuring as the contact angle can be doubled. This research shows that it is feasible to manufacture hydrophobic microstructures with a laser cutting process