Isolation and structure elucidation of parnafungins, antifungal natural products that inhibit mRNA polyadenylation

The Candida albicans Fitness Test, a whole-cell screening platform, was used to profile crude fermentation extracts for novel antifungal natural products with interesting mechanisms of action. An extract with intrinsic antifungal activity from the fungus Fusarium larvarum displayed a Fitness Test profile that strongly implicated mRNA processing as the molecular target responsible for inhibition of fungal growth. Isolation of the active components from this sample identified a novel class of isoxazolidinone-containing natural products, which we have named parnafungins. These natural products were isolated as an interconverting mixture of four structural- and stereoisomers. The isomerization of the parnafungins was due to a retro-Michael ring-opening and subsequent reformation of a xanthone ring system. This interconversion was blocked by methylation of an enol moiety. Structure elucidation of purified parnafungin derivatives was accomplished by X-ray crystallography and NMR analysis. The biochemical target of these natural products has been identified as the fungal polyadenosine polymerase. Parnafungins demonstrated broad spectrum antifungal activity with no observed activity against gram-positive or gram-negative bacteria. The intact isoxazolidinone ring was required for antifungal activity. In addition, the natural products were efficacious in a mouse model of disseminated candidiasis.     

Dopant‐Free Hydrogels with Intrinsic Photoluminescence and Biodegradable Properties

Photoluminescent hydrogels that function as both injectable scaffolds and fluorescent imaging probes hold great potential for therapeutics delivery and tissue engineering. Current fluorescent hydrogels are fabricated by either conjugating or doping a fluorescent dye, fluorescent protein, lanthanide chelate, or quantum dot into polymeric hydrogel matrix. Their biomedical applications are severely limited due to drawbacks such as photostability, carcinogenesis, and toxicity associated with the above‐mentioned dopants. Here, a successful development of dopant‐free photoluminescent hydrogels in situ formed by crosslinking of biocompatible polymer precursors is reported, which can be synthesized by incorporating an amino acid to a citric acid based polyester oligomer followed by functionalization of multivalent crosslinking group through a convenient transesterification reaction using Candida Antarctica Lipase B as a catalyst. It is demonstrated that the newly developed hydrogels possess tunable degradation, intrinsic photoluminescence, mechanical properties, and exhibit sustained release of various molecular weight dextrans. In vivo study shows that the hydrogels formed in situ following subcutaneous injection exhibit excellent biocompatibility and emit strong fluorescence under visible light excitation without the need of using any traditional organic dyes. Their in vivo degradation profiles are then depicted by noninvasively monitoring fluorescence intensity of the injected hydrogel implants.     

Different Reactivity of Rutile and Anatase TiO2 Nanoparticles: Synthesis and Surface States of Nanoparticles of Mixed-Valence Magnéli Oxides

Magnéli phases Ti_nO_2n−1 (3<n≤10) are mixed Ti⁴⁺/Ti³⁺ oxides with high electrical conductivity. When used for water remediation or electrochemical energy storage and conversion, they are nanostructured and exposed to various environments. Therefore, understanding their surface reactivity is of prime importance. Such studies have been hindered by carbon contamination from syntheses. Herein, this synthetic and characterization challenge is addressed through a new approach to 50 nm carbon-free Ti₄O₇ and Ti₆O₁₁ nanoparticles. It takes advantage of the different reactivities of rutile and anatase TiO₂ nanoparticles towards H₂, to use the former as precursor of Ti_nO_2n−1 and the latter as a diluting agent. This approach is combined with silica templating to restrain particle growth. The surface reactivity of the Magnéli nanoparticles under different atmospheres was then evaluated quantitatively by synchrotron-radiation-based X-ray photoelectron spectroscopy, which revealed oxidized surfaces with lower conductivity than the core. This finding sheds a new light on the charge transfer occurring in these materials.     

The impact of preventive activities on the economics of production systems: Modeling and application

In this paper, the impact of preventive activities on the economics of production systems has been discussed. A defective production system has been used to evaluate the financial return of a system with and without preventive activity. A mathematical model has been developed to simulate the situation. A practical case in the automotive industry has been used to verify the model. According to this research, it has been found that preventive activities will affect the return of the production system, and the effect depends on the cost of the action that has been taken.     

Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult

Background  

Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood.     

A stable multiwavelength SOA-based fiber ring laser with ultra-narrow wavelength spacing

This investigation demonstrates a stable multiwavelength fiber ring laser with ultra-narrow wavelength spacing using a semiconductor optical amplifier (SOA). A delay interferometer and a mirror are used as a double-pass interferometer to improve the signal-to-noise ratio in this experiment. Up to 181 stable lasing wavelengths with a wavelength spacing of 10.7 GHz and a signal-to-noise ratio of over 24 dB are produced at room temperature.     

On the exploration of linear latent effect for multivariate modeling

A data analysis method is proposed to derive a latent structure matrix from a sample covariance matrix. The matrix can be used to explore the linear latent effect between two sets of observed variables. Procedures with which to estimate a set of dependent variables from a set of explanatory variables by using latent structure matrix are also proposed. The proposed method can assist the researchers in improving the effectiveness of the SEM models by exploring the latent structure between two sets of variables. In addition, a structure residual matrix can also be derived as a by-product of the proposed method, with which researchers can conduct experimental procedures for variables combinations and selections to build various models for hypotheses testing. These capabilities of data analysis method can improve the effectiveness of traditional SEM methods in data property characterization and models hypotheses testing. Case studies are provided to demonstrate the procedure of deriving latent structure matrix step by step, and the latent structure estimation results are quite close to the results of PLS regression. A structure coefficient index is suggested to explore the relationships among various combinations of variables and their effects on the variance of the latent structure.     

Lens Sag Measurement of Microlens Array Using Optical Interferometric Microscope

This study attempted to develop a detection system for lens sag of the microlens array in real time using an optical automatic inspection framework to link with the computer through a camera. An image processing technique was applied to detect the spherical microlens array, and then, the results were compared.The system light source used laser light and applied CCD to collocate with the microscope array to form an automatic optical detection system for an optical interferometric microscope. It applied the principle of the Fizeau interferometer, illuminated the surface of microlens array, and formed the phase difference required by the interference of two lights through the laser light reflected by the reference plane and the surface of the microlens array, thus, forming an interference fringe.When the sag of the microlens was much longer than the wave length of the detection light source, the fringe would be densely distributed, thus, only a few central fringes were clear in the microscopic image. An image processing method was used to search the center of the interference fringe and a creative algorithm was utilized to obtain the lens sag of the microlens. As proved by the experiment, lens sag of 4 microlens arrays were detected in real time, with a minimum detection error of 0.08 μm, and a maximum detection error of 4 μm (error value 1 ~ 9%), according to different sample processes. This system featured a simple structure and is applicable to non-contact detection and detection of different-sized microlens arrays.     

New fluorescent amide-functionalized phenylethynylthiophene low molecular weight gelator

[reaction: see text]. An amide-functionalized phenylethynylthiophene gelator has been synthesized. Self-assembly of this molecule via cooperative hydrogen bonding and pi-stacking induced gelation of a variety of organic solvents. The presence of aggregates was confirmed by concentration-dependent absorption and fluorescence properties. SEM and TEM studies reveal the formation of fiberlike nanostructure.