Gliotoxin and related epidithiodiketopiperazines (ETP) from diverse fungi feature highly functionalized hydroindole scaffolds with an array of medicinally and ecologically relevant activities. Mutation analysis, heterologous reconstitution, and biotransformation experiments revealed that a cytochrome P450 monooxygenase (GliF) from the human-pathogenic fungus Aspergillus fumigatus plays a key role in the formation of the complex heterocycle. In vitro assays using a biosynthetic precursor from a blocked mutant showed that GliF is specific to ETPs and catalyzes an unprecedented heterocyclization reaction that cannot be emulated with current synthetic methods. In silico analyses indicate that this rare biotransformation takes place in related ETP biosynthetic pathways. 相似文献
Methods for postirradiation characterization of bulk (cm3) irradiated materials or even spent nuclear fuels are sparse due to their extremely radioactive nature. While several methods exist to characterize smaller volumes (<?1 mm3) of such samples, selecting these volumes from larger samples is challenging. X-ray-based methods are prohibitive due to the strong γ-radiation from the sample flooding the detectors. Neutron-based methods available in the proximity of irradiation reactors allow for thermal neutron radiography or computed tomography using a small reactor source, but one cannot assess isotope distributions or microstructural features such as phases, texture, or strain from diffraction measurements due to flux limitations. We present herein a pathway to provide pulsed neutron characterization of bulk irradiated samples using time-of-flight neutron diffraction for microstructural characterization and energy-resolved neutron imaging for assessment of isotopic densities and distributions. Ultimately, laser-driven pulsed neutron sources may allow deployment of these techniques pool-side at irradiation reactors.
ABSTRACTThis paper proposes the multiple-hypotheses image segmentation and feed-forward neural network classifier for food recognition to improve the performance. Initially, the food or meal image is given as input. Then, the segmentation is applied to identify the regions, where a particular food item is located using salient region detection, multi-scale segmentation, and fast rejection. Then, the features of every food item are extracted by the global feature and local feature extraction. After the features are obtained, the classification is performed for each segmented region using a feed-forward neural network model. Finally, the calorie value is computed with the aid of (i) food volume and (ii) calorie and nutrition measure based on mass value. The experimental results and performance evaluation are validated. The outcome of the proposed method attains 0.947 for Macro Average Accuracy (MAA) and 0.959 for Standard Accuracy (SA), which provides better classification performance. 相似文献
Effects of LO-phonon contribution on the electronic and the optical properties are investigated in a Cd0.8Zn0.2Se/ZnSe quantum dot in the presence of magnetic field strength. The magneto-polaron induced hydrogenic binding energy as a function of dot radius in the wide band gap quantum dot is calculated. The oscillator strength and the spontaneous lifetime are studied taking into account the spatial confinement, magnetic field strength and the phonon contribution. Numerical calculations are carried out using variational formulism within the single band effective mass approximation. The optical properties are computed with the compact density matrix method. The magneto-polaron induced optical gain as a function of photon energy is observed. The results show that the optical telecommunication wavelength in the fiber optic communications can be achieved using CdSe/ZnSe semiconductors and it can be tuned with the proper applications of external perturbations. 相似文献
The family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs) comprises numerous biocatalysts capable of C=O or C=C reduction. The highly homologous noroxomaritidine reductase (NR) from Narcissus sp. aff. pseudonarcissus and Zt_SDR from Zephyranthes treatiae, however, are SDRs with an extended imine substrate scope. Comparison with a similar SDR from Asparagus officinalis (Ao_SDR) exhibiting keto-reducing activity, yet negligible imine-reducing capability, and mining the Short-Chain Dehydrogenase/Reductase Engineering Database indicated that NR and Zt_SDR possess a unique active-site composition among SDRs. Adapting the active site of Ao_SDR accordingly improved its imine-reducing capability. By applying the same strategy, an unrelated SDR from Methylobacterium sp. 77 (M77_SDR) with distinct keto-reducing activity was engineered into a promiscuous enzyme with imine-reducing activity, thereby confirming that the ability to reduce imines can be rationally introduced into members of the “classical” SDR enzyme family. Thus, members of the SDR family could be a promising starting point for protein approaches to generate new imine-reducing enzymes. 相似文献
The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity. 相似文献