Orchestration of Enzymatic Processing by Thiazole/Oxazole-Modified Microcin Dehydrogenases

Predstavljena je metoda procjene utjecaja životnog vijeka proizvoda na okoliš (LCA). Dan je prikaz povijesnog razvoja i pokušaja pronalaska načina kako obuhvaćanjem unosa i iznosa koji utječu na proizvod i proizvodnju istog smanjiti opterećenje i štetu koju proizvode na okoliš. Također je prikazana i ISO normizacija. Objašnjen je postupak provedbe analize te sve bitne pretpostavke i posljedice koje vode do konačnog rezultata analize. Za potrebe provedbe LCA analize razvijeni su i brojni računalni alati, od kojih je prikazan primjer računalnog alata Gabi. Nakon opisa opće LCA metodologije i opisa samih proizvoda, prikazana je provedba LCA analize na primjeru tri odabrana proizvoda.In this paper is presented a method for estimating the environmental impact of product life cycle assessment (LCA). Method provides an overview of the historical development and attempts to find ways to reduce inputs and outputs that influence the product and production by reducing the enviromental damage. Also the ISO standardization is given. The procedure for carrying out analysis and all relevant assumptions and consequences that bring the final result of the analysis is explained. For the implementation of the LCA analysis a number of computer tools have been developed, one of which is an example of a software tool Gabi. After describing the general LCA methodology and description of the products, the implementation of the LCA analysis on the example of three selected products is made

Investigation and Optimization of the Impact of Printing Orientation on Mechanical Properties of Resin Sample in the Low-Force Stereolithography Additive Manufacturing

The mechanical properties of resin samples in low-force stereolithography additive manufacturing were affected by the printing orientation, and were investigated and optimized to achieve excellent single or comprehensive tensile strength, compressive strength, and flexural modulus. The resin samples were fabricated using a Form3 3D printer based on light curing technology according to the corresponding national standards, and they were detected using a universal testing machine to test their mechanical properties. The influence of the printing orientation was represented by the rotation angle of the resin samples relative to the x–axis, y–axis and z–axis, and the parameters was selected in the range 0°–90° with an interval of 30°. The multiple regression models for the mechanical properties of the prepared resin samples were obtained based on least square estimation, which offered a foundation from which to optimize the parameters of the printing orientation by cuckoo search algorithm. The optimal parameters for the tensile strength, compressive strength and flexural modulus were ‘α = 45°, β = 25°, γ = 90°’, ‘β = 0°, β = 51°, γ = 85°’ and ‘α = 26°, β = 0°, γ = 90°’, respectively, which obtained the improvements of 80.52%, 15.94%, and 48.85%, respectively, relative to the worst conditions. The mechanism was qualitatively discussed based on the force analysis. The achievements obtained in this study proved that optimization of the printing orientation could improve the mechanical properties of the fabricated sample, which provided a reference for all additive manufacturing methods

Orchestration of Enzymatic Processing by Thiazole/Oxazole-Modified Microcin Dehydrogenases

Thiazole/oxazole-modified microcins (TOMMs) comprise a structurally diverse family of natural products with varied bioactivities linked by the presence of posttranslationally installed thiazol­(in)­e and oxazol­(in)­e heterocycles. The detailed investigation of the TOMM biosynthetic enzymes from Bacillus sp. Al Hakam (Balh) has provided significant insight into heterocycle biosynthesis. Thiazoles and oxazoles are installed by the successive action of an ATP-dependent cyclodehydratase (C- and D-protein) and a FMN-dependent dehydrogenase (B-protein), which are responsible for azoline formation and azoline oxidation, respectively. Although several studies have focused on the mechanism of azoline formation, many details regarding the role of the dehydrogenase (B-protein) in overall substrate processing remain unknown. In this work, we evaluated the involvement of the dehydrogenase in determining the order of ring formation as well as the promiscuity of the Balh and microcin B17 cyclodehydratases to accept a panel of noncognate dehydrogenases. In support of the observed promiscuity, a fluorescence polarization assay was utilized to measure binding of the dehydrogenase to the cyclodehydratase using the intrinsic fluorescence of the FMN cofactor. Ultimately, the noncognate dehydrogenases were shown to possess cyclodehydratase-independent activity. A previous study identified a conserved Lys–Tyr motif to be important for dehydrogenase activity. Using the tools developed in this study, the Lys–Tyr motif was shown neither to alter complex formation with the cyclodehydratase nor the reduction potential. Taken together with the known crystal structure of a homologue, our data suggest that the Lys–Tyr motif is of catalytic importance. Overall, this study provides a greater level of insight into the complex orchestration of enzymatic activity during TOMM biosynthesis

Adjustable Sound Absorber of Multiple Parallel-Connection Helmholtz Resonators with Tunable Apertures Prepared by Low-Force Stereolithography of Photopolymer Resin

The variable noise spectrum for many actual application scenarios requires a sound absorber to adapt to this variation. An adjustable sound absorber of multiple parallel-connection Helmholtz resonators with tunable apertures (TA–MPCHRs) is prepared by the low-force stereolithography of photopolymer resin, which aims to improve the applicability of the proposed sound absorber for noise with various frequency ranges. The proposed TA–MPCHR metamaterial contains five metamaterial cells. Each metamaterial cell contains nine single Helmholtz resonators. It is treated as a basic structural unit for an array arrangement. The tunable aperture is realized by utilizing four segments of extendable cylindrical chambers with length l0, which indicates that the length of the aperture l is in the range of [l0, 4l0], and that it is tunable. With a certain group of specific parameters for the proposed TA–MPCHR, the influence of the tunable aperture with a variable length is investigated by acoustic finite element simulation with a two-dimensional rotational symmetric model. For the given noise spectrum of certain actual equipment with four operating modes, the TA–MPCHR sample with a limited total thickness of 40 mm is optimized, which is made of photopolymer resin by the low-force stereolithography, and its actual average sound absorption coefficients for the frequency ranges of 500–800 Hz, 550–900 Hz, 600–1000 Hz and 700–1150 Hz reach 0.9203, 0.9202, 0.9436 and 0.9561, respectively. Relative to common non-adjustable metamaterials, the TA–MPCHR made of photopolymer resin can reduce occupied space and improve absorption efficiency, which is favorable in promoting its practical applications in the noise pollution prevention

Discovery of potent non-urea inhibitors of soluble epoxide hydrolase

A class of potent non-urea inhibitors of soluble epoxide hydrolase was discovered via high throughput screening and SARs-guided modification. Soluble epoxide hydrolase (sEH) is a novel target for the treatment of hypertension and vascular inflammation. A new class of potent non-urea sEH inhibitors was identified via high throughput screening (HTS) and chemical modification. IC 50s of the most potent compounds range from micromolar to low nanomolar

Iron traffics in circulation bound to a siderocalin (Ngal)–catechol complex

The lipocalins are secreted proteins that bind small organic molecules. Scn-Ngal [known as Neutrophil Gelatinase Associated Lipocalin, Siderocalin, Lipocalin 2] sequesters bacterial iron chelators, called siderophores, and consequently blocks bacterial growth. However, Scn-Ngal is also prominently expressed in aseptic diseases, implying that it binds additional ligands and serves additional functions. Using chemical screens, crystallography, and fluorescence methods, we report that Scn-Ngal binds iron together with a small metabolic product called catechol. The formation of the complex blocked the reactivity of iron and permitted its transport once introduced into circulation in vivo. Scn-Ngal then recycled its iron in endosomes by a pH sensitive mechanism. Since catechols derive from bacterial and mammalian metabolism of dietary compounds, the Scn-Ngal:catechol:iron complex represents an unforeseen microbial-host interaction, which mimics Scn-Ngal:siderophore interactions, but instead traffics iron in aseptic tissues. These results identify an endogenous siderophore, which may link the disparate roles of Scn-Ngal in different diseases