Exploration of GH94 Sequence Space for Enzyme Discovery Reveals a Novel Glucosylgalactose Phosphorylase Specificity

The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis.     

Non‐geostationary satellite orbit communications satellite constellations history

This special issue of the journal on ‘constellations’ comes at a critical time in their development as a second wave of such non‐geostationary satellite orbit (NGSO) systems is being planned and deployed. These mega‐constellations as they have become known are, with a few exceptions, very much larger than those in the first wave and are focused on broadband and 5G applications rather than speech and narrow band data as those deployed in the first wave during the 1990s. However, as we explain in this editorial, there are many similarities in the design and business plans to the first wave and, perhaps, many similar lessons to be learned.     

丹尼尔斯大厦 加拿大多伦多

正多伦多大学丹尼尔斯建筑、景观和设计学院的设计采用了分期的方法,包括修复和扩建以前称为"知识学院"的标志性建筑,将现有建筑物改造成与教学和需求更相关的框架体系。这个十九世纪遗址的总体规划是通过对预期用途模式和场地生态的分析而制定的,目的是重新定位校园西南角与安大略湖的轴线,并为学院创造新的特性。丹尼尔斯建筑、景观和设计学院需要一个可持续发展的新型工     

Transfer learning between crop types for semantic segmentation of crops versus weeds in precision agriculture

Agricultural robots rely on semantic segmentation for distinguishing between crops and weeds to perform selective treatments and increase yield and crop health while reducing the amount of chemicals used. Deep‐learning approaches have recently achieved both excellent classification performance and real‐time execution. However, these techniques also rely on a large amount of training data, requiring a substantial labeling effort, both of which are scarce in precision agriculture. Additional design efforts are required to achieve commercially viable performance levels under varying environmental conditions and crop growth stages. In this paper, we explore the role of knowledge transfer between deep‐learning‐based classifiers for different crop types, with the goal of reducing the retraining time and labeling efforts required for a new crop. We examine the classification performance on three datasets with different crop types and containing a variety of weeds and compare the performance and retraining efforts required when using data labeled at pixel level with partially labeled data obtained through a less time‐consuming procedure of annotating the segmentation output. We show that transfer learning between different crop types is possible and reduces training times for up to 80%. Furthermore, we show that even when the data used for retraining are imperfectly annotated, the classification performance is within 2% of that of networks trained with laboriously annotated pixel‐precision data.     

Sulfonylguanidine Derivatives as Potential Antimelanoma Agents

Sulfonylguanidines are interesting bioactive compounds with a broad range of applications in the treatment of different pathologies. 2-Aminobenzazole-based structures are well employed in the development of new anticancer drugs. Two series of novel N-benzazol-2-yl-N′-sulfonyl guanidine derivatives were synthesized with the sulfonylguanidine in either an extra- or intracyclic frame. They were evaluated for their antiproliferative activity against malignant melanoma tumor cells, thus allowing structure-activity relationships to be defined. Additionally, NCI-60 screening was performed for the best analogue to study its efficiency against a panel of other cancer cell lines. The stability profile of this promising compound was then validated. During the synthetic process, an unexpected new deamidination of the sulfonylguanidine towards sulfonamide function was also identified.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Developing conductive immiscible polystyrene/polypropylene blends with a percolated conducting polyaniline/polyamide filler by tuning its specific interactions with the styrene-based triblock compatibilizer grafted with maleic anhydride

An approach to induce conductivity in immiscible polystyrene/polypropylene (PS/PP) blends is described using a percolated conducting polyaniline/polyamide (PANI/PA) filler combined with a polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene-graft-maleic anhydride compatibilizer. The approach is based on the ability of the compatibilizer to concomitantly stabilize the cocontinuous morphology and to improve the state of dispersion of the PANI/PA filler. Selective localization of PANI/PA in the PS phase with improved filler dispersion is achieved with the optimal master batch (MB) preparation technique followed by its optimized sequence addition to the blend components. This results in an increase in the dc conductivity by six decades as compared with that of the neat compatibilized blend at an effective 4.8-wt % PANI concentration. An investigation of the effect of functionality and concentration of the filler and the compatibilizer on the filler connectivity in the blend is performed. The prevailing specific interactions are analyzed by Fourier transform infrared spectroscopy and thermogravimetric analysis of the MBs. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48433.