Operating together, these two mechanisms enable the achievement of highly efficient optoelectronic conversion.Methionyl-tRNA synthetase (MetRS) is a chemically validated drug target in the kinetoplastid parasites Trypanosoma brucei and Leishmania donovani. To date, all kinetoplastid MetRS inhibitors described bind in a similar way to an expanded methionine pocket and an adjacent, auxiliary pocket. In the current study we have identified a structurally novel class of inhibitors containing a 4,6-diamino substituted pyrazolopyrimidine core ('MetRS02' series). Crystallographic studies revealed that 'MetRS02' compounds bind to an allosteric pocket in L. major MetRS not previously described and enzymatic studies demonstrated a non-competitive mode of inhibition. Homology modelling of the Trypanosoma cruzi MetRS enzyme revealed key differences in the allosteric pocket between the T. cruzi and Leishmania enzymes. These provide a likely explanation for the lower 'MetRS02' potencies that we observed for the T. cruzi enzyme compared to the Leishmania enzyme. The identification of a new series of MetRS inhibitors and the discovery of a new binding site in kinetoplastid MetRS enzymes provides a novel strategy in the search for new therapeutics for kinetoplastid diseases.Giant unilamellar vesicles (GUVs) made up of phospholipid bilayer membranes (liposomes) and elastic capsules with a crosslinked, polymerized membrane, have emerged as biomimetic alternatives to investigate biological cells such as leukocytes and erythrocytes, respectively. This review looks at the similarities and differences in electrohydrodynamics (EHD) of vesicles and capsules under electric fields that determines their electro-mechanical response. The physics of EHD is illustrated through several examples such as electro-deformation of single and compound, spherical and cylindrical, charged and uncharged vesicles in uniform and non-uniform electric fields and the relevance and challenges are discussed. Both small and large deformation results are discussed. The use of EHD in understanding complex interfacial kinetics in capsules, as well as synthesis of non-spherical capsules using electric fields, are also presented. Finally, the review looks at the large electro-deformation of water-in-water capsules and the relevance of constitutive laws in their response.Improving our comprehension of the weight and spatial distribution of urban built environment stocks is essential for informing urban resource, waste, and environmental management, but this is often hampered by inaccuracy and inconsistency of the typology and material composition data of buildings and infrastructure. Here, we have integrated big data mining and analytics techniques and compiled a local material composition database to address these gaps, for a detailed characterization of the quantity, quality, and spatial distribution (in 500 m × 500 m grids) of the urban built environment stocks in Beijing in 2018. We found that 3,621 megatons (140 ton/cap) of construction materials were accumulated in Beijing's buildings and infrastructure, equaling to 1,141 Mt of embodied greenhouse gas emissions. Buildings contribute the most (63% of total, roughly half in residential and half in non-residential) to the total stock and the subsurface stocks account for almost half. Spatially, the belts between 3 to 7 km from city center (approximately 5 t/m2) and commercial grids (approximately 8 t/m2) became the densest.  https://www.selleckchem.com/products/tolebrutinib-sar442168.html  Correlation analyses between material stocks and socioeconomic factors at a high resolution reveal an inverse relationship between building and road stock densities and suggest that Beijing is sacrificing skylines for space in urban expansion. Our results demonstrate that harnessing emerging big data and analytics (e.g., Point of Interest data and web crawling) could help realize more spatially refined characterization of built environment stocks and the role of such information and urban planning in urban resource, waste, and environmental strategies.Pyrazine-based compounds are of great importance in medicinal chemistry. Due to their heteroaromatic nature, they uniquely combine properties of heteroatoms (polar interactions) with the properties of aromatic moieties (non-polar interactions). This review summarizes results of a systematic analysis of RCSB PDB database focused on important binding interactions of pyrazine-based ligands co-crystallized in protein targets. The most frequent interaction of pyrazine was hydrogen bond to pyrazine nitrogen atom as acceptor, followed by weak hydrogen bond with pyrazine hydrogen as donor. We also identified intramolecular hydrogen bonds within pyrazine ligands, π-interactions, coordination to metal ions and few halogen bonds in chloropyrazines. In many cases the binding mode of the pyrazine fragment was complex, involving combination of several interactions. We conclude that pyrazine as a molecular fragment should not be perceived as a simple aromatic isostere, but rather as a readily interacting moiety of drug-like molecules with high potential for interactions to proteins.SynBioHub is a repository for synthetic genetic designs represented in the Synthetic Biology Open Language (SBOL). To integrate SynBioHub into more synthetic biology workflows, its data processing capabilities need to be expanded. To this end, a plugin interface has been developed. Plugins can be developed for data submission, visualization, and download. This framework was tested by the development of three example plugins, one of each type one allowing the submission of SnapGene files, one visualizing the co-use of different genetic parts, and one preparing plasmid maps for download.For a more comprehensive characterization of molecular heterogeneities of matter, multimodal mass spectrometry imaging must be developed to take advantage of the complementarity of information available through different ionization mechanisms. We report the design, implementation, and performance validation of a laser desorption imaging interface composed of add-on components that adapt a commercial Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging interface for dual imaging of Picosecond Infrared Laser Mass Spectrometry (PIRL-MS) with DESI-MS. The interface utilizes hardware elements and data analysis pipelines already established for DESI-MS imaging, and was further validated in cancer margin assessments using human medulloblastoma cancers. The PIRL-MS images were robust and reproducible across multiple experimental runs on independently prepared xenograft tumors, and could be segmented into cancer and healthy regions in concordance with pathology using a variety of supervised and unsupervised clustering methods.