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Influence of Laser Processing Parameters on the Corrosion Behavior in 316L Stainless Steel Laser Powder Depositions
Mechanical Engineerin
Cell-Type Specific Transcriptomic Profiling to Dissect Mechanisms of Differential Dendritogenesis
The establishment, maintenance and modulation of cell-type speciļ¬c neural architectures are critically important to the formation of functional neural networks. At the neuroanatomical level, differential patterns of dendritic arborization directly impact neural function and connectivity, however the molecular mechanisms underlying the speciļ¬cation of distinct dendrite morphologies remain incompletely understood. To address this question, we analyzed global gene expression from puriļ¬ed populations of wild-type class I and class IV Drosophila melanogaster dendritic arborization (da) sensory neurons compared to wild-type whole larval RNA using oligo DNA microarray expression proļ¬ling. Herein we present detailed experimental methods and bioinformatic anal- yses to correspond with our data reported in the Gene Expression Omnibus under accession number GSE46154. We further provide R code to facilitate data accession, perform quality controls, and conduct bioinformatic analyses relevant to this dataset. Our cell-type speciļ¬c gene expression datasets provide a valuable resource for guiding further investigations designed to explore the molecular mechanisms underlying differential patterns of neuronal patterning
Spatio-Temporal Dynamics of Intrinsic Networks in Functional Magnetic Imaging Data Using Recurrent Neural Networks
We introduce a novel recurrent neural network (RNN) approach to account for temporal dynamics and dependencies in brain networks observed via functional magnetic resonance imaging (fMRI). Our approach directly parameterizes temporal dynamics through recurrent connections, which can be used to formulate blind source separation with a conditional (rather than marginal) independence assumption, which we call RNN-ICA. This formulation enables us to visualize the temporal dynamics of both first order (activity) and second order (directed connectivity) information in brain networks that are widely studied in a static sense, but not well-characterized dynamically. RNN-ICA predicts dynamics directly from the recurrent states of the RNN in both task and resting state fMRI. Our results show both task-related and group-differentiating directed connectivity
Identification of a 1-deoxy-D-xylulose-5-phosphate synthase (DXS) mutant with improved crystallographic properties
In this report, we describe a truncated Deinococcus radiodurans 1-deoxy-D-xylulose-5-phosphate synthase (DXS) protein that retains enzymatic activity, while slowing protein degradation and showing
improved crystallization properties. With modern drug-design approaches relying heavily on the
elucidation of atomic interactions of potential new drugs with their targets, the need for co-crystal
structures with the compounds of interest is high. DXS itself is a promising drug target, as it catalyzes
the first reaction in the 2-C-methyl-D-erythritol 4-phosphate (MEP)-pathway for the biosynthesis of the
universal precursors of terpenes, which are essential secondary metabolites. In contrast to many bacteria
and pathogens, which employ the MEP pathway, mammals use the distinct mevalonate-pathway for the
biosynthesis of these precursors, which makes all enzymes of the MEP-pathway potential new targets for
the development of anti-infectives. However, crystallization of DXS has proven to be challenging: while
the first X-ray structures from Escherichia coli and D. radiodurans were solved in 2004, since then only
two additions have been made in 2019 that were obtained under anoxic conditions. The presented site of
truncation can potentially also be transferred to other homologues, opening up the possibility for the
determination of crystal structures from pathogenic species, which until now could not be crystallized.
This manuscript also provides a further example that truncation of a variable region of a protein can lead
to improved structural data
First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization
The development of drug resistance by Mycobacterium tuberculosis and other pathogenic bacteria emphasizes the need for new antibiotics. Unlike animals, most bacteria synthesize isoprenoid precursors through the MEP pathway. 1-Deoxy-D-xylulose 5-phosphate synthase (DXPS) catalyzes the first reaction of the MEP pathway and is an attractive target for the development of new antibiotics. We report here the successful use of a loop truncation to crystallize and solve the first DXPS structures of a pathogen, namely M. tuberculosis (MtDXPS). The main difference found to other DXPS structures is in the active site where a highly coordinated water was found, showing a new mechanism for the enamine-intermediate stabilization. Unlike other DXPS structures, a "fork-like" motif could be identified in the enamine structure, using a different residue for the interaction with the cofactor, potentially leading to a decrease in the stability of the intermediate. In addition, electron density suggesting a phosphate group could be found close to the active site, provides new evidence for the D-GAP binding site. These results provide the opportunity to improve or develop new inhibitors specific for MtDXPS through structure-based drug design
First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization
The development of drug resistance by Mycobacterium tuberculosis and other pathogenic bacteria
emphasizes the need for new antibiotics. Unlike animals, most bacteria synthesize isoprenoid
precursors through the MEP pathway. 1-Deoxy-d-xylulose 5-phosphate synthase (DXPS) catalyzes the
frst reaction of the MEP pathway and is an attractive target for the development of new antibiotics.
We report here the successful use of a loop truncation to crystallize and solve the frst DXPS structures
of a pathogen, namely M. tuberculosis (MtDXPS). The main diference found to other DXPS structures
is in the active site where a highly coordinated water was found, showing a new mechanism for
the enamine-intermediate stabilization. Unlike other DXPS structures, a āfork-likeā motif could be
identifed in the enamine structure, using a diferent residue for the interaction with the cofactor,
potentially leading to a decrease in the stability of the intermediate. In addition, electron density
suggesting a phosphate group could be found close to the active site, provides new evidence for
the D-GAP binding site. These results provide the opportunity to improve or develop new inhibitors
specifc for MtDXPS through structure-based drug design
Synthesis of Newly Formulated Aluminium Composite through Powder Metallurgy using Waste Bone Material
The increasing concern for sustainable materials and waste management has led to innovative approaches in material science. This study explores the potential benefit of aggregate waste in the production of aluminum composites practicing powder metallurgy techniques. The aim is to investigate the feasibility of incorporating bone material into aluminium matrices to enhance the compositeās mechanical properties. The research involves several key steps. Firstly, waste bone material is collected and processed to obtain a fine powder suitable for powder metallurgy. Various techniques such as grinding, milling, or pulverization are employed to achieve the desired particle size distribution. Next, the bone powder is mixed with aluminium powder in predetermined ratios to create composite blends. The composite blends are then subjected to compaction using powder metallurgy techniques, including cold pressing and sintering. The compaction process aims to consolidate the powders and facilitate the formation of a solid composite structure. The aluminum composites mechanical characteristics are then assessed. The effects of incorporating bone material are assessed using tests on tensile strength, ductility, hardness, and other relevant mechanical properties. Comparative analysis is performed between the composites with bone material and traditional aluminium composites to assess any improvements or changes in performance
Evaluation of a Hybrid Boltzmann-Continuum Method for High Speed Nonequilibrium Flows
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83556/1/AIAA-2010-1569-683.pd
Decentralized Analysis of Brain Imaging Data: Voxel-Based Morphometry and Dynamic Functional Network Connectivity
In the field of neuroimaging, there is a growing interest in developing collaborative frameworks that enable researchers to address challenging questions about the human brain by leveraging data across multiple sites all over the world. Additionally, efforts are also being directed at developing algorithms that enable collaborative analysis and feature learning from multiple sites without requiring the often large data to be centrally located. In this paper, we propose two new decentralized algorithms: (1) A decentralized regression algorithm for performing a voxel-based morphometry analysis on structural magnetic resonance imaging (MRI) data and, (2) A decentralized dynamic functional network connectivity algorithm which includes decentralized group ICA and sliding-window analysis of functional MRI data. We compare results against those obtained from their pooled (or centralized) counterparts on the same data i.e., as if they are at one site. Results produced by the decentralized algorithms are similar to the pooled-case and showcase the potential of performing multi-voxel and multivariate analyses of data located at multiple sites. Such approaches enable many more collaborative and comparative analysis in the context of large-scale neuroimaging studies
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