Assembly Tools Research Articles

Deep Neural Implicit Representation of Accessibility for Multi-Axis Manufacturing

One of the main concerns in design and process planning for multi-axis additive and subtractive manufacturing is collision avoidance between moving objects (e.g., tool assemblies) and stationary objects (e.g., part unified with fixtures). The collision measure for various pairs of relative rigid translations and rotations between the two pointsets can be conceptualized by a compactly supported scalar field over the 6D non-Euclidean configuration space. Explicit representation and computation of this field is costly in both time and space. If we fix O(m) sparsely sampled rotations (e.g., tool orientations), computation of the collision measure field as a convolution of indicator functions of the 3D pointsets over a uniform grid (i.e., voxelized geometry) of resolution O(n3) via fast Fourier transforms (FFTs) scales as in O(mn3logn) in time and O(mn3) in space. In this paper, we develop an implicit representation of the collision measure field via deep neural networks (DNNs). We show that our approach is able to accurately interpolate the collision measure from a sparse sampling of rotations, and can represent the collision measure field with a small memory footprint. Moreover, we show that this representation can be efficiently updated through fine-tuning to more efficiently train the network on multi-resolution data, as well as accommodate incremental changes to the geometry (such as might occur in iterative processes such as topology optimization of the part subject to CNC tool accessibility constraints).

Graph Theory in DNA Sequencing: Unveiling Genetic Patterns

Graph theory, a branch of mathematics that studies the properties and relationships of graphs, has emerged as a powerful tool in addressing the complexities of DNA sequencing. This paper highlights the application of graph theory in DNA sequencing and its implications in various aspects of genomics research. One fundamental concept in graph theory applied to DNA sequencing is the construction of the de Bruijn graph. This graph represents overlapping k-mers, subsequences of length k, as nodes, with edges connecting adjacent k-mers. By constructing and analyzing the de Bruijn graph, researchers can infer the underlying DNA sequence, detect errors, resolve repetitive regions, and identify structural variations in the genome. Graph algorithms such as Overlap path, Eulerian path and Hamiltonian path have been adapted to reconstruct complete DNA sequences from fragmented reads obtained through sequencing. These algorithms leverage the connectivity information present in the de Bruijn graph to traverse and assemble the reads, enabling the reconstruction of long DNA sequences accurately. the application of graph theory in DNA sequencing has revolutionized the field of genomics by providing powerful computational tools for DNA assembly, sequence analysis, and functional annotation. By leveraging graph theory concepts and algorithms, researchers can unravel the intricate information embedded within DNA sequences, leading to deeper insights into the genetic basis of life and its applications in various fields, including medicine, agriculture, and evolutionary biology. Future developments in graph-based algorithms and computational techniques hold promise for further enhancing our ability to unlock the secrets encoded within the vast realm of DNA sequences.

WebQUAST: online evaluation of genome assemblies.

Selecting proper genome assembly is key for downstream analysis in genomics studies. However, the availability of many genome assembly tools and the huge variety of their running parameters challenge this task. The existing online evaluation tools are limited to specific taxa or provide just a one-sided view on the assembly quality. We present WebQUAST, a web server for multifaceted quality assessment and comparison of genome assemblies based on the state-of-the-art QUAST tool. The server is freely available at https://www.ccb.uni-saarland.de/quast/. WebQUAST can handle an unlimited number of genome assemblies and evaluate them against a user-provided or pre-loaded reference genome or in a completely reference-free fashion. We demonstrate key WebQUAST features in three common evaluation scenarios: assembly of an unknown species, a model organism, and a close variant of it.

Research on ERS point registration of large-size measurement field based on neural network non-uniform temperature field

PurposeLarge size of aircraft assembly tooling structure and complex measurement environment exist. The laid enhanced reference points (ERS) are subject to a combination of nonuniform temperature fields and measurement errors, resulting in increased measurement registration errors. In view of the nonuniform temperature field and measurement errors affecting the ERS point registration problem, the purpose of this paper is to propose a neural network-based ERS point registration compensation method for large-size measurement fields under a nonuniform temperature field.Design/methodology/approachThe approach is to collect ERS point information and temperature data, normalize the collected data to complete the data structure design and complete the construction of the neural network prediction model by data training. The data learning is performed to complete the prediction model construction, and the prediction model is used to complete the compensation analysis of ERS points. Finally, the algorithm is verified through experiments and engineering practice.FindingsExperimental results show that the proposed neural network-based ERS point prediction and compensation method for nonuniform temperature fields effectively predicts ERS point deformation under nonuniform temperature fields compared with the conventional method. After the compensation analysis, the registration error is effectively reduced to improve registration accuracy. Reducing the combined effect of environmental nonuniform temperature field and measurement error has apparent advantages.Originality/valueThe method reduces the registration error caused by combining a nonuniform temperature field and measurement error. It can be used for aircraft assembly site prediction and registration error compensation analysis, which is essential to improve measurement accuracy further.

Development of a Tetracycline-Inducible System for Conditional Gene Expression in Lactococcus lactis and Streptococcus thermophilus.

Inducible gene expression systems are invaluable tools for the functional characterization of genes and in the construction of protein overexpression hosts. Controllable expression is especially important for the study of essential and toxic genes or genes where the level of expression tightly influences their cellular effect. Here, we implemented the well-characterized tetracycline-inducible expression system in two industrially important lactic acid bacteria, Lactococcus lactis and Streptococcus thermophilus. Using a fluorescent reporter gene, we show that optimization of the repression level is necessary for efficient induction using anhydrotetracycline in both organisms. Random mutagenesis in the ribosome binding site of the tetracycline repressor TetR in Lactococcus lactis indicated that altering the expression levels of TetR was necessary for efficient inducible expression of the reporter gene. Through this approach, we achieved plasmid-based, inducer-responsive, and tight gene expression in Lactococcus lactis. We then verified the functionality of the optimized inducible expression system in Streptococcus thermophilus following its chromosomal integration using a markerless mutagenesis approach and a novel DNA fragment assembly tool presented herein. This inducible expression system holds several advantages over other described systems in lactic acid bacteria, although more efficient techniques for genetic engineering are still needed to realize these advantages in industrially relevant species, such as S. thermophilus. Our work expands the molecular toolbox of these bacteria, which can accelerate future physiological studies. IMPORTANCE Lactococcus lactis and Streptococcus thermophilus are two industrially important lactic acid bacteria globally used in dairy fermentations and, therefore, are of considerable commercial interest to the food industry. Moreover, due to their general history of safe usage, these microorganisms are increasingly being explored as hosts for the production of heterologous proteins and various chemicals. Development of molecular tools in the form of inducible expression systems and mutagenesis techniques facilitates their in-depth physiological characterization as well as their exploitation in biotechnological applications.

Single-Pass Grain Corn Harvest and Stubble Shredding: Performance of Three Corn Header Configurations as Effected by Harvesting Speed and Cutting Height

This study aims to evaluate the efficiency of a new type of corn header equipped with flail knives that shreds corn stubble close to the ground. A field trial was carried out to quantify the influence of the shredding tool design (flail knives, standard knives, horizontal choppers disengaged), harvesting speed (1.5, 3.0, 4.5, 6.0 km/h) and cutting height (approx. 20 cm variation, 4 levels) on the power consumption of the corn header, engine load and fuel consumption of the combine harvester. The regression analyses revealed that modifications of the shredding tool assembly have significant effects on the parameters of the functional relationships. The power consumption of the flail knives configuration was 15 kW/row unit at 6 km/h at the lowest cutting height setting, making it compatible with most current combine harvester models. The additional power demand and fuel consumption that arise when switching to the new shredding tool design (flail knives) show a wide range, depending on the initial situation. Compared to the standard knives at 6 km/h, the additional power consumption was 3.6–5.5 kW/row unit and the additional fuel consumption was 2.6–3.9 L/ha. Compared to the configuration with disengaged horizontal choppers, it was 5.3–6.6 kW/row unit and 3.9–5.1 L/ha, respectively. At 90% engine load the additional power requirement was 1.6–3.1 kW/row unit and the additional fuel consumption was 2.9–5.6 L/ha compared to the standard knives configuration and 2.6–3.6 kW/row unit and 5.6–7.2 L/ha respectively, compared to the configuration with disengaged horizontal choppers.

First report of Leek yellow stripe virus, Onion yellow dwarf virus, and the putative allium polerovirus A in elephant garlic (Allium ampeloprasum) in Brazil.

Five elephant garlic plants (Allium ampeloprasum L.) showing leaf symptoms of chlorotic streaks and mosaic (Figure 1A and B) were collected, in September 2021, in an experimental area in municipality of Rio do Sul (27°11'07"S, 49°39'39"W), State of Santa Catarina, Brazil. Total RNA was extracted using TRIzol® reagent (Invitrogen, USA), according to the manufacturer's instructions to investigate viral infection. The RNA from all five plants were pooled into a single sample for cDNA library construction with the TruSeq Stranded Total RNA with Ribo-Zero Plant (Illumina) kit, which was then sequenced on the Illumina HiSeq2500 platform (Proteimax Biotechnology LTDA). After high throughput sequencing (HTS), 49 million raw reads (each 151nt) were generated. They were trimmed with the BBduk tool and de novo assembled with the Tadpole assembler tool (Geneious Software version 2022). A total of 28,345 contigs were generated and searched against the NCBI virus genome database using BLASTn and BLASTx, with positive results for two potyviruses, leek yellow stripe virus (LYSV), onion yellow dwarf virus (OYDV), and the putative polerovirus allium polerovirus A (APVA). The trimmed reads were mapped with the BBmap tool (Bushell 2014), using reference sequences for LYSV (NC_004011), OYDV (NC_005029), and APVA isolate Won (MH898527). A total of 806,060 reads were mapped, resulting in the nearly complete genome of LYSV (isolate RDS22-2, 10,268 bp, ON565071), which shared the highest (89.41%) nucleotide (nt) identity with LYSV isolate MG (KP258216). The nearly complete genome of OYDV (isolate RDS22-1, 10,519 bp, ON565070) was assembled using 311,467 reads, being 90.21% nt identical to OYDV isolate G-118 (KF632714). The APVA genome (isolate RDS22-3, 4,367 bp, ON565072, Figure 1C) was assembled from 116,303 reads and it shared the highest (90.73%) nt identity with APVA isolate Won. Subsequently, each sample was RT-PCR screened separately for potyviruses and poleroviruses, using the generic primer pairs NIb2F/NIb3R (Zheng et al., 2010) and Pol-G-F/Pol-G-R (Knierim et al., 2010), respectively. Amplified DNA fragments with approximately 350 bp and 1000 bp were obtained for potyviruses and poleroviruses, respectively, and were sent for Sanger sequencing (ACTGene, Alvorada, Brazil). The Sanger derived partial sequences shared 98 to 100% nt identities with corresponding HTS-derived sequences. The most common virus was LYSV, which was found in three of the five tested samples, whereas OYDV and APVA were only found in one sample each. The plants were also screened with specific primers for each virus, and none of the samples revealed mixed infections. Elephant garlic is primarily utilized for industrial garlic production in several countries, and it is now being researched in Brazil for the same purpose. It can be observed from this study that elephant garlic is susceptible to two of the most common viruses in garlic (LYSV and OYDV), which must be considered in the future while developing resistant varieties or in using thermotherapy and shoot tip/meristem culture to recover virus-free cultivars. LYSV and OYDV have already been described in Brazil infecting Allium sativum (Kitajima 2020). The only complete APVA sequence available is from China (Isolate Won), but no further characterization of the virus has been performed and published. The occurrence of this virus in Brazil highlights the importance of further research to obtain a more robust virus characterization.

Benchmarking genome assembly methods on metagenomic sequencing data.

Metagenome assembly is an efficient approach to reconstruct microbial genomes from metagenomic sequencing data. Although short-read sequencing has been widely used for metagenome assembly, linked- and long-read sequencing have shown their advancements in assembly by providing long-range DNA connectedness. Many metagenome assembly tools were developed to simplify the assembly graphs and resolve the repeats in microbial genomes. However, there remains no comprehensive evaluation of metagenomic sequencing technologies, and there is a lack of practical guidance on selecting the appropriate metagenome assembly tools. This paper presents a comprehensive benchmark of 19 commonly used assembly tools applied to metagenomic sequencing datasets obtained from simulation, mock communities or human gut microbiomes. These datasets were generated using mainstream sequencing platforms, such as Illumina and BGISEQ short-read sequencing, 10x Genomics linked-read sequencing, and PacBio and Oxford Nanopore long-read sequencing. The assembly tools were extensively evaluated against many criteria, which revealed that long-read assemblers generated high contig contiguity but failed to reveal some medium- and high-quality metagenome-assembled genomes (MAGs). Linked-read assemblers obtained the highest number of overall near-complete MAGs from the human gut microbiomes. Hybrid assemblers using both short- and long-read sequencing were promising methods to improve both total assembly length and the number of near-complete MAGs. This paper also discussed the running time and peak memory consumption of these assembly tools and provided practical guidance on selecting them.

A Digital Twin system of reconfigurable tooling for monitoring and evaluating in aerospace assembly

Assembly tooling is essential equipment in aircraft production. Reconfigurable tooling can adapt to multiple aircraft products by reorganizing modular components. Its service state directly determines the final quality, production cycle, and economic cost of the aircraft assembly. This research developed a reusable Digital Twin (DT) system for reconfigurable tooling to monitor and evaluate its service state. A virtual entity of the DT system is established, containing geometric, physical, behavioral, and rule models. Particularly, both geometric-material similarity and individuality of tooling modules are considered, and calibration parameters are introduced into the behavioral model to ensure the consistency between the virtual and the physical entities. Rules governing positioning deviation identification, assembly sequence, and bolt tightening angle are also included in the rule model, so that the indicative processing data is supplied to evaluate the service state of the tooling and guide the assembly process. The high accuracy and generalizability of the developed DT system for monitoring and evaluating the service state of the tooling are verified by assembly experiments.

Rational search of genetic design space for a heterologous terpene metabolic pathway in Streptomyces

Modern tools in DNA synthesis and assembly give genetic engineers control over the nucleotide-level design of complex, multi-gene systems. Systematic approaches to explore genetic design space and optimize the performance of genetic constructs are lacking. Here we explore the application of a five-level Plackett-Burman fractional factorial design to improve the titer of a heterologous terpene biosynthetic pathway in Streptomyces. A library of 125 engineered gene clusters encoding the production of diterpenoid ent-atiserenoic acid (eAA) via the methylerythritol phosphate pathway was constructed and introduced into Streptomyces albidoflavus J1047 for heterologous expression. The eAA production titer varied within the library by over two orders of magnitude and host strains showed unexpected and reproducible colony morphology phenotypes. Analysis of Plackett-Burman design identified expression of dxs, the gene encoding the first and the flux-controlling enzyme, having the strongest impact on eAA titer, but with a counter-intuitive negative correlation between dxs expression and eAA production. Finally, simulation modeling was performed to determine how several plausible sources of experimental error/noise and non-linearity impact the utility of Plackett-Burman analyses.

Danfoss tooling aids production of reliable hose assemblies

Danfoss Power Solutions recently launched, in Europe, a complete hose assembly tooling portfolio. It has been developed to accelerate production speeds, ensure optimal assembly performance and minimise the risk of assembly errors that can cause leaks or safety issues.

Benzo-Fused-Ring Toolbox Based on Palladium/Norbornene Cooperative Catalysis: Methodology Development and Applications in Natural Product Synthesis.

ConspectusBenzo-fused skeletons are ubiquitous in agrochemicals, medicines, natural products, catalysts, and other organic function materials. The assembly of these skeletons in an efficient manner is an actively explored field in organic synthesis. Palladium/norbornene (Pd/NBE) cooperative catalysis is a powerful tool for the expeditious assembly of polysubstituted arenes through bis-functionalization of the ortho and ipso positions of aryl iodides in one operation. Owing to the efforts of Lautens, Catellani, and others, an array of Pd/NBE-promoted annulations for the syntheses of diversified benzo-fused rings have been developed. However, these methods have not been broadly applied in total synthesis yet.Our group is interested in efficient and practical total synthesis of biologically active molecules. In the past 7 years, we have been devoted to the development of new annulation strategies for the assembly of common benzo-fused skeletons through Pd/NBE-promoted reactions of aryl iodides with novel bifunctional reagents. In this Account, we summarize our laboratory's systematic efforts in this direction. First, readily available epoxides and aziridines were exploited as versatile bifunctional alkylating reagents, which enables quick assembly of a series of valuable benzo-fused heterocycles, including isochromans, dihydrobenzofurans, 1,3-cis-tetrahydroisoquinolines (THIQs), 1,3-trans-THIQs, etc. Second, a convergent access to 5-7-membered benzo-fused carbocycles (including indanes and tetrahydronaphthalenes) was developed by Pd/NBE-promoted annulation of aryl iodides with simple olefinic alcohol-containing alkylating reagents. Third, a Pd/NBE-promoted annulation between aryl iodides and cyclohexanone-containing amination reagents was developed for the construction of benzo-fused N-containing bridged scaffolds. Thus, we have established a practical and versatile toolbox for the quick assembly of diversified benzo-fused skeletons. These new annulation reactions are of high chemo-, regio-, and stereoselectivities with good step and atom economy. Moreover, they are able to rapidly increase molecular complexity from simple building blocks. Finally, their synthetic value has been demonstrated by immediate adoption in several efficient total syntheses of medicines and complex natural products. Compared to conventional synthetic logics, the Pd/NBE-promoted annulation toolbox allows the development of highly convergent strategies, which significantly improves the overall synthetic efficiency.We believe the results presented in this Account will have significant implications beyond our research. It can be envisaged that new Pd/NBE-promoted annulations as well as new applications in complex total synthesis will be revealed in the near future.

Protein assembly: Controllable design strategies and applications in biology

AbstractProtein assembly is the structural basis for the collaboration between proteins to accomplish life activities due to its realization of the domain‐limited and precise spatial arrangement of proteins. Therefore, artificial manipulation of protein self‐assembly has profound implications in areas such as exploring the mysteries of life and developing biomaterials. In this review, we not only summarize the classical assembly strategies and the structures of exquisite protein assemblies, but also aim to generalize the flexible and controllable assembly tools and the “interaction” between the assembled protein‐based materials and the external environment. On the basis of this, the application, challenges and further development of protein assembly in biology are reviewed.

Optimization and application of non-native Phragmites australis transcriptome assemblies.

Phragmites australis (common reed) has a cosmopolitan distribution and has been suggested as a model organism for the study of invasive plant species. In North America, the non-native subspecies (ssp. australis) is widely distributed across the contiguous 48 states in the United States and large parts of Canada. Even though millions of dollars are spent annually on Phragmites management, insufficient knowledge of P. australis impeded the efficiency of management. To solve this problem, transcriptomic information generated from multiple types of tissue could be a valuable resource for future studies. Here, we constructed forty-nine P. australis transcriptomes assemblies via different assembly tools and multiple parameter settings. The optimal transcriptome assembly for functional annotation and downstream analyses was selected among these transcriptome assemblies by comprehensive assessments. For a total of 422,589 transcripts assembled in this transcriptome assembly, 319,046 transcripts (75.5%) have at least one functional annotation. Within the transcriptome assembly, we further identified 1,495 transcripts showing tissue-specific expression pattern, 10,828 putative transcription factors, and 72,165 candidates for simple sequence repeats markers. The identification and analyses of predicted transcripts related to herbicide- and salinity-resistant genes were shown as two applications of the transcriptomic information to facilitate further research on P. australis. Transcriptome assembly and selection would be important for the transcriptome annotation. With this optimal transcriptome assembly and all relative information from downstream analyses, we have helped to establish foundations for future studies on the mechanisms underlying the invasiveness of non-native P. australis subspecies.

GALA: a computational framework for de novo chromosome-by-chromosome assembly with long reads

High-quality genome assembly has wide applications in genetics and medical studies. However, it is still very challenging to achieve gap-free chromosome-scale assemblies using current workflows for long-read platforms. Here we report on GALA (Gap-free long-read Assembly tool), a computational framework for chromosome-based sequencing data separation and de novo assembly implemented through a multi-layer graph that identifies discordances within preliminary assemblies and partitions the data into chromosome-scale scaffolding groups. The subsequent independent assembly of each scaffolding group generates a gap-free assembly likely free from the mis-assembly errors which usually hamper existing workflows. This flexible framework also allows us to integrate data from various technologies, such as Hi-C, genetic maps, and even motif analyses to generate gap-free chromosome-scale assemblies. As a proof of principle we de novo assemble the C. elegans genome using combined PacBio and Nanopore sequencing data and a rice cultivar genome using Nanopore sequencing data from publicly available datasets. We also demonstrate the proposed method’s applicability with a gap-free assembly of the human genome using PacBio high-fidelity (HiFi) long reads. Thus, our method enables straightforward assembly of genomes with multiple data sources and overcomes barriers that at present restrict the application of de novo genome assembly technology.

Protocol for transcriptome assembly by the TransBorrow algorithm.

High-throughput RNA-seq enables comprehensive analysis of the transcriptome for various purposes. However, this technology generally generates massive amounts of sequencing reads with a shorter read length. Consequently, fast, accurate, and flexible tools are needed for assembling raw RNA-seq data into full-length transcripts and quantifying their expression levels. In this protocol, we report TransBorrow, a novel transcriptome assembly software specifically designed for short RNA-seq reads. TransBorrow is employed in conjunction with a splice-aware alignment tool (e.g. Hisat2 and Star) and some other transcriptome assembly tools (e.g. StringTie, Cufflinks, and Scallop). The protocol encompasses all necessary steps, starting from downloading and processing raw sequencing data to assembling the full-length transcripts and quantifying their expressed abundances. The execution time of the protocol may vary depending on the sizes of processed datasets and computational platforms.

Structome: a tool for the rapid assembly of datasets for structural phylogenetics.

Protein structures carry signal of common ancestry and can therefore aid in reconstructing their evolutionary histories. To expedite the structure-informed inference process, a web server, Structome, has been developed that allows users to rapidly identify protein structures similar to a query protein and to assemble datasets useful for structure-based phylogenetics. Structome was created by clustering of the structures in RCSB PDB using 90% sequence identity and representing each cluster by a centroid structure. Structure similarity between centroid proteins was calculated, and annotations from PDB, SCOP, and CATH were integrated. To illustrate utility, an H3 histone was used as a query, and results show that the protein structures returned by Structome span both sequence and structural diversity of the histone fold. Additionally, the pre-computed nexus-formatted distance matrix, provided by Structome, enables analysis of evolutionary relationships between proteins not identifiable using searches based on sequence similarity alone. Our results demonstrate that, beginning with a single structure, Structome can be used to rapidly generate a dataset of structural neighbours and allows deep evolutionary history of proteins to be studied. Structome is available at: https://structome.bii.a-star.edu.sg.

The Impact Of Human Resources Management Practices On Employee Performance: A Comparative Study Between Jordan And United Arab Emirates

This study aims to determine the impact of human resources management practices on employee performance: a comparative study in Jordanian and universities. The study population consisted of 600 participants, including 300 academics from Saudi universities and 300 from Jordanian universities, representing various specializations and academic ranks. A comparative cross-sectional design was used. Research a structured questionnaire as primary data. Assembly tool, The questionnaire included approved measures to evaluate human resources management practices (recruitment, training, performance appraisal, compensation, employee development) and employee performance indicators (productivity, job satisfaction, commitment). Questionnaires the questionnaire consists of two sections: one of them focuses on evaluating implementation and evaluation. Perceived effectiveness of human resource management practices, while others evaluated employee performance measures. It aimed to measure levels of productivity, job satisfaction, and commitment among academics. The comparative analysis revealed distinct patterns in human resources management practices between Jordanian and Saudi universities. Both regions emphasized training and performance evaluation, although with different intensities. It is worth noting that Saudi universities have shown a stronger focus on compensation strategies. The study found significant correlations between HRM practices and employee performance measures in both contexts. Training programs showed a significant positive correlation with productivity and job satisfaction in Jordanian universities, while compensation showed a more clear impact on productivity in Saudi universities. Recommendations were made to develop customized human resource management strategies taking into account the cultural nuances in each region. Strengthening training initiatives: Strengthening training programs to improve productivity and job satisfaction among academics. Emphasis on compensation policies: Greater emphasis on compensation strategies in Saudi universities to enhance employee productivity. Longitudinal studies: Conduct longitudinal studies to monitor the sustainable impact of human resource management practices on employee performance. Culturally Sensitive Human Resource Management, Implement culturally sensitive human resource management practices to ensure effectiveness across diverse workforce demographics.

Hybrid core-shell particles for mRNA systemic delivery.

mRNA based infectious disease vaccines have opened the venue for development of novel nucleic acids-based therapeutics. For all mRNA therapeutics dedicated delivery systems are required, where different functionalities and targeting abilities need to be optimized for the respective applications. One option for advanced formulations with tailored properties are lipid-polymer hybrid nanoparticles with complex nanostructure, which allow to combine features of several already well described nucleic acid delivery systems. Here, we explored hyaluronic acid (HA) as coating of liposome-mRNA complexes (LRCs) to investigate effects of the coating on surface charge, physicochemical characteristics and biological activity. HA was electrostatically attached to positively charged complexes, forming hybrid LRCs (HLRCs). At different N/P ratios, physico-chemical characterization of the two sets of particles showed similarity in size (around 200nm) and mRNA binding abilities, while the presence of the HA shell conferred a negative surface charge to otherwise positive complexes. High transfection efficiency of LRCs and HLRCs in vitro has been obtained in THP-1 and human monocytes derived from PBMC, an interesting target cell population for cancer and immune related pathologies. In mice, quantitative biodistribution of radiolabeled LRC and HLRC particles, coupled with bioluminescence studies to detect the protein translation sites, hinted towards both particles' accumulation in the hepatic reticuloendothelial system (RES). mRNA translated proteins though was found mainly in the spleen, a major source for immune cells, with preference for expression in macrophages. The results showed that surface modifications of liposome-mRNA complexes can be used to fine-tune nanoparticle physico-chemical characteristics. This provides a tool for assembly of stable and optimized nanoparticles, which are prerequisite for future therapeutic interventions using mRNA-based nanomedicines.

Finding Their Data Voice: Practices and Challenges of Dashboard Users.

Dashboards are the ubiquitous means of data communication within organizations. Yet we have limited understanding of how they factor into data practices in the workplace, particularly for data workers who do not self-identify as professional analysts. We focus on data workers who use dashboards as a primary interface to data, reporting on an interview study that characterizes their data practices and the accompanying barriers to seamless data interaction. While dashboards are typically designed for data consumption, our findings show that dashboard users have far more diverse needs. To capture these activities, we frame data workers' practices as data conversations: conversations with data capture classic analysis (asking and answering data questions), while conversations through and around data involve constructing representations and narratives for sharing and communication. Dashboard users faced substantial barriers in their data conversations: their engagement with data was often intermittent, dependent on experts, and involved an awkward assembly of tools. We challenge the visualization and analytics community to embrace dashboard users as a population and design tools that blend seamlessly into their work contexts.