GRID-Based Three-Dimensional Pharmacophores I: FLAPpharm, a Novel Approach for Pharmacophore Elucidation

AbstractAlthough X-ray based 3D virtual histology is an emerging tool for the analysis of biological tissue, it falls short in terms of specificity when compared to conventional histology. Thus, the aim was to establish a novel approach that combines 3D information provided by microCT with high specificity that only (immuno-)histochemistry can offer. For this purpose, we developed a software frontend, which utilises an elastic transformation technique to accurately co-register various histological and immunohistochemical stainings with free propagation phase contrast synchrotron radiation microCT. We demonstrate that the precision of the overlay of both imaging modalities is significantly improved by performing our elastic registration workflow, as evidenced by calculation of the displacement index. To illustrate the need for an elastic co-registration approach we examined specimens from a mouse model of breast cancer with injected metal-based nanoparticles. Using the elastic transformation pipeline, we were able to co-localise the nanoparticles to specifically stained cells or tissue structures into their three-dimensional anatomical context. Additionally, we performed a semi-automated tissue structure and cell classification. This workflow provides new insights on histopathological analysis by combining CT specific three-dimensional information with cell/tissue specific information provided by classical histology.

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Artificial Tumor Microenvironments in Neuroblastoma

Cancers ◽

10.3390/cancers13071629 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1629

Author(s):

Colin H. Quinn ◽

Andee M. Beierle ◽

Elizabeth A. Beierle

Keyword(s):

Extracellular Matrix ◽

Three Dimensional ◽

Therapeutic Interventions ◽

3D Bioprinting ◽

Culture Studies ◽

In Vivo Models ◽

Novel Treatments ◽

Tumor Microenvironments ◽

Novel Approach

In the quest to advance neuroblastoma therapeutics, there is a need to have a deeper understanding of the tumor microenvironment (TME). From extracellular matrix proteins to tumor associated macrophages, the TME is a robust and diverse network functioning in symbiosis with the solid tumor. Herein, we review the major components of the TME including the extracellular matrix, cytokines, immune cells, and vasculature that support a more aggressive neuroblastoma phenotype and encumber current therapeutic interventions. Contemporary treatments for neuroblastoma are the result of traditional two-dimensional culture studies and in vivo models that have been translated to clinical trials. These pre-clinical studies are costly, time consuming, and neglect the study of cofounding factors such as the contributions of the TME. Three-dimensional (3D) bioprinting has become a novel approach to studying adult cancers and is just now incorporating portions of the TME and advancing to study pediatric solid. We review the methods of 3D bioprinting, how researchers have included TME pieces into the prints, and highlight present studies using neuroblastoma. Ultimately, incorporating the elements of the TME that affect neuroblastoma responses to therapy will improve the development of innovative and novel treatments. The use of 3D bioprinting to achieve this aim will prove useful in developing optimal therapies for children with neuroblastoma.

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Identification of the conserved long non-coding RNAs in myogenesis

BMC Genomics ◽

10.1186/s12864-021-07615-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Anupam Bhattacharya ◽

Simang Champramary ◽

Tanya Tripathi ◽

Debajit Thakur ◽

Ilya Ioshikhes ◽

...

Keyword(s):

Gene Regulation ◽

Muscle Development ◽

Three Dimensional ◽

C2c12 Cells ◽

Mouse Muscle ◽

Rna Molecules ◽

Expression Of Genes ◽

Novel Approach ◽

Non Coding Rna ◽

Topologically Associated Domains

Abstract Background Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. Results In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. Conclusions With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

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Three-dimensional in situ morphometrics of Mycobacterium tuberculosis infection within lesions by optical mesoscopy and novel acid-fast staining

Scientific Reports ◽

10.1038/s41598-020-78640-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Robert J. Francis ◽

Gillian Robb ◽

Lee McCann ◽

Bhagwati Khatri ◽

James Keeble ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Three Dimensional ◽

Large Field ◽

Staining Procedure ◽

3D Analysis ◽

Mycobacterium Tuberculosis Infection ◽

In Vivo Models ◽

Novel Approach

AbstractTuberculosis (TB) preclinical testing relies on in vivo models including the mouse aerosol challenge model. The only method of determining colony morphometrics of TB infection in a tissue in situ is two-dimensional (2D) histopathology. 2D measurements consider heterogeneity within a single observable section but not above and below, which could contain critical information. Here we describe a novel approach, using optical clearing and a novel staining procedure with confocal microscopy and mesoscopy, for three-dimensional (3D) measurement of TB infection within lesions at sub-cellular resolution over a large field of view. We show TB morphometrics can be determined within lesion pathology, and differences in infection with different strains of Mycobacterium tuberculosis. Mesoscopy combined with the novel CUBIC Acid-Fast (CAF) staining procedure enables a quantitative approach to measure TB infection and allows 3D analysis of infection, providing a framework which could be used in the analysis of TB infection in situ.

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Osteogenic Properties of 3D-Printed Silica-Carbon-Calcite Composite Scaffolds: Novel Approach for Personalized Bone Tissue Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22020475 ◽

2021 ◽

Vol 22 (2) ◽

pp. 475

Author(s):

Parastoo Memarian ◽

Francesco Sartor ◽

Enrico Bernardo ◽

Hamada Elsayed ◽

Batur Ercan ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Bone Tissue ◽

Cell Attachment ◽

Three Dimensional ◽

Bone Tissue Regeneration ◽

Hemolysis Assay ◽

Novel Approach ◽

Related Transcription Factor ◽

Diphenyl Tetrazolium Bromide

Carbon enriched bioceramic (C-Bio) scaffolds have recently shown exceptional results in terms of their biological and mechanical properties. The present study aims at assessing the ability of the C-Bio scaffolds to affect the commitment of canine adipose-derived mesenchymal stem cells (cAD-MSCs) and investigating the influence of carbon on cell proliferation and osteogenic differentiation of cAD-MSCs in vitro. The commitment of cAD-MSCs to an osteoblastic phenotype has been evaluated by expression of several osteogenic markers using real-time PCR. Biocompatibility analyses through 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) activity, hemolysis assay, and Ames test demonstrated excellent biocompatibility of both materials. A significant increase in the extracellular alkaline phosphatase (ALP) activity and expression of runt-related transcription factor (RUNX), ALP, osterix (OSX), and receptor activator of nuclear factor kappa-Β ligand (RANKL) genes was observed in C-Bio scaffolds compared to those without carbon (Bio). Scanning electron microscopy (SEM) demonstrated excellent cell attachment on both material surfaces; however, the cellular layer on C-Bio fibers exhibited an apparent secretome activity. Based on our findings, graphene can improve cell adhesion, growth, and osteogenic differentiation of cAD-MSCs in vitro. This study proposed carbon as an additive for a novel three-dimensional (3D)-printable biocompatible scaffold which could become the key structural material for bone tissue reconstruction.

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A Novel Approach for Operating Speed Continuous Predication Based on Alignment Space Comprehensive Index

Journal of Advanced Transportation ◽

10.1155/2017/9862949 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Ying Yan ◽

Gengping Li ◽

Jinjun Tang ◽

Zhongyin Guo

Keyword(s):

Field Experiments ◽

Prediction Models ◽

Three Dimensional ◽

Safety Evaluation ◽

Driving Safety ◽

Operating Speed ◽

Passenger Cars ◽

Comprehensive Index ◽

Novel Approach ◽

Lane Width

Operating speed is a critical indicator for road alignment consistency design and safety evaluation. Although extensive studies have been conducted on operating speed prediction, few models can finish practical continuous prediction at each point along alignment on multilane highways. This study proposes a novel method to estimate the operating speed for multilane highways in China from the aspect of the three-dimensional alignment combination. Operating speed data collected in field experiments on 304 different alignment combination sections are detected by means of Global Positioning System. First, the alignment comprehensive index (ACI) is designed and introduced to describe the function accounting for alignment continuity and driving safety. The variables used in ACI include horizontal curve radius, change rate of curvature, deflection angle of curve, grade, and lane width. Second, the influence range of front and rear alignment on speed is determined on the basis of drivers’ fixation range and dynamical properties of vehicles. Furthermore, a prediction model based on exponential relationships between road alignment and speeds is designed to predict the speed of passenger cars and trucks. Finally, three common criteria are utilized to evaluate the effectiveness of the prediction models. The results indicate that the prediction models outperform the other two operating speed models for their higher prediction accuracy.

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Design of a Didactical Activity for the Analysis of Uncertainties in Thermography through the Use of Robust Statistics as Teacher-Oriented Approach

Remote Sensing ◽

10.3390/rs13030402 ◽

2021 ◽

Vol 13 (3) ◽

pp. 402

Author(s):

Pablo Rodríguez-Gonzálvez ◽

Manuel Rodríguez-Martín

Keyword(s):

Open Source ◽

Robust Statistics ◽

Three Dimensional ◽

Learning Material ◽

Novel Approach ◽

Learning Programs ◽

Institutional Learning ◽

Thermographic Image ◽

Visualization Techniques ◽

Free Open Source

The thermography as a methodology to quantitative data acquisition is not usually addressed in the degrees of university programs. The present manuscript proposes a novel approach for the acquisition of advanced competences in engineering courses associated with the use of thermographic images via free/open-source software solutions. This strategy is established from a research based on the statistical and three-dimensional visualization techniques over thermographic imagery to improve the interpretation and comprehension of the different sources of error affecting the measurements and, thereby, the conclusions and analysis arising from them. The novelty is focused on the detection of non-normalities in thermographic images, which is illustrates in the experimental section. Additionally, the specific workflow for the generation of learning material related with this aim is raised for asynchronous and e-learning programs. These virtual materials can be easily deployed in an institutional learning management system, allowing the students to work with the models by means of free/open-source solutions easily. Subsequently, the present approach will give new tools to improve the application of professional techniques, will improve the students’ critical sense to know how to interpret the uncertainties in thermography using a single thermographic image, therefore they will be better prepared to face future challenges with more critical thinking.

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Fabrication of nitrogen-doped hierarchical porous carbons from Sargassum as advanced electrode materials for supercapacitors

New Journal of Chemistry ◽

10.1039/d1nj02970c ◽

2021 ◽

Author(s):

Feiqiang Guo ◽

Yinbo Zhan ◽

Xiaopeng Jia ◽

Huiming Zhou ◽

Shuang Liang ◽

...

Keyword(s):

High Performance ◽

Nitrogen Doping ◽

Electrode Materials ◽

Three Dimensional ◽

Koh Activation ◽

Porous Carbons ◽

Nitrogen Doped ◽

Novel Approach ◽

Hierarchical Porous ◽

Hierarchical Porous Carbons

Using Sargassum as the precursor, a novel approach was developed to synthesize three-dimensional porous carbons as high-performance electrode materials for supercapacitors via KOH activation and subsequent nitrogen-doping employing melamine as...

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Opening and closure of Iranian back-arc basins: A seismic tomography view

10.5194/egusphere-egu21-5209 ◽

2021 ◽

Author(s):

Nalan Lom ◽

Abdul Qayyum ◽

Derya Gürer ◽

Douwe G. van der Meer ◽

Wim Spakman ◽

...

Keyword(s):

Seismic Tomography ◽

Subduction Zones ◽

Three Dimensional ◽

Plate Motion ◽

Limited Information ◽

Three Dimensional Model ◽

Slab Geometry ◽

Novel Approach ◽

Sanandaj Sirjan Zone ◽

Back Arc

<p>Iran is a mosaic of continental blocks that are surrounded by Tethyan oceanic relics. Remnants of these oceanic rock assemblages are exposed around the Central Iranian Microcontinent (CIM), discretely along the Sanandaj-Sirjan Zone and in Jaz-Murian. The ophiolite belts surrounding the CIM are mainly assumed to represent narrow back-arc basins that opened in Cretaceous and closed before the Eocene. Although these ophiolites are exposed as small pieces on continental crust today, they represent oceans wide enough to form supra-subduction ophiolites and arc-related magmatic rocks which suggest that their palaeogeographic width was at least some hundreds of kilometers. Current models for the palaeogeographic dimension, opening and closure of these basins are highly schematic. They usually seem plausible in two-dimensional reconstructions, however a single three-dimensional model explaining whole Iran and its surrounding regions has not been fully accomplished.&#160; This is mostly because while the geological record provides constraints on the origin and ages of the subducted ocean floor, it provides limited information about onset and cessation of the subduction and almost no constraints on the dimension of these oceans and the subduction zones that consumed them.</p><p>In this study, we follow a novel approach in estimating the dimension and evolution of these back-arc basin by using seismic tomography. Seismic tomography has revealed that we can image and trace subducted lithosphere relics. Imaged mantle structure is now being used to link sinking slabs with sutures and to define shape of a slab. Systematic comparison of regions where the timing of subduction is reasonably well constrained by geological data showed that slabs sink gradually through the mantle at rates more or less the same. This perspective enabled us to study slab shape as a function of absolute trench motion. While mantle stationary trenches tend to create steep slabs or slab walls, the flat-lying segments are formed where the overlying trenches are mobile relative to the mantle, normal facing during roll-back, overturned during slab advance. &#160;Under the assumption of vertical sinking after break-off, it is also possible to locate the palaeo-trenches. &#160;When combined with absolute plate motion reconstructions, tomographically determined volume and size of the subducted lithosphere can also be used to estimate the size/width of the prehistoric oceans. To this end, we build on and further develop concepts that relate absolute trench motion during subduction to modern slab geometry to evaluate the possible range of dimensions associated with opening and closure of the Iranian back-arc basins.</p>

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