Synthesis of DNA Origami Scaffolds: Current and Emerging Strategies

DNA origami nanocarriers have emerged as a promising tool for many biomedical applications, such as biosensing, targeted drug delivery, and cancer immunotherapy. These highly programmable nanoarchitectures are assembled into any shape or size with nanoscale precision by folding a single-stranded DNA scaffold with short complementary oligonucleotides. The standard scaffold strand used to fold DNA origami nanocarriers is usually the M13mp18 bacteriophage’s circular single-stranded DNA genome with limited design flexibility in terms of the sequence and size of the final objects. However, with the recent progress in automated DNA origami design—allowing for increasing structural complexity—and the growing number of applications, the need for scalable methods to produce custom scaffolds has become crucial to overcome the limitations of traditional methods for scaffold production. Improved scaffold synthesis strategies will help to broaden the use of DNA origami for more biomedical applications. To this end, several techniques have been developed in recent years for the scalable synthesis of single stranded DNA scaffolds with custom lengths and sequences. This review focuses on these methods and the progress that has been made to address the challenges confronting custom scaffold production for large-scale DNA origami assembly.

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A mini DNA-RNA hybrid origami nanobrick

Nanoscale Advances ◽

10.1039/d1na00026h ◽

2021 ◽

Author(s):

Lifeng Zhou ◽

Arun Richard Chandrasekaran ◽

Mengwen Yan ◽

Vibhav A. Valsangkar ◽

Jeremy I. Feldblyum ◽

...

Keyword(s):

Nucleic Acid ◽

Dna Origami ◽

Complex Geometries ◽

Single Stranded Dna ◽

Dna Scaffold

DNA origami is typically used to fold a long single-stranded DNA scaffold into nanostructures with complex geometries using many short DNA staple strands. Integration of RNA into nucleic acid nanostructures...

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Cyanobacteria—From the Oceans to the Potential Biotechnological and Biomedical Applications

Marine Drugs ◽

10.3390/md19050241 ◽

2021 ◽

Vol 19 (5) ◽

pp. 241

Author(s):

Shaden A. M. Khalifa ◽

Eslam S. Shedid ◽

Essa M. Saied ◽

Amir Reza Jassbi ◽

Fatemeh H. Jamebozorgi ◽

...

Keyword(s):

Bioactive Compounds ◽

Biomedical Applications ◽

Large Scale ◽

Biological Activities ◽

Scale Production ◽

Pharmacological Activities ◽

Large Scale Production ◽

Marine Products ◽

Hiv 1 ◽

Successful Phase

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.

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Vanadium Redox Flow Batteries: A Review Oriented to Fluid-Dynamic Optimization

Energies ◽

10.3390/en14010176 ◽

2020 ◽

Vol 14 (1) ◽

pp. 176

Author(s):

Iñigo Aramendia ◽

Unai Fernandez-Gamiz ◽

Adrian Martinez-San-Vicente ◽

Ekaitz Zulueta ◽

Jose Manuel Lopez-Guede

Keyword(s):

Large Scale ◽

Numerical Models ◽

Fluid Dynamic ◽

Renewable Energy Sources ◽

Vanadium Redox Flow Battery ◽

Redox Flow Batteries ◽

Design Flexibility ◽

Flow Batteries ◽

Exchange Membrane ◽

Vanadium Redox

Large-scale energy storage systems (ESS) are nowadays growing in popularity due to the increase in the energy production by renewable energy sources, which in general have a random intermittent nature. Currently, several redox flow batteries have been presented as an alternative of the classical ESS; the scalability, design flexibility and long life cycle of the vanadium redox flow battery (VRFB) have made it to stand out. In a VRFB cell, which consists of two electrodes and an ion exchange membrane, the electrolyte flows through the electrodes where the electrochemical reactions take place. Computational Fluid Dynamics (CFD) simulations are a very powerful tool to develop feasible numerical models to enhance the performance and lifetime of VRFBs. This review aims to present and discuss the numerical models developed in this field and, particularly, to analyze different types of flow fields and patterns that can be found in the literature. The numerical studies presented in this review are a helpful tool to evaluate several key parameters important to optimize the energy systems based on redox flow technologies.

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GAKTpore: Stereological Characterisation Methods for Porous Foams in Biomedical Applications

Materials ◽

10.3390/ma14051269 ◽

2021 ◽

Vol 14 (5) ◽

pp. 1269

Author(s):

Gareth Sheppard ◽

Karl Tassenberg ◽

Bogdan Nenchev ◽

Joel Strickland ◽

Ramy Mesalam ◽

...

Keyword(s):

Tissue Engineering ◽

Biomedical Applications ◽

Large Scale ◽

Collagen Scaffold ◽

Porous Structures ◽

Tissue Engineering Scaffolds ◽

Biological Responses ◽

Sem Micrograph ◽

Cell Adhesion And Proliferation ◽

Characterisation Methods

In tissue engineering, scaffolds are a key component that possess a highly elaborate pore structure. Careful characterisation of such porous structures enables the prediction of a variety of large-scale biological responses. In this work, a rapid, efficient, and accurate methodology for 2D bulk porous structure analysis is proposed. The algorithm, “GAKTpore”, creates a morphology map allowing quantification and visualisation of spatial feature variation. The software achieves 99.6% and 99.1% mean accuracy for pore diameter and shape factor identification, respectively. There are two main algorithm novelties within this work: (1) feature-dependant homogeneity map; (2) a new waviness function providing insights into the convexity/concavity of pores, important for understanding the influence on cell adhesion and proliferation. The algorithm is applied to foam structures, providing a full characterisation of a 10 mm diameter SEM micrograph (14,784 × 14,915 px) with 190,249 pores in ~9 min and has elucidated new insights into collagen scaffold formation by relating microstructural formation to the bulk formation environment. This novel porosity characterisation algorithm demonstrates its versatility, where accuracy, repeatability, and time are paramount. Thus, GAKTpore offers enormous potential to optimise and enhance scaffolds within tissue engineering.

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Equity Effects of Congestion Charges: An Exploratory Analysis with MATSim

Transportation Research Record Journal of the Transportation Research Board ◽

10.3141/2670-10 ◽

2017 ◽

Vol 2670 (1) ◽

pp. 75-82 ◽

Cited By ~ 2

Author(s):

Lucas Meyer de Freitas ◽

Oliver Schuemperlin ◽

Milos Balac ◽

Francesco Ciari

Keyword(s):

Travel Time ◽

Large Scale ◽

Agent Based ◽

Promising Tool ◽

Travel Time Savings ◽

Time Savings ◽

Time Changes ◽

High Level ◽

Congestion Charging ◽

Equity Effects

This paper shows an application of the multiagent, activity-based transport simulation MATSim to evaluate equity effects of a congestion charging scheme. A cordon pricing scheme was set up for a scenario of the city of Zurich, Switzerland, to conduct such an analysis. Equity is one of the most important barriers toward the implementation of a congestion charging system. After the challenges posed by equity evaluations are examined, it is shown that agent-based simulations with heterogeneous values of time allow for an increased level of detail in such evaluations. Such detail is achieved through a high level of disaggregation and with a 24-h simulation period. An important difference from traditional large-scale models is the low degree of correlation between travel time savings and welfare change. While traditional equity analysis is based on travel time savings, MATSim shows that choice dimensions not included in traditional models, such as departure time changes, can also play an important role in equity effects. The analysis of the results in light of evidence from the literature shows that agent-based models are a promising tool to conduct more complete equity evaluations not only of congestion charges but also of transport policies in general.

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Remote Sensing of Sea Surface Artificial Floating Plastic Targets with Sentinel-2 and Unmanned Aerial Systems (Plastic Litter Project 2019)

Remote Sensing ◽

10.3390/rs12122013 ◽

2020 ◽

Vol 12 (12) ◽

pp. 2013

Author(s):

Konstantinos Topouzelis ◽

Dimitris Papageorgiou ◽

Alexandros Karagaitanakis ◽

Apostolos Papakonstantinou ◽

Manuel Arias Ballesteros

Keyword(s):

Remote Sensing ◽

Large Scale ◽

Field Experiments ◽

Spectral Unmixing ◽

Sea Surface ◽

Spectral Signature ◽

Unmanned Aerial Systems ◽

Real Environment ◽

Promising Tool ◽

Sentinel 2

Remote sensing is a promising tool for the detection of floating marine plastics offering extensive area coverage and frequent observations. While floating plastics are reported in high concentrations in many places around the globe, no referencing dataset exists either for understanding the spectral behavior of floating plastics in a real environment, or for calibrating remote sensing algorithms and validating their results. To tackle this problem, we initiated the Plastic Litter Projects (PLPs), where large artificial plastic targets were constructed and deployed on the sea surface. The first such experiment was realised in the summer of 2018 (PLP2018) with three large targets of 10 × 10 m. Hereafter, we present the second Plastic Litter Project (PLP2019), where smaller 5 × 5 m targets were constructed to better simulate near-real conditions and examine the limitations of the detection with Sentinel-2 images. The smaller targets and the multiple acquisition dates allowed for several observations, with the targets being connected in a modular way to create different configurations of various sizes, material composition and coverage. A spectral signature for the PET (polyethylene terephthalate) targets was produced through modifying the U.S. Geological Survey PET signature using an inverse spectral unmixing calculation, and the resulting signature was used to perform a matched filtering processing on the Sentinel-2 images. The results provide evidence that under suitable conditions, pixels with a PET abundance fraction of at least as low as 25% can be successfully detected, while pinpointing several factors that significantly impact the detection capabilities. To the best of our knowledge, the 2018 and 2019 Plastic Litter Projects are to date the only large-scale field experiments on the remote detection of floating marine litter in a near-real environment and can be used as a reference for more extensive validation/calibration campaigns.

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Nanoparticles for Biomedicine: Coagulation During Synthesis and Applications

Annual Review of Chemical and Biomolecular Engineering ◽

10.1146/annurev-chembioeng-060718-030203 ◽

2019 ◽

Vol 10 (1) ◽

pp. 155-174 ◽

Cited By ~ 3

Author(s):

Fabian H.L. Starsich ◽

Inge K. Herrmann ◽

Sotiris E. Pratsinis

Keyword(s):

Colloidal Stability ◽

Body Fluids ◽

Particle Interactions ◽

Coupling Effects ◽

Synthesis Of Nanoparticles ◽

Nanoparticle Suspensions ◽

Scalable Synthesis ◽

Scalable Methods ◽

Protein Rich

Nanoparticle-based systems offer fascinating possibilities for biomedicine, but their translation into clinics is slow. Missing sterile, reproducible, and scalable methods for their synthesis along with challenges in characterization and poor colloidal stability of nanoparticles in body fluids are key obstacles. Flame aerosol technology gives proven access to scalable synthesis of nanoparticles with diverse compositions and architectures. Although highly promising in terms of product reproducibility and sterility, this technology is frequently overlooked, as its products are of fractal-like aggregated and/or agglomerated morphology. However, coagulation is a widely occurring phenomenon in all kinds of particle-based systems. In particular, protein-rich body fluids encountered in biomedical settings often lead to destabilization of colloidal nanoparticle suspensions in vivo. We aim to provide insights into how particle–particle interactions can be measured and controlled. Moreover, we show how particle coupling effects driven by coagulation may even be beneficial for certain sensing, therapeutic, and bioimaging applications.

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Microwave Dielectric Property Retrieval from Open-Ended Coaxial Probe Response with Deep Learning

10.36227/techrxiv.16992394.v1 ◽

2021 ◽

Author(s):

Cemanur Aydinalp ◽

Sulayman Joof ◽

Mehmet Nuri Akinci ◽

Ibrahim Akduman ◽

Tuba Yilmaz

Keyword(s):

Deep Learning ◽

Dielectric Property ◽

Large Scale ◽

Real Data ◽

Learning Model ◽

Data Generation ◽

Retrieval Technique ◽

Design Flexibility ◽

A New Technique ◽

Deep Learning Model

In the manuscript, we propose a new technique for determination of Debye parameters, representing the dielectric properties of materials, from the reflection coefficient response of open-ended coaxial probes. The method retrieves the Debye parameters using a deep learning model designed through utilization of numerically generated data. Unlike real data, using synthetically generated input and output data for training purposes provides representation of a wide variety of materials with rapid data generation. Furthermore, the proposed method provides design flexibility and can be applied to any desired probe with intended dimensions and material. Next, we experimentally verified the designed deep learning model using measured reflection coefficients when the probe was terminated with five different standard liquids, four mixtures,and a gel-like material.and compared the results with the literature. Obtained mean percent relative error was ranging from 1.21±0.06 to 10.89±0.08. Our work also presents a large-scale statistical verification of the proposed dielectric property retrieval technique.

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Introduction of Surface Loops as a Tool for Encapsulin Functionalization.

10.1101/2021.05.13.444092 ◽

2021 ◽

Author(s):

Sandra Michel-Souzy ◽

Naomi M. Hamelmann ◽

Sara Zarzuela-Pura ◽

Jos M. J. Paulusse ◽

Jeroen J. L. M. Cornelissen

Keyword(s):

Biomedical Applications ◽

Large Scale ◽

Thermotoga Maritima ◽

Scale Production ◽

Structure Property ◽

Protein Subunit ◽

Protein Cages ◽

Notable Increase ◽

The Stability ◽

Surface Loops

Encapsulin based protein cages are nanoparticles with different biomedical applications, such as targeted drug delivery or imaging agents. These particles are biocompatible and can be produced in bacteria, allowing large scale production and protein engineering. In order to use these bacterial nanocages in different applications, it is important to further explore the potential of their surface modification and optimize their production. In this study we design and show new surface modifications of the Thermotoga maritima (Tm) and Brevibacterium linens (Bl) encapsulins. Two new loops on Tm encapsulin with a His-tag insertion after the residue 64 and the residue 127, and the modification of the C-terminal on Bl encapsulin, are reported. The multi-modification of the Tm encapsulin enables up to 240 different functionalities on the cage surface, resulting from 4 potential modifications per protein subunit. We furthermore report an improved protocol giving a better stability and providing a notable increase of the production yield of the cages. Finally, we tested the stability of different encapsulin variants over a year and the results show a difference in stability arising from the tag insertion position. These first insights in the structure-property relationship of encapsulins, with respect to the position of a function loop, allow for further study of the use of these protein nanocages in biomedical applications.

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Structural elaboration in police organizations: an exploration

Policing An International Journal of Police Strategies and Management ◽

10.1108/pijpsm-01-2016-0008 ◽

2017 ◽

Vol 40 (2) ◽

pp. 351-365 ◽

Cited By ~ 2

Author(s):

Alicia L. Jurek ◽

Matthew C. Matusiak ◽

Randa Embry Matusiak

Keyword(s):

Large Scale ◽

Structural Complexity ◽

Essential Elements ◽

Multiple Time ◽

Police Departments ◽

Content Type ◽

Police Organizations ◽

The Usa ◽

Multiple Time Points ◽

American Police

Purpose The current research explores the structural elaboration of municipal American police organizations, specifically, the structural complexity of police organizations and its relationship to time. The purpose of this paper is to describe and test essential elements of the structural elaboration hypothesis. Design/methodology/approach The authors explore the structural elaboration hypothesis utilizing a sample of 219 large police departments across the USA. Data are drawn from multiple waves of the Law Enforcement Management and Administrative Statistics survey and are analyzed using tobit and OLS regression techniques. Findings While there is some evidence that police departments are becoming more elaborate, little evidence for the structural elaboration hypothesis as a function of time is found. Originality/value This project is the first to specifically explore the structural elaboration hypothesis across multiple time points. Additionally, results highlight structural trends across a panel of large American police organizations and provide potential explanations for changes. Suggestions for large-scale policing data collection are also provided.

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