scholarly journals De-Novo-Designed Translational Repressors for Multi-Input Cellular Logic

2018 ◽  
Author(s):  
Jongmin Kim ◽  
Yu Zhou ◽  
Paul Carlson ◽  
Mario Teichmann ◽  
Friedrich C. Simmel ◽  
...  
Keyword(s):  
High Performance ◽  
Dynamic Range ◽  
De Novo ◽  
Nand Gate ◽  
Genetic Circuits ◽  
High Performing ◽  
Molecular Programming ◽  
Cellular Logic ◽  
Translational Regulators ◽  
Sequence Constraints

ABSTRACTSynthetic biology aims to apply engineering principles toward the development of novel biological systems for biotechnology and medicine. Despite efforts to expand the set of high-performing parts for genetic circuits, achieving more complex circuit functions has often been limited by the idiosyncratic nature and crosstalk of commonly utilized parts. Here, we present a molecular programming strategy that implements RNA-based repression of translation usingde-novo-designed RNAs to realize high-performance orthogonal parts with mRNA detection and multi-input logic capabilities. These synthetic post-transcriptional regulators, termed toehold repressors and three-way junction (3WJ) repressors, efficiently suppress translation in response to cognate trigger RNAs with nearly arbitrary sequences using thermodynamically and kinetically favorable linear-linear RNA interactions. Automatedin silicooptimization of thermodynamic parameters yields improved toehold repressors with up to 300-fold repression, while in-cell SHAPE-Seq measurements of 3WJ repressors confirm their designed switching mechanism in living cells. Leveraging the absence of sequence constraints, we identify eight- and 15-component sets of toehold and 3WJ repressors, respectively, that provide high orthogonality. The modularity, wide dynamic range, and low crosstalk of the repressors enable their direct integration into ribocomputing devices that provide universal NAND and NOR logic capabilities and can perform multi-input RNA-based logic. We demonstrate these capabilities by implementing a four-input NAND gate and the expression NOT((A1 AND A2) OR (B1 AND B2)) inEscherichia coli. These features make toehold and 3WJ repressors important new classes of translational regulators for biotechnological applications.

Precise and Convergence Pattern Was Obtained in the Detection of Mammary Gland Carcinoma Using Molybdenum Enhanced Poly Taurine Nano-biofilms Compared to Pathological Examination

2021 ◽  
Author(s):  
Hassan Nasrollahpour ◽  
Balal Khalilzadeh ◽  
Reza Rahbarghazi ◽  
Nevin Erk ◽  
Mohammad-Reza Rashidi ◽  
...  
Keyword(s):  
High Performance ◽  
Dynamic Range ◽  
De Novo ◽  
Molybdenum Trioxide ◽  
Synthesis Method ◽  
Pathological Examination ◽  
Breast Cancer Patients ◽  
Limit Of Quantification ◽  
Tissue Samples ◽  
Her 2

Abstract The development of high-performance sensing frameworks for the diagnosis of anaplastic changes is the subject of debate. The lack of on-time diagnosis in patients with suspicious cancers can affect the prognosis and survival rate. As a correlate, the emergence of de novo strategies for the development of transducing frameworks has an inevitable role in advanced biosensing. The combination of green chemistry procedures with eco-friendly and biocompatible materials is of high desirability in this context. The synthesis of new biocompatible and cost-effective nanomaterials to meet the emerging needs of rising demands appeals to new synthetic methodologies. Here, we applied the electrochemical synthesis method to the fabrication of biocompatible and subtly governed Molybdenum trioxide/poly taurine nano-bio films for the monitoring of human epidermal growth factor receptor-2 (HER-2) in sera from breast cancer patients. Morphological and elemental assessments were performed using scanning electron microscope, energy dispersive X-Ray spectroscopy, and dot mapping analyses. In addition, HER-2 immunohistochemistry (IHC) staining was performed on tissue samples and data compared to the values obtained by Molybdenum trioxide/poly taurine nano-bio films. We also noted our platform is eligible for feasible, rapid, and specific determination of HER-2 factor in human samples. The method had a lower limit of quantification of 0.000001 ng mL-1 and a linear dynamic range between 0.1 ng mL-1 and 0.000001 ng mL-1. IHC imaging showed that the degree of anaplastic changes in breast samples (intensity of HER-2 factor) was closely associated with the intensity of signals obtained by our developed immunosensor.

scholarly journals High-performance chemical and light-inducible recombinases in mammalian cells and mice

2019 ◽  
Author(s):  
Benjamin H. Weinberg ◽  
Jang Hwan Cho ◽  
Yash Agarwal ◽  
N. T. Hang Pham ◽  
Leidy D. Caraballo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
High Performance ◽  
Genome Engineering ◽  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Genetic Circuits ◽  
Control Of Gene Expression ◽  
Gene Expression Control ◽  
High Performance Systems

ABSTRACTSite-specific DNA recombinases are some of the most powerful genome engineering tools in biology. Chemical and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, the availability of inducible recombinases is scarce due to the challenge of engineering high performance systems with low basal activity and sufficient dynamic range. This limitation constrains the sophistication of genetic circuits and animal models that can be created. To expand the number of available inducible recombinases, here we present a library of >20 orthogonal split recombinases that can be inducibly dimerized and activated by various small molecules, light, and temperature in mammalian cells and mice.Furthermore, we have engineered inducible split Cre systems with better performance than existing inducible Cre systems. Using our orthogonal inducible recombinases, we created a “genetic switchboard” that can independently regulate the expression of 3 different cytokines in the same cell. To demonstrate novel capability with our split recombinases, we created a tripartite inducible Flp and a 4-Input AND gate. We have performed extensive quantitative characterization of the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs in terms of signal-to-noise ratio (SNR). To facilitate sharing of this set of reagents, we have deposited our library to Addgene. This library thus significantly expands capabilities for precise and multiplexed mammalian gene expression control.

scholarly journals Model-guided design of mammalian genetic programs

2021 ◽  
Vol 7 (8) ◽  
pp. eabe9375
Author(s):  
J. J. Muldoon ◽  
V. Kandula ◽  
M. Hong ◽  
P. S. Donahue ◽  
J. D. Boucher ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Computational Models ◽  
Biological Complexity ◽  
Genetic Circuits ◽  
Cellular Functions ◽  
High Performing ◽  
Design Objective ◽  
Complex Functions ◽  
Mammalian Genetic ◽  
Analog Processing

Genetically engineering cells to perform customizable functions is an emerging frontier with numerous technological and translational applications. However, it remains challenging to systematically engineer mammalian cells to execute complex functions. To address this need, we developed a method enabling accurate genetic program design using high-performing genetic parts and predictive computational models. We built multifunctional proteins integrating both transcriptional and posttranslational control, validated models for describing these mechanisms, implemented digital and analog processing, and effectively linked genetic circuits with sensors for multi-input evaluations. The functional modularity and compositional versatility of these parts enable one to satisfy a given design objective via multiple synonymous programs. Our approach empowers bioengineers to predictively design mammalian cellular functions that perform as expected even at high levels of biological complexity.

scholarly journals SERS Biosensor Based on Engineered 2D-Aperiodic Nanostructure for In-Situ Detection of Viable Brucella Bacterium in Complex Matrix

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 886
Author(s):  
Massimo Rippa ◽  
Riccardo Castagna ◽  
Domenico Sagnelli ◽  
Ambra Vestri ◽  
Giorgia Borriello ◽  
...  
Keyword(s):  
High Performance ◽  
Foodborne Pathogen ◽  
Surface Enhanced Raman Spectroscopy ◽  
High Performing ◽  
Sensing Platform ◽  
Food Detection ◽  
Raman Enhancement ◽  
Surface Enhanced ◽  
Surface Enhanced Raman ◽  
In Situ Detection

Brucella is a foodborne pathogen globally affecting both the economy and healthcare. Surface Enhanced Raman Spectroscopy (SERS) nano-biosensing can be a promising strategy for its detection. We combined high-performance quasi-crystal patterned nanocavities for Raman enhancement with the use of covalently immobilized Tbilisi bacteriophages as high-performing bio-receptors. We coupled our efficient SERS nano-biosensor to a Raman system to develop an on-field phage-based bio-sensing platform capable of monitoring the target bacteria. The developed biosensor allowed us to identify Brucella abortus in milk by our portable SERS device. Upon bacterial capture from samples (104 cells), a signal related to the pathogen recognition was observed, proving the concrete applicability of our system for on-site and in-food detection.

scholarly journals Decoupling electron and phonon transport in single-nanowire hybrid materials for high-performance thermoelectrics

2021 ◽  
Vol 7 (20) ◽  
pp. eabe6000
Author(s):  
Lin Yang ◽  
Madeleine P. Gordon ◽  
Akanksha K. Menon ◽  
Alexandra Bruefach ◽  
Kyle Haas ◽  
...  
Keyword(s):  
Thermal Conductivity ◽  
Thermal Transport ◽  
Electrical Transport ◽  
High Performance ◽  
Figure Of Merit ◽  
Phonon Transport ◽  
Core Shell ◽  
Nanowire Diameter ◽  
High Performing ◽  
Polycrystalline Thin Films

Organic-inorganic hybrids have recently emerged as a class of high-performing thermoelectric materials that are lightweight and mechanically flexible. However, the fundamental electrical and thermal transport in these materials has remained elusive due to the heterogeneity of bulk, polycrystalline, thin films reported thus far. Here, we systematically investigate a model hybrid comprising a single core/shell nanowire of Te-PEDOT:PSS. We show that as the nanowire diameter is reduced, the electrical conductivity increases and the thermal conductivity decreases, while the Seebeck coefficient remains nearly constant—this collectively results in a figure of merit, ZT, of 0.54 at 400 K. The origin of the decoupling of charge and heat transport lies in the fact that electrical transport occurs through the organic shell, while thermal transport is driven by the inorganic core. This study establishes design principles for high-performing thermoelectrics that leverage the unique interactions occurring at the interfaces of hybrid nanowires.

scholarly journals Integrating high-performing electrochemical transducers in lateral flow assay

2021 ◽  
Author(s):  
Antonia Perju ◽  
Nongnoot Wongkaew
Keyword(s):  
High Performance ◽  
Point Of Care ◽  
Low Cost ◽  
High Sensitivity ◽  
Lateral Flow ◽  
Analytical Performance ◽  
Label Free ◽  
High Performing ◽  
Lateral Flow Assays ◽  
Electrochemical Transducers

AbstractLateral flow assays (LFAs) are the best-performing and best-known point-of-care tests worldwide. Over the last decade, they have experienced an increasing interest by researchers towards improving their analytical performance while maintaining their robust assay platform. Commercially, visual and optical detection strategies dominate, but it is especially the research on integrating electrochemical (EC) approaches that may have a chance to significantly improve an LFA’s performance that is needed in order to detect analytes reliably at lower concentrations than currently possible. In fact, EC-LFAs offer advantages in terms of quantitative determination, low-cost, high sensitivity, and even simple, label-free strategies. Here, the various configurations of EC-LFAs published are summarized and critically evaluated. In short, most of them rely on applying conventional transducers, e.g., screen-printed electrode, to ensure reliability of the assay, and additional advances are afforded by the beneficial features of nanomaterials. It is predicted that these will be further implemented in EC-LFAs as high-performance transducers. Considering the low cost of point-of-care devices, it becomes even more important to also identify strategies that efficiently integrate nanomaterials into EC-LFAs in a high-throughput manner while maintaining their favorable analytical performance.

scholarly journals High-performance magneto-rheological clutches for direct-drive actuation: Design and development

2021 ◽  
pp. 1045389X2110069
Author(s):  
Sergey Pisetskiy ◽  
Mehrdad Kermani
Keyword(s):  
High Performance ◽  
Degrees Of Freedom ◽  
Dynamic Range ◽  
Complete Analysis ◽  
Mass Ratio ◽  
Direct Drive ◽  
Element Analysis ◽  
Prototype Development ◽  
Magneto Rheological ◽  
Hall Sensors

This paper presents an improved design, complete analysis, and prototype development of high torque-to-mass ratio Magneto-Rheological (MR) clutches. The proposed MR clutches are intended as the main actuation mechanism of a robotic manipulator with five degrees of freedom. Multiple steps to increase the toque-to-mass ratio of the clutch are evaluated and implemented in one design. First, we focus on the Hall sensors’ configuration. Our proposed MR clutches feature embedded Hall sensors for the indirect torque measurement. A new arrangement of the sensors with no effect on the magnetic reluctance of the clutch is presented. Second, we improve the magnetization of the MR clutch. We utilize a new hybrid design that features a combination of an electromagnetic coil and a permanent magnet for improved torque-to-mass ratio. Third, the gap size reduction in the hybrid MR clutch is introduced and the effect of such reduction on maximum torque and the dynamic range of MR clutch is investigated. Finally, the design for a pair of MR clutches with a shared magnetic core for antagonistic actuation of the robot joint is presented and experimentally validated. The details of each approach are discussed and the results of the finite element analysis are used to highlight the required engineering steps and to demonstrate the improvements achieved. Using the proposed design, several prototypes of the MR clutch with various torque capacities ranging from 15 to 200 N·m are developed, assembled, and tested. The experimental results demonstrate the performance of the proposed design and validate the accuracy of the analysis used for the development.

scholarly journals High-performance chemical- and light-inducible recombinases in mammalian cells and mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin H. Weinberg ◽  
Jang Hwan Cho ◽  
Yash Agarwal ◽  
N. T. Hang Pham ◽  
Leidy D. Caraballo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
High Performance ◽  
Genome Engineering ◽  
Genetic Circuits ◽  
Control Of Gene Expression ◽  
Expression Control ◽  
Gene Expression Control ◽  
High Performance Systems ◽  
Spatiotemporal Control

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.

scholarly journals Understanding High Performance in Late Second Language (L2) Acquisition—What Is the Secret? A Contrasting Case Study in L2 French

Languages ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 32
Author(s):  
Fanny Forsberg Lundell ◽  
Klara Arvidsson
Keyword(s):  
Language Learning ◽  
High Performance ◽  
Native Speaker ◽  
Age Of Onset ◽  
Learning Experience ◽  
Host Community ◽  
L2 Acquisition ◽  
Attribute Importance ◽  
High Performing ◽  
High Performers

Adult L2 acquisition has often been framed within research on the Critical Period Hypothesis, and the age factor is one of the most researched topics of SLA. However, several researchers suggest that while age is the most important factor for differences between child and adult SLA, variation in adult SLA is more dependent on social and psychological factors than on age of onset. The present qualitative study investigates the role of migratory experience, language use/social networks, language learning experience, identity and attitudes for high performance among Swedish L1 French L2 users in France. The study constitutes an in-depth thematic analysis of interviews with six high-performing individuals and four low-performing individuals. The main results show that the high performers differ from the low performers on all dimensions, except for attitudes towards the host community. High performers are above all characterized by self-reported language aptitude and an early interest in languages, which appears to have led to rich exposure to French. Also, they exhibit self-regulatory behaviors and attribute importance to being perceived as a native speaker of French—both for instrumental and existential reasons.

A High-Performance Signal Processing System for Monopulse Tracking Radar

2011 ◽  
Vol 383-390 ◽  
pp. 471-475
Author(s):  
Yong Bin Hong ◽  
Cheng Fa Xu ◽  
Mei Guo Gao ◽  
Li Zhi Zhao
Keyword(s):  
Signal Processing ◽  
High Performance ◽  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Processing System ◽  
Digital Signal ◽  
Radar Signal ◽  
Signal Processing System ◽  
Parallel Pipelined ◽  
Tracking Radar

A radar signal processing system characterizing high instantaneous dynamic range and low system latency is designed based on a specifically developed signal processing platform. Instantaneous dynamic range loss is a critical problem when digital signal processing is performed on fixed-point FPGAs. In this paper, the problem is well resolved by increasing the wordlength according to signal-to-noise ratio (SNR) gain of the algorithms through the data path. The distinctive software structure featuring parallel pipelined processing and “data flow drive” reduces the system latency to one coherent processing interval (CPI), which significantly improves the maximum tracking angular velocity of the monopulse tracking radar. Additionally, some important electronic counter-countermeasures (ECCM) are incorporated into this signal processing system.

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