Cell-based biosensors have great potential to detect various toxic and pathogenic contaminants in aqueous environments. However, frequently they cannot meet practical requirements due to insufficient ...sensing performance. To address this issue, we investigated a modular, cascaded signal amplifying methodology. We first tuned intracellular sensory receptor densities to increase sensitivity, and then engineered multi-layered transcriptional amplifiers to sequentially boost output expression level. We demonstrated these strategies by engineering ultrasensitive bacterial sensors for arsenic and mercury, and improved detection limit and output up to 5,000-fold and 750-fold, respectively. Coupled by leakage regulation approaches, we developed an encapsulated microbial sensor cell array for low-cost, portable and precise field monitoring, where the analyte can be readily quantified via displaying an easy-to-interpret volume bar-like pattern. The ultrasensitive signal amplifying methodology along with the background regulation and the sensing platform will be widely applicable to many other cell-based sensors, paving the way for their real-world applications.
Abstract
The upper dentition of Crocidura exhibits polymorphic characters that were revealed for the first time in this study via high-resolution X-ray computed microtomography. Our analyses of 11 ...Crocidura species and selected Diplomesodon, Suncus and Sylvisorex species from different geographical regions and size groups revealed the most complex character states of upper dentition in the Ethiopian endemic species Crocidura yaldeni. A three-dimensionally based geometric morphometric analysis revealed the dependence of variation in skull muzzle shape on alterations in general upper dentition, such as a reduction in the number of antemolars. Principal components analysis revealed highly significant shape alterations and morphological trajectories in C. yaldeni (and more moderate ones in Suncus murinus) toward the Sorex-like morphotype in the outgroup, and less significant shape alterations in Crocidura obscurior, Crocidura phanluongi and Crocidura sapaensis with double-rooted third antemolar. Cladistic analysis based on a new data matrix for 20 species and 46 characters allowed us to determine the directions of the morphological trajectories: the apomorphic state of the most complex antemolars of C. yaldeni is associated with deviating skull muzzle shape changes, which we determined to be attributable to neomorphosis, and the less significant alterations in the shape of other Crocidura with complex antemolars are attributable to regional adaptation.
The spatial organization of membrane-bound ligands is thought to regulate receptor-mediated signaling. However, direct regulation of receptor function by nanoscale distribution of ligands has not yet ...been demonstrated, to our knowledge. We developed rationally designed DNA origami nanostructures modified with ligands at well-defined positions. Using these 'nanocalipers' to present ephrin ligands, we showed that the nanoscale spacing of ephrin-A5 directs the levels of EphA2 receptor activation in human breast cancer cells. Furthermore, we found that the nanoscale distribution of ephrin-A5 regulates the invasive properties of breast cancer cells. Our ligand nanocaliper approach has the potential to provide insight into the roles of ligand nanoscale spatial distribution in membrane receptor-mediated signaling.
In this retrospective study, we analyzed the association between tumor budding and perineural invasion as well as their prognostic role in pancreatic ductal adenocarcinoma. A total of
N
= 119 ...patients resected for pancreatic ductal carcinoma from 1996 to 2015 were included. Clinical and standard histopathological parameters were retrieved from the patient’s records. One representative hematoxylin and eosin section from the tumor region was examined for perineural invasion and tumor budding using light microscopy. Tumor budding was assessed independently using two different methods: in the first approach, the number of buds was counted over three fields of 0.237 mm
2
at 40-fold magnification; in the second approach, tumor budding was quantified according to the recommendation of the International Tumor Budding Consensus Conference (ITBCC) over a field of 0.785 mm
2
at 20-fold magnification. Linear and logistic regression was applied to delineate association between perineural invasion, tumor budding, and other parameters; Kaplan-Meier and Cox regression were used in the survival analysis. Regardless of the quantification approach, high tumor budding was a significant negative prognostic factor in the univariable Cox regression (> 5 buds/0.237 mm
2
, hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.06–2.61,
p
= 0.027; ≥ 10 buds/0.785 mm
2
, HR 1.68, 95% CI 1.07–2.64,
p
= 0.024). In the multivariable model adjusting for stage and standard histopathological parameters, lymph vessel invasion (HR = 2.43, 95% CI 1.47–4.03,
p
= 0.001) and tumor budding > 5 buds/0.237 mm
2
(HR = 1.70, 95% CI 1.07–2.7,
p
= 0.026) were independent negative prognostic factors, while adjuvant therapy was a positive prognostic factor (HR = 0.54, 95% CI 0.33–0.86,
p
= 0.009). No significant prognostic value could be delineated for perineural invasion. In conclusion, tumor budding is an independent negative prognostic factor in pancreatic ductal adenocarcinoma associated with lymph node metastasis. The prognostic role of perineural invasion remains uncertain.
We studied the micellar and solubilizing properties of aqueous solutions of unfractionated rhamnolipids produced by Pseudomonas aeruginosa. We used nuclear magnetic resonance (NMR) diffusometry, ...dynamic light scattering, and conductometry to measure the critical micelle concentration (CMC) of rhamnolipid solutions and determined the effective hydrodynamic radii of rhamnolipid monomers and micelles. Based on selective measurements of the self‐diffusion coefficients of molecules, performed by NMR diffusometry, the solubilizing properties of rhamnolipids were studied depending on their concentration in solution; aromatic hydrocarbons, benzene, toluene, ethylbenzene, and para‐xylene were taken as solubilizates. On the basis of the measurement results, we estimated the distribution coefficient of the solubilizate between the micellar (solubilized) and free (in the aqueous phase) states and the solubilizing capacity of rhamnolipid micelles.
Micellar and solubilizing properties of aqueous solutions of rhamnolipids produced by Pseudomonas aeruginosa were studied depending on their concentration in the solution. Aromatic hydrocarbons, benzene, toluene, ethylbenzene, and para‐xylene were taken as solubilizates. The distribution coefficient of the solubilizate between the micellar and free states and the solubilizing capacity of rhamnolipid micelles were estimated.
Influenza is one of the most contagious and rapidly spreading infectious diseases and an important global cause of hospital admissions and mortality. There are some amounts of the virus in the air ...constantly. These amounts is generally not enough to cause disease in people, due to infection prevention by healthy immune systems. However, at a higher concentration of the airborne virus, the risk of human infection increases dramatically. Early detection of the threshold virus concentration is essential for prevention of the spread of influenza infection. This review discusses different approaches for measuring the amount of influenza A virus particles in the air and assessing their infectiousness. Here we also discuss the data describing the relationship between the influenza virus subtypes and virus air transmission, and distribution of viral particles in aerosol drops of different sizes.
Buildings are connected to multiple information systems such as Building Management Systems (BMS), Energy Management Systems (EMS), Internet of Things (IoT) devices, Building Information Models ...(BIM), electricity grid, weather services, etc. Modern data-driven smart building software applications demand seamless integration of the above systems and their data. These applications range from monitoring and analytics to data-driven real-time control of building assets and are only efficient if they are reusable, modular and scalable. However, the lack of a system architecture with well-defined Application Programming Interfaces (APIs) that integrates the above systems to provide access to systems and their data poses a significant challenge for developing and deploying such reusable, modular and scalable applications. With the absence of such architecture, the existing applications often rely on ad-hoc tooling, repetitive methods and inefficient data handling practices. In response to the challenges outlined above, this article presents the design and implementation of a system architecture with data-driven smart building applications in mind. The architecture aims to improve the overall reusability, modularity and scalability of smart building applications. The proposed system architecture relies on the Zachman framework and consists of services in five categories, i.e., 1) legacy systems, 2) modern applications, 3) third-party systems, 4) integration software, 5) databases, and 6) user interfaces. The proposed architecture closely resembles the MACH architectural principles: a) Microservices; b) Application Programming Interfaces (API)-first (exposing functionality via APIs), c) Cloud-based components, and d) Headless principles (front-end and back-end logic are decoupled). The proposed architecture is implemented as a proof-of-concept along with three smart building applications, namely 1) a Digital Twin application integrating sensor data with a BIM model, 2) a web application integrating real-time sensor data with semantic graphs, and 3) a data exploratory tool using sensor data, the Brick ontology and Grafana dashboards. Future implementations also include real-time control applications. The proposed architecture and the implementations show a reusable, modular and scalable architecture blueprint that can be used to develop similar architectures for the smart building domain.
•An abnormal decrease in diffusion coefficients occurred when the system approached the cloud point.•An abnormal increase in the diffusion coefficients occurred at temperatures above the cloud ...point.•These abnormalities are explained by changes in the size of the diffusing objects from the micelles to dehydrated aggregates and their destruction by thermal motion.
We have investigated solutions of oxyethylated alkylphenols (neonols) in a mixture of ordinary and heavy water with equal densities of the neonols and the aqueous mixture. The equal densities allow exclusion of sedimentation effects and study of the evolution of micelles and neonol aggregates in the range from room temperature to above the cloud point. The self-diffusion coefficients of neonols were measured by NMR and the effective hydrodynamic radii of micelles and neonol aggregates were calculated using the Stokes-Einstein relation. An abnormal decrease in neonols diffusion coefficients occurred when the system approached the cloud point, while an abnormal increase in the diffusion coefficients occurred at temperatures above the cloud point. We explained the abnormal temperature behavior of the diffusion coefficients of neonols by changes in the size of the diffusing objects from the spherical and spherocylindrical micelles to dehydrated aggregates and the destruction of micelles by thermal motion and by formation of aggregates with sizes of the order 102 nm at temperatures above the cloud point. Conclusions about the increase in the hydrodynamic radii of the micelles with increasing temperature up to the cloud point and about the formation of dehydrated aggregates above the cloud point are confirmed by the results of DLS studies.
Through the use of optical tweezers we performed controlled translocations of DNA–protein complexes through nanocapillaries. We used RNA polymerase (RNAP) with two binding sites on a 7.2 kbp DNA ...fragment and a dCas9 protein tailored to have five binding sites on λ-DNA (48.5 kbp). Measured localization of binding sites showed a shift from the expected positions on the DNA that we explained using both analytical fitting and a stochastic model. From the measured force versus stage curves we extracted the nonequilibrium work done during the translocation of a DNA–protein complex and used it to obtain an estimate of the effective charge of the complex. In combination with conductivity measurements, we provided a proof of concept for discrimination between different DNA–protein complexes simultaneous to the localization of their binding sites.
This article presents a new approach to preparing the precursors of complex oxide systems Al2O3-ZrO2-MXOY (M = Mg, Ce). The approach is based on the electrogeneration and interaction of reagents with ...electrolyte components in a coaxial electrochemical reactor. The design of the electrolyzer provides the suspension homogenization due to the turbulence induced by the intensive hydrogen bubbles and electrolyte movement in opposite directions relative to the central electrode in a closed space. Hydrogen evolution leads to the mixing of the solution. The transfer of OH− ions generated at the cathode into the electrolyte and interaction with metal ions (Zr, Al, Ce, Mg) leads to the formation of hydroxoaqua complexes of these metals. They participate in the polycondensation reaction, forming polymerized hydroxides and oxyhydroxides, which are the basis of the primary particles. The process of hydroxylation of nanoparticle surface of the formed precursors of oxide systems stabilizes the dispersion and prevents particle aggregation. The stabilized tetragonal t-ZrO2 was obtained by sintering the precursor of the synthesized oxide system at 1100 °C with the formation of an alumina phase (γ-Al2O3, or an aluminum–magnesium spinel MgAl2O4) with a low CeO2 content (2–3 wt%).
PDF
