Vilhelmsengarza3618

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We have developed a rapid and sensitive single-well dual-parametric method introduced in linked RAS nucleotide exchange and RAS/RAF-RBD interaction assays. RAS mutations are frequent drivers of multiple different human cancers, but the development of therapeutic strategies has been challenging. Traditionally, efforts to disrupt the RAS function have focused on nucleotide exchange inhibitors, GTP-RAS interaction inhibitors, and activators increasing GTPase activity of mutant RAS proteins. As the amount of biological knowledge grows, targeted biochemical assays enabling high-throughput screening have become increasingly interesting. We have previously introduced a homogeneous quenching resonance energy transfer (QRET) assay for nucleotide binding studies with RAS and heterotrimeric G proteins. Here, we introduce a novel homogeneous signaling technique called QTR-FRET, which combine QRET technology and time-resolved Förster resonance energy transfer (TR-FRET). The dual-parametric QTR-FRET technique enables the linking of guanine nucleotide exchange factor-induced Eu3+-GTP association to RAS, monitored at 615 nm, and subsequent Eu3+-GTP-loaded RAS interaction with RAF-RBD-Alexa680 monitored at 730 nm. Both reactions were monitored in a single-well assay applicable for inhibitor screening and real-time reaction monitoring. This homogeneous assay enables separable detection of both nucleotide exchange and RAS/RAF interaction inhibitors using low nanomolar protein concentrations. To demonstrate a wider applicability as a screening and real-time reaction monitoring method, the QTR-FRET technique was also applied for G(i)α GTP-loading and pertussis toxin-catalyzed ADP-ribosylation of G(i)α, for which we synthesized a novel γ-GTP-Eu3+ molecule. The study indicates that the QTR-FRET detection technique presented here can be readily applied to dual-parametric assays for various targets.Potentiometric pH probes remain the gold standard for the detection of pH but are not sufficiently sensitive to reliably detect ocean acidification at adequate frequency. Here, potentiometric probes are made dramatically more sensitive by placing a capacitive electronic component in series to the pH probe while imposing a constant potential over the measurement circuit. learn more Each sample change now triggers a capacitive current transient that is easily identified between the two equilibrium states, and is integrated to reveal the accumulated charge. This affords dramatically higher precision than with traditional potentiometric probes. pH changes down to 0.001 pH units are easily distinguished in buffer and seawater samples, at a precision (standard deviation) of 28 μpH and 67 μpH, respectively, orders of magnitude better than what is possible with potentiometric pH probes.Graphene oxide (GO) is a promising 2D material for adsorbents and membranes, in particular, for the CO2 separation process. However, CO2 diffusion and sorption in GO and its layered structures are still not well understood because of its heterogeneous structure. Here we report CO2 sorption in GO and its derivatives (e.g., reduced GO (rGO)) in powders and films. These CO2 sorption behaviors reveal that GO is highly CO2-philic via complex CO2-functional-group-surface interactions, as compared with graphite and rGOs. Even in highly interlocked, lamellar GO films, CO2 molecules above a certain threshold pressure can diffuse into GO interlayers, causing GO films to swell and leading to dramatic increases in CO2 sorption. Intercalated water in GO interlayers can be removed by preferential CO2 sorption without any changes in the GO chemical structure. This finding helps to explain the origin of CO2 affinity with GO and has implications for preparing anhydrous GO assemblies for various applications.Identifying biomolecules for disease diagnosis requires simple, accurate, and reliable analytical techniques. Multiple signal transduction pathways have promoted the development of various biological analysis systems. However, most systems are largely limited by a single mechanism or model analysis, which can easily lead to false-positive/negative results. Herein, we report a covalent organic framework (COF) (TpPa-1) functionalized with a dye (fluorescein sodium) and design this hybrid material (TpPa-1@Dye) to fabricate hydrogels for subsequent analysis with the indicator displacement assay (IDA) method. Selecting a suitable metal cation (Cr3+) for the preparation of hydrogels can reduce the background fluorescence, improve the detection sensitivity, and increase the corresponding sensing selectivity. The TpPa-1@Dye functions as an indicator in the IDA-in-COF system, and Cr3+ is a receptor of the analyte (sialic acid (SA), a biomarker for ovarian cancer diagnosis). Based on the above studies, the integrative logic operations (AND + IMP) are further established, it helps in elucidating the design rules of the IDA-in-COF approach. This work represents the first effort in designing IDA-in-COF luminescent sensors with an On-Off-On mechanism to determine biomarkers and provides a new approach for developing hybrid COF luminescent materials as analysis platforms for human health monitoring.Novel cores for high performance nonfullerene acceptors (NFAs) remain to be developed. In this work, two new n-type nitrogen-containing organic heterocyclic NFAs, namely, BDTN-BF and BDTN-Th, were designed and synthesized based on a new seven fused-ring core (BDTN) with two different end-capping groups. As a result, BDTN-BF possessed similar absorption spectra in solution and solid state to BDTN-Th, but a slightly higher maximum molar extinction coefficient. Manufacturing the polymer solar cells with PM6 as the donor, the photovoltaic performance of BDTN-BF and BDTN-Th was investigated. The PM6BDTN-BF-based device achieved the highest power conversion efficiency (PCE) of 11.54% with a high Jsc of 20.20 mA cm-2, a fill factor (FF) of 61.46%, and a large Voc of 0.93 V, and the energy loss (Eloss) was calculated to be 0.48 eV. Comparatively, the PM6BDTN-Th-based device achieved the maximum PCE value of only 3.53% because of inadequate Jsc and FF. The higher Jsc and FF for the PM6BDTN-BF-based device was mainly due to the effective electron transfer from PM6 to BDTN-BF, more balanced μh/μe, higher electron mobility of the neat film, better charge collection and dissociation efficiency, and more favorable morphology.