A competitive and reversible deactivation approach to catalysis-based quantitative assays

Catalysis-based signal amplification makes optical assays highly sensitive and widely useful in chemical and biochemical research. However, assays must be fine-tuned to avoid signal saturation, substrate depletion and nonlinear performance. Furthermore, once stopped, such assays cannot be restarted, limiting the dynamic range to two orders of magnitude with respect to analyte concentrations. In addition, abundant analytes are difficult to quantify under catalytic conditions due to rapid signal saturation. Herein, we report an approach in which a catalytic reaction competes with a concomitant inactivation of the catalyst or consumption of a reagent required for signal generation. As such, signal generation proceeds for a limited time, then autonomously and reversibly stalls. In two catalysis-based assays, we demonstrate restarting autonomously stalled reactions, enabling accurate measurement over five orders of magnitude, including analyte levels above substrate concentration. This indicates that the dynamic range of catalysis-based assays can be significantly broadened through competitive and reversible deactivation

An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R)

Background: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper (R) test. Methods: Ten international pathology institutions participated in this study and determined messenger RNA expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with the MammaTyper (R) test. Samples were measured repeatedly on different days within the local laboratories, and reproducibility was assessed by means of variance component analysis, Fleiss' kappa statistics, and interclass correlation coefficients (ICCs). Results: Total variations in measurements of centrally and locally prepared RNA extracts were comparable; therefore, statistical analyses were performed on the complete dataset. Intersite reproducibility showed total SDs between 0.21 and 0.44 for the quantitative single-marker assessments, resulting in ICC values of 0.980-0.998, demonstrating excellent agreement of quantitative measurements. Also, the reproducibility of binary single-marker results (positive/negative), as well as the molecular subtype agreement, was almost perfect with kappa values ranging from 0.90 to 1.00. Conclusions: On the basis of these data, the MammaTyper (R) has the potential to substantially improve the current standards of breast cancer diagnostics by providing a highly precise and reproducible quantitative assessment of the established breast cancer biomarkers and molecular subtypes in a decentralized workup.Peer reviewe

Capillary electrophoresis -- high resolution inductively coupled plasma mass spectrometry: elemental speciation and applications in pharmaceutical process research

The high efficiency of capillary electrophoresis (CE) was combined with the element specificity and low detection limits of high resolution inductively coupled plasma mass spectrometry (HR-ICP MS) for rapid elemental speciation. A novel sheath flow interface coupled to a PFA Teflon micro-flow concentric nebulizer was developed to provide an efficient method for interfacing capillary electrophoresis with the inductively coupled plasma. The sheath interface provides control over the nebulizer induced laminar flow in the separation capillary allowing the tradeoff between separation efficiency and analysis time to be selected. In chapter 3, this CE-HR-ICP-MS system was used to study various hydration/hydrolysis processes of hexachloro complexes of Rh in aqueous solutions. The migration speed of various mixed aquo/chloro rhodium species through the capillary depends on the charges they carry, which is dictated by the solution pH as well as their aging period in the solution. Several Rh species were tentatively identified according to their relative mobilities and their equilibrium distributions were quantified using peak area calculation in the experiments. In chapter 4, to meet the need of speciation analysis for applications in pharmaceutical process research, a non-aqueous CE with HR-ICP-MS detection method was developed. The novel sheath interface between the CE and ICP-MS enabled the use of CE with up to 100% organic electrolyte without organic loading in the plasma. Two unique aspects of non-aqueous CE, non-aqueous CE with wide-bore capillaries and influence of organic solvent on the CE separation selectivity were discussed. Information on chemical speciation is much needed in mechanistic and kinetic studies on catalyst formation processes in pharmaceutical research. In chapter 5, non-aqueous CE-ICP-MS speciation analysis was applied to the identification and quantification of various rhodium species involved in a ligand exchange process leading to formation of catalyst dirhodium(II) tetrakis[methyl 2-oxopyrrolidin-5(S)-carboxylate]. A variety of reaction intermediates were identified and quantified along the pathway to formation of the desired product. This has provided new insights into the mechanism and kinetics of the reaction. In chapter 6, the feasibility of the determination of sub ppm to percentage levels of halogen elements (fluorine, chlorine, bromine, and iodine) in solid organic compounds and drug substances by HR-ICP-MS was investigated. In chapter 7, the application of HR-ICP-MS for the determination of isotopic composition of enriched stable isotope calcium samples is described. The interferences from 40Ar isotope at the calcium mass 40 are greatly minimized by operating the ICP-MS in the cool plasma mode. The rest polyatomic ions are overcome by high resolution mode of the ICP-MS.Ph.D.Includes bibliographical references (p. 269-270)

Event-triggered model-free adaptive predictive control for multi-area power systems under deception attacks

This paper focuses on the event-triggered model-free adaptive predictive load frequency control (LFC) problem for multi-area power systems under false data injection (FDI) attacks. First, the power system model is assumed to be unknown, and the nonlinear power system is converted into an equivalent linear data model using the input and output data of the powerline system. The FDI attacks on the power system is also modeled, and a Bernoulli stochastic process is used to represent whether the data is transmitted successfully or not. Second, the equivalent linear data model to predicts upcoming events, and a new event-triggered model-free adaptive predictive control scheme is designed via the predictions. And a RBF neural network disturbance estimator is designed to estimate and compensate for the effects caused by disturbances, and then power system stability is analyzed. An event-triggered scheme is also developed in the design of the LFC in order to save communication and computational burden. The results show that the designed control algorithm is data-driven independent of the power system structure and does not require the measurement of any system state signals. Finally, the effectiveness and correctness of the scheme is verified by a three-area numerical example and simulation results

Data‐driven iterative learning trajectory tracking control for wheeled mobile robot under constraint of velocity saturation

Abstract Considering the wheeled mobile robot (WMR) tracking problem with velocity saturation, we developed a data‐driven iterative learning double loop control method with constraints. First, the authors designed an outer loop controller to provide virtual velocity for the inner loop according to the position and pose tracking error of the WMR kinematic model. Second, the authors employed dynamic linearisation to transform the dynamic model into an online data‐driven model along the iterative domain. Based on the measured input and output data of the dynamic model, the authors identified the parameters of the inner loop controller. The authors considered the velocity saturation constraints; we adjusted the output velocity of the WMR online, providing effective solutions to the problem of velocity saltation and the saturation constraint in the tracking process. Notably, the inner loop controller only uses the output data and input of the dynamic model, which not only enables the reliable control of WMR trajectory tracking, but also avoids the influence of inaccurate model identification processes on the tracking performance. The authors analysed the algorithm's convergence in theory, and the results show that the tracking errors of position, angle and velocity can converge to zero in the iterative domain. Finally, the authors used a simulation to demonstrate the effectiveness of the algorithm

Evaluation of C–reactive protein and fibrinogen in comparison to CEA and CA72–4 as diagnostic biomarkers for colorectal cancer

Carcinoembryonic antigen (CEA) and carbohydrate antigen 72–4 (CA72–4) are commonly used markers for colorectal cancer (CRC) in clinical applications. However, low positivity rate and sensitivity limits their clinical effectiveness. In this study, we explored the potential of C–reactive protein (CRP) and fibrinogen to improve the diagnostic efficiency of traditional biomarkers of CRC. The concentrations of CRP and fibrinogen in plasma were significantly higher in CRC patients compared with benign or healthy controls. The area under the ROC curves (AUCs) showed that the diagnostic efficacy of CRP and fibrinogen was 0.745 (95% CI: 0.712–0.779) and 0.699 (95% CI: 0.663–0.734), respectively. AUC increased to 0.750 (95% CI: 0.716–0.784) when CRP and fibrinogen were combined. It also further improved to 0.889 (95% CI: 0.866–0.913) when CRP and fibrinogen were integrated with CEA and CA72–4. Moreover, this combination increased the maximum area under AUC to 0.857 (95% CI: 0.830–0.883), which effective differentiated CRC from benign disease. Overall, this study found that CRP and fibrinogen were highly expressed in the plasma of CRC patients, suggesting their potential to improve the diagnostic efficiency of traditional biomarkers of CRC

Influence of biotic and abiotic factors on flea species population dynamics on Lasiopodomys brandtii

Brandt's Vole (Lasiopodomys brandtii) is one of the most abundant rodent species in the grasslands of Inner Mongolia, China, and one of the main carriers of Yersinia pestis, the plague bacterium. There have been several instances of plague transmission among L. brandtii, and all of their dominant flea species are known carriers of plague. Little work has been done to understand the regulation of flea abundance on L. brandtii by biotic and abiotic factors. Here, we examine the impacts of host and climate variation on flea abundance on L. brandtii in May, July, and September of 2021 in the East Ujumqin Banner, Xilinhot City, Inner Mongolia Autonomous Region. We arrived at the following conclusions: 1) There were 8 flea species representing 2 families and 5 genera collected from L. brandtii, and Frontopsylla luculenta, Neopsylla pleskei orientalis, and Amphipsylla primaris mitis were most common. 2) Host body weight, host age, season, temperature, and humidity are key factors influencing flea abundance on L. brandtii. 3) Flea species vary in their respective responses to factors

Association between Serum Vitamin C and the Blood Pressure: A Systematic Review and Meta-Analysis of Observational Studies

Background. Hypertension is regarded as a major and independent risk factor of cardiovascular diseases, and numerous studies observed an inverse correlation between vitamin C intake and blood pressure. Aim. Our aim is to investigate the relationship between serum vitamin C and blood pressure, including the concentration differences and the correlation strength. Method. Two independent researchers searched and screened articles from the National Library of Medicine, Cochrane Library, Web of Science, China National Knowledge Infrastructure, VIP databases, and WANFANG databases. A total of 18 eligible studies were analyzed in the Reviewer Manager 5.3 software, including 14 English articles and 4 Chinese articles. Results. In the evaluation of serum vitamin C levels, the concentration in hypertensive subjects is 15.13 μmol/L lower than the normotensive ones (mean difference=−15.13, 95% CI [-24.19, -6.06], and P=0.001). Serum vitamin C has a significant inverse relation with both systolic blood pressure (Fisher’s Z=−0.17, 95% CI [-0.20, -0.15], P<0.00001) and diastolic blood pressure (Fisher’s Z=−0.15, 95% CI [-0.20, -0.10], P<0.00001). Conclusions. People with hypertension have a relatively low serum vitamin C, and vitamin C is inversely associated with both systolic blood pressure and diastolic blood pressure

Ambient fabrication of large-area graphene films via a synchronous reduction and assembly strategy

A synchronous reduction and assembly strategy is designed to fabricate large-area graphene films and patterns with tunable transmittance and conductivity. Through an oxidation–reduction reaction between the metal substrate and graphene oxide, graphene oxide is reduced to chemically converted graphene and is organized into highly ordered films in situ. This work will form the precedent for industrial-scale production of graphene materials for future applications in electronics and optoelectronics