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关键词： Affinity measurements   Pre-equilibrium titration curves   High-affinity interactions   Therapeutic antibodies  

摘要： Equilibrium titration curves have been used to determine the affinity of biomolecules using a variety of platforms and technologies. Such measurements, however, are experimentally limited by the time that is needed for the system to reach the equilibrium, which may exceed the time during which the studied biomolecules are stable. We propose here a kinetic model to analyze titration curves obtained prior to full equilibration of the system.

关键词： End-point detection   Intelligent photometric titration system   Curve-fitting   Micro-flow injection titrator   Chemical oxygen demand determination  

摘要： The characteristics of the signals during the process of chemical oxygen demand (COD) titration are analyzed in this paper. The signals are derived for normalized titration curves of reactions having the color mutation reaction. After analyzing the characteristics, the critical control points are observed. The switch, stop and end points are searched by the algorithm on a computer. Based on this three-point method, a new intelligent photometric titration system is constructed for COD, without using the calibration curves. Using this system, a new intelligent photometric titrator has been built for COD for automatic sampling and intelligent titrating. Under computer control, the process of titration is conducted intelligently and accurately;no manual operation or assistance is required. The titration chamber was homemade. The optimized conditions of the titration system are as follows: the titrant was consecutively micro-flow injected into the chamber with a velocity of 0.00576 mL.s(-1);100 points per second of the titrating process signal were collected;and the homemade agitator blade stirred at a speed of 420 rpm. The preferences tested by actual samples proved that this titrator meets the requirements of the standard method and is suitable for use in experiments. Overall, our approach facilitates adoption of an intelligent titrimetry system for the determination of photometric titration.

关键词： electrostatics   Gaussian-based dielectric function   pKa's   Poisson-Boltzmann equation   proteins   salt concentration  

摘要： DelPhiPKa is a widely used and unique approach to compute pK(a)'s of ionizable groups that does not require molecular surface to be defined. Instead, it uses smooth Gaussian-based dielectric function to treat computational space via Poisson-Boltzmann equation (PBE). Here, we report an expansion of DelPhiPKa functionality to enable inclusion of salt in the modeling protocol. The method considers the salt mobile ions in solvent phase without defining solute-solvent boundary. Instead, the ions are penalized to enter solute interior via a desolvation penalty term in the Boltzmann factor in the framework of PBE. Hence, the concentration of ions near the protein is balanced by the desolvation penalty and electrostatic interactions. The study reveals that correlation between experimental and calculated pK(a)'s is improved significantly by taking into consideration the presence of salt. Furthermore, it is demonstrated that DelphiPKa reproduces the salt sensitivity of experimentally measured pK(a)'s. Another new development of DelPhiPKa allows for computing the pK(a)'s of polar residues such as cysteine, serine, threonine and tyrosine. With this regard, DelPhiPKa is benchmarked against experimentally measured cysteine and tyrosine pK(a)'s and for cysteine it is shown to outperform other existing methods (DelPhiPKa RMSD of 1.73 vs RMSD between 2.40 and 4.72 obtained by other existing pK(a) prediction methods).

关键词： Macro-plastic   Leachate   Endocrine-disrupting compounds   Eco-toxicology   Marine debris  

摘要： Plastic debris is an emerging worldwide threat to marine biota. Marine species may face unique challenges in low-flow estuarine systems with a high abundance of "macro-sized" (> 4.75 mm) plastic due to the leaching of constituents and adsorbed contaminants. To simulate this leaching process, plastic samples recovered from the North Pacific Gyre along with corresponding UV-irradiated virgin plastic and non-irradiated virgin plastic counterparts were incubated in saltwater for 30 days at ambient temperatures ranging from 17 to 25 degrees C. Following solid-phase extraction, water samples were fractionated with sequential methanol elution from 10 to 100% and evaluated using in vitro assays assessing estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) activities. In vivo responses (vitellogenin [vtg] and cytochrome p450 1A [cyp 1a] mRNA) were measured following 5-day exposures in Japanese medaka (Oryzias latipes) larvae (3 days post hatch). Estrogenic plasticizers, co-planar PCBs and PAHs were quantified in the extracts using targeted GC-MS/MS and UPLC-MS/MS. In vitro estrogenicity showed highest activity in the 70% methanol fraction for all plastic leachate exposures. Whole extract in vitro estradiol equivalent (EEQ) values were 4.34 +/- 2.65, 8.79 +/- 2.09 and 13.78 +/- 3.64 ng/L, for virgin plastic, UV-irradiated virgin plastic and North Pacific Gyre-recovered plastic, respectively (mean +/- SD). Significant vtg induction was observed in medaka larvae exposed to leachate extracts from North Pacific Gyre recovered plastic and UV-irradiated virgin plastic (9.9-fold, p = 0.039 and 10.1-fold, p = 0.042, respectively). Chemically-determined EEQ values were also localized in the 70% methanol fraction. Whole leachate extract chemical EEQ values were 0.33 +/- 0.07, 1.64 +/- 0.62 and 11.4 +/- 2.13 ng/L, for virgin plastic, UV-irradiated virgin plastic and North Pacific Gyre-recovered plastic, respectively. In-vitro AhR activity was highest in the 70% methanol elution w

关键词： electroconvulsive therapy   ECT   titration   dosing strategies  

摘要： Background: Although the dosage of electroconvulsive therapy (ECT) stimulus has a major impact on the efficacy and safety of this treatment, the method used to determine an optimal dosage remains a matter of debate. Objective: We investigated factors influencing the seizure threshold (ST) in a large-sample study and compared age-based and titration dosing methods in terms of charge. Methods: A retrospective study examined data from 503 patients across France and Canada. The patients underwent right unilateral (RUL) or bitemporal (BT) ECT during a titration session before undergoing ECT. Seizure threshold and charge differences between age-based and titrationpredicted methods were derived for each RUL and BT patient and compared according to sex, age, and anesthetic agents. Results: Based on our results, ST is a function of electrode placement, sex, age, and anesthetic agents. Titration and age-based methods led to completely different patterns of charges for the same electrode placement, especially in elderly and inwomen in the RUL group. Regressionmodels showed that differences between the age-based and titration methods varied with respect to age, sex, and anesthetic agent. Specifically, significant effects of sex and age were observed for RUL ECT and of sex and anesthetics for BT ECT. Conclusions: This study revealed that several factors significantly influence the prediction of ECT dose, depending on individuals and treatment modalities. Caution should be exercised when using nonindividualized methods to calculate ST.

关键词： Obstructive sleep apnea   Continuous positive airway pressure   Drug-induced sleep endoscopy   Polysomnography   Apnea-hypopnea index  

摘要： Purpose The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE). Methods A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels. Results A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively, by Spearman correlation). Patients with concentric collapse of the velum or lateral oropharyngeal collapse were associated with a significantly higher CPAP titration level (P < 0.001 and P = 0.043, respectively, by nonparametric Mann-Whitney U test;P < 0.001 and P = 0.004, respectively, by Spearman correlation). No significant association was found between the CPAP titration level and any other collapse at the tongue base or epiglottis. Conclusions By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

关键词： Acute respiratory distress syndrome   Ventilator-associated lung injury   Respiratory mechanics   Transpulmonary pressure   Intra-abdominal pressure  

摘要： Purpose: Pulmonary recruitment and positive end-expiratory pressure (PEEP) titrated according to minimal static elastance of the respiratory system (PEEPEstat,RS) compared to PEEP set according to the ARDSNetwork table (PEEPARDSNetwork) as a strategy to prevent ventilator-associated lung injury (VALI) in patients with acute respiratory distress syndrome (ARDS) increases mortality. Alternatively, avoiding negative end-expiratory transpulmonary pressure has been discussed as superior PEEP titration strategy. Therefore, we tested whether PEEPEstat,RS or PEEPARDSNetwork prevent negative end-expiratory transpulmonary pressure in ARDS patients. Material and methods: Thirteen patients with moderate to severe ARDS were studied at PEEPARDSNetwork versus PEEPEstat,RS. Patients were then grouped post hoc according to the end-expiratory transpulmonary pressure (positive or negative). Results: 7 out of 13 patients showed negative end-expiratory transpulmonary pressures (Ptp-) with both strategies (PEEPARDSNetwork: - 5.4 +/- 3.5 vs. 2.2 +/- 3.7 cm H2O, p = .005;PEEPEstat,RS: - 3.6 +/- 15 vs. 35 +/- 3.3 cm H2O, p < .001). Ptp- was associated with higher infra-abdominal pressure and lower end-expiratory lung volume with both PEEP strategies. Conclusions: In patients with moderate-to-severe ARDS, PEEP titrated according to the minimal static elastance of the respiratory system or according to the ARDSNetwork table did not prevent negative end-expiratory transpulmonary pressure. (C) 2018 Elsevier Inc. All rights reserved.

关键词： Analytical chemistry   Actinide   Americium oxide   Plutonium  

摘要： Presented here are three case studies that demonstrate the breadth of bulk actinide analytical chemistry at Los Alamos National Laboratory (LANL). This laboratory was established during the Manhattan Project and is still considered one of the premier analytical laboratories for special nuclear materials characterization around the globe. First, the analytical chemistry of Pu-238 is presented, showcasing the unique challenges of this high activity isotope. Next, the analysis of (AmO2)-Am-241 is discussed from the perspective of supporting nascent production at LANL. Finally, the analytical chemistry support of the production of plutonium non-destructive assay standards is discussed. These examples paint a picture of the analytical capabilities needed to meet the dynamic challenges of LANL's nuclear programs.

关键词： Upper-Division Undergraduate   Analytical Chemistry   Laboratory Instruction   Hands-On Learning/Manipulatives   Drugs/Pharmaceuticals   Titration/Volumetric Analysis   Quantitative Analysis   Curriculum   Applications of Chemistry   Problem Solving/Decision Making  

摘要： Potency assays of pharmaceutical products are designed to measure the amount of an active ingredient in a sample. They are important quality control tools for all medications, including intravenous (IV) admixture fluid bags which are commonly prepared by pharmacists in healthcare facilities via extemporaneous compounding. An interdisciplinary laboratory module was created by combining the learning outcomes of a pharmacy compounding course with the classic undergraduate chemistry quantitative analysis course. The pharmacy students prepared the IV bags of calcium gluconate or magnesium sulfate in isotonic saline vehicle based on given prescriptions. The analytical chemistry students applied United States Pharmacopeia complexometric titration methods to determine the concentration of calcium or magnesium in the IV fluid and convert it to mass for each bag. The analytical results allowed the pharmacy students to confirm whether their IV bags met the passing criteria for the labeled claimed mass. This transformative learning experience provides an interesting real-life application for a quantitative analysis laboratory course and highlights the importance of quality control in the pharmacy compounding course.