A specific HPLC-UV method for the determination of cysteine and related aminothiols in biological samples

We present a highly selective and sensitive method for the determination of cysteine (Cys) and related aminothiols that play important roles in health and disease. The key step in the analysis is treatment with 1,1′-thiocarbonyldiimidazole (TCDI) that rapidly and quantitatively reacts with both the amino and thiol groups to form stable cyclic dithiocarbamates with intense UV absorption. Cys, homocysteine (hCys), and cysteinylglycine in plasma (75 μl), urine (100 μl), or cerebrospinal fluid (100–500 μl) were determined by separating and measuring their cyclic derivatives by a high performance liquid chromatograph (HPLC) connected to a UV detector. The chromatograms obtained using TCDI contained fewer and better-resolved peaks than those produced by less selective reagents used previously. Using chemically similar 2-methylcysteine as the internal standard, high repeatability (variation of less than 5%) and adequate sensitivity to detect small increments (10–20%) in the concentrations of cysteinylglycine and hCys were achieved. The HPLC method can also be modified to measure -penicillamine (greater than 0.8 μM) in plasma (50 μl) providing a potential method to monitor plasma levels of this drug in patients.     

A Sharp Inequality of Markov Type for Polynomials Associated with Laguerre Weight

The best possible constant A_n in an inequality of Markov type

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, where ·_[0, ∞) denotes the sup-norm on the half real line [0, ∞) and p_n is an arbitrary polynomial of degree at most n, is determined in terms of the weighted Chebyshev polynomials associated with the Laguerre weight e^−x on [0, ∞).     

Erratum to ``On a conjecture of Koike on identities between Thompson series and Rogers-Ramanujan functions'

This note gives a correction to formula (A.18) of Appendix A.

     

Development,validation, and implementation of capillary gel electrophoresis as a replacement for SDS‐PAGE for purity analysis of IgG2 mAbs

Capillary gel electrophoresis (CGE) methods with UV detection were developed for reduced and non‐reduced mAb analysis. These methods can be used to evaluate mAb purity, offering more reproducible quantitation compared with that of traditional SDS‐PAGE methods. These CGE methods have been utilized as platform technology for bioprocess development, formulation development, mAb characterization, drug substance/drug product release testing as well as a required methodology for stability testing. We have found these CGE methods to be applicable across a platform of mAbs in preclinical and clinical development, with the majority of mAbs requiring no modification to the method conditions. This methodology has been ICH validated and transferred to several supporting organizations. The data presented herein describes the development of CGE methodology, platform application to mAb purity analysis, ICH validation, reliability metrics, and considerations on technology enhancement for improved performance and throughput.     

Noise bandwidth dependence of soliton phase in simulations of stochastic nonlinear Schrödinger equations

We demonstrate that soliton perturbation theory, though widely used, predicts an incorrect phase distribution for solitons of stochastically driven nonlinear Schr?dinger equations in physically relevant parameter regimes. We propose a simple variational model that accounts for the effect of radiation on phase evolution and correctly predicts its distribution.     

Divergent C?H Insertion–Cyclization Cascades of N‐Allyl Ynamides

Gold carbene reactivity patterns were accessed by ynamide insertion into a C(sp³) H bond. A substantial increase in molecular complexity occurred through the cascade polycyclization of N‐allyl ynamides to form fused nitrogen‐heterocycle scaffolds. Exquisite selectivity was observed despite several competing pathways in an efficient gold‐catalyzed synthesis of densely functionalized C(sp³)‐rich polycycles and a copper‐catalyzed synthesis of fused pyridine derivatives. The respective gold–keteniminium and ketenimine activation pathways have been explored through a structure–reactivity study, and isotopic labeling identified turnover‐limiting C H bond‐cleavage in both processes.     

Polyfluorinated cycloalkoxyphenyl ether systems as dopants for liquid crystal display applications

The effects on response times of representative commercially available dielectrically negative (−LC) and positive (+LC) type liquid crystal mixtures doped with small quantities of various tetrafluorinated cycloalkoxyphenyl ether derivatives were investigated. The synthesis of various polyfluoroaryl systems by nucleophilic aromatic substitution processes is described and electro-optical measurements concerning the rise and decay times and voltage holding ratios of each doped LC formulation are reported. The response time of the dielectrically negative LC host was improved upon doping with each of the tetrafluorinated cycloalkoxyphenyl ether derivatives, although no improvement in the performance of the dielectrically positive LC host was achieved.     

Episodic paroxysmal laryngospasm: Voice and pulmonary function assessment and management

Episodic paroxysmal laryngospasm (EPL) is a sign of laryngeal dysfunction, often without a specific organic etiology, which can masquerade as asthma, vocal fold paralysis, or a functional voice disorder. The intermittent respiratory distress of EPL may precipitate an apparent upper airway obstructive emergency, resulting in unnecessary endotracheal intubation, cardiopulmonary resuscitation, or tracheostomy. During 27 months, seven women and three men, ages 30–76 years, were assessed by a high diagnostic index of suspicion, an intensive history including psychosocial factors, physical examination of the airways, provocative asthma testing, and swallowing studies. Videolaryngoscopy, stroboscopy, and pulmonary flow-volume loop testing were definitive. The classic appearance was paradoxic inspiratory adduction of the anterior vocal folds with a posterior diamond-shaped glottic gap. During an attack of stridor or wheezing, attenuation of the inspiratory flow rate as depicted by the flow-volume loop suggested partial extrathoracic upper airway obstruction. Swallowing evaluation by videolaryngoscopy and videoesophagography may uncover gastroesophageal reflux disease. Hallmarks of management include patient and family education by observation of laryngoscopic videos, a specific speech therapy program, psychotherapy, and medical treatment of associated disorders. Electromyography may become a valuable future adjunct. Unlike laryngeal dystonia, patients with EPL do not benefit from botulinum toxin type A.     

Synthesis of 4-alkoxy-Δ3-pyrrolin-2-ones and tetramic acids

Acetoacetic ester is converted into 4-alkoxy-Δ³-pyrrolin-2-ones which can be hydrolyzed to give tetramic acids.