Simultaneous determination of the repertoire of classical neurotransmitters released from embryonal carcinoma stem cells using online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry

Dynamic, continuous, and simultaneous multi-analysis of transmitters is important for the delineation of the complex interactions between the neuronal and intercellular communications. But the analysis of the whole repertoire of classical transmitters of diverse structure is challenging due to their different physico-chemical properties and to their high polarity feature which leads to poor retention in traditional reversed-phase columns during LC–MS analysis. Here, an online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry (online MD-HILIC–MS/MS) detection method was developed for the simultaneous measurement of the repertoire of classical transmitters (acetylcholine, serotonin, dopamine, norepinephrine, glutamate, GABA, and glycine). Stable isotope labeled internal standards and authentic matrix have been applied to guarantee reliable results. The method was successfully employed to reveal the characteristics of transmitter release from embryonal carcinoma stem cells. The method features simple procedure (no sample preparation), high recovery (≥73%), high accuracy (89.36% ≤ RE ≤ 116.89%), good reproducibility (2.18% ≤ RSD ≤ 14.56%), and sensitive limits of detection (2 pg for acetylcholine, serotonin, and glutamate, 10 pg for dopamine, norepinephrine, GABA, and glycine). It can be flexibly applied to determine the contents of the classical transmitters in other biological matrix samples with minor changes.     

Fast CEC-MS using poly(dimethylsiloxane) microinjector, short packed column, and low-sheath-flow interface

A fast CEC-MS approach based on a microinjector and a short CEC column was developed. Poly(dimethylsiloxane) was used as the substrate for microinjector fabrication. A short capillary column (～5 cm) packed with 5 μm octadecyl silica particles was inserted into the microinjector. The microinjector CEC device was interfaced to ESI-MS using a low-flow sheath liquid interface. The device delivers the advantages of sample introduction, pre-concentration, elution, and fast analysis as in chip-CEC yet avoids the difficulty of packing stationary material into the chip. The online pre-concentration and CEC-MS analysis capabilities of this device were demonstrated by analysis of a six-triazine mixture. A signal enhancement of 20-99-fold was achieved with a sample loading time of 180 s.     

Multi-residue analysis of pesticides in tea by online SEC-GC/MS

A multi-residue method for the analysis of pesticides in tea was developed by online size exclusion chromatography (SEC)-GC/MS with full scan mode. The sample was fortified with chlorpyrifos-d(10) isotope internal standard and extracted by acetonitrile. After purification by primary secondary amine sorbent and solvent exchange by SEC mobile phase, the sample was detected by online SEC-GC/MS. The purification result of the online system was evaluated by comparing the correlation between Chinese cabbage and tea matrix. The factors for method optimization included sample preparation, matrix effects and the instrument parameters of each online component. Scatter plot was introduced in this study to directly illustrate the results of the condition optimization and matrix effects in the online system. For most of the pesticides, the average recoveries ranged from 70 to 130% and the RSD were below 15%. The feasibility of the application of full scan mode in multi-residue determination of trace amounts of pesticides (LODs below 0.01 mg/kg) in a complex matrix was discussed.     

Design of online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) hyphenated systems for quantitative analysis of small organic compounds in biological matrices

Three online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method examples are presented where two different types of chromatographic columns or solvent systems were coupled to meet specific analytical objectives: (i) SPE of target analytes by restricted access media from high ionic strength urine matrix was coupled with reversed phase LC-MS/MS conditions accommodating high ionization potentials of the analytes (urinary bisphenol A and other phenolic derivatives); (ii) strong cation exchange SPE of analytes of diverse polarity and pK(a) was coupled with reversed phase LC-MS/MS analysis (urinary atrazine metabolites); (iii) pre-concentration of low pg per sample analytes by weak anion exchange SPE was hyphenated with ion pair LC-MS analysis (intracellular nucleotide triphosphate analogs). With these examples we suggest a conductive generic work flow for the development of online SPE-LC-MS methods and show how advanced commercial LC devices and software allow for the design of complex yet highly versatile analytical separation systems suited to the unique physicochemical properties of the target analytes.     

Optimal dynamic advertising policies in the presence of continuously distributed time lags

The Nerlove-Arrow model of optimal dynamic advertising policies is generalized by incorporating a continuously distributed lag between advertising expenditures and increases in the stock of goodwill. This leads to a control problem where the equation of motion is given by an integro-differential equation. The transitory and steady-state properties of the optimal policies are examined, both for a general lag function and for a gamma distributed lag. The dependence of the steady-state solution on the parameters of the gamma distribution is also investigated. An example is given using specific demand and cost functions.     

An online fiber-optic UV-visible detector for continuous free-flow electrophoresis

A PC-controlled, scanning online UV detector for continuous free-flow electrophoresis (CFFE) was designed to allow for single UV wavelength monitoring across a 1-D array of 48 longitudinal flow cells interfaced to a CFFE apparatus. In the detection scheme, the UV light is sequentially passed through each of the flow cells. The design integrates online acquisition of absorbance spectra of components separated by CFFE. Benzoic acid standard solutions were used to examine the performance of the detector. Chloroquine diphosphate and 4-nitrophenol were used as test solutes to determine the detector's ability to distinguish analytes separated in the CFFE.     

Generalized Nonlinear Variational-Like Inequalities

This study investigates how to dynamically allocate resources with a given budget for advertising through Web portals using keyword-activated banner ads on the Internet. Identifying the factors that affect the potential number of banner ad clickthroughs in each portal, we show that the process of budget allocation between the two types of portals (generic vs specialized) that leads to the largest banner clicksthrough in the long run is an optimal control problem. Using techniques of dynamic programming, we find analytical solutions for the optimal budgeting decisions. Our analysis shows that an advertisers optimal portal budgeting depends nonlinearly on the number of visitors who type the same trigger keyword and the average clicksthrough rates, as well as on the advertiser and ad effectiveness. Further, we find that the maximal number of banner clickthroughs from both portals, at time t, depends on the remaining budget until the end of the planning period. The analytical results have useful managerial insight. One of the interesting features of our solution shows that, while a large visitor base may favor the generic portal, other parameters may affect it unfavorably: e.g., lower clickthrough rates of keyword banners from a more heterogeneous audience. Using a specificaction that is consistent with empirical observations, we show that, in the long run, an advertiser must always spend more ad money at the specialized portal.     

Monitoring industrial wastewater by online GC-MS with direct aqueous injection

An online GC–MS-system for automated monitoring of crude wastewater at a complex chemical production site is presented. The modular system is, in principal, based on commercial equipment, but utilizes a special, two-stage injector, which consists of a splitless vaporization chamber on top of a PTV injector filled with Tenax. This set-up enables direct injection of wastewater. Almost 140 volatile and semi-volatile compounds are calibrated down to 1 mg L⁻¹, which is sufficient for analysis of the influent of the wastewater-treatment plant. Two instruments analyze alternately, every 20 min, and the instrument cycle time is 40 min. The quantitative results are transferred to a database which is connected to a process-control system. Depending on the nature and concentration of a compound, an alarm can be generated and the wastewater stream can be diverted into an “off spec tank” if necessary. The GC–MS-system operates quasi-continuously with a system availability >98%. Data quality is automatically controlled in each run and by daily analysis of a quality-control sample. The development of a novel stacked PTV–PTV injector design to expand the range of analytes to selected basic compounds is described.     

On the sum minimization version of the online bin covering problem

Given a set of m identical bins of size 1, the online input consists of a (potentially infinite) stream of items in (0,1]. Each item is to be assigned to a bin upon arrival. The goal is to cover all bins, that is, to reach a situation where a total size of items of at least 1 is assigned to each bin. The cost of an algorithm is the sum of all used items at the moment when the goal is first fulfilled. We consider three variants of the problem, the online problem, where there is no restriction of the input items, and the two semi-online models, where the items arrive sorted by size, that is, either by non-decreasing size or by non-increasing size. The offline problem is considered as well.