Evaluation of high-field asymmetric waveform ion mobility spectrometry coupled to nanoelectrospray ionization for bioanalysis in drug discovery

The potential of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to nanoelectrospray ionization (nanoESI) as a method to improve sample throughput for bioanalysis in a discovery pharmaceutical setting was explored in this work. The ability of FAIMS to separate gas-phase ions in the millisecond timescale was exploited to eliminate the need for liquid chromatography. Samples were introduced into the FAIMS electrodes/mass spectrometer using offline nanoESI at 20 nL/min and 1.5 kV. Signals were averaged for 30 s after which the next sample could be analyzed. The separation of simple mixtures, e.g., the removal of metabolite and endogenous interferences from parent drug, was demonstrated. Moreover, the application of nanoESI attenuated the ion suppression effects that normally plague conventional electrospray. On average, approximately two-thirds of the neat sample signal intensity was preserved in extracted plasma samples. Standard curves were prepared for several compounds and linearity was obtained over approximately two to three orders of magnitude. This methodology was further tested with the analysis of plasma samples from a mouse pharmacokinetic study. Concentration values determined using nanoESI-FAIMS were comparable to those determined using conventional LC/MS as demonstrated by percent differences of less than 30%. This work demonstrated the proof of concept that the combination of FAIMS and nanospray ionization can be a potentially useful tool to improve the throughput of discovery bioanalysis.     

Independent component analysis of nanomechanical responses of cantilever arrays

The ability to detect and identify chemical and biological elements in air or liquid environments is of far reaching importance. Performing this task using technology that minimally impacts the perceived environment is the ultimate goal. The development of functionalized cantilever arrays with nanomechanical sensing is an important step towards this goal. This report couples the feature extraction abilities of independent component analysis (ICA) and the classification techniques of neural networks to analyze the signals produced by microcantilever-array-based nanomechanical sensors. The unique capabilities of this analysis unleash the potential of this sensing technology to accurately identify chemical mixtures and concentrations. Furthermore, it is demonstrated that the knowledge of how the sensor array reacts to individual analytes in isolation is sufficient information to decode mixtures of analytes—a substantial benefit, significantly increasing the analytical utility of these sensing devices.     

Robust aspects of solutions in deterministic multiple objective linear programming

We study questions of robustness of linear multiple objective problems in the sense of post-optimal analysis, that is, we study conditions under which a given efficient solution remains efficient when the criteria/objective matrix undergoes some alterations. We consider addition or removal of certain criteria, convex combination with another criteria matrix, or small perturbations of its entries. We provide a necessary and sufficient condition for robustness in a verifiable form and give two formulae to compute the radius of robustness.     

Expanding neighborhood search–GRASP for the probabilistic traveling salesman problem

The Probabilistic Traveling Salesman Problem is a variation of the classic traveling salesman problem and one of the most significant stochastic routing problems. In probabilistic traveling salesman problem only a subset of potential customers need to be visited on any given instance of the problem. The number of customers to be visited each time is a random variable. In this paper, a variant of the well-known Greedy Randomized Adaptive Search Procedure (GRASP), the Expanding Neighborhood Search–GRASP, is proposed for the solution of the probabilistic traveling salesman problem. expanding neighborhood search–GRASP has been proved to be a very efficient algorithm for the solution of the traveling salesman problem. The proposed algorithm is tested on a numerous benchmark problems from TSPLIB with very satisfactory results. Comparisons with the classic GRASP algorithm and with a Tabu Search algorithm are also presented. Also, a comparison is performed with the results of a number of implementations of the Ant Colony Optimization algorithm from the literature and in six out of ten cases the proposed algorithm gives a new best solution.     

The reality of Mathematics

The power of mathematics is discussed as a way of expressing reasoning, aesthetics and insight in symbolic non-verbal communication. The human culture of discovering mathematical ways of thinking in the enterprise of exploring the understanding of the nature and the evolution of our world through hypotheses, theories and experimental affirmation of the scientific notion of algorithmic and non-algorithmic ‘computation’, is examined and commended upon.     

Local saddle point and a class of convexification methods for nonconvex optimization problems

A class of general transformation methods are proposed to convert a nonconvex optimization problem to another equivalent problem. It is shown that under certain assumptions the existence of a local saddle point or local convexity of the Lagrangian function of the equivalent problem (EP) can be guaranteed. Numerical experiments are given to demonstrate the main results geometrically.     

An Algorithm for the Job Shop Scheduling Problem based on Global Equilibrium Search Techniques

The job shop scheduling problem is considered, and an algorithm based on the global equilibrium search method is proposed for its solution. Computational experiments using well-known benchmark problems are presented. Several new upper bounds for these problems are obtained.Research partially supported by NSF and AirForce grants.     

Potential of Global Positioning System (GPS) to measure frequencies of oscillations of engineering structures

Global Positioning System (GPS) has been successfully used to measure displacements of oscillating flexible civil engineering structures such as long suspension bridges and high-rise buildings, and to derive their modal frequencies, usually up to 1 Hz, but there is evidence that these limits can be exceeded using high frequency GPS receivers. Based on systematic experiments in computer controlled oscillations with one- and three-degrees of freedom we investigated the potential of GPS, first to record higher oscillation frequencies, at least up to 4 Hz at the minimum resolution level of this instrument for kinematic applications (?5 mm), and second, to identify more than one dominant frequency. Data were processed using least squares-based spectral analysis and wavelet techniques which permit to analyze entire time series, even those of too short duration or those characterized by gaps, in both the frequency and the time domain.The ability of GPS to accurately measure frequencies of oscillations of relatively rigid (modal frequencies 1-4 Hz) civil engineering structures is demonstrated in the cases of two bridges.The outcome of this study is that GPS is suitable for the identification of dynamic characteristics of even relatively rigid (modal frequencies up to 4 Hz) civil engineering structures excited by various loads (wind, traffic, earthquakes, etc.) if displacements are above the uncertainty level of the method (?5 mm). Structural health monitoring of a wide range of structures appears therefore a promising field of application of GPS.     

2,2′:6′,2″-Terpyridine[hydroxypropyl-β-cyclodextrin] 1:3 complex used as chelating agent for the determination of iron with a sensitive, selective and fast liquid chromatographic method

In the present work, 2,2′:6′,2″-Terpyridine (terpy), a substance with very poor aqueous solubility, was dissolved in water, after formation of its inclusion complex with hydroxypropyl-β-cyclodextrin (HPβCD), in a 1:3 stoichiometry. The obtained [terpy:(HPβCD)₃] supramolecule, with enhanced aqueous solubility, enables its usage as a reagent at RP-LC methods. It was found that, terpy after inclusion complexation retains unaffected the ability of binding to Fe²⁺. It was also observed that, the stable, reddish-purple [Fe(terpy)]²⁺ complex was formed quantitatively in a wide pH range (2-9). Subsequently, iron as active substance or impurity in a drug product, can be determined through UV-vis measurements of [Fe(terpy)₂]²⁺. Speed, sensitivity and selectivity are the most important features of the isocratic RP-LC method, developed to determine iron in pharmaceutical formulations. The duration of the chromatographic separation was less than 4.0 min. The method was linear, precise and accurate from 0.17 to 2.2 mg l⁻¹ of iron and the detection limit was found to be 5 μg l⁻¹. The absorbance at 318 and 552 nm allowed the quantitation of Fe (II) and Fe (III) after reduction, as well as of total Fe (II + III). Moreover, there were no interferences from Fe³⁺, Ni²⁺, Co²⁺ or Cu²⁺.