An automated, sheathless capillary electrophoresis-mass spectrometry platform for discovery of biomarkers in human serum

A capillary electrophoresis-mass spectrometry (CE-MS) method has been developed to perform routine, automated analysis of low-molecular-weight peptides in human serum. The method incorporates transient isotachophoresis for in-line preconcentration and a sheathless electrospray interface. To evaluate the performance of the method and demonstrate the utility of the approach, an experiment was designed in which peptides were added to sera from individuals at each of two different concentrations, artificially creating two groups of samples. The CE-MS data from the serum samples were divided into separate training and test sets. A pattern-recognition/feature-selection algorithm based on support vector machines was used to select the mass-to-charge (m/z) values from the training set data that distinguished the two groups of samples from each other. The added peptides were identified correctly as the distinguishing features, and pattern recognition based on these peptides was used to assign each sample in the independent test set to its respective group. A twofold difference in peptide concentration could be detected with statistical significance (p-value < 0.0001). The accuracy of the assignment was 95%, demonstrating the utility of this technique for the discovery of patterns of biomarkers in serum.     

Simulating Withdrawal Behaviors in Work Organizations: An Example of a Virtual Society

This article discusses computational modeling as a research discipline increasingly accessible to researchers in the social and behavioral sciences, a method necessary to allow us to address several important questions. Construction and use of virtual societies in which complex behavioral processes may be simulated in exquisite detail is possible because of the capacity and speed of desk top computers combined with requisite theoretical and methodological developments. Modeling has strengths orthogonal and complementary to those of the experimental tradition and correlational analyses of individual differences. These strengths can be exploited in many areas of psychology. Behavioral processes within a segment of a virtual society can be simulated with extreme levels of realism using overarching theoretical and empirical framework; segments can be combined to provide more macro statements. Variables that represent forces impinging on individuals from the macro-environment; variables that characterize relatively more micro-environments such as a work organization or the family or a classroom; and individual-level variables that summarize attitudinal, cognitive, and value states or traits can be included easily in simulations. Researchers can decompose and evaluate the interplay of multi-level causal forces as they interact within different theoretical models of how individuals enact different, interrelated behaviors. Temporal dynamics of behavioral processes, not well addressed by traditional research disciplines, can be exploited in modeling to permit the realistic study of dynamical, nonlinear systems. These points are illustrated by results from a program designed to simulate the process by which individuals withdraw from aversive work situations.     

A note on the interlacing of zeros and orthogonality

Let be a sequence of monic polynomials with deg(t_n)=n such that, for each n∈N, the zeros of t_n are real and simple and t_n and t_n+1 have no common zeros. We discuss the connection between the orthogonality of the sequence, the positivity of a certain ratio, and the interlacing of the zeros of t_n and t_n+1 for n≥1, n∈N.     

Square integrable holomorphic functions on infinite-dimensional Heisenberg type groups

We introduce a class of non-commutative, complex, infinite-dimensional Heisenberg like Lie groups based on an abstract Wiener space. The holomorphic functions which are also square integrable with respect to a heat kernel measure μ on these groups are studied. In particular, we establish a unitary equivalence between the square integrable holomorphic functions and a certain completion of the universal enveloping algebra of the “Lie algebra” of this class of groups. Using quasi-invariance of the heat kernel measure, we also construct a skeleton map which characterizes globally defined functions from the L ²(ν)-closure of holomorphic polynomials by their values on the Cameron–Martin subgroup.     

Novel polyisoprenylated benzophenone derivatives from Garcinia paucinervis

Four novel polyisoprenylated benzophenone derivatives, paucinones A-D (1-4), were isolated from the leaves of the plant Garcinia paucinervis. Paucinones A-C (1-3) contained an unexpected cyclohexane-spiro-tetrahydrofuran moiety. A 1-methylene-3,3-dimethylcyclohexane group never reported before was found in the structure of paucinone D (4). The structures of these compounds were elucidated with spectroscopic evidences. The relative stereochemistries of 1-4 were determined by NOESY correlations. These compounds showed significant cytotoxicities against HeLa cells.     

Zeros of Jacobi polynomials Pn( α, β)$ P_{n}^{(\alpha ,\beta)} $, − 2 < α, β < − 1

The sequence of Jacobi polynomials \(\{P_{n}^{(\alpha ,\beta )}\}_{n = 0}^{\infty }\) is orthogonal on (??1,1) with respect to the weight function (1 ? x)^α(1 + x)^β provided α > ??1,β > ??1. When the parameters α and β lie in the narrow range ??2 < α, β < ??1, the sequence of Jacobi polynomials \(\{P_{n}^{(\alpha ,\beta )}\}_{n = 0}^{\infty }\) is quasi-orthogonal of order 2 with respect to the weight function (1 ? x)^α+?1(1 + x)^β+?1 and each polynomial of degree n,n ≥?2, in such a Jacobi sequence has n real zeros. We show that any sequence of Jacobi polynomials \(\{P_{n}^{(\alpha ,\beta )}\}_{n = 0}^{\infty }\) with ??2 < α, β < ??1, cannot be orthogonal with respect to any positive measure by proving that the zeros of Pn??1(α,β) do not interlace with the zeros of Pn(α,β) for any \(n \in \mathbb {N},\)n ≥?2, and any α,β lying in the range ??2 < α, β < ??1. We also investigate interlacing properties satisfied by the zeros of equal degree Jacobi polynomials Pn(α,β),Pn(α,β+?1) and Pn(α+?1,β+?1) where ??2 < α, β < ??1. Upper and lower bounds for the extreme zeros of quasi-orthogonal order 2 Jacobi polynomials Pn(α,β) with ??2 < α, β < ??1 are derived.     

Determination of the benzodiazepin-2-ones by circular dichroism

Formation constants for the 1:1 complexation equilibrium reactions between β-cyclodextrin and the drugs, clonazepam, delorazepam, diazepam (Valium), flurazepam (Dalmane), lorazepam, medazepam, nitrazepam, nordiazepam, oxazepam, and temazepam, were measured by using circular dichroism spectropolarimetry. The range in values is almost one order of magnitude, suggesting a strong structural dependence in the interlocking between the host and different guests. Enthalpy and entropy data for the lorazepam interaction are consistent with data from several earlier studies. Direct determinations of diazepam and flurazepamm in pharmaceutical products are within ±2% of the prescribed amounts.     

Scanning tunneling microscopy investigation of the structure of methanethiolate on Ag(111)

Scanning tunneling microscopy (STM) has been used to investigate the structure of the ordered methanethiolate overlayer formed on Ag(111) by reaction at room temperature with dimethyl disulfide. High-resolution images show an ordered structure with three inequivalent atomic-scale protrusions within each ( radical7 x radical7)R19 degrees surface unit mesh which can be reconciled with methanethiolate species on a regular lateral submesh, similar to that proposed in the multilayer ( radical7 x radical7)R19 degrees -S sulfide phase previously reported. STM imaging during dynamic dosing also provides evidence for a significant change in the outermost layer Ag atom density, consistent with a reconstructed surface model. Possible models for this reconstruction are presented and discussed in the light of available information.