High-resolution biomarker discovery: Moving from large-scale proteome profiling to quantitative validation of lead candidates

Diverse proteomic techniques based on protein MS have been introduced to systematically characterize protein perturbations associated with disease. Progress in clinical proteomics is essential for personalized medicine, wherein treatments will be tailored to individual needs based on patient stratification using noninvasive disease monitoring procedures to reveal the most appropriate therapeutic targets. However, breakthroughs await the successful development and application of a robust proteomic pipeline capable of identifying and rigorously assessing the relevance of multiple candidate proteins as informative diagnostic and prognostic indicators or suitable drug targets involved in a pathological process. While steady progress has been made toward more comprehensive proteome profiling, the emphasis must now shift from in depth screening of reference samples to stringent quantitative validation of selected lead candidates in a broader clinical context. Here, we present an overview of the emerging proteomic strategies for high-throughput protein detection focused primarily on targeted MS/MS as the basis for biomarker verification in large clinical cohorts. We discuss the conceptual promise and practical pitfalls of these methods in terms of achieving higher dynamic range, higher throughput, and more reliable quantification, highlighting research avenues that merit additional inquiry.     

Variation in the local motion statistics of real-life optic flow scenes

Optic flow motion patterns can be a rich source of information about our own movement and about the structure of the environment we are moving in. We investigate the information available to the brain under real operating conditions by analyzing video sequences generated by physically moving a camera through various typical human environments. We consider to what extent the motion signal maps generated by a biologically plausible, two-dimensional array of correlation-based motion detectors (2DMD) not only depend on egomotion, but also reflect the spatial setup of such environments. We analyzed the local motion outputs by extracting the relative amounts of detected directions and comparing the spatial distribution of the motion signals to that of idealized optic flow. Using a simple template matching estimation technique, we are able to extract the focus of expansion and find relatively small errors that are distributed in characteristic patterns in different scenes. This shows that all types of scenes provide suitable motion information for extracting ego motion despite the substantial levels of noise affecting the motion signal distributions, attributed to the sparse nature of optic flow and the presence of camera jitter. However, there are large differences in the shape of the direction distributions between different types of scenes; in particular, man-made office scenes are heavily dominated by directions in the cardinal axes, which is much less apparent in outdoor forest scenes. Further examination of motion magnitudes at different scales and the location of motion information in a scene revealed different patterns across different scene categories. This suggests that self-motion patterns are not only relevant for deducing heading direction and speed but also provide a rich information source for scene structure and could be important for the rapid formation of the gist of a scene under normal human locomotion.     

A symbolic summation approach to Feynman integral calculus

Given a Feynman parameter integral, depending on a single discrete variable N$N$ and a real parameter ε$\epsilon$, we discuss a new algorithmic framework to compute the first coefficients of its Laurent series expansion in ε$\epsilon$. In a first step, the integrals are expressed by hypergeometric multi-sums by means of symbolic transformations. Given this sum format, we develop new summation tools to extract the first coefficients of its series expansion whenever they are expressible in terms of indefinite nested product–sum expressions. In particular, we enhance the known multi-sum algorithms to derive recurrences for sums with complicated boundary conditions, and we present new algorithms to find formal Laurent series solutions of a given recurrence relation.     

Reduced order optimization for model predictive control using principal control moves

In order to reduce the computational complexity of model predictive control (MPC) a proper input signal parametrization is proposed in this paper which significantly reduces the number of decision variables. This parametrization can be based on either measured data from closed-loop operation or simulation data. The snapshots of representative time domain data for all manipulated variables are projected on an orthonormal basis by a Karhunen-Loeve transformation. These significant features (termed principal control moves, PCM) can be reduced utilizing an analytic criterion for performance degradation. Furthermore, a stability analysis of the proposed method is given. Considerations on the identification of the PCM are made and another criterion is given for a sufficient selection of PCM. It is shown by an example of an industrial drying process that a strong reduction in the order of the optimization is possible while retaining a high performance level.     

Form-Profiling of Optics Using the Geometry Measuring Machine and the M-48 CMM at NIST

We are developing an instrument, the Geometry Measuring Machine (GEMM), to measure the profile errors of aspheric and free form optical surfaces, with measurement uncertainties near 1 nm. Using GEMM, an optical profile is reconstructed from local curvatures of a surface, which are measured at points on the optic’s surface. We will describe a prototype version of GEMM, its repeatability with time, a measurements registry practice, and the calibration practice needed to make nanometer resolution comparisons with other instruments. Over three months, the repeatability of GEMM is 3 nm rms, and is based on the constancy of the measured profile of an elliptical mirror with a radius of curvature of about 83 m. As a demonstration of GEMM’s capabilities for curvature measurement, profiles of that same mirror were measured with GEMM and the NIST Moore M-48 coordinate measuring machine. Although the methods are far different, two reconstructed profiles differ by 22 nm peak-to-valley, or 6 nm rms. This comparability clearly demonstrates that with appropriate calibration, our prototype of the GEMM can measure complex-shaped optics.     

Inside Front Cover: Towards See‐Through Displays: Fully Transparent Thin‐Film Transistors Driving Transparent Organic Light‐Emitting Diodes (Adv. Mater. 6/2006)

The first fully transparent organic light‐emitting diode (OLED) pixels, fabricated by integrating transparent OLEDs on top of transparent thin‐film transistors (TTFTs), are demonstrated on p. 738 by Riedl and co‐workers, and shown schematically on the inside cover. With an average transmittance of more than 70 % in the visible part of the spectrum (400–750 nm), the presented active pixels pave the way to the realization of fully transparent active matrix displays.     

Science and technology in the region: The output of regional science and technology, its strengths and its leading institutions

Summary We operationalize scientific output in a region by means of the number of articles (as in the SciSearch database) per year and technology output by means of the number of patent applications (as in the database of the European Patent Office) per priority year. All informetric analyses were done using the DIALOG online-system. The main research questions are the following: Which scientific and technological fields or topics are most influent within a region and which institutions or companies are mainly publishing articles or holding patents? Do the distributions of regional science and technology fields and of publishing institutions follow the well-known informetric function? Are there - as it is expected - only few fields and few institutions which dominate the region? Is there a connection between the economic power of a region and the regional publication and patent output? Examples studied in detail are seven German regions: Aachen, Düsseldorf, Hamburg, Köln (Cologne), Leipzig - Halle - Dessau, München (Munich), and Stuttgart. Three different indicators were used, science and technology attraction of a region (number of scientific articles and patents), science and technology intensity (articles and patents per 1,000 inhabitants), and science and technology density (articles and patents per 1 billion EURO gross value added). Top region concerning both attraction and intensity is Munich, concerning density it is Aachen.