Quantification of heart fatty acid binding protein as a biomarker for drug-induced cardiac and musculoskeletal necroses

Heart fatty acid binding protein (Fabp3) is a cytosolic protein expressed primarily in heart, and to a lesser extent in skeletal muscle, brain, and kidney. During myocardial injury, the Fabp3 level in serum is elevated rapidly, making it an ideal early marker for myocardial infarction. In this study, an MS‐based selected reaction monitoring method (LC‐SRM) was developed for quantifying Fabp3 in rat serum. Fabp3 was enriched first through an immobilized antibody, and the protein was digested on beads directly. A marker peptide of Fabp3 was quantified using LC‐SRM with a stable isotope‐labeled peptide standard. For six quality control samples with Fabp3 ranging from 0.256 to 25 ng, the average recovery following the procedure was about 73%, and the precision (%CV) between replicates was less than 7%. The Fabp3 concentrations in rat serum peaked 1 h after isoproterenol treatment, and returned to baseline levels 24 h after the dose. Elevated Fabp3 levels were also detected in rats administered with a PPAR α/δ agonist, which has shown to cause skeletal muscle necrosis. Fabp3 can be used as a biomarker for both cardiac and skeletal necroses. The cross‐validation of the LC‐SRM method with an existing ELISA method is described.     

Polychronization: computation with spikes

We present a minimal spiking network that can polychronize, that is, exhibit reproducible time-locked but not synchronous firing patterns with millisecond precision, as in synfire braids. The network consists of cortical spiking neurons with axonal conduction delays and spike-timing-dependent plasticity (STDP); a ready-to-use MATLAB code is included. It exhibits sleeplike oscillations, gamma (40 Hz) rhythms, conversion of firing rates to spike timings, and other interesting regimes. Due to the interplay between the delays and STDP, the spiking neurons spontaneously self-organize into groups and generate patterns of stereotypical polychronous activity. To our surprise, the number of coexisting polychronous groups far exceeds the number of neurons in the network, resulting in an unprecedented memory capacity of the system. We speculate on the significance of polychrony to the theory of neuronal group selection (TNGS, neural Darwinism), cognitive neural computations, binding and gamma rhythm, mechanisms of attention, and consciousness as "attention to memories."     

Stochastic neural networks

The first purpose of this paper is to present a class of algorithms for finding the global minimum of a continuous-variable function defined on a hypercube. These algorithms, based on both diffusion processes and simulated annealing, are implementable as analog integrated circuits. Such circuits can be viewed as generalizations of neural networks of the Hopfield type, and are called diffusion machines.Our second objective is to show that learning in these networks can be achieved by a set of three interconnected diffusion machines: one that learns, one to model the desired behavior, and one to compute the weight changes.This research was supported in part by U.S. Army Research Office Grant DAAL03-89-K-0128.     

An Analysis of Chorioretinal Thermal Response to Intense Light Exposure

An analytical expression has been obtained for the transient temperature distribution produced when the retina is irradiated by a high-intensity light source. The following factors are included in the analysis: (1) structurally the fundus consists of layers of material which have different physical properties, (2) absorption of energy from the light beam follows the Beer-Lambert law, (3) energy is absorbed in the sclera as well as in the pigment epithelium and choroid, (4) heat is removed from the fundus by blood circulating through the capillaries of the choroid, and (5) intensity of the light source may vary with time. Computed values indicate that absorption of energy in the sclera and removal of heat by convection are both important for longer irradiation times, which agrees with recent experimental observations. The asymptotic response to a train of pulses is presented also.     

组合了电源控制、用户输入功能的单刀单掷按钮开关

本设计实例介绍了对某种旧设计的增强措施(参考资料1)。图1中的电路使用常开型单刀单掷按钮开关S1,它代替了原始设计要求的单刀双掷开关。您可以使用膜片开关来大大简化该器件的工业设计并增强它的人机控制特性。另外,该电路消除了流过未动作开关的电流,由此略微减少了工作模式中的泄漏电流。     

Balanced timed regular expressions

Several classes of regular expressions for timed languages accepted by timed automata have been suggested in the literature. In this article we introduce balanced timed regular expressions with colored parentheses which are equivalent to timed automata, and, differently from existing definitions, do not refer to clock values, and do not use additional operations such as intersection and renaming.     

Seismic Performance and Deformation of Levees: Four Case Studies

During the 1989 Loma Prieta earthquake the Pajaro River levees near Watsonville, Calif., spread laterally at multiple locations. Four of these locations are discussed in this paper. At one location, an industrial facility was also damaged and a dispute arose as to whether lateral spreading of the adjacent levee was the cause. Stability analyses were made of the industrial site for conditions before, during, and after the earthquake. To confirm the findings, analyses were also made of three other nearby locations where the actual deformation was documented and the subsurface conditions are well defined. The calculated levee deformations at the four locations are quite consistent with the observed movements (up to 60 cm). This experience provides increased confidence in the methods of analysis described, for the characterized subsurface conditions, and the range of ground motions experienced. Additional analyses made using the more recently developed multilinear regression lateral-spreading model (e.g., Youd et al. in 1999) yielded inconsistent results.     

Yielding, authoritarianism, and authoritarian ideology regarding groups.

This investigation was prompted by Asch's (1952) discussion of the personal and social significance of yielding to group pressure. For the person, yielding requires the inhibition of overt and perhaps implicit responses to objective situational requirements. For the group, malignant processes may arise and develop, unchecked by those members in whom goals of personal security predominate over group goals. In the present study, the view was taken that both meanings of yielding are assigned positive value in two separate ideologies concerning the group-individual relation. One of these is termed "conformity" and the other is "rugged individualism." In the study, group pressure was simulated by announcing bogus group judgments to small groups of Ss whose apparent task was to match one of three lines of variable length with a standard line. Questionnaires were used to measure variables, which were: the ideology of conformity (IC), the ideology of rugged individualism (RI), ethnocentrism (E), and authoritarianism (F). The questionnaires were administered to 91 college students, both day school and evening. It was found that the correlation with the F scale was .48 (P     

Nanobody Paratope Ensembles in Solution Characterized by MD Simulations and NMR

Variable domains of camelid antibodies (so-called nanobodies or V_HH) are the smallest antibody fragments that retain complete functionality and therapeutic potential. Understanding of the nanobody-binding interface has become a pre-requisite for rational antibody design and engineering. The nanobody-binding interface consists of up to three hypervariable loops, known as the CDR loops. Here, we structurally and dynamically characterize the conformational diversity of an anti-GFP-binding nanobody by using molecular dynamics simulations in combination with experimentally derived data from nuclear magnetic resonance (NMR) spectroscopy. The NMR data contain both structural and dynamic information resolved at various timescales, which allows an assessment of the quality of protein MD simulations. Thus, in this study, we compared the ensembles for the anti-GFP-binding nanobody obtained from MD simulations with results from NMR. We find excellent agreement of the NOE-derived distance maps obtained from NMR and MD simulations and observe similar conformational spaces for the simulations with and without NOE time-averaged restraints. We also compare the measured and calculated order parameters and find generally good agreement for the motions observed in the ps–ns timescale, in particular for the CDR3 loop. Understanding of the CDR3 loop dynamics is especially critical for nanobodies, as this loop is typically critical for antigen recognition.     

Asymmetric tensor field visualization for surfaces

Asymmetric tensor field visualization can provide important insight into fluid flows and solid deformations. Existing techniques for asymmetric tensor fields focus on the analysis, and simply use evenly-spaced hyperstreamlines on surfaces following eigenvectors and dual-eigenvectors in the tensor field. In this paper, we describe a hybrid visualization technique in which hyperstreamlines and elliptical glyphs are used in real and complex domains, respectively. This enables a more faithful representation of flow behaviors inside complex domains. In addition, we encode tensor magnitude, an important quantity in tensor field analysis, using the density of hyperstreamlines and sizes of glyphs. This allows colors to be used to encode other important tensor quantities. To facilitate quick visual exploration of the data from different viewpoints and at different resolutions, we employ an efficient image-space approach in which hyperstreamlines and glyphs are generated quickly in the image plane. The combination of these techniques leads to an efficient tensor field visualization system for domain scientists. We demonstrate the effectiveness of our visualization technique through applications to complex simulated engine fluid flow and earthquake deformation data. Feedback from domain expert scientists, who are also co-authors, is provided.