PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.     

Structure-oriented rational design of chymotrypsin inhibitor models

Three peptides modelling a highly potent, 35-residue chymotrypsininhibitor (Schistocerca gregaria chymotrypsin inhibitor) weredesigned and synthesized by convergent peptide synthesis. Foreach model peptide, the inhibitory constant (K_i) on chymotrypsinand the solution structure were determined. In addition, moleculardynamics calculations were performed for all of them. Two modelscontaining approximately half of the parent inhibitor (17 of35 residues) were designed and subsequently found to have nosubstantial inhibitory activity (K_i values in the mM range).The third model composed of 24 amino acid residues proved tobe an effective (K_i 10^–7) inhibitor of bovine chymotrypsin.Both the solution structure properties determined by NMR spectroscopyand the dynamic behaviour of the latter model system are comparableto the native inhibitor. In contrast, the structure and dynamicsof the first two related model peptides show characteristicdifferences. We suggest that the conformation and flexibilityof the modelled protease inhibitor are crucial for its biologicalefficiency. Moreover, the structural and dynamic features ofthe binding loop (28–33) and those of the rest of themolecule appear to be interdependent. Most importantly, thesestructural characteristics can be rationally modified, at leastpartially, by peptide design. Received March 7, 2003; revised August 25, 2003; accepted August 26, 2003.     

A conformance test suite for TTCN-3 tools

With more than 10 years of maturing through industrial use and standardization, the Testing and Test Control Notation (TTCN-3) has become a widely used technology that many businesses depend upon for ensuring their product quality. With the rising number of supporters and tools, the demand for a means to assess the standards compliance of TTCN-3 tools has increased. In this article, we describe the motivation, approach, methodology, and results of the still ongoing project to develop a standardized conformance test suite for TTCN-3 tools. We discuss the challenges involved in creating such a test suite, the way to deal with imposed resource limitations of the project, and where we think the effort is heading.     

Learning to Locate Informative Features for Visual Identification

Object identification is a specialized type of recognition in which the category (e.g. cars) is known and the goal is to recognize an object’s exact identity (e.g. Bob’s BMW). Two special challenges characterize object identification. First, inter-object variation is often small (many cars look alike) and may be dwarfed by illumination or pose changes. Second, there may be many different instances of the category but few or just one positive “training” examples per object instance. Because variation among object instances may be small, a solution must locate possibly subtle object-specific salient features, like a door handle, while avoiding distracting ones such as specular highlights. With just one training example per object instance, however, standard modeling and feature selection techniques cannot be used. We describe an on-line algorithm that takes one image from a known category and builds an efficient “same” versus “different” classification cascade by predicting the most discriminative features for that object instance. Our method not only estimates the saliency and scoring function for each candidate feature, but also models the dependency between features, building an ordered sequence of discriminative features specific to the given image. Learned stopping thresholds make the identifier very efficient. To make this possible, category-specific characteristics are learned automatically in an off-line training procedure from labeled image pairs of the category. Our method, using the same algorithm for both cars and faces, outperforms a wide variety of other methods.     

A new double imaging velocity focusing coincidence experiment: i(2)PEPICO

The vacuum ultraviolet (VUV) beamline of the Swiss Light Source has been upgraded after two years of operation. A new, turntable-type monochromator was constructed at the Paul Scherrer Institut, which allows for fast yaw-alignment as well as quick grating change and exchange. In addition to the original imaging photoelectron photoion coincidence endstation (iPEPICO), a second, complementary double imaging setup (i(2)PEPICO) has been built. Volatile samples can be introduced at room temperature or in a molecular beam, a pyrolysis source allows for radical production, and non-volatile solids can be evaporated in a heated cell. Monochromatic VUV radiation ionizes the sample and both photoelectrons and photoions are velocity map imaged onto two fast position sensitive detectors and detected in delayed coincidence. High intensity synchrotron radiation leads to ionization rates above 10(5) s(-1). New data acquisition and processing approaches are discussed for recording coincidence processes at high rates. The setup is capable of resolving pulsed molecular beam profiles and the synchrotron time structure temporally. The latter is shown by photoelectron autocorrelation, which displays both the 1.04 MHz ring clock frequency as well as resolving the micro-pulses with a separation of 2 ns. Kinetic energy release analysis on the dissociative photoionization of CF(4) indicates a dissociation mechanism change in the Franck-Condon allowed energy range of the first ion state.     

Seaweed Allelopathy Against Coral: Surface Distribution of a Seaweed Secondary Metabolite by Imaging Mass Spectrometry

Coral reefs are in global decline, with seaweeds increasing as corals decrease. Although seaweeds inhibit coral growth, recruitment, and survivorship, the mechanism of these interactions is poorly understood. Here, we used field experiments to show that contact with four common seaweeds induces bleaching on natural colonies of Porites rus. Controls in contact with inert, plastic mimics of seaweeds did not bleach, suggesting seaweed effects resulted from allelopathy rather than shading, abrasion, or physical contact. Bioassay-guided fractionation of the hydrophobic extract from the red alga Phacelocarpus neurymenioides revealed a previously characterized antibacterial metabolite, neurymenolide A, as the main allelopathic agent. For allelopathy of lipid-soluble metabolites to be effective, the compounds would need to be deployed on algal surfaces where they could transfer to corals on contact. We used desorption electrospray ionization mass spectrometry (DESI-MS) to visualize and quantify neurymenolide A on the surface of P. neurymenioides, and we found the molecule on all surfaces analyzed, with highest concentrations on basal portions of blades.     

Real-time heating and power characterization of cells in standard cell designs

In today's digital electronic integrated circuits device heating is one of the most critical issues. Overheating can cause failures in functionality and device malfunction. In certain circumstances overheating of ICs can cause physical destruction of the device itself. This paper introduces a solution to determine cell and gate heating curves across the standard cell IC's surface. The presented methodology and toolset is tightly integrated into standardized logic simulator engines thus providing digital circuit designers a low-level, cell-resolution temperature distribution map during logic simulations. Actual temperatures of each consisting cell of the design can be monitored throughout the whole logic simulation. By being able to monitor temperatures of digital cells during initial simulations, it allows us to detect hot-spots and overheating caused malfunctions far before manufacture. By using the spatial location and temperature magnitude of hot-spots acquired from the presented methodology, place and route (P&R) tools can be driven to change cell placement and routing in order to avoid heating caused failures. Additionally, cooling solutions can be developed using the simulated temperature maps of the IC's surface. This paper also presents various aspects of power characterization methods which were used throughout the experiments.     

Ground-based full-sky imaging polarimetry of rapidly changing skies and its use for polarimetric cloud detection

For elimination of the shortcomings of imaging polarimeters that take the necessary three pictures sequentially through linear-polarization filters, a three-lens, three-camera, full-sky imaging polarimeter was designed that takes the required pictures simultaneously. With this polarimeter, celestial polarization patterns can be measured even if rapid temporal changes occur in the sky: under cloudy sky conditions, or immediately after sunrise or prior to sunset. One of the possible applications of our polarimeter is the ground-based detection of clouds. With use of the additional information of the degree and the angle of polarization patterns of cloudy skies measured in the red (650 nm), green (550 nm), and blue (450 nm) spectral ranges, improved algorithms of radiometric cloud detection can be offered. We present a combined radiometric and polarimetric algorithm that performs the detection of clouds more efficiently and reliably as compared with an exclusively radiometric cloud-detection algorithm. The advantages and the limits of three-lens, three-camera, full-sky imaging polarimeters as well as the possibilities of improving our polarimetric cloud detection method are discussed briefly.