From relative to absolute quantification of tryptic peptides with tandem mass tags: application to cerebrospinal fluid

Quantification is a major task in proteomics. Among the different analytical strategies to enable peptide and protein quantification, tagging with isotopic labels has emerged as a practical, versatile, and efficient alternative. In particular, isobaric labels, such as TMT or iTRAQ, are now widely employed to make relative comparison of the protein amounts in separate biological samples with tandem mass spectrometry (MS/MS). We used herein a shotgun proteomic approach based on labelling with tandem mass tags (TMTs) for the relative quantification of proteins, and the absolute quantification of their tryptic peptides in human cerebrospinal fluid (CSF). First, the comparison of ante- and post-mortem CSF samples was carried out for the discovery of protein marker candidates of brain-damage disorders. Second, tryptic peptides representative of these candidates were measured in CSF using reporter-ion calibration curves. These works highlighted the advantages and limitations of such strategies for quantification purposes in proteomics.     

Radiofluorinated Pyrimidine‐2,4,6‐triones as Molecular Probes for Noninvasive MMP‐Targeted Imaging

Matrix metalloproteinases (MMPs) are zinc‐ and calcium‐dependent endopeptidases. Representing a subfamily of the metzincin superfamily, MMPs are involved in the proteolytic degradation of components of the extracellular matrix. Unregulated MMP expression, MMP dysregulation and locally increased MMP activity are common features of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others. Therefore, activated MMPs are suitable biological targets for the specific visualization of such pathologies, in particular by using radiolabeled MMP inhibitors (MMPIs). The aim of this work was to develop a radiofluorinated molecular probe for noninvasive in vivo imaging for the detection of up‐regulated levels of activated MMPs in the living organism. Fluorinated MMPIs ( 26 , 31 and 38 ) based on the pyrimidine‐2,4,6‐trione lead structure RO 28‐2653 ( 1 ) were synthesized, and their MMP inhibition potency was evaluated in vitro. The radiosynthesis and the in vivo biodistribution of the first ¹⁸F‐labeled prototype, MMP‐targeted tracer [¹⁸F] 26 , suitable for molecular imaging by means of positron emission tomography (PET) were realized.     

Computing Nash Equilibria for Scheduling on Restricted Parallel Links

We consider the problem of routing n users on m parallel links under the restriction that each user may only be routed on a link from a certain set of allowed links for the user. So, this problem is equivalent to the correspondingly restricted scheduling problem of assigning n jobs to m parallel machines. In a Nash equilibrium, no user may improve its own Individual Cost (latency) by unilaterally switching to another link from its set of allowed links.     

Dissolution of Alumina, Sintering, and Crystallization in Glass Ceramic Composites for LTCC

Sintering and microstructure evolution of alkali-free calcium–alumo–borosilicate glass/α-Al₂O₃ composites (mean particle size ca. 2 μm) for low-temperature cofired ceramics were studied during heating at 5 K/min by heating microscopy, thermal analysis (DTA), X-ray diffraction (XRD), and electron microscopy (SEM). Composites fully densify at ≈830°C, not essentially influenced by the dissolution of alumina and glass crystallization. Thus wollastonite, as first crystalline phase, was detectable at 840°C. Above 900°C, a pronounced crystallization of anorthite is evident, reaching 60 wt% at 1050°C. Rietveld analyses of XRD data revealed that anorthite precipitates at the expenses of alumina, which declines from ≈33 to <10 wt%, and wollastonite, which fully declines from its maximum of ≈19 wt%. Based on XRD, we discuss the evolution of crystal mass fractions, the residual glass composition, the glass viscosity, and the effective shear viscosity of the composites under study during heating.     

Real-time triangulation of point streams

Hand-held laser scanners are commonly used in industry for reverse engineering and quality measurements. In this process, it is difficult for the human operator to scan the target object completely and uniformly. Therefore, an interactive triangulation of the scanned points can assist the operator in this task. In this paper, we describe the technical and implementational details of our real-time triangulation approach for point streams, presented at the 17th International Meshing Roundtable. Our method computes a triangulation of the point stream generated by the laser scanner online, i.e., the data points are added to the triangulation as they are received from the scanner. Multiple scanned areas and areas with a higher point density result in a finer mesh and a higher accuracy. On the other hand, the vertex density adapts to the estimated surface curvature. To guide the operator, the resulting triangulation is rendered with a visualization of its uncertainty and the display of an optimal scanning direction.     

Reconfigurable handling system

The demand for more versatile assembly and handling systems to facilitate customized production is gaining in importance, especially with regard to the constantly-increasing cost pressure, to expansion of the range of product versions and the shortening of innovation cycles. As a cost-effective approach for frequently changing assembly tasks, a novel manipulation concept has been developed by combining given robot technologies. This new handling system has a modular and adaptable layout, which consists of several mobile arms to manipulate the object in six-dimensional Cartesian space. After grasping, when the arms are attached to the object, the mechanical architecture is similar to parallel manipulators or cooperating robots. As the mounting and gripping points of the arms can easily be changed, the manipulator can be reconfigured so as to match the user’s preferences and needs. In addition to the kinematic adaption the regarding task, the hardware and new functions can be reconfigured as well. Contact elements, measurement and assembly devices as well as testing modules can easily be in integrated in the concept. A modular automatic control concept combined with a self-optimizing planning tool helps the user to find the optimal configuration and realize it in an economic way.     

Lateralized processing of speech prosodies in the temporal cortex: a 3-T functional magnetic resonance imaging study

Prosodic modulation of speech provides information about emotional states of speakers (affective prosodies) or serves as syntactic markers to change linguistic aspects of speech (linguistic prosodies). Previous electrophysiological investigations and studies on patients with right or left hemisphere damage showed nonuniform results with respect to lateralization of prosodic processing. In this study 20 healthy right-handed volunteers were investigated with functional magnetic resonance imaging of the acoustically responsive areas on the supratemporal plane while detecting phonemes as control targets or prosodies in strings of nonsense syllables and adjectives, the latter randomly intonated in a declarative, interrogative, commanding, happy, or sad fashion. In control task A the phoneme /a/ was detected in the syllables. In control task B the phoneme /a/ was detected in the adjectives, and in the experimental task C the sad intonations (affective) and in the experimental task D the interrogative intonations (linguistic) had to be detected in the same material. In task A intensity-weighted volumes of activated voxels were not different in the two hemispheres (laterality index 0). In task B with an irrelevant phoneme detection with respect to prosodic material, the population split into two subgroups with similar right or left hemispheric lateralization of activity leading to an absolute laterality index of 26.8 across all subjects. During detection of affective prosodies (task C), lateralization was maintained yet the absolute laterality index reduced to 14.5, while there was no lateralization during detection of linguistic prosodies. The sum of activations in the two hemispheres was the same across all tasks and subgroups, which suggests that the lateralizations occurring with presentation and detection of prosodic material depend on a redistribution of activity between hemispheres.     

Double hashing with passbits

Double hashing with bucket capacity one is augmented with multiple passbits to obtain significant reduction to unsuccessful search lengths. This improves the analysis of Martini et al. [P.M. Martini, W.A. Burkhard, Double hashing with multiple passbits, Internat. J. Found. Theoret. Comput. Sci. 14 (6) (2003) 1165-1188] by providing a closed form expression for the expected unsuccessful search lengths.     

Knowledge based support for manufacturing of microstructures

 In the Institute of Applied Computer Science (IAI) in the Forschungszentrum Karlsruhe (FZK) information technologies are developed and applied to support the design and manufacturing process for micromechanical structures. The information related kernel of the computer integrated manufacturing (CIM) consists of different semantic domains. At the beginning of the whole manufacturing process, the designer has to construct the microstructure with a CAD system for mechanical construction. After application of design rule checks, based on heuristics from human experts, these constructions are the references for the quality control of the real fabricated structures. The knowledge in form of design rules needs as well deeper knowledge, stored in the different partial modes of the process model and the product model as well dynamical results of the different integrated tools for design, simulation and optimization. Especially this fact is the kernel to produce cost efficient because distinguishing between possible and impossible structures in a very early stage of manufacturing. Received: 30 October 1995 / Accepted: 20 May 1996     

Oscillatory-sensitization model of repeated drug exposure: cocaine's effects on shock-induced hypoalgesia

1. The authors have recently proposed that the sensitization produced by repeated exposure to drugs or stress may give way to an alternating pattern of increases and decreases in the response to each subsequent exposure (i.e., oscillate), as the limits of the physiological system are approached. 2. Evidence for oscillation has been obtained for 6 drug/non-drug stressors and 9 neurochemical or endocrine endpoints. This paper extends the model to a behavioral outcome. 3. In the first experiment, rats were given 0, 1, 2 or 3 pretreatments with cocaine hydrochloride (COC; 12 mg/kg i.p.), separated by 1-week intervals, and then were tested for footshock-induced hypoalgesia (5-sec, 2-mA), as measured by withdrawal latencies from a hot-plate. 4. The second experiment replicated the first and extended the pretreatment sequence to 5 COC injections. 5. In both experiments, shock significantly increased latencies over the no-shock controls. COC enhanced shock-induced hypoalgesia and this sensitization reached its maximum after 2 COC pretreatments. Thereafter, oscillation developed such that the sensitization was attenuated by 3 as compared to 2 COC injections, enhanced by 4 injections, and reattenuated after 5 COC pretreatments. 6. These data complement other findings by demonstrating that the oscillation model extends to a stress-induced behavioral outcome.