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.     

Genome-Wide Investigation of Multifocal and Unifocal Prostate Cancer—Are They Genetically Different?

Prostate cancer is widely observed to be biologically heterogeneous. Its heterogeneity is manifested histologically as multifocal prostate cancer, which is observed more frequently than unifocal prostate cancer. The clinical and prognostic significance of either focal cancer type is not fully established. To investigate prostate cancer heterogeneity, the genetic profiles of multifocal and unifocal prostate cancers were compared. Here, we report observations deduced from tumor-tumor comparison of copy number alteration data of both focal categories. Forty-one fresh frozen prostate cancer foci from 14 multifocal prostate cancers and eight unifocal prostate cancers were subjected to copy number variation analysis with the Affymetrix SNP 6.0 microarray tool. With the investigated cases, tumors obtained from a single prostate exhibited different genetic profiles of variable degrees. Further comparison identified no distinct genetic pattern or signatures specific to multifocal or unifocal prostate cancer. Our findings suggest that samples obtained from multiple sites of a single unifocal prostate cancer show as much genetic heterogeneity and variability as separate tumors obtained from a single multifocal prostate cancer.     

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.