UNTERSUCHUNG DER VERTEILUNG VERSCHIEDENER MIT LÖSUNGSMITTELFREIEN (ÄTHER FREIEN) KATALITISCHEN GRIGNARD-VERFAHREN HERGESTELLTEN PHENYLÄTHOXYSILANE

The distribution of the product mixtures from the one-step catalytic Grignard syntheses was investigated in the case of phenylethoxysilanes. It was stated, that the Fuoss distribution theory can be used for describing of the distribution of the differently substituted phenylethoxysilanes formed in the reaction-mixture only if the dependence of α and ß distribution coefficients on the R/Si (Phenyl-Silicon atom) ratio was taken into account during the reaction

Quantum superposition principle and gravitational collapse: Scattering times for spherical shells

A quantum theory of spherically symmetric thin shells of null dust and their gravitational field is studied. In Nucl. Phys. 603 (2001) 515 (hep-th/0007005), it has been shown how superpositions of quantum states with different geometries can lead to a solution of the singularity problem and black hole information paradox: the shells bounce and re-expand and the evolution is unitary. The corresponding scattering times will be defined in the present paper. To this aim, a spherical mirror of radius R_m is introduced. The classical formula for scattering times of the shell reflected from the mirror is extended to quantum theory. The scattering times and their spreads are calculated. They have a regular limit for R_m\to 0 and they reveal a resonance at E_m = c^4R_m/2G. Except for the resonance, they are roughly of the order of the time the light needs to cross the flat space distance between the observer and the mirror. Some ideas are discussed of how the construction of the quantum theory could be changed so that the scattering times become considerably longer.Comment: 30 pages and 5 figures; the post-referee version: shortened and some formulations improved; to be published in Physical Revie

The Bb fragment of complement factor B acts as a B cell growth factor.

The process of B cell growth and differentiation into plasma cells is highly regulated and may be influenced by a large number of inflammatory mediators, including complement components. We have studied the regulatory influence of Bb, a 60-kD peptide created during the cleavage of complement Factor B by Factor D and C3b. Purified Bb alone had no effect on proliferation and differentiation of human splenic or tonsillar B cells. However, when B cells were activated by Staphylococcus aureus Cowan I (SAC), Bb enhanced proliferation in a dose-dependent manner. Bb also enhanced proliferation when cocultured with SAC and suboptimal concentrations of purified 60-kD B cell growth factor (HMW-BCGF), a previously described lymphokine that is known to possess growth-promoting activity. However, Bb had no effect on cells treated with optimal concentrations of HMW-BCGF. Like HMW-BCGF, Bb's major effect was on the larger in vivo activated B cells. Half-maximal enhancement of proliferation was reached at a Bb concentration of 1-10 nM. Of note is the fact that antibody to Factor B recognized HMW-BCGF, and an mAb to HMW-BCGF also recognized Factor B and Bb, but not Ba. Moreover, radiolabeled Bb bound saturably to activated B cells and to an EBV-transformed human B cell line. The binding of Bb was inhibited by HMW-BCGF but not by Ba or IgG. Thus, Bb is antigenically and functionally related to HMW-BCGF, and can act as a B cell growth and differentiation factor at potentially physiologic concentrations. These data suggest that Bb may be important in amplifying the immune response in areas of inflammation. Since complement activation occurs at inflammatory sites long before induction of HMW-BCGF synthesis, Bb may be an early signal for the clonal expansion of antigen-activated B cells

Identification of a Small Molecule Inhibitor of Importin β Mediated Nuclear Import by Confocal On-Bead Screening of Tagged One-Bead One-Compound Libraries

In eukaryotic cells, proteins and RNAs are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably,leptomycin B. However, up to now no small molecule inhibitors of nuclear import have been described. Here we have used our automated confocal nanoscanning and bead picking method (CONA) for on-bead screening of a one-bead one-compound library to identify the first such import inhibitor, karyostatin 1A. Karyostatin 1A binds importin beta with high nanomolar affinity and specifically inhibits importin alpha/beta mediated nuclear import at low micromolar concentrations in vitro and in living cells, without perturbing transportin mediated nuclear import or CRM1 mediated nuclear export. Surface plasmon resonance binding-experiments suggest that karyostatin 1A acts by disrupting the interaction between importin p and the OPase Ran. As a selective inhibitor of the importin alpha/beta import pathway, karyostatin 1A will provide a valuable tool for future studies of nucleocytoplasmic trafficking.</p

The STRANDS project: long-term autonomy in everyday environments

Thanks to the efforts of the robotics and autonomous systems community, the myriad applications and capacities of robots are ever increasing. There is increasing demand from end users for autonomous service robots that can operate in real environments for extended periods. In the Spatiotemporal Representations and Activities for Cognitive Control in Long-Term Scenarios (STRANDS) project (http://strandsproject.eu), we are tackling this demand head-on by integrating state-of-the-art artificial intelligence and robotics research into mobile service robots and deploying these systems for long-term installations in security and care environments. Our robots have been operational for a combined duration of 104 days over four deployments, autonomously performing end-user-defined tasks and traversing 116 km in the process. In this article, we describe the approach we used to enable long-term autonomous operation in everyday environments and how our robots are able to use their long run times to improve their own performance

Regional integration of long-term national dense GNSS network solutions

The EUREF Permanent Network Densification is a collaborative effort of 26 European GNSS analysis centers providing series of daily or weekly station position estimates of dense national and regional GNSS networks, in order to combine them into one homogenized set of station positions and velocities. During the combination, the station meta-data, including station names, DOMES numbers, and position offset definitions were carefully homogenized, position outliers were efficiently eliminated, and the results were cross-checked for any remaining inconsistencies. The results cover the period from March 1999 to January 2017 (GPS week 1000-1933) and include 31 networks with positions and velocities for 3192 stations, well covering Europe. The positions and velocities are expressed in ITRF2014 and ETRF2014 reference frames based on the Minimum Constraint approach using a selected set of ITRF2014 reference stations. The position alignment with the ITRF2014 is at the level of 1.5, 1.2, and 3.2 mm RMS for the East, North, Up components, respectively, while the velocity RMS values are 0.17, 0.14, and 0.38 mm/year for the East, North, and Up components, respectively. The high quality of the combined solution is also reflected by the 1.1, 1.1, and 3.5 mm weighted RMS values for the East, North, and Up components, respectively

Context-Dependent Requirement for dE2F during Oncogenic Proliferation

The Hippo pathway negatively regulates the cell number in epithelial tissue. Upon its inactivation, an excess of cells is produced. These additional cells are generated from an increased rate of cell division, followed by inappropriate proliferation of cells that have failed to exit the cell cycle. We analyzed the consequence of inactivation of the entire E2F family of transcription factors in these two settings. In Drosophila, there is a single activator, dE2F1, and a single repressor, dE2F2, which act antagonistically to each other during development. While the loss of the activator dE2F1 results in a severe impairment in cell proliferation, this defect is rescued by the simultaneous loss of the repressor dE2F2, as cell proliferation occurs relatively normally in the absence of both dE2F proteins. We found that the combined inactivation of dE2F1 and dE2F2 had no significant effect on the increased rate of cell division of Hippo pathway mutant cells. In striking contrast, inappropriate proliferation of cells that failed to exit the cell cycle was efficiently blocked. Furthermore, our data suggest that such inappropriate proliferation was primarily dependent on the activator, de2f1, as loss of de2f2 was inconsequential. Consistently, Hippo pathway mutant cells had elevated E2F activity and induced dE2F1 expression at a point when wild-type cells normally exit the cell cycle. Thus, we uncovered a critical requirement for the dE2F family during inappropriate proliferation of Hippo pathway mutant cells

Characterization of a K+-induced conformational switch in a human telomeric DNA oligonucleotide using 2-aminopurine fluorescence

Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucletotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a ‘basket’ topology of four antiparallel strands; in contrast, Tel22 in K(+) solutions consists of a mixture of unknown topologies. Our previous studies on the mechanism of folding of Tel22 and similar telomere analogs utilized changes in UV absorption between 270 and 325 nm that report primarily on G-quartet formation and stacking showed that quadruplex formation occurs within milliseconds upon mixing with an appropriate cation. In the current study, we assessed the dynamics and equilibria of folding of specific loops by using Tel22 derivatives in which the dA residues were serially substituted with the fluorescent reporter base, 2-aminopurine (2-AP). Tel22 folding induced by Na(+) or K(+) assessed by changes in 2-AP fluorescence consists of at least three kinetic steps with time constants spanning a range of ms to several hundred seconds. Na(+)-dependent equilibrium titrations of Tel22 folding could be approximated as a cooperative two-state process. In contrast, K(+)-dependent folding curves were biphasic, revealing that different conformational ensembles are present in 1 mM and 30 mM K(+). This conclusion was confirmed by (1)H NMR. Molecular dynamics simulations revealed a K(+) binding pocket in Tel22 located near dA1 that is specific for the so-called hybrid-1 conformation in which strand 1 is in a parallel arrangement. The possible presence of this topologically specific binding site suggests that K(+) may play an allosteric role in regulating telomere conformation and function by modulating quadruplex tertiary structure