Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.     

IV-Controlling in einem Systemhaus

This paper analyses the characteristics of software houses as service providers. The tasks of internal IT-services are determined from these characteristics and a reporting system for the IT-controlling is outlined. The concept results from the analysis of one of the 25 largest German software houses. The paper concludes with a case study of the fiscal year 2000 IT-controlling report of the above-mentioned firm.     

Resolvability theory for the multiple-access channel

We study the randomness needed for approximating the output distribution of a multiple-access channel, where the original input processes are independent of each other. The approximation is achieved by simulating (possibly alternative) input processes at each of the entries, where the sources of randomness available for the simulators are independent of each other, and the simulators do not cooperate. The resolvability region of a multiple-access channel is defined as the set of all random-bit rate pairs at which accurate output approximation is possible, where the simulation accuracy is measured by the variational distance between finite-dimensional output distributions. Inner and outer bounds on the resolvability region are derived, and close relations between the concepts of resolvability region and capacity region are demonstrated     

On-line H NMR spectroscopic investigation of hydrogen bonding in supercritical and near critical CO2–methanol up to 35 MPa and 403 K

On-line NMR spectroscopy can beneficially be applied to studies of supercritical and near-critical fluids as an alternative to optical spectroscopy. Up to now high pressure NMR experiments are predominantly accomplished using custom made NMR batch reactors. The authors present a novel high pressure cell with displacement plunger for on-line NMR experiments on compressible fluids which can be used in conjunction with commercially available SCF NMR flow probes. The on-line technique offers advantages compared to stopped flow techniques such as enhanced control of mixture composition and reaction parameters as well as the facility of engagement into the reaction. The new apparatus is used for NMR studies on hydrogen bonding of methanol in near critical and supercritical carbon dioxide up to 403 K and 35 MPa for which data on the chemical shift of the hydroxyl group and methyl group are reported and interpreted.     

Sequential amplitude estimation in multiuser communications

Considers the problem of multiuser amplitude estimation, i.e., the problem of estimating the amplitudes of several digital communications signals superimposed in the same channel. This problem is of importance in communications environments such as spread-spectrum radio networks, in which nonorthogonal multiplexing is used. Multiuser amplitude estimation is a critical prerequisite to the optimum demodulation of such signals using, for example, Verdu's algorithm. In the present paper, a sequential detection-estimation approach is applied to this problem, and several estimation paradigms, including the method of moments and likelihood-based estimators, are considered. The consistency, asymptotic variance, and complexity of these estimators are examined. A new method of constructing a recursive consistent and asymptotically efficient estimation algorithm out of a consistent estimator sequence is also suggested and is applied to the current setup. It is seen that detector-estimators that use these estimators in Verdu's algorithm result, asymptotically, in (known-amplitude) optimum error probabilities with little relative increase in complexity per demodulated bit     

Multifactorial assessment of bulimia nervosa.

Investigated a multifactorial approach to the assessment of bulimia nervosa by means of hierarchical factor analysis. 245 bulimia nervosa patients and 68 patients with either anorexia nervosa or eating disorders not otherwise specified were administered a self-report battery that was organized into 21 dimensions relevant to eating disorder patients. When dimensions from this battery were subjected to hierarchical factor analysis, support for bulimia nervosa as a unique diagnostic category was obtained. However, the emergence of 3 secondary factors and 6 primary factors suggests that bulimia nervosa can also be described more complexly. The emergence of a multifactorial model of bulimia nervosa that incorporates several existing unidimensional models suggests the potential for both divergent and complicated clinical presentation in bulimia nervosa patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In Google We Trust: Users' Decisions on Rank, Position, and Relevance

An eye tracking experiment revealed that college student users have substantial trust in Google's ability to rank results by their true relevance to the query. When the participants selected a link to follow from Google's result pages, their decisions were strongly biased towards links higher in position even if the abstracts themselves were less relevant. While the participants reacted to artificially reduced retrieval quality by greater scrutiny, they failed to achieve the same success rate. This demonstrated trust in Google has implications for the search engine's tremendous potential influence on culture, society, and user traffic on the Web.     

Physiological phosphorylation of protein kinase A at Thr-197 is by a protein kinase A kinase

Phosphorylation of the catalytic subunit of cyclic AMP-dependent protein kinase, or protein kinase A, on Thr-197 is required for optimal enzyme activity, and enzyme isolated from either animal sources or bacterial expression strains is found phosphorylated at this site. Autophosphorylation of Thr-197 occurs in Escherichia coli and in vitro but is an inefficient intermolecular reaction catalyzed primarily by active, previously phosphorylated molecules. In contrast, the Thr-197 phosphorylation of newly synthesized protein kinase A in intact S49 mouse lymphoma cells is both efficient and insensitive to activators or inhibitors of intracellular protein kinase A. Using [35S]methionine-labeled, nonphosphorylated, recombinant catalytic subunit as the substrate in a gel mobility shift assay, we have identified an activity in extracts of protein kinase A-deficient S49 cells that phosphorylates catalytic subunit on Thr-197. The protein kinase A kinase activity partially purified by anion-exchange and hydroxylapatite chromatography is an efficient catalyst of protein kinase A phosphorylation in terms of both a low Km for ATP and a rapid time course. Phosphorylation of wild-type catalytic subunit by the kinase kinase activates the subunit for binding to a pseudosubstrate peptide inhibitor of protein kinase A. By both the gel shift assay and a [gamma-32P]ATP incorporation assay, the enzyme is active on wild-type catalytic subunit and on an inactive mutant with Met substituted for Lys-72 but inactive on a mutant with Ala substituted for Thr-197. Combined with the results from mutant subunits, phosphoamino acid analysis suggests that the enzyme is specific for phosphorylation of Thr-197.