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.     

Agility through discipline: a debate

While Beck asserts that agility is only possible through greater discipline on the part of everyone involved, Boehm counters that you don't broaden the definition of "discipline" by rejecting parts of it. Yet, from inside extreme programming, it seems that the only way to achieve the desired results is to view the world in 'both-and" terms instead of "either-or" terms.     

Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults

A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions.     

CMOS on FZ-high resistivity substrate for monolithic integration ofSiGe-RF-circuitry and readout electronics

The choice of a highly resistive substrate for silicon millimeter-wave integrated circuits (SIMMWIC) imposed by the requirement of low RF-substrate losses requires the adaptation of a CMOS process on float zone silicon (FZ). A comparison of n- and p-channel devices realized on high resistivity substrate (p-type, 5000 Ω·cm) and standard CMOS substrates (CZ, n-type, 4-6 Ω·cm) is given. Using careful process design, we obtained device characteristics on FZ-substrates that are closely similar to those on standard material, thus allowing direct transfer of existing circuit designs     

Modeling phosphorus in the upper Etowah River basin: identifying sources under uncertainty.

The Uniform Covering by Probabilistic Rejection (UCPR) algorithm was used, in conjunction with the Soil and Water Assessment Tool (SWAT) model, to identify P loads from point source and nonpoint source polluters in the upper Etowah River basin (UERB) in Georgia. The key findings of the research are as follows. The mean absolute error was preferred over the root mean square error as a search criterion for the UCPR algorithm when water quality observations are scarce. The undocumented P load from point sources in the UERB was consistently estimated as about 43 kg/d by the proposed method; but the method was not able to identify the broiler litter application rate to the poultry/beef operation pastures. Point sources (both documented and undocumented), poultry/beef operation pastures, and forests are the three major contributors of P. During 1992-1996, on average they accounted for 36.4, 31.7, and 17.2% of P load from the UERB, respectively.