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.     

Evaluation of passive microwave snow water equivalent algorithms in the depth hoar-dominated snowpack of the Kuparuk River Watershed, Alaska, USA

This research investigates the utility of passive microwave remote sensing instruments to accurately determine snow water equivalent (SWE) over large spatial extents. Three existing Special Sensor Microwave Imager (SSM/I) snow water equivalent algorithms produced by Chang, Tait and Goodison were evaluated for their ability to determine snow water equivalent in a snowpack containing substantial depth hoar, large faceted snow crystals. The Kuparuk River Watershed (8140 km²) test site on the North Slope of Alaska was chosen for its snowpack containing a think depth hoar layer and long history of ground truth data. A new regional snow water equivalent algorithm was developed to determine if it could produce better results than the existing algorithms in an area known to contain significant depth hoar. The four algorithms were tested to see how well they could determine snow water equivalent: (1) on a per pixel basis, (2) across swath-averaged spatial bands of approximately 850 km², and (3) on a watershed scale. The algorithms were evaluated to see if they captured the annual spatial distribution in snow water equivalent over the watershed. Results show that the algorithms developed by Chang and from this research are generally within 3 cm of the spatially averaged snow water equivalents over the entire watershed. The algorithms produced by Chang, Tait, and in this research were able to predict the basin-wide ground measured snow water equivalent value within a percent error range from −32.4% to 24.4% in the years with a typical snowpack. None of the algorithms produce accurate results on a pixel-by-pixel scale, with errors ranging from −26% to 308%.     

Bodies, antibodies, and neighborhood-density effects in masked form priming.

Facilitatory priming effects due to similarity of orthographic form are obtained for high-N target words provided that they have low-frequency bodies and the body is shared between the prime and target (e.g., perd-HERD). Conversely, it is shown that low-N target words show priming regardless of the frequency of the body, provided that the prime and target do not share the same body (e.g., drice-DRIVE). If the body is shared, then priming occurs only for targets with low-frequency bodies. These results suggest that neighborhood density should be defined in terms of both individual letter units and subsyllabic units and that both types of density jointly determine priming. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Efficient generation of a reshaped human mAb specific for the {alpha} toxin of Clostridium perfringens

We have used the technique of antibody reshaping to producea humanized antibody specific for the a toxin of Clostridiumperfringens. The starting antibody was from a mouse hybridomafrom which variable (V) region nucleo-tide sequences were determined.The complementarity-determining regions (CDRs) from these Vregions were then inserted into human heavy and light chainV region genes with human constant region gene fragments subsequentlyadded. The insertion of CDRs alone into human frameworks didnot produce a functional reshaped antibody and modificationsto the V region framework were required. With minor frameworkmodifications, the affinity of the original murine mAb was restoredand even exceeded. Where affinity was increased, an alteredbinding profile to overlapping peptides was observed. Computermodelling of the reshaped heavy chain V regions suggested thatamino acids adjacent to CDRs can either contribute to, or distort,CDR loop conformation and must be adjusted to achieve high bindingaffinity.     

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.     

Computational modeling and elementary process analysis in visual word recognition.

An attempt is made to isolate the assumptions that make a connectionist approach to visual word recognition distinctive. These include the commitment to distributed representations, the claim that there is no distinction between lexical and nonlexical systems in the naming task, and the claim that it is possible to map from orthography to meaning without using localized representations. It is argued that merely demonstrating that a network model can perform these tasks is not sufficient and that a detailed theory of how the network performs its tasks must accompany the simulation, because a simulation is not equivalent to an explanation. It is argued that further progress requires detailed modeling and experimental study of the elementary processes assumed to be involved in networks and that it is premature to dismiss alternative models of lexical access such as serial search models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preventing weight gain in adults: A pound of prevention.

Evaluated the feasibility and effectiveness of a program for weight gain prevention (WGP) in normal adults. 219 Ss were randomized to either WGP treatment or no treatment for 12 mo. The treatment group received monthly newsletters relating to weight management, participated in a financial incentive system, and were offered an optional 4-session education course in the 6th mo of the program. Results demonstrate high interest in WGP among Ss who were not objectively overweight. Participation, as measured by return of postcards sent with each newsletter, was approximately 75%. Results after 1 yr show a net weight loss of 1.8 lb in the group receiving the program compared with controls. 82% of participants maintained or lost weight, compared with 56% of controls. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Forty-Five Years After Broadbent (1958): Still No Identification Without Attention.

According to D. E. Broadbent's (1958) selective filter theory, people do not process unattended stimuli beyond the analysis of basic physical properties. This theory was later rejected on the basis of numerous findings that people identify irrelevant (and supposedly unattended) stimuli. A careful review of this evidence, however, reveals strong reasons to doubt that these irrelevant stimuli were in fact unattended. This review exposed a clear need for new experiments with tight control over the locus of attention. The authors present 5 such experiments using a priming paradigm. When steps were taken to ensure that irrelevant stimuli were not attended, these stimuli produced no priming effects. Hence, the authors found no evidence that unattended stimuli can be identified. The results support a modern version of Broadbent's selective theory, updated to reflect recent research advances. (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.