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.     

Isothermic growth of one spherulite around circular obstacles in a polypropylene foil

Growth of one spherulite within a thin foil of polypropylene around one circular obstacle or around combinations of circular obstacles is investigated. For each obstacle there exists a region of shadow, seen from the nucleus of the spherulite, which influences the growth of the spherulite. Within any region of shadow the growth fronts are evolvents of the obstacle's boundary, because the spherulite grows isotropically. When two growth fronts belonging to one spherulite meet each other inside the shadow, an intrinsic grain boundary is formed for each obstacle. Additionally, growth of one spherulite around a rectangular obstacle and a spherical obstacle is investigated.     

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.     

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.     

Spatially resolved X-ray diffraction phase mapping and α → β → α transformation kinetics in the heat-affected zone of commercially pure titanium arc welds

Spatially resolved X-ray diffraction (SRXRD) is used to map the α → β → α phase transformation in the heat-affected zone (HAZ) of commercially pure titanium gas tungsten arc welds. In situ SRXRD experiments were conducted using a 180-μm-diameter X-ray beam at the Stanford Synchrotron Radiation Laboratory (SSRL) (Stanford, CA) to probe the phases present in the HAZ of a 1.9 kW weld moving at 1.1 mm/s. Results of sequential linear X-ray diffraction scans made perpendicular to the weld direction were combined to construct a phase transformation map around the liquid weld pool. This map identifies six HAZ microstructural regions between the liquid weld pool and the base metal: (1) α-Ti that is undergoing annealing and recrystallization; (2) completely recrystallized α-Ti; (3) partially transformed α-Ti, where α-Ti and β-Ti coexist; (4) single-phase β-Ti; (5) back-transformed α-Ti; and (6) recrystallized α-Ti plus back-transformed α-Ti. Although the microstructure consisted predominantly of α-Ti, both prior to and after the weld, the crystallographically textured starting material was altered during welding to produce different α-Ti textures within the resulting HAZ. Based on the travel speed of the weld, the α → β transformation was measured to take 1.83 seconds during heating, while the β → α transformation was measured to take 0.91 seconds during cooling. The α → β transformation was characterized to be dominated by long-range diffusional growth on the leading (heating) side of the weld, while the β → α transformation was characterized to be predominantly massive on the trailing (cooling) side of the weld, with a massive growth rate on the order of 100 μm/s.     

Creep-induced local lattice parameter changes in a monocrystalline nickel-base superalloy

The γ-γ lattice mismatch of specimens of the monocrystalline nickel-base superalloy SRR 99 has been measured by a high-resolution X-ray diffraction technique for the undeformed state and after high-tem-perature creep deformation. During creep deformation beyond the minimum creep rate (total strain =0.5%), the lattice mismatches, measured in and perpendicular to the [001] stress axis, respectively, un-dergo changes in opposite directions. This reflects the buildup of a complex deformation-induced triaxial state of internal stress in the phases y and γ. The overall resolved shear stresses that act in γ and y due to the combined action of the external and internal stresses are estimated, and the conditions under which cutting of the γ phase by dislocations should occur are discussed.