Wnt/beta-catenin/Tcf signaling: A critical pathway in gastrointestinal tumorigenesis

Cancers of the gastrointestinal tract, including the liver, bile ducts, and pancreas, constitute the largest group of malignant tumors. Colorectal cancer is one of the most common neoplastic diseases in Western countries and one of the leading causes of cancer-related deaths. Inactivation of the adenomatous polyposis coli (APC) tumor-suppressor gene during early adenoma formation is thought to be the first genetic event in the process of colorectal carcinogenesis followed by mutations in oncogenes like K-Ras and tumor-suppressor genes like p53. Identification of the interaction of APC with the proto-oncogene beta-catenin has linked colorectal carcinogenesis to the Wnt-signal transduction pathway. The main function of APC is thought to be the regulation of free beta-catenin in concert with the glycogen synthase kinase 3beta (GSK-3beta) and Axin proteins. Loss of APC function, inactivation of Axin or activating beta-catenin mutations result in the cellular accumulation of beta-catenin. Upon translocation to the nucleus beta-catenin serves as an activator of T-cell factor (Tcf)-dependent transcription leading to an increased expression of several specific target genes including c-Myc, cyclin D1, MMP-7, and ITF-2. While APC mutations are almost exclusively found in colorectal cancers, deregulation of Wnt/beta-catenin/Tcf signaling is also common in other gastrointestinal and extra-gastrointestinal human cancers. In a fraction of hepatocellular carcinomas the Writ pathway is deregulated by inactivation of Axin or stabilizing mutations of beta-catenin. The majority of hepatoblastomas and a group of gastric cancers also carry beta-catenin mutations. Clearly, this pathway harbors great potential for future applications in cancer diagnostics, staging, and therapy. Copyright (C) 2002 S. Karger AG, Basel

Impact of Agricultural Development on the Environment: Issues in the Research Collaboration with Developing Countries. The Orientation of German Agricultural Research

Statement by D.F.R. Bommer of the Arbeitsgruppe für Tropische und Subtropische Agrarforschung (ATSAF) on environmental considerations in West German agricultural policy, agricultural research, and bilateral development aid.Dr. Bommer presented the report at the CGIAR mid term meeting in May 1988

Impact of energy dissipation on interface shapes and on rates for dewetting from liquid substrates

We revisit the fundamental problem of liquid-liquid dewetting and perform a detailed comparison of theoretical predictions based on thin-film models with experimental measurements obtained by atomic force microscopy (AFM). Specifically, we consider the dewetting of a liquid polystyrene (PS) layer from a liquid polymethyl methacrylate (PMMA) layer, where the thicknesses and the viscosities of PS and PMMA layers are similar. The excellent agreement of experiment and theory reveals that dewetting rates for such systems follow no universal power law, in contrast to dewetting scenarios on solid substrates. Our new energetic approach allows to assess the physical importance of different contributions to the energy-dissipation mechanism, for which we analyze the local flow fields and the local dissipation rates.Comment: 15 pages, 5 figure

Droplets on liquids and their long way into equilibrium

The morphological paths towards equilibrium droplets during the late stages of the dewetting process of a liquid film from a liquid substrate is investigated experimentally and theoretically. As liquids, short chained polystyrene (PS) and polymethyl-methacrylate (PMMA) are used, which can be considered as Newontian liquids well above their glass transition temperatures. Careful imaging of the PS/air interface of the droplets during equilibration by \emph{in situ} scanning force microscopy and the PS/PMMA interface after removal of the PS droplets reveal a surprisingly deep penetration of the PS droplets into the PMMA layer. Droplets of sufficiently small volumes develop the typical lens shape and were used to extract the ratio of the PS/air and PS/PMMA surface tensions and the contact angles by comparison to theoretical exact equilibrium solutions of the liquid/liquid system. Using these results in our dynamical thin-film model we find that before the droplets reach their equilibrium they undergo several intermediate stages each with a well-defined signature in shape. Moreover, the intermediate droplet shapes are independent of the details of the initial configuration, while the time scale they are reached depend strongly on the droplet volume. This is shown by the numerical solutions of the thin-film model and demonstrated by quantitative comparison to experimental results

Earthquake hazard and risk analysis for natural and induced seismicity: towards objective assessments in the face of uncertainty.

The fundamental objective of earthquake engineering is to protect lives and livelihoods through the reduction of seismic risk. Directly or indirectly, this generally requires quantification of the risk, for which quantification of the seismic hazard is required as a basic input. Over the last several decades, the practice of seismic hazard analysis has evolved enormously, firstly with the introduction of a rational framework for handling the apparent randomness in earthquake processes, which also enabled risk assessments to consider both the severity and likelihood of earthquake effects. The next major evolutionary step was the identification of epistemic uncertainties related to incomplete knowledge, and the formulation of frameworks for both their quantification and their incorporation into hazard assessments. Despite these advances in the practice of seismic hazard analysis, it is not uncommon for the acceptance of seismic hazard estimates to be hindered by invalid comparisons, resistance to new information that challenges prevailing views, and attachment to previous estimates of the hazard. The challenge of achieving impartial acceptance of seismic hazard and risk estimates becomes even more acute in the case of earthquakes attributed to human activities. A more rational evaluation of seismic hazard and risk due to induced earthquakes may be facilitated by adopting, with appropriate adaptations, the advances in risk quantification and risk mitigation developed for natural seismicity. While such practices may provide an impartial starting point for decision making regarding risk mitigation measures, the most promising avenue to achieve broad societal acceptance of the risks associated with induced earthquakes is through effective regulation, which needs to be transparent, independent, and informed by risk considerations based on both sound seismological science and reliable earthquake engineering

Publish or perish? The increasing importance of publications for prospective economics professors in Austria, Germany and Switzerland

Tenure decisions depend, among other factors, on a candidate�s career age and publication record. We measure publications in units of both Top 5 journals and of the European Economic Review (EER), associating publication output with journals indexed in EconLit. We find that the average age of a professor in the year of his/her first appointment is 38, i.e. approximately 8 years after completing the PhD. Between 1970 and 2006, the average publication record at the time of the first appointment is equivalent to 1.5 standardized Top 5 articles (one co-author, 20 pages) or 2.3 standardized EER articles. Publication records vary across sub fields and improve over time. We predict that someone running for a tenured job after 2011 should (average of all fields) aim at an average equivalent of 4 standardized Top 5 articles or 6 standardized EER articles

New insights into nonclassical light emission from defects in multi-layer hexagonal boron nitride

In recent years, mono-layers and multi-layers of hexagonal boron nitride (hBN) have been demonstrated as host materials for localized atomic defects that can be used as emitters for ultra-bright, non-classical light. The origin of the emission, however, is still subject to debate. Based on measurements of photon statistics, lifetime and polarization on selected emitters, we find that these atomic defects do not act as pure single photon emitters. Our results strongly and consistently indicate that each zero phonon line of individual emitters comprises two independent electronic transitions. These results give new insights into the nature of the observed emission and hint at a double defect nature of emitters in multi-layer hBN