Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype.

The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon adenoma to carcinoma in situ, and its loss inhibits growth of human colorectal tumor xenografts and intestinal adenomas in Apc(min/+) mice, while its transgenic overexpression promotes colorectal tumorigenesis. Furthermore, in intestinal tumors PROX1 is a direct and dose-dependent target of the beta-catenin/TCF signaling pathway, responsible for the neoplastic transformation. Our data underscore the complexity of cancer pathogenesis and implicate PROX1 in malignant tumor progression through the regulation of cell polarity and adhesion.

Constraints on effective field theory parameters for the Lambda N -> NN transition

The relation between the low-energy constants appearing in the effective field theory description of the Lambda N -> NN transition potential and the parameters of the one-meson-exchange model previously developed is obtained. We extract the relative importance of the different exchange mechanisms included in the meson picture by means of a comparison to the corresponding operational structures appearing in the effective approach. The ability of this procedure to obtain the weak baryon-baryon-meson couplings for a possible scalar exchange is also discussed.

Constraints on effective field theory parameters for the Lambda N -> NN transition

The relation between the low-energy constants appearing in the effective field theory description of the Lambda N -> NN transition potential and the parameters of the one-meson-exchange model previously developed is obtained. We extract the relative importance of the different exchange mechanisms included in the meson picture by means of a comparison to the corresponding operational structures appearing in the effective approach. The ability of this procedure to obtain the weak baryon-baryon-meson couplings for a possible scalar exchange is also discussed.

An epidemiologic study to determine the prevalence of the HLA-B*5701 allele among HIV-positive patients in Europe.

OBJECTIVES: HLA-B*5701 is a major histocompatibility complex class I allele associated with an immunologically-mediated hypersensitivity reaction to abacavir. The objectives of this study were to evaluate HLA-B*5701 prevalence among European, HIV-1-infected patients and to compare the local and central laboratory screening results. METHODS: Data were combined from six multicentre, prospective studies involving 10 European countries in which HIV-1-infected patients (irrespective of treatment experience or previous HLA-B*5701 screening), >or=18 years of age, were evaluated for HLA-B*5701 carriage, determined by the central and local laboratory methods. RESULTS: A total of 9720 patients from 272 centres were included in the analysis. The overall estimate of HLA-B*5701 prevalence in Europe was 4.98%, with country-specific estimates ranging from 1.53 to 7.75%. HLA-B*5701 prevalence was highest in the self-reported white population (6.49%) and lowest in the black population (0.39%). Local laboratory results had a high specificity (99.9%) and sensitivity (99.2%) when compared with the central laboratory results. CONCLUSION: This study supports data from previous studies regarding the prevalence of HLA-B*5701 in the HIV population and the variation of HLA-B*5701 prevalence between different racial groups. The high specificity and sensitivity of local laboratory results, suggests that clinicians can be confident in using local laboratories for pretreatment HLA-B*5701 screening. However, it is essential that local laboratories participate in HLA-B*5701-specific quality assurance programs to maintain 100% sensitivity. In HIV-infected patients, pretreatment HLA-B*5701 screening may allow more informed decisions regarding abacavir use and has the potential to significantly reduce the frequency of abacavir-related hypersensitivity reactions and costs associated with managing these reactions.

Patterns and transitions in substance use among young Swiss men: a latent transition analysis approach

This study investigates the potential stages of drug use. Data from the longitudinal Cohort Study on Substance Use Risk Factors were used (N = 5,116). Drug use (alcohol, tobacco, and 16 illicit drugs) over the previous 12 months was assessed at two time points. Patterns and trajectories of drug use were studied using latent transition analysis (LTA). This study's substantive contributions are twofold. First, the pattern of drug use displayed the well-known sequence of drug involvement (licit drugs to cannabis to other illicit drugs), but with an added distinction between two kinds of illicit drugs ("middle-stage" drugs: uppers, hallucinogens, inhaled drugs; and "final-stage" drugs: heroin, ketamine, GHB/GBL, research chemicals, crystal meth, and spice). Second, subgroup membership was stable over time, as the most likely transition was remaining in the same latent class.

Brittle to ductile transition in a fiber bundle with strong heterogeneity

We analyze the failure process of a two-component system with widely different fracture strength in the framework of a fiber bundle model with localized load sharing. A fraction 0≤α≤1 of the bundle is strong and it is represented by unbreakable fibers, while fibers of the weak component have randomly distributed failure strength. Computer simulations revealed that there exists a critical composition αc which separates two qualitatively different behaviors: Below the critical point, the failure of the bundle is brittle, characterized by an abrupt damage growth within the breakable part of the system. Above αc, however, the macroscopic response becomes ductile, providing stability during the entire breaking process. The transition occurs at an astonishingly low fraction of strong fibers which can have importance for applications. We show that in the ductile phase, the size distribution of breaking bursts has a power law functional form with an exponent μ=2 followed by an exponential cutoff. In the brittle phase, the power law also prevails but with a higher exponent μ=92. The transition between the two phases shows analogies to continuous phase transitions. Analyzing the microstructure of the damage, it was found that at the beginning of the fracture process cracks nucleate randomly, while later on growth and coalescence of cracks dominate, which give rise to power law distributed crack sizes.

Multidelayed random walks: Theory and application to the neolithic transition in Europe

We present a model in which particles (or individuals of a biological population) disperse with a rest time between consecutive motions (or migrations) which may take several possible values from a discrete set. Particles (or individuals) may also react (or reproduce). We derive a new equation for the effective rest time T˜ of the random walk. Application to the neolithic transition in Europe makes it possible to derive more realistic theoretical values for its wavefront speed than those following from the single-delayed framework presented previously [J. Fort and V. Méndez, Phys. Rev. Lett. 82, 867 (1999)]. The new results are consistent with the archaeological observations of this important historical process

Das geplante "Datenschutz-Gesetz": eine Bedrohung der medizinisch-epidemiologischen Forschung in der Schweiz? [The proposed law on safeguarding of data: a threat to medical-epidemiologic research in Switzerland?].

The draft of the new law on the confidentiality of personal data severely curtails medical and epidemiological research. This might be detrimental and dangerous to public health. The project therefore has to be amended.

Equilibrium curves and growth models to deal with forests in transition to uneven-aged structure : application in two sample stands

Abstract