[Histomorphological and molecular-pathological prognostic factors in colorectal cancer]. / Histomorphologische und molekularpathologische Prognosefaktoren beim kolorektalen Karzinom.

Colorectal carcinomas are the second most common cancer and cause of cancer death in Germany for both men and women. Different aspects of morphological, immunohistochemical, and molecular pathological prognostic factors of colorectal carcinomas and their precursors were investigated. We demonstrated the prognostic relevance and importance of a precise classification of pericolonic tumor deposits (PTDs) in the pT category of the TNM classification. Furthermore, we demonstrated that patients with regional lymph node metastases after neoadjuvant chemoradiotherapy (nCRT) in rectal carcinomas with ypN0 status do not have a worse prognosis than patients without signs of preoperative lymph node metastases.Molecular pathological examinations of so-called serrated colorectal fibroblastic polyps as possible precursor lesions of colorectal carcinomas showed that their epithelial area represents a true neoplastic component and thus allows for their consideration in the context of a risk assessment for colorectal carcinomas.

Evidence for a glassy state in strongly driven carbon.

Here, we report results of an experiment creating a transient, highly correlated carbon state using a combination of optical and x-ray lasers. Scattered x-rays reveal a highly ordered state with an electrostatic energy significantly exceeding the thermal energy of the ions. Strong Coulomb forces are predicted to induce nucleation into a crystalline ion structure within a few picoseconds. However, we observe no evidence of such phase transition after several tens of picoseconds but strong indications for an over-correlated fluid state. The experiment suggests a much slower nucleation and points to an intermediate glassy state where the ions are frozen close to their original positions in the fluid.

X-ray scattering measurements of strong ion-ion correlations in shock-compressed aluminum.

The strong ion-ion correlation peak characteristic of warm dense matter (WDM) is observed for the first time using simultaneous angularly, temporally, and spectrally resolved x-ray scattering measurements in laser-driven shock-compressed aluminum. Laser-produced molybdenum x-ray line emission at an energy of 17.9 keV is employed to probe aluminum compressed to a density of ρ>8 g/cm(3). We observe a well pronounced peak in the static structure factor at a wave number of k=4.0 Å(-1). The measurements of the magnitude and position of this correlation peak are precise enough to test different theoretical models for the ion structure and show that only models taking the complex interaction in WDM into account agree with the data. This also demonstrates a new highly accurate diagnostic to directly measure the state of compression of warm dense matter.

Probing the complex ion structure in liquid carbon at 100 GPa.

We present the first direct experimental test of the complex ion structure in liquid carbon at pressures around 100 GPa, using spectrally resolved x-ray scattering from shock-compressed graphite samples. Our results confirm the structure predicted by ab initio quantum simulations and demonstrate the importance of chemical bonds at extreme conditions similar to those found in the interiors of giant planets. The evidence presented here thus provides a firmer ground for modeling the evolution and current structure of carbon-bearing icy giants like Neptune, Uranus, and a number of extrasolar planets.

Screening of ionic cores in partially ionized plasmas within linear response.

We employ a pseudopotential approach to investigate the screening of ionic cores in partially ionized plasmas. Here, the effect of the tightly bound electrons is condensed into an effective potential between the (free) valence electrons and the ionic cores. Even for weak electron-ion coupling, the corresponding screening clouds show strong modifications from the Debye result for elements heavier than helium. Modifications of the theoretically predicted x-ray scattering signal and implications on measurements are discussed.

Measurement of short-range correlations in shock-compressed plastic by short-pulse x-ray scattering.

We have performed short-pulse x-ray scattering measurements on laser-driven shock-compressed plastic samples in the warm dense matter regime, providing instantaneous snapshots of the system evolution. Time-resolved and angularly resolved scattered spectra sensitive to the correlation effects in the plasma show the appearance of short-range order within a few interionic separations. Comparison with radiation-hydrodynamic simulations indicates that the shocked plastic is compressed with a temperature of a few electron volts. These results are important for the understanding of the thermodynamic behavior of strongly correlated matter for conditions relevant to both laboratory astrophysics and inertial confinement fusion research.

Ion structure in warm dense matter: benchmarking solutions of hypernetted-chain equations by first-principle simulations.

We investigate the microscopic structure of strongly coupled ions in warm dense matter using ab initio simulations and hypernetted chain (HNC) equations. We demonstrate that an approximate treatment of quantum effects by weak pseudopotentials fails to describe the highly degenerate electrons in warm dense matter correctly. However, one-component HNC calculations for the ions agree well with first-principles simulations if a linearly screened Coulomb potential is used. These HNC results can be further improved by adding a short-range repulsion that accounts for bound electrons. Examples are given for recently studied light elements, lithium and beryllium, and for aluminum where the extra short-range repulsion is essential.

Deep brain stimulation of globus pallidus internus in a 16-year-old boy with severe tourette syndrome and mental retardation.

A 16- year-old boy with long-standing severe Tourette syndrome (TS) and mental retardation, non-responsive to complex pharmocological and behavioural treatment was selected for bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi). Pre-operative and post-operative Yale Tourette syndrome scale (YTSS) scores and several other scores were used to quantify the effect of DBS up to one year follow-up. Although subscores of the YTSS improved, the overall outcome of chronic GPi-DBS showed no substantial therapeutic effect. This finding is in contrast to markedly improved TS of the only two adolescent TS patients in whom DBS has been performed so far. In this article we discuss possible reasons for the poor therapeutic effect of GPi-DBS in our patient contributing to the on-going debate on DBS inclusion criteria for adolescent TS patients.

Measurements of ionic structure in shock compressed lithium hydride from ultrafast x-ray Thomson scattering.

We present the first ultrafast temporally, spectrally, and angularly resolved x-ray scattering measurements from shock-compressed matter. The experimental spectra yield the absolute elastic and inelastic scattering intensities from the measured density of free electrons. Laser-compressed lithium-hydride samples are well characterized by inelastic Compton and plasmon scattering of a K-alpha x-ray probe providing independent measurements of temperature and density. The data show excellent agreement with the total intensity and structure when using the two-species form factor and accounting for the screening of ion-ion interactions.

Structure of strongly coupled multicomponent plasmas.

We investigate the short-range structure in strongly coupled fluidlike plasmas using the hypernetted chain approach generalized to multicomponent systems. Good agreement with numerical simulations validates this method for the parameters considered. We found a strong mutual impact on the spatial arrangement for systems with multiple ion species which is most clearly pronounced in the static structure factor. Quantum pseudopotentials were used to mimic diffraction and exchange effects in dense electron-ion systems. We demonstrate that the different kinds of pseudopotentials proposed lead to large differences in both the pair distributions and structure factors. Large discrepancies were also found in the predicted ion feature of the x-ray scattering signal, illustrating the need for comparison with full quantum calculations or experimental verification.

Expression of the mouse Delta1 gene during organogenesis and fetal development.

Cell-to-cell communication mediated by the evolutionary conserved Notch signalling pathway regulates cell fate decisions and patterning in various tissues in diverse organisms (Artavanis-Tsakonas et al., 1995, Science 268, 225-232). Signalling between neighboring cells is transduced by binding of DSL and Notch proteins which interact as ligand (DSL) and receptor (Notch). Mouse Delta1 (delta-like 1; Dll1) encodes one of the four known mammalian DSL proteins and is essential for normal somitogenesis and neuronal differentiation. Here, we describe Delta1 expression during organogenesis and fetal development using the highly sensitive histochemical detection of the lacZ gene product expressed from a targeted Delta1:lacZ knock-in allele (Dll1(lacZ)). We find that Delta1 is expressed in epithelial ducts of several organs, skeletal and smooth muscles, the central nervous system, as well as some sensory epithelia.

Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse.

BACKGROUND: The process of somitogenesis can be divided into three major events: the prepatterning of the mesoderm; the formation of boundaries between the prospective somites; and the cellular differentiation of the somites. Expression and functional studies have demonstrated the involvement of the murine Notch pathway in somitogenesis, although its precise role in this process is not yet well understood. We examined the effect of mutations in the Notch pathway elements Delta like 1 (Dll1), Notch1 and RBPJkappa on genes expressed in the presomitic mesoderm (PSM) and have defined the spatial relationships of Notch pathway gene expression in this region. RESULTS: We have shown that expression of Notch pathway genes in the PSM overlaps in the region where the boundary between the posterior and anterior halves of two consecutive somites will form. The Dll1, Notch1 and RBPJkappa mutations disrupt the expression of Lunatic fringe (L-fng), Jagged1, Mesp1, Mesp2 and Hes5 in the PSM. Furthermore, expression of EphA4, mCer 1 and uncx4.1, markers for the anterior-posterior subdivisions of the somites, is down-regulated to different extents in Notch pathway mutants, indicating a global alteration of pattern in the PSM. CONCLUSIONS: We propose a model for the mechanism of somite border formation in which the activity of Notch in the PSM is restricted by L-fng to a boundary-forming territory in the posterior half of the prospective somite. In this region, Notch function activates a set of genes that are involved in boundary formation and anterior-posterior somite identity.