Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: Genetic reclassification and correlation with clinical features

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder predisposing to predominantly colorectal cancer (CRC) and endometrial cancer frequently due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2 and also MSH6 in families seen to demonstrate an excess of endometrial cancer. As a consequence, tumors in HNPCC reveal alterations in the length of simple repetitive genomic sequences like poly-A, poly-T, CA or GT repeats (microsatellites) in at least 90% of the cases. Aim of the Study: The study cohort consisted of 25 HNPCC index patients ( 19 Amsterdam positive, 6 Bethesda positive) who revealed a microsatellite stable (MSS) - or low instable (MSI-L) - tumor phenotype with negative mutation analysis for the MMR genes MLH1 and MSH2. An extended marker panel (BAT40, D10S197, D13S153, D18S58, MYCL1) was analyzed for the tumors of these patients with regard to three aspects. First, to reconfirm the MSI-L phenotype found by the standard panel; second, to find minor MSIs which might point towards an MSH6 mutation, and third, to reconfirm the MSS status of hereditary tumors. The reconfirmation of the MSS status of tumors not caused by mutations in the MMR genes should allow one to define another entity of hereditary CRC. Their clinical features were compared with those of 150 patients with sporadic CRCs. Results: In this way, 17 MSS and 8 MSI-L tumors were reclassified as 5 MSS, 18 MSI-L and even 2 MSI-H ( high instability) tumors, the last being seen to demonstrate at least 4 instable markers out of 10. Among all family members, 87 malignancies were documented. The mean age of onset for CRCs was the lowest in the MSI-H-phenotyped patients with 40.5 +/- 4.9 years (vs. 47.0 +/- 14.6 and 49.8 +/- 11.9 years in MSI-L- and MSS-phenotyped patients, respectively). The percentage of CRC was the highest in families with MSS-phenotyped tumors (88%), followed by MSI-L-phenotyped ( 78%) and then by MSI-H-phenotyped (67%) tumors. MSS tumors were preferentially localized in the distal colon supposing a similar biologic behavior like sporadic CRC. MSH6 mutation analysis for the MSI-L and MSI-H patients revealed one truncating mutation for a patient initially with an MSS tumor, which was reclassified as MSI-L by analyzing the extended marker panel. Conclusion: Extended microsatellite analysis serves to evaluate the sensitivity of the reference panel for HNPCC detection and permits phenotype confirmation or upgrading. Additionally, it confirms the MSS status of hereditary CRCs not caused by the common mutations in the MMR genes and provides hints to another entity of hereditary CRC. Copyright (C) 2004 S. Karger AG, Basel

Pion-nucleon scattering in a meson-exchange model

The pi-N interaction is studied within a meson-exchange model and in a coupled-channels approach which includes the channels pi-N, eta-N, as well as three effective pi-pi-N channels namely rho-N, pi-Delta, and sigma-N. Starting out from an earlier model of the Julich group systematic improvements in the dynamics and in some technical aspects are introduced. With the new model an excellent quantitative reproduction of the pi-N phase shifts and inelasticity parameters in the energy region up to 1.9 GeV and for total angular momenta J leq 3/2 is achieved. Simultaneously, good agreement with data for the total and differential pi-N -> eta-N transition cross sections is obtained. The connection of the pi_N dynamics in the S_{11} partial wave with the reaction pi-N -> eta-N is discussed.Comment: 32 pages, 9 figure

Subthreshold antiproton production in proton-carbon reactions

Data from KEK on subthreshold antiproton as well as on pi(+-) and K(+-) production in proton-nucleus reactions are described at projectile energies between 3.5 and 12.0 GeV. We use a model which considers a hadron-nucleus reaction as an incoherent sum over collisions of the projectile with a varying number of target nucleons. It samples complete events and allows thus for the simultaneous consideration of all particle species measured. The overall reproduction of the data is quite satisfactory. It is shown that the contributions from the interaction of the projectile with groups of several target nucleons are decisive for the description of subthreshold production. Since the collective features of subthreshold production become especially significant far below the threshold, the results are extrapolated down to COSY energies. It is concluded that an antiproton measurement at ANKE-COSY should be feasible, if the high background of other particles can be efficiently suppressed.Comment: 15 pages, 5 figures, gzipped tar file, submitted to J. Phys. G v2: Modification of text due to demands of referee

A Unified Model for Two Localisation Problems: Electron States in Spin-Degenerate Landau Levels, and in a Random Magnetic Field

A single model is presented which represents both of the two apparently unrelated localisation problems of the title. The phase diagram of this model is examined using scaling ideas and numerical simulations. It is argued that the localisation length in a spin-degenerate Landau level diverges at two distinct energies, with the same critical behaviour as in a spin-split Landau level, and that all states of a charged particle moving in two dimensions, in a random magnetic field with zero average, are localised.Comment: 7 pages (RevTeX 3.0) plus 4 postscript figure

Intrinsic Tunneling in Cuprates and Manganites

The most anisotropic high temperature superconductors like Bi2Sr2CaCu2O8, as well as the recently discovered layered manganite La1.4Sr1.6Mn2O7 are layered metallic systems where the interlayer current transport occurs via sequential tunneling of charge carriers. As a consequence, in Bi2Sr2CaCu2O8 adjacent CuO2 double layers form an intrinsic Josephson tunnel junction while in in La1.4Sr1.6Mn2O7 tunneling of spin polarized charge carriers between adjacent MnO2 layers leads to an intrinsic spin valve effect. We present and discuss interlayer transport experiments for both systems. To perform the experiments small sized mesa structures were patterned on top of single crystals of the above materials defining stacks of a small number of intrinsic Josephson junctions and intrinsic spin valves, respectively.Comment: 6 pages, 8 figure

Effects of nutrient enrichment on seagrass population dynamics: evidence and synthesis from the biomass-density relationships

The available data from experimental and descriptive studies on seagrass biomass and density responses to nutrient enrichment were analysed to assess the intraspecific mechanisms operating within seagrass populations and whether biomass-density relationships can provide relevant metrics for monitoring seagrasses. The response of shoot biomass and density to nutrient enrichment was dependent on the type of study; the short-term positive response of biomass and density in experimental studies reveals context-specific nutrient limitation of seagrasses. The long-term negative response of descriptive studies probably results from ecosystem-scale events related to nutrient enrichment such as increased turbidity, algal blooms, epiphyte loads and anoxia. Most seagrass species analysed lie in the nonthinning part of the theoretical biomass-density curves. A simultaneous increase in biomass and decrease in density, evidence of self-thinning, were only observed in 4 of 28 studies. The analysis of both the static and the dynamic biomass-density relationships revealed that the slopes increase under nutrient enrichment. Surprisingly, the species-specific slopes (log B-log D) were higher than one, revealing that the B/D ratio, that is, the average shoot biomass, increases with density in all seagrass species analysed. Nutrient enrichment further enhanced this effect as biomass-density slopes increased to even higher values. The main drivers behind the increasing biomass-density slopes under nutrient enrichment were the increase in shoot biomass at densities above a species-specific threshold and/or its decrease below that threshold. Synthesis. Contrasting short- and long-term responses of both biomass and density of seagrasses to nutrient enrichment suggest that the former, positive ones result from nutrient limitation, whereas the later, negative ones are mediated by whole ecosystem responses. In general, shoot biomass of seagrasses increases with density, and nutrient enrichment enhances this effect. Experimental testing of facilitation processes related to clonal integration in seagrasses needs to be done to reveal whether they determine the low incidence of self-thinning and the intriguing biomass-density relationships of seagrass species. The increasing slopes and decreasing intercepts of the species-specific dynamic biomass-density relationships of seagrasses and the decreasing coefficients of variation of both biomass and density constitute relevant, easy-to-collect metrics that may be used in environmental monitoring.EU project ECO-LAGUNES [SOE1/P2/F153]; COST Action [ES0906]; FCT [SFRH/BPD/37368/2007, SFRH/BPD/75307/2010]; NSERC PGSD; Killam Trustinfo:eu-repo/semantics/publishedVersio

Poly ionic liquid Nanovesicle Templated Carbon Nanocapsules Functionalized with Uniform Iron Nitride Nanoparticles as Catalytic Sulfur Host for Li S Batteries

Poly ionic liquid s PIL are common precursors for heteroatom doped carbon materials. Despite a relatively higher carbonization yield, the PIL to carbon conversion process faces challenges in preserving morphological and structural motifs on the nanoscale. Assisted by a thin polydopamine coating route and ion exchange, imidazolium based PIL nanovesicles were successfully applied in morphology maintaining carbonization to prepare carbon composite nanocapsules. Extending this strategy further to their composites, we demonstrate the synthesis of carbon composite nanocapsules functionalized with iron nitride nanoparticles of an ultrafine, uniform size of 3 5 nm termed FexN C . Due to its unique nanostructure, the sulfur loaded FexN C electrode was tested to efficiently mitigate the notorious shuttle effect of lithium polysulfides LiPSs in Li S batteries. The cavity of the carbon nanocapsules was spotted to better the loading content of sulfur. The well dispersed iron nitride nanoparticles effectively catalyze the conversion of LiPSs to Li2S, owing to their high electronic conductivity and strong binding power to LiPSs. Benefiting from this well crafted composite nanostructure, the constructed FexN C S cathode demonstrated a fairly high discharge capacity of 1085 mAh g 1 at 0.5 C initially, and a remaining value of 930 mAh g 1 after 200 cycles. In addition, it exhibits an excellent rate capability with a high initial discharge capacity of 889.8 mAh g 1 at 2 C. This facile PIL to nanocarbon synthetic approach is applicable for the exquisite design of complex hybrid carbon nanostructures with potential use in electrochemical energy storage and conversio

Kaon effective mass and energy from a novel chiral SU(3)-symmetric Lagrangian

A new chiral SU(3) Lagrangian is proposed to describe the properties of kaons and antikaons in the nuclear medium, the ground state of dense matter and the kaon-nuclear interactions consistently. The saturation properties of nuclear matter are reproduced as well as the results of the Dirac-Br\"{u}ckner theory. Our numerical results show that the kaon effective mass might be changed only moderately in the nuclear medium due to the highly non-linear density effects. After taking into account the coupling between the omega meson and the kaon, we obtain similar results for the effective kaon and antikaon energies as calculated in the one-boson-exchange model while in our model the parameters of the kaon-nuclear interactions are constrained by the SU(3) chiral symmetry.Comment: 13 pages, Latex, 3 PostScript figures included; replaced by the revised version, to appear in Phys. Rev.

Quantum Collective Creep: a Quasiclassical Langevin Equation Approach

The dynamics of an elastic medium driven through a random medium by a small applied force is investigated in the low-temperature limit where quantum fluctuations dominate. The motion proceeds via tunneling of segments of the manifold through barriers whose size grows with decreasing driving force $f$. In the limit of small drive, at zero-temperature the average velocity has the form $v\propto\exp[-{\rm const.}/\hbar^{\alpha} f^{\mu}]$. For strongly dissipative dynamics, there is a wide range of forces where the dissipation dominates and the velocity--force characteristics takes the form $v\propto\exp[-S(f)/\hbar]$, with $S(f)\propto 1/ f^{(d+2\zeta)/(2-\zeta)}$ the action for a typical tunneling event, the force dependence being determined by the roughness exponent $\zeta$ of the $d$-dimensional manifold. This result agrees with the one obtained via simple scaling considerations. Surprisingly, for asymptotically low forces or for the case when the massive dynamics is dominant, the resulting quantum creep law is {\it not} of the usual form with a rate proportional to $\exp[-S(f)/\hbar]$; rather we find $v\propto \exp\{-[S(f)/\hbar]^2\}$ corresponding to $\alpha=2$ and $\mu= 2(d+2\zeta-1)/(2-\zeta)$, with $\mu/2$ the naive scaling exponent for massive dynamics. Our analysis is based on the quasi-classical Langevin approximation with a noise obeying the quantum fluctuation--dissipation theorem. The many space and time scales involved in the dynamics are treated via a functional renormalization group analysis related to that used previously to treat the classical dynamics of such systems. Various potential difficulties with these approaches to the multi-scale dynamics -- both classical and quantum -- are raised and questions about the validity of the results are discussed.Comment: RevTeX, 30 pages, 8 figures inserte