Laboratory experiments were conducted to assess the influence of dike geometry on the breaching of non‐cohesive homogeneous fluvial dikes. Both the channel‐side and floodplain‐side dike slopes and ...the crest length were varied systematically. The time‐evolution of the breach discharge and breach width was monitored. Dikes having a larger volume per unit width lead to a more gradual increase in breach discharge and in breach width during the first stage of breach expansion (i.e., phase of rapid erosion). In contrast, the later stage of gradual breach widening is less influenced by the dike geometry. The breach hydrographs were observed to follow three distinct patterns, which are explained based on the relative magnitude of two characteristic time scales and of a normalized form of the dike unit volume.
Plain Language Summary
Fluvial dikes are structures built along rivers to protect population and property from flooding. However, failure of fluvial dikes leads to devastating human, economic and environmental consequences worldwide. Within this context, we conducted laboratory experiments to assess the influence of dike geometry on the breaching of fluvial dikes made out of homogeneous non‐cohesive material. The side slopes of a trapezoidal dike and its crest length were varied systematically. The time‐evolution of both the breach width and the discharge passing through the breach was recorded. It turned out that dikes having a larger volume per unit width lead to a slower increase in breach discharge and in breach width at the beginning of the experiment (i.e., phase of rapid erosion). In contrast, the rest of the experiment (i.e., phase of gradual breach widening) is less influenced by the dike geometry. It appeared that the breach discharge evolution observed during the different tests follows three distinct patterns, which are explained based on the dike volume per unit width and flow parameters.
Key Points
Based on laboratory experiments, the influence of dike geometry (channel‐side and floodplain‐side slopes and crest length) on breach hydrograph and widening has been assessed
Three types of breach hydrographs have been identified and related to the inflow discharge and the dike geometry
The conditions of occurrence of the three types of breach hydrographs have been clarified based on a simple conceptual model
A nonintrusive, high‐resolution laser profilometry technique (LPT) has been developed for continuous monitoring of the three‐dimensional (3‐D) evolving breach in laboratory models of noncohesive ...fluvial dikes. This simple and low‐cost setup consists of a commercial digital video camera and a sweeping red diode 30 mW laser projecting a sheet over the dike. The 2‐D image coordinates of each deformed laser profile incident on the dike are transformed into 3‐D object coordinates using the direct linear transformation (DLT) algorithm. All 3‐D object coordinates computed over a laser sweeping cycle are merged to generate a cloud of points describing the instantaneous surface. The DLT‐based image processing algorithm uses control points and reference axes, so that no prior knowledge is needed on the position, orientation, and intrinsic characteristics of the camera, nor on the laser position. Because the dike is partially submerged, ad hoc refraction correction has been developed. Algorithms and instructions for the implementation of the LPT are provided. Reconstructions of a dike geometry with the LPT and with a commercial laser scanner are compared in dry conditions. Using rigid dike geometries, the repeatability of the measurements, the refraction correction, and the dike reconstruction have been evaluated for submerged conditions. Two laboratory studies of evolving fluvial dike breaching due to flow overtopping have been conducted to demonstrate the LPT capabilities and accuracy. The LPT has advantages in terms of flexibility and spatiotemporal resolution, but high turbidity and water surface waves may lead to inaccurate geometry reconstructions.
Key Points
A high resolution Laser Profilometry Technique has been developed for continuously monitoring the three dimensional dike breach shape
The capabilities of the Laser Profilometry Technique have been assessed based on dedicated laboratory tests
Reliable, time‐resolved database of the evolving dike breach geometry has been collected for testing the accuracy of numerical models
Dopamine and cAMP-regulated phosphoprotein, Mr 32,000 (DARPP-32), is overexpressed during the gastric carcinogenesis cascade. Here, we investigated the role of DARPP-32 in promoting resistance to ...treatment with TRAIL.
In vitro cell models including stable expression and knockdown of DARPP-32 were used. The role of DARPP-32 in regulating TRAIL-dependent apoptosis was evaluated by clonogenic survival assay, Annexin V staining, immunofluorescence, quantitative reverse transcriptase PCR, Western blot, and luciferase reporter assays.
Stable expression of DARPP-32 in MKN-28 cells enhanced cell survival and suppressed TRAIL-induced cytochrome c release and activation of caspase-8, -9, and -3. Conversely, short hairpin RNA-mediated knockdown of endogenous DARPP-32 sensitized the resistant MKN-45 cells to TRAIL-induced apoptosis and enhanced TRAIL-mediated activation of caspase-8, -9, and -3. DARPP-32 induced BCL-xL expression through activation of Src/STAT3 signaling, and treatment with the Src-specific inhibitor PP1 abrogated DARPP-32-dependent BCL-xL upregulation and cell survival in MKN-28 cells. The TRAIL treatment induced caspase-dependent cleavage of NF-κBp65 protein; this cleavage was prevented by DARPP-32, thus maintaining NF-κB activity and the expression of its target, FLIP(S) protein. This suggests that upregulation of BCL-xL could play a possible role in blocking the mitochondria intrinsic apoptosis pathway, whereas the DARPP-32 effect on the NF-κB/FLIP(S) axis could serve as an additional negative feedback loop that blocks TRAIL-induced activation of caspase-8.
Our findings uncover a novel mechanism of TRAIL resistance mediated by DARPP-32, whereby it inhibits the intrinsic apoptosis pathway through upregulation of BCL-xL, and the extrinsic apoptosis pathway through the NF-κB/FLIP(S) axis.
DNA Copy Number Losses in Human Neoplasms Knuutila, Sakari; Aalto, Yan; Autio, Kirsi ...
The American journal of pathology,
09/1999, Letnik:
155, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This review summarizes reports of recurrent DNA sequence copy number losses in human neoplasms detected by comparative genomic hybridization. Recurrent losses that affect each of the chromosome arms ...in 73 tumor types are tabulated from 169 reports. The tables are available online at
http://www.amjpathol.org and
http://www.helsinki.fi/∼lgl_www/CMG.html. The genes relevant to the lost regions are discussed for each of the chromosomes. The review is supplemented also by a list of known and putative tumor suppressor genes and DNA repair genes (see Table 1, online). Losses are found in all chromosome arms, but they seem to be relatively rare at 1q, 2p, 3q, 5p, 6p, 7p, 7q, 8q, 12p, and 20q. Losses and their minimal common overlapping areas that were present in a great proportion of the 73 tumor entities reported in Table 2 (see online. are (in descending order of frequency): 9p23-p24 (48%), 13q21 (47%), 6q16 (44%), 6q26-q27 (44%), 8p23 (37%), 18q22-q23 (37%), 17p12-p13 (34%), 1p36.1 (34%), 11q23 (33%), 1p22 (32%), 4q32-qter (31%), 14q22-q23 (25%), 10q23 (25%), 10q25-qter (25%),15q21 (23%), 16q22 (23%), 5q21 (23%), 3p12-p14 (22%), 22q12 (22%), Xp21 (21%), Xq21 (21%), and 10p12 (20%). The frequency of losses at chromosomes 7 and 20 was less than 10% in all tumors. The chromosomal regions in which the most frequent losses are found implicate locations of essential tumor suppressor genes and DNA repair genes that may be involved in the pathogenesis of several tumor types.
MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and ...functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas and its function in poorly differentiated gastric non-signet ring cell carcinoma (non-SRCC) type cells. Immunohistochemical analysis using tissue microarray (TMA) showed a significant difference in MUC4 expression between normal adjacent (n = 45) and gastric adenocarcinoma (n = 83; P < 0.001). MUC4 expression was not associated with tumour type, stage or with the degree of differentiation. To gain further insight into the significance of MUC4 expression in gastric non-SRCC cells, MUC4 was ectopically expressed in AGS, a poorly differentiated gastric non-signet ring cell line. The MUC4 overexpressing cells (AGS-MUC4) showed a significant increase (P < 0.005) in cell motility and a decrease in cellular aggregation as compared with the vector-transfected cells. Furthermore, in vivo tumorigenicity analysis revealed that animals transplanted with the MUC4 overexpressing cells (AGS-MUC4) had a greater incidence of tumours (83%) in comparison to empty vector control (17%). In addition, the expression of MUC4 resulted in enhanced expression of total cellular ErbB2 and phosphorylated ErbB2. In conclusion, our results showed that MUC4 is overexpressed in gastric adenocarcinoma tissues, and that it has a role in promoting aggressive properties in poorly differentiated gastric non-SRCC cells through the activation of the ErbB2 oncoprotein.
A model-dependent amplitude analysis of the decay B0→D(K0Sπ+π−)K∗0 is performed using proton-proton collision data corresponding to an integrated luminosity of 3.0fb−1, recorded at s√=7 and 8TeV by ...the LHCb experiment. The CP violation observables x± and y±, sensitive to the CKM angle γ, are measured to bex−=−0.15±0.14±0.03±0.01,y−=0.25±0.15±0.06±0.01,x+=0.05±0.24±0.04±0.01,y+=−0.65+0.24−0.23±0.08±0.01,where the first uncertainties are statistical, the second systematic and the third arise from the uncertainty on the D→K0Sπ+π− amplitude model. These are the most precise measurements of these observables. They correspond to γ=(80+21−22)∘ and rB0=0.39±0.13, where rB0 is the magnitude of the ratio of the suppressed and favoured B0→DK+π− decay amplitudes, in a Kπ mass region of ±50MeV around the K∗(892)0 mass and for an absolute value of the cosine of the K∗0 decay angle larger than 0.4.
Production cross-sections of prompt charm mesons are measured with the first data from $pp$ collisions at the LHC at a centre-of-mass energy of $13\,\mathrm{TeV}$. The data sample corresponds to an ...integrated luminosity of $4.98 \pm 0.19\,\mathrm{pb}^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^{0}$, $D^{+}$, $D_{s}^{+}$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\mathrm{T}}$, and rapidity, $y$, and cover the range $0 < p_{\mathrm{T}} < 15\,\mathrm{GeV}/c$ and $2.0 < y < 4.5$. The ratios of the integrated cross-sections between charm mesons agree with previously measured fragmentation fractions. The inclusive $c\overline{c}$ cross-section within the range of $0 < p_{\mathrm{T}} < 8\,\mathrm{GeV}/c$ is found to be \ \sigma(pp \to c\overline{c}X) = 2940 \pm 3 \pm 180 \pm 160\,\mu\mathrm{b} \ where the uncertainties are due to statistical, systematic and fragmentation fraction uncertainties, respectively.
The $B_s^0 \rightarrow J/\psi \phi \phi$ decay is observed in $pp$ collision data corresponding to an integrated luminosity of 3 fb$^{-1}$ recorded by the LHCb detector at centre-of-mass energies of ...7 TeV and 8 TeV. This is the first observation of this decay channel, with a statistical significance of 15 standard deviations. The mass of the $B_s^0$ meson is measured to be $5367.08\,\pm \,0.38\,\pm\, 0.15$ MeV/c$^2$. The branching fraction ratio $\mathcal{B}(B_s^0 \rightarrow J/\psi \phi \phi)/\mathcal{B}(B_s^0 \rightarrow J/\psi \phi)$ is measured to be $0.0115\,\pm\, 0.0012\, ^{+0.0005}_{-0.0009}$. In both cases, the first uncertainty is statistical and the second is systematic. No evidence for non-resonant $B_s^0 \rightarrow J/\psi \phi K^+ K^-$ or $B_s^0 \rightarrow J/\psi K^+ K^- K^+ K^-$ decays is found.
An angular analysis of the $B^{0}\rightarrow K^{*0}(\rightarrow K^{+}\pi^{-})\mu^{+}\mu^{-}$ decay is presented. The dataset corresponds to an integrated luminosity of $3.0\,{\mbox{fb}^{-1}}$ of $pp$ ...collision data collected at the LHCb experiment. The complete angular information from the decay is used to determine $C\!P$-averaged observables and $C\!P$ asymmetries, taking account of possible contamination from decays with the $K^{+}\pi^{-}$ system in an S-wave configuration. The angular observables and their correlations are reported in bins of $q^2$, the invariant mass squared of the dimuon system. The observables are determined both from an unbinned maximum likelihood fit and by using the principal moments of the angular distribution. In addition, by fitting for $q^2$-dependent decay amplitudes in the region $1.1<q^{2}<6.0\mathrm{\,Ge\kern -0.1em V}^{2}/c^{4}$, the zero-crossing points of several angular observables are computed. A global fit is performed to the complete set of $C\!P$-averaged observables obtained from the maximum likelihood fit. This fit indicates differences with predictions based on the Standard Model at the level of 3.4 standard deviations. These differences could be explained by contributions from physics beyond the Standard Model, or by an unexpectedly large hadronic effect that is not accounted for in the Standard Model predictions.