2,080 research outputs found
Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer
BACKGROUND: Amplifications at 6p22.3 are prevalent in advanced stage bladder cancer (TCC). Previous studies have identified SOX4, CDKAL, and E2F3 as targets of this amplification and therefore potential oncogenes, but the more telomeric DEK gene too has been reported as overexpressed and amplified. We have therefore investigated whether the intermediate region harboring the oncogene candidate ID4 is also part of the amplicon. RESULTS: Expression of E2F3, DEK, and ID4 was investigated by real-time RT-PCR in 28 TCC compared to 6 normal bladder tissues and in 15 TCC cell lines compared to cultured normal urothelial cells. Expression of E2F3 as well as DEK increased on average in tumor vs. normal tissues (3-fold and 2.5-fold, resp.), but only the increase for E2F3 was statistically significant (p = 0.039). ID4 overexpression was observed in selected specimens. Each of the three genes was overexpressed in several cell lines, up to 150-fold (ID4), 30-fold (E2F3), and 9-fold (DEK), but these increases were not correlated to each other. Instead, moderate (DEK) to excellent (ID4) correlations were observed with copy number increases of microsatellites near each gene. Microsatellite copy number increases were highly heterogeneous across the investigated several Mb region revealing at least three subregions of amplification. CONCLUSION: Extending previous reports, our data indicate that the 6p22.3 amplicon in TCC is highly heterogeneous and targets several genes in a variable fashion. Among these, expression of E2F3 and DEK appear to be generally increased in TCC, with additional increases caused by amplifications. In contrast, over-expression of ID4, which is normally predominantly expressed in testes and brain, appears to depend more strictly on gene amplification. Accordingly, the effect of amplifications at 6p22.3 in bladder cancer is expected to be non-uniform, thereby contributing to the highly variable biological and clinical behavior of advanced stage tumors. ID4 is a potential oncogene in a small subset of bladder cancers
I-BEAT: New ultrasonic method for single bunch measurement of ion energy distribution
The shape of a wave carries all information about the spatial and temporal
structure of its source, given that the medium and its properties are known.
Most modern imaging methods seek to utilize this nature of waves originating
from Huygens' principle. We discuss the retrieval of the complete kinetic
energy distribution from the acoustic trace that is recorded when a short ion
bunch deposits its energy in water. This novel method, which we refer to as
Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a generalization of the
ionoacoustic approach. Featuring compactness, simple operation,
indestructibility and high dynamic ranges in energy and intensity, I-BEAT is a
promising approach to meet the needs of petawatt-class laser-based ion
accelerators. With its capability of completely monitoring a single, focused
proton bunch with prompt readout it, is expected to have particular impact for
experiments and applications using ultrashort ion bunches in high flux regimes.
We demonstrate its functionality using it with two laser-driven ion sources for
quantitative determination of the kinetic energy distribution of single,
focused proton bunches.Comment: Paper: 17 Pages, 3 figures Supplementary Material 16 pages, 7 figure
Space as a low-temperature regime of graphs
I define a statistical model of graphs in which 2-dimensional spaces arise at
low temperature. The configurations are given by graphs with a fixed number of
edges and the Hamiltonian is a simple, local function of the graphs.
Simulations show that there is a transition between a low-temperature regime in
which the graphs form triangulations of 2-dimensional surfaces and a
high-temperature regime, where the surfaces disappear. I use data for the
specific heat and other observables to discuss whether this is a phase
transition. The surface states are analyzed with regard to topology and
defects.Comment: 22 pages, 12 figures; v3: published version; J.Stat.Phys. 201
Evidence for a regulatory role of Cullin-RING E3 ubiquitin ligase 7 in insulin signalling
Dysfunctional regulation of signalling pathways downstream of the insulin receptor plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. In this study we report both in vitro and in vivo experimental evidence for a role of Cullin-RING E3 ubiquitin ligase 7 (CRL7) in the regulation of insulin signalling and glucose homeostasis. We show that Cul7â/â mouse embryonic fibroblasts displayed enhanced AKT and Erk MAP kinase phosphorylation upon insulin stimulation. Depletion of CUL7 by RNA interference in C2C12 myotubes led to increased activation of insulin signalling pathways and cellular glucose uptake, as well as a reduced capacity of these cells to execute insulin-induced degradation of insulin receptor substrate 1 (IRS1). In vivo, heterozygosity of either Cul7 or Fbxw8, both key components of CRL7, resulted in elevated PI3 kinase / AKT activation in skeletal muscle tissue upon insulin stimulation when compared to wild-type controls. Finally, Cul7+/â or Fbxw8+/â mice exhibited enhanced insulin sensitivity and plasma glucose clearance. Collectively, our findings point to a yet unrecognized role of CRL7 in insulin-mediated control of glucose homeostasis by restraining PI3 kinase / AKT activities in skeletal muscle cells
Multiferroicity in an organic charge-transfer salt: Electric-dipole-driven magnetism
Multiferroics, showing simultaneous ordering of electrical and magnetic
degrees of freedom, are remarkable materials as seen from both the academic and
technological points of view. A prominent mechanism of multiferroicity is the
spin-driven ferroelectricity, often found in frustrated antiferromagnets with
helical spin order. There, similar to conventional ferroelectrics, the
electrical dipoles arise from an off-centre displacement of ions. However,
recently a different mechanism, namely purely electronic ferroelectricity,
where charge order breaks inversion symmetry, has attracted considerable
interest. Here we provide evidence for this exotic type of ferroelectricity,
accompanied by antiferromagnetic spin order, in a two-dimensional organic
charge-transfer salt, thus representing a new class of multiferroics. Quite
unexpectedly for electronic ferroelectrics, dipolar and spin order arise nearly
simultaneously. This can be ascribed to the loss of spin frustration induced by
the ferroelectric ordering. Hence, here the spin order is driven by the
ferroelectricity, in marked contrast to the spin-driven ferroelectricity in
helical magnets.Comment: 8 pages, 9 figures (including 4 pages and 6 figures in supplementary
information). Version 2 with minor errors corrected (legend of Fig. 3c and
definition of vectors e and Q
The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.
The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-Îł (IFNÎł) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-Îą (TNFÎą) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFÎą production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNÎł compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice
I-BEAT: Ultrasonic method for online measurement of the energy distribution of a single ion bunch
The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens' principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a refinement of the ionoacoustic approach. With its capability of completely monitoring a single, focused proton bunch with prompt readout and high repetition rate, I-BEAT is a promising approach to meet future requirements of experiments and applications in the field of laser-based ion acceleration. We demonstrate its functionality at two laser-driven ion sources for quantitative online determination of the kinetic energy distribution in the focus of single proton bunches
Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
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