1,619 research outputs found
Sequential gene promoter methylation during HPV-induced cervical carcinogenesis
We aimed to link DNA methylation events occurring in cervical carcinomas to distinct stages of HPV-induced transformation. Methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) analysis of cervical carcinomas revealed promoter methylation of 12 out of 29 tumour suppressor genes analysed, with MGMT being most frequently methylated (92%). Subsequently, consecutive stages of HPV16/18-transfected keratinocytes (n=11), ranging from pre-immortal to anchorage-independent phenotypes, were analysed by MS-MLPA. Whereas no methylation was evident in pre-immortal cells, progression to anchorage independence was associated with an accumulation of frequent methylation events involving five genes, all of which were also methylated in cervical carcinomas. TP73 and ESR1 methylation became manifest in early immortal cells followed by RARÎČ and DAPK1 methylation in late immortal passages. Complementary methylation of MGMT was related to anchorage independence. Analysis of nine cervical cancer cell lines, representing the tumorigenic phenotype, revealed in addition to these five genes frequent methylation of CADM1, CDH13 and CHFR. In conclusion, eight recurrent methylation events in cervical carcinomas could be assigned to different stages of HPV-induced transformation. Hence, our in vitro model system provides a valuable tool to further functionally address the epigenetic alterations that are common in cervical carcinomas
The AMANDA Neutrino Telescope and the Indirect Search for Dark Matter
With an effective telescope area of order 10^4 m^2, a threshold of ~50 GeV
and a pointing accuracy of 2.5 degrees, the AMANDA detector represents the
first of a new generation of high energy neutrino telescopes, reaching a scale
envisaged over 25 years ago. We describe its performance, focussing on the
capability to detect halo dark matter particles via their annihilation into
neutrinos.Comment: Latex2.09, 16 pages, uses epsf.sty to place 15 postscript figures.
Talk presented at the 3rd International Symposium on Sources and Detection of
Dark Matter in the Universe (DM98), Santa Monica, California, Feb. 199
Ribosome Display Selection of a Murine IgG1 Fab Binding Affibody Molecule Allowing Species Selective Recovery Of Monoclonal Antibodies
Affinity reagents recognizing constant parts of antibody molecules are invaluable tools in immunotechnology applications, including purification, immobilization, and detection of immunoglobulins. In this article, murine IgG1, the primary isotype of monoclonal antibodies (mAbs) was used as target for selection of novel binders from a combinatorial ribosome display (RD) library of 1011 affibody molecules. Four rounds of selection using three different mouse IgG1 mAbs as alternating targets resulted in the identification of binders with broad mIgG1 recognition and dissociation constants (KD) in the low nanomolar to low micromolar range. For one of the binders, denoted Zmab25, competition in binding to full length mIgG1 by a streptococcal protein G (SPG) fragment and selective affinity capture of mouse IgG1 Fab fragments after papain cleavage of a full mAb suggest that an epitope functionally overlapping with the SPG-binding site in the CH1 domain of mouse IgG1 had been addressed. Interestingly, biosensor-based binding experiments showed that neither human IgG1 nor bovine Ig, the latter present in fetal bovine serum (FBS) was recognized by Zmab25. This selective binding profile towards murine IgG1 was successfully exploited in species selective recovery of two different mouse mAbs from complex samples containing FBS, resembling a hybridoma culture supernatant
Proposal of an extended t-J Hamiltonian for high-Tc cuprates from ab initio calculations on embedded clusters
A series of accurate ab initio calculations on Cu_pO-q finite clusters,
properly embedded on the Madelung potential of the infinite lattice, have been
performed in order to determine the local effective interactions in the CuO_2
planes of La_{2-x}Sr_xCuO_4 compounds. The values of the first-neighbor
interactions, magnetic coupling (J_{NN}=125 meV) and hopping integral
(t_{NN}=-555 meV), have been confirmed. Important additional effects are
evidenced, concerning essentially the second-neighbor hopping integral
t_{NNN}=+110meV, the displacement of a singlet toward an adjacent colinear
hole, h_{SD}^{abc}=-80 meV, a non-negligible hole-hole repulsion
V_{NN}-V_{NNN}=0.8 eV and a strong anisotropic effect of the presence of an
adjacent hole on the values of the first-neighbor interactions. The dependence
of J_{NN} and t_{NN} on the position of neighbor hole(s) has been rationalized
from the two-band model and checked from a series of additional ab initio
calculations. An extended t-J model Hamiltonian has been proposed on the basis
of these results. It is argued that the here-proposed three-body effects may
play a role in the charge/spin separation observed in these compounds, that is,
in the formation and dynamic of stripes.Comment: 24 pages, 4 figures, submitted to Phys. Rev.
Monitoring of platinum surface contamination in seven Dutch hospital pharmacies using inductively coupled plasma mass spectrometry
Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector
Data from the AMANDA-B10 detector taken during the austral winter of 1997
have been searched for a diffuse flux of high energy extraterrestrial
muon-neutrinos, as predicted from, e.g., the sum of all active galaxies in the
universe. This search yielded no excess events above those expected from the
background atmospheric neutrinos, leading to upper limits on the
extraterrestrial neutrino flux. For an assumed E^-2 spectrum, a 90% classical
confidence level upper limit has been placed at a level E^2 Phi(E) = 8.4 x
10^-7 GeV cm^-2 s^-1 sr^-1 (for a predominant neutrino energy range 6-1000 TeV)
which is the most restrictive bound placed by any neutrino detector. When
specific predicted spectral forms are considered, it is found that some are
excluded.Comment: Submitted to Physical Review Letter
Search for Point Sources of High Energy Neutrinos with AMANDA
This paper describes the search for astronomical sources of high-energy
neutrinos using the AMANDA-B10 detector, an array of 302 photomultiplier tubes,
used for the detection of Cherenkov light from upward traveling
neutrino-induced muons, buried deep in ice at the South Pole. The absolute
pointing accuracy and angular resolution were studied by using coincident
events between the AMANDA detector and two independent telescopes on the
surface, the GASP air Cherenkov telescope and the SPASE extensive air shower
array. Using data collected from April to October of 1997 (130.1 days of
livetime), a general survey of the northern hemisphere revealed no
statistically significant excess of events from any direction. The sensitivity
for a flux of muon neutrinos is based on the effective detection area for
through-going muons. Averaged over the Northern sky, the effective detection
area exceeds 10,000 m^2 for E_{mu} ~ 10 TeV. Neutrinos generated in the
atmosphere by cosmic ray interactions were used to verify the predicted
performance of the detector. For a source with a differential energy spectrum
proportional to E_{nu}^{-2} and declination larger than +40 degrees, we obtain
E^2(dN_{nu}/dE) <= 10^{-6}GeVcm^{-2}s^{-1} for an energy threshold of 10 GeV.Comment: 46 pages, 22 figures, 4 tables, submitted to Ap.
First Results from KamLAND: Evidence for Reactor Anti-Neutrino Disappearance
KamLAND has been used to measure the flux of 's from distant
nuclear reactors. In an exposure of 162 tonyr (145.1 days) the ratio of
the number of observed inverse -decay events to the expected number of
events without disappearance is for energies 3.4 MeV. The deficit of events is
inconsistent with the expected rate for standard propagation at
the 99.95% confidence level. In the context of two-flavor neutrino oscillations
with CPT invariance, these results exclude all oscillation solutions but the
`Large Mixing Angle' solution to the solar neutrino problem using reactor
sources.Comment: 6 pages, 6 figure
Muon Track Reconstruction and Data Selection Techniques in AMANDA
The Antarctic Muon And Neutrino Detector Array (AMANDA) is a high-energy
neutrino telescope operating at the geographic South Pole. It is a lattice of
photo-multiplier tubes buried deep in the polar ice between 1500m and 2000m.
The primary goal of this detector is to discover astrophysical sources of high
energy neutrinos. A high-energy muon neutrino coming through the earth from the
Northern Hemisphere can be identified by the secondary muon moving upward
through the detector. The muon tracks are reconstructed with a maximum
likelihood method. It models the arrival times and amplitudes of Cherenkov
photons registered by the photo-multipliers. This paper describes the different
methods of reconstruction, which have been successfully implemented within
AMANDA. Strategies for optimizing the reconstruction performance and rejecting
background are presented. For a typical analysis procedure the direction of
tracks are reconstructed with about 2 degree accuracy.Comment: 40 pages, 16 Postscript figures, uses elsart.st
- âŠ