534 research outputs found
Targeting of cytotoxic peptides to haematological malignancies.
Amphipathic peptides with an a-helical structure disrupt membranes rich in negatively charged phospholipids and have antibiotic properties. They are toxic to eukaryotic cells if internalised by a suitable targeting mechanism. We have targeted one such peptide D(KLAKLAK)2 to haemopoetic cells by conjugating it to monoclonal antibodies which recognise lineage-specific cell-surface molecules. An anti-CD33: peptide conjugate was cytotoxic to one of three CD33-positive myeloid leukaemia lines, whereas an anti- CD 19: peptide conjugate efficiently killed three out of three B lymphoid lines with IC50 in the low nanomolar range. Cell lines which did not express the relevant antigen were resistant to the conjugates at the concentrations used. Peptide conjugated to anti-CD 19 and anti-CD33 antibodies had cytotoxic activity towards cells isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML) respectively. CLL cells isolated from heavily pre-treated patients or from poor risk category individuals, as determined by elevated expression of the ZAP-70 protein tyrosine kinase, were as sensitive to the conjugate as were untreated or good risk category patients. Cell death was shown to be by an apoptotic mechanism and independent of the level of expression of anti-apoptotic proteins Bcl-2, Mcl-1 and XIAP. In addition the conjugate acted synergistically with chlorambucil. The data here suggest that anti-CD 19 D(KLAKLAK)2 displays a highly selective and potent cytotoxic activity against CLL cells and may be of therapeutic value in the treatment of this incurable leukaemia. We also panned a phage display library in an attempt to isolate a peptide that would bind to CD33 and thereby create a peptide with both targeting and cytotoxic activity towards malignant myeloid cells
Parity Effects in Stacked Nanoscopic Quantum Rings
The ground state and the dielectric response of stacked quantum rings are
investigated in the presence of an applied magnetic field along the ring axis.
For odd number of rings and an electric field perpendicular to the axis, a
linear Stark effect occurs at distinct values of the magnetic field. At those
fields energy levels cross in the absence of electric field. For even values of
a quadratic Stark effect is expected in all cases, but the induced electric
polarization is discontinuous at those special magnetic fields. Experimental
consequences for related nanostructures are discussed.Comment: typos corrected, to appear Phys. Rev. B (Rapid Communication) 15 Au
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Deep-inelastic positron-proton interactions at low values of Bjorken-x down
to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons
are studied with the H1 experiment at HERA. The inclusive cross section for
pi^0 mesons produced at small angles with respect to the proton remnant (the
forward region) is presented as a function of the transverse momentum and
energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x.
Measurements are also presented of the transverse energy flow in events
containing a forward pi^0 meson. Hadronic final state calculations based on QCD
models implementing different parton evolution schemes are confronted with the
data.Comment: 27 pages, 8 figures and 3 table
Low Q^2 Jet Production at HERA and Virtual Photon Structure
The transition between photoproduction and deep-inelastic scattering is
investigated in jet production at the HERA ep collider, using data collected by
the H1 experiment. Measurements of the differential inclusive jet
cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the
transverse energy and the pseudorapidity of the jets in the virtual
photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3
< y < 0.6. The interpretation of the results in terms of the structure of the
virtual photon is discussed. The data are best described by QCD calculations
which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure
Hadron Production in Diffractive Deep-Inelastic Scattering
Characteristics of hadron production in diffractive deep-inelastic
positron-proton scattering are studied using data collected in 1994 by the H1
experiment at HERA. The following distributions are measured in the
centre-of-mass frame of the photon dissociation system: the hadronic energy
flow, the Feynman-x (x_F) variable for charged particles, the squared
transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a
function of x_F. These distributions are compared with results in the gamma^* p
centre-of-mass frame from inclusive deep-inelastic scattering in the
fixed-target experiment EMC, and also with the predictions of several Monte
Carlo calculations. The data are consistent with a picture in which the
partonic structure of the diffractive exchange is dominated at low Q^2 by hard
gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.
Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA
An investigation of the hadronic final state in diffractive and
non--diffractive deep--inelastic electron--proton scattering at HERA is
presented, where diffractive data are selected experimentally by demanding a
large gap in pseudo --rapidity around the proton remnant direction. The
transverse energy flow in the hadronic final state is evaluated using a set of
estimators which quantify topological properties. Using available Monte Carlo
QCD calculations, it is demonstrated that the final state in diffractive DIS
exhibits the features expected if the interaction is interpreted as the
scattering of an electron off a current quark with associated effects of
perturbative QCD. A model in which deep--inelastic diffraction is taken to be
the exchange of a pomeron with partonic structure is found to reproduce the
measurements well. Models for deep--inelastic scattering, in which a
sizeable diffractive contribution is present because of non--perturbative
effects in the production of the hadronic final state, reproduce the general
tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil
A Search for Selectrons and Squarks at HERA
Data from electron-proton collisions at a center-of-mass energy of 300 GeV
are used for a search for selectrons and squarks within the framework of the
minimal supersymmetric model. The decays of selectrons and squarks into the
lightest supersymmetric particle lead to final states with an electron and
hadrons accompanied by large missing energy and transverse momentum. No signal
is found and new bounds on the existence of these particles are derived. At 95%
confidence level the excluded region extends to 65 GeV for selectron and squark
masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure
Measurement of D* Meson Cross Sections at HERA and Determination of the Gluon Density in the Proton using NLO QCD
With the H1 detector at the ep collider HERA, D* meson production cross
sections have been measured in deep inelastic scattering with four-momentum
transfers Q^2>2 GeV2 and in photoproduction at energies around W(gamma p)~ 88
GeV and 194 GeV. Next-to-Leading Order QCD calculations are found to describe
the differential cross sections within theoretical and experimental
uncertainties. Using these calculations, the NLO gluon momentum distribution in
the proton, x_g g(x_g), has been extracted in the momentum fraction range
7.5x10^{-4}< x_g <4x10^{-2} at average scales mu^2 =25 to 50 GeV2. The gluon
momentum fraction x_g has been obtained from the measured kinematics of the
scattered electron and the D* meson in the final state. The results compare
well with the gluon distribution obtained from the analysis of scaling
violations of the proton structure function F_2.Comment: 27 pages, 9 figures, 2 tables, submitted to Nucl. Phys.
Measurement of Leading Proton and Neutron Production in Deep Inelastic Scattering at HERA
Deep--inelastic scattering events with a leading baryon have been detected by
the H1 experiment at HERA using a forward proton spectrometer and a forward
neutron calorimeter. Semi--inclusive cross sections have been measured in the
kinematic region 2 <= Q^2 <= 50 GeV^2, 6.10^-5 <= x <= 6.10^-3 and baryon p_T
<= MeV, for events with a final state proton with energy 580 <= E' <= 740 GeV,
or a neutron with energy E' >= 160 GeV. The measurements are used to test
production models and factorization hypotheses. A Regge model of leading baryon
production which consists of pion, pomeron and secondary reggeon exchanges
gives an acceptable description of both semi-inclusive cross sections in the
region 0.7 <= E'/E_p <= 0.9, where E_p is the proton beam energy. The leading
neutron data are used to estimate for the first time the structure function of
the pion at small Bjorken--x.Comment: 30 pages, 9 figures, 2 tables, submitted to Eur. Phys.
- …