165 research outputs found
Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphomaâa long-term follow-up study
Background High-dose chemotherapy followed by autologous stem-cell transplantation (HCT-ASCT) is a promising approach in eligible patients with primary central nervous system lymphoma (PCNSL). We report long-term data of patients who were treated according to HCT-ASCT containing protocols. Patients and methods We analyzed survival and relapse rates in 43 (<67 years) immunocompetent patients with newly diagnosed PCNSL being treated according to two different high-dose methotrexate-based protocols followed by high-dose carmustine/thiotepa (BCNU/TT) plus ASCT (±whole brain irradiation). Analysis was conducted for all patients (intention-to-treat) and those patients who actually received HCT-ASCT (per-protocol). Results Thirty-four patients achieved complete remission, of those 12 relapsed (35%), while 6 of them relapsed 5 years after diagnosis. After a median follow-up of 120 months, median overall survival (OS) was reached after 104 months. Two- and 5-year OS was 81% and 70% and 2- and 5-year event-free survival (EFS) was 81% and 67%, respectively. In per-protocol analysis (N=34), 5-year OS and EFS was 82% and 79%, respectively. HCT-ASCT associated related mortality was not observed. Conclusions Sequential high-dose MTX containing chemotherapy followed by high-dose carmustine/thiotepa plus ASCT (±whole brain irradiation) is safe and leads to high survival rates in eligible patients with newly diagnosed PCNS
Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope
The nuclear pore complex (NPC) mediates nucleocytoplasmic transport through the
nuclear envelope. How the NPC assembles into this double membrane boundary has remained
enigmatic. Here, we captured temporally staged assembly intermediates by correlating live cell
imaging with high-resolution electron tomography and super-resolution microscopy. Intermediates
were dome-shaped evaginations of the inner nuclear membrane (INM), that grew in diameter and
depth until they fused with the flat outer nuclear membrane. Live and super-resolved fluorescence
microscopy revealed the molecular maturation of the intermediates, which initially contained the
nuclear and cytoplasmic ring component Nup107, and only later the cytoplasmic filament
component Nup358. EM particle averaging showed that the evagination base was surrounded by
an 8-fold rotationally symmetric ring structure from the beginning and that a growing mushroomshaped
density was continuously associated with the deforming membrane. Quantitative structural
analysis revealed that interphase NPC assembly proceeds by an asymmetric inside-out extrusion of
the INM
Ionization dynamics in expanding clusters studied by XUV pump probe spectroscopy
he expansion and disintegration dynamics of xenon clusters initiated by the ionization with femtosecond soft x ray extreme ultraviolet XUV pulses were studied with pump probe spectroscopy using the autocorrelator setup of the Free Electron LASer in Hamburg FLASH facility. The ionization by the first XUV pulse of 92 eV photon energy 8 1012 W cm amp; 8722;2 leads to the generation of a large number of quasi free electrons trapped by the space charge of the cluster ions. A temporally delayed, more intense probe 4 1013 W cm amp; 8722;2 pulse substantially increases a population of nanoplasma electrons providing a way of probing plasma states in the expanding cluster by tracing the average charge of fragment ions. The results of the study reveal a timescale for cluster expansion and disintegration, which depends essentially on the initial cluster size. The average charge state of fragment ions, and thus the cluster plasma changes significantly on a timescale of 1 3 p
Imaging Molecular Structure through Femtosecond Photoelectron Diffraction on Aligned and Oriented Gas-Phase Molecules
This paper gives an account of our progress towards performing femtosecond
time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe
setup combining optical lasers and an X-ray Free-Electron Laser. We present
results of two experiments aimed at measuring photoelectron angular
distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and
dissociating, laseraligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss
them in the larger context of photoelectron diffraction on gas-phase molecules.
We also show how the strong nanosecond laser pulse used for adiabatically
laser-aligning the molecules influences the measured electron and ion spectra
and angular distributions, and discuss how this may affect the outcome of
future time-resolved photoelectron diffraction experiments.Comment: 24 pages, 10 figures, Faraday Discussions 17
Coulomb explosion imaging of small organic molecules at LCLS.
Fragmentation of small organic molecules by intense few-femtosecond X-ray free-electron laser pulses has been studied using Coulomb explosion imaging. By measuring kinetic energies and emission angles of the ionic fragments in coincidence, we disentangle different fragmentation pathways, for certain cases can reconstruct molecular geometry at the moment of explosion, and show how it depends on LCLS pulse duration
towards time-resolved imaging of molecular structure
We demonstrate an experimental method to record snapshot diffraction images of
polyatomic gas-phase molecules, which can, in a next step, be used to probe
time-dependent changes in the molecular geometry during photochemical
reactions with femtosecond temporal and angstrom spatial resolution.
Adiabatically laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) molecules were
imaged by diffraction of photoelectrons with kinetic energies between 31 and
62 eV, created from core ionization of the fluorine (1s) level by â80 fs x-ray
free-electron-laser pulses. Comparison of the experimental photoelectron
angular distributions with density functional theory calculations allows
relating the diffraction images to the molecular structure
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Probing nucleobase photoprotection with soft x-rays
Nucleobases absorb strongly in the ultraviolet region, leading to molecular excitation into reactive states. The molecules avoid the photoreactions by funnelling the electronic energy into less reactive states on an ultrafast timescale via non-Born-Oppenheimer dynamics. Current theory on the nucleobase thymine discusses two conflicting pathways for the photoprotective dynamics. We present our first results of our free electron laser based UV-pump soft x-ray-probe study of the photoprotection mechanism of thymine. We use the high spatial sensitivity of the Auger electrons emitted after the soft x-ray pulse induced core ionization. Our transient spetra show two timescales on the order of 200 fs and 5 ps, in agreement with previous (all UV) ultrafast experiments. The timescales appear at different Auger kinetic energies which will help us to decipher the molecular dynamics
Imaging single cells in a beam of live cyanobacteria with an X-ray laser
There exists a conspicuous gap of knowledge about the organization of life at mesoscopic levels. Ultra-fast coherent diffractive imaging with X-ray free-electron lasers can probe structures at the relevant length scales and may reach sub-nanometer resolution on micron-sized living cells. Here we show that we can introduce a beam of aerosolised cyanobacteria into the focus of the Linac Coherent Light Source and record diffraction patterns from individual living cells at very low noise levels and at high hit ratios. We obtain two-dimensional projection images directly from the diffraction patterns, and present the results as synthetic X-ray Nomarski images calculated from the complex-valued reconstructions. We further demonstrate that it is possible to record diffraction data to nanometer resolution on live cells with X-ray lasers. Extension to sub-nanometer resolution is within reach, although improvements in pulse parameters and X-ray area detectors will be necessary to unlock this potential
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