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Biomedical subjects

I Hartl

Publications and source records attributed to I Hartl.

9 recordsLinked to original sources
PubMed2006

Fiber-laser frequency combs with subhertz relative linewidths.

We investigate the comb linewidths of self-referenced, fiber-laser-based frequency combs by measuring the heterodyne beat signal between two independent frequency combs that are phase locked to a common cw optical reference. We demonstrate that the optical comb lines can exhibit instrument-limited, subhertz relative linewidths across the comb spectra from 1200 to 1720 nm with a residual integrated optical phase jitter of approximately 1 rad in a 60 mHz to 500 kHz bandwidth. The projected relative pulse timing jitter is approximately 1 fs. This performance approaches that of Ti:sapphire frequency combs.

Journal Article↗
PubMed2005

Library-based selection of retroviruses selectively spreading through matrix metalloprotease-positive cells.

Viruses conditionally replicating in cancer cells form an attractive novel class of antitumoral agents. To engineer such viruses infectivity can be coupled with proteolytic activity of the target cell by modifying the envelope (Env) protein of murine leukaemia virus (MLV) with blocking domains that prevent cell entry unless they are cleaved off by tumour-associated proteases like the matrix metalloproteases (MMP). Here we show that MLV variants selectively spreading through MMP-positive cells can be evolved from virus libraries, in which a standard MMP-2 substrate peptide connecting the blocking domain CD40L with the Env protein was diversified. Passaging the virus library on human fibrosarcoma or glioma cell lines resulted in the selection of about 10 virus clones, of which the three most frequent ones were shown to become activated by MMPs and to be replication competent on MMP-positive cells only. On these cells, the selected linker peptides improved the spreading by several orders of magnitude in vitro, as well as in tumour xenografts in vivo, approaching the kinetic of the unmodified wild-type virus. The data suggest that retroviral protease substrate libraries form a potent tool for the engineering of viruses conditionally replicating in a given cancer cell type of interest.

Animals↗
PubMed2004

Frequency metrology with a turnkey all-fiber system.

The repetition rate and carrier-envelope phase offset frequencies of a turnkey, all-fiber-based continuum generator were phase locked to a hydrogen maser. The frequency of the hydrogen maser was calibrated with a highly stable cesium atomic clock, and therefore a fully phase-locked optical frequency comb with well-defined absolute frequencies was obtained. In contrast with the commonly used Ti:sapphire-laser-based systems, we have accomplished a fully turnkey system with no user-adjustable parts. To evaluate the performance of this novel system, we performed absolute frequency measurements in the telecommunications region and at 1064 nm and compared them with our traditional Ti:sapphire-based comb.

Journal Article↗
PubMed2004

Chirped pulse amplification with a nonlinearly chirped fiber Bragg grating matched to the Treacy compressor.

We demonstrate a fiber chirped pulse amplification system that uses an engineered nonlinearly chirped fiber Bragg grating stretcher dispersion matched to the Treacy compressor. The seed pulses at 1558 nm are stretched to 720 ps, amplified by more than 50 dB to 6.5-microJ energy, and recompressed to 940 fs. After almost 1000 times compression the pulses are within 30% of the bandwidth limit and have a contrast ratio of better than 30 dB.

Journal Article↗
PubMed2003

High-resolution optical coherence microscopy for high-speed, in vivo cellular imaging.

Optical coherence microscopy (OCM) is demonstrated with a high-speed, broadband, reflective-grating phase modulator and a femtosecond Ti:Al2O3 laser. The novel system design permits high-resolution OCM imaging in a new operating regime in which a short coherence gate is used to relax the requirement for high-numerical-aperture confocal axial sectioning. In vivo cellular imaging is demonstrated in the Xenopus laevis tadpole and in human skin with a 3-microm coherence gate and a 30-microm confocal gate. The ability to achieve cellular imaging with a lower numerical aperture should facilitate the development of miniaturized probes for in vivo imaging applications.

Animals↗
PubMed2003

Directed evolution of retroviruses activatable by tumour-associated matrix metalloproteases.

Protease-activatable retroviral vectors offer the possibility of targeted gene transfer into cancer cells expressing a unique set of proteases as, for example, the matrix metalloproteases (MMPs). However, it is difficult to predict which substrate sequence will be optimally cleaved by a given tumour cell type. Therefore, we developed a novel approach that allows the selection of MMP-activatable retroviruses from libraries of viruses displaying combinatorially diversified protease substrates. Starting from a virus harbouring a standard MMP-2 substrate motif, after only two consecutive cycles of diversification and in vivo selection, MMP-activatable viruses were recovered. Biochemical characterization of the selected viruses revealed that their linker peptides showed a considerably increased sensitivity for MMP-2 cleavage, and interestingly also improved the particle incorporation rate of the Env protein. Owing to the optimized linker peptide, the selected viruses exhibited a greatly enhanced spreading efficiency through human fibrosarcoma cells, while having retained the dependency on MMP activation. Moreover, cell entry efficiency and virus titres were considerably improved as compared to the parental virus displaying the standard MMP-2 substrate. The results presented imply that retroviral protease substrate libraries allow the definition of MMP substrate specificities under in vivo conditions as well as the generation of optimally adapted tumour-specific viruses.

Cell Line↗
PubMed1993

Quantitative EEG before and after open heart surgery in children. A significant decrease in the beta and alpha 2 bands postoperatively.

Quantitative EEGs of 30 patients undergoing open heart surgery were investigated before, 6 days, 11 days and 44 days after operation. The study was conducted in order to investigate whether quantitative EEGs can show postoperative changes in children after open heart surgery. In 28 children, no new neurological signs of cerebral involvement were seen postoperatively. The most striking feature in these children was a significant decrease in the beta and the alpha 2 bands 6 and 11 days postoperatively. The pattern in the delta band was dominated by an increase 6 days postoperatively. Except for a slight decrease in alpha 2 waves, all variables were restored to preoperative values at 44 days after the operation. We found a significant decrease in plasma sodium and chloride after surgery but children with no or slight declines (1-3 mmol/l) also showed increased slow activity postoperatively. Therefore we conclude that an organic brain syndrome, although usually mild and transient, is a general phenomenon after open heart surgery.

Adolescent↗
PubMedDate not supplied

[The anion gap--screening for hyperlactatemia in critically ill children?].

Serum lactate provides important information about tissue perfusion in critically ill patients. Aim of this study is to evaluate anion gap as a screening method to detect hyperlactatemia at a pediatric intensive care unit. In infants and children of different ages and diagnosis we determined blood gases, electrolytes and lactate. Sensitivity of anion gap was increasing with increasing hyperlactatemia. For the total population the test exhibited a sensitivity of 64% and a specificity of 76%, respectively. The power of anion gap as a screening method to detect hyperlactatemia was similarly fair for all age groups. Therefore hyperlactatemia has also to be included in the differential diagnosis of non-anion gap metabolic acidosis.

Acid-Base Equilibrium↗