Macroscopic effects in attosecond pulse generation

We examine how the generation and propagation of high-order harmonics in a partly ionized gas medium affect their strength and synchronization. The temporal properties of the resulting attosecond pulses generated in long gas targets can be significantly influenced by macroscopic effects, in particular by the intensity in the medium and the degree of ionization. Under some conditions, the use of gas targets longer than the absorption length can lead to the generation of self-compressed attosecond pulses. We show this effect experimentally, using long argon-filled gas cells as generating medium.Comment: 5 pages 4 figure

Adiabatic mechanism of the multiply charged ion production by a laser field through ATI states of an atom

ATI can be followed by an inelastic collision of the ionized electron with the parent atomic particle resulting in an excitation of the ion. It may be a continuum state excitation producing the doubly charged ion or a discrete state which also enhances the doubly charged ion production. Absorption of a few quanta above the atomic threshold is sufficient to make this mechanism work. As a result the two-electron processes can take place even in moderate fields. The example of two-electron excitations of He atoms in a 780 nm laser field with intensity above $10^{14}$W/cm$^2$ is discussedComment: 12 pages, Revtex, 1 Postscript figure. Accepted for publication in Phys.Lett.

Prorenin, its maturation and the (pro)renin receptor

The renin-angiotensin system (RAS) is a key biochemical pathway controlling homeostasis and blood pressure. The initial step of the RAS is carried out by renin to produce angiotensin (Ang) I which is converted to Angll by the angiotensin-converting enzyme (ACE). Renin is synthesized as a pro-enzyme which can be activated in dense core granules of the renal juxtaglomerular cells or released as prorenin. There is evidence that prorenin can, in addition, be activated in a reversible manner, via a prorenin receptor. Recently, a specific (pro)renin receptor was identified in human tissues. Binding ofthis receptor to (pro)renin caused increased cleavage of angiotensinogen and stimulation of an intracellular signalling pathway. The aim of this thesis is to investigate the biology of prorenin, its maturation and the (pro)renin receptor.Expression of the mouse putative (pro)renin receptor (RR) was detected by RT-PCR in all tissues and cell lines examined including human mesangial cells previously reported to be negative for RR. Mouse RR was also present during development from E9.5. The mouse and rat RR cDNA were found to be highly homologous (92% and 91%, respectively) to the human cDNA. Surprisingly, the translated human, mouse and rat cDNAs exhibited sequence identity with a small protein co-purifying with a bovine vacuolar-ATPase called M8-9 which had not been reported previously. V-ATPases are critical for cell survival. Phylogenic studies revealed RR is highly conserved between species and likely to be important physiologically. The role of RR was investigated in a high circulating prorenin rat model [TGR(Cyplal-Ren2)], in which (pro)renin triggers malignant hypertension (MH).Uptake of prorenin by the heart previously demonstrated in this transgenic model may be mediated by RR. In the present study, the animals, from a new colony, had a gradual hypertensive response. Cardiovascular stiffening was measured using echo(cardio)graphy. Despite an obvious hypertrophic remodeling and longer exposure to the inducer, no signs of microinfarctions or inflammatory infiltration cells were observed in the heart. Fibrinoid necrosis of small intra-renal vessels with glomerulosclerosis and mesenteric artery remodeling were also observed. The phenotype differs from the original work. Surprisingly, RR was not up-regulated. The reasons for the phenotypic differences between TGR(Cyplal-Ren2) colonies were examined. Two main observations were made: dietary sodium levels appear to correlate with the severity of MH and TGR(Cyplal-Ren2) animals reported in this thesis had a lower pathogen load.To investigate the possible role of RR, a prorenin decoy peptide was used to attempt to ameliorate the MH phenotype in TGR(Cyplal-Ren2) animals. This peptide which competes with prorenin for binding to RR, has been showed to improve vascular injuries in diabetic nephropathy. In TGR(Cyplal-Ren2), however, no changes in the MH phenotype could be observed, except in the mesentery in which less severe fibrinoid necrosis developed.To complement work on RR, prorenin maturation and renin storage were studied during development. The data showed the complete absence of renin granules in mouse kidneys before birth. This indicates that renin could not be stored and may not be processed through the regulated pathway as observed in the adult. Low sodium diet and ACE inhibition triggered (pro)renin granules to be produced in the foetal kidney. Two ACE inhibitors differing in their ability to cross the placenta were used. The data suggest that foetal renin granule formation is under dual control from both foetal and maternal RAS.Although the (pro)renin receptor may be important physiologically, the data presented in this thesis suggest a more fundamental role in cell biology than had previously been recognised. The lack of evidence for regulation of RR in a model of high prorenin and malignant hypertension suggests that the function of this protein may need to be re-assessed

Study of the spatial and temporal coherence of high order harmonics

We apply the theory of high-order harmonic generation by low-frequency laser fields in the strong field approximation to the study of the spatial and temporal coherence properties of the harmonics. We discuss the role of dynamically induced phases of the atomic polarization in determining the optimal phase matching conditions and angular distributions of harmonics. We demonstrate that the phase matching and the spatial coherence can be controlled by changing the focusing parameters of the fundamental laser beam. Then we present a detailed study of the temporal and spectral properties of harmonics. We discuss how the focusing conditions influence the individual harmonic spectra and time profiles, and how the intensity dependence of the dynamically induced phase leads to a chirp of the harmonic frequency. This phase modulation can be used to control the temporal and spectral properties of the harmonic radiation. Temporally, the harmonic chirped pulse can be recompressed to very small durations. Spectrally, chirping of the fundamental beam may be employed to compensate for the dynamically induced chirp and to control the individual harmonic spectrum. Finally, we discuss the short pulse effects, in particular nonadiabatic phenomena and the possibility of generating attosecond pulses.Comment: Latex file with 37 pages, 25 postscript figures. to appear in Advances in Atomic, Molecular and Optical Physic