Ultrafast Relaxation Dynamics of the Antiferrodistortive Phase in Ca Doped SrTiO_{3}.

The ultrafast dynamics of the octahedral rotation in Ca:SrTiO_{3} is studied by time-resolved x-ray diffraction after photoexcitation over the band gap. By monitoring the diffraction intensity of a superlattice reflection that is directly related to the structural order parameter of the soft-mode driven antiferrodistortive phase in Ca:SrTiO_{3}, we observe an ultrafast relaxation on a 0.2 ps timescale of the rotation of the oxygen octahedron, which is found to be independent of the initial temperature despite large changes in the corresponding soft-mode frequency. A further, much smaller reduction on a slower picosecond timescale is attributed to thermal effects. Time-dependent density-functional-theory calculations show that the fast response can be ascribed to an ultrafast displacive modification of the soft-mode potential towards the normal state induced by holes created in the oxygen 2p states.

Experimental Study and Modeling of the UV-Vis and Infrared Spectra of the [VO(O2)Hheida]- Complex Dissolved in Water.

Combined theoretical and experimental studies of the [VO(O2)Hheida]- anion dissolved in water that may serve as a functional model for vanadium haloperoxidase enzymes have been performed. The geometrical structure and absorption and vibrational spectra of this system have been evaluated within the framework of density functional theory (DFT). The obtained theoretical results on the equilibrium structure and optical spectra are in quite good agreement with the experimental data. With the aid of the combination of UV-visible spectroscopy and electronic structure calculations, it has been revealed that, in the apparent absorption spectra of the [VO(O2)Hheida]- anion, the highest in energy band corresponds to a ligand to metal electron excitation, while the band with a maximum at 430 nm arises from the peroxo group. The calculations also reproduce quite well the positions, intensities and the grouping of frequencies in the near-infrared (NIR) spectra. The visualization of the calculated vibrations in the energy range of 400-1100 cm-1 has been presented.

Optimisation of a sol-gel synthesis route for the preparation of MgF2 particles for a large scale coating process.

A synthesis route for the preparation of optically transparent magnesium fluoride sols using magnesium acetate tetrahydrate as precursor is described. The obtained magnesium fluoride sols are stable for several months and can be applied for antireflective coatings on glass substrates. Reaction parameters in the course of sol synthesis are described in detail. Thus, properties of the precursor materials play a crucial role in the formation of the desired magnesium fluoride nanoparticles, this is drying the precursor has to be performed under defined mild conditions, re-solvation of the dried precursor has to be avoided and addition of water to the final sol-system has to be controlled strictly. Important properties of the magnesium fluoride sols like viscosity, particle size distribution, and structural information are presented as well.

A sphingosine kinase inhibitor combined with temozolomide induces glioblastoma cell death through accumulation of dihydrosphingosine and dihydroceramide, endoplasmic reticulum stress and autophagy.

Glioblastomas (GBMs) are very aggressive tumors with low chemosensitivity. The DNA-alkylating agent temozolomide (TMZ) is currently the most efficient chemotoxic drug for GBM therapy; however, many patients develop resistance to TMZ. Combining TMZ with another agent could present an improved treatment option if it could overcome TMZ resistance and avoid side effects. Sphingosine kinase inhibitors (SKIs) have emerged as anticancer agents. Sphingosine kinases are often overexpressed in tumors where their activity of phosphorylating sphingosine (Sph) contributes to tumor growth and migration. They control the levels of the pro-apoptotic ceramide (Cer) and Sph and of the pro-survival sphingosine-1 phosphate. In the present work, TMZ was combined with a specific SKI, and the cytotoxic effect of each drug alone or in combination was tested on GBM cell lines. The combination of sublethal doses of both agents resulted in the cell death potentiation of GBM cell lines without affecting astrocyte viability. It triggered a caspase-3-dependent cell death that was preceded by accumulation of dihydrosphingosine (dhSph) and dihydroceramide (dhCer), oxidative stress, endoplasmic reticulum stress, and autophagy. Autophagy was identified as the crucial switch that facilitated induction of this cell death potentiation. The sublethal dose of the inhibitor induced these stress events, whereas that of TMZ induced the destructive autophagy switch. Remarkably, neither Cer nor Sph, but rather the Cer intermediates, dhSph and dhCer, was involved in the cytotoxicity from the combination. Cell lines sensitive to the combination expressed low levels of the antioxidant enzyme glutathione peroxidase-1, indicating this enzyme as a potential marker of sensitivity to such treatment. This work shows for the first time a strong interaction between a SKI and TMZ, leading to a tumor cell-specific death induction. It further demonstrates the biological relevance of dihydrosphingolipids in cell death mechanisms and emphasizes the potential of drugs that affect sphingolipid metabolism for cancer therapy.

Changes in response properties of rostral ventromedial medulla neurons during prolonged inflammation: modulation by neurokinin-1 receptors.

Activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) can facilitate pain transmission in conditions such as inflammation, and thereby contribute to hyperalgesia. Since blockade of NK-1 receptors in the RVM can attenuate hyperalgesia produced by prolonged inflammation, we examined the role of NK-1 receptors in changes of response properties of RVM neurons following four days of hind paw inflammation with complete Freund's adjuvant. Recordings were made from functionally identified ON, OFF and NEUTRAL cells in the RVM. Spontaneous activity and responses evoked by a series of mechanical (10, 15, 26, 60, 100, and 180 g) and heat (34-50 °C) stimuli applied to the inflamed and non-inflamed hind paws were determined before and at 15 and 60 min after injection of the NK-1-antagonist L-733,060 or vehicle into the RVM. Prolonged inflammation did not alter the proportions of functionally-identified ON, OFF and NEUTRAL cells. ON cells exhibited enhanced responses to mechanical (60-100g) and heat (48-50 °C) stimuli applied to the inflamed paw, which were attenuated by L-733,060 but not by vehicle. Inhibitory responses of OFF cells evoked by mechanical stimuli applied to the inflamed paw were also inhibited by L-733,060, but responses evoked by stimulation of the contralateral paw were increased. Heat-evoked responses of OFF cells were not altered by L-733,060. Also, neither L-733,060 nor vehicle altered spontaneous ongoing discharge rate of RVM neurons. These data indicate that NK-1 receptors modulate excitability of ON cells which contribute to both mechanical and heat hyperalgesia, whereas NK-1 modulation of OFF cells contributes to mechanical hyperalgesia during prolonged inflammation.

TLR9 agonists induced cell death in Burkitt's lymphoma cells is variable and influenced by TLR9 polymorphism.

Toll-like receptor 9 (TLR9) triggering is a promising novel strategy to combat cancer as it induces innate and adaptive immunity responses. B-cell lymphoma is unique in this context as tumor cells express TLR9 and may harbor latent Epstein-Barr virus (EBV), a gamma-herpesvirus with remarkable oncogenic potential when latent. Latent EBV may be promoted by TLR9 triggering via suppression of lytic EBV. Here, we elaborated an initial assessment of the impact of TLR9 triggering on EBV-positive and EBV-negative B-cell lymphoma using Burkitt's lymphoma (BL) cell lines as an in vitro model. We show that, independent of the presence of EBV, the TLR9 ligand oligodeoxynucleotide (ODN) CpG-2006 may or may not induce caspase-dependent cell death in BL cells. Moreover, ODN CpG-2006-induced cell death responses of BL cells were associated with TLR9 single-nucleotide polymorphisms (SNPs) rs5743836 or rs352140, which we detected in primary BL tumors and in peripheral blood from healthy individuals at similar frequencies. Thus, our findings suggest that the effect of TLR9 agonists on BL cells should be tested in vitro before installment of therapy and TLR9 SNPs in BL patients should be determined as potential biological markers for the therapeutic response to treatment targeting innate immunity.

Introgression of genomic components from Chinese Brassica rapa contributes to widening the genetic diversity in rapeseed (B. napus L.), with emphasis on the evolution of Chinese rapeseed.

In spite of its short history of being an oil crop in China, the Chinese semi-winter rapeseed (Brassica napus L., 2n = 38, AACC) has been improved rapidly by intentional introgression of genomic components from Chinese B. rapa (2n = 20, AA). As a result, the Chinese semi-winter rapeseed has diversified genetically from the spring and winter rapeseed grown in the other regions such as Europe and North America. The objectives of this study were to investigate the roles of the introgression of the genomic components from the Chinese B. rapa in widening the genetic diversity of rapeseed and to verify the role of this introgression in the evolution of the Chinese rapeseed. Ten lines of the new type of rapeseed, which were produced by introgression of Chinese B. rapa to Chinese normal rapeseed, were compared for genetic diversity using amplified fragment length polymorphism (AFLP) with three groups of 35 lines of the normal rapeseed, including 9 semi-winter rapeseed lines from China, 9 winter rapeseed lines from Europe and 17 spring rapeseed lines from Northern Europe, Canada and Australia. Analysis of 799 polymorphic fragments revealed that within the groups, the new type rapeseed had the highest genetic diversity, followed by the semi-winter normal rapeseed from China. Spring and winter rapeseed had the lowest genetic diversity. Among the groups, the new type rapeseed group had the largest average genetic distance to the other three groups. Principal component analysis and cluster analysis, however, could not separate the new type rapeseed group from Chinese normal rapeseed group. Our data suggested that the introgression of Chinese B. rapa could significantly diversify the genetic basis of the rapeseed and play an important role in the evolution of Chinese rapeseed. The use of new genetic variation for the exploitation of heterosis in Brassica hybrid breeding is discussed.

Three-dimensional topographic angiography in chorioretinal vascular disease.

PURPOSE: To evaluate a new angiographic technique that offers three-dimensional imaging of chorioretinal vascular diseases. METHODS: Fluorescein (FA) and indocyanine green angiography (ICGA) were performed using a confocal scanning laser ophthalmoscope. Tomographic series with 32 images per set were taken over a depth of 4 mm at an image frequency of 20 Hz. An axial analysis was performed for each x/y position to determine the fluorescence distribution along the z-axis. The location of the onset of fluorescence at a defined threshold intensity was identified and a depth profile was generated. The overall results of fluorescence topography were displayed in a gray scale-coded image and three-dimensional relief. RESULTS: Topographic angiography delineated the choriocapillary surface covering the posterior pole with exposed larger retinal vessels. Superficial masking of fluorescence by hemorrhage or absorbing fluid did not preclude detection of underlying diseases. Choroidal neovascularization (CNV) appeared as a vascular formation with distinct configuration and prominence. Chorioretinal infiltrates exhibited perfusion defects with dye pooling. Retinal pigment epithelium detachments (PEDs) demonstrated dynamic filling mechanisms. Intraretinal extravasation in retinal vascular disease was detected within a well-demarcated area with prominent retinal thickening. CONCLUSIONS: Confocal topographic angiography allows high-resolution three-dimensional imaging of chorioretinal vascular and exudative diseases. Structural vascular changes (e.g., proliferation) are detected in respect to location and size. Dynamic processes (e.g., perfusion defects, extravasation, and barrier dysfunction) are clearly identified and may be quantified. Topographic angiography is a promising technique in the diagnosis, therapeutic evaluation, and pathophysiological evaluation of macular disease.

Confocal laser scanning fluorescence topography: a new method for three-dimensional functional imaging of vascular structures.

Three-dimensional topography of perfused vascular structures is possible via confocal laser scanning of intravascular fluorescence. The lateral resolution is given by the spot size of the scanning laser beam (optimally 10 microm at the retina). The axial resolution, however, depends on the accuracy of detection of the surface of the fluorescent structure, which is typically one order of magnitude higher (30 microm at the retina) than the confocal resolution. The vascular structure is stained with an appropriate fluorescent dye prior to the investigation using standard systemic dye injection. Confocal scanning of the fluorescence in planes of different depths within the vascular structure under investigation leads to a three-dimensional data set. Signal processing includes passive eye tracking, lateral averaging and axial determination of the surface of the fluorescent structure. The potential of this new technique is demonstrated by showing the topography of physiological vessel structures as well as of selected vascular diseases such as cone dystrophy, RPE detachment, choroidal haemangioma and retinal laser coagulation. Confocal laser angioscopic fluorescence topography (CLAFT) measures the three-dimensional surface structure of functional (perfused) vasculature and surrounding leakage. CLAFT may help to diagnose and quantify status and time course of vascular diseases.

The human gut bacteria Bacteroides thetaiotaomicron and Fusobacterium varium produce putrescine and spermidine in cecum of pectin-fed gnotobiotic rats.

Pectin is a soluble indigestible polysaccharide that stimulates cecal polyamine formation in rats. Bacteroides and fusobacteria, two numerically dominant bacterial population groups in the large intestine, were found to synthesize in vitro high amounts of spermidine and putrescine. The purpose of this study was to elucidate the effect of pectin on the polyamine production by defined bacterial species in vivo. Germfree male Wistar rats (n = 18) were randomly assigned to one of three treatments: (i) monoassociation with Bacteroides thetaiotaomicron + fiber-free diet; (ii) diassociation with B. thetaiotaomicron + Fusobacterium varium + fiber-free diet or (iii) diassociation with B. thetaiotaomicron + F. varium + fiber-free diet + 10% pectin. The cecal contents of monoassociated rats fed fiber-free diet contained large amounts (1.51+/-0.21 micromol/dry total cecum content) of spermidine which was the major polyamine. The cecum of diassociated rats fed the fiber-free diet contained even higher concentrations of spermidine (2.53+/-0.21 micromol/dry total cecum content) and also putrescine, which was now the dominant polyamine (putrescine 0.32+/-0.28 vs. 3.01+/-0.28 micromol/dry total cecum content; monoassociation vs. diassociation). Pectin consumption by diassociated rats led to an additional increase in the cecal concentrations of all polyamines: putrescine, spermidine and spermine were 40, 37 and 100%, respectively, higher in the diassociated rats consuming the pectin diet than in those consuming the pectin-free diet. Since the microbial counts in the cecum did not differ in the diassociated treatment groups, the elevated concentrations of polyamines observed in the pectin group must have been due to stimulated bacterial polyamine synthesis. The decline of individual polyamines from cecum to feces detected at the end of the study in all treatment groups and the high microbial counts in the cecum and in feces suggest that bacterial polyamines are absorbed in cecum and colon. Pectin stimulates intestinal microbes to synthesize large amounts of polyamines which may be utilized by the host.

[Confocal indocyanine green angiography with 3-dimensional topography. Results in choroid neovascularization (CNV)]. / Konfokale Indozyaningrün-Angiographie mit dreidimensionaler Topographie. Ergebnisse bei chorioidaler Neovaskularisation (CNV).

BACKGROUND: Confocal indocyanin green angiography (ICGA) offers detailed two-dimensional imaging of choroidal pathologies. However, the spatial extension of lesions is not reproduced. We developed a novel method for three-dimensional documentation of choroidal vascular abnormalities. METHODS: Focal series were performed using a laser scanning ophthalmoscope (Heidelberg Retina Angiograph). Thirty-two images within a distance of 4 mm were taken at a frequency of 20 Hz. Following correction of dislocation, a surface of normalized fluorescence intensity was determined and displayed topographically. RESULTS: In physiological eyes three-dimensional ICGA demonstrates the homogeneous concavity of the choroid with prominent overlay of retinal vessels. Classic choroidal neovascularization (CNV) imposes as substantial elevation. Occult CNV are demarcated despite negative conventional ICGA due to reduction of blocking phenomena. Therapeutic interventions such as photocoagulation, photodynamic therapy and surgery induce a resolution of CNV with or without residual defects within the choroidal pattern. CONCLUSION: Topographic ICGA allows for the first time in-vivo representation of prominence and depth of vascularized pathologies and provides a tool for improved diagnostic and therapeutic evaluation.

Dietary guar gum and pectin stimulate intestinal microbial polyamine synthesis in rats.

The effects of two highly fermentable dietary fibers (guar gum and pectin) on the type and concentrations of cecal polyamines as affected by the intestinal microflora were studied in groups of germ-free (n = 10/group) and conventional rats (n = 6/group). Both germ-free and conventional rats were randomly assigned to one of three treatments as follows: 1) fiber-free control diet, 2) control diet + 10% guar gum and 3) control diet + 10% pectin. In germ-free rats, guar gum and pectin had no effect on cecal polyamine concentrations. Putrescine was confirmed to be the major endogenous polyamine within the gut lumen. In cecal contents of conventional rats, both guar gum and pectin led to the appearance of cadaverine and to elevated putrescine concentrations in comparison with the fiber-free control diet (1.35 +/- 0.15 and 2.27 +/- 0.32, respectively, vs. 0.20 +/- 0.03 micromol/g dry weight, P < 0.05). The cecal cadaverine concentration was higher in pectin- than in guar-fed rats (8.20 +/- 0.89 vs. 1.92 +/- 0.27 micromol/g dry weight, P < 0.05). Counts of total bacteria, bacteroides, fusobacteria and enterobacteria were higher (P < 0.05) in rats fed guar gum and pectin. Bifidobacteria were found exclusively in guar-fed rats. In vitro studies on selected species representing the numerically dominant population groups of the human gut flora (bacteroides, fusobacteria, anaerobic cocci and bifidobacteria) were examined for their ability to synthesize intracellular polyamines. These experiments demonstrated the ability of bacteroides, fusobacteria and anaerobic cocci to synthesize high amounts of putrescine and spermidine. Calculations based on these results suggest that the intestinal microflora are a major source of polyamines in the contents of the large intestine.

Single-shot spatially resolved characterization of laser-induced shock waves in water.

We have developed an optical method for single-shot spatially resolved shock-wave peak-pressure measurements. A schlieren technique and streak photography were used to follow the propagation of the shock wave. The shock position r as a function of time was extracted from the streak images by digital image-processing techniques. The resulting r(t) curves were differentiated with respect to time to yield shock-wave velocities that were converted to shock pressures with the aid of the equation of the state of the medium. Features and limitations of the technique are demonstrated and discussed on the basis of measurements of shock-wave amplitudes generated by laser-induced breakdown in water. For this purpose, laser pulses of 6-ns duration and pulse energies of 1 and 10 mJ were focused into a cuvette containing water. Complete p(t) curves were obtained with a temporal resolution in the subnanosecond range. The total acquisition and processing time for a single event is ~2 min. The shock-peak pressures at the source were found to be 8.4 ? 1.5 and 11.8 ? 1.6 GPa for pulse energies of 1 and 10 mJ, respectively. Within the first two source radii, the shock-wave pressure p(r) was found to decay on average in proportion to r(-1.3?0.2) for both pulse energies. Thereafter the pressure dropped in proportion to r(-2.2?0.1). In water the method can be used to measure shock-wave amplitudes exceeding 0.1 GPa. Because it is a single-shot technique, the method is especially suited for investigating events with large statistical variations.

Feeding resistant starch affects fecal and cecal microflora and short-chain fatty acids in rats.

The effects of different forms of resistant potato starch (RS) on the major microbial population groups and short-chain fatty acids (SCFA) in the cecum and feces of rats were studied over a 5-mo feeding period. Thirty 8-wk-old male Wistar rats, averaging 210 g initial body weight, were adapted for 7 d to a balanced basal diet containing 60% waxy maize starch devoid of any RS. On d 8, three groups of 10 rats each were fed diets containing the following forms of starch: 1) rapidly digestible waxy maize starch (basal diet), 2) a mixture of 83.3% waxy maize starch and 16.7% native granular potato starch (RS 1), or 3) a mixture of 33.3% waxy maize starch and 66.7% modified potato starch (RS 2). The final RS content in RS 1 and RS 2 was 10%. Fecal samples were collected at d 8 and 1, 3, and 5 mo after the start of the experiment. Cecal contents were taken after 5 mo. The colony counts of microbial groups did not vary with time in the control or the RS 1 group (P > .05). Only the number of Bacteroides/fusobacteria decreased between mo 1 and 5 in rats fed RS 1 (P < .05). The RS 2 diet led to a significant increase in total culturable bacteria, lactobacilli, streptococci, and enterobacteria between mo 1 and 5. The RS 1 and RS 2 diets stimulated the growth of bifidobacteria. Cecal numbers of lactobacilli, streptococci, and enterobacteria were higher in rats fed RS 2 than in rats fed RS 1 or control diet (P < .05). Lactobacillus cellobiosus occurred only in rats fed RS 1 or RS 2. Acetate increased in mo 3 compared with d 8 in all groups (P < .05). The fecal and cecal SCFA displayed higher concentrations of acetate and propionate and a higher molar proportion of propionate in RS 2 than in RS 1 or control rats (P < .05). Stimulation of bifidobacteria, lactobacilli, and SCFA may be useful for the suppression of pathogenic organisms in the colon.

Shielding properties of laser-induced breakdown in water for pulse durations from 5 ns to 125 fs.

The shielding effectiveness of laser-induced breakdown from focused, visible laser pulses from 5 ns to 125 fs is determined from measurements of transmission of energy through the focal volume. The shielding efficiency decreases as a function of pulse duration from 5 ns to 300 fs and increases from 300 fs to 125 fs. The results are compared with past studies at similar pulse durations. The results of the measurements support laser-induced breakdown models and may lead to an optimization of laser-induced breakdown in ophthalmic surgery by reduction of collateral effects.

Influence of ablation plume dynamics on the formation of central islands in excimer laser photorefractive keratectomy.

PURPOSE: The aim of this study was to understand the dynamics of ablation products during excimer laser photorefractive keratectomy, and their influence on the formation of central islands. METHOD: Laser flash photography was used to investigate the dynamics of ablation products during photorefractive keratectomy. The ablation plume over polymethyl methacrylate (PMMA) and porcine cornea targets ablated with different zone diameters was imaged at various times between 10 musec and 100 msec after the ablating laser pulse. On PMMA targets, the profiles of the resulting ablation craters were measured. RESULTS: In all cases, the ablation products formed a ring vortex. The plume velocities on cornea were found to be approximately twice as fast as on PMMA for all zone diameters. For both materials, the ablation plume evolves faster for smaller zone diameters. Central islands were observed for zone diameters between 1 and 7 mm on PMMA substrates. The islands became more pronounced with increasing zone diameter. CONCLUSIONS: A major cause for the formation of central islands was found to be particle redeposition at the center of the ablation zone. Because of the vortex dynamics, redeposition of particles favorably occurs at the center of the ablation zone. Additionally, the dynamics of the ablation plume lead to a concentration of airborne particles over the center of the ablation zone, which also may contribute to the creation of central islands by partial absorption of the next excimer laser pulse.

Influence of two infant formulas and human milk on the development of the faecal flora in newborn infants.

The establishment of the faecal flora of 39 full-term infants fed exclusively on breast milk (n = 20) or with two different modern adapted cow's milk formulas (n = 19) was studied during the first 3 months of life. One formula investigated was based on 100% bovine casein as the protein source whereas the other formula contained bovine milk proteins with a whey/casein ratio of 60:40. A faecal flora rich in bifidobacteria was found in all study groups; the growth of putrefactive bacteria (especially Bacteroides spp.), however, was limited. In formula-fed infants, significantly higher bacterial counts of enterococci and clostridia were detected compared to breast milk-fed infants. Similarities and differences due to the feeding regimen were particularly reflected in the pattern of the anaerobic bacterial species. Bifidobacterium bifidum, B. infantis and B. breve constituted the majority of the bifidobacterial flora independent of the type of milk feeding. Other bifidobacterial species such as B. longum, B. adolescentis, B. parabifidum and B. pseudo-catenulatum were detected in high numbers and at low frequencies in breastfed infants. The latter three were observed in infants fed the whey/casein formula as well. It seems that infants fed a casein formula develop a faecal flora more like that of breastfed infants concerning Lactobacillus spp. (especially L. fermentum and L. brevis).

An algorithm for the fast registration of image sequences obtained with a scanning laser ophthalmoscope.

There is a need to quantify images of retinal pathology so that the natural progression and response to various forms of treatment such as laser therapy can be reliably monitored. The images obtained with a scanning laser ophthalmoscope are better than those from a traditional fundus camera, and the method of data collection leads naturally to digitization and quantitative techniques. However, during any angiographic sequence, there will inevitably be eye movement and it is essential that this be corrected for prior to the application of quantitative analysis. This article presents an algorithm (the smart localized binary correlation algorithm) for the automatic registration of fluorescein or indocyanine green angiograms which is based on localized correlation of binary templates in binary thresholded gradient images. The use of this algorithm decreases the calculation time up to 180 times when compared with the fastest applicable algorithm found in the literature. The algorithm only detects translational movement of the images but proves to be robust against rotational movement for the small angles (< 4 degrees) encountered in ophthalmic imaging. Registration accuracy is estimated to be +/- 2 pixels.