Interactions of the chemokines CXCL11 and CXCL12 in human tumor cells

BACKGROUND The chemokines, CXCL12 and CXCL11, are upregulated in tumors from many organs and control their progression. CXCL12 and CXCL11 affect tumor cell functions by either binding their prime receptors, CXCR4 and CXCR3, respectively, and/or CXCR7 as a common second chemokine receptor. In humans, CXCR3 exists in the functional splice variants, CXCR3A and CXCR3B, which either have pro- or anti-tumor activity, respectively. Despite the intimate crosstalk between the CXCL12- and CXCL11-system, the impact of a combination of CXCL12 and CXCL11 on tumor progression remains vague. METHODS In the present work, we have analyzed CXCL12 and CXCL11 for combined effects on migration, invasion, proliferation, and cytostatic-induced apoptosis of the human tumor cells, A549, A767, A772, DLD-1, and MDA-MB-231. RESULTS We demonstrate that the mode of interaction differs with respect to cell type and function and allows for either potentiation, attenuation or no changes of cellular responses. The divergent responses are not the result of the distinct use of different CXCL12- and CXCL11-receptors by the respective tumor cells, but in case of cell migration seem to be associated with the activation of p38 signaling pathways. CONCLUSIONS Our findings point to therapeutic limitations of ongoing efforts to selectively target CXCR3, CXCR4, or CXCR7 in cancer patients, and rather favor individualized targeting strategies

Synthesis and characterisation of alpha-carboxynitrobenzyl photocaged l-aspartates for applications in time-resolved structural biology

We report a new synthetic route to a series of α-carboxynitrobenzyl photocaged ⌊-aspartates for application in time-resolved structural biology. The resulting compounds were characterised in terms of UV/Vis absorption properties, aqueous solubility and stability, and photocleavage rates (τ = μs to ms) and quantum yields (φ = 0.05 to 0.14)

Spectral focusing of broadband silver electroluminescence in nanoscopic FRET-LEDs

Few inventions have shaped the world like the incandescent bulb. Edison used thermal radiation from ohmically heated conductors, but some noble metals also exhibit ‘cold’ electroluminescence in percolation films1,2, tunnel diodes3, electromigrated nanoparticle aggregates4,5, optical antennas6 or scanning tunnelling microscopy7,8,9. The origin of this radiation, which is spectrally broad and depends on applied bias, is controversial given the low radiative yields of electronic transitions. Nanoparticle electroluminescence is particularly intriguing because it involves localized surface-plasmon resonances with large dipole moments. Such plasmons enable very efficient non-radiative fluorescence resonance energy transfer (FRET) coupling to proximal resonant dipole transitions. Here, we demonstrate nanoscopic FRET–light-emitting diodes which exploit the opposite process, energy transfer from silver nanoparticles to exfoliated monolayers of transition-metal dichalcogenides10. In diffraction-limited hotspots showing pronounced photon bunching, broadband silver electroluminescence is focused into the narrow excitonic resonance of the atomically thin overlayer. Such devices may offer alternatives to conventional nano-light-emitting diodes11 in on-chip optical interconnects

Astrocytic expression of the chemokine receptor CXCR7/ACKR3 in the diseased CNS

Fulltext: Based on our previous demonstration of CXCR7 as the major mediator of CXCL12 signalling in cultured astrocytes, we have now characterized astrocytic CXCR7 expression in the diseased CNS and compared that to the expression of the second CXCL12 receptor, CXCR4. In the intact brain of adult rats CXCR7 and CXCR4 were expressed by GFAP-immunoreactive astrocytes forming the superficial glia limitans. Outside the glia limitans scattered and faint immunolabelling for CXCR7 and CXCR4 was present in very few additional GFAP-expressing astrocytes. In contrast to the restricted expression in the healthy CNS, a striking increase in CXCR7 expression was detectable in reactive astrocytes in rats with experimental brain infarcts (MCAO), in the spinal cord of rats with experimental autoimmune encephalomyelitis (EAE) as well as after mechanical compression. None of these pathologies was associated with substantial increases in astrocytic CXCR4 expression. Together, our findings favor the hypothesis of a crucial role of astrocytic CXCR7 in the progression of various CNS pathologies

Astrocytic expression of the chemokine receptor CXCR7/ACKR3 in the diseased CNS

Fulltext: Based on our previous demonstration of CXCR7 as the major mediator of CXCL12 signalling in cultured astrocytes, we have now characterized astrocytic CXCR7 expression in the diseased CNS and compared that to the expression of the second CXCL12 receptor, CXCR4. In the intact brain of adult rats CXCR7 and CXCR4 were expressed by GFAP-immunoreactive astrocytes forming the superficial glia limitans. Outside the glia limitans scattered and faint immunolabelling for CXCR7 and CXCR4 was present in very few additional GFAP-expressing astrocytes. In contrast to the restricted expression in the healthy CNS, a striking increase in CXCR7 expression was detectable in reactive astrocytes in rats with experimental brain infarcts (MCAO), in the spinal cord of rats with experimental autoimmune encephalomyelitis (EAE) as well as after mechanical compression. None of these pathologies was associated with substantial increases in astrocytic CXCR4 expression. Together, our findings favor the hypothesis of a crucial role of astrocytic CXCR7 in the progression of various CNS pathologies

Gadopentetate Dimeglumine Excretion into Human Breast Milk during Lactation

PURPOSE To analyze the amount of gadopentetate dimeglumine excreted into human breast milk following intravenous injection of a clinical dose. MATERIALS AND METHODS Gadopentetate dimeglumine was injected intravenously in 20 lactating women (23-38 years of age). Breast-feeding was interrupted for at least 24 hours. Serial samples of expressed milk were collected and analyzed for gadolinium concentration by means of inductively coupled plasma atomic emission spectrometry at a wavelength of 342.247 nm. RESULTS The cumulative amount of gadolinium excreted in human breast milk during 24 hours was 0.57 micromol +/- 0.71 (SD; range, 0.05-3.0 micromol). The excreted dose was thus less than 0.04% of the administered intravenous dose (range, 0.001%-0.04%; mean, 0.009% +/- 0.010) for all cases. CONCLUSION Less than 0.04% of administered gadopentetate dimeglumine is excreted into human breast milk. The amount transferred to a nursing infant orally would be far more than 100 times less than the permitted intravenous dose (200 micromol per kilogram of body weight) for neonates. The recommendation of a 24-hour suspension of breast-feeding for lactating women should thus be reconsidered

Gadopentetate dimeglumine excretion into human breast milk during lactation

PURPOSE To analyze the amount of gadopentetate dimeglumine excreted into human breast milk following intravenous injection of a clinical dose. MATERIALS AND METHODS Gadopentetate dimeglumine was injected intravenously in 20 lactating women (23-38 years of age). Breast-feeding was interrupted for at least 24 hours. Serial samples of expressed milk were collected and analyzed for gadolinium concentration by means of inductively coupled plasma atomic emission spectrometry at a wavelength of 342.247 nm. RESULTS The cumulative amount of gadolinium excreted in human breast milk during 24 hours was 0.57 micromol +/- 0.71 (SD; range, 0.05-3.0 micromol). The excreted dose was thus less than 0.04% of the administered intravenous dose (range, 0.001%-0.04%; mean, 0.009% +/- 0.010) for all cases. CONCLUSION Less than 0.04% of administered gadopentetate dimeglumine is excreted into human breast milk. The amount transferred to a nursing infant orally would be far more than 100 times less than the permitted intravenous dose (200 micromol per kilogram of body weight) for neonates. The recommendation of a 24-hour suspension of breast-feeding for lactating women should thus be reconsidered

Grundlagen fuer diodengepumpte Nd-dotierte Festkoerperlaser hoher Leistung. Teilvorhaben: Grundlagen fuer die Realisierung von Hochleistungslaserdioden im W- und Kilowattbereich als Lichtquelle fuer das Pumpen von Festkoerperlasern und die Materialbearbeitung Abschlussbericht

The temperature behaviour of semiconductor lasers has a distinct influence on their application to pumping solid state lasers and material processing. The goal was to carry out experimental and theoretical investigations with particular attention to the temperature dependence of the emission properties, in order to increase output power, efficiency, and lifetime of such devices. Potential use in vacuum deposited Pb-Sn solders have been tested for mounting high-power laser diodes and arrays. For the chip mounting, a special apparatus device has been developed. By means of the Finite-Element Method, numerical simulations of the temperature behaviour of GaAlAs/GaAs high-power laser diodes have been performed. From calculated two- and three-dimensional temperature distributions, design rules for the construction of high-power laser diodes could be derived. A model has been developed, which allows a unified description of output power and efficiency as functions of the internal loss processes. Using this model, quantum well laser structures have been examined with respect to their optimization. The facet temperature was measured by means of photoluminescence and micro-Raman spectroscopy. Under operating conditions, facet temperatures as high as 100 C have been measured for GaAlAs/GaAs lasers. The error was about #+-#4K. For one special structure, it was possible to measure the temperature distribution along the resonator by means of electroluminescence. (orig.)SIGLEAvailable from TIB Hannover: F95B2059+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Hochleistungsdiodenlaser und diodengepumpte Festkoerperlaser. Thema: Optische und thermische Eigenschaften von Hochleistungslaserdioden Abschlussbericht

Investigations of optical and thermal properties of high power laser diodes (HLDs) provided a lot of new results for achieving a better diode performance by using the knowledge of optimization of the semiconductor structure and the thermal architecture of diode laser. Theoretical modeling was done for obtaining better understanding of the interaction between thermal and optical processes in laser diodes in particular in the facet region. The calculated temperatures of the laser facets for certain operation parameters were in good agreement with the data obtained in micro-Raman facet temperature measurements. Further theoretical and experimental results were achieved on the catastrophical optical damage (COD) mechanism in the facet region. Finite Elemente Modeling (FEM) was used to investigate the influence of different structure and material parameters e.g. layer thickness, material composition, doping concentration, and parameters of the thermal architecture on the thermal behavior of the diodes. The transient temperature behavior of high power laser diodes was monitored for different mounting configurations. The diode behavior from ns pulses up to cw-operation was measured in detail. Nondestructive methods have been developed for both strain characterization and defect estimation. A new optical scanning technique based on photocurrent spectroscopy was developed successfully to find out local weakpoints upon aging. With the near-field scanning optical microscopy (NSOM) technique these processes were characterized in sub-#mu#m region. Fourier transform spectroscopy was used to obtain the rise of the defect concentration and the levels depths of the defect created upon aging. (orig.)SIGLEAvailable from TIB Hannover: F98B470+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman