Magnetism in iridate heterostructures leveraged by structural distortions.

Fundamental control of magnetic coupling through heterostructure morphology is a prerequisite for rational engineering of magnetic ground states. We report the tuning of magnetic interactions in superlattices composed of single and bilayers of SrIrO3 inter-spaced with SrTiO3 in analogy to the Ruddlesden-Popper series iridates. Magnetic scattering shows predominately c-axis antiferromagnetic orientation of the magnetic moments for the bilayer, as in Sr3Ir2O7. However, the magnetic excitation gap, measured by resonant inelastic x-ray scattering, is quite different between the two structures, evidencing a significant change in the stability of the competing magnetic phases. In contrast, the single layer iridate hosts a more bulk-like gap. We find these changes are driven by bending of the c-axis Ir-O-Ir bond, which is much weaker in the single layer, and subsequent local environment changes, evidenced through x-ray diffraction and magnetic excitation modeling. Our findings demonstrate how large changes in the magnetic interactions can be tailored and probed in spin-orbit coupled heterostructures by engineering subtle structural modulations.

Watt-level narrow-linewidth fibered laser source at 852 nm for FIB application.

We realize a 1 W all-fibered polarized compact and robust laser source at 852 nm for laser cooling of cesium atoms. The architecture is based on the sum-frequency generation of 1540 and 1908 nm lasers, realized through a periodically poled lithium niobate waveguide with a conversion efficiency of 40%. A linewidth of 20 kHz is achieved with the development of a distributed feedback fiber laser at 1908 nm. The operation of this laser source is demonstrated on a focused ion beam (FIB) experiment based on cold cesium atoms.

Watt-level green random laser at 532 nm by SHG of a Yb-doped fiber laser.

We have developed a watt-level random laser at 532 nm. The laser is based on a 1064 nm random distributed ytterbium (Yb) gain-assisted fiber laser seed with a 0.35 nm linewidth and 900 mW polarized output power. A study for the optimal length of the random distributed mirror was carried out. A Yb-doped fiber master oscillator power amplifier architecture is used to amplify the random seeder laser without additional spectral broadening up to 20 W. By using a periodically poled lithium niobate crystal in a single-pass configuration, we generate in excess of 1 W random laser at 532 nm by second-harmonic generation (SHG) with an efficiency of 9%. The green random laser exhibits an instability <1%, an optical signal-to-noise ratio >70 dB, a 0.1 nm linewidth, and excellent beam quality.

Watt-level single-frequency tunable neodymium MOPA fiber laser operating at 915-937 nm.

We have developed a Watt-level single-frequency tunable fiber laser in the 915-937 nm spectral window. The laser is based on a neodymium-doped fiber master oscillator power amplifier architecture, with two amplification stages using a 20 mW extended cavity diode laser as seed. The system output power is higher than 2 W from 921 to 933 nm, with a stability better than 1.4% and a low relative intensity noise.

Impact of x-ray dose on track formation and data analysis for CR-39-based proton diagnostics.

The nuclear track detector CR-39 is used extensively for charged particle diagnosis, in particular proton spectroscopy, at inertial confinement fusion facilities. These detectors can absorb x-ray doses from the experiments in the order of 1-100 Gy, the effects of which are not accounted for in the previous detector calibrations. X-ray dose absorbed in the CR-39 has previously been shown to affect the track size of alpha particles in the detector, primarily due to a measured reduction in the material bulk etch rate [Rojas-Herrera et al., Rev. Sci. Instrum. 86, 033501 (2015)]. Similar to the previous findings for alpha particles, protons with energies in the range 0.5-9.1 MeV are shown to produce tracks that are systematically smaller as a function of the absorbed x-ray dose in the CR-39. The reduction of track size due to x-ray dose is found to diminish with time between exposure and etching if the CR-39 is stored at ambient temperature, and complete recovery is observed after two weeks. The impact of this effect on the analysis of data from existing CR-39-based proton diagnostics on OMEGA and the National Ignition Facility is evaluated and best practices are proposed for cases in which the effect of x rays is significant.

High-energy femtosecond fiber laser at 976 nm.

We report on a passively mode-locked fiber laser emitting around 976nm. The self-starting mode locking is achieved in an unidirectional ring cavity by means of nonlinear polarization evolution. Stable single-pulse operation is observed for 480mW of average output power. This all-normal dispersion laser generates naturally chirped pulses with 1ps duration. The repetition rate is 40.6MHz, resulting in 12nJ pulse energy. External compression using bulk grating shortens the pulse duration down to 286fs.

Cyclobutane pyrimidine dimers are photosensitised by carprofen plus UVA in human HaCaT cells.

Every year in the UK about 75,000 cases of non-melanoma skin cancer (NMSC) are registered, and about 9500 people are diagnosed with cutaneous melanoma (CM). The main risk factor for these cancers is exposure to sunlight. The effects of light on skin are wavelength dependent, with wavelengths in the UVB waveband (280-315 nm) being the most carcinogenic. UVB is directly absorbed by DNA, producing dimeric pyrimidine photoproducts including cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimodone photoproducts (6-4PP). However UVA (315-400 nm) can also produce CPD, induce skin tumours in mice, and has been shown to be mutagenic in cell culture. Although the precise role of UVA in human skin cancer remains to be elucidated, it comprises the major portion of solar UV radiation, transmits through window glass and can be delivered in high doses from tanning lamps. Non-steroidal anti-inflammatory drugs (NSAIDs), in particular the 2-aryl propionic acid derivatives, are a well-documented group of photosensitising chemicals producing clinical phototoxic and photoallergic reactions. We have used carprofen, a model compound from this group to see if it could amplify the effects of UVA and contribute to the formation of CPD by UVA. Preliminary work has shown that carprofen combined with low doses of UVA (lambda(max): 365 nm; 5 J/cm(2)) can produce both strand breaks (SB) and CPD in human skin or blood cells. CPD were detected indirectly by both an immunofluorescence method and as T4 endonuclease V sensitive sites in the comet assay. These findings show that compounds other than fluoroquinolones and psoralen derivatives may contribute to CPD formation in skin cells in combination with UVA.

Experimental investigation of Brillouin and Raman scattering in a 2SG sulfide glass microstructured chalcogenide fiber.

In this work, we investigate the Brillouin and Raman scattering properties of a Ge15Sb20S65 chalcogenide glass microstructured single mode fiber around 1.55 microm. Through a fair comparison between a 2-m long chalcogenide fiber and a 7.9-km long classical single mode silica fiber, we have found a Brillouin and Raman gain coefficients 100 and 180 larger than fused silica, respectively.

Complete experimental characterization of stimulated Brillouin scattering in photonic crystal fiber.

We provide a complete experimental characterization of stimulated Brillouin scattering in a 160 m long solid-core photonic crystal fiber, including threshold and spectrum measurements as well as position-resolved mapping of the Brillouin frequency shift. In particular, a three-fold increase of the Brillouin threshold power is observed, in excellent agreement with the spectrally-broadened Brillouin gain spectrum. Distributed measurements additionally reveal that the rise of the Brillouin threshold results from the broadband nature of the gain spectrum all along the fiber and is strongly influenced by strain. Our experiments confirm that these unique fibers can be exploited for the passive control or the suppression of Brillouin scattering.

High power and high energy ultrashort pulse generation with a frequency shifted feedback fiber laser.

The highest average power that has been achieved with a frequency-shifted feedback modelocked fiber laser is reported. Subpicosecond pulses with 40 kW peak power are obtained by this technique for the first time by using external pulse compression. The pulsing is self starting and environmentally stable. The measured pulse energy in modelocked operation is 120 nJ. The pulses could be compressed to 855 fs. The pulse energy was increased to 1muJ with controlled Q-switched modelocking.

Can St John's wort (hypericin) ingestion enhance the erythemal response during high-dose ultraviolet A1 therapy?

BACKGROUND: St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high-dose UVA1 therapy. OBJECTIVES: To assess the phototoxicity risk of SJW ingestion. METHODS: Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high-output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70-77 mW cm(-2)) on the photoprotected lower back skin at eight 1.5-cm(2) test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 microg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter. RESULTS: The median MED and D(0.025), an objective measure of MED, were lower at all time-points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm(-2), range 10-56) than at baseline (median 20 J cm(-2), range 14-56) (P = 0.047). Similarly, the median D(0.025) at 8 h postirradiation was lower after SJW (median 22.0 J cm(-2), range 15.2-53.9) than at baseline (median 33.7 J cm(-2), range 22.9-136.0) (P = 0.014). The MED and D(0.025) were also significantly different at the 48-h and 4-h time-points, respectively. Significance was not reached at the 24-h time-point. Median intensity of postirradiation erythema increased at all time-points after ingestion of SJW. Despite these differences, the maximum slope of the dose-response curve was not increased after SJW ingestion. CONCLUSIONS: These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.

Photogenotoxicity of hypericin in HaCaT keratinocytes: implications for St. John's Wort supplements and high dose UVA-1 therapy.

Extract of St. John's Wort (Hypericum perforatum) is commonly used as natural remedy for treatment of mild to moderate depression. However, it contains a powerful photoactive component, hypericin, which can cause a severe photodermatitis when eaten by grazing animals (hypericism). In humans, there is evidence that supplementation with St. John's Wort can reduce the minimal erythemal dose (MED) in patients undergoing high dose UVA-1 phototherapy. This is a recent development in phototherapy where the most erythemogenic parts of the UVA spectrum are filtered out, allowing delivery of higher doses of the longer wavelengths of UVA. Although current published evidence suggests that the plasma levels of hypericin are unlikely to cause clinical phototoxicity, it has been established that photoactive compounds can cause DNA damage at sub-toxic and sub-erythemal doses, the effects of which might not be apparent for many years after the event. The present study used HaCaT keratinocytes to investigate the photoclastogenic ability of hypericin on irradiation with UVA. The results show that although the combination of hypericin and UVA light increased the genotoxic burden, when all factors are taken into account, the risk of significant photogenotoxic damage incurred by the combination of Hypericum extracts and UVA phototherapy may be low in the majority of individuals.

Can a positive photopatch test be elicited by subclinical irritancy or allergy plus suberythemal UV exposure?

Photopatch test (PhPT) interpretation is difficult and clinical relevance is not always apparent. A positive PhPT may reflect photocontact allergy or phototoxicity. We hypothesized that it may also reflect the additive or synergistic effects of a suberythemal reaction to a contact irritant [e.g. sodium lauryl sulfate (SLS)] or allergen (e.g. nickel) and suberythemal UV exposure. 10 nickel allergic volunteers had duplicate SLS and nickel series applied on either side of the back for 24 h and 48 h, respectively. After removal, one side was irradiated with 5 J/cm(2) UVA or the dose below the minimal erythema dose for solar-simulated radiation (SSR). The minimal irritancy dose (MID) for SLS and the minimal allergenic dose (MAD) for nickel were determined visually and objectively by erythema meter. While photoaugmentation of subclinical contact allergy or irritancy occurred in some subjects, photosuppression occurred in roughly an equal number. UVA changed the nickel MAD at 48 h in 2 of 5 volunteers but not the SLS MID. SSR changed the nickel MAD in 4 of 5 and the SLS MID in 3 of 5. 2 subjects (none after UVA) showed erythema only in the irradiated set of patches, which could have been interpreted as a positive PhPT. We have demonstrated photoaugmentation and photosuppression of contact allergy and irritancy, which could result in false-positive or false-negative interpretation of PhPTs.

The effect of photofrin on DNA strand breaks and base oxidation in HaCaT keratinocytes: a comet assay study.

Photodynamic therapy (PDT) kills cells via the production of singlet oxygen and other reactive oxygen species. PDT causes chromosomal damage and mutation to cultured cells. However, DNA damage does not contribute to the phototoxic effect. To study the effect of Photofrin-PDT-induced DNA damage, we used the comet assay in combination with endonuclease III and formamidopyrimidine DNA glycosylase and a human keratinocyte cell line to investigate photogenotoxicity and its prevention by tocopherol (TOC). This study shows that PDT induced DNA damage in HaCaT cells at doses allowing cells to survive 7 days after irradiation. alpha-TOC did not prevent the acute cell lysis caused by Photofrin-PDT but did prevent Photofrin-PDT-induced DNA damage. However, the concentration of TOC that conferred protection (100 microM) was higher than is detected in human serum. Base oxidation was also measured using the comet assay. Although TOC could prevent frank DNA strand breaks caused by PDT, it was unable to decrease the level of base oxidation as revealed by enzyme-sensitive sites. It is suggested that the potential genotoxic risk from laser-PDT could be low, and that topical micro-TOC at a high concentration may be useful in preventing some types of DNA damage without preventing acute photolysis after Photofrin-PDT.

Synergistic activation of p53-dependent transcription by two cooperating damage recognition pathways.

High level activation of p53-dependent transcription occurs following cellular exposure to genotoxic damaging agents such as UV-C, while ionizing radiation damage does not induce a similarly potent induction of p53-dependent gene expression. Reasoning that one of the major differences between UV-C and ionizing radiation damage is that the latter does not inhibit general transcription, we attempted to reconstitute p53-dependent gene expression in ionizing irradiated cells by co-treatment with selected transcription inhibitors that alone do not activate p53. p53-dependent transcription can be dramatically enhanced by the treatment of ionizing irradiated cells with low doses of DRB, which on its own does not induce p53 activity. The mechanism of ionizing radiation-dependent activation of p53-dependent transcription using DRB is more likely due to inhibition of gene transcription rather than prolonged DNA damage, as the non-genotoxic and general transcription inhibitor Roscovitine also synergistically activates p53 function in ionizing irradiated cells. These results identify two distinct signal transduction pathways that cooperate to fully activate p53-dependent gene expression: one responding to lesions induced by ionizing radiation and the second being a kinase pathway that regulates general RNA Polymerase II activity.

Comparison of an in vitro cellular phototoxicity model against controlled clinical trials of fluoroquinolone skin phototoxicity.

Many therapeutic drugs induce phototoxic skin responses following exposure to solar or artificial ultraviolet radiation sources. Several in vitro model systems have been developed to predict drug phototoxicity but none have been conducted in parallel with controlled clinical phototoxicity studies on systemically administered pharmaceuticals. The in vitro phototoxicity of eight fluoroquinolone (FQ) antibiotics (ciprofloxacin, grepafloxacin, lomefloxacin, norfloxacin, ofloxacin, trovafloxacin, BAYy3118, moxifloxacin) was determined by exposing Chinese hamster fibroblasts to UVA radiation. Cell damage was quantified with standard MTT or neutral red assays and an in vitro phototoxic index calculated (PI(vit)=% cell viability with UVA alone /% cell viability with UVA+FQ) for each endpoint. Clinical photosensitizing ability of the eight systemically administered FQ was investigated using double-blind, placebo and positive controlled, clinical skin phototesting of normal subjects. Minimal erythema doses at 365+/-30nm were determined before and after 6-7 days of FQ ingestion and PI(clin) (minimal erythema dose without FQ/minimal erythema dose with FQ) calculated. Linear regression analysis of PI(vit) vs PI(clin) gave correlations of up to 0.893. Principal components analysis of PI(vit), daily dose, plasma levels and photophysical (absorption) properties of the eight FQ showed that phototoxic (arbitrarily defined as PI(clin)> or =2) and non-phototoxic (PI(clin)<2) FQ could be completely discriminated using these parameters, and that the in vitro models were able to rank the relative phototoxic potential of the eight FQ.

The phototumorigenic fluoroquinolone, lomefloxacin, photosensitises p53 accumulation and transcriptional activity in human skin cells.

The fluoroquinolone antibiotic, lomefloxacin, is phototoxic in human skin exposed to UVA radiation, photosensitises DNA strand breaks and pyrimidine dimers in human keratinocytes in vitro, and is phototumorigenic in mouse skin. The p53 tumour suppressor protein is activated by a variety of cellular insults including UV radiation, to become a transcription factor for downstream markers such as the cyclin-kinase inhibitor p21CIP1/WAF1 or cause caspase transactivation which cleaves poly ADP ribose polymerase (PARP) as an early step in apoptosis. We have investigated these molecular defence responses in human skin cells treated with lomefloxacin and UVA radiation in vitro. Western blots revealed that lomefloxacin photosensitised the stabilisation of p53 protein in human fibroblasts. Lomefloxacin also photosensitised p53 transcriptional activity in amelanotic melanoma cells expressing wild-type p53 and stably transfected with a construct containing a beta-galactosidase reporter gene downstream from a p53 consensus binding sequence. Neither photosensitised production of H2O2 nor the resultant DNA strand breaks, appeared to be involved in this effect. Interestingly, p21CIP1/WAFI protein was upregulated by lomefloxacin in the dark by a p53-independent mechanism. Lomefloxacin also photosensitised the degradation of nuclear PARP, suggestive of caspase mediated, early apoptotic events.

The phototumorigenic fluoroquinolone lomefloxacin photosensitizes pyrimidine dimer formation in human keratinocytes in vitro.

The fluoroquinolone antibiotic lomefloxacin is phototoxic, photogenotoxic, photomutagenic and photosensitizes tumorigenesis in mouse skin. We have used T4 endonuclease V to demonstrate that lomefloxacin photosensitizes pyrimidine dimer formation in a human keratinocyte line (HaCaT). A possible mechanism for this effect would be triplet-triplet energy transfer. However, there is indirect evidence that the lomefloxacin triplet yield is very low, making this reaction less likely. The finding that lomefloxacin photosensitizes production of highly mutagenic pyrimidine dimers correlates with its ability to initiate skin tumor formation in mice. Until the potential of other fluoroquinolones to photosensitize dimer formation is explored it may be unadvisable to prescribe these antibiotics to patients with defective DNA repair capacity (e.g. xeroderma pigmentosum).

Environmentally stable picosecond ytterbium fiber laser with a broad tuning range.

We demonstrate a widely tunable passively mode-locked fiber laser operating at a fundamental frequency of 80 MHz with an output power of 90 mW. The laser is capable of generating 5-ps pulses in the region 1010-1064 nm. A strong mode-locking mechanism promoted by frequency-shifted feedback allows us to operate in simultaneous Q-switched and mode-locked regimes and to obtain peak power in excess of 1.2 kW.