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At SRON, we have been developing X-ray TES micro-calorimeters as backup technology for the X-ray Integral Field Unit (X-IFU) of the Athena mission, demonstrating excellent resolving powers both under DC and AC bias. We also developed a frequency-domain multiplexing (FDM) readout technology, where each TES is coupled to a superconducting band-pass LC resonator and AC biased at MHz frequencies through a common readout line. The TES signals are summed at the input of a superconducting quantum interference device (SQUID), which performs a first amplification at cryogenic stage. Custom analog front-end electronics and digital boards take care of further amplifying the signals at room temperature and of the modulation/demodulation of the TES signals and bias carrier, respectively. We report on the most recent developments on our FDM technology, which involves a two-channel demonstration with a total of 70 pixels with a summed energy resolution of 2.34 ± 0.02 eV at 5.9 keV without spectral performance degradation with respect to single-channel operation. Moreover, we discuss prospects towards the scaling-up to a larger multiplexing factor up to 78 pixels per channel in a 1–6 MHz readout bandwidth. [ABSTRACT FROM AUTHOR]

With applications in cosmology, infrared astronomy and CMB survey, frequency-division multiplexing (FDM) proved to be a viable readout for transition-edge sensors (TESs). We investigate the occurrence of out-of-band resonances (OBR) which could constrain the bandwidth of the FDM readout of TES bolometers. The study includes SPICE modeling of the entire setup including the cryogenic harness, LC filters, Superconducting Quantum Interference Device (SQUID) and room-temperature amplifier. Simulation results show that the long harness (for flight model) could cause multiple reflections that generate repetitive spikes in the spectrum. Peaks of the OBR are mainly due to the parasitic capacitances at the input of SQUID. Implementing a low-pass RC circuit (snubber) at the input of the SQUID dampened the OBR. As a result, the first peak only appears around 20 MHz which is a safe margin for the 1 MHz - 3.8 MHz FDM in use in the prototype readout. Using a spectrum analyzer and broadband LNAs, we also measured the OBR for the prototype FDM readout in the laboratory up to 500 MHz. The measurement was conducted at temperatures of 50 mK and 4 K and for various biasing of the DC SQUID. It turns out that OBRs are more intense at 50 mK and are caused by the harness impedance mismatch rather than the SQUID. Simulation codes and supporting materials are available at https://github.com/githubamin/LT-Spice-Simulation-of-FDM-readout. [ABSTRACT FROM AUTHOR]

We present a characterization of the sensitivity of TES X-ray micro-calorimeters to environmental conditions under frequency-domain multiplexing (FDM) readout. In the FDM scheme, each TES in a readout chain is in series with a LC band-pass filter and AC biased with an independent carrier at MHz range. Using TES arrays, cold readout circuitry and warm electronics fabricated at SRON and SQUIDs produced at VTT Finland, we characterize the sensitivity of the detectors to bias voltage, bath temperature and magnetic field. We compare our results with the requirements for the Athena X-IFU instrument, showing the compliance of the measured sensitivities. We find in particular that FDM is intrinsically insensitive to the magnetic field because of TES design and AC readout. [ABSTRACT FROM AUTHOR]

We report measured T c of superconducting Ti/Au bilayer strips with a width W varying from 5 to 50 µm. The strips were fabricated based on a Ti/Au bilayer that consists of a 41-nm-thick Ti layer to which a 280-nm-thick Au layer was added. We find that the T c drops as W decreases and the declining trend almost perfectly follows T c / [ mK ] = - 738.4 [ μ m ] 2 / W 2 + 91.0 , where T c (W = ∞) of 91 mK is consistent with the intrinsic T c of the bilayer. The result is interpreted as a consequence of the lateral inverse proximity effect originated in normal-metal microstructures, namely Au overhangs that exist at the edges of the Ti/Au bilayer. The T c shift from the intrinsic T c should be anticipated in addition to the longitudinal proximity effect from superconducting Nb leads when one designs Ti/Au TESs. [ABSTRACT FROM AUTHOR]

The X-IFU is the cryogenic spectrometer onboard the future ATHENA X-ray observatory. It is based on a large array of TES microcalorimeters, which work in combination with a Cryogenic AntiCoincidence detector (CryoAC). This is necessary to reduce the particle background level thus enabling part of the mission science goals. Here we present the first joint test of X-IFU TES array and CryoAC Demonstration Models, performed in a FDM setup. We show that it is possible to operate properly both detectors, and we provide a preliminary demonstration of the anti-coincidence capability of the system achieved by the simultaneous detection of cosmic muons. [ABSTRACT FROM AUTHOR]

Large arrays of transition edge sensors (TESs) are the baseline for a number of future space observatories. For instance, the X-ray integral field unit (X-IFU) instrument on board the ATHENA space telescope will consist of ∼ 3000 TESs with high energy resolution ( 2 eV at X-ray energies up to 7 keV). In this contribution we report on the development of an X-ray TES array as a backup detector technology for X-IFU. The baseline readout technology for this mission is time domain multiplexing where the detectors are DC biased. Specifically, we report on the characterization of four different Ti/Au TESs with the following dimensions ( L × W ): 30 × 15 , 30 × 30 , 50 × 25 and 50 × 50 μ m 2 , all of which are coupled to a 2.3 μ m thick Au absorber of area 240 × 240 μ m 2 . We have performed our characterization using our standard frequency domain multiplexing readout connecting only pixels at low frequencies, where nonlinear effects due to the AC biasing are negligible. Promising energy resolution has been obtained, for instance 1.78 ± 0.10 eV and 1.75 ± 0.10 eV at 5.9 keV for the 50 × 25 and 50 × 50 μ m 2 detectors respectively. Uniformity over a kilo-pixel array (of detectors with the same geometry) has been also studied, confirming the high quality of our fabrication process. [ABSTRACT FROM AUTHOR]

Frequency-domain multiplexing (FDM) is the baseline readout system for the X-ray Integral Field Unit on board the Athena mission. Under the FDM scheme, TESs are coupled to a passive LC filter and biased with alternating current (AC bias) at MHz frequencies. Using high-quality-factor LC filters and room-temperature electronics developed at SRON and low-noise two-stage SQUID amplifiers provided by VTT, we have recently demonstrated good performance with the FDM readout of Mo/Au TES calorimeters with Au/Bi absorbers. We have achieved a performance requested for the demonstration model with the single-pixel AC bias ( Δ E = 1.8 eV ) and nine-pixel multiplexing ( Δ E = 2.6 eV ) modes. We have also demonstrated 14-pixel multiplexing with an average energy resolution of 3.3 eV, which is limited by nonfundamental issues related to FDM readout in our laboratory setup. [ABSTRACT FROM AUTHOR]

Superconducting transition-edge sensors (TESs) are highly sensitive detectors. Based on the outstanding performance on spectral resolution, the X-ray integral field unit (X-IFU) instrument on-board athena will be equipped with a large array of TES-based microcalorimeters. For optimal performance in terms of the energy resolution, it is essential to limit undesirable nonlinearity effects in the TES detector. Weak-link behavior induced on the TES by superconducting leads is such a nonlinearity effect. We designed and fabricated smart test structures to study the effect of the superconducting leads on the intrinsic transition curve of our TiAu-based TES bilayer. We measured and analyzed the resistance versus temperature transition curves of the test structures. We found relations of long-distance proximity effects with TES length and different lead materials. Based on these results, we can redesign and further optimize our TES-based X-ray detectors. [ABSTRACT FROM AUTHOR]

We are developing a transition edge sensor (TES) microcalorimeter array based on a Ti/Au superconducting bilayer, as a backup option for the X-IFU instrument on the Athena X-ray observatory. The array is read out by a frequency-division multiplexing readout system using a 1–5 MHz frequency band. Extensive research collaborations between NASA/Goddard and SRON have led to new design rules for microcalorimeters such as low resistivity of the superconductor bilayer, moderately high ohmic resistance of the TES by changing the aspect ratio and no extra metal strips. We have improved our detector fabrication process according to these design principles and produced TES arrays. Although single-pixel characterizations of these arrays are ongoing, the best energy resolution of 2.0 eV for 5.9 keV X-ray has been observed with a 120 × 20 μm2 TES with a normal resistance of 150 mΩ, biased at 2.2 MHz frequency. This shows that our Ti/Au TES array has a potential to fulfill the detector requirements of the X-IFU instrument. [ABSTRACT FROM AUTHOR]

We are developing X-ray microcalorimeters as a backup option for the baseline detectors in the X-IFU instrument on board the ATHENA space mission led by ESA and to be launched in the early 2030s. 5 × 5 mixed arrays with TiAu transition-edge sensor (TES), which have different high aspect ratios and thus high resistances, have been designed and fabricated to meet the energy resolution requirement of the X-IFU instrument. Such arrays can also be used to optimize the performance of the frequency domain multiplexing (FDM) readout and lead to the final steps for the fabrication of a large detector array. In this work, we present the experimental results from tens of the devices with an aspect ratio (length-to-width) ranging from 1-to-1 up to 6-to-1, measured in a single-pixel mode with a FDM readout system developed at SRON/VTT. We observed a nominal energy resolution of about 2.5 eV at 5.9 keV at bias frequencies ranging from 1 to 5 MHz. These detectors are proving to be the best TES microcalorimeters ever reported in Europe, intending to meet the requirements of the X-IFU instrument, but also those of other future challenging X-ray space missions, fundamental physics experiments, plasma characterization and material analysis. [ABSTRACT FROM AUTHOR]

We are developing the frequency division multiplexing (FDM) read-out for the superconducting transition-edge sensors arrays of the X-IFU instrument on board of Athena and of the SAFARI instrument on board of SPICA. An essential component of the FDM is the array of narrow band superconducting resonators, each consisting of lithographically made inductors and capacitors. In the standard FDM configuration, the LC resonators are connected in series with the input coil of a low noise two-stage SQUID amplifier. In this work, we have modified the electrical scheme to weakly couple the SQUID amplifier from the LC filters in order to measure their intrinsic properties. We report on the intrinsic losses and on the noise of high-Q superconducting LC resonators, with resonant frequencies ranging between 1 and 5 MHz, measured at temperatures from 70 to 500 mK. The LC resonators show very low losses with values smaller than 0.5 m Ω at equilibrium temperatures below 100 mK. We demonstrate that the LC resonators noise is thermal between 500 and 70 mK. [ABSTRACT FROM AUTHOR]

Efficient use of the available frequency space for frequency domain multiplexing is essential for space-based TES detector applications such as the X-IFU instrument on the Athena X-ray telescope. For cross talk reasons, there exists a lower limit on the distance between neighbouring pixels in frequency space, so that accurate control of the resonance frequency helps to use the available frequency space. Independently, from the point of view of efficient sinusoidal bias voltage generation, placing the frequencies on a grid with a fixed spacing helps to avoid the effects of nonlinearity on the detector performance. Inevitable tolerances in the lithographic production of LC bandpass filters and margins in the design of stray inductances limit the relative accuracy of the resonance frequencies to a few times 10-3. In this paper we will propose a new method which uses the active SQUID readout electronics at room temperature to further fine-tune the resonance frequencies of the LC filters beyond the manufacturing limitations. [ABSTRACT FROM AUTHOR]

Frequency-division multiplexing is the baseline read-out system for large arrays of superconducting transition-edge sensors (TES’s) under development for the X-ray and infrared instruments like X-IFU (Athena) and SAFARI, respectively. In this multiplexing scheme, the sensors are ac-biased at different frequencies from 1 to 5 MHz and operate as amplitude modulators. Weak superconductivity is responsible for the complex TES resistive transition, experimentally explored in great detail so far, both with dc- and ac-biased read-out schemes. In this paper, we will review the current status of our understanding of the physics of the TES’s and their interaction with the ac bias circuit. In particular, we will compare the behaviour of the TES nonlinear impedance, across the superconducting transition, for several detector families, namely: high-normal-resistance TiAu TES bolometers, low-normal-resistance MoAu TES microcalorimeters and high-normal-resistance TiAu TES microcalorimeters. [ABSTRACT FROM AUTHOR]

We are developing kilo-pixel arrays of transition-edge sensors (TESs) for the X-ray Integral Field Unit on ESA’s Athena observatory. Previous measurements of AC-biased Mo/Au TESs have highlighted a frequency-dependent loss mechanism that results in broader transitions and worse spectral performance compared to the same devices measured under DC bias. In order to better understand the nature of this loss, we are now studying TES pixels in different geometric configurations. We present measurements on devices of different sizes and with different metal features used for noise mitigation and X-ray absorption. Our results show how the loss mechanism is strongly dependent upon the amount of metal in close proximity to the sensor and can be attributed to induced eddy current coupling to these features. We present a finite element model that successfully reproduces the magnitude and geometry dependence of the losses. Using this model, we present mitigation strategies that should reduce the losses to an acceptable level. [ABSTRACT FROM AUTHOR]

The impact of various crosstalk mechanisms on the performance of the Athena X-IFU instrument has been assessed with detailed end-to-end simulations. For the crosstalk in the electrical circuit, a detailed model has been developed. In this contribution, we test this model against measurements made with an FDM laboratory setup and discuss the assumption of deterministic crosstalk in the context of the weak link effect in the detectors. We conclude that crosstalk levels predicted by the model are conservative with respect to the observed levels. [ABSTRACT FROM AUTHOR]

Athena is a European X-ray observatory, scheduled for launch in $$\sim $$ 2028. Athena will employ a high-resolution imaging spectrometer called X-ray integral field unit (X-IFU), consisting of an array of $$\sim $$ 4000 transition edge sensor (TES) microcalorimeter pixels. For the readout of X-IFU, we are developing frequency domain multiplexing, which is the baseline readout system. In this paper, we report on the performance of a TES X-ray calorimeter array fabricated at Goddard Space Flight Center (GSFC) at MHz frequencies for the baseline of X-IFU detector. During single-pixel AC bias characterization, we measured X-ray energy resolutions (at 6 keV) of about 2.9 eV at both 2.3 and 3.7 MHz. Furthermore, in the multiplexing mode, we measured X-ray energy resolutions of about 2.9 eV at 1.3 and 1.7 MHz. [ABSTRACT FROM AUTHOR]

SRON is developing ultra-low-noise transition edge sensors (TESs) based on a superconducting Ti/Au bilayer on a suspended SiN island with SiN legs for SAFARI aboard SPICA. We have two major concerns about realizing TESs with an ultra-low NEP of $$2\times 10^{-19}~\hbox {W}/\sqrt{{\text {Hz}}}$$ : achieving lower thermal conductance and no excess noise with respect to the phonon noise. To realize TESs with phonon-noise-limited NEPs, we need to make thinner ( $${<}0.25~\upmu \hbox {m}$$ ) and narrower ( $${<}1~\upmu \hbox {m}$$ ) SiN legs. With deep reactive-ion etching, three types of TESs were fabricated in combination with different SiN island sizes and the presence or absence of an optical absorber. Those TESs have a thin $$(0.20~\upmu \hbox {m}$$ ), narrow (0.5-0.7 $$\upmu \hbox {m}$$ ), and long (340-460 $$\upmu \hbox {m}$$ ) SiN legs and show $$T_{\mathrm {c}}$$ of $${\sim }93~\hbox {mK}$$ and $$R_{\mathrm {n}}$$ of $${\sim }158~\hbox {m}{\Omega }$$ . These TESs were characterized under AC bias using our frequency-division multiplexing readout (1-3 MHz) system. TESs without the absorber show NEPs as low as $$1.1\,\times \,10^{-19}~\hbox {W}/\sqrt{{\text {Hz}}}$$ with a reasonable response speed ( $${<}1~\hbox {ms}$$ ), which achieved the phonon noise limit. For TESs with the absorber, we confirmed a higher $$\hbox {NEP}_{\mathrm {el}} ({\sim }5\,\times \,10^{-19}~\hbox {W}/\sqrt{{\text {Hz}}}$$ ) than that of TESs without the absorber likely due to stray light. The lowest NEP can make the new version of SAFARI with a grating spectrometer feasible. [ABSTRACT FROM AUTHOR]

It has been recently demonstrated that superconducting transition edge-sensors behave as weak-links due to longitudinally induced superconductivity from the leads with higher $$T_c$$ . In this work we study the implication of this behaviour for transition-edge sensors (TES)-based bolometers and microcalorimeter under ac bias. The TESs are read-out at frequencies between 1 and $$5 \,\mathrm {MHz}$$ by a frequency domain multiplexer based on a linearised two-stage SQUID amplifier and high- $$Q$$ lithographically made superconducting $$LC$$ resonators. In particular, we focus on SRON TiAu TES bolometers with a measured dark noise equivalent power of $$3.2\times 10^{-19}\,{\mathrm{W}/\sqrt{\mathrm{Hz}}}$$ developed for the short wavelength band for the instrument SAFARI on the SPICA telescope. [ABSTRACT FROM AUTHOR]

At SRON we are developing Frequency Domain Multiplexing for the read-out of superconducting transition edge sensor microcalorimeters for future X-ray astrophysical missions. We will report on the performance of Goddard Space Flight Center pixels under AC bias in the MHz frequency range. Superconducting flux transformers are used to improve the impedance matching between the low ohmic TESs and the SQUID. We connected 5 pixels to the LC filters with resonant frequencies ranging between 1 and 5 MHz. For X-ray photons of 6 keV we measured a best X-ray energy resolution of 3.6 eV at 1.4 MHz, consistent with the integrated Noise Equivalent Power. In addition, we improved the electrical circuit by optimizing the coupling ratio of the impedance matching transformer. In addition, we improved electrical circuit for impedance matching; modified transformer coupling ratio. As a result, we got the integrated noise equivalent power resolution of 2.7 eV at 2.5 MHz. A characterization of the detector response as a function of the AC bias voltage, bias frequency and the applied magnetic field is presented. [ABSTRACT FROM AUTHOR]

We have fabricated multilayer readout wiring transition edge sensors (TES), which enable us to realize both large effective area and high-energy resolution for future X-ray astrophysical missions, such as diffuse intergalactic oxygen surveyor. By sandwiching a SiO $$_2$$ insulation layer between Al superconducting signal and return lines, self/mutual inductances and self fielding of bias leads are expected to be reduced. We fabricated $$4\times 4$$ and $$20\times 20$$ TES array on the multilayer wiring and tested their performance. Under the low temperature condition, several pixels in the TES array showed sharp superconducting transitions at around $$\sim $$ 300 mK. We also succeeded in detecting X-ray signals from the $$4\times 4$$ TES, contrary to the previous results of $$20\times 20$$ TES. We further investigated the reasons for the differences between the $$4\times 4$$ TES and the $$20\times 20$$ TES, and present future plans for improving the multilayer TES array fabrication. [ABSTRACT FROM AUTHOR]

Operation of TES-based bolometers in a resistance locked loop (RLL), i.e. keeping the operating resistance constant by means of feedback on the bias voltage, provides a number of attractive properties for applications. In combination with frequency domain multiplexing, the technique reduces electrical cross talk, and provides a more detector load independent behaviour with respect to operation under standard voltage bias. This paper shows a quantitative estimation of the large signal properties under the RLL, and shows a comparison with the situation under voltage bias. Furthermore, an unorthodox, low-bandwidth mode of operation will be discussed, from the perspective of the electro-thermal stability in the RLL. [ABSTRACT FROM AUTHOR]

We have developed Ti/Au bilayer transition-edge sensor (TES) microcalorimeters for future X-ray astrophysical satellite missions such as DIOS. One possible concern on the space use of TES microcalorimeters is its radiation tolerance. We have evaluated the performance of a Ti/Au bilayer (30/40 nm thick) TES microcalorimeter with 1.5 $$\upmu $$ m thick Au absorber, before and after irradiation of 150 MeV proton beam with a total dose of 10 krad, corresponding to 10 years in the low Earth orbit. No significant changes on transition temperature, sensitivity, normal resistance, and critical current were observed. The energy resolution for 5.9 keV X-rays was 5.6 $$\pm $$ 0.3 eV (FWHM) after the irradiation, which was slightly worse than 5.1 $$\pm $$ 0.3 eV before the irradiation. We consider that our TES has sufficient radiation tolerance in orbit. [ABSTRACT FROM AUTHOR]

We designed and fabricated an active gas-gap heat switch (AGGHS), which ON/OFF the heat conduction between the 1st stage (0.05-2 K) and the 2nd stage (1-4 K) of a double-stage adiabatic demagnetization refrigerator (DADR). Our design geometrically separates two components which dominates the ON or OFF performance, and achieved heat conductivity of 6 mW/K (ON) or 4 μW/K (OFF) at 2 K. The ON/OFF is controlled by a heater attached to the charcoal box to adsorb/deadsorb He gas inside. We introduced the AGGHS to the DADR and successfully cooled the detector stage down to 60 mK, working properly more than a year. [ABSTRACT FROM AUTHOR]

Significant fraction of the cosmic diffuse soft X-ray emission (0.1-1 keV) is caused by the Solar Wind Charge eXchange (SWCX) process between the solar wind ion (C, N, O etc.) and the interplanetary neutral matter. It is difficult to identify spectral features of SWCX with the spectral resolution of existing X-ray astronomy satellites. We are developing a laboratory experimental system with transition edge sensor (TES) X-ray microcalorimeters, in order to clarify the SWCX mechanism. This experiment is designed to measure Charge eXchange (CX) X-rays using Electron Cyclotron Resonance Ion Source (ECRIS) that generates multi-charged ions. Emission lines (O: 2p→1s; 654 eV) by CX between O and neutral He atom is aimed to be measured with energy resolution better than 10 eV. The TES microcalorimeter is cooled by a double-stage adiabatic demagnetization refrigerator (DADR), however, our TES microcalorimeter are not working potentially due to magnetic field contamination. This paper reports our experimental system, present results, and future prospects. [ABSTRACT FROM AUTHOR]

The tyrosine kinase c-Src is upregulated in various human cancers; however, the molecular mechanisms underlying c-Src-mediated tumor progression remain unclear. Here we show that downregulation of microRNA (miR)-542-3p is tightly associated with tumor progression via c-Src-related oncogenic pathways. In c-Src-transformed fibroblasts and human cancer cells that overexpress c-Src, miR-542-3p is substantially downregulated, and the ectopic expression of miR-542-3p suppresses tumor growth. We identified the integrin-linked kinase (ILK) as a conserved target of miR-542-3p. ILK upregulation promotes cell adhesion and invasion by activating the integrin-focal adhesion kinase (FAK)/c-Src pathway, and can also contribute to tumor growth via the AKT and glycogen synthase kinase 3β pathways. MiR-542-3p expression is downregulated by the activation of c-Src-related signaling molecules, including epidermal growth factor receptor, K-Ras and Ras/Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase. In human colon cancer tissues, downregulation of miR-542-3p is significantly correlated with the upregulation of c-Src and ILK. Our results suggest that the novel c-Src-miR-542-3p-ILK-FAK circuit plays a crucial role in controlling tumor progression. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose ((18)F-FDG) has been studied in thymic epithelial tumors. We evaluated the usefulness of (18)F-FDG PET for monitoring after treatment in unresectable thymic epithelial tumors. Method: Twelve patients with unresectable/metastatic thymic epithelial tumors underwent PET study with (18)F-FDG before and after chemotherapy or radiotherapy. Response and survival were analyzed according to the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of the mediastinum (T/M ratio). Results: Partial response (PR) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) was noted in 4 (33%) of 12 patients, and partial metabolic response (PMR) was observed in 6 (50%) of 12 patients. PR was observed in 4 of 6 patients with PMR. In 6 patients with any response, the T/M ratio at post-treatment was significantly lower than at baseline (p = 0.0017). In 6 patients with stable disease (SD), stable metabolic disease (SMD) was observed in 5 by use of (18)F-FDG PET. No statistically significant difference of (18)F-FDG uptake between at baseline and post-therapy was observed in 6 patients with SD (p = 0.4157) and SMD (p = 0.8419). Although the overall survival after treatment showed no statistically significant difference between PMR and SMD or progressive metabolic disease in the whole group of patients including thymoma, a statistically significant difference in the overall survival was observed between 5 patients with PMR and 5 patients with non-PMR (p = 0.0280). Conclusion: Our preliminary study suggests that (18)F-FDG PET is useful for monitoring response and outcome after treatment in unresectable thymic epithelial tumors. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) metastasis from non-small-cell lung cancer (NSCLC) is relatively rare. As most patients with GI metastasis are diagnosed on the occasion of serious complications, such as ileus or perforation, the appropriate diagnosis is important. Here, we report a case of NSCLC metastatic to the small intestine diagnosed at initial staging using ¹⁸F-fluorodeoxyglucose positron emission tomography. [ABSTRACT FROM AUTHOR]

Lipid peroxide levels, the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px), and the development of tanning in the skin of C57 BL/6 mice were assessed for long periods, from very early to late stages, after acute or chronic UVB irradiation. Acute UVB irradiation produced an increase in lipid peroxide levels that peaked 18 h after irradiation, after which the levels declined to a minimum 2-3 days after irradiation and then gradually rose to baseline. Chronic irradiation caused the lipid peroxide level to fall to a minimum at 0.5-1.0 weeks, after which it gradually returned to baseline by the third week. SOD and GSH-Px activities decreased sharply after acute irradiation, reaching a minimum 18 h after irradiation. Following chronic irradiation, these enzyme levels peaked after 0.5 weeks, and thereafter declined gradually to the original levels 3 weeks after irradiation. In contrast, catalase activity did not change significantly. Tanning began to increase at 1.5 weeks after irradiation, with an accelerated rate of increase from the third week. Although UVB has been reported only to decrease or impair reactive oxygen species (ROS) scavenging enzyme activity, we postulate the following from our results: (1) the increase in lipid peroxide levels observed after irradiation was due to UVB-induced ROS; (2) the parallel decrease in enzyme activities may have been due to inactivation by ROS; (3) the decrease in lipid peroxide levels following the peak at 18-h resulted from the scavenging effect of increasing SOD and GSH-Px activities, and (4) the increase in these two enzyme activities was the result of their induction by the increased lipid peroxides or ROS. In addition, these results seem to suggest a possible correlation of melanogenesis with UVB-induced ROS. [ABSTRACT FROM AUTHOR]

Comedonal bacteria, Propionibacterium acnes, P. granulosum and coagulase-negative staphylococci (CNS) seem to play an important initiating role in the inflammatory process by producing neutrophil chemotactic factors. The attracted neutrophils, after phagocytosis, release inflammatory factors such as reactive oxygen species (ROS). We investigated the effects of minocycline at subminimal inhibitory concentrations (sub-MIC), i.e. one-tenth MIC, on the production of human neutrophil chemotactic factors in comedonal bacteria, and on several inflammatory parameters of neutrophils, including neutrophil phagocytosis and generation of ROS (O, HO, O $${\text{H}}^{\text{.}} $$ ). ROS generation in a cell-free, xanthinexanthine oxidase system was also assessed. Production of neutrophil chemotactic factors in all strains of P. acnes, P. granulosum and CNS were significantly suppressed by sub-MIC minocycline. Sub-MIC minocycline effectively reduced three kinds of neutrophil-generated ROS (O, HO, O $${\text{H}}^{\text{.}} $$ ). However, neutrophil phagocytosis and the ROS generated in a cell-free system were not markedly changed in the presence of sub-MIC minocycline. The results suggest that sub-MIC minocycline has an anti-inflammatory effect by inhibiting the production of neutrophil chemotactic factors in comedonal bacteria as well as ROS generated by neutrophils in the inflammatory process of acne. [ABSTRACT FROM AUTHOR]

It has been shown that acne, hyperpigmentation and lentigo malignant are more or less related pathogenetically to reactive oxygen species (ROS). It has recently been reported that azelaic acid is effective in treating these conditions and that it possesses anti-enzymatic and anti-mitochondrial activity, including cytochrome-P reductase and 5α-reductase in microsomal preparations with nicotinamide adenine dinucleotide phosphate (NADPH). We therefore investigated the effects of azelaic acid on human neutrophil functions, such as chemotaxis, phagocytosis and ROS generation. ROS generation in a cell-free system was also assessed. The results revealed that neutrophil chemotaxis and phagocytosis as well as ROS generated in a xanthine - xanthine-oxidase system were not significantly changed in the presence of azelaic acid. However, azelaic acid markedly decreased Oand OH generated by neutrophils. It may be concluded that the reported clinical effectiveness of azelaic acid is partly due to its inhibitory action on neutrophil-generated ROS, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation. [ABSTRACT FROM AUTHOR]

Metronidazole is clinically effective in treating not only rosacea but also acne inflammation. Yet it is generally considered not to be very effective in inhibiting the growth of anaerobic Propionibacterium acnes. We report here our investigation into the synergistic effects of metronidazole and palmitoleic acid on the anaerobic growth of P. acnes as well as on human neutrophil functions, including the generation of reactive oxygen species (ROS). Both metronidazole and palmitoleic acid, when used alone, only slightly inhibited the growth of P. acnes, and no significant decrease in human neutrophil functions, including the generation of ROS, was observed. But metronidazole used in the presence of palmitoleic acid markedly inhibited the anaerobic growth of P. acnes and decreased ROS generation by neutrophils. However, ROS generated in the xanthine-xanthine oxidase system were not affected. Metronidazole was shown to be clinically effective by decreasing neutrophil-generated ROS at the sites of inflammation with the aid of palmitoleic acid, which is generally present in human skin. By inhibiting oxidative tissue injury under in vivo conditions, treatment with metronidazole results in remarkable improvement of rosacea and acne. [ABSTRACT FROM AUTHOR]

Resistive indices (RI) in the anterior cerebral artery (ACA), basilar artery (BA), middle cerebral artery (MCA) and descending aorta (DA) were obtained in 15 small-for-dates (SFD) infants who were, growth retarded because of maternal pregnancy-induced hypertension and in 20 appropriate-for-dates (AFD) infants matched for gestational age between 24 h and 48 h after birth. The RIs in the MCA, ACA and BA were significantly lower, while the RI in the DA was significantly higher, in the SFD infants than in the AFD infants. These changes in RIs in the SFD infants might be similar to the "brain sparing" effect as reported in growth-retarded fetuses. [ABSTRACT FROM AUTHOR]

We present a case of Dandy-Walker malformation associated with occipital meningocele, microphthalmia, and cleft palate. Small numbers of cases of Dandy-Walker malformation with occipital meningocele have been described in the literature, but to our knowledge, non of these also had microphthalmia or cleft palate. This association suggests that time of intrauterine origin of Dandy-Walker syndrome was in the sixth or seventh embryonic week. In the diagnosis, both CT cisternography and direct neurosonography over the occipital meningocele was useful for the demonstration of a posterior fossa cyst which communicated with the fourth ventricle and the occipital meningocele. [ABSTRACT FROM AUTHOR]