CYP35: Xenobiotically induced gene expression in the nematode Caenorhabditis elegans

Although over 80 cytochrome P450 (CYP) encoding genes have been identified in the genome of the nematode Caenorhabditis elegans very little is known about their involvement in biotransformation. This paper demonstrates a concentration-dependent relationship of C. elegans CYP35A1, A2, A5, and C1 gene expression in response to four organic xenobiotics, namely atrazine, PCB52, fluoranthene, and lansoprazole. The toxicity of these xenobiotics was determined using a reproduction assay. CYP-specific messenger RNA expression was analyzed by semi-quantitative RT-PCR resulting in a strongly increasing, concentration-dependent induction well below the EC50 for reproduction. For PCB52, approximately 0.5% of the EC50 induces a 2-fold increase of CYP35 gene expression. Using a double mutant and multiple RNAi of CYP35A/C it was possible to diminish the reproduction decline caused by PCB52 and fluoranthene.Peer Reviewe

Long-Term Experience of Chemoradiotherapy Combined with Deep Regional Hyperthermia for Organ Preservation in High-Risk Bladder Cancer (Ta, Tis, T1, T2).

BackgroundThe aim of this study was to evaluate the efficacy and safety of chemoradiotherapy (RCT) combined with regional deep hyperthermia (RHT) of high-risk bladder cancer after transurethral resection of bladder tumor (TUR-BT).Materials and methodsBetween 1982 and 2016, 369 patients with pTa, pTis, pT1, and pT2 cN0-1 cM0 bladder cancer were treated with a multimodal treatment after TUR-BT. All patients received radiotherapy (RT) of the bladder and regional lymph nodes. RCT was administered to 215 patients, RCT + RHT was administered to 79 patients, and RT was used in 75 patients. Treatment response was evaluated 4-6 weeks after treatment with TUR-BT.ResultsComplete response (CR) overall was 83% (290/351), and in treatment groups was RT 68% (45/66), RCT 86% (178/208), and RCT + RHT 87% (67/77). CR was significantly improved by concurrent RCT compared with RT (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.05-5.12; p = .037), less influenced by hyperthermia (OR, 2.56; 95% CI, 0.88-8.00; p = .092). Overall survival (OS) after RCT was superior to RT (hazard ratio [HR], 0.7; 95% CI, 0.50-0.99; p = .045). Five-year OS from unadjusted Kaplan-Meier estimates was RCT 64% versus RT 45%. Additional RHT increased 5-year OS to 87% (HR, 0.32; 95% CI, 0.18-0.58; p = .0001). RCT + RHT compared with RCT showed a significantly better bladder-preservation rate (HR, 0.13; 95% CI, 0.03-0.56; p = .006). Median follow-up was 71 months. The median number of RHT sessions was five.ConclusionThe multimodal treatment consisted of a maximal TUR-BT followed by RT; concomitant platinum-based chemotherapy combined with RHT in patients with high-grade bladder cancer improves local control, bladder-preservation rate, and OS. It offers a promising alternative to surgical therapies like radical cystectomy.Implications for practiceRadical cystectomy with appropriate lymph node dissection has long represented the standard of care for muscle-invasive bladder cancer in medically fit patients, despite many centers reporting excellent long-term results for bladder preserving strategies. This retrospective analysis compares different therapeutic modalities in bladder-preservation therapy. The results of this study show that multimodal treatment consisting of maximal transurethral resection of bladder tumor followed by radiotherapy, concomitant platinum-based chemotherapy combined with regional deep hyperthermia in patients with Ta, Tis, T1-2 bladder carcinomas improves local control, bladder-preservation rate, and survival. More importantly, these findings offer a promising alternative to surgical therapies like radical cystectomy. The authors hope that, in the future, closer collaboration between urologists and radiotherapists will further improve treatments and therapies for the benefit of patients

A large aperture reflective wave-plate for high-intensity short-pulse laser experiments

We report on a reflective wave-plate system utilizing phase-shifting mirrors (PSM) for a continuous variation of elliptical polarization without changing the beam position and direction. The scalability of multilayer optics to large apertures and the suitability for high-intensity broad-bandwidth laser beams make reflective wave-plates an ideal tool for experiments on relativistic laser-plasma interaction. Our measurements confirm the preservation of the pulse duration and spectrum when a 30-fs Ti:Sapphire laser beam passes the system

Characterization of encapsulated graphene layers using extreme ultraviolet coherence tomography

Many applications of two-dimensional materials such as graphene require the encapsulation in bulk material. While a variety of methods exist for the structural and functional characterization of uncovered 2D materials, there is a need for methods that image encapsulated 2D materials as well as the surrounding matter. In this work, we use extreme ultraviolet coherence tomography to image graphene flakes buried beneath 200 nm of silicon. We show that we can identify mono-, bi-, and trilayers of graphene and quantify the thickness of the silicon bulk on top by measuring the depth-resolved reflectivity. Furthermore, we estimate the quality of the graphene interface by incorporating a model that includes the interface roughness. These results are verified by atomic force microscopy and prove that extreme ultraviolet coherence tomography is a suitable tool for imaging 2D materials embedded in bulk materials

A high resolution extreme ultraviolet spectrometer system optimized for harmonic spectroscopy and XUV beam analysis

We present a modular extreme ultraviolet (XUV) spectrometer system optimized for a broad spectral range of 12-41 nm (30-99 eV) with a high spectral resolution of λ/Δλ 784 ± 89. The spectrometer system has several operation modes for (1) XUV beam inspection, (2) angular spectral analysis, and (3) imaging spectroscopy. These options allow for a versatile use in high harmonic spectroscopy and XUV beam analysis. The high performance of the spectrometer is demonstrated using a novel cross-sectional imaging method called XUV coherence tomography. © 2019 Author(s)

Absolute EUV reflectivity measurements using a broadband high-harmonic source and an in situ single exposure reference scheme

We present a tabletop setup for extreme ultraviolet (EUV) reflection spectroscopy in the spectral range from 40 to 100 eV by using high-harmonic radiation. The simultaneous measurements of reference and sample spectra with high energy resolution provide precise and robust absolute reflectivity measurements, even when operating with spectrally fluctuating EUV sources. The stability and sensitivity of EUV reflectivity measurements are crucial factors for many applications in attosecond science, EUV spectroscopy, and nano-scale tomography. We show that the accuracy and stability of our in situ referencing scheme are almost one order of magnitude better in comparison to subsequent reference measurements. We demonstrate the performance of the setup by reflective near-edge x-ray absorption fine structure measurements of the aluminum L2/3 absorption edge in α-Al2O3 and compare the results to synchrotron measurements

Observation of ultrafast solid-density plasma dynamics using femtosecond X-ray pulses from a free-electron laser

The complex physics of the interaction between short pulse high intensity lasers and solids is so far hardly accessible by experiments. As a result of missing experimental capabilities to probe the complex electron dynamics and competing instabilities, this impedes the development of compact laser-based next generation secondary radiation sources, e.g. for tumor therapy [Bulanov2002,ledingham2007], laboratory-astrophysics [Remington1999,Bulanov2015], and fusion [Tabak2014]. At present, the fundamental plasma dynamics that occur at the nanometer and femtosecond scales during the laser-solid interaction can only be elucidated by simulations. Here we show experimentally that small angle X-ray scattering of femtosecond X-ray free-electron laser pulses facilitates new capabilities for direct in-situ characterization of intense short-pulse laser plasma interaction at solid density that allows simultaneous nanometer spatial and femtosecond temporal resolution, directly verifying numerical simulations of the electron density dynamics during the short pulse high intensity laser irradiation of a solid density target. For laser-driven grating targets, we measure the solid density plasma expansion and observe the generation of a transient grating structure in front of the pre-inscribed grating, due to plasma expansion, which is an hitherto unknown effect. We expect that our results will pave the way for novel time-resolved studies, guiding the development of future laser-driven particle and photon sources from solid targets

Observation of Ultrafast Solid-Density Plasma Dynamics Using Femtosecond X-Ray Pulses from a Free-Electron Laser

The complex physics of the interaction between short-pulse ultrahigh-intensity lasers and solids is so far difficult to access experimentally, and the development of compact laser-based next-generation secondary radiation sources, e.g., for tumor therapy, laboratory astrophysics, and fusion, is hindered by the lack of diagnostic capabilities to probe the complex electron dynamics and competing instabilities. At present, the fundamental plasma dynamics that occur at the nanometer and femtosecond scales during the laser-solid interaction can only be elucidated by simulations. Here we show experimentally that small-angle x-ray scattering of femtosecond x-ray free-electron laser pulses facilitates new capabilities for direct in situ characterization of intense short-pulse laser-plasma interactions at solid density that allows simultaneous nanometer spatial and femtosecond temporal resolution, directly verifying numerical simulations of the electron density dynamics during the short-pulse high-intensity laser irradiation of a solid density target. For laser-driven grating targets, we measure the solid density plasma expansion and observe the generation of a transient grating structure in front of the preinscribed grating, due to plasma expansion. The density maxima are interleaved, forming a double frequency grating in x-ray free-electron laser projection for a short time, which is a hitherto unknown effect. We expect that our results will pave the way for novel time-resolved studies, guiding the development of future laser-driven particle and photon sources from solid targets